EA037544B1 - USE OF 1H-PYRAZOLO[4,3-b]PYRIDINES AS PDE1 INHIBITORS - Google Patents

Abstract

The invention provides 1H-pyrazolo[4,3-b]pyridin-7-amines of formula (I)as PDE1 inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders.

Description

The technical field to which the invention relates

The present invention provides compounds that are inhibitors of the PDE1 enzyme and their use as a medicament, in particular for the treatment of neurodegenerative disorders and mental disorders. The present invention also provides pharmaceutical compositions containing the compounds of the present invention and methods of treating disorders using the compounds of the present invention.

Background to the invention

Throughout this application, references to various publications are provided in their entirety. The disclosures of these publications are hereby incorporated into this application by reference for a more complete description of the prior art to which the present invention relates.

Secondary messengers cyclic nucleotides (cN), such as cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), play a major role in the intracellular signaling cascade, regulating cN-dependent protein kinases (PKA and PKG), EPAC (phosphate-activated protein) metabolism and / or cN-driven cation channels. In neurons, this involves the activation of cAMP- and cGMP-dependent kinases and the subsequent phosphorylation of proteins involved in the early regulation of synaptic transmission, as well as in the differentiation and survival of neurons. Intracellular concentrations of cAMP and cGMP are strictly regulated by the rate of biosynthesis by cyclases and the rate of degradation by phosphodiesterases (PDE, EC 3.1.4.17). PDEs are two-metal hydrolases that inactivate cAMP / cGMP through catalytic hydrolysis of the 3'-ester bond to form an inactive 5'-monophosphate. Since PDEs are the only means of degradation of cyclic cAMP and cGMP nucleotides in cells, PDEs play an indispensable role in signaling involving cyclic nucleotides. The catalytic activity of PDEs mediates cN degradation over a wide range of cN concentrations in all cells, and their diverse regulatory mechanisms mediate integration and cross-linking with multiple signaling pathways. Specific PDEs target discrete compartments within cells where they control cN levels and form a microenvironment for multiple cN signalosomes (Sharron H. Francis, Mitsi A. Blount, and Jackie D. Corbin. Physiol Rev 2011, 91: 651-690).

Based on the substrate specificity, the PDE family can be divided into three groups: 1) cAMP-specific PDEs, which include PDE4, PDE7 and PDE8, 2) cGMP-selective enzymes - PDE5 and PDE9, and 3) two-substrate PDEs - PDE1, PDE2, PDE3, as well as PDE10 and PDE11.

Previously referred to as calmodulin-stimulated PDE (CaM-PDE), PDE1 is unique in that it is regulated in a Ca ²⁺ dependent manner by calmodulin (CaM, a ^{16 kDa Ca 2+} binding protein) complexed with four Ca ²⁺ ( for a review see Sharron H. Francis, Mitsi A. Blount, and Jackie D. Corbin. Physiol. Rev. 2011, 91: 651-690). Thus, PDE1 represents an interesting regulatory relationship between cyclic nucleotides and intracellular Ca ²⁺ . The PDE1 family is encoded by three genes: PDEIA (mapped to human chromosome 2q32), PDE1B (position on human chromosome, hcl: 12q13), and PDEIC (hcl: 7p14.3). They have alternative promoters and, due to alternative splicing, form a variety of proteins that differ in their regulatory properties, affinity for the substrate, specific activities, CaM activation constants, tissue distribution, and molecular weight. More than 10 isoforms have been identified in humans. Their molecular weight ranges from 58 to 86 kDa per monomer. The N-terminal regulatory domain, which contains two Ca ²⁺ / CaM-binding domains and two phosphorylation sites, delimits their respective proteins and modulates their biochemical functions. PDE1 is a two-substrate PDE, with the PDE1C subtype having the same activity against cAMP and cGMP (Km <1-3 μM), while the PDE1A and PDE1B subtypes are characterized by a preference for cGMP (Km for cGMP <1-3 μM, and for cAMP »10-30 μM).

Large numbers of PDE1 subtypes are noted in the brain, and they are localized mainly in the striatum (PDE1B), hippocampus (PDE1 A) and cerebral cortex (PDEIA), and this localization is conserved across species (Amy Bernard et al. Neuron 2012, 73, 1083-1099). In the cerebral cortex, PDE1A is present mainly in the deep layers 5 and 6 of the cerebral cortex (output layers), and it is used as a specific marker for the deep layers of the cerebral cortex. PDE1 inhibitors increase levels of cN secondary messengers, resulting in increased neuronal excitability.

Thus, PDE1 is a therapeutic target for the regulation of intracellular signaling pathways, mainly in the nervous system, and PDE1 inhibitors can increase the levels of cAMP / cGMP secondary messengers, which leads to modulation of processes in neurons and to the expression of genes associated with neuronal plasticity, neurotrophic factors and neuroprotective molecules. These properties of increasing neuronal plasticity, together with the modulation of synaptic transmission, make PDE1 inhibitors good candidates as therapeutic agents for many neurological and mental pathological conditions. Evaluation of inhibition

- 1,037544 PDE1 tori in animal models (for a review see, for example, Blokland et al. Expert Opinion on Therapeutic Patents (2012), 22 (4), 349-354; and Medina, AE Frontiers in Neuropharmacology (2011), 5 (Feb.), 21) demonstrated the potential for therapeutic use of PDE1 inhibitors in neurological disorders such as, for example, Alzheimer's, Parkinson's and Huntington's diseases, and in mental disorders such as, for example, attention deficit / hyperactivity disorder (ADHD), depression, anxiety, narcolepsy, cognitive impairment and cognitive impairment associated with schizophrenia (CIAS), and restless legs syndrome. Patent applications have also been filed claiming that PDE1 inhibitors are useful in diseases that can be ameliorated by increased progesterone signaling, such as female sexual dysfunction (eg, WO 2008/070095).

The compounds of the present invention may provide an alternative to current commercially available agents for the treatment of neurodegenerative and / or psychiatric disorders, agents that are not effective in all patients. Thus, there remains a need for alternative treatments for such diseases.

Brief description of the invention

PDE1 enzymes are expressed in the central nervous system (CNS), making this gene family a promising source of new targets for the treatment of mental and neurodegenerative disorders.

Accordingly, the present invention relates to compounds of formula (I)

R1

(I) where L is selected from the group consisting of NH, CH ₂ , S and O;

R1 is selected from the group consisting of hydrogen, linear or branched C ₁ -C ₆ alkyl, C _r C ₃ fluoroalkyl, and saturated monocyclic C ₃ -C ₆ cycloalkyl;

R2 is selected from the group consisting of linear or branched C ₁ -C ₈ alkyl, saturated monocyclic C ₃ -C ₈ cycloalkyl, oxetanyl, tetrahydrofuranyl, and tetrahydropyranyl; all of which may optionally be substituted one or more times with one or more substituents selected from the group consisting of methyl, fluoro, hydroxy, cyano and methoxy;

R3 is methyl substituted with phenyl, pyridonyl, pyridinyl, pyrimidinyl or pyrazinyl, all of which may optionally be substituted one or more times with one or more substituents selected from the group consisting of halogen, cyano, C ₁ -C ₃ alkyl, C _r C ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy and C ₁ -C ₃ alkoxy; or

R3 is methyl substituted with 5-membered heteroaryl, which is optionally substituted with one or more substituents selected from halogen, cyano, C ₁ -C ₃ alkyl, C ₁ C ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy and C ₁ -C ₃ alkoxy; or

R3 is ethyl substituted with phenyl, pyridonyl, pyridinyl, pyrimidinyl or pyrazinyl, all of which may be optionally substituted one or more times with one or more substituents selected from the group consisting of halogen, cyano, C ₁ -C ₃ alkyl, C ₁ C ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy and C ₁ -C ₃ alkoxy; or

R3 is ethyl substituted with 5-membered heteroaryl, which is optionally substituted with one or more substituents selected from halogen, cyano, C ₁ -C ₃ alkyl, C ₁ C ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy and C ₁ -C ₃ alkoxy; or

L is CH ₂ and R3 is NH substituted with phenyl, pyridonyl, pyridinyl, pyrimidinyl or pyrazinyl, all of which may optionally be substituted one or more times with one or more substituents selected from the group consisting of halogen, cyano, C ₁ -C ₃ alkyl, C ₁ -C ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy and C ₁ -C ₃ alkoxy; or

L is CH ₂ and R ₃ is NH substituted with 5-membered heteroaryl, which is optionally substituted with one or more substituents selected from halogen, cyano, C ₁ -C ₃ alkyl, C ₁ -C ₃ fluoroalkyl, C ₁ - C ₃ fluoroalkoxy and C ₁ -C ₃ alkoxy;

R4 represents phenyl, pyridinyl or pyridonyl, all of which may be optionally substituted one or several times with one or more substituents selected from the group consisting of halogen, cyano, C ₁ -C ₄ alkyl, C ₁ -C ₄ fluoroalkyl, C _d C ₄ deuterioalkyl, C ₁ -C ₃ fluoroalkoxy, cyclopropyloxy, C ₁ -C ₃ alkoxy, C ₁ -C ₃ deuterioalkoxy and —N — R5R6, where each of R5 and R6 is independently selected from H, C ₁ -C ₃ alkyl and C ₁ -C ₃ deuterioalkyl; or

R4 represents a 5-membered heteroaryl which is optionally substituted by one or more substituents selected from halo, cyano, C ₁ -C ₄ alkyl, C ₁ -C ₄ fluoroalkyl, C ₁ - 2 037 544

FROM.' ₄ deuterioalkyl. _C1-C3 fluoroalkoxy, cyclopropyloxy, _C1-C3 alkoxy, _C1-C3 deyterioalkoksi and -NR5R6, where each of R5 and R6 is independently selected from H, _C1-C3 alkyl and C1-C ₃ deyterioalkila; or

R4 represents a 4-, 5- or 6-membered saturated heterocycle which in all cases may be optionally substituted with one or more substituents selected from oxo, C1C ₄ alkyl and C ₁ -C ₄ fluoroalkyl;

and their pharmaceutically acceptable salts.

Reference to compound I includes the free base of compound I, pharmaceutically acceptable salts of compound I such as acid addition salts of compound I, racemic mixtures of compound I, or the corresponding enantiomer and / or optical isomer of compound I, and polymorphic and amorphous forms of compound I, as well as tautomeric forms Compounds I. In addition, the compounds of the present invention can exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol and the like. In general, for the purposes of the present invention, the solvated forms are considered equivalent to the unsolvated forms.

In one embodiment, the present invention relates to a compound of formula (I) for use in therapy.

In one embodiment, the present invention relates to a pharmaceutical composition comprising a compound of formula (I) and one or more pharmaceutically acceptable carriers or excipients.

In one embodiment, the present invention relates to a compound of formula (I) for use in the treatment of a neurodegenerative disorder selected from the group consisting of Alzheimer's disease, Parkinson's disease and Huntington's disease, or in the treatment of a mental disorder such as attention deficit / hyperactivity disorder (ADHD ), depression, anxiety, narcolepsy, cognitive impairment and cognitive impairment associated with schizophrenia (CIAS), or another brain disorder like restless legs syndrome.

In one embodiment, the present invention provides a method for treating a neurodegenerative disorder selected from the group consisting of Alzheimer's disease, Parkinson's disease and Huntington's disease, or treating a mental disorder such as attention deficit / hyperactivity disorder (ADHD), depression, anxiety, narcolepsy , cognitive impairment and cognitive impairment associated with schizophrenia (CIAS), or other brain disease like restless legs syndrome, the method comprising administering a therapeutically effective amount of a compound of formula (I) to a patient in need thereof.

In one embodiment, the present invention relates to the use of a compound of formula (I) for the manufacture of a medicament for the treatment of a neurodegenerative disorder selected from the group consisting of Alzheimer's disease, Parkinson's disease and Huntington's disease, or for the treatment of a mental disorder such as attention deficit disorder. hyperactivity disorder (ADHD), depression, anxiety, narcolepsy, cognitive impairment and cognitive impairment associated with schizophrenia (CIAS), or another brain disorder like restless legs syndrome.

Definitions.

PDE1 enzymes.

The PDE1 family of isozymes includes numerous PDE1 isoforms formed as splicing variants. It includes three subtypes, PDE1A, PDE1B and PDE1C, which are further subdivided into different isoforms. In the context of the present invention, PDE1 and PDE1 enzymes are synonymous and refer to the PDE1A, PDE1B and PDE1C enzymes, as well as their isoforms, unless otherwise indicated.

PDE1 inhibitors.

In the context of the present invention, a compound is considered a PDE1 inhibitor if the amount required to achieve the IC ₅₀ level for any of the three PDE1 isoforms is 10 μmol / L or less, preferably less than 9 μmol / L, for example 8 μmol / L or less , for example 7 μmol / L or less, for example 6 μmol / L or less, for example 5 μmol / L or less, for example 4 μmol / L or less, for example 3 μmol / L or less, more preferably 2 μmol / L or less, for example 1 μmol / L or less, in particular 500 nM or less.

In general, the compounds of the present invention exhibit selectivity for the PDE1B isoform, which means that these compounds are more potent as PDE1B inhibitors than as PDE1A and / or PDE1C inhibitors. In preferred embodiments, said compounds are at least twice as strong, five times as strong, or ten times as strong as PDE1B inhibitors than as PDE1A and / or PDE1C inhibitors. In more preferred embodiments, said compounds are at least fifteen times stronger or twenty times stronger as PDE1B inhibitors than as PDE1A and / or PDE1C inhibitors.

In preferred embodiments, the amount of PDE1 inhibitor required to achieve a PDE1B IC ₅₀ level is 400 nM or less, such as 300 nM or less,

200 nM or less, 100 nM or less, or even 80 nM or less, for example 50 nM or less, for example 25 nM or less. Selectivity for the PDE1B isoform can prevent potentially undesirable effects associated with inhibition of PDE1A and / or PDE1C. For example, potentially unwanted peripheral effects.

Deputies.

In this context, optionally substituted means that the specified particle may or may not be substituted, and if it is substituted, it contains one, two or three substituents. It is understood that if no substituents are indicated for the optionally substituted moiety, then the position is occupied by a hydrogen atom.

Used in the context of the present invention, the terms halogen and halogen are used interchangeably and mean fluorine, chlorine, bromine or iodine.

The range shown may be interchangeably denoted by - (dash) or by words from to, for example, the term C ₁ -C ₃ alkyl is equivalent to the term C ₁ to C ₃ alkyl.

The terms C ₁ -C ₃ alkyl, _C1-C4 alkyl, C1-C ₃ alkyl, C ₁ -C ₆ alkyl, C ₁ -C ₇ alkyl and C 1 C ₈ alkyl represent a linear (i.e., unbranched) or branched, a saturated hydrocarbon containing from one to eight carbon atoms, inclusive. Examples of such groups include, but are not limited to, methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, 2-methyl-2-propyl, 2-methyl-1-butyl, n-hexyl, n-heptyl, and n-octyl.

The term C ₁ -C ₃ fluoroalkyl means C ₁ -C ₃ alkyl substituted with one or more fluorine atoms.

The terms _{C 1} -C ₄ deuterioalkyl and C _{1 -C 3} deuterioalkyl mean C ₁ -C ₄ alkyl and C ₁ -C ₃ alkyl, where one or more hydrogen atoms are deuterium. Examples of the C ₁ -C ₃ deuterioalkyl include, but are not limited to, trideuterioethyl, 1,1-dideuterioethyl, 2,2,2-trideuterioethyl, and 1,1,2,2,2 pentadeuterioethyl.

The term saturated monocyclic C ₃ -C ₈ cycloalkyl means cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.

The term 5-membered heteroaryl means a 5-membered aromatic monocyclic ring containing 1 to 4 carbon atoms and one or more heteroatoms selected from oxygen, nitrogen and sulfur. Examples include, without limitation, thiazolyl, oxazolyl, isoxazolyl, triazolyl, pyrazolyl, tetrazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, and thiophenyl.

The term C ₁ -C ₃ alkoxy means a moiety of the formula —OR ′, where R ′ is C ₁ -C ₃ alkyl as defined above.

The term C1-C ₃ fluoroalkoxy means a moiety of the formula —OR ', where R' is Cl — C ₃ fluoroalkyl as defined above.

The term _C1-C3 deyterioalkoksi mean _Cl-C3 alkoxy wherein one or more hydrogen atoms are defined as deuterium. Examples include, but are not limited to, trideuterioethoxy, 1,1dideuterioethoxy, 2,2,2-trideuterioethoxy, and 1,1,2,2,2-pentadeuterioethoxy.

The terms 4-, 5-, or 6-membered saturated heterocycle refer to a saturated monocyclic ring containing 1 to 3, 4, or 5 carbon atoms and one or more heteroatoms selected from oxygen, nitrogen and sulfur. Examples include, without limitation, oxazolidin-2-one, azetidin-2-one, imidazolidin-2-one, pyrrolidin-2-one, imidazolidin-2,4-dione, oxazolidin-2,4-dione, or piperidin-2-one.

Isomeric and tautomeric forms.

Where the compounds of the present invention contain one or more chiral centers, reference to any of the compounds will, unless otherwise indicated, encompass the enantiomerically or diastereomerically pure compound, as well as mixtures of enantiomers or diastereomers in any ratio. For example, the compound of Example 15 is prepared as a racemate and is embraced as (R) -5- (2-ethoxypyridin-3-yl) -1-methyl-N- (1- (1-methyl-1H- pyrazol-4-yl) ethyl) -1H-pyrazolo [4,3-b] pyridin7-amine, and (S) -5- (2-ethoxypyridin-3-yl) -1-methyl-N- (1- (1-methyl-1H-pyrazol-4-yl) ethyl) -1Hpyrazolo [4,3-b] pyridin-7-amine, as well as mixtures of these two enantiomers in any ratio, including the racemic mixture. The R-enantiomer of the compound of Example 15 was designated 15a, while the S-enantiomer was designated 15b.

When a compound according to the present invention is designated by the ending enantiomer 1 or enantiomer 2, it is intended that said enantiomer may be either the S enantiomer or the R enantiomer. Those. enantiomer 1 can be either the S-enantiomer or the R-enantiomer, and enantiomer 2 can be either the S-enantiomer or the R-enantiomer. If both enantiomer 1 and enantiomer 2 have been exemplified for a compound, then one is the S-enantiomer and the other is the R-enantiomer. For example, the compound representing Example 123 is 5- (2-ethoxy-3-pyridyl) -3-methyl-N - [(5methyl-1,3,4-oxagiazol-2-yl) methyl] -1- [1-methylnropyl] pyrazolo [4,3-b] pyridin-7-amine, enantiomer 1; and the compound of Example 124 is 5- (2-ethoxy-3-pyridyl) -3-methyl-N [(5-methyl-1,3,4-oxadiazol-2-yl) methyl] -1- [1-methylpropyl] pyrazolo [4,3-b] pyridine-7-amine, enantiomer 2.

- 4 037544

Therefore, if, for example, it can be determined that the compound of Example 123 is the R-enantiomer, then the compound of Example 124 will be the S-enantiomer, and vice versa.

Some compounds according to the present invention have been exemplified in only one enantiomeric form, such as Example 125: 5- (2-ethoxy-3-pyridyl) -N - [(5-methoxy-3 -pyridyl) methyl] -3-methyl-1- [1-methylnropyl] pyrazolo [4,3b] pyridin-7-amine, enantiomer 2, which was obtained from 1- (sec-butyl) -5- (2-ethoxypyridine -3-yl) -3methyl-1H-pyrazolo [4,3-b] pyridin-7-amine, enantiomer 2. In this case, it follows that the corresponding enantiomer (enantiomer 1) can be obtained in a similar way from 1- (sec- butyl) -5- (2ethoxypyridin-3-yl) -3-methyl-1H-pyrazolo [4,3-b] pyridin-7-amine, enantiomer 1. Thus, the corresponding enantiomer (enantiomer 1) is also a compound in in accordance with the present invention, which may be separately claimed. Example 125 thus encompasses both enantiomeric forms, each of which can be claimed separately, although only enantiomer 2 was obtained and tested in the PDE1 assay. The R enantiomer of Example 125 was designated 125a, with the S enantiomer designated 125b. The same principle applies for other exemplary compounds for which only one enantiomer has been obtained.

The absolute stereochemistry of a compound of the present invention can be determined by X-ray crystallography or vibrational circular dichroism.

In addition, some of the compounds of the present invention may exist in different tautomeric forms, and it is contemplated that any tautomeric forms these compounds may form are within the scope of the present invention.

Deuterated compounds.

The present invention also provides deuterated compounds. The term deuterated compound means a compound containing one or more atoms, which are defined as deuterium.

It is recognized that elements are present with natural isotope ratios in most synthetic compounds and lead to the inherent incorporation of deuterium. The natural abundance of hydrogen isotopes such as deuterium is approximately 0.015%. Thus, when used herein, the designation of an atom as deuterium in position means that the relative abundance of deuterium is substantially greater than the naturally significant abundance of deuterium. Any atom not designated as a specific isotope is intended to be any stable isotope of that atom, as will be apparent to one of ordinary skill in the art. Any atom not designated as deuterium is present in an amount approximately corresponding to its natural relative abundance.

In some embodiments, the designation of the position as D in the compound has a minimum deuterium incorporation of more than 50% at that position. In some embodiments, the designation of the position as D in the compound has a minimum deuterium incorporation of more than 60%, such as more than 65%, such as more than 70%, such as more than 75%, such as more than 80% at that position. In a preferred embodiment, designating the position as D in the compound has a minimum deuterium incorporation of more than 85%, for example, more than 90%, at that position. In a more preferred embodiment, the designation of the position as D in the compound has a minimum deuterium incorporation of more than 95%, for example, more than 97%, for example, more than 99% at that position.

Deuterated compounds of the present invention are those wherein one or more substituent atoms at the R4 position are deuterium.

Pharmaceutically acceptable salts.

The compounds of the present invention are generally administered as the free substance or as a pharmaceutically acceptable salt thereof. When a compound of formula (I) contains a free base, such salts are conventionally prepared by treating a solution or suspension of a free base of formula (I) with a molar equivalent of a pharmaceutically acceptable acid. Typical examples of suitable organic and inorganic acids are described below.

Pharmaceutically acceptable salts in the present context are intended to mean non-toxic, i. E. physiologically acceptable salts. The term pharmaceutically acceptable salts includes salts formed with organic and / or inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, nitrous acid, sulfuric acid, benzoic acid, citric acid, gluconic acid, lactic acid, maleic acid, succinic acid, tartaric acid, acetic acid, propionic acid, oxalic acid, maleic acid, fumaric acid, glutamic acid, pyroglutamic acid, salicylic acid, salicylic acid, saccharin, and sulfonic acids such as methanesulfonic acid, ethanesulfonic acid, toluenesulfonic acid, and benzene sulfonic acid. Some of the acids listed above are di- or tribasic acids, i. E. acids containing two or three ki- 5,037,544 slot hydrogen atoms such as phosphoric acid, sulfuric acid, fumaric acid and maleic acid.

Additional examples of suitable acids and bases for forming pharmaceutically acceptable salts can be found, for example, in the Stahl and Wermuth (Eds) Handbook of Pharmaceutical salts. Properties, selection, and use, Wiley-VCH, 2008.

A therapeutically effective amount.

In this context, the term therapeutically effective amount of a compound means an amount sufficient to cure, alleviate or partially stop the clinical manifestations of a given disease and its complications in a therapeutic intervention involving the administration of said compound. An amount sufficient to accomplish this is defined as a therapeutically effective amount. Effective amounts for each target will depend on the severity of the disease or injury, as well as the weight and general condition of the subject. It should be understood that the determination of the appropriate dosage can be achieved using routine experimentation, by constructing a matrix of values and testing various points in the matrix, which is within the skill of the skilled practitioner.

Treatment and implementation of treatment.

In this context, the expression treatment or treatment is intended to mean monitoring and caring for a patient with the aim of alleviating, stopping, partially stopping or delaying the development of a clinical manifestation of a disease or curing a disease. The patient to be treated is preferably a mammal, in particular a human.

Routes of administration.

The pharmaceutical compositions can be specially formulated for administration by any suitable route, such as oral, rectal, nasal, buccal, sublingual, transdermal, and parenteral (eg, subcutaneous, intramuscular and intravenous) routes, with the oral route being preferred.

It will be appreciated that the route will depend on the general condition and age of the subject to be treated, the nature of the condition to be treated, and the active ingredient.

Pharmaceutical formulations and excipients.

Further, the term excipient or pharmaceutically acceptable excipient means pharmaceutical excipients, including, but not limited to, fillers, anti-stick agents, binders, coatings, colorants, disintegrating agents, flavors, glidants, lubricants, preservatives, sorbents, sweeteners, solvents , carrier media and auxiliaries.

The present invention also provides a pharmaceutical composition comprising a compound of formula (I), such as one of the compounds disclosed in the experimental section herein. The present invention also provides a method for preparing a pharmaceutical composition containing a compound of formula (I). Pharmaceutical compositions in accordance with the present invention can be formulated with pharmaceutically acceptable excipients according to conventional techniques such as those disclosed in Remington, The Science and Practice of Pharmacy, 22 ^th edition (2012), Edited by Allen, Loyd V., Jr.

Pharmaceutical compositions for oral administration include solid oral dosage forms such as tablets, capsules, powders and granules; and liquid oral dosage forms such as solutions, emulsions, suspensions and syrups, as well as powders and granules for dissolving or suspending in a suitable liquid.

Solid oral dosage forms can be in the form of discrete units (eg tablets or hard or soft capsules), each containing a predetermined amount of the active ingredient and, preferably, one or more suitable excipients. If desired, solid dosage forms can be prepared with coatings such as enteric coatings, or they can be formulated to provide controlled release of the active ingredient, such as sustained or sustained release, in accordance with methods well known in the art. If desired, the solid dosage form can be a saliva-disintegrating dosage form, such as an orally dispersible tablet.

Examples of excipients suitable for the solid oral formulation include, but are not limited to, microcrystalline cellulose, corn starch, lactose, mannitol, povidone, croscarmellose sodium, sucrose, cyclodextrin, talc, gelatin, pectin, magnesium stearate, stearic acid and lower cellulose. Similarly, the solid formulation may include sustained or sustained release formulation auxiliaries known in the art, such as glyceryl monostearate and hypromellose. If a solid material is used for oral administration, the composition can be prepared, for example, by mixing the active ingredient with solid excipients and then compressing the mixture in a standard tabletting machine; or a composition, for example in the form of a powder, granules or minitablets

- 6 037544 can be placed, for example, in a hard capsule. The amount of solid excipient will vary significantly, but will generally range from about 25 mg to about 1 g per unit dose.

Liquid oral dosage forms can be presented, for example, as tinctures, syrups, oral drops or liquid-filled capsules. Liquid oral dosage forms can also be presented in the form of powders to obtain a solution or suspension in an aqueous or non-aqueous liquid. Examples of excipients suitable for the oral liquid formulation include, but are not limited to, ethanol, propylene glycol, glycerin, polyethylene glycols, poloxamers, sorbitol, polysorbate, mono- and diglycerides, cyclodextrins, coconut oil, palm oil, and water. Liquid oral dosage forms can be prepared, for example, by dissolving or suspending the active ingredient in an aqueous or non-aqueous liquid, or by including the active ingredient in an oil-in-water or water-in-oil liquid emulsion.

In solid and liquid oral formulations, additional excipients such as colorants, flavors, preservatives, etc. can be used.

Pharmaceutical compositions for parenteral administration include sterile aqueous and non-aqueous solutions, dispersions, suspensions or emulsions for injection or infusion, concentrates for injection or infusion, and sterile powders to be resuspended as sterile solutions or dispersions for injection or infusion prior to use. Examples of excipients suitable for parenteral formulation include, but are not limited to, water, coconut oil, palm oil, and cyclodextrin solutions. If necessary, aqueous formulations should be appropriately buffered and isotonic with sufficient saline or glucose.

Other types of pharmaceutical compositions include suppositories, inhalers, creams, gels, skin patches, implants, and formulations for buccal or sublingual administration.

It is necessary that the excipients used for any pharmaceutical composition correspond to the intended route of administration and be compatible with the active ingredients.

Doses.

In one embodiment, the compound of the present invention is administered in an amount of from about 0.001 to about 100 mg / kg body weight per day. In particular, the daily dose can range from 0.01 to about 50 mg / kg of body weight per day. The exact dosage will depend on the frequency and route of administration, gender, age, weight and general condition of the subject to be treated, the nature and severity of the condition being treated, any concomitant diseases being treated, the intended effect of the treatment, and other factors known to those skilled in the art. this field of technology.

A typical oral dose for adults will be in the range of 0.1-1000 mg / day of a compound of the present invention, eg 1-500 mg / day, eg 1-100 mg / day or 1-50 mg / day. For convenience, the compounds of the present invention are administered in a unit dosage form containing said compounds in an amount of from about 0.1 to 500 mg, for example 10, 50, 100, 150, 200 or 250 mg of a compound of the present invention.

Detailed description of the invention

The present inventors have identified compounds that are PDE1 inhibitors and as such are useful in the treatment of neurodegenerative and psychiatric disorders. The present invention thus provides compounds of formula (I) which are effective in inhibiting PDE1 for use as a medicament in the treatment of a mammal, preferably a human.

The present invention provides a compound of formula (I), or a pharmaceutically acceptable acid addition salt thereof, as well as a pharmaceutical composition containing such a compound, for use in the treatment of a brain disorder which may be a neurodegenerative disorder or a mental disorder. In a preferred embodiment, the neurodegenerative disorder is selected from the group consisting of Alzheimer's disease, Parkinson's disease, and Huntington's disease. In another preferred embodiment, the mental disorder is selected from the group consisting of attention deficit / hyperactivity disorder (ADHD), depression, anxiety, narcolepsy, cognitive impairment, and cognitive impairment associated with schizophrenia (CIAS). Other brain dysfunctions may include, for example, restless legs syndrome.

The present invention further provides a method of treating a brain disorder, which may be a neurodegenerative or mental disorder, the method comprising administering to said mammal a pharmaceutically effective amount of a compound of formula (I). Examples of neurodegenerative disorders that can be treated in accordance with the present invention include Alzheimer's disease, Parkinson's disease and Gene-7 037544 Tington's disease, the method comprising administering to a subject a therapeutically effective amount of a compound of formula (I). Examples of mental disorders that can be treated in accordance with the present invention include attention deficit / hyperactivity disorder (ADHD), depression, narcolepsy, cognitive impairment, and cognitive impairment associated with schizophrenia (CIAS). Other brain disorders to be treated can be, for example, restless legs syndrome.

Embodiments of the invention

The following embodiments of the invention are disclosed. The first embodiment is designated E1, the second embodiment is designated E2, and so on.

In a first embodiment E1, the present invention relates to compounds of formula (I).

E1. Compound of formula (I)

where L is selected from the group consisting of NH, CH ₂ , S and O;

R1 is selected from the group consisting of hydrogen, linear or branched C ₁ -C ₆ alkyl, _{C 1 C 3} fluoroalkyl, and saturated monocyclic C ₃ -C ₆ cycloalkyl;

R2 is selected from the group consisting of straight or branched _C1-C8 alkyl, monocyclic saturated C ₃ -C ₈ cycloalkyl, oxetanyl, tetrahydrofuranyl and tetrahydropyranyl; all of which may optionally be substituted one or more times with one or more substituents selected from the group consisting of methyl, fluoro, hydroxy, cyano and methoxy;

R3 is methyl substituted by phenyl piridonilom, pyridinyl, pyrimidinyl or pyrazinyl, all of which may be optionally substituted one or several times with one or more substituents selected from the group consisting of halogen, cyano, C ₁ -C ₃ alkyl, C1S ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy and C ₁ -C ₃ alkoxy; or

R3 represents methyl, substituted 5-membered heteroaryl which is optionally substituted by one or more substituents selected from halo, cyano, C ₁ -C ₃ alkyl, C1S ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy, and C ₁ -C ₃ alkoxy; or

R3 is ethyl substituted with phenyl, pyridonyl, pyridinyl, pyrimidinyl or pyrazinyl, all of which may be optionally substituted one or more times with one or more substituents selected from the group consisting of halogen, cyano, C ₁ -C ₃ alkyl, C1C ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy and C ₁ -C ₃ alkoxy; or

R3 is ethyl substituted 5-membered heteroaryl which is optionally substituted by one or more substituents selected from halo, cyano, C ₁ -C ₃ alkyl, C1S ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy, and C ₁ -C ₃ alkoxy; or

L is CH ₂ and R3 is NH substituted with phenyl, pyridonyl, pyridinyl, pyrimidinyl or pyrazinyl, all of which may optionally be substituted one or more times with one or more substituents selected from the group consisting of halogen, cyano, C ₁ -C ₃ alkyl, C ₁ -C ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy and C ₁ -C ₃ alkoxy; or

L is CH ₂ and R3 is NH substituted with 5-membered heteroaryl, which is optionally substituted with one or more substituents selected from halogen, cyano, C ₁ -C ₃ alkyl, C ₁ -C ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy and C ₁ -C ₃ alkoxy;

R4 represents phenyl, pyridinyl or pyridonyl, all of which may be optionally substituted one or several times with one or more substituents selected from the group consisting of halogen, cyano, C1-C ₄ alkyl, C ₁ -C ₄ fluoroalkyl, C 1 -C C ₄ deuterioalkyl, C ₁ -C ₃ fluoroalkoxy, cyclopropyloxy, C ₁ -C ₃ alkoxy, C ₁ -C ₃ deuterioalkoxy, and —N — R5R6, where R5 and R6 are each independently selected from H, C ₁ -C ₃ alkyl, and C ₁ -C ₃ deuterioalkyl; or

R4 represents a 5-membered heteroaryl which is optionally substituted by one or more substituents selected from halo, cyano, C1C ₄ alkyl, C1C ₄ fluoroalkyl, C1C deyterioalkila _4, C ₁ -C ₃ fluoroalkoxy, cyclopropyloxy, C ₁ - C ₃ alkoxy, C ₁ -C ₃ deuterioalkoxy, and —NR5R6, where each of R5 and R6 is independently selected from H, C ₁ -C ₃ alkyl, and C ₁ -C ₃ deuterioαalkyl; or

R4 is a 4-, 5- or 6-membered saturated heterocycle, which in all cases may be optionally substituted with one or more substituents selected from oxo, C ₁ C ₄ alkyl and C _{1 -C 4} fluoroalkyl;

and their pharmaceutically acceptable salts.

E2. A connection according to embodiment 1, where

L is selected from the group consisting of NH, CH2, S, and O;

R1 is selected from the group consisting of hydrogen, linear or branched C ₁ -C ₆ alkyl, C1- 8 037 544

C ₃ fluoroalkyl and saturated monocyclic C ₃ -C ₆ cycloalkyl;

R2 is selected from the group consisting of linear or branched C ₁ -C ₈ alkyl, saturated monocyclic C ₃ -C ₈ cycloalkyl, oxetanyl, tetrahydrofuranyl, and tetrahydropyranyl; all of which may optionally be substituted one or more times with one or more substituents selected from the group consisting of methyl, fluoro, hydroxy, cyano and methoxy;

R3 is methyl substituted with phenyl, pyridonyl, pyridinyl, pyrimidinyl or pyrazinyl, all of which may optionally be substituted one or more times with one or more substituents selected from the group consisting of halogen, cyano, C ₁ -C ₃ alkyl, C ₁ C ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy and C ₁ -C ₃ alkoxy; or

R3 is methyl substituted with 5-membered heteroaryl which is optionally substituted with one or more substituents selected from halogen, cyano, C ₁ -C ₃ alkyl, CiC ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy, and C ₁ -C ₃ alkoxy; or

R3 is ethyl substituted with phenyl, pyridonyl, pyridinyl, pyrimidinyl or pyrazinyl, all of which may be optionally substituted one or more times with one or more substituents selected from the group consisting of halogen, cyano, C ₁ -C ₃ alkyl, C ₁ C ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy and C ₁ -C ₃ alkoxy; or

R3 is ethyl substituted with 5-membered heteroaryl, which is optionally substituted with one or more substituents selected from halogen, cyano, C ₁ -C ₃ alkyl, C ₁ C ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy and C ₁ -C ₃ alkoxy;

R4 is phenyl, pyridinyl or pyridonyl, all of which may optionally be substituted one or more times with one or more substituents selected from the group consisting of halogen, cyano, C ₁ -C ₃ alkyl, C ₁ -C ₃ fluoroalkyl, C ₁ -C ₃ deuterioalkyl, C ₁ -C ₃ fluoroalkoxy, cyclopropyloxy, C ₁ -C ₃ alkoxy, C ₁ -C ₃ deuterioalkoxy and -N-R5R6, where each of R5 and R6 is independently selected from H, C ₁ -C ₃ alkyl and C ₁ -C ₃ deuterioalkyl; or

R4 is 5-membered heteroaryl, which is optionally substituted with one or more substituents selected from halogen, cyano, C ₁ -C ₃ alkyl, C ₁ -C ₃ fluoroalkyl, C ₁ C ₃ deuterioalkyl, C ₁ -C ₃ fluoroalkoxy, cyclopropyloxy , C ₁ -C ₃ alkoxy, C ₁ -C ₃ deuterioalkoxy and —NR5R6, where each of R5 and R6 is independently selected from H, C ₁ -C ₃ alkyl, and C ₁ -C ₃ deuterioalkyl; or

R4 is a 4-, 5- or 6-membered saturated heterocycle, which in all cases may optionally be substituted with one or more substituents selected from oxo, C ₁ C ₄ alkyl, and C ₁ -C ₄ fluoroalkyl.

E3. A compound according to any one of embodiments 1 or 2, wherein L is NH.

E4. A compound according to any one of Embodiments 1 or 2, wherein L is CH2.

E5. A compound according to any one of Embodiments 1 or 2, wherein L is S.

E6. A compound according to any one of embodiments 1 or 2, wherein L is O.

E7. A connection according to embodiment 1, where

L is CH2 and R3 is NH substituted with phenyl, pyridonyl, pyridinyl, pyrimidinyl or pyrazinyl, all of which may optionally be substituted one or more times with one or more substituents selected from the group consisting of halogen, cyano, C ₁ -C ₃ alkyl, C ₁ -C ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy and C ₁ -C ₃ alkoxy; or

L is CH ₂ and R3 is NH substituted with 5-membered heteroaryl, which is optionally substituted with one or more substituents selected from halogen, cyano, C ₁ -C ₃ alkyl, C ₁ -C ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy and C ₁ -C ₃ alkoxy.

E8. A compound according to any one of Embodiments 1-7, wherein R2 is selected from the group consisting of linear or branched C ₁ -C ₈ alkyl, saturated monocyclic C ₃ C ₈ cycloalkyl, oxetanyl, tetrahydrofuranyl, and tetrahydropyranyl, all of which are unsubstituted ...

E9. The compound according to embodiment 8, wherein R2 is selected from the group consisting of linear or branched C ₁ -C ₄ alkyl, cyclopropyl, oxetanyl, tetrahydrofuranyl, and tetrahydropyranyl.

E10. A compound according to any one of Embodiments 1-9, wherein R3 is methyl substituted with phenyl, pyridonyl, pyridinyl, pyrimidinyl, or pyrazinyl, all of which may optionally be substituted with one or more of methyl.

E11. A compound according to embodiment 10, wherein R3 is methyl substituted with phenyl, pyridonyl, pyridinyl, pyrimidinyl, or pyrazinyl, all of which may be substituted with one methyl.

E12. A compound according to embodiment 10, wherein R3 is methyl substituted with phenyl, pyridonyl, pyridinyl, pyrimidinyl, or pyrazinyl, all of which

- 9 037544 are unsubstituted.

E13. A compound according to any one of embodiments 1-9, wherein R3 is ethyl substituted with phenyl, pyridonyl, pyridinyl, pyrimidinyl, or pyrazinyl, all of which may optionally be substituted with one or more methyl.

E14. The compound according to Embodiment 13, wherein R3 is ethyl substituted with phenyl, pyridonyl, pyridinyl, pyrimidinyl, or pyrazinyl, all of which may be substituted with one methyl.

E15. The compound according to Embodiment 13, wherein R3 is ethyl substituted with phenyl, pyridonyl, pyridinyl, pyrimidinyl, or pyrazinyl, all of which are unsubstituted.

E16. A compound according to any one of Embodiments 1-9, wherein R3 is methyl substituted with 5 membered heteroaryl, which is optionally substituted with one or more of methyl.

E17. A compound according to any one of Embodiments 1-9, wherein R3 is ethyl substituted with 5 membered heteroaryl, which is optionally substituted with one or more of methyl.

E18. A compound according to any one of embodiments 16-17, wherein said 5 membered heteroaryl is substituted with one methyl.

E19. A compound according to any one of embodiments 16-17, wherein said 5 membered heteroaryl is unsubstituted.

E20. A compound according to any of embodiments 16-19, wherein said 5 membered heteroaryl is selected from thiazolyl, oxazolyl, isoxazolyl, triazolyl, pyrazolyl, tetrazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, and thiophenyl.

E21. A compound according to any one of Embodiments 1-20, wherein R4 is phenyl, pyridinyl, or pyridonyl, all of which may be optionally substituted once with a substituent selected from the group consisting of halogen, C ₁ -C ₃ α alkyl and C ₁ -C ₃ alkoxy.

E22. A compound according to any one of Embodiments 1-20, wherein R4 is 5-membered heteroaryl, which is optionally substituted with one or more substituents selected from C ₁ -C ₃ α-alkyl and C ₁ -C ₃ fluoro-α-alkyl.

E23. A compound according to embodiment 22 wherein R4 is a 5 membered heteroaryl optionally substituted with one or two methyl groups.

E24. A compound according to any one of Embodiments 22-23, wherein said 5 membered heteroaryl is selected from thiazolyl, oxazolyl, isoxazolyl, triazolyl, pyrazolyl, tetrazolyl, imidazolyl, oxadiazolyl and thiadiazolyl, and thiophenyl.

E25. A compound according to any one of embodiments 1-20, wherein R4 represents a 4-, 5- or 6-membered saturated heterocycle which in all cases can be optionally substituted once with a substituent selected from oxo, C 1-C ₄ alkyl, and C 1 C ₄ fluoroalkyl.

E26. A compound according to any of Embodiments 1-3 and 8-25 of Formula (Ib)

R1

^ NH (lb), where R1 is selected from the group consisting of hydrogen, linear or branched C ₁ -C ₆ alkyl and saturated monocyclic C ₃ -C ₆ cycloalkyl;

R2 is selected from the group consisting of straight or branched _C1-C8 alkyl, monocyclic saturated C ₃ -C ₈ cycloalkyl, oxetanyl, tetrahydrofuranyl and tetrahydropyranyl, all of which one or more times by one or more substituents selected from the group can be optionally substituted consisting of methyl, fluorine, hydroxy, cyano and methoxy;

R3 is methyl substituted with phenyl, pyridonyl or pyridinyl, all of which may optionally be substituted one or more times with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ α alkyl and methoxy; or

R3 is methyl substituted with 5-membered heteroaryl which is optionally substituted with one or more substituents selected from C ₁ -C ₃ α-alkyl and C ₁ -C ₃ fluoro-α-alkyl; or

R3 is ethyl substituted with phenyl, pyridonyl or pyridinyl, all of which may optionally be substituted one or more times with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ α alkyl and methoxy; or

R3 is ethyl substituted with 5-membered heteroaryl which is optionally substituted with one or more substituents selected from C ₁ -C ₃ α-alkyl and C ₁ -C ₃ fluoro-α-alkyl;

R4 is phenyl, pyridinyl or pyridonyl, all of which may optionally be

- 10 037544 substituted one or more times with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkyl and C ₁ -C ₃ alkoxy; or

R4 is 5-membered heteroaryl which is optionally substituted with one or more substituents selected from C ₁ -C ₃ alkyl and C ₁ -C ₃ fluoroalkyl;

and its pharmaceutically acceptable salts.

E27. A compound according to embodiment 1, wherein the compound is selected from the group consisting of

1: 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-A-N-methyl-1,3,4-oxadiazol-2-yl) methyl] pyrazolo [4,3-0] pyridin-7-amine;

2: 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-TU - [(5-methylthiazol-2-yl) methyl] pyrazolo [4.3-6] pyridin-7-amine;

3: 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-TU - [(5-methylisoxazol-3-yl) methyl] pyrazolo [4.3-6] pyridin-7-amine;

4: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TV- [(2-methyloxazol-5 - yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine ;

5: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TV- [(2-methyltriazol-4-yl) methyl] pyrazolo [4,3-T>] pyridin-7-amine ;

6: 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-L - [(1-methyltriazol-4-yl) methyl] pyrazolo [4,3-T>] pyridin-7-amine ;

7: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TU- (1 // - pyrazol-4-ylmethyl) pyrazolo [4,3-Z>] pyridin-7-amine;

8: 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-TU - [(2-methyltetrazol-5-yl) methyl] pyrazolo [4,3-T>] pyridin-7-amine ;

9: 5 - (2-ethoxypyr idin-3-yl) -1 -isopropyl-3-methyl-A - ((1-methyl-177-pyrazole-

4-yl) methyl) -1 // - pyrazolo [4,3-T>] pyridin-7-amine;

10: 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-A - [(3-methylisoxazol-5-yl) methyl] pyrazolo [4,3-T>] pyridin-7-amine ;

11: 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-A - [(2-methylthiazol-4-yl) methyl] pyrazolo [4,3-T>] pyridin-7-amine ;

12: 1 -cyclopropyl-5- (2-ethoxy-3-pyridyl) -3 -methyl-A - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-T>] pyridin-7-amine ;

13: 5- (2-ethoxy-3-pyridyl) -A - [(1-methylpyrazol-4-yl) methyl] -1-propylpyrazolo [4,3-T>] pyridin-7-amine;

14: 5 - (2-ethoxypyr idin-3-yl) -L - ((1 -methyl- 1 // - pyrazol-4-yl) methyl) -1 - (oxetan-3-yl) -1 // - pyrazolo [4,3-T>] pyridin-7-amine;

15: 5 - (2-ethoxypyr idin-3-yl) -1 -methyl-A- (1 - (1 -methyl- 1 // - pyrazol-4-yl) ethyl) -

1 // - pyrazolo [4,3-b} pyridin-7-amine;

16: 5 - (2-ethoxypyr idin-3-yl) -1-methyl-A - ((1-methyl-17 / -pyrazol-4-yl) methyl) -

1 // - pyrazolo [4,3-b} pyridin-7-amine;

17: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(1-methyl imidazol-2-yl) methyl] pyrazolo [4,3-T>] pyridin-7-amine;

18: 5 - (2-ethoxypyr idin-3-yl) -1 -isopropyl-A - ((1 -methyl- 1 // - pyrazol-5 - yl) methyl) - 1 // - pyrazolo [4,3 - B} pyrid-in-7-amine;

19: 5 - (2-ethoxypyr idin-3-yl) -1 -isopropyl-A - ((1 -methyl- 1 // - pyrazol-3 - yl) methyl) - 1 // - pyrazolo [4,3 - B} pyrid-in-7-amine;

- 11 037544

20: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl - # - (thiazol-2-ylmethyl) pyrazolo [4.3

B] pyridin-7-amine;

21: 5- (2-ethoxy-3-pyrid yl) -1-isopropyl - # - [(1-methylimidazol-4yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine;

22: 5- (2-ethoxy-3-pyridyl) -1 -isopropyl - # - (4-pyridylmethyl) pyrazolo [4,3 -

B] pyridin-7-amine;

23: 5- (2-ethoxy-3-pyridyl) -1 -isopropyl - # - (m-tolylmethyl) pyrazolo [4,3 -

B] pyridin-7-amine;

24: 5- (2-ethoxy-3-pyridyl) -1 -isopropyl - # - (p-tolylmethyl) pyrazolo [4,3 -

B] pyridin-7-amine;

25: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl - # - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine;

26: 5 - (2-ethoxy-3-pyridyl) -1-ethyl - # - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine;

27: 5 - (2-ethoxy-3-pyrid yl) -3 -methyl - # - [(1-methylpyrazol-4-yl) methyl] -1 - (oxetan-3-yl) pyrazolo [4,3- / >] pyridin-7-amine;

28: 5 - (2-ethoxy-3-pyridyl) -1,3-dimethyl - # - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine;

29: 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl - # - [(4-methylthiazol-2-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine ;

0: 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl - # - [(3-methyl-1,2,4oxadiazol-5-yl) methyl] pyrazolo [4,3 - /> ] pyridin-7-amine;

31: 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl - # - [(1-methyl-1,2,4-triazole ·

-yl) methyl] pyrazolo [4,3-b \ pyridin-7-amine;

32: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl - # - [(2-methylthiazol-5 - yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine ;

33: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl - # - [(5-methyl-1,3,4-thiadiazol-2-yl) methyl] pyrazolo [4,3- />] pyridin-7-amine;

34: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl - # - [(5-methyl-3-thienyl) methyl] pyrazolo [4,3-b \ pyrid in-7-amine ;

5: 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl - # - [(4-methyl-2-thienyl) methyl] pyrazolo [4,3-b \ pyrid in-7-amine ;

- 12 037544

6: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TV- [(5-methyl-2-thienyl) methyl] pyrazolo [4,3-A] pyrid-yn-7-amine;

37: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TV- [(2-methyloxazol-4-yl) methyl] pyrazolo [4,3-A] pyridin-7-amine;

38: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-A - [(5-methyl-oxazol-2-yl) methyl] pyrazolo [4,3-Z>] pyridine-7-amine ;

39: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-A- (I / 7-p irazol-3-ylmethyl) pyrazolo [4,3-A] pyridin-7-amine;

40: 5 - (2-ethoxy-3-pyrid yl) -A- (1 // - imidazol-4-ylmethyl) -1 -isopropyl-3-methylpyrazolo [4,3-A] pyridin-7-amine;

41: A-benzyl-5- (2-ethoxy-3-pyridyl) -1-isopropylpyrazolo [4,3-A] pyridin-7-amine;

42: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(3-methylisoxazol-5-yl) methyl] pyrazolo [4,3-A] pyridin-7-amine;

43: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(5-methyl-1,2,4-oxadiazol-3 - yl) methyl] pyrazolo [4,3-A] pyridine- 7-amine;

44: TV- [(1,5-d-immethylpyrazol-3-yl) methyl] -5 - (2-ethoxy-3-pyridyl) -1 - isopropylpyrazolo [4,3 - A] pyridin-7-amine;

45: 3 - (1-isopropyl-3-methyl-7 - (((1-methyl-1 // - pyrazol-4-yl) methyl) amino) - \ H-pyrazolo [4,3 -A] pyridine -5-yl) -1-methylpyridin-2 (1D) -one;

46: 5 - (2-ethoxypyr idin-3-yl) -1 -isopropyl-3 - methyl-L - ((2-methyl- \ H-imid azol-4-yl) methyl) - 1 // - pyrazolo [ 4,3-A] pyridin-7-amine;

47: 5 - (2-ethoxypyr idin-3-yl) -1 -isopropyl-3 - methyl-L - ((5 -methyl- 1 // - pyrazole-

-yl) methyl) - 1 // - pyrazolo [4,3 -A] pyridin-7-amine;

48: 5 - (2-ethoxypyr idin-3-yl) -1 -ethyl-3 - methyl-A - ((1 -methyl- 1 // - pyrazol-4-yl) methyl) - 1 // - pyrazolo [ 4,3-A] pyrid-yn-7-amine;

49: 3 - (1-isopropyl-3-methyl-7 - (((1-methyl-1 // - pyrazol-4-yl) methyl) amino) - \ H-pyrazolo [4,3 -A] pyridine -5-yl) -1-methylpyridin-2 (1D) -one;

50: 5 - (2-ethoxypyr idin-3-yl) -1 -isopropyl-3-methyl-TA - ((4-methyloxazol-2-yl) methyl) - 1 // - pyrazolo [4,3 -A] pyrid in-7-amine;

51: TV - ((1,2-dimethyl-1 // - imidazol-4-yl) methyl) -5 - (2-ethoxypyr idin-3-yl) -1 - isopropyl-3-methyl-1 // - pyrazolo [4,3-A] pyrid-yn-7-amine;

- 13 037544

52: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TV- [(5-methyl-1,2,4-oxadiazol-3-yl) methyl] pyrazolo [4,3- />] pyridin-7-amine;

53: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-L- (1,2,4-oxad iazol-3-ylmethyl) pyrazolo [4,3-A] pyridine-7- amine;

54: N- [(1,5-d-immethylpyrazol-3-yl) methyl] -5 - (2-ethoxy-3-pyridyl) -1 - isopropyl-3-methylpyrazolo [4,3 - />] pyridine-7 -amine,

55: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-A - [(5-methyl-177-1,2,4-triazol-3-yl) methyl] pyrazolo [4, 3 - />] pyridin-7-amine;

56: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(1-methyl-1,2,4-triazol-3 - yl) methyl] pyrazolo [4,3 -A] pyridine- 7-amine;

57: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-77- (177-pyrazol-3-ylmethyl) pyrazolo [4,3-A] pyridin-7-amine;

58: 5 - (2-ethoxypyr idin-3-yl) -1 -isopropyl-3 - methyl-A - ((1-methyl-1H-imidazol-4-yl) methyl) -177-pyrazolo [4,3- />] pyridin-7-amine-2,2,2-trifluoroacetate;

59: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-ACh 1,3,4-oxad iazol-2-ylmethyl) pyrazolo [4,3-A] pyridin-7-amine;

60: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TU - [(1-methylpyrazol-3-yl) methyl] pyrazolo [4,3-A] pyridin-7-amine;

61: 5- (1,3-dimethylpyrazol-4-yl) -1 -isopropyl-3-methyl-AD! 1-methylpyrazol-4 * yl) methyl] pyrazolo [4,3-A] pyridin-7-amine;

62: 1 -isopropyl-5 - (2-methoxy-3-pyridyl) -3-methyl-AD! 1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-A] pyridin-7-amine;

63: 1-isopropyl-5 - (2-methoxyphenyl) -3-methyl-TV- [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-A] pyridin-7-amine;

64: 1-isopropyl-3-methyl-L ^d - [(1-methylpyrazol-4-yl) methyl] -5-phenylpyrazolo [4,3-A] pyridin-7-amine;

65: 1-isopropyl-3-methyl-T \ / - [(1-methylpyrazol-4-yl) methyl] -5- (2-methyl-3-thienyl) pyrazolo [4,3-A] pyrid in-7 -amine;

66: 5- (1,5-dimethylpyrazol-4-yl) -1 -isopropyl-3-methyl-AD! 1-methylpyrazol-4 * yl) methyl] pyrazolo [4,3-A] pyridin-7-amine;

67: 5 - (2-ethoxy-3-pyrid yl) -3-methyl-1 - [1-methylpropyl] -TV - [(1-methylpyrazole-

3-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine, enantiomer 2;

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68: 3-methyl-1 - [1-methylpropyl] -TV- [(2-methyltetrazol-5-yl) methyl] -5 - (2-propoxy-3-pyridyl) pyrazolo [4,3-L \ pyridine- 7-amine, enantiomer 2;

69: 5 - (2-ethoxy-3-pyridyl) -1 - [1-methylpropyl] -TV- [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine , enantiomer 1;

70: 5 - (2-ethoxy-3-pyridyl) -1 - [1-methylpropyl] -TV- [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine , enantiomer 2;

71: 5- (2-ethoxy-3-pyrid yl) -1 -isopropyl-TV- [(4-methylthiazol-5 - yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine;

72: 5 - [[5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methylpyrazolo [4,3-L \ pyridine-

7-yl] oxymethyl] -2-methyloxazole;

73: 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-TU- (pyrimidin-4-ylmethyl) pyrazolo [4,3-L \ pyridin-7-amine;

74: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TU- (pyrimidin-2-ylmethyl) pyrazolo [4,3-Z>] pyridin-7-amine;

75: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TU - [(4-methylpyrimidin-2-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine ;

76: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TU- (pyrazin-2-ylmethyl) pyrazolo [4,3-b \ pyridin-7-amine;

77: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TV-f [2- (trifluoromethyl) -3 - pyridyl] methyl] pyrazolo [4,3-b \ pyrid in-7 -amine;

8: 4- [[[5 - (2-ethoxy-3-pyridyl) -1-isopropyl-3-methylpyrazolo [4,3 -

B] pyridin-7-yl] amino] methyl] -1-methylpyridin-2-one;

79: 5 - (2- (ethylamino) pyridin-3-yl) -1 -isopropyl-3 - methyl-L - ((1 -methyl- \ H-pyrazol-4-yl) methyl) - 1 // - pyrazolo [4,3-b \ pyridin-7-amine;

81: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(4-methoxy-2-pyridyl) methyl] -3-methylpyrazolo [4.3 - />] pyridin-7-amine;

82: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(6-methoxypyrazin-2-yl) methyl] -

-methylpyrazolo [4,3-b} pyridin-7-amine;

83: 5- (2-ethoxy-3-pyridyl) -TU - [(5-fluoropyrimidin-2-yl) methyl] -1-isopropyl-

-methylpyrazolo [4,3-b \ pyridin-7-amine;

84: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TU - [(2-methyl-3-pyrid yl) methyl] pyrazolo [4,3-b} pyrid yn-7- amine;

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5: 5 - (2-ethoxy-3-pyridyl) -? / - [(2-fluoro-3-pyridyl) methyl] -1 -isopropyl-3 methylpyrazolo [4,3 - />] pyridin-7-amine;

86: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl -? / - [(2-methoxy-3-pyridyl) methyl] -3 methylpyrazolo [4,3 - />] pyridin-7-amine;

87: 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl -? / - [(6-methyl-3 pyrid yl) methyl] pyrazolo [4,3-b \ pyrid in-7 -amine;

88: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl -? / - [(2-methoxyphenyl) methyl] -3-methylpyrazolo [4,3 - />] pyridin-7-amine;

89: 5 - (2-ethoxy-3-pyrid yl) -? / - [(2-fluorophenyl) methyl] -1 -isopropyl-3-methylpyrazolo [4,3 - />] pyridin-7-amine;

90: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl -? / - [[2- (trifluoromethyl) phenyl] methyl] pyrazolo [4,3 - />] pyridin-7-amine ;

91: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl -? / - [(3-methoxypyrazin-2-yl) methyl] -

-methylpyrazolo [4,3-b \ pyridin-7-amine;

92: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl -? / - [(4-methoxy-3-pyridyl) methyl] -3 - methylpyrazolo [4,3 - />] pyridin-7-amine ;

93: 1-isopropyl-3-methyl -? / - [(2-methyltetrazol-5-yl) methyl] -5- (2-propoxy-3-pyrid yl) pyrazolo [4,3-b \ pyridine-7- amine;

94: 1-isopropyl-3-methyl -? / - [(1-methylpyrazol-4-yl) methyl] -5 - (2-propoxy-3-pyrid yl) pyrazolo [4,3-b \ pyridine-7- amine;

95: 1-isopropyl-5 - (2-methoxy-3-pyridyl) -? / - [(2-methoxy-3-pyridyl) methyl] -3 methylpyrazolo [4,3 - />] pyridin-7-amine;

96: 1-isopropyl-5 - (2-methoxy-3-pyridyl) -? / - [(6-methoxy-3-pyridyl) methyl] -3 methylpyrazolo [4,3 - />] pyridin-7-amine;

97: 5 - (2-isopropoxy-3-pyridyl) -1 -isopropyl-3-methyl -? / - [(1 -methylpyrazole-

4-yl) methyl] pyrazolo [4,3-b \ pyridin-7-amine;

98: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 -methyl -? / - (1 Η-1,2,4-triazol-3-ylmethyl) pyrazolo [4,3-b \ pyridine -7-amine;

99: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl -? / - (2? / - tetrazol-5-ylmethyl) pyrazolo [4,3-b \ pyridin-7-amine;

100: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl -? / - (2-pyridylmethyl) pyrazolo [4,3 - />] pyridin-7-amine;

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101: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TV- [(6-methyl-2-pyrid yl) methyl] pyrazolo [4,3-b} pyrid in-7- amine;

102: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(6-methoxy-2-pyridyl) methyl] -3-methylpyrazolo [4.3 - />] pyridin-7-amine;

103: 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-TU - [(2-methyl-4-pyrid yl) methyl] pyrazolo [4,3 -A] pyrid in-7- amine;

104: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(2-methoxy-4-pyridyl) methyl] -3-methylpyrazolo [4.3 - />] pyridin-7-amine;

105: 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TU - [(2-methylpyrimidin-4-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine ;

106: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(5-methoxy-3-pyridyl) methyl] -3-methylpyrazolo [4.3 - />] pyridin-7-amine;

107: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TV-f [6- (trifluoromethyl) -2-pyrid yl] methyl] pyrazolo [4,3-A] pyridin- 7-amine;

108: 3 - [[[5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methylpyrazolo [4.3 b} pyridin-7-yl] amino] methyl] -1-methylpyridin-2-one ;

109: 5 - (2-ethoxy-3-pyrid yl) -TU - [(1-ethylpyrazol-4-yl) methyl] -1 -isopropyl-3 - methylpyrazolo [4,3 - />] pyridin-7-amine ;

110: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TU - [(1-propylpyrazol-4-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine ;

111: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(6-methoxy-3-pyridyl) methyl] -3-methylpyrazolo [4.3 - />] pyridin-7-amine;

112: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(5-methoxy-2-pyridyl) methyl] -3-methylpyrazolo [4.3 - />] pyridin-7-amine;

113: 5- (2-ethoxy-3-pyridyl) -3-methyl-TV - [(2-methylthiazol-4-yl) methyl] -1- (oxetan-3-yl) pyrazolo [4,3- / >] pyridin-7-amine;

114: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(5-methoxypyrazin-2-yl) methyl] -

-methylpyrazolo [4,3-A] pyridin-7-amine;

115: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TU- (3-pyrid ylmethyl) pyrazolo [4,3 - />] pyridin-7-amine;

116: 5 - (2-ethoxy-3-pyrid yl) -TU - [(6-fluoro-3-pyridyl) methyl] -1 -isopropyl-3 - methylpyrazolo [4,3 - />] pyridin-7-amine ;

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117: TV- [[6- (difluoromethyl) -3-pyridyl] methyl] -5 - (2-ethoxy-3-pyridyl) -1 isopropyl-3-methylpyrazolo [4,3 - />] pyridine-7- amine,

118: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(3-methoxy-2-pyridyl) methyl] -3 methylpyrazolo [4.3-0] pyridin-7-amine;

119: 5 - (2-ethoxy-3-pyrid yl) -3-methyl-1 - [1-methylpropyl] -N - (\ H-pyrazol-3 ylmethyl) pyrazolo [4,3 - />] pyridine-7 -amine, enantiomer 1;

120: 5 - (2-ethoxy-3-pyrid yl) -3-methyl-1 - [1-methylpropyl] -N- (17 / -p irazol-3 - ylmethyl) pyrazolo [4,3 - />] pyridine -7-amine, enantiomer 2;

121: 5- (2-ethoxy-3-pyridyl) -3 -methyl-1 - [1 -methylpropyl] -T5 - [(1-methyl-1,2,4-triazol-3-yl) methyl] pyrazolo [ 4.3 - />] pyridin-7-amine, enantiomer 1;

122: 5- (2-ethoxy-3-pyridyl) -3 -methyl-1 - [1-methylpropyl] -T5 - [(1-methyl-1,2,4-triazol-3-yl) methyl] pyrazolo [ 4.3 - />] pyridin-7-amine, enantiomer 2;

123: 5 - (2-ethoxy-3-pyrid yl) -3-methyl-TV- [(5-methyl-1,3,4-oxad iazol-2-yl) methyl] -1 - [1-methylpropyl] pyrazolo [4,3-b \ pyridin-7-amine, enantiomer 1;

124: 5 - (2-ethoxy-3-pyrid yl) -3-methyl-TV- [(5-methyl-1,3,4-oxad iazol-2-yl) methyl] -1 - [1-methylpropyl] pyrazolo [4,3-b \ pyridin-7-amine, enantiomer 2;

125: 5 - (2-ethoxy-3-pyrid yl) -T5 - [(5-methoxy-3-pyridyl) methyl] -3 -methyl-1 - [1-methylpropyl] pyrazolo [4,3 - />] pyridin-7-amine, enantiomer 2;

126: 5 - (2-ethoxy-3-pyridyl) -T5 - [(2-methoxy-4-pyridyl) methyl] -3-methyl-1 - [1-methylpropyl] pyrazolo [4,3 - />] pyridin-7-amine, enantiomer 2;

127: 5 - (2-ethoxy-3-pyrid yl) -3-methyl-1 - [1-methylpropyl] -N- [(2-methyltetrazole

5-yl) methyl] pyrazolo [4,3-th] pyridin-7-amine, enantiomer 2;

128: 5 - (2-ethoxy-3-pyrid yl) -3-methyl-TV- [(5-methyl-1,2,4-oxad iazol-3 - yl) methyl] -1 - [1-methylpropyl] pyrazolo [4,3-b \ pyridin-7-amine, enantiomer 2;

129: 5 - (2-ethoxy-3-pyrid yl) -3-methyl-TV- [(2-methyloxazol-4-yl) methyl] -1 - [1-methylpropyl] pyrazolo [4,3 - />] pyridin-7-amine, enantiomer 2;

130: 5 - (2-ethoxy-3-pyrid yl) -T5- (1 // - imidazol-4-ylmethyl) -3 -methyl-1 - [1 - methylpropyl] pyrazolo [4,3 - />] pyridine -7-amine, enantiomer 2;

131: 5- (2-ethoxy-3-pyridyl) -3-methyl-1- [1-methylpropyl] -T5 - [(5-methyl-1 / 7pyrazol-3-yl) methyl] pyrazolo [4,3- />] pyridin-7-amine, enantiomer 2;

132: 5 - (2-ethoxy-3-pyrid yl) -3-methyl-TV- [(1-methylimidazol-4-yl) methyl] -1 - [1-methylpropyl] pyrazolo [4,3-0] pyridine -7-amine, enantiomer 2;

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3: 5 - (2-ethoxy-3-pyrid yl) -3-methyl-TV- [(2-methyloxazol-5-yl) methyl] -1 - [1-methylpropyl] pyrazolo [4,3 - />] pyridin-7-amine, enantiomer 2;

134: 3-methyl-1 - [1-methylpropyl] -N- [(1-methyl-1,2,4-triazol-3-yl) methyl] -5- (2-propoxy-3-pyridyl) pyrazolo [4, 3 - />] pyridin-7-amine, enantiomer 2;

135: 3-methyl-1 - [1-methylpropyl] -5 - (2-propoxy-3-pyrid yl) -A- (17 / -p irazol-3 ylmethyl) pyrazolo [4,3 - />] pyridine -7-amine, enantiomer 2;

136: 5 - (2-ethoxy-3-pyridyl) -1 - [1-methylpropyl] -N- (17 / -p irazol-3 - ylmethyl) pyrazolo [4,3 - />] pyridin-7-amine, enantiomer 1;

137: 5 - (2-ethoxy-3-pyridyl) -1 - [1-methylpropyl] -N- (17 / -p irazol-3 - ylmethyl) pyrazolo [4,3 - />] pyridin-7-amine, enantiomer 2;

138: 5 - (2-ethoxy-3-pyrid yl) -A ^f - [(5-methyl-1,3,4-oxad iazol-2-yl) methyl] -1 - [1-methylpropyl] pyrazolo [4 , 3 - />] pyridin-7-amine, enantiomer 1;

139: 5 - (2-ethoxy-3-pyrid yl) -A - [(5-methyl-1,3,4-oxad iazol-2-yl) methyl] -1 - [1-methylpropyl] pyrazolo [4, 3 - />] pyridin-7-amine, enantiomer 2;

140: 5 - (2-ethoxy-3-pyridyl) -1 - [1-methylpropyl] -7V - [(1-methyl-1,2,4-triazol-3 - yl) methyl] pyrazolo [4,3- />] pyridin-7-amine, enantiomer 1;

141: 5 - (2-ethoxy-3-pyridyl) -1 - [1-methylpropyl] -7V - [(1-methyl-1,2,4-triazol-3 - yl) methyl] pyrazolo [4,3- />] pyridin-7-amine, enantiomer 2;

142: 1-isopropyl-3-methyl-A - [(1-methylimidazol-4-yl) methyl] -5 - (2-propoxy-3 pyrid yl) pyrazolo [4,3-L \ pyridin-7-amine;

143: 1-isopropyl-3-methyl-5 - (2-propoxy-3-pyridyl) -A- (17 / -pyrazol-3-ylmethyl) pyrazolo [4,3-L \ pyridin-7-amine;

144: 5 - (2-ethoxy-3-pyrid yl) -3 -methyl-1 - [1-methylpropyl] -N - (\ H-1,2,4-triazole-

3-ylmethyl) pyrazolo [4,3 - />] pyridin-7-amine, enantiomer 2;

145: 1-isopropyl-3-methyl-A - [(1-methyl-1,2,4-triazol-3-yl) methyl] -5- (2-propoxy-3-pyridyl) pyrazolo [4,3- />] pyridin-7-amine;

146: 1-isopropyl-3-methyl-5- (2-propoxy-3-pyrid yl) -A '- (1 Η-1,2,4-triazol-3-ylmethyl) pyrazolo [4,3-b \ pyridin-7-amine;

147: 1-isopropyl-3-methyl-7Y - [(1-methylpyrazol-4-yl) methyl] -5-thiazol-2ylpyrazolo [4,3-] pyridin-7-amine;

148: 1-isopropyl-3 - methyl-A - [(1-methylpyrazol-4-yl) methyl] -5- (5-methylthiazole-

2-yl) pyrazolo [4,3 - />] pyridin-7-amine;

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149: 1-isopropyl-3-methyl-TV- [(1-methylpyrazol-4-yl) methyl] -5- (4-methylthiazole-

2-yl) pyrazolo [4,3 - />] pyridin-7-amine;

150: 3 - [1-isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3 - />] pyridin-5-yl] -5-methyloxazolidin-2-one ;

151: 3 - [1 -isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3 - />] pyridin-5-yl] oxazolidin-2-one;

152: 1 - [1 -isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4.3 - />] pyridin-5-yl] azetidin-2-one;

153: 1-tert-butyl-3 - [1 -isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3 - />] pyridin-5-yl] imidazolidine- 2-she;

154: 1 - [1 -isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3 - />] pyridin-5-yl] pyrrolidin-2-one;

155: 3 - [1-isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3 - />] pyridin-5-yl] -4-methyloxazolidin-2-one ;

156: 4-ethyl-3 - [1-isopropyl-3-methyl-7 - [(1-methylpyrazol-4yl) methylamino] pyrazolo [4,3 - />] pyridin-5-yl] oxazolidin-2-one;

157: TV- [[5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methylpyrazolo [4,3-L \ pyridin7-yl] methyl] -5-methoxypyridine-3-amine;

158: TV- [[5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methylpyrazolo [4,3-L \ pyridin7-yl] methyl] -1-methyl-1,2,4-triazole - 3 - amine;

159: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-7- [2- (5-methoxy-3-pyridyl) ethyl] -3-methylpyrazolo [4,3-T>] pyridine;

160: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-7 - [2- (1-methyl-1,2,4-triazole

-yl) ethyl] pyrazolo [4,3-b \ pyridine;

161: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TV- [(2-methyl-1,2,4-triazole-

-yl) methyl] pyrazolo [4,3-b \ pyridin-7-amine;

162: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TV- [(4-methyl-1,2,4-triazole-

-yl) methyl] pyrazolo [4,3-b \ pyridin-7-amine;

163: 5 - (2-ethoxy-3-pyrid yl) -3-methyl-TV- [(1-methyl-1,2,4-triazol-3-yl) methyl] -1 - (oxetan-3-yl ) pyrazolo [4,3 - />] pyridin-7-amine;

164: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylsulfanyl] pyrazolo [4.3 - />] pyridine;

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165: # - [[1 - (difluoromethyl) pyrazol-4-yl] methyl] -5- (2-ethoxy-3-pyridyl) -1 isopropyl-3-methylpyrazolo [4,3 - />] pyridine-7- amine,

166: 5 - (2-ethoxy-3-pyrid yl) - # - [[5 - (fluoromethyl) isoxazol-3-yl] methyl] -1 - isopropyl-3-methylpyrazolo [4,3 - />] pyridine- 7-amine;

167: 5 - (2-ethoxy-3-pyrid yl) - # - [[3 - (fluoromethyl) isoxazol-5-yl] methyl] -1 - isopropyl-3-methylpyrazolo [4,3 - />] pyridine- 7-amine;

168: 1-isopropyl-3-methyl-TV- [(1-methylpyrazol-4-yl) methyl] -5-oxazol-2-ylpyrazolo [4,3-L \ pyridin-7-amine;

169: 1-isopropyl-3-methyl-TV- [(1-methylpyrazol-4-yl) methyl] -5 - (3-methyltriazole

4-yl) pyrazolo [4.3-7>] pyrid-yn-7-amine;

170: 1 -isopropyl-5 - (2-methoxy-3-pyridyl) -3 -methyl-TV- [[2- (trifluoromethyl) -3-pyridyl] methyl] pyrazolo [4,3-b \ pyridyl in-7 -amine;

171: 3- [1-isopropyl-7 - [(2-methoxy-3-pyridyl) methylamino] -3-methylpyrazolo [4,3 - />] pyridin-5-yl] -1 // - pyridin-2- she is;

172: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(3-methoxy-4-pyridyl) methyl] -3-methylpyrazolo [4.3 - />] pyridin-7-amine;

173: 1-isopropyl-5 - (2-methoxy-3-pyridyl) -3-methyl-TU - [(2-methylthiazol-5 - yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine ;

174: 5 - (2-cyclopropoxypyridin-3-yl) -1 -isopropyl-TU - ((2-methoxypyridin-3 - yl) methyl) -3 -methyl- 1 # -pyrazolo [4,3 -7>] pyridin-7-amine;

175: 1-isopropyl-TU - ((2-methoxypyridin-3-yl) methyl) -3 -methyl-5 - (1 -methyl- \ H-pyrazol-5-yl) -1 # -pyrazolo [4,3 - />] pyridin-7-amine;

176: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(5-methoxypyrimidin-2-yl) methyl] -3-methylpyrazolo [4.3 - />] pyridin-7-amine;

177: 3 - [1-isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3 - />] pyridin-5-yl] -1 # -pyridin-2- she is;

178: TV- [[2- (difluoromethyl) -3-pyridyl] methyl] -5 - (2-ethoxy-3-pyridyl) -1 isopropyl-3-methylpyrazolo [4,3 - />] pyridin-7-amine ;

179: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(6-methoxypyrimidin-4-yl) methyl] -3-methylpyrazolo [4.3 - />] pyridin-7-amine;

180: 5 - (2- (ethoxy-1,1 -d2) nHp idin-3-yl) -1 -isopropyl-TU - ((2-methoxypyrid in-3 - yl) methyl) -3 -methyl- 1 # -pyrazolo [4,3-T>] pyridin-7-amine;

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181: 5 - (2- (ethoxy-05) pyridin-3-yl) -1 -isopropyl -? / - ((2-methoxypyridin-3 yl) methyl) -3 -methyl- 1 // - pyrazolo [ 4,3 th] pyridin-7-amine;

182: 5- (2- (ethoxy-2,2,2-0h) pyridin-3-yl) -1-isopropyl -? / - ((2-methoxypyridin3-yl) methyl) -3 -methyl- 1 // -pyrazolo [4,3-b \ pyridin-7-amine;

183: 1 -isopropyl -? / - ((2-methoxypyridin-3-yl) methyl) -3 -methyl-5- (2 (trifluoromethyl) pyridin-3-yl) -1 // - pyrazolo [4,3- />] pyridin-7-amine;

184: 3 - (difluoro methyl) -5 - (2-ethoxypyr idin-3-yl) -1 -isopropyl -? / - ((1 -methyl- \ H-pyrazol-4-yl) methyl) - 1 // -pyrazolo [4,3-b \ pyridin-7-amine;

185: 1-isopropyl-3-methyl -? / - ((1 -methyl- 1 // - pyrazol-4-yl) methyl) -5- (III- 1,2,4-triazol- 1 -yl) - 1 // - pyrazolo [4,3th] pyridin-7-amine;

186: 3 - [1-isopropyl-3-methyl-7 - [(1-methyl-1,2,4-triazol-3 - yl) methylamino] pyrazolo [4,3 - />] pyridin-5-yl] -1 // - pyridin-2-one;

187: 3 - [1 -isopropyl-3-methyl-7- (1 // - pyrazole-3 -ylmethylamino) pyrazolo [4,3 -

B] pyridin-5-yl] -1 // - pyridin-2-one;

188: 5 - [2- (d ifluoromethoxy) -3-pyridyl] -1 -isopropyl -? / - [(2-methoxy-3 - pyrid yl) methyl] -3 -methylpyrazolo [4,3-th] pyridine- 7-amine;

189: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl -? / - [(4-methoxypyrimidin-2-yl) methyl] -3-methylpyrazolo [4,3 - />] pyridin-7-amine ;

190: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl -? / - [(4-methoxypyrimidin-5 - yl) methyl] -3-methylpyrazolo [4,3 - />] pyridin-7-amine ;

191: 5 - (2-ethoxy-3-pyridyl) -? / - [(2-ethoxy-3-pyridyl) methyl] -1 -isopropyl-3 - methylpyrazolo [4,3 - />] pyridine-7- amine;

192: 5 - [2- (dimethylamino) -3-pyridyl] -1 -isopropyl -? / - [(4-methoxyphenyl) methyl] -3-methylpyrazolo [4,3 - />] pyridin-7-amine;

193: 3 - [1 -isopropyl-3-methyl-7- [[2- (trifluoromethyl) -3 - pyridyl] methylamino] pyrazolo [4,3-b \ pyridin-5-yl] -1 // - pyridin -2-she;

194: 1-isopropyl-3-methyl-5- (3-methylisoxazol-4-yl) -? / - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3 - />] pyridine-7- amine;

195: 1-isopropyl-3-methyl-5- (1-methyl- \ H-1,2,4-triazol-5-yl) -? / - ((1-methyl-1H-pyrazol-4-yl) methyl) - 1 // - pyrazolo [4,3-b \ pyridin-7-amine;

196: 1-isopropyl-3-methyl-5 - (2-propoxy-3 - p ir id yl) -A ^f - (17 / -pyrazol-4-ylmethyl) pyrazolo [4,3-b \ pyridine-7- amine;

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197: 5 - (2-ethoxy-3-pyridyl) - # - [(2-methoxy-3-pyridyl) methyl] -3 -methyl-1 (oxetan-3-yl) pyrazolo [4,3 - />] pyridin-7-amine;

198: 5- (2- (ethyl (methyl) amino) pyridin-3-yl) -1 -isopropyl - # - (4methoxybenzyl) -3-methyl-1 # -pyrazolo [4,3 - />] pyridine-7 -amine;

199: 5 - (2-ethoxypyr idin-3-yl) -3 - (fluoromethyl) -1 -isopropyl - # - ((1-methyl-1 # pyrazol-4-yl) methyl) - 1 # -pyrazolo [4 , 3-b \ pyridin-7-amine;

200: 1-isopropyl-3-methyl - # - ((1-methyl- 1 # -pyrazol-4-yl) methyl) -5 - (4-methyloxazol-5-yl) -1 # -pyrazolo [4.3 - />] pyridin-7-amine;

201: 5- [2- (dimethylamino) -3-pyridyl] -1-isopropyl-3-methyl - # - [(1methylpyrazol-4-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine ;

202: 1-isopropyl-3-methyl - # - ((1-methyl- 1 # -pyrazol-4-yl) methyl) -5 - (4-methyloxazol-2-yl) -1 # -pyrazolo [4.3 - />] pyridin-7-amine;

203: 1-isopropyl-3-methyl - # - [(1-methylpyrazol-4-yl) methyl] -5- (4-methyl-1,2,4-triazol-3-yl) pyrazolo [4,3 - B} pyridin-7-amine;

and pharmaceutically acceptable salts of any of these compounds.

E28. A compound according to embodiment 1, wherein the compound is selected from the group consisting of

1: 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl - # - [(5-methyl-1,3,4-oxadiazol-2-yl) methyl] pyrazolo [4,3- d] pyridin-7-amine;

2: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl - # - [(5-methylthiazol-2 - yl) methyl] pyrazolo [4,3-] pyridin-7-amine;

3: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl - # - [(5-methylisoxazol-3-yl) methyl] pyrazolo [4,3-] pyridin-7-amine;

4: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl - # - [(2-methyloxaz ol-5 - yl) methyl] pyrazolo [4,3-b] pyridin-7-amine ;

5: 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl - # - [(2-methyltriazol-4-yl) methyl] pyrazolo [4,3-] pyridin-7-amine;

6: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl - # - [(1-methyltriazol-4-yl) methyl] pyrazolo [4,3-ό] pyridin-7-amine;

7: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl - # - (1 # -pyrazol-4-ylmethyl) pyrazolo [4,3-] pyridin-7-amine;

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8: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TV- [(2-methyltetrazol-5 yl) methyl] pyrazolo [4,3-A] pyridin-7-amine;

9: 5 - (2-ethoxypyr idin-3-yl) -1 -isopropyl-3 - methyl-A - ((1 -methyl- \ H-pyrazol4-yl) methyl) -1 // - pyrazolo [4,3 -A] pyridin-7-amine;

10: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TV- [(3-methylisoxazol-5 yl) methyl] pyrazolo [4.3 - />] pyridin-7-amine;

11: 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-A - [(2-methylthiazol-4yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine;

12: 1 -cyclopropyl-5 - (2-ethoxy-3-pyridyl) -3 -methyl-A - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine ;

13: 5 - (2-ethoxy-3-pyrid yl) -A - [(1-methylpyrazol-4-yl) methyl] -1-propylpyrazolo [4,3-A] pyridin-7-amine;

14: 5 - (2-ethoxypyr idin-3-yl) -A - ((1 -methyl- 1 // - pyrazol-4-yl) methyl) -1 - (oxetan-3-yl) -1 // - pyrazolo [4.3-0] pyridin-7-amine;

15: 5 - (2-ethoxypyr idin-3-yl) -1 -methyl-A- (1 - (1 -methyl- 1 // - pyrazol-4-yl) ethyl) -

1 // - pyrazolo [4,3-A] pyridin-7-amine (racemic);

a: (R) -5 - (2-ethoxypyrid in-3 -yl) -1 -methyl-A- (1 - (1-methyl-1 H-pyrazol-4-yl) ethyl) -1 H-pyrazolo [4,3-b] pyridin-7-amine;

15b: (S) -5 - (2-ethoxypyr idin-3-yl) -1 - methyl-A- (1 - (1-methyl-1 H-pyrazol-4yl) ethyl) -1 H-pyrazolo [4, 3-b] pyridin-7-amine;

16: 5 - (2-ethoxypyr idin-3-yl) -1 -methyl-TA - ((1 -methyl- 1 // - pyrazol-4-yl) methyl) -

1 // - pyrazolo [4,3-A] pyridin-7-amine;

17: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(1-methylimidazol-2-yl) methyl] pyrazolo [4.3 - />] pyridin-7-amine;

18: 5 - (2-ethoxypyr idin-3-yl) -1 -isopropyl-A - ((1 -methyl- 1 // - pyrazol-5 - yl) methyl) - 1 // - pyrazolo [4,3 - A] pyrid in-7-amine;

19: 5 - (2-ethoxypyr idin-3-yl) -1 -isoprop yl-A '- ((1 -methyl- 1 // - pyrazol-3 - yl) methyl) - 1 // - pyrazolo [4, 3 -A] pyrid-yn-7-amine;

20: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-A- (thiazol-2-ylmethyl) pyrazolo [4,3 -

A] pyridin-7-amine;

21: 5- (2-ethoxy-3-pyrid yl) -1 -isopropyl-TV- [(1-methylimidazol-4-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine;

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22: 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-L- (4-pyrid yl methyl) pyrazolo [4.3 L] pyridin-7-amine;

23: 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-L- (m-tol yl methyl) pyrazolo [4.3 L] pyridin-7-amine;

24: 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-L- (p-tol yl methyl) pyrazolo [4,3 -

B] pyridin-7-amine;

25: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine;

26: 5 - (2-ethoxy-3-pyridyl) -1-ethyl-TV- [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine;

27: 5 - (2-ethoxy-3-pyrid yl) -3-methyl-TV- [(1-methylpyrazol-4-yl) methyl] -1 - (oxetan-3-yl) pyrazolo [4,3- / >] pyridin-7-amine;

28: 5 - (2-ethoxy-3-pyridyl) -1,3-d-imethyl-TV- [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine;

29: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-T5 - [(4-methylthiazol-2-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine ;

0: 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-T5 - [(3-methyl-1,2,4oxadiazol-5-yl) methyl] pyrazolo [4,3 - /> ] pyridin-7-amine;

31: 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-T5 - [(1-methyl-1,2,4-triazol · 3-yl) methyl] pyrazolo [4,3- B \ pyrid in-7-amine;

32: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-T5 - [(2-methylthiazol-5 - yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine ;

33: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-T5 - [(5-methyl-1,3,4-thiadiazol-2-yl) methyl] pyrazolo [4,3- />] pyridin-7-amine;

34: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-T5 - [(5-methyl-3 - thienyl) methyl] pyrazolo [4,3-L \ pyrid in-7-amine ;

35: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-T5 - [(4-methyl-2-thienyl) methyl] pyrazolo [4,3-L \ pyrid in-7-amine ;

36: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-T5 - [(5-methyl-2-thienyl) methyl] pyrazolo [4,3-L \ pyrid in-7-amine ;

7: 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-T5 - [(2-methyloxazol-4-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine ;

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8: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TV- [(5-methyloxazol-2-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine ;

39: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-L- (I // - pirazol-3-ylmethyl) pyrazolo [4,3-A] pyridin-7-amine;

40: 5 - (2-ethoxy-3-pyrid yl) -L- (I // - and mid azol-4-ylmethyl) -1 -isopropyl-3 - methylpyrazolo [4,3 - />] pyridine-7 -amine;

41: TC-benzyl-5- (2-ethoxy-3-pyridyl) -1-isopropylpyrazolo [4.3 - />] pyridin-7-amine;

42: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(3-methylisoxazol-5 - yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine;

43: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(5-methyl-1,2,4-oxadiazol-3 - yl) methyl] pyrazolo [4,3 - />] pyridine -7-amine;

44: TV- [(1,5-d-immethylpyrazol-3-yl) methyl] -5 - (2-ethoxy-3-pyridyl) -1 - isopropylpyrazolo [4,3 - A] pyridin-7-amine;

45: 3 - (1-isopropyl-3-methyl-7 - (((1-methyl-1 // - pyrazol-4-yl) methyl) amino) - \ H-pyrazolo [4,3 -A] pyridine -5-yl) -1-methylpyridin-2 (1D) -one;

46: 5 - (2-ethoxypyr idin-3-yl) -1 -isopropyl-3 - methyl-L - ((2-methyl- \ H-imid azol-4-yl) methyl) - 1 // - pyrazolo [ 4,3-A] pyridin-7-amine;

47: 5 - (2-ethoxypyr idin-3-yl) -1 -isopropyl-3 - methyl-L - ((5 -methyl- 1 // - pyrazole-

-yl) methyl) - 1 // - pyrazolo [4,3 -T>] pyridin-7-amine;

48: 5 - (2-ethoxypyr idin-3-yl) -1-ethyl-3 - methyl-A - ((1 -methyl- 1 // - pyrazol-4-yl) methyl) - 1 / Lpyrazolo [4, 3 -A] pyrid-yn-7-amine;

49: 3 - (1-isopropyl-3-methyl-7 - (((1-methyl-1 // - pyrazol-4-yl) methyl) amino) - \ H-pyrazolo [4,3 -A] pyridine -5-yl) -1-methylpyridin-2 (1D) -one;

50: 5 - (2-ethoxypyr-idin-3-yl) -1 -isopropyl-3-methyl-TU - ((4-methyloxazol-2-yl) methyl) - 1 / Lpyrazolo [4,3-A] pyridine -7-amine;

51: TU - ((1,2-dimethyl-1 // - imidazol-4-yl) methyl) -5- (2-ethoxypyridin-3-yl) -1isopropyl-3 -methyl- 1 // - pyrazolo [4 , 3 -A] pyrid-yn-7-amine;

52: 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TU - [(5-methyl-1,2,4-oxadiazol-3-yl) methyl] pyrazolo [4,3- />] pyridin-7-amine;

53: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TU- (1,2,4-oxadiazol-3-ylmethyl) pyrazolo [4,3-A] pyridin-7-amine ;

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54: TV - [(1,5-d-immethylpyrazol-3-yl) methyl] -5 - (2-ethoxy-3-pyridyl) -1 - isopropyl-3-methylpyrazolo [4,3 - />] pyridine-7 -amine,

55: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TV- [(5-methyl-177-1,2,4-triazol-3-yl) methyl] pyrazolo [4, 3 - />] pyridin-7-amine;

56: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(1-methyl-1,2,4-triazol-3 - yl) methyl] pyrazolo [4,3 - />] pyridine -7-amine;

57: 5 - (2-ethoxy-3-pyridyl) -1-isopropyl-A- (177-pyrazol-3-ylmethyl) pyrazolo [4,3-L \ pyridin-7-amine;

58: 5 - (2-ethoxypyr idin-3-yl) -1 -isopropyl-3 - methyl-A - ((1 -methyl- \ H-imidazol-4-yl) methyl) -1 // - pyrazolo [4 , 3 - />] pyridin-7-amine-2,2,2-trifluoroacetate;

59: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-ACh 1,3,4-oxadiazol-2-ylmethyl) pyrazolo [4,3-L \ pyridin-7-amine;

60: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TU - [(1-methylpyrazol-3 - yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine ;

61: 5- (1,3-dimethylpyrazol-4-yl) -1 -isopropyl-3-methyl-TU - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3 - />] pyridine-7 -amine;

62: 1-isopropyl-5 - (2-methoxy-3-pyridyl) -3-methyl-TU - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine ;

63: 1-isopropyl-5 - (2-methoxyphenyl) -3-methyl-TV- [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine;

64: 1-isopropyl-3-methyl-TU - [(1-methylpyrazol-4-yl) methyl] -5-phenylpyrazolo [4,3-L \ pyridin-7-amine;

65: 1-isopropyl-3-methyl-TU - [(1-methylpyrazol-4-yl) methyl] -5- (2-methyl-3-thienyl) pyrazolo [4,3-L \ pyridin-7-amine ;

66: 5- (1,5-dimethylpyrazol-4-yl) -1 -isopropyl-3-methyl-TU - [(1-methylpyrazol-4 · yl) methyl] pyrazolo [4,3 - />] pyridine-7 -amine;

67а: (7 /) - 5 - (2-ethoxy-3-pyridyl) -3 -methyl-1 - [1-methylpropyl] -TV- [(1 methylpyrazol-3-yl) methyl] pyrazolo [4,3- T>] pyridin-7-amine;

67b: (S) -5 - (2-ethoxy-3-pyridyl) -3 -methyl-1 - [1-methylpropyl] -TV- [(1 methylpyrazol-3-yl) methyl] pyrazolo [4,3-b ] pyridin-7-amine;

68а: (7 /) - 3-methyl-1- [1-methylpropyl] -7 / - [(2-methyltetrazol-5-yl) methyl] -5- (2propoxy-3-pyridyl) pyrazolo [4,3- T>] pyridin-7-amine;

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68b: (8) -3-methyl-1- [1-methylpropyl] -A - [(2-methyltetrazol-5-yl) methyl] -5- (2propoxy-3-pyridyl) pyrazolo [4,3-b] pyridin-7-amine;

69: (R) -5- (2-ethoxy-3-pyridyl) -1 - [1-methylpropyl] -TV - [(1-methylpyrazole-4yl) methyl] pyrazolo [4,3-b \ pyridine-7- amine or (8) -5- (2-ethoxy-3-pyridyl) -1 - [1 methylpropyl] -TV - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridine-7 -amine;

70: (R) -5- (2-ethoxy-3-pyridyl) -1 - [1-methylpropyl] -TV - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b \ pyridine- 7-amine or (8) -5- (2-ethoxy-3-pyridyl) -1 - [1 methylpropyl] -TV - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridine -7-amine;

71: 5- (2-ethoxy-3-pyrid yl) -1 -isopropyl-TV- [(4-methylthiazol-5 - yl) methyl] pyrazolo [4,3-T>] pyridin-7-amine;

72: 5 - [[5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methylpyrazolo [4,3-L \ pyridine-

7-yl] oxymethyl] -2-methyloxazole;

73: 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-TU- (pyrimidin-4-ylmethyl) pyrazolo [4,3-L \ pyridin-7-amine;

74: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TU- (pyrimidin-2-ylmethyl) pyrazolo [4,3-L \ pyridin-7-amine;

75: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TU - [(4-methylpyrimidin-2-yl) methyl] pyrazolo [4,3-T>] pyridin-7-amine ;

76: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TU- (pyrazin-2-ylmethyl) pyrazolo [4,3-b \ pyridin-7-amine;

77: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TV-f [2- (trifluoromethyl) -3 - pyridyl] methyl] pyrazolo [4,3-b \ pyrid in-7 -amine;

8: 4- [[[5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methylpyrazolo [4,3 -

B] pyridin-7-yl] amino] methyl] -1-methylpyridin-2-one;

79: 5 - (2- (ethylamino) pyridin-3-yl) -1 -isopropyl-3 - methyl-L - ((1 -methyl- \ H-pyrazol-4-yl) methyl) - 1 // - pyrazolo [4,3-b \ pyridin-7-amine;

81: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(4-methoxy-2-pyridyl) methyl] -3-methylpyrazolo [4,3-T>] pyridin-7-amine;

82: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(6-methoxypyrazin-2-yl) methyl] -

-methylpyrazolo [4,3-b} pyridin-7-amine;

83: 5- (2-ethoxy-3-pyridyl) -TU - [(5-fluoropyrimidin-2-yl) methyl] -1-isopropyl-

-methylpyrazolo [4,3-b \ pyridin-7-amine;

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84: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TV- [(2-methyl-3 pyrid yl) methyl] pyrazolo [4,3-A] pyrid in-7-amine ;

85: 5 - (2-ethoxy-3-pyrid yl) -A - [(2-fluoro-3-pyridyl) methyl] -1 -isopropyl-3 methylpyrazolo [4,3 - />] pyridin-7-amine;

86: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(2-methoxy-3-pyridyl) methyl] -3 methylpyrazolo [4,3 - />] pyridin-7-amine;

87: 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TU - [(6-methyl-3 - pyrid yl) methyl] pyrazolo [4,3 -A] pyrid yn-7- amine;

88: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(2-methoxyphenyl) methyl] -3-methylpyrazolo [4.3 - />] pyridin-7-amine;

89: 5 - (2-ethoxy-3-pyrid yl) -TU - [(2-fluorophenyl) methyl] -1 -isopropyl-3-methylpyrazolo [4,3 - />] pyridin-7-amine;

90: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TV-f [2- (trifluoromethyl) phenyl] methyl] pyrazolo [4.3 - />] pyridin-7-amine;

91: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(3-methoxypyrazin-2-yl) methyl] -

-methylpyrazolo [4,3-A] pyridin-7-amine;

92: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(4-methoxy-3-pyridyl) methyl] -3-methylpyrazolo [4.3 - />] pyridin-7-amine;

93: 1-isopropyl-3-methyl-TU - [(2-methyltetrazol-5-yl) methyl] -5- (2-propoxy-3-pyrid yl) pyrazolo [4,3-A] pyridin-7-amine ;

94: 1-isopropyl-3-methyl-A - [(1-methylpyrazol-4-yl) methyl] -5 - (2-propoxy-3-pyrid yl) pyrazolo [4,3-A] pyridin-7-amine ;

95: 1-isopropyl-5 - (2-methoxy-3-pyridyl) -TU- [(2-methoxy-3-pyridyl) methyl] -3 methylpyrazolo [4,3 - />] pyridin-7-amine;

96: 1-isopropyl-5 - (2-methoxy-3-pyridyl) -TU- [(6-methoxy-3-pyridyl) methyl] -3 methylpyrazolo [4,3 - />] pyridin-7-amine;

97: 5 - (2-isopropoxy-3-pyridyl) -1 -isopropyl-3-methyl-TV- [(1-methylpyrazole-

4-yl) methyl] pyrazolo [4,3-A] pyrid-yn-7-amine;

98: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-ACh 1H-1,2,4-triazol-3-ylmethyl) pyrazolo [4,3-A] pyridin-7-amine ;

99: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TU- (2 // - tetrazol-5-ylmethyl) pyrazolo [4,3-A] pyridin-7-amine;

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100: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-L- (2-pyridylmethyl) pyrazolo [4.3 - />] pyridin-7-amine;

101: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TV- [(6-methyl-2-pyrid yl) methyl] pyrazolo [4,3-b \ pyrid in-7-amine;

102: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(6-methoxy-2-pyridyl) methyl] -3 methylpyrazolo [4.3 - />] pyridin-7-amine;

103: 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-TU - [(2-methyl-4pyrid yl) methyl] pyrazolo [4,3-b \ pyridin-7-amine;

104: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(2-methoxy-4-pyridyl) methyl] -3 methylpyrazolo [4.3 - />] pyridin-7-amine;

105: 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TU - [(2-methylpyrimidin-4-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine ;

106: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(5-methoxy-3-pyridyl) methyl] -3 methylpyrazolo [4.3 - />] pyridin-7-amine;

107: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TV-f [6- (trifluoromethyl) -2-pyrid yl] methyl] pyrazolo [4,3-b \ pyridin- 7-amine;

108: 3 - [[[5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methylpyrazolo [4,3 -

B] pyridin-7-yl] amino] methyl] -1-methylpyridin-2-one;

109: 5 - (2-ethoxy-3-pyrid yl) -TU - [(1-ethylpyrazol-4-yl) methyl] -1 -isopropyl-3 - methylpyrazolo [4,3 - />] pyridin-7-amine ;

110: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TU - [(1-propylpyrazol-4-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine ;

111: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(6-methoxy-3-pyridyl) methyl] -3 methylpyrazolo [4.3 - />] pyridin-7-amine;

112: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(5-methoxy-2-pyridyl) methyl] -3 methylpyrazolo [4.3 - />] pyridin-7-amine;

113: 5- (2-ethoxy-3-pyridyl) -3-methyl-TV - [(2-methylthiazol-4-yl) methyl] -1- (oxetan-3-yl) pyrazolo [4,3- / >] pyridin-7-amine;

114: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(5-methoxypyrazin-2-yl) methyl]

-methylpyrazolo [4,3-b \ pyridin-7-amine;

115: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-LCZ-pyrid ylmethyl) pyrazolo [4,3 - />] pyridin-7-amine;

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116: 5 - (2-ethoxy-3-pyridyl) -? / - [(6-fluoro-3-pyridyl) methyl] -1 -isopropyl-3-methylpyrazolo [4,3 - />] pyridin-7-amine ;

117: A- [[6- (difluoromethyl) -3-pyridyl] methyl] -5 - (2-ethoxy-3-pyridyl) -1 isopropyl-3-methylpyrazolo [4,3 - />] pyridine-7- amine,

118: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl -? / - [(3 - methoxy-2-pyridyl) methyl] -3 - methylpyrazolo [4,3 - />] pyridine-7- amine;

119: (R) -5 - (2-ethoxy-3-pyridyl) -3 -methyl-1 - [1-methylpropyl] -N- (177-pyrazol-3 ylmethyl) pyrazolo [4,3-L \ pyridine- 7-amine or (S) -5 - (2-ethoxy-3-pyridyl) -3 -methyl-1 - [1 methylpropyl] -N- (1 H-pyrazol-3-ylmethyl) pyrazolo [4,3-b ] pyridin-7-amine;

120: (R) -5 - (2-ethoxy-3-pyridyl) -3 -methyl-1 - [1-methylpropyl] -N- (I R-p irazol-3 ylmethyl) pyrazolo [4,3-b} pyridin-7-amine or (8) -5 - (2-ethoxy-3-pyridyl) -3 -methyl-1 - [1 methylpropyl] -N- (1 H-pyrazol-3-ylmethyl) pyrazolo [4.3 -B] pyridin-7-amine;

121: (R) -5 - (2-ethoxy-3-pyridyl) -3 -methyl-1 - [1-methylpropyl] -? / - [(1-methyl-1,2,4-triazol-3-yl ) methyl] pyrazolo [4,3 - />] pyridin-7-amine or (8) -5- (2-ethoxy-3-pyridyl) -3methyl-1 - [1-methylpropyl] -? / - [( 1-methyl-1,2,4-triazol-3-yl) methyl] pyrazolo [4.3b] pyridin-7-amine;

122: (R) -5 - (2-ethoxy-3-pyridyl) -3 -methyl-1 - [1-methylpropyl] - # - [(1-methyl-1,2,4-triazol-3-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine or (8) -5- (2-ethoxy-3-pyridyl) -3methyl-1 - [1-methylpropyl] -? / - [(1 -methyl-1,2,4-triazol-3-yl) methyl] pyrazolo [4.3b] pyridin-7-amine;

123: (R) -5 - (2-ethoxy-3-pyridyl) -3 -methyl -? / - [(5-methyl-1,3,4-oxad iazol-2-yl) methyl] -1 - [ 1-methylpropyl] pyrazolo [4,3-b \ pyrid in-7-amine or (8) -5 - (2-ethoxy-3 pyrid yl) -3-methyl -? / - [(5 -methyl-1, Iazol-2-yl) methyl 3,4-oxade] -1 - [1 methylpropyl] pyrazolo [4,3-b] pyridin-7-amine;

124: (R) -5 - (2-ethoxy-3-pyridyl) -3 -methyl -? / - [(5-methyl-1,3,4-oxad iazol-2-yl) methyl] -1 - [ 1-methylpropyl] pyrazolo [4,3-b} pyrid in-7-amine or (8) -5 - (2-ethoxy-3 pyrid yl) -3-methyl -? / - [(5-methyl-1, Iazol-2-yl) methyl 3,4-oxade] -1 - [1 methylpropyl] pyrazolo [4,3-b] pyridin-7-amine;

125а: (7?) - 5- (2-ethoxy-3-pyridyl) -? / - [(5-methoxy-3-pyridyl) methyl] -3-methyl-1 [1-methylpropyl] pyrazolo [4.3 - />] pyridin-7-amine;

125b: (8) -5 - (2-ethoxy-3-pyridyl) -? / - [(5-methoxy-3-pyridyl) methyl] -3 -methyl-1 [1-methylpropyl] pyrazolo [4,3- B] pyridin-7-amine;

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126a: (R) -5 - (2-ethoxy-3 - p ir id yl) - # [(2-methoxy-4-π ir id yl) methyl] -3 -methyl-1 [1-methylpropyl] pyrazolo [ 4,3-b \ pyridin-7-amine;

126b: (S) -5 - (2-ethoxy-3-pyridyl) - # - [(2-methoxy-4-pyridyl) methyl] -3 -methyl-1 [1-methylpropyl] pyrazolo [4,3-b ] pyridin-7-amine;

127а: (R) -5 - (2-ethoxy-3-pyridyl) -3 -methyl-1 - [1-methylpropyl] - # - [(2methyltetrazol-5-yl) methyl] pyrazolo [4,3-b \ pyridin-7-amine;

127b: (8) -5- (2-ethoxy-3-pyridyl) -3-methyl-1 - [1-methylpropyl] -M - [(2methyltetrazol-5-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine;

128a: (R) -5 - (2-ethoxy-3-pyridyl) -3 -methyl - # - [(5-methyl-1,2,4-oxadiazol-3 yl) methyl] -1 - [1-methylpropyl ] pyrazolo [4,3-b \ pyridin-7-amine;

128b: (S) -5- (2-ethoxy-3-pyridyl) -3-methyl - # - [(5-methyl-1,2,4-oxadiazol-Zyl) methyl] -1 - [1-methylpropyl] pyrazolo [4,3-b] pyrid-yn-7-amine;

129а: (R) -5 - (2-ethoxy-3-pyridyl) -3 -methyl - # - [(2-methyloxazol-4-yl) methyl] -1 - [1 methylpropyl] pyrazolo [4,3- / >] pyridin-7-amine;

129b: (8) -5 - (2-ethoxy-3-pyridyl) -3 -methyl - # - [(2-methyloxazol-4-yl) methyl] -1 - [1 methylpropyl] pyrazolo [4,3-b ] pyridin-7-amine;

130а: (R) -5 - (2-ethoxy-3-pyridyl) - # - (1 #-azol-4-ylmethyl) -3-methyl-1 - [1 methylpropyl] pyrazolo [4,3 - /> ] pyridin-7-amine;

130b: (8) -5 - (2-ethoxy-3-pyridyl) - # - (1 H-imidazol-4-ylmethyl) -3 -methyl-1 - [1 methylpropyl] pyrazolo [4,3-b] pyridine -7-amine;

131а: (R) -5 - (2-ethoxy-3-pyridyl) -3 -methyl-1 - [1-methylpropyl] - # - [(5-methyl- \ Npyrazol-3-yl) methyl] pyrazolo [4 , 3-b \ pyrid in-7-amine;

131b: (S) -5- (2-ethoxy-3-pyridyl) -3-methyl-1 - [1-methylpropyl] - # - [(5-methyl-1Hpyrazol-3-yl) methyl] pyrazolo [4, 3-b] pyrid-yn-7-amine;

132а: (R) -5 - (2-ethoxy-3-pyridyl) -3 -methyl - # - [(1-azol-4-yl methylimide) methyl] -1 [1-methylpropyl] pyrazolo [4,3- B \ pyridin-7-amine;

132b: (8) -5 - (2-ethoxy-3-pyridyl) -3 -methyl - # - [(1-methylimidazol-4-yl) methyl] -1 [1-methylpropyl] pyrazolo [4,3-b ] pyridin-7-amine;

133а: (R) -5 - (2-ethoxy-3-pyridyl) -3 -methyl - # - [(2-methyloxazol-5-yl) methyl] -1 - [1 methylpropyl] pyrazolo [4,3- / >] pyridin-7-amine;

133b: (8) -5 - (2-ethoxy-3-pyridyl) -3 -methyl - # - [(2-methyloxazol-5-yl) methyl] -1 - [1 methylpropyl] pyrazolo [4,3-b ] pyridin-7-amine;

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134a: (5) -3-methyl-1 - [1-methylpropyl] -7V - [(1-methyl-1,2,4-triazol-3-yl) methyl] -5 (2-propoxy-3-pyridyl ) pyrazolo [4,3 - />] pyridin-7-amine;

134b: (5) -3-methyl-1 - [1-methylpropyl] -N- [(1-methyl-1,2,4-triazol-3-yl) methyl] -5 (2-propoxy-3-pyridyl ) pyrazolo [4,3-b] pyridin-7-amine;

135a: (R) -3 -methyl-1 - [1-methylpropyl] -5 - (2-propoxy-3-p irid yl) -A- (1H-pyrazol3-ylmethyl) pyrazolo [4,3-b \ pyridin-7-amine;

135b: (5) -3-methyl-1 - [1-methylpropyl] -5- (2-propoxy-3-pyridyl) -M- (1 H-pyrazol3-ylmethyl) pyrazolo [4,3-b] pyridine- 7-amine;

136: (5) -5 - (2-ethoxy-3-pyridyl) -1 - [1-methylpropyl] -N- (IH- and irazol-3 - ylmethyl) pyrazolo [4,3 - />] pyridine- 7-amine or (5) -5- (2-ethoxy-3-pyridyl) -1- [1 methylpropyl] -N- (1 H-pyrazol-3-ylmethyl) pyrazolo [4,3-b] pyridine-7 -amine;

137: (5) -5 - (2-ethoxy-3-pyridyl) -1 - [1 -methylpropyl] -N- (IH- and irazol-3 - ylmethyl) pyrazolo [4,3 - />] pyridine- 7-amine or (5) -5- (2-ethoxy-3-pyridyl) -1- [1 methylpropyl] -N- (1 H-pyrazol-3-ylmethyl) pyrazolo [4,3-b] pyridine-7 -amine;

138: (5) -5 - (2-ethoxy-3-pyridyl) - # - [(5-methyl-1,3,4-oxadiazol-2-yl) methyl] -1 -

[1-methylpropyl] pyrazolo [4,3 - (>] pyridin-7-amine or (5) -5- (2-ethoxy-3-pyridyl) - # - [(5 methyl-1,3,4- oxadiazol-2-yl) methyl] -1- [1-methylpropyl] pyrazolo [4,3-b] pyridine-7amine;

139: (5) -5 - (2-ethoxy-3-pyridyl) - # - [(5-methyl-1,3,4-oxadiazol-2-yl) methyl] -1 -

[1-methylpropyl] pyrazolo [4,3-th] pyridin-7-amine or (5) -5- (2-ethoxy-3-pyridyl) - # - [(5 methyl-1,3,4-oxadiazole -2-yl) methyl] -1- [1-methylpropyl] pyrazolo [4,3-b] pyridine-7amine;

140: (5) -5 - (2-ethoxy-3-pyridyl) -1 - [1-methylpropyl] - # - [(1-methyl-1,2,4-triazol3-yl) methyl] pyrazolo [4, 3 -Z>] pyrid in-7-amine or (5) -5- (2-ethoxy-3-pyridyl) -1 - [1 methylpropyl] - # - [(1-methyl-1,2,4-triazole -3-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine;

141: (5) -5 - (2-ethoxy-3-pyridyl) -1 - [1-methylpropyl] - # - [(1-methyl-1,2,4-triazol3-yl) methyl] pyrazolo [4, 3 -Z>] pyrid in-7-amine or (5) -5- (2-ethoxy-3-pyridyl) -1 - [1 methylpropyl] - # - [(1-methyl-1,2,4-triazole -3-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine;

142: 1-isopropyl-3-methyl-TV- [(1-azol-4-yl methylimide) methyl] -5 - (2-propoxy-3-pyridyl) pyrazolo [4,3-th] pyridin-7-amine ;

143: 1-isopropyl-3-methyl-5 - (2-propoxy-3-pyridyl) - # - (1H-pyrazol-3-ylmethyl) pyrazolo [4,3-b \ pyridin-7-amine;

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144a: (R) -5 - (2-ethoxy-3-pyridyl) -3 -methyl-1 - [1 -methylpropyl] -N- (1 Η-1,2,4triazol-3-ylmethyl) pyrazolo [4, 3-A] pyridin-7-amine;

144b: (S) -5- (2-ethoxy-3-pyridyl) -3-methyl-1 - [1-methylpropyl] -N- (1 Η-1,2,4triazol-3-ylmethyl) pyrazolo [4, 3-b] pyridin-7-amine;

145: 1-isopropyl-3-methyl-TV- [(1-methyl-1,2,4-triazol-3-yl) methyl] -5 - (2-propoxy-3-pyridyl) pyrazolo [4,3 - A] pyridin-7-amine;

146: 1-isopropyl-3-methyl-5 - (2-propoxy-3-pyridyl) -A- (1H-1,2,4-triazol-3-ylmethyl) pyrazolo [4,3-A] pyridine-7 -amine;

147: 1-isopropyl-3-methyl-TV- [(1-methylpyrazol-4-yl) methyl] -5-thiazol-2-ylpyrazolo [4.3 - A] pyridin-7-amine;

148: 1-isopropyl-3-methyl-TV- [(1-methylpyrazol-4-yl) methyl] -5- (5-methylthiazole-

2-yl) pyrazolo [4,3-A] pyridin-7-amine;

149: 1-isopropyl-3 - methyl-A - [(1-methylpyrazol-4-yl) methyl] -5- (4-methylthiazole-

2-yl) pyrazolo [4,3-A] pyridin-7-amine;

150: 3 - [1 -isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3-A] pyridin-5-yl] -5-methyloxazolidin-2-one;

151: 3 - [1 -isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3-A] pyridin-5-yl] oxazolidin-2-one;

152: 1 - [1 -isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3-A] pyridin-5-yl] azetidin-2-one;

153: 1-tert-butyl-3 - [1-isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3-A] pyridin-5-yl] imidazolidin-2 -she is;

154: 1 - [1 -isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3-A] pyridin-5-yl] pyrrolidin-2-one;

155: 3 - [1 -isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3-A] pyridin-5-yl] -4-methyloxazolidin-2-one;

156: 4-ethyl-3 - [1-isopropyl-3-methyl-7 - [(1-methylpyrazol-4yl) methylamino] pyrazolo [4,3-A] pyridin-5-yl] oxazolidin-2-one;

157: TV- [[5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methylpyrazolo [4,3-A] pyridin7-yl] methyl] -5-methoxypyridine-3-amine;

158: TV- [[5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methylpyrazolo [4,3-A] pyridin7-yl] methyl] -1-methyl-1,2,4-triazole - 3 - amine;

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9: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-7- [2- (5-methoxy-3-pyridyl) ethyl] -3 methylpyrazolo [4.3 -7>] pyridine;

160: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-7 - [2- (1-methyl-1,2,4-triazol3-yl) ethyl] pyrazolo [4,3- B \ pyridine;

161: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TV- [(2-methyl-1,2,4-triazole-

-yl) methyl] pyrazolo [4,3-b \ pyridin-7-amine;

162: 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-T5 - [(4-methyl-1,2,4-triazole-

-yl) methyl] pyrazolo [4,3-b \ pyridin-7-amine;

163: 5 - (2-ethoxy-3-pyrid yl) -3-methyl-TV- [(1-methyl-1,2,4-triazol-3-yl) methyl] -1 - (oxetan-3-yl ) pyrazolo [4,3 - />] pyridin-7-amine;

164: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylsulfanyl] pyrazolo [4.3 - />] pyridine;

165: TV- [[1 - (difluoromethyl) pyrazol-4-yl] methyl] -5 - (2-ethoxy-3-pyridyl) -1 isopropyl-3-methylpyrazolo [4,3 - />] pyridine-7 -amine,

166: 5 - (2-ethoxy-3-pyrid yl) -L- [[5 - (fluoro methyl) isoxazol-3-yl] methyl] -1 - isopropyl-3-methylpyrazolo [4,3 - />] pyridine -7-amine;

167: 5 - (2-ethoxy-3-pyrid yl) -L- [[3 - (fluoromethyl) isoxazol-5-yl] methyl] -1 - isopropyl-3-methylpyrazolo [4,3 - />] pyridine- 7-amine;

168: 1-isopropyl-3-methyl-A - [(1-methylpyrazol-4-yl) methyl] -5-oxazol-2-ylpyrazolo [4,3-b \ pyridin-7-amine;

169: 1-isopropyl-3 - methyl-A - [(1-methylpyrazol-4-yl) methyl] -5 - (3-methyltriazole

4-yl) pyrazolo [4,3-b \ pyridin-7-amine;

170: 1 -isopropyl-5 - (2-methoxy-3-pyridyl) -3 -methyl-TV-f [2- (trifluoromethyl) -3 - pyridyl] methyl] pyrazolo [4,3-b \ pyridyl in-7 -amine;

171: 3- [1-isopropyl-7 - [(2-methoxy-3-pyridyl) methylamino] -3methylpyrazolo [4.3 - />] pyridin-5-yl] -1 // - pyridin-2-one;

172: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(3-methoxy-4-pyridyl) methyl] -3-methylpyrazolo [4.3 - />] pyridin-7-amine;

173: 1-isopropyl-5 - (2-methoxy-3-pyridyl) -3 -methyl-T5 - [(2-methylthiazol-5 - yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine ;

174: 5 - (2-cyclopropoxypyridin-3-yl) -1 -isopropyl-TU - ((2-methoxypyridin-3 - yl) methyl) -3 -methyl- 1 // - pyrazolo [4,3 -7> ] pyridin-7-amine;

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175: 1-isopropyl-TU - ((2-methoxypyridin-3-yl) methyl) -3 -methyl-5 - (1 -methyl- \ Npyrazol-5-yl) -1 // - pyrazolo [4,3- />] pyridin-7-amine;

176: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TU - [(5-methoxypyrimidin-2yl) methyl] -3-methylpyrazolo [4,3 - />] pyridin-7-amine;

177: 3 - [1-isopropyl-3-methyl-7 - [(1-methylpyrazol-4yl) methylamino] pyrazolo [4,3 - />] pyridin-5-yl] -1 // - pyridin-2-one ;

178: A- [[2- (d ifluoromethyl) -3-pyridyl] methyl] -5 - (2-ethoxy-3-pyridyl) -1 isopropyl-3-methylpyrazolo [4,3 - />] pyridine-7- amine;

179: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(6-methoxypyrimidin-4-yl) methyl] -3-methylpyrazolo [4.3 - />] pyridin-7-amine;

180: 5 - (2- (ethoxy-1,1 -d2) nnpidin-3-yl) -1 -isopropyl-U - ((2-methoxypyrid in-3 - yl) methyl) -3 -methyl-1 // -pyrazolo [4,3-T>] pyridin-7-amine;

181: 5 - (2- (3TOKCH-ds) nHp idin-3-yl) -1 -isopropyl-TU - ((2-methoxypyridin-3 - yl) methyl) -3 -methyl- 1 // - pyrazolo [ 4,3-T>] pyridin-7-amine;

182: 5- (2- (etoksi-2,2,2-dz) pyridin-3-yl) -l-isopropyl-TV - ((2-metokcipiridin3-yl) methyl) -3 -methyl-1 // - pyrazolo [4,3-A] pyridin-7-amine;

183: 1 -isopropyl-TU - ((2-methoxypyridin-3-yl) methyl) -3 -methyl-5- (2- (trifluoromethyl) pyridin-3-yl) -1 // - pyrazolo [4,3- />] pyridin-7-amine;

184: 3 - (difluoro methyl) -5 - (2-ethoxypyr idin-3-yl) -1 -isopropyl-TU - ((1 -methyl- \ H-pyrazol-4-yl) methyl) - 1 // - pyrazolo [4.3 - A] pyridin-7-amine;

185: 1-isopropyl-3-methyl-A - ((1-methyl-III-pyrazol-4-yl) methyl) -5- (III-1,2,4triazol-1-yl) -1 // - pyrazolo [4,3 - />] pyridin-7-amine;

186: 3 - [1-isopropyl-3-methyl-7 - [(1-methyl-1,2,4-triazol-3 - yl) methylamino] pyrazolo [4,3 - />] pyridin-5-yl] -1 // - pyridin-2-one;

187: 3 - [1 -isopropyl-3-methyl-7- (1 // - pyrazole-3 -ylmethylamino) pyrazolo [4,3 -

Z>] pyridin-5-yl] - 1 // - pyridin-2-one;

188: 5 - [2- (d ifluoromethoxy) -3-pyridyl] -1 -isopropyl-U - [(2-methoxy-3 - pyrid yl) methyl] -3 -methylpyrazolo [4,3 -T>] pyridine- 7-amine;

189: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TU - [(4-methoxypyrimidin-2-yl) methyl] -3-methylpyrazolo [4.3 - />] pyridin-7-amine;

190: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(4-methoxypyrimidin-5 - yl) methyl] -3-methylpyrazolo [4.3 - />] pyridin-7-amine;

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191: 5 - (2-ethoxy-3-pyridyl) -? / - [(2-ethoxy-3-pyridyl) methyl] -1 -isopropyl-3 - methylpyrazolo [4,3 - />] pyridin-7-amine ;

192: 5 - [2- (dimethylamino) -3-pyridyl] -1 -isopropyl -? / - [(4-methoxyphenyl) methyl] -3-methylpyrazolo [4,3 - />] pyridin-7-amine;

193: 3 - [1 -isopropyl-3-methyl-7- [[2- (trifluoromethyl) -3 - pyridyl] methylamino] pyrazolo [4,3-L \ pyridin-5-yl] -1 // - pyridin -2-she;

194: 1-isopropyl-3-methyl-5- (3-methylisoxazol-4-yl) -? / - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3 - />] pyridine-7- amine;

195: 1-isopropyl-3-methyl-5 - (1-methyl-1 // - 1,2,4-triazol-5-yl) -? / - ((1-methyl-1 // - pyrazole-4 -yl) methyl) - 1 // - pyrazolo [4,3-b \ pyridin-7-amine;

196: 1-isopropyl-3-methyl-5 - (2-propoxy-3-pyridyl) -? / - (1 // - pyrazol-4-ylmethyl) pyrazolo [4,3-b \ pyridin-7-amine;

197: 5 - (2-ethoxy-3-pyridyl) -? / - [(2-methoxy-3-pyridyl) methyl] -3 -methyl-1 - (oxetan-3-yl) pyrazolo [4,3- />] pyridin-7-amine;

198: 5- (2- (ethyl (methyl) amino) pyridin-3-yl) -1 -isopropyl -? / - (4-methoxybenzyl) -3-methyl-1 // - pyrazolo [4,3 - /> ] pyridin-7-amine;

199: 5 - (2-ethoxypyr idin-3-yl) -3 - (fluoromethyl) -1 -isopropyl -? / - ((1 -methyl-1 // - pyrazol-4-yl) methyl) - 1 // -pyrazolo [4,3-b \ pyridin-7-amine;

200: 1 -isopropyl-3-methyl -? / - ((1 -methyl- 1 // - pyrazol-4-yl) methyl) -5 - (4-methyloxazol-5-yl) -1 // - pyrazolo [ 4.3 - />] pyridin-7-amine;

201: 5- [2- (dimethylamino) -3-pyridyl] -1-isopropyl-3-methyl -? / - [(1methylpyrazol-4-yl) methyl] pyrazolo [4,3 - />] pyridine-7- amine;

202: 1 -isopropyl-3-methyl -? / - ((1 -methyl- 1 // - pyrazol-4-yl) methyl) -5 - (4-methyloxazol-2-yl) -1 // - pyrazolo [ 4.3 - />] pyridin-7-amine;

203: 1-isopropyl-3-methyl -? / - [(1-methylpyrazol-4-yl) methyl] -5- (4-methyl-1,2,4triazol-3-yl) pyrazolo [4,3-b \ pyridin-7-amine;

and pharmaceutically acceptable salts of any of these compounds.

E29. A compound according to embodiment 1, wherein the compound is selected from the group consisting of:

6: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl -? / - [(1 -methyltriazol-4-yl) methyl] pyrazolo [4,3 - />] pyridine-7- amine;

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7: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TU- (1 // - pyrazol-4-ylmethyl) pyrazolo [4.3 Ch] pyridin-7-amine;

21: 5- (2-ethoxy-3-pyrid yl) -1-isopropyl-TV - [(1-methylimidazol-4-yl) methyl] pyrazolo [4, PP] pyridin-7-amine;

29: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TU - [(4-methylthiazol-2-yl) methyl] pyrazolo [4, PP] pyridin-7-amine;

32: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl P / - [(2-methylthiazol-5 - yl) methyl] pyrazolo [4, ZP] pyridin-7-amine;

39: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-ACh I Ch-p irazol-3-ylmethyl) pyrazolo [4,3-A] pyridin-7-amine;

47: 5 - (2-ethoxypyridin-3-yl) -1 -isopropyl-3-methyl-ACh (5-methyl-14-pyrazole-

-yl) methyl) - 14-pyrazolo [4.3 Ch] pyridin-7-amine;

50: 5 - (2-ethoxypyr idin-3-yl) -1 -isopropyl-3-methyl-T \ H (4-methyloxazol-2-yl) methyl) - 14-pyrazolo [4.3 Ch] pyridin- 7-amine;

56: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(1-methyl-1,2,4-triazol-3 - yl) methyl] pyrazolo [4, ZC] pyridine-7- amine;

57: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-AD 14-pyrazol-3-ylmethyl) pyrazolo [4.3 Ch] pyridin-7-amine;

67а: (7?) - 5 - (2-ethoxy-3-pyridyl) -3 -methyl-1 - [1-methylpropyl] -TV- [(1 methylpyrazol-3-yl) methyl] pyrazolo [4, ZC] pyridin-7-amine;

67b: (S) -5 - (2-ethoxy-3-pyridyl) -3 -methyl-1 - [1-methylpropyl] -TV - [(1 methylpyrazol-3-yl) methyl] pyrazolo [4,3-b ] pyridin-7-amine;

77: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TV-f [2- (trifluoromethyl) -3 - pyridyl] methyl] pyrazolo [4.3 Ch] pyrid yn-7- amine;

82: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(6-methoxypyrazin-2-yl) methyl] -

-methylpyrazolo [4.3 Ch] pyrid-in-7-amine;

85: 5 - (2-ethoxy-3-pyrid yl) Ch / - [(2-fluoro-3-pyridyl) methyl] -1 -isopropyl-3-methylpyrazolo [4, PP] pyridin-7-amine;

86: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(2-methoxy-3-pyridyl) methyl] -3-methylpyrazolo [4, PP] pyridin-7-amine;

88: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(2-methoxyphenyl) methyl] -3-methylpyrazolo [4, PP] pyridin-7-amine;

- 38 037544

89: 5 - (2-ethoxy-3-pyridyl) -? / - [(2-fluorophenyl) methyl] -1 -isopropyl-3-methylpyrazolo [4,3 - />] pyridin-7-amine;

90: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TV- [[2- (trifluoromethyl) phenyl] methyl] pyrazolo [4.3 - />] pyridin-7-amine;

92: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(4-methoxy-3-pyridyl) methyl] -3-methylpyrazolo [4.3 - />] pyridin-7-amine;

94: 1-isopropyl-3 - methyl-A - [(1-methylpyrazol-4-yl) methyl] -5 - (2-propoxy-3-pyrid yl) pyrazolo [4,3-L \ pyridin-7-amine ;

100: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TU- (2-pyridylmethyl) pyrazolo [4.3 - />] pyridin-7-amine;

101: 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-TU - [(6-methyl-2pyrid yl) methyl] pyrazolo [4,3-L \ pyridin-7-amine;

107: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-TV-f [6- (trifluoromethyl) -2-pyrid yl] methyl] pyrazolo [4,3-b \ pyridin- 7-amine;

111: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(6-methoxy-3-pyridyl) methyl] -3-methylpyrazolo [4.3 - />] pyridin-7-amine;

113: 5- (2-ethoxy-3-pyridyl) -3-methyl-TV - [(2-methylthiazol-4-yl) methyl] -1- (oxetan-3-yl) pyrazolo [4,3- / >] pyridin-7-amine;

118: 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(3-methoxy-2-pyridyl) methyl] -3-methylpyrazolo [4.3 - />] pyridin-7-amine;

119: (R) -5 - (2-ethoxy-3-pyridyl) -3 -methyl-1 - [1-methylpropyl] -TV- (1 // - pyrazol-3 ylmethyl) pyrazolo [4,3 - /> ] pyridin-7-amine or (5) -5- (2-ethoxy-3-pyridyl) -3-methyl-1- [1 methylpropyl] -N- (1 H-pyrazol-3-ylmethyl) pyrazolo [4, 3-b] pyridin-7-amine;

120: (R) -5 - (2-ethoxy-3-pyridyl) -3 -methyl-1 - [1 -methylpropyl] -TV- (I // - p irazol-3 ylmethyl) pyrazolo [4,3- / >] pyridin-7-amine or (5) -5- (2-ethoxy-3-pyridyl) -3-methyl-1- [1 methylpropyl] -N- (1 H-pyrazol-3-ylmethyl) pyrazolo [4 , 3-b] pyridin-7-amine;

135a: (R) -3-methyl-1 - [1-methylpropyl] -5- (2-propoxy-3-pyridyl) -TU- (1 // - pyrazol3-ylmethyl) pyrazolo [4,3 -b \ pyridin-7-amine;

135b: (S) -3-methyl-1 - [1-methylpropyl] -5- (2-propoxy-Z-p irid yl) -L '- (1 H-pyrazol3-ylmethyl) pyrazolo [4,3- B] pyridin-7-amine;

- 39 037544

6: (R) -5 - (2-ethoxy-3-pyridyl) -1 - [1-methylpropyl] -N- (I R-p irazol-3 ylmethyl) pyrazolo [4,3 - />] pyridine-7 -amine or (5) -5- (2-ethoxy-3-pyridyl) -1- [1methylpropyl] -Ν- (1 H-pyrazol-3-ylmethyl) pyrazolo [4,3-b] pyridin-7-amine ;

137: (R) -5 - (2-ethoxy-3-pyridyl) -1 - [1-methylpropyl] -Ν- (I R-p irazol-3 ylmethyl) pyrazolo [4,3 - />] pyridine-7 -amine or (5) -5- (2-ethoxy-3-pyridyl) -1- [1methylpropyl] -Ν- (1 H-pyrazol-3-ylmethyl) pyrazolo [4,3-b] pyridin-7-amine ;

137: (R) -5 - (2-ethoxy-3-pyridyl) -1 - [1-methylpropyl] -A ^f - (l N-p irazol-3 - ylmethyl) pyrazolo [4,3 - />] pyridine -7-amine or (5) -5- (2-ethoxy-3-pyridyl) -1- [1methylpropyl] -Ν- (1 H-pyrazol-3-ylmethyl) pyrazolo [4,3-b] pyridine-7 -amine;

140: (R) -5 - (2-ethoxy-3-pyridyl) -1 - [1-methylpropyl] -7V - [(1-methyl-1,2,4-triazole-

3-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine or (5) -5- (2-ethoxy-3-pyridyl) -1- [1methylpropyl] -H - [(1-methyl -1,2,4-triazol-3-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine;

141: (R) -5 - (2-ethoxy-3-pyridyl) -1 - [1-methylpropyl] -7V - [(1-methyl-1,2,4-triazole-

3-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine or (5) -5- (2-ethoxy-3-pyridyl) -1- [1methylpropyl] -H - [(1-methyl -1,2,4-triazol-3-yl) methyl] pyrazolo [4,3 - />] pyridin-7-amine;

180: 5 - (2- (ethoxy-1,1 -d2) nnpidin-3-yl) -1 -isopropyl-Y - ((2-methoxypyrid in-3 - yl) methyl) -3-methyl-1H-pyrazolo [4,3-b] pyridin-7-amine;

181: 5 - (2- (3TOKCH-d5) nHp idin-3-yl) -1 -isopropyl-Ya - ((2-methoxypyridin-3 - yl) methyl) -3-methyl-1Н-pyrazolo [4, 3-b] pyridin-7-amine;

182: 5- (2- (etoksi-2,2,2-dz) pyridin-3-yl) -l-isopropyl-I - ((2-metoksypyridin-

-yl) methyl) -3 -methyl-1 H-pyrazolo [4,3-b] pyrid in-7-amine;

191: 5 - (2-ethoxy-3-pyridyl) -A - [(2-ethoxy-3-pyridyl) methyl] -1 -isopropyl-3-methylpyrazolo [4,3-b] pyridin-7-amine;

and pharmaceutically acceptable salts of any of these compounds.

E30. A compound according to any one of Embodiments 1-29, wherein said compound has an IC50 value for PDE1A, PDE1B or PDE1C, determined as described in the PDE1 Inhibition Assay section of 10 μmol / L or less, for example 5 μmol / L or less, for example 4 μmol / L or less, for example 3 μmol / L or less, for example 2 μmol / L or less, for example 1 μmol / L or less, for example 500 nM or less, for example 400 nM or less, for example 300 nM or less, for example 200 nM or less, for example 100 nM or less.

E31. A compound according to any one of Embodiments 1-29 for use in therapy.

E32. A compound according to any one of Embodiments 1-29 for use as a medicament.

E33. A pharmaceutical composition comprising a therapeutically effective amount of a compound of any one of Embodiments 1-29 and one or more pharmaceutically acceptable carriers, diluents, and excipients.

E34. A compound according to any one of embodiments 1-29 for use in the treatment of a neurodegenerative disorder selected from the group consisting of Alzheimer's disease, Parkinson's disease and Huntington's disease, or for the treatment of a mental disorder such as attention deficit / hyperactivity disorder (ADHD), depression, anxiety, narcolepsy, cognitive impairment and cognitive impairment associated with schizophrenia (CIAS), or another brain disorder like restless legs syndrome.

E35. A method of treating a neurodegenerative disorder selected from the group consisting of Alzheimer's disease, Parkinson's disease and Huntington's disease, or treating a mental disorder such as attention deficit / hyperactivity disorder (ADHD), depression, anxiety, narcolepsy, cognitive impairment, and cognitive impairment associated with schizophrenia (CIAS) or other brain disease like restless legs syndrome, the method comprising administering a therapeutically effective amount of a compound according to any one of embodiments 1-29 to a patient in need thereof.

E36. Use of a compound in accordance with any of Embodiments 1-29 to manufacture

- 40 037544 For the treatment of a medication for the treatment of a neurodegenerative disorder selected from the group consisting of Alzheimer's disease, Parkinson's disease and Huntington's disease, or for the treatment of a mental disorder such as attention deficit / hyperactivity disorder (ADHD), depression, anxiety, narcolepsy, cognitive impairment and cognitive impairment associated with schizophrenia (CIAS), or another brain disorder like restless legs syndrome.

All references, including publications, patent applications, and patents cited herein, are incorporated herein by reference in their entirety and to the same extent as if it were indicated that each reference is individually and specifically incorporated by reference and incorporated into in its entirety (to the maximum extent permitted by law).

Headings and subheadings are used herein for convenience only and should not be construed as limiting the present invention in any way.

The use of all kinds of examples or typical phrases (including so, for example, for example, and as such) in this description is intended solely to better illuminate the present invention and is not a limitation of the scope of the present invention, unless otherwise indicated.

The citation and inclusion of patent documents in this document is for convenience only and does not represent any assessment of the validity, patentability and / or legal effect of such patent documents.

The present invention includes all modifications and equivalents of the subject matter set forth in the claims appended to this document in accordance with applicable law.

Compounds of the present invention

Table 1

Compounds of the present invention

Example Compound PDE1A, IC50 (nM) PDE1B, IC50 (nM) PDE1C, 1C ₅ o (nM) one 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TV - [(5-methyl-1,3,4-oxadiazol-2yl) methyl] pyrazolo [4,3-b} pyridine-7 -amine eighteen 1.6 40 2 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TU - [(5-methylthiazol-2yl) methyl] pyrazolo [4,3-L \ pyridin-7-amine 0.46 0.071 4.9 3 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TV- [(5-methylisoxazol-3 yl) methyl] pyrazolo [4,3-b} pyridin-7-amine 0.8 oh and 3 four 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TU - [(2-methyloxazol-5yl) methyl] pyrazolo [4,3-b} pyridin-7-amine 8.6 0.86 nineteen five 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TV- [(2-methyltriazol-4yl) methyl] pyrazolo [4,3-b} pyridin-7-amine AND 1.8 28 6 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TV- [(1-methyltriazol-4yl) methyl] pyrazolo [4,3-b} pyridin-7-amine 4.8 0.22 5.6 7 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TU- (1 # -pyrazole-4ylmethyl) pyrazolo [4,3 - />] pyridin-7-amine 21 1.1 37 eight 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TU - [(2-methyltetrazol-5yl) methyl] pyrazolo [4,3-] pyridin-7-amine 2.9 0.34 8.9 nine 5 - (2-ethoxypyrid in-3 -yl) -1 -isopropyl-3 methyl-LSP 1 -methyl- 1 # -pyrazol-4yl) methyl) - 1 # -pyrazolo [4,3 -T>] pyridine- 7- amine 2.6 0.49 17

- 41 037544

10 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TV- [(3-methylisoxazol-5 yl) methyl] pyrazolo [4,3-b} pyridin-7-amine 4.1 0.47 fourteen and 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TU - [(2-methylthiazol-4yl) methyl] pyrazolo [4,3-b} pyridin-7-amine 9.6 0.72 thirty 12 1 -cyclopropyl-5 - (2-ethoxy-3-pyridyl) -3 methyl-TV- [(1-methylpyrazol-4yl) methyl] pyrazolo [4,3-b} pyridin-7-amine 200 60 690 13 5 - (2-ethoxy-3 - p ir id yl) -L- [(1 methylpyrazol-4-yl) methyl] -1 propylpyrazolo [4,3 - />] pyridin-7-amine 90 fifteen 340 fourteen 5- (2-ethoxypyridin-3-yl) -TU - ((1-methyl-1Yapirazol-4-yl) methyl) -1 - (oxetan-3-yl) -1 Yapirazolo [4,3-T>] pyrid in-7-amine 450 38 300 fifteen 5 - (2-ethoxypyr idin-3-yl) -1 -methyl-L- (1 - (1 methyl-1H-pyrazol-4-yl) ethyl) - \ Npyrazolo [4,3-T>] pyridin- 7-amine (racemic) 820 200 36% inhibition at 10 μM sixteen 5 - (2-ethoxypyrid in-3-yl) -1-methyl-TU - ((1 methyl-1H-pyrazol-4-yl) methyl) - 1Hpyrazolo [4,3-T>] pyrid in-7- amine 670 92 1800 17 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(1 methylimidazol-2-yl) methyl] pyrazolo [4,3 b} pyridin-7-amine 700 54 970 eighteen 5 - (2-ethoxypyrid in-3-yl) -1 -isopropyl-TV ((1-methyl-1H-pyrazol-5-yl) methyl) -1 Yapirazolo [4,3-T>] pyrid in-7- amine 450 73 640 nineteen 5 - (2-ethoxypyrid in-3-yl) -1 -isopropyl-TV ((1 -methyl-1H-pyrazol-3-yl) methyl) - 1Hpyrazolo [4,3-T>] pyrid in-7- amine 66 4.6 150 twenty 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV (thiazol-2-ylmethyl) pyrazolo [4.3 L] pyridin-7-amine 520 37 600 21 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(1 methylimidazol-4-yl) methyl] pyrazolo [4,3 L] pyridin-7-amine 8.9 0.44 29 22 5- (2-ethoxy-3-pyridyl) -1-isopropyl-TU- (4pyridylmethyl) pyrazolo [4,3-L \ pyridine-7amine 250 fifty 430 23 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TU- (mtolylmethyl) pyrazolo [4,3 - />] pyridine-7amine 240 38 750 24 5- (2-ethoxy-3-pyridyl) -1-isopropyl-TU- (ptolylmethyl) pyrazolo [4,3 - />] pyridine-7amine 380 160 1200 25 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(1 methylpyrazol-4-yl) methyl] pyrazolo [4,3b \ pyridin-7-amine 56 4.6 150 26 5 - (2-ethoxy-3-pyridyl) -1-ethyl - # - [(1 methylpyrazol-4-yl) methyl] pyrazolo [4,3b] pyridin-7-amine 140 22 440 27 5 - (2-ethoxy-3-pyridyl) -3-methyl-TU - [(1 methylpyrazol-4-yl) methyl] -1 - (oxetan-3 yl) pyrazolo [4,3 - />] pyridine-7 -amine 94 6.6 170

- 42 037544

28 5- (2-ethoxy-3-pyridyl) -1,3-dimethyl-TU - [(1 methylpyrazol-4-yl) methyl] pyrazolo [4,3- B] pyridin-7-amine 550 85 1900 29 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TU - [(4-methylthiazol-2yl) methyl] pyrazolo [4,3-b} pyridin-7-amine 27 1.1 44 thirty 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TV - [(3-methyl-1,2,4-oxadiazol-5yl) methyl] pyrazolo [4,3-L \ pyridine-7 -amine fifteen 1,3 31 31 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TV - [(1-methyl-1,2,4-triazol-3 yl) methyl] pyrazolo [4,3-L \ pyridine- 7-amine 1,2 oh and 2.1 32 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TU - [(2-methylthiazol-5yl) methyl] pyrazolo [4,3-L \ pyridin-7-amine 4.6 0.14 6.2 33 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TV - [(5-methyl-1,3,4-thiadiazol-2yl) methyl] pyrazolo [4,3-b} pyridine-7 -amine 1.6 0.41 7.9 34 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TU - [(5-methyl-3-thienyl) methyl] pyrazolo [4,3 -T>] pyrid in-7amine 8.1 1.8 21 35 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TU - [(4-methyl-2thienyl) methyl] pyrazolo [4,3 -T>] pyrid in-7amine 7.3 1.7 32 36 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TU - [(5-methyl-2thienyl) methyl] pyrazolo [4,3 -T>] pyrid in-7amine 24 5.2 41 37 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TU - [(2-methyloxazol-4yl) methyl] pyrazolo [4,3-b} pyridin-7-amine 5.9 0.43 eighteen 38 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TU - [(5-methyloxazol-2yl) methyl] pyrazolo [4,3-b} pyridin-7-amine 1.1 0.24 13 39 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TU- (1 // - pyrazole-3ylmethyl) pyrazolo [4,3 - /] pyridin-7-amine 8.1 0.43 13 40 5- (2-ethoxy-3-pyrid yl) -TU- (1 // - imidazole-4ylmethyl) -1 -isopropyl-3 methylpyrazolo [4,3 -T>] pyridin-7-amine fourteen one 32 41 TU-benzyl-5 - (2-ethoxy-3-pyridyl) -1 isopropylpyrazolo [4,3-L \ pyridin-7-amine 500 45 500 42 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(3 methylisoxazol-5-yl) methyl] pyrazolo [4,3 L] pyridin-7-amine 82 5.8 180 43 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(5 methyl-1,2,4-oxadiazol-3 yl) methyl] pyrazolo [4,3-b \ pyridin-7-amine thirty 2.4 80 44 TV- [(1,5-dimethylpyrazol-3-yl) methyl] -5 - (2ethoxy-3-pyridyl) -1 isopropylpyrazolo [4,3-b} pyridin-7-amine nineteen 1.4 70

- 43 037544

45 3- (1-isopropyl-3-methyl-7 - (((1-methyl-1 Yapirazol-4-yl) methyl) amino) - 1Hpyrazolo [4,3-A] pyridin-5-yl) -1methylpyridin-2 (1Я) -on eight 0.62 sixteen 46 5 - (2-ethoxypyrid in-3-yl) -1 -isopropyl-3 methyl-I - ((2-methyl-1H-imidazole-4- yl) methyl) -1N-pyrazolo [4,3 - />] pyridine-7amine five 0.42 9,7 47 5 - (2-ethoxypyrid in-3-yl) -1 -isopropyl-3 methyl-HP (5-methyl-1H-pyrazol-3 yl) methyl) - 1H-pyrazolo [4,3-A] pyridine-7amine 1.6 0.069 1.8 48 5 - (2-ethoxypyrid in-3-yl) -1-ethyl-3-methylH - ((1-methyl-1H-pyrazol-4-yl) methyl) -1Japirazolo [4,3-A] pyridine-7 -amine 38 6.3 170 49 3 - (1 -isopropyl-3-methyl-7 - (((1-methyl-1Hpyrazol-4-yl) methyl) amino) - \ Npyrazolo [4,3 - />] pyridin-5-yl) -1methylpyridine- 2 (1Ya) -on 170 twenty 420 fifty 5 - (2-ethoxypyrid in-3-yl) -1 -isopropyl-3 methyl-I - ((4-methyloxazol-2-yl) methyl) -1 Yapirazolo [4,3 - />] pyridin-7-amine -2,2,2trifluoroacetate nine 0.5 sixteen 51 I - ((1,2-dimethyl-1H-imidazol-4-yl) methyl) 5 - (2-ethoxypyrid in-3-yl) -1 -isopropyl-3 methyl- 1H-pyrazolo [4,3 - A ] pyrid yn-7-amine 2,2,2-trifluoroacetate 53 9.1 88 52 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TV - [(5-methyl-1,2,4-oxadiazol-Zyl) methyl] pyrazolo [4,3-A] pyridine-7 -amine 1.9 0.17 4.4 53 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-R- (1,2,4-oxadiazol-3-ylmethyl) pyrazolo [4,3 - />] pyridin-7-amine 9.3 0.89 17 54 TV- [(1,5-dimethylpyrazol-3-yl) methyl] -5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methylpyrazolo [4,3 - A] pyridin-7-amine 0.39 0.18 4.6 55 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TV - [(5-methyl-1H-1,2,4-triazol-3 yl) methyl] pyrazolo [4,3 -A] pyridine-7-amine 3.4 0.51 5.5 56 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(1 methyl-1,2,4-triazole-3 - yl) methyl] pyrazolo [4,3-A] pyridin-7-amine sixteen one 45 57 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV (1H-pyrazol-3-ylmethyl) pyrazolo [4.3 A] pyridin-7-amine 98 4.8 170 58 5 - (2-ethoxypyrid in-3-yl) -1 -isopropyl-3 methyl-I - ((1-methyl-1H-imidazole-4- yl) methyl) -1H-pyrazolo [4,3 - />] pyridine-7amine-2,2,2-trifluoroacetate 1.1 0.17 2.1 59 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-R- (1,3,4-oxadiazol-2ylmethyl) pyrazolo [4,3 - />] pyridin-7-amine 55 12 120 60 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TV- [(1-methylpyrazol-3 yl) methyl] pyrazolo [4,3-A] pyridin-7-amine 6.5 0.59 12

- 44 037544

61 5- (1,3-d-immethylpyrazol-4-yl) -1 -isopropyl 3 -methyl-TV- [(1-methylpyrazol-4yl) methyl] pyrazolo [4,3-L \ pyridin-7-amine 550 120 680 62 1 -isopropyl-5 - (2-methoxy-3-pyridyl) -3 methyl-TV- [(1-methylpyrazol-4yl) methyl] pyrazolo [4,3-b} pyridin-7-amine sixteen 2.4 21 63 1 -isopropyl-5 - (2-methoxyphenyl) -3 -methylTU - [(1-methylpyrazole-4- yl) methyl] pyrazolo [4,3-b} pyridin-7-amine 64 9.4 twenty 64 1-isopropyl-3-methyl-TU - [(1-methylpyrazol4-yl) methyl] -5-phenylpyrazolo [4.3 b} pyridin-7-amine 52 12 47 65 1 -isopropyl-3-methyl-TV- [(1-methylpyrazol4-yl) methyl] -5- (2-methyl-3thienyl) pyrazolo [4,3-b \ pyridin-7-amine 7.9 1,2 sixteen 66 5- (1,5-d imethylpyrazol-4-yl) -1 -isopropyl3-methyl-TV- [(1 -methylpyrazol-4- yl) methyl] pyrazolo [4,3-b} pyridin-7-amine 210 59 220 67 5 - (2-ethoxy-3-pyrid yl) -3-methyl-1 - [1 methylpropyl] -TV - [(1-methylpyrazol-3 yl) methyl] pyrazolo [4,3-b} pyridin-7-amine , enantiomer 2 9.6 0.64 27 68 3-methyl-1 - [1-methylpropyl] -TV- [(2-methyltetrazol-5-yl) methyl] -5- (2-propoxy3-pyridyl) pyrazolo [4,3 - />] pyridine-7amine, enantiomer 2 0.79 0.14 1,3 69 5 - (2-ethoxy-3-pyridyl) -1 - [1-methylpropyl] TU - [(1-methylpyrazol-4yl) methyl] pyrazolo [4,3-b} pyridin-7-amine, enantiomer 1 fourteen 1,2 40 70 5 - (2-ethoxy-3-pyridyl) -1 - [1-methylpropyl] TU - [(1-methylpyrazol-4yl) methyl] pyrazolo [4,3-b \ pyridin-7-amine, enantiomer 2 140 fourteen 360 71 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(4methylthiazol-5-yl) methyl] pyrazolo [4.3 L] pyridin-7-amine 170 eighteen 180 72 5 - [[5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methylpyrazolo [4,3 - />] pyridin-7yl] oxymethyl] -2-methyl oxazol fourteen 2.4 39 73 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TU- (pyrimidin-4ylmethyl) pyrazolo [4,3 - />] pyridin-7-amine 81 9.2 140 74 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TU- (pyrimidin-2ylmethyl) pyrazolo [4,3-th] pyridin-7-amine 2.1 0.34 8.1 75 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TV- [(4-methylpyr imidin-2yl) methyl] pyrazolo [4,3-b} pyridin-7-amine 9.9 0.81 33 76 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TU- (pyrazin-2-ylmethyl) pyrazolo [4,3 - B] pyridin-7-amine 23 2.9 32

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77 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TV- [[2- (trifluoromethyl) -3 pyridyl] methyl] pyrazolo [4,3 - />] pyridine-7amine 21 0.22 64 78 4- [[[5 - (2-ethoxy-3-pyridyl) -1-isopropyl-3 methylpyrazolo [4,3 - />] pyridin-7yl] amino] methyl] -1-methylpyridin-2-one 27 3.2 44 79 5 - (2- (ethylamino) pyridin-3-yl) -1 isopropyl-3-methyl -? / - ((1-methyl- \ Npyrazol-4-yl) methyl) - 1H-pyrazolo [4,3 - B] pyridin-7-amine 230 31 260 81 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(4methoxy-2-pyridyl) methyl] -3 methylpyrazolo [4,3 -T>] pyridin-7-amine one 0.26 4.7 82 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(6methoxypyrazin-2-yl) methyl] -3 methylpyrazolo [4,3 -T>] pyridin-7-amine sixteen one 35 83 5 - (2-ethoxy-3-pyridyl) -? / - [(5 fluoropyrimidin-2-yl) methyl] -1 -isopropyl3-methylpyrazolo [4,3 -T>] pyridin-7-amine 17 1,2 38 84 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl -? / - [(2-methyl-3 pyridyl) methyl] pyrazolo [4,3 - />] pyridine-7- amine nineteen 1.8 23 85 5 - (2-ethoxy-3-pyridyl) -? / - [(2-fluoro-3 pyridyl) methyl] -1 -isopropyl-3 methylpyrazolo [4,3-L \ pyridin-7-amine 8.4 0.22 27 86 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl -? / - [(2methoxy-3-pyridyl) methyl] -3 methylpyrazolo [4,3 -T>] pyridin-7-amine twenty 0.36 68 87 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl -? / - [(6-methyl-3pyridyl) methyl] pyrazolo [4,3 - />] pyridine-7- amine 6.3 0.95 13 88 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl -? / - [(2methoxyphenyl) methyl] -3 methylpyrazolo [4,3 -T>] pyridin-7-amine 110 5.1 170 89 5- (2-ethoxy-3-pyridyl) -? / - [(2fluorophenyl) methyl] -1 -isopropyl-3 methylpyrazolo [4,3 -T>] pyridin-7-amine 61 1.5 93 90 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl -? / - [[2 (trifluoromethyl) phenyl] methyl] pyrazolo [4,3 b \ pyridin-7-amine 270 12 640 91 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl -? / - [(3 methoxypyrazin-2-yl) methyl] -3 methylpyrazolo [4,3 -T>] pyridin-7-amine 27 2,3 70 92 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl -? / - [(4methoxy-3-pyridyl) methyl] -3 methylpyrazolo [4,3 -T>] pyridin-7-amine 47 2.7 110 93 1-isopropyl-3-methyl -? / - [(2-methyltetrazol5-yl) methyl] -5 - (2-propoxy-3 pyridyl) pyrazolo [4,3 - />] pyridin-7-amine 4.3 0.96 17

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94 1-isopropyl-3-methyl - # - [(1-methylpyrazol4-yl) methyl] -5 - (2-propoxy-3 pyridyl) pyrazolo [4,3 - />] pyridin-7-amine 1.4 0.065 4.9 95 1 -isopropyl-5 - (2-methoxy-3-pyridyl) - # [(2-methoxy-3-pyridyl) methyl] -3 methylpyrazolo [4,3 - />] pyridin-7-amine 42 6.4 28 96 1 -isopropyl-5 - (2-methoxy-3-pyridyl) - # [(6-methoxy-3-pyridyl) methyl] -3 methylpyrazolo [4,3 - />] pyridin-7-amine eighteen 3.8 5.3 97 5 - (2-isopropoxy-3-pyridyl) -1 -isopropyl- 3-methyl-TV- [(1-methylpyrazol-4yl) methyl] pyrazolo [4,3-b} pyridin-7-amine 1.4 0.6 9.1 98 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl - # - (\ H-1,2,4-triazol-3-ylmethyl) pyrazolo [4,3 - />] pyridin-7-amine 7.2 0.58 21 99 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl - # - (2 # -tetrazol-5ylmethyl) pyrazolo [4,3 - />] pyridin-7-amine 0.73 0.31 3.8 100 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl - # - (2-pyridylmethyl) pyrazolo [4,3Z>] pyridin-7-amine 6.3 0.39 21 101 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl - # - [(6-methyl-2pyridyl) methyl] pyrazolo [4,3 - />] pyridine-7- amine twenty 0.9 43 102 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl - # - [(6methoxy-2-pyridyl) methyl] -3 methylpyrazolo [4,3 - />] pyridin-7-amine eight 0.73 34 103 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl - # - [(2-methyl-4pyridyl) methyl] pyrazolo [4,3 - />] pyridine-7- amine 5.4 2.9 17 104 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl - # - [(2methoxy-4-pyridyl) methyl] -3 methylpyrazolo [4,3 -T>] pyridin-7-amine 2.2 0.16 6.3 105 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TV- [(2-methylpyr imidin-4yl) methyl] pyrazolo [4,3-b} pyridin-7-amine 54 12 150 106 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(5 methoxy-3-pyridyl) methyl] -3 methylpyrazolo [4,3 -T>] pyridin-7-amine 2.1 0.45 3.9 107 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TV- [[6- (trifluoromethyl) -2pyridyl] methyl] pyrazolo [4,3 - />] pyridine-7amine 110 5.6 170 108 3 - [[[5 - (2-ethoxy-3-pyridyl) -1-isopropyl-3 methylpyrazolo [4,3 - />] pyridin-7yl] amino] methyl] -1-methylpyridin-2-one 2.8 0.36 12 109 5 - (2-ethoxy-3-pyridyl) - # - [(1-ethylpyrazol4-yl) methyl] -1 -isopropyl-3 methylpyrazolo [4,3 -T>] pyridin-7-amine 4.9 0.66 AND 110 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl - # - [(1-propylpyrazole-4yl) methyl] pyrazolo [4,3-L \ pyridin-7-amine AND 1.1 8.5

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111 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl - # - [(6methoxy-3-pyridyl) methyl] -3 methylpyrazolo [4,3 - />] pyridin-7-amine 28 1.4 68 112 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(5 methoxy-2-pyridyl) methyl] -3 methylpyrazolo [4,3 - />] pyridin-7-amine 61 12 100 OF 5 - (2-ethoxy-3-pyridyl) -3 -methyl - # - [(2methylthiazol-4-yl) methyl] -1 - (oxetan-3 yl) pyrazolo [4,3 - />] pyridine-7- amine 110 5.7 130 114 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(5 methoxypyrazin-2-yl) methyl] -3 methylpyrazolo [4,3 - />] pyridin-7-amine 24 3 46 115 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl - # - (3-pyridylmethyl) pyrazolo [4.3 b} pyridin-7-amine fifteen 2 31 116 5 - (2-ethoxy-3-pyridyl) - # - [(6-fluoro-3-pyridyl) methyl] -1 -isopropyl-3 methylpyrazolo [4,3-b \ pyridin-7-amine 21 2.4 46 117 # - [[6- (difluoromethyl) -3-pyridyl] methyl] -5 (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methylpyrazolo [4,3 - />] pyridin-7-amine eighteen 2,3 26 118 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl - # - [(3-methoxy-2-pyridyl) methyl] -3 methylpyrazolo [4,3 -0] pyridin-7-amine 13 0.42 88 119 5 - (2 is xi-3-pyrid yl) -3 -methyl-1 - [1 methylpropyl] - # - (\ H-pyrazol-3 ylmethyl) pyrazolo [4,3-b \ pyridin-7-amine, enantiomer 1 12 0.56 29 120 5 - (2-ethoxy-3-pyrid yl) -3-methyl-1 - [1 methylpropyl] - # - (\ H-pyrazol-3 ylmethyl) pyrazolo [4,3-b \ pyridin-7-amine, enantiomer 2 4.6 0.27 7.6 121 5 - (2-ethoxy-3-pyrid yl) -3-methyl-1 - [1 methylpropyl] - # - [(1-methyl-1,2,4-triazol-3 yl) methyl] pyrazolo [4,3 -B \ pyridin-7-amine, enantiomer 1 four 0.47 10 122 5 - (2-ethoxy-3-pyrid yl) -3-methyl-1 - [1 methylpropyl] - # - [(1-methyl-1,2,4-triazol-3 yl) methyl] pyrazolo [4,3 -L \ pyridin-7-amine, enantiomer 2 2.2 0.15 3.5 123 5- (2-ethoxy-3-pyridyl) -3 -methyl - # - [(5 methyl-1,3,4-oxad iazol-2-yl) methyl] -1 - [1 methylpropyl] pyrazolo [4,3 - />] pyridine-7amine, enantiomer 1 54 7 130 124 5- (2-ethoxy-3-pyridyl) -3 -methyl - # - [(5 methyl-1,3,4-oxad iazol-2-yl) methyl] -1 - [1 methylpropyl] pyrazolo [4,3 - />] pyridine-7amine, enantiomer 2 9,7 1.1 21 125 5 - (2-ethoxy-3-pyrid yl) - # - [(5-methoxy-3 pyrid yl) methyl] -3 -methyl-1 - [1 - methylpropyl] pyrazolo [4,3 - />] pyridine-7amine, enantiomer 2 one 0.32 4.3 126 5- (2-ethoxy-3-pyrid yl) - # - [(2-methoxy-4pyrid yl) methyl] -3 -methyl-1 - [1 - methylpropyl] pyrazolo [4,3 - />] pyridine-7amine, enantiomer 2 5.4 0.51 8.4

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127 5 - (2-ethoxy-3-pyrid yl) -3 -methyl-1 - [1 methylpropyl] -4 - [(2-methyltetrazol-5yl) methyl] pyrazolo [4.3 Ch] pyridin-7-amine, enantiomer 2 1.8 0.31 5.1 128 5 - (2-ethoxy-3-pyridyl) -3-methyl P / - [(5 methyl-1,2,4-oxadiazol-3-yl) methyl] -1 - [1 methylpropyl] pyrazolo [4, ZC] pyridine -7amine, enantiomer 2 1,2 0.26 4.1 129 5- (2-ethoxy-3-pyridyl) -3 -methyl P / - [(2methyloxazol-4-yl) methyl] -1 - [1 methylpropyl] pyrazolo [4, ZP] pyridine-7amine, enantiomer 2 AND 1,2 25 130 5- (2-ethoxy-3-pyridyl) -4- (14-imidazole-4ylmethyl) -3-methyl-1 - [1 - methylpropyl] pyrazolo [4, ZC] pyridine-7amine, enantiomer 2 AND 0.86 25 131 5 - (2-ethoxy-3-pyrid yl) -3 -methyl-1 - [1 methylpropyl] -L ^g - [(5-methyl-14-pyrazol-3yl) methyl] pyrazolo [4.3 Ch] pyridine- 7-amine, enantiomer 2 0.35 0.042 0.46 132 5 - (2-ethoxy-3-pyridyl) -3-methyl P / - [(1 methylimidazol-4-yl) methyl] -1 - [1 methylpropyl] pyrazolo [4, ZP] pyridine-7amine, enantiomer 2 0.14 0.045 0.52 133 5- (2-ethoxy-3-pyridyl) -3 -methyl P / - [(2methyloxazol-5-yl) methyl] -1 - [1 methylpropyl] pyrazolo [4, PP] pyridine-7amine, enantiomer 2 AND 1,3 23 134 3-methyl-1 - [1-methylpropyl] -4 - [(1-methyl1,2,4-triazol-3-yl) methyl] -5 - (2-propoxy-3 pyrid yl) pyrazolo [4, ZC] pyridin-7-amine, enantiomer 2 0.96 0.12 1.5 135 3-methyl-1 - [1-methylpropyl] -5 - (2-propoxy3 - pirid yl) -L- (1H- and irazol-3 ylmethyl) pyrazolo [4.3 Ch] pyridin-7-amine, enantiomer 2 1.9 0.095 3.6 136 5 - (2-ethoxy-3-pyridyl) -1 - [1-methylpropyl] N- {1H-pyrazol-3 -ylmethyl) pyrazolo [4,3 />] pyridin-7-amine, enantiomer 1 62 3.2 100 137 5 - (2-ethoxy-3-pyridyl) -1 - [1-methylpropyl] N- (1H-pyrazol-3-ylmethyl) pyrazolo [4.3 A] pyridin-7-amine, enantiomer 2 180 12 340 138 5 - (2-ethoxy-3-pyrid yl) Ch / - [(5-methyl-1,3,4 oxad iazol-2-yl) methyl] -1 - [1 methylpropyl] pyrazolo [4, ZC] pyridine-7amine , enantiomer 1 93 6.8 180 139 5 - (2-ethoxy-3-pyrid yl) Ch / - [(5-methyl-1,3,4 oxad iazol-2-yl) methyl] -1 - [1 methylpropyl] pyrazolo [4, ZC] pyridine-7amine , enantiomer 2 330 35 530 140 5 - (2-ethoxy-3-pyridyl) -1 - [1-methylpropyl] TV- [(1-methyl-1,2,4-triazol-3 yl) methyl] pyrazolo [4.3 Ch] pyridine-7 -amine, enantiomer 1 32 1.7 52

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141 5 - (2-ethoxy-3-pyridyl) -1 - [1-methylpropyl] I - [(1-methyl-1,2,4-triazol-3 yl) methyl] pyrazolo [4,3 -6] pyridine- 7-amine, enantiomer 2 44 2.2 76 142 1 -isopropyl-3-methyl-TV- [(1 methylimide azol-4-yl) methyl] -5 - (2propoxy-3-pyridyl) pyrazolo [4,3 L} pyridin-7-amine 0.26 0.1 0.8 143 1-isopropyl-3-methyl-5 - (2-propoxy-3 pyrid yl) -TU- (1H-pyrazole-3ylmethyl) pyrazolo [4,3 - />] pyridin-7-amine 3.8 0.26 9.2 144 5 - (2-ethoxy-3-pyrid yl) -3-methyl-1 - [1 methylpropyl] -H- (1H-1,2,4-triazole-3ylmethyl) pyrazolo [4,3-b \ pyridine-7 -amine, enantiomer 2 fourteen 1.1 23 145 1 -isopropyl-3-methyl-TV - [(1-methyl-1,2,4triazol-3-yl) methyl] -5 - (2-propoxy-3-pyridyl) pyrazolo [4,3 - />] pyridine- 7-amine 0.41 0.095 1,2 146 1-isopropyl-3-methyl-5 - (2-propoxy-3 pyridyl) -H- (1H-1,2,4-triazole-3ylmethyl) pyrazolo [4,3 - />] pyridin-7-amine 3.9 0.51 fourteen 147 1-isopropyl-3-methyl-TV- [(1-methylpyrazol4-yl) methyl] -5-thiazol-2-ylpyrazolo [4,3b} pyridin-7-amine 12 2.1 28 148 1 -isopropyl-3-methyl-TV- [(1-methylpyrazol4-yl) methyl] -5 - (5-methylthiazol-2yl) pyrazolo [4,3 - />] pyridin-7-amine 110 58 86 149 1-isopropyl-3-methyl-TV- [(1-methylpyrazol4-yl) methyl] -5- (4-methylthiazol-2yl) pyrazolo [4,3 - />] pyridin-7-amine 29 2.4 69 150 3 - [1 -isopropyl-3-methyl-7 - [(1 methylpyrazol-4yl) methylamino] pyrazolo [4,3 - />] pyridin-5yl] -5-methyloxazolidin-2-one 44 33 13 151 3 - [1-isopropyl-3-methyl-7 - [(1 methylpyrazol-4yl) methylamino] pyrazolo [4,3 - />] pyridin-5yl] oxazolidin-2-one 10 4.7 12 152 1 - [1-isopropyl-3-methyl-7 - [(1 methylpyrazol-4yl) methylamino] pyrazolo [4,3 - />] pyridin-5yl] azetidin-2-one 48 32 61 153 1-tert-butyl-3 - [1-isopropyl-3-methyl-7 [(1-methylpyrazol-4yl) methylamino] pyrazolo [4,3 - />] pyridin-5yl] imide azolid in-2-one 130 76 270 154 1 - [1 -isopropyl-3-methyl-7 - [(1 methylpyrazol-4yl) methylamino] pyrazolo [4,3 - />] pyridin-5yl] pyrrolidin-2-one 26 3.6 49 155 3 - [1-isopropyl-3-methyl-7 - [(1 methylpyrazol-4yl) methylamino] pyrazolo [4,3 - />] pyridin-5yl] -4-methyloxazolidin-2-one 8.2 4.9 3.9

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156 4-ethyl-3 - [1-isopropyl-3-methyl-7 - [(1 methylpyrazol-4yl) methylamino] pyrazolo [4,3 - />] pyridin-5yl] oxazolidin-2-one 31 31 5.1 157 TV- [[5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methylpyrazolo [4,3-T>] pyridin-7-yl] methyl] 5-methoxypyridine-3-amine 34 fourteen 77 158 TV- [[5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methylpyrazolo [4,3 -T>] pyridin-7-yl] methyl] 1 -methyl-1,2,4-triazole- Z-amine 23 4.9 fifty 159 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-7 - [2 (5-methoxy-3-pyridyl) ethyl] -3 methylpyrazolo [4,3-b \ pyridine 270 70 1600 160 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-7- [2- (1-methyl-1,2,4-triazol-3 yl) ethyl] pyrazolo [4,3 -T> ] pyridine 23 3.9 56 161 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TV- [(2-methyl-1,2,4-triazol-3 yl) methyl] pyrazolo [4,3-b} pyridine- 7-amine 60 6.6 120 162 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-TV- [(4-methyl-1,2,4-triazol-3 yl) methyl] pyrazolo [4,3-L \ pyridine- 7-amine 100 13 180 163 5 - (2-ethoxy-3-pyridyl) -3-methyl-TU - [(1 methyl-1,2,4-triazol-3-yl) methyl] -1 (oxetane-3-yl) pyrazolo [4, 3 -T>] pyridine-7- amine 120 fourteen 120 164 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methyl-7 - [(1-methylpyrazole-4yl) methyl sulfanil] pyrazole o [4,3 />] pyridine 6.8 1.6 25 165 N- [[1 - (difluoromethyl) pyrazol-4-yl] methyl] 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methylpyrazolo [4,3 -T>] pyridin-7-amine 73 5.9 110 166 5 - (2-ethoxy-3-pirid yl) -A- [[5 (fluoromethyl) isoxazol-3-yl] methyl] -1 isopropyl-3-methylpyrazolo [4.3 b} pyridin-7-amine 2.1 0.16 7.2 167 5 - (2-ethoxy-3-p irid yl) -A - [[3 (fluoromethyl) isoxazol-5-yl] methyl] -1 isopropyl-3-methylpyrazolo [4,3 L] pyridin-7-amine AND one 33 168 1-isopropyl-3-methyl-TV - [(1-methylpyrazol4-yl) methyl] -5-oxazol-2-ylpyrazolo [4,3 b \ pyridin-7-amine fourteen 2.6 36 169 1 -isopropyl-3-methyl-TV- [(1-methylpyrazol4-yl) methyl] -5- (3-methyltriazol-4yl) pyrazolo [4,3 - />] pyridin-7-amine 610 85 170 170 1 -isopropyl-5 - (2-methoxy-3-pyridyl) -3 methyl-TV- [[2- (trifluoromethyl) -3 pyridyl] methyl] pyrazolo [4,3 - />] pyridine-7amine 42 5.3 46

- 51 037544

171 3 - [1-isopropyl-7 - [(2-methoxy-3 pyrid yl) methylamino] -3 methylpyrazolo [4,3-b] pyridin-5-yl] - \ Npyridin-2-one 290 47 420 172 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(3-methoxy-4-pyridyl) methyl] -3 methylpyrazolo [4,3 -T>] pyridin-7-amine 40 5.5 46 173 1-isopropyl-5 - (2-methoxy-3-pyridyl) -3 methyl-TU - [(2-methylthiazol-5yl) methyl] pyrazolo [4,3-b} pyridin-7-amine 49 6.3 26 174 5 - (2-cyclopropoxypyrid in-3-yl) -1 isopropyl-TU - ((2-methoxypyridin-3yl) methyl) -3 -methyl- 1H-pyrazolo [4,3 b} pyridin-7-amine eighteen 1.5 52 175 1-isopropyl-TU - ((2-methoxypyridin-3 yl) methyl) -3 -methyl-5 - (1 -methyl- 1 // - pyrazol5-yl) - III-pyrazolo [4,3-b} pyridine -7-amine 83 17 130 176 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TV- [(5 methoxypyr imid in-2-yl) methyl] -3 methylpyrazolo [4,3 -T>] pyridin-7-amine 81 12 93 177 3 - [1 -isopropyl-3-methyl-7 - [(1 methylpyrazol-4yl) methylamino] pyrazolo [4,3 - />] pyridin-5yl] -1 // - pyridin-2-one 130 twenty 180 178 TV- [[2- (d ifluoromethyl) -3-pyridyl] methyl] -5 (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methylpyrazolo [4,3-T>] pyridin-7-amine 31 3.2 63 179 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TU - [(6methoxypyrimid in-4-yl) methyl] -3 methylpyrazolo [4,3 -T>] pyridin-7-amine 2.8 0.51 7 180 5 - (2- (ethoxy-1,1 -d2) nnp idin-3-yl) -1 isopropyl-TU - ((2-methoxypyridin-3yl) methyl) -3 -methyl- 1 // - pyrazolo [4, 3 - A] pyridin-7-amine 27 0.77 78 181 5- (2- (ethoxy-05) pyridin-3-yl) -1 isopropyl-TU - ((2-methoxypyridin-3yl) methyl) -3 -methyl- 1H-pyrazolo [4.3 b} pyridine-7 -amine 31 1.6 84 182 5 - (2- (ethoxy-2,2,2-0h) pyrid in-3-yl) -1 isopropyl-TU - ((2-methoxypyridin-3yl) methyl) -3 -methyl- 1 // - pyrazolo [ 4.3 A] pyridin-7-amine 24 1.1 61 183 1-isopropyl-TU - ((2-methoxypyr idin-3 yl) methyl) -3-methyl-5- (2 (trifluoromethyl) pyridin-3-yl) -1 // pyrazolo [4,3-T>] pyrid in-7-amine 290 38 350 184 3 - (difluoro methyl) -5 - (2-ethoxypyridin-3 yl) -1 -isopropyl-TU - ((1-methyl- 1H-pyrazol4-yl) methyl) -1H-pyrazolo [4,3 - /> ] pyridine-7- amine 13 2.4 45 185 1 -isopropyl-3-methyl-A - ((1-methyl- \ Npyrazol-4-yl) methyl) -5- (1H-1,2,4-triazol-1 yl) -1H-pyrazolo [4,3 - />] pyridin-7-amine 100 24 92

- 52 037544

186 3 - [1-isopropyl-3-methyl-7 - [(1-methyl-1,2,4triazol-3-yl) methylamino] pyrazolo [4,3 L] pyridin-5-yl] - 177-pyridin -2-he 64 fifteen 130 187 3 - [1-isopropyl-3-methyl-7- (177-pyrazol-3 ylmethylamino) pyrazolo [4,3-T>] pyridin-5yl] - 1H-pyrid in-2-one 140 eighteen 250 188 5 - [2- (difluoromethoxy) -3 -pyridyl] -1 isopropyl-TU - [(2-methoxy-3pyridyl) methyl] -3 -methylpyrazolo [4.3 L] pyridin-7-amine 61 7.8 60 189 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TU - [(4methoxypyrimid in-2-yl) methyl] -3 methylpyrazolo [4,3 -T>] pyridin-7-amine 3.9 0.49 nineteen 190 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-TU - [(4methoxypyr imidin-5-yl) methyl] -3 methylpyrazolo [4,3 -T>] pyridin-7-amine 74 7.9 94 191 5 - (2-ethoxy-3-pyridyl) -A- [(2-ethoxy-3 pyridyl) methyl] -1 -isopropyl-3 methylpyrazolo [4,3 -T>] pyridin-7-amine 160 10 400 192 5 - [2- (dimethylamino) -3-pyridyl] -1 isopropyl-A - [(4-methoxyphenyl) methyl] -3methylpyrazolo [4,3-T>] pyridin-7-amine 630 71 490 193 3 - [1 -isopropyl-3-methyl-7- [[2 (trifluoromethyl) -Zpyrid yl] methylamino] pyrazolo [4.3 L] pyridin-5-yl] - 177-pyrid in-2-one 320 54 880 194 1-isopropyl-3-methyl-5 - (3-methylisoxazol4-yl) - # - [(1-methylpyrazol-4yl) methyl] pyrazolo [4,3-b} pyridin-7-amine 95 23 21 195 1 -isopropyl-3-methyl-5 - (1-methyl-177-1,2,4triazol-5-yl) -TU - ((1 -methyl- 1 // - pyrazol-4yl) methyl) -177-pyrazolo [4,3 - /] pyridine-7amine 420 110 160 196 1-isopropyl-3-methyl-5 - (2-propoxy-3 pyrid yl) -LCh1 / 7-pyrazole-4ylmethyl) pyrazolo [4,3 - />] pyridin-7-amine eighteen 1.7 27 197 5- (2-ethoxy-3-pyridyl) -TU - [(2-methoxy-3 pyridyl) methyl] -3 -methyl-1 - (oxetan-3 yl) pyrazolo [4,3-T>] pyridine-7 -amine 190 13 190 198 5 - (2- (ethyl (methyl) amino) pyridin-3-yl) -1 isopropyl-TU- (4-methoxybenzyl) -3-methyl177-pyrazolo [4,3-b] pyridin-7-amine 1100 240 1000 199 5 - (2-ethoxypyrid in-3-yl) -3 - (fluoromethyl) -1 isopropyl-TU - ((1-methyl- 177-pyrazol-4yl) methyl) - 177-pyrazolo [4,3 -T >] pyridine-7- amine 7.4 0.75 26 200 1-isopropyl-3-methyl -? / - ((1-methyl-177pyrazol-4-yl) methyl) -5- (4-methyloxazol-5yl) -177-pyrazolo [4,3 - /] pyridine-7- amine 98 eighteen 110 201 5 - [2- (dimethylamino) -3-pyridyl] -1 isopropyl-3-methyl-TV- [(1-methylpyrazole-4yl) methyl] pyrazolo [4,3-T>] pyridin-7-amine 2100 230 2100 202 1 -isopropyl-3 - methyl-A - ((1-methyl-177pyrazol-4-yl) methyl) -5- (4-methyloxazol-2yl) -1 / 7-pyrazolo [4,3-T>] pyridine- 7-amine 92 fourteen 170 203 1-isopropyl-3-methyl-TU - [(1-methylpyrazol4-yl) methyl] -5 - (4-methyl-1,2,4-triazol-3 yl) pyrazolo [4,3-b] pyridine-7 -amine 410 180 420

Table 1 lists the IC ₅₀ values for PDE1 inhibition by the compounds of the present invention. The IC ₅₀ value means the concentration (nM) of the compound required to achieve 50%

- 53 037544 inhibition of the PDE1 enzyme at a given substrate concentration. Assays for PDE1 are described in the experimental section.

Experimental section

Preparation of compounds of the present invention are general methods.

Compounds of formula (I) can be prepared using the methods described below in combination with synthetic methods known from the field of organic chemistry, or modifications that are familiar to those of ordinary skill in the art. The starting materials used herein are commercially available or can be obtained using conventional methods known in the art, such as those described in standard reference literature such as Compendium of Organic Synthetic Methods, Vol. I-XIII (published by Wiley-Interscience, ISSN: 1934-4783). Preferred methods include, without limitation, the methods described below.

The schemes depict methods useful in the synthesis of compounds of the present invention. They do not limit the scope of the present invention in any way.

Method 1.

Scheme 1

where R1 is as described for Formula I and R is hydrogen, or R is R2 as described for Formula I.

Compounds of general formula IV (Scheme 1) can be prepared from compounds of general formulas II and III.

Method 2.

Scheme 2

wherein R1 is as described for Formula I and R is R2 as described for Formula I or a protecting group such as para-hydroxybenzyl.

Compounds of general formula IV (Scheme 2) can be prepared from compounds of general formulas II, III and V described in the literature (for example, in international patent application WO 2013142307).

Method 3.

Scheme 3

where R1 is as described for Formula I, R is R2 as described for Formula I, or R is a protecting group such as para-hydroxybenzyl and Y is halogen such as chlorine or bromine.

Compounds of general formula VIII (Scheme 3) can be obtained by nitration of compounds

- 54 037544 of general formula IV followed by reduction. Compounds of general formula XI can be prepared by reacting compounds of general formula VIII with methyl 3-chloro-3-oxopropanoate followed by ring closure in the presence of a base such as sodium ethoxide or sodium methoxide. Hydrolysis and decarboxylation of compounds of general formula XI, followed by treatment with phosphoryl trichloride or phosphoryl tribromide, leads to compounds of general formula XIII.

Method 4.

Scheme 4

where R1 and R2 are described for Formula I, R is a protecting group such as para-hydroxybenzyl, Y is a halogen such as chlorine or bromine, and Z is a leaving group such as chlorine, bromine, iodine or methanesulfonate group, or Z represents a hydroxy group.

Compounds of general formula XIV (Scheme 4) can be obtained by removing the protective group from compounds of general formula XIII, where R is a protective group. If the protecting group is para-hydroxybenzyl, the removal of the protecting group can be carried out by treatment with an acid such as trifluoroacetic acid. Compounds of general formula XIII can be prepared by reacting compounds of general formula XIV with compounds of general formula XV in the presence of a base such as cesium carbonate, or using Mitsunobu reaction conditions when Z is hydroxy.

Method 5.

Scheme 5

where R1, R2, R3 and R4 are described for formula I, L is NH, O or S, and R are hydroxy groups, or R together with a boron atom form 4,4,5,5-tetramethyl-1,3,2 dioxaborolane group. Y is halogen such as chlorine or bromine.

Compounds of general formula XVII (Scheme 5) can be prepared by treating compounds of general formula XIII with compounds of general formula XVI in the presence of a base such as, without limitation, cesium fluoride or N, N-diisopropylethylamine. Compounds of general formula I can be prepared from compounds of general formulas XVII and XVIII in the presence of a palladium catalyst such as [1,1'-bis (diphenylphosphino) ferrocene] palladium (P) dichloride and a base such as potassium carbonate or otherwise the reaction conditions of the Suzuki-Miyaura coupling known to chemists who are specialists in the field of organic synthesis.

Method 6.

Scheme 6

where Rl, R2, R3 and R4 are described for formula I, R are hydroxy groups, or R together with

55 037544 with a boron atom form a 4,4,5,5-tetramethyl-1,3,2-dioxaborolane group, and Pg is a protecting group such as para-hydroxybenzyl. Y is halogen such as chlorine or bromine.

Compounds of general formula XX (Scheme 6) can be prepared by treating compounds of general formula XIII with compounds of general formula XIX in the presence of a base such as, without limitation, cesium fluoride or N, N-diisopropylethylamine. Compounds of general formula XXI can be prepared from compounds of general formulas XX and XVIII in the presence of a palladium catalyst such as [1,1'-bis (diphenylphosphino) ferrocene] palladium (II) dichloride and a base such as potassium carbonate, or otherwise the reaction conditions of the Suzuki-Miyaura coupling known to chemists who are specialists in the field of organic synthesis. Compounds of general formula XXII can be obtained by removing the protective group from compounds of general formula XXI. If the protecting group is para-hydroxybenzyl, the removal of the protecting group can be carried out by treatment with an acid such as trifluoroacetic acid. Compounds of general formula I can be prepared by reductive amination of compounds of general formula XXII with a suitable aldehyde or ketone.

Method 7.

Scheme 7

where R1, R2, and R3 are described for formula I, L is NH, O or S, R are hydroxy groups, or R together with a boron atom form 4,4,5,5-tetramethyl-1,3,2-dioxaborolane group. Y is halogen such as chlorine or bromine.

Compounds of general formula XXIV (Scheme 7) can be prepared from compounds of general formulas XIII and XXIII in the presence of a palladium catalyst such as [1,1'bis (diphenylphosphino) ferrocene] palladium (II) dichloride and a base such as potassium carbonate, or under other conditions of the Suzuki-Miyaura coupling reaction known to chemists who are skilled in the field of organic synthesis. Compounds of general formula XXV can be prepared by treating compounds of general formula XXIV with compounds of general formula XVI in the presence of a base such as, without limitation, cesium fluoride or N, N-diisopropylethylamine. Compounds of general formula I can be prepared by treating compounds of general formula XXV with sodium ethoxide.

Method 8.

Scheme 8

where R1, R2, R3, R4 and L are described for formula I, and M is ZnCl or SnR ₃ , where R are alkyl groups such as butyl or methyl. Y is halogen such as chlorine or bromine.

Compounds of general formula I (Scheme 8) can be prepared from compounds of general formulas XVII and XXVI in the presence of a palladium catalyst such as Pd (PPh ₃ ) ₄ , or under other conditions of the Stille or Negisi coupling reaction known to chemists who are specialists in the field organic synthesis.

- 56 037544

Method 9.

Scheme 9

where R1, R2, R3 and L are described for formula I, and M is ZnCl or Sn (R) ₃ , where R are alkyl groups such as butyl or methyl. Y is halogen such as chlorine or bromine. R4 is described for formula I, wherein the point of attachment for R4 is nitrogen.

Compounds of general formula I (Scheme 9) can be prepared from compounds of general formulas XVII and XXVII in the presence of a copper catalyst such as CuI in combination with a ligand, or a palladium catalyst such as Pd ₂ (dba) ₃ in combination with Xantphos, and a base such as CS ₂ CO ₃ using reaction conditions known to chemists who are skilled in the field of organic synthesis.

Method 10.

Scheme 10

where R1, R2 and R4 are described for formula I, L is CH ₂ , and R3 is methyl substituted with phenyl, pyridonyl, pyridinyl, pyrimidinyl or pyrazinyl, all of which may optionally be substituted one or more times with one or more substituents, selected from the group consisting of halogen, cyano, C ₁ -C ₃ alkyl, C ₁ -C ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy, and C ₁ -C ₃ alkoxy; or R3 represents a methyl, substituted 5-membered heteroaryl which is optionally substituted by one or more substituents selected from halo, cyano, C1S ₃ alkyl, C ₁ -C ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy, and C ₁ -C ₃ alkoxy ... R5 is phenyl, pyridonyl, pyridinyl, pyrimidinyl or pyrazinyl, all of which may be optionally substituted one or more times with one or more substituents selected from the group consisting of halogen, cyano, C ₁ -C ₃ alkyl, C ₁ -C ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy and C ₁ -C ₃ alkoxy; or R5 is 5-membered heteroaryl which is optionally substituted with one or more substituents selected from halogen, cyano, C ₁ -C ₃ alkyl, C ₁ -C ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy, and C ₁ -C ₃ alkoxy ... Y is halogen such as chlorine or bromine. X is halogen such as iodine or bromine.

Compounds of general formula XXVIII (Scheme 10) can be obtained by treating compounds of general formula XIII with a reagent such as i-PrMgCl-LiCl, followed by treatment with N, Ndimethylformamide. Compounds of general formula XXIX can be prepared by treating compounds of general formula XXVIII with a reagent such as 1-diazo-1-dimethoxyphosphorylpropan-2-one and a base such as CS2CO3.

Compounds of general formula XXXI can be prepared from compounds of general formulas XXIX and XXX in the presence of a palladium catalyst such as [1,1'-bis (diphenylphosphino) ferrocene] palladium (11) dichloride, a base such as triethylamine, and a copper catalyst such as CuI, using reaction conditions known to chemists who are skilled in the field of organic synthesis. Compounds of general formula I can be prepared by treating compounds of general formula XXXI with palladium on carbon in a hydrogen atmosphere.

- 57 037544

Method 11.

Scheme 11

where R1, R2 and R4 are described for formula I, L is CH ₂ , and R3 is NH substituted with phenyl, pyridonyl, pyridinyl, pyrimidinyl, or pyrazinyl, all of which may optionally be substituted one or more times with one or more substituents, selected from the group consisting of halogen, cyano, C ₁ -C ₃ alkyl, C ₁ -C ₃ ftorαlkila, C ₁ -C ₃ ftorαlkoksi and C ₁ -C ₃ alkoxy; or L is CH ₂ and R3 is NH substituted with 5-membered heteroaryl, which is optionally substituted with one or more substituents selected from halogen, cyano, C ₁ -C ₃ alkyl, C ₁ -C ₃ fluoroalkyl, C ₁ - C ₃ fluoroalkoxy and C ₁ -C ₃ alkoxy. R5 is phenyl, pyridonyl, pyridinyl, pyrimidinyl or pyrazinyl, all of which may optionally be substituted one or more times with one or more substituents selected from the group consisting of halogen, cyano, C ₁ -C ₃ alkyl, C ₁ -C ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy and C ₁ -C ₃ alkoxy; or R5 is a 5-membered heteroaryl which is optionally substituted by one or more substituents selected from halo, cyano, C ₁ -C ₃ alkyl, C ₁ -C ₃ ftorαlkila, C ₁ -C ₃ ftorαlkoksi and C _r C ₃ alkoxy. Y is halogen such as chlorine or bromine.

Compounds of general formula XVII (Scheme 11) can be obtained by reductive amination of compounds of general formula XXVIII with compounds of general formula XXXII.

Method 12.

Scheme 12

R1 R1 R1

XXXV ¹ where R1, R2, R3 and R4 are described for formula I, and L is sulfur. Y is halogen such as chlorine or bromine. Pg is a protecting group such as 6-methylheptylpropano-3-at. Lg represents a leaving group such as chlorine, bromine, iodine, 4methylbenzenesulfonate or methanesulfonate.

Compounds of general formula XXXIII (Scheme 12) can be prepared by treating compounds of general formula XIII with a reagent such as 6-methylheptyl-3-mercaptopropanoate in the presence of a base such as diisopropylethylamine. Compounds of general formula XXXIV can be prepared by the same methods as described in methods 5, 8 and 9. Compounds of general formula I can be prepared by deprotection of compounds of general formula XXXIV using a base such as potassium t-butoxide, followed by by alkylation with compounds of general formula XXXVI.

Method 13.

Scheme 13

where R1, R2, R3 and R4 are described for formula I, and L is NH. Pg is a protecting group such as p-methoxybenzyl and Lg is a leaving group such as chlorine, bromine, iodine, 4-methylbenzenesulfonate or methanesulfonate.

Compounds of general formula XXXVII (Scheme 13) can be prepared by deprotonation of co-58 037544 compounds of general formula XXI with a base such as sodium hydride, followed by alkylation with compounds of general formula XXXVI. Compounds of the general formula! I can be obtained by removing the protecting group (Pg) using reaction conditions known to chemists who are skilled in the field of organic synthesis, for example by treatment with trifluoroacetic acid when Pg is n-methoxybenzyl.

LC-MS methods.

Method A.

An Agilent 1200 LCMS with an ELS detector was used. Phenomenex Luna-C18, 5 μm; 2.0x50 mm; column temperature: 50 ° C; solvent system: A = water / trifluoroacetic acid (99.9: 0.1) and B = acetonitrile / trifluoroacetic acid (99.95: 0.05); method: linear gradient elution with A: B = 90:10 to 0: 100 in 4.0 min and at a flow rate of 0.8 ml / min.

Method B.

An Agilent 1200 LCMS with an ELS detector was used. Column: Waters XBridge ShieldRP18, 2.1x50mm, 5μm; column temperature: 40 ° C; solvent system: A = water / ammonia (99.95: 0.05) and B = acetonitrile; method: linear gradient elution with A: B = 95: 5 to 0: 100 in 4.0 min and at a flow rate of 0.8 ml / min.

Method C.

An Agilent 1200 LCMS with an ELS detector was used. Phenomenex Luna-C18, 5 μm; 2.0x50 mm; column temperature: 50 ° C; solvent system: A = water / trifluoroacetic acid (99.9: 0.1) and B = acetonitrile / trifluoroacetic acid (99.95: 0.05); method: linear gradient elution with A: B = 99: 1 to 0: 100 in 4.0 min and at a flow rate of 0.8 ml / min.

Method D.

Acquity UPLC-MS from Waters was used. Column: Acquity UPLC VEN C18, 1.7 μm, 2.1x50 mm; column temperature: 60 ° C; solvent system: A = water / trifluoroacetic acid (99.965: 0.035) and B = acetonitrile / water / trifluoroacetic acid (94.965: 5: 0.035); method: linear gradient elution with A: B = 90:10 to 0: 100 in 1.0 min and at a flow rate of 1.2 ml / min.

Method E.

Acquity UPLC-MS from Waters was used. Column: Acquity UPLC VEN C18, 1.7 μm, 2.1x50 mm; column temperature: 60 ° C; solvent system: A = water / formic acid (99.9: 0.1) and B = acetonitrile / water / formic acid (94.9: 5: 0.1); method: linear gradient elution with A: B = 90:10 to 0: 100 in 1.0 min and at a flow rate of 1.2 ml / min.

Method F.

An Agilent 1200 LCMS with an ELS detector was used. Column: Waters XBridge ShieldRP18, 2.1x50mm, 5μm; column temperature: 40 ° C; solvent system: A = water / ammonia (99.95: 0.05) and B = acetonitrile; method: linear gradient elution with A: B = 85:15 to 0: 100 in 3.4 min and at a flow rate of 0.8 ml / min.

Method G.

An Agilent 1200 LCMS with an ELS detector was used. Column: Agilent TC-C18, 5 μm; 2.1x50 mm; column temperature: 50 ° C; solvent system: A = water / trifluoroacetic acid (99.9: 0.1) and B = acetonitrile / trifluoroacetic acid (99.95: 0.05); method: linear gradient elution with A: B = 99: 1 to 0: 100 in 4.0 min and at a flow rate of 0.8 ml / min.

Method N.

An Agilent 1200 LCMS with an ELS detector was used. Column: Waters XBridge ShieldRP18, 2.1x50mm, 5μm; column temperature: 40 ° C; solvent system: A = water / ammonia (99.95: 0.05) and B = acetonitrile; method: linear gradient elution with A: B = 70:30 to 0: 100 in 3.4 min and at a flow rate of 0.8 ml / min.

Method I.

An Agilent 1200 LCMS with an ELS detector was used. Phenomenex Luna-C18, 5 μm; 2.0x50 mm; column temperature: 50 ° C; solvent system: A = water / trifluoroacetic acid (99.9: 0.1) and B = acetonitrile / trifluoroacetic acid (99.95: 0.05); method: linear gradient elution with A: B = 75:25 to 0: 100 in 3.4 min and at a flow rate of 0.8 ml / min.

Method J.

Waters Autopurification was used. Column: XSelect CSH С18, 3.5 μm, 4.6x50 mm; column temperature: 25 ° C; solvent system: A = water / formic acid (99.9: 0.1) and B = acetonitrile / trifluoroacetic acid (99.9: 0.1); method: linear gradient elution with A: B = 97: 3 to 10:90 in 2.5 min and at a flow rate of 2.5 ml / min.

Method K.

Waters Autopurification was used. Column: XSelect CSH С18, 3.5 μm, 4.6x50 mm; column temperature: 25 ° C; solvent system: A = water / formic acid (99.9: 0.1) and B = acetonitrile / trifluoroacetic acid (99.9: 0.1); method: linear gradient elution with A: B =

- 59 037544 from 97: 3 to 10:90 in 2.5 minutes, then with A: B = 10:90 for 1 minute. The flow rate was 2.5 ml / min.

Intermediate connections.

Obtaining ethyl 3-methyl-1H-pyrazole-5-carboxylate

A solution of ethyl 2,4-dioxopentanoate (20 g, 126 mmol, 18 ml) and hydrazine hydrate (6.96 g, 139 mmol, 6.76 ml) in ethanol (400 ml) was stirred at 0 ° С for 1 h The mixture was concentrated to give ethyl 3-methyl-1H-pyrazole-5-carboxylate (19 g, 123 mmol, 97% yield).

Obtaining ethyl 1,3-dimethyl-1 H-pyrazole-5-carboxylate

To a solution of ethyl 3-methyl-1H-pyrazole-5-carboxylate (19.5 g, 126 mmol) in DMF (200 ml) was added Me ₂ SO ₄ (23.8 g, 189 mmol, 17.9 ml). The mixture was stirred at 80 ° C for 18 hours. After cooling to 0 ° C, the mixture was diluted with ice, then aqueous ammonia solution (25%) was added to adjust the pH to 8. The mixture was then extracted with ethyl acetate (300 ml x 3), the combined organic layers washed with brine (50 ml), dried and concentrated. The crude mixture was purified by flash chromatography using petroleum ether: ethyl acetate = 5: 1 to give ethyl 1,3-dimethyl 1H-pyrazole-5-carboxylate (15 g, 89 mmol, 71% yield).

Obtaining ethyl 2- (methoxyimino) -4-oxopentanoate

Stirred a mixture of ethyl 2,4-dioxopentanoate (27 g, 171 mmol, 24 ml) and methoxylamine (15 g, 179 mmol, 13.6 ml) in ethanol (150 ml) at 25 ° C for 18 h under nitrogen atmosphere ... The mixture was concentrated. The crude mixture was purified by flash chromatography on silica gel with petroleum ether: ethyl acetate = 10: 1 to give ethyl 2- (methoxyimino) -4-oxopentanoate (19.9 g, 103 mmol, 60% yield).

¹ H NMR (chloroform-d 400 MHz): δ 4.34 (q, J = 6.8 Hz, 2H), 4.07 (s, 3H), 3.71 (s, 2H), 2.21 ( s, 3H), 1.35 (d, J = 7.6 Hz, 3H).

Preparation of ethyl 1 -isopropyl-3-methyl-1 H-pyrazole-5-carboxylate

To a solution of ethyl 2- (methoxyimino) -4-oxopentanoate (14.6 g, 78.0 mmol) in ethanol (200 ml) was added isopropylhydrazine hydrochloride (17.25 g, 156 mmol). The mixture was stirred at 80 ° C for 18 hours. The mixture was concentrated. _{Saturated aqueous NaHCO 3 was} added to the residue to adjust the pH to 7. The mixture was then extracted with dichloromethane (100 ml x 3), the combined organic layers were washed with brine, dried over Na ₂ SO ₄ and concentrated. The crude mixture was purified by flash chromatography on silica gel with petroleum ether: ethyl acetate = 10: 1 to give ethyl 1-isopropyl-3-methyl-1H-pyrazole-5-carboxylate (12.3 g, 62.7 mmol , yield 80%).

1H NMR (chloroform-d 400 MHz): δ 6.59 (s, 1H), 5.41-5.44 (m, 1H), 4.35-4.29 (m, 2H), 2.29 ( s, 3H), 1.48 (d, J = 6.8 Hz, 6H), 1.39-1.35 (m, 3H).

Obtaining ethyl 1 -isopropyl-3-methyl-4-nitro-1 H-pyrazole-5-carboxylate

Into a solution of ethyl 1-isopropyl-3-methyl-1H-pyrazole-5-carboxylate (8 g, 40.8 mmol) and (2,2,2 trifluoroacetyl) -2,2,2-trifluoroacetate (59.9 g, 285.4 mmol, 39.7 ml) in TFA (80 ml) was slowly added ammonium nitrate (6.5 g, 81.5 mmol, 3.8 ml) at 0 ° C. The mixture was stirred at 20 ° C for 18 hours. The solution was cooled to 0 ° C and then neutralized with an aqueous solution of K2CO3 and the product was extracted with ethyl acetate: dichloromethane = 40: 1 (205 ml x 4). The combined organic layers were washed with brine (150 ml), dried over Na ₂ SO ₄ and concentrated to give ethyl 1-isopropyl-3methyl-4-nitro-1H-pyrazole-5-carboxylate (9.8 g).

Ethyl 1-ethyl-3-methyl-4-nitro-1H-pyrazole-5-carboxylate was prepared in a similar manner from ethylhydrazine.

Ethyl 1-cyclopropyl-3-methyl-4-nitro-1H-pyrazole-5-carboxylate was prepared in a similar manner from cyclopropylhydrazine.

(±) -Ethyl-1- (sec-butyl) -3-methyl-1H-pyrazole-5-carboxylate was prepared in a similar manner from (±) -sec-butylhydrazine hydrochloride.

Obtaining ethyl 3-methyl-4-nitro-1 H-pyrazole-5-carboxylate

Ethyl 3-methyl-1H-pyrazole-5-carboxylate (12 g, 78 mmol) was added portionwise to fuming nitric acid (140 g, 2.2 mol, 100 ml) at 0 ° C. The mixture was stirred at 15 ° C for 16 hours. The mixture was poured onto ice (200 g) and adjusted to pH 7 with saturated aqueous K ₂ CO ₃ . The mixture was extracted with ethyl acetate (500 ml x 2). The organic layer was washed with H 2 O (500 ml), brine (500 ml), dried over Na ₂ SO ₄ , filtered and concentrated to give ethyl 3-methyl-4-nitro-1H-pyrazole-5-carboxylate (13 g, 65 mmol, yield 84%).

¹ H NMR (chloroform-d 400 MHz) δ 11.41 (brs, 1H), 4.47-4.42 (m, 2H), 2.64 (s, 3H), 1.39 (t, J = 7.2 Hz, 3H).

Preparation of ethyl 1- (4-methoxybenzyl) -3-methyl-4-nitro-III-pyrazole-5-carboxylate and ethyl 1- (4-methoxybenzyl) -5-methyl-4-nitro-1H-pyrazole-3-carboxylate \ / ^C1

H ° ~ \ 7— 'RMV pn r

EU ₂ C. D \ = / EtO ₂ C _n ' ^Et0 2 ^C ^ N

Γ? Ν _______ Υ ' _Ν Γ Ν-ΡΜΒ

Ο ₂ Ν ^ \ О ₂ Ы ^X D ° ₂ Ν ^ \

To a solution of ethyl 3-methyl-4-nitro-1H-pyrazole-5-carboxylate (4.40 g, 22.1 mmol) in dry DMF (50 ml) was added 1- (chloromethyl) -4-methoxybenzene (4, 15 g, 26.5 mmol, 3.6 ml) and K2CO3 (6.11 g, 44.2 mmol). The mixture was stirred at 15 ° C for 16 hours. The mixture was concentrated and water (20 ml) was added. The mixture was extracted with ethyl acetate (20 ml x 2). The combined organic layers were washed with H ₂ O (20 ml x 2), brine (20 ml), dried over Na ₂ SO ₄ , filtered and concentrated. The residue was purified by flash chromatography on silica gel (0 to 50% ethyl acetate in petroleum ether) to give ethyl 1- (4-methoxybenzyl) -3-methyl-4-nitro-1H-pyrazole-5-carboxylate (2, 80 g, 8.77 mmol, 40% yield) and ethyl 1- (4-methoxybenzyl) -5-methyl-4-nitro-1H-pyrazole-3-carboxylate (3.50 g, 11 mmol, 50% yield ).

Preparation of ethyl 4-amino-1-isopropyl-3-methyl-1 H-pyrazole-5-carboxylate

IEtO ₂ C _x J ^ 'EOrC ^' ^

O ₂ N ^Z \

To a solution of ethyl 1-isopropyl-3-methyl-4-nitro-1H-pyrazole-5-carboxylate (10.23 g, 42.41 mmol) in ethyl acetate (200 ml) was added Pd-C (10%, 2, 0 g, wet) in a nitrogen atmosphere. The suspension was degassed under vacuum and flushed with hydrogen several times. The mixture was stirred under a hydrogen atmosphere (30 psi) at 40 ° C for 18 hours. The mixture was filtered and the residue was washed with ethyl acetate (150 ml x 3), the combined filtrates were concentrated to give ethyl 4-amino-1-isopropyl- 3-methyl 1H-pyrazole-5-carboxylate (8.96 g).

Ethyl 4-amino-1- (4-methoxybenzyl) -3-methyl-1H-pyrazole-5-carboxylate was prepared similarly from ethyl 1 - (4-methoxybenzyl) -3-methyl-4-nitro-1 H- pyrazole-5-carboxylate.

Ethyl 4-amino-1-ethyl-3-methyl-1H-pyrazole-5-carboxylate was prepared in a similar manner from ethyl 1ethyl-3-methyl-4-nitro-1H-pyrazole-5-carboxylate.

Ethyl 4-amino-1-cyclopropyl-3-methyl-1H-pyrazole-5-carboxylate was prepared in a similar manner from ethyl 1-cyclopropyl-3-methyl-4-nitro-1H-pyrazole-5-carboxylate.

Ethyl 4-amino-1,3-dimethyl-1H-pyrazole-5-carboxylate was prepared in a similar manner from ethyl 1,3-dimethyl-4-nitro-1H-pyrazole-5-carboxylate.

- 61 037544 (±) -Ethyl-4-amino-1- (sec-butyl) -3-methyl-1H-pyrazole-5-carboxylate was obtained in a similar manner from (±) -ethyl-1 - (sec-butyl) - 3-methyl-1 H-pyrazole-5-carboxylate.

Preparation of ethyl 1 -isopropyl-4- (3-methoxy-3-oxopropanamido) -3-methyl-1 H-pyrazole-5-carboxylate

To a solution of ethyl 4-amino-1-isopropyl-3-methyl-1H-pyrazole-5-carboxylate (7.96 g, 37.7 mmol) in dichloromethane (150 ml) was added methyl 3-chloro-3-oxopropanoate (5.14 g, 37.7 mmol, 4.02 ml). The mixture was stirred at 50 ° C for 45 minutes. After the reaction mixture was cooled to room temperature, the mixture was partitioned between dichloromethane (200 ml) and saturated aqueous NaHCO ₃ (100 ml), the aqueous phase was extracted with dichloromethane (100 ml x 2), the combined organic layers were washed with brine (50 ml) , dried over MgSO ₄ and concentrated to give ethyl 1-isopropyl-4- (3-methoxy-3-oxopropanamido) -3-methyl-1H-pyrazole-5-carboxylate (11.7 g, 37 mmol,> 95% yield) ...

Ethyl 4- (3-methoxy-3-oxopropanamido) -1- (4-methoxybenzyl) -3-methyl-1H-pyrazole-5-carboxylate was prepared similarly from ethyl 4-amino-1- (4-methoxybenzyl) -3-methyl-1H-pyrazole-5-carboxylate.

Ethyl 1-ethyl-4- (3-methoxy-3-oxopropanamido) -3-methyl-1H-pyrazole-5-carboxylate was prepared similarly from ethyl 4-amino-1-ethyl-3-methyl-1H-pyrazole -5-carboxylate.

Ethyl 1-cyclopropyl-4- (3-methoxy-3-oxopropanamido) -3-methyl-1H-pyrazole-5-carboxylate was prepared in a similar manner from ethyl 4-amino-1-cyclopropyl-3-methyl-1H-pyrazole -5-carboxylate.

Ethyl 4- (3-methoxy-3-oxopropanamido) -1,3-dimethyl-1H-pyrazole-5-carboxylate was prepared similarly from ethyl 4-amino-1,3-dimethyl-1H-pyrazole-5-carboxylate ...

(±) -Ethyl-1 - (sec-butyl) -4- (3-methoxy-3-oxopropanamido) -3-methyl-1H-pyrazole-5-carboxylate was prepared in a similar manner from (±) -ethyl-4- amino-1- (sec-butyl) -3-methyl-1H-pyrazole-5-carboxylate.

Preparation of methyl 5,7-dihydroxy-1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine-6-carboxylate

NaOEt (5 , 45 g, 80 mmol). The mixture was stirred at 20 ° C for 1 hour. The mixture was concentrated. The crude product (10.62 g) was used in the next step without further purification.

Methyl 5,7-dihydroxy-1- (4-methoxybenzyl) -3-methyl-1H-pyrazolo [4,3-b] pyridine-6-carboxylate was prepared similarly from ethyl 4- (3-methoxy-3- oxopropanamido) -1- (4-methoxybenzyl) -3-methyl-1Hpyrazole-5-carboxylate.

Methyl 1-ethyl-5,7-dihydroxy-3-methyl-1 H-pyrazolo [4,3-L] pyridine-6-carboxylate was prepared in a similar manner from ethyl 1-ethyl-4- (3-methoxy-3 -oxopropanamido) -3-methyl-1H-pyrazole-5-carboxylate.

Methyl 1-cyclopropyl-5,7-dihydroxy-3-methyl-1H-pyrazolo [4,3-b] pyridine-6-carboxylate was prepared in a similar manner from ethyl 1-cyclopropyl-4- (3-methoxy-3- oxopropanamido) -3-methyl-1H-pyrazole-5carboxylate.

Methyl 5,7-dihydroxy-1,3-dimethyl-1H-pyrazolo [4,3-b] pyridine-6-carboxylate was prepared similarly from ethyl 4- (3-methoxy-3-oxopropanamido) -1,3 -dimethyl-1H-pyrazole-5-carboxylate.

(±) -Methyl-1- (sec-butyl) -5,7-dihydroxy-3-methyl-1H-pyrazolo [4,3-b] pyridine-6-carboxylate was prepared in a similar manner from (±) -ethyl-1 - (sec-butyl) -4- (3-methoxy-3-oxopropanamido) -3-methyl-1Hpyrazole-5-carboxylate.

Preparation of 1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine-5,7-diol

Stirred a mixture of methyl 5,7-dihydroxy-1-isopropyl-3-methyl-1 H-pyrazolo [4,3-b] pyridine-6-carboxylate (10.62 g, 40.04 mmol) in aqueous NaOH solution (2N. , 150 ml) at 110 ° С for 6 h. The mixture was cooled to 0 ° С, then a saturated aqueous solution of KHSO4 was added with pH adjustment to

- 62 037544

2-3. The resulting mixture was filtered and the residue was washed with water (50 ml x 3) then dried to give 1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine-5,7-diol α (7 g, 32.43 mmol, yield 81%).

1H NMR (DMSO-d6 400 MHz) δ 11.02 (brs, 1H), 5.50 (s, 1H), 5.11-5.08 (m, 1H), 2.24 (s, 3H), 1.37 (d, J = 6.8 Hz, 6H).

1- (4-Methoxybenzyl) -3-methyl-1H-pyrαzolo [4,3-b] pyridine-5,7-diol was prepared in a similar manner from methyl-5,7-dihydroxy-1- (4-methoxybenzyl) -3 -methyl-1H-pyrazolo [4,3-b] pyridine-6-carboxylate.

1-Ethyl-3-methyl-1H-pyrazolo [4,3-b] pyridine-5,7-diol was obtained in a similar manner from methyl-1-ethyl5,7-dihydroxy-3-methyl-1 H-pyrazolo [4, 3-b] pyridine-6-carboxylate.

1-Cyclopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine-5,7-diol was obtained in a similar manner from methyl 1 -cyclopropyl-5,7-dihydroxy-3-methyl-1 H-pyrazolo [4, 3-b] pyridine-6-carboxylate.

1,3-Dimethyl-1H-pyrazolo [4,3-b] pyridine-5,7-diol was prepared in a similar manner from 1-cyclopropyl-3methyl-1H-pyrazolo [4,3-b] pyridine-5,7-diol ...

(±) -1- (sec-Butyl) -3-methyl-1H-pyrazolo [4,3-b] pyridine-5,7-diol was prepared similarly from (±) methyl-1- (sec-butyl) - 5,7-dihydroxy-3-methyl-1H-pyrazolo [4,3-b] pyridine-6-carboxylate.

Preparation of 5,7-dichloro-1-isopropyl-3-methyl-1 H-pyrazolo [4,3-b] pyridine

Stir a mixture of 1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine-5,7-diol (3.50 g, 16.9 mmol) in phosphoryl trichloride (30 ml) at 80 ° C for 18 h. The mixture was stirred at 85 ° C for an additional 1 h. The mixture was concentrated and then water (50 ml) was added slowly followed by the addition of saturated aqueous NaHCO ₃ solution adjusting the pH to 7. The aqueous phase was extracted with ethyl acetate (70 ml x 3) , the combined organic layers were washed with brine (50 ml), dried over Na ₂ SO ₄ and concentrated. The crude product was purified by flash chromatography with petroleum ether: ethyl acetate = 20: 1 to give 5,7-dichloro-1-isopropyl-3-methyl-1Hpyrazolo [4,3-b] pyridine (3.50 g, 14.3 mmol, 85% yield).

¹ H NMR (chloroform-d 400 MHz) δ 7.28 (s, 1H), 5.48-5.41 (m, 1H), 2.62 (s, 3H), 1.57 (d, J = 4.8 Hz, 6H).

The following compounds were prepared in a similar manner:

5,7-dibromo-1-isopropyl-3-methyl-1 H-pyrazolo [4,3-b] pyridine from 1-isopropyl-3-methyl-1H pyrazolo [4,3-b] pyridine-5,7- diol and phosphoryl tribromide;

1H NMR (chloroform-d 400 MHz) δ 7.60 (s, 1H), 5.61-5.55 (m, 1H), 2.63 (s, 3H), 1.57 (d, J = 6 , 4 Hz, 6H);

5,7-dibromo-1-ethyl-3-methyl-1H-pyrazolo [4,3-b] pyridine from 1-ethyl-3-methyl-1H-pyrazolo [4,3b] pyridine-5,7-diol and phosphoryl tribromide;

5,7-dichloro-1,3-dimethyl-1 H-pyrazolo [4,3-b] pyridine from 1,3-dimethyl-1 H-pyrazolo [4,3-b] pyridine 5,7-diol and phosphoryl trichloride;

1H NMR (chloroform-d 400 MHz) δ 7.29 (s, 1H), 4.29 (s, 3H), 2.60 (s, 3H);

- 63 037544 (±) -5,7-dibromo-1- (sec-butyl) -3-methyl-1H-pyrazolo [4,3-b] pyridine from (±) -1- (sec-butyl) -3 -methyl 1 H-pyrazolo [4,3-b] pyridine-5,7-diol and phosphoryl tribromide;

5,7-dibromo-1-cyclopropyl-3-methyl-1 H-pyrazolo [4,3-b] pyridine from 1-cyclopropyl-3-methyl-1H pyrazolo [4,3-b] pyridine-5,7-diol and phosphoryl tribromide;

¹ H NMR (chloroform-d 400 MHz) δ 7.63 (s, 1H), 3.99-3.88 (m, 1H), 2.57 (s, 3H), 1.41-1.38 ( m, 2H), 1.221.19 (m, 2H);

5,7-dibromo-1 - (4-methoxybenzyl) -3-methyl-1 H-pyrazolo [4,3-b] pyridine from 1 - (4-methoxybenzyl) -3 methyl-1H-pyrazolo [4,3- b] pyridine-5,7-diol and phosphoryl tribromide. Preparation of 5,7-dibromo-3-methyl1H-pyrazolo [4,3-b] pyridine

Heat a solution of 5,7-dibromo-1- (4-methoxybenzyl) -3-methyl-1H-pyrazolo [4,3-b] pyridine (650 mg, 1.58 mmol) in TFA (5 ml) at 80 ° C for 2 h. The mixture was concentrated and the residue was dissolved in H2O (5 ml). The mixture was adjusted to pH 7 with saturated aqueous NaHCO ₃ and extracted with ethyl acetate (20 ml x 2). The combined organic layers were washed with H 2 O (20 ml), brine (20 ml), dried over Na ₂ SO ₄ , filtered and concentrated to give 5,7-dibromo-3-methyl-1Hpyrazolo [4,3-b] pyridine (450 mg, 1.55 mmol, 98% yield).

Preparation of 5,7-dibromo-3-methyl-1 - (oxetane-3-yl) -1 H-pyrazolo [4,3-b] pyridine

To a solution of 5,7-dibromo-3-methyl-1H-pyrazolo [4,3-b] pyridine (340 mg, 1.17 mmol) in dry DMF (10 ml) was added 3-iodoxetane (323 mg, 1.76 mmol) and CS2CO3 (762 mg, 2.34 mmol). The mixture was heated with microwave radiation at 100 ° C for 1 h. The mixture was concentrated and water (20 ml) was added. The mixture was extracted with ethyl acetate (20 ml x 2). The combined organic layers were washed with H ₂ O (20 ml x 2), brine (20 ml), dried over Na ₂ SO ₄ , filtered and concentrated. The residue was purified by flash chromatography on silica gel (0 to 50% ethyl acetate in petroleum ether) to give 5,7-dibromo-3-methyl-1- (oxetan-3-yl) -1H-pyrazolo [4,3- b] pyridine (200 mg, 49% yield).

Preparation of (-) - 5,7-dibromo-1- (sec-butyl) -3-methyl-1H-pyrazolo [4,3-b] pyridine and (+) - 5,7-dibromo-1 (sec-butyl ) -3-methyl-1H-pyrazolo [4,3-b] pyridine

Purified (±) -5,7-dibromo-1- (sec-butyl) -3-methyl-1H-pyrazolo [4,3-b] pyridine (2.2 g, 6.34 mmol) twice using SFC with obtaining (+) - 5,7-dibromo-1- (sec-butyl) -3-methyl-1H-pyrazolo [4,3b] pyridine (800 mg) (Rt = 6.25 min) and (-) - 5 , 7-dibromo-1- (sec-butyl) -3-methyl-1H-pyrazolo [4,3b] pyridine (900 mg) (Rt = 6.28 min).

(+) - 5,7-Dibromo-1- (sec-butyl) -3-methyl-1H-pyrazolo [4,3-b] pyridine;

¹ H NMR (chloroform-d, 400 MHz): δ 7.60 (s, 1H), 5.41-5.32 (m, 1H), 2.63 (s, 3H), 2.13-2, 07 (m, 1H),

- 64 037544

1.87-1.83 (m, 1H), 1.54 (d, J = 6.4 Hz, 3H), 0.79 (t, J = 7.6 Hz, 3H). SFC-MS: tR = 6.25 min, ee% = 100%; [ab ²⁰ =

2.60 (c = 1.0, dichloromethane).

(-) - 5,7-Dibromo-1- (sec-butyl) -3-methyl-1H-pyrazolo [4,3-b] pyridine;

¹ H NMR (chloroform-d, 400 MHz): δ 7.60 (s, 1H), 5.41-5.32 (m, 1H), 2.63 (s, 3H), 2.13-2, 07 (m, 1H), 1.87-1.83 (m, 1H), 1.55 (d, J = 6.8 Hz, 3H), 0.79 (t, J = 7.6 Hz, 3H ). SFC-MS: tR = 6.5 min, ee% = 97.87%; [a] D ²⁰ = -2.90 (c = 1.0, dichloromethane).

SFC condition 1.

Instrument: Thar SFC-1; Column: (s, s) WHELK-01 (250 mm x 30 mm, 5 μm); mobile phase: A: supercritical CO ₂ , B: isopropyl alcohol (0.1% NH ₃ H ₂ O), A: B = 85:15 at 60 ml / min; pace. columns: 38 ° C; spray pressure: 100 bar; atomizer temperature: 60 ° C; evaporator temperature: 20 ° C; trimmer temperature: 25 ° С; wavelength: 220 nm.

SFC condition 2.

Instrument: Thar SFC-13; Column: (s, s) WHELK-O1 (250 mm x 30 mm, 5 μm); mobile phase: A: supercritical CO ₂ , B: isopropyl alcohol (0.1% ZNH ₃ H ₂ O), A: B = 85: 15 at 60 ml / min; pace. columns: 38 ° C; spray pressure: 100 bar; atomizer temperature: 60 ° C; evaporator temperature: 20 ° C; trimmer temperature: 25 ° С; wavelength: 220 nm.

Obtaining 4,6-dibromo-2-methylpyridin-3-amine

Bg

Vg ₂ , AcON ^Vg

^! 2 '2

Bg

Cooled a solution of 6-bromo-2-methylpyridin-3-amine (24 g, 128 mmol) and AcOH (14.7 ml, 257 mmol) in MeOH (200 ml) to 0 ° C, added Br ₂ (36.9 g , 230.9 mmol, 11.9 ml) and stirred at 0 ° C for 5 h. The mixture was quenched with saturated aqueous Na ₂ SO ₃ (500 ml), extracted with ethyl acetate (300 ml x 3). The organic layer was washed with brine (200 ml), dried over Na ₂ SO ₄ and concentrated in vacuo. The residue was purified by silica gel chromatography (petroleum ether: ethyl acetate = 2: 1) to give 4,6-dibromo-2-methylpyridin-3-amine (30 g, 87% yield).

Preparation of 5,7-dibromo-1H-pyrazolo [4,3-b] pyridine

To a mixture of 4,6-dibromo-2-methylpyridin-3-amine (15.0 g, 56.4 mmol) and AcOK (13.8 g, 141 mmol) in AcOH (30 ml) and toluene (200 ml) was added isopentyl nitrite (13.2 g, 112.8 mmol). The mixture was stirred at 25 ° C for 1 h, then at 60 ° C for 19 h. The mixture was concentrated in vacuo, diluted with water (300 ml) and extracted with ethyl acetate (200 ml x 2). The organic layer was washed with brine (100 ml), dried over Na ₂ SO ₄ and concentrated in vacuo to give 5,7-dibromo-Spirazolo [4,3-b] pyridine (5.4 g, 30% yield).

Preparation of 5,7-dibromo-1-ethyl-1H-pyrazolo [4,3-b] pyridine

Iodoethane was added to a mixture of 5,7-dibromo-1H-pyrazolo [4,3-b] pyridine (1 g, 3.6 mmol) and CS2CO3 (12.4 g, 7.2 mmol) in anhydrous DMF (10 ml) (0.8 g, 5.4 mmol). The mixture was stirred at 0 ° C for 0.5 h. The mixture was diluted with water (20 ml), extracted with ethyl acetate (30 ml x 2). The organic layer was washed with water (20 ml), brine (20 ml) and dried with Na ₂ SO ₄ , concentrated in vacuo. The residue was purified by silica gel chromatography (petroleum ether: ethyl acetate = 10: 1 to 5: 1) to give 5,7-dibromo-1-ethyl-1H-pyrazolo [4,3-b] pyridine (0.56 g , yield 51%).

1H NMR (DMSO-d ₆ 400 MHz) δ 8.37 (s, 1H), 7.98 (s, 1H), 4.72 (q, J = 7.2 Hz, 2H), 1.42 (t , J = 7.2 Hz, 3H).

The following compounds were prepared in a similar manner:

5,7-dibromo-1-isopropyl-1H-pyrazolo [4,3-b] pyridine from 5,7-dibromo-1H-pyrazolo [4,3-b] pyridine and 2-iodopropane;

¹ H NMR (DMSO-d6 400 MHz) δ 8.36 (s, 1H), 7.94 (s, 1H), 5.62-5.55 (m, 1H), 1.49 (d, J = 6.0 Hz, 6H);

- 65 037544

5,7-dibromo-1-propyl-1H-pyrαzolo [4,3-b] pyridine from 5,7-dibromo-1H-pyrαzolo [4,3-b] pyridine and 1 iodopropane;

¹ H NMR (chloroform-d 400 MHz) δ 8.14 (s, 1H), 7.64 (s, 1H), 4.67 (t, J = 7.2 Hz, 2H), 1.98 - 1 , 89 (m, 2H), 0.94 (t, J = 7.6 Hz, 3H);

5,7-dibromo-1-methyl-1H-pyrαzolo [4,3-b] pyridine from 5,7-dibromo-1H-pyrαzolo [4,3-b] pyridine and iodomethane;

1H NMR (chloroform-d 400 MHz) δ 8.13 (s, 1H), 7.64 (s, 1H), 4.38 (s, 3H);

(±) -5,7-dibromo-1- (sec-butyl) -3-methyl-1H-pyrαzolo [4,3-b] pyridine from 5,7-dibromo-1H-pyrαzolo [4,3b] pyridine and (±) -2-iodobutane.

Preparation of (+) - 5,7-dibromo-1- (sec-butyl) -1H-pyrαzolo [4,3-b] pyridine butyl) -1H-pyrαzolo [4,3-b] pyridine and (-) - 5 , 7-dibromo-1- (sec-

(±) -5,7-Dibromo-1-sec-butylpyrαzolo [4,3-b] pyridine (5.2 g, 15.6 mmol) was separated by SFC using a column: AD (250 mm x 50 mm, 10 μm); mobile phase: [0.1% NH ₃ H ₂ O in isopropyl alcohol]; In%: 20% - 20%, min.

(+) - 5,7-Dibromo-1- (sec-butyl) -1H-pyrazolo [4,3-b] pyridine (2.5 g) (Rt = 3.137 min) ([a] _D ²⁰ = 1, 40) (c = 1.0, ethanol).

(-) - 5,7-Dibromo-1- (sec-butyl) -1H-pyrazolo [4,3-b] pyridine (2.5 g) (Rt = 2.808 min.) ([A] _D ²⁰ = - 1.60) (c = 1.0, ethanol).

Preparation of 5-chloro-1-isopropyl-N- (4-methoxybenzyl) -3-methyl-1H-pyrazolo [4,3-b] pyridin-7-amine

Into a solution of 5,7-dichloro-1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine (100 mg, 410 μmol) and (4methoxyphenyl) methanamine (67 mg, 492 μmol, 64 μL) in NMP (5 ml) was added CsF (124 mg, 819 μmol, 30 μl). The mixture was stirred at 100 ° C for 18 h. Water (20 ml) was added and the mixture was filtered and concentrated in vacuo. The crude mixture was purified by flash chromatography using petroleum ether: ethyl acetate = 3: 1 to give 5-chloro-1-isopropyl-N- (4-methoxybenzyl) -3-methyl1H-pyrazolo [4,3-b] pyridine -7-amine (80 mg, 215 μmol, 53% yield);

1H NMR (chloroform-d 400 MHz) δ 7.32 (d, J = 8.4 Hz, 2H), 6.95 (d, J = 8.4 Hz, 2H), 6.39 (s, 1H) , 4.79 (brs, 1H), 4.70-4.63 (m, 1H), 4.39 (d, J = 4.4Hz, 2H), 3.85 (s, 3H), 2, 56 (s, 3H), l, 57 (d, J = 6.4Hz, 6H).

Preparation of 5- (2-ethoxypyridin-3-yl) -1-isopropyl-N- (4-methoxybenzyl) -3-methyl-1H-pyrαzolo [4,3b] pyridin-7-amine

- 66 037544

To a solution of 5-chloro-1-isopropyl-N- (4-methoxybenzyl) -3-methyl-1H-pyrazolo [4,3-b] pyridin-7-amine (60 mg, 174 μmol) in dioxane (2 ml) and H2O (0.5 ml) were added Pd (1,1'-bis (diphenylphosphino) ferrocene) O ₂ (25 mg, 35 μmol) and CS ₂ CO ₃ (141.72 mg, 435 μmol) and (2-ethoxypyridine -3yl) boronic acid (52 mg, 313 μmol). The mixture was stirred at 100 ° C for 1 hour while heating with microwave radiation. Water (30 ml) was added and the mixture was extracted with ethyl acetate (30 ml x 3). The combined organic layers were washed with brine (20 ml), dried over Na ₂ SO ₄ and concentrated. The crude mixture was purified by flash chromatography using petroleum ether: ethyl acetate = 1: 1 to 0: 1 to give 5- (2-ethoxypyridin-3-yl) -1isopropyl-N- (4-methoxybenzyl) -3- methyl-1H-pyrazolo [4,3-b] pyridin-7-amine (50 mg, 67% yield);

1H NMR (chloroform-d 400 MHz) δ 8.27-8.25 (m, 1H), 8.17-8.16 (m, 1H), 7.32 (d, J = 8.8 Hz, 2H ), 7.22 (s, 1H), 7.03-7.00 (m, 1H), 6.95 (d, J = 8.4 Hz, 2H), 4.81-4.76 (m, 1H), 4.65 (brs, 1H), 4.47-4.41 (m, 4H), 3.84 (s, 3H), 2.65 (s, 3H), 1.60 (d, J = 6.4 Hz, 6H), 1.36 (t, J = 7.2 Hz, 3H).

The following connections:

5- (2-fluoropyridin-3-yl) -1 -isopropyl-N- (4-methoxybenzyl) -3-methyl-1H-pyrazolo [4,3-b] pyridine-7amine

derived from 5-bromo-1-isopropyl-N- (4-methoxybenzyl) -3-methyl-1H-pyrazolo [4,3-b] pyridin-7-amine and (2-fluoropyridin-3-yl) boronic acid;

3- (1-isopropyl-7 - ((4-methoxybenzyl) amino) -3-methyl-III-pyrazolo [4,3-b] pyridin-5-yl) pyridin2 (1I) -one

obtained from 5-chloro-1-isopropyl-N- (4-methoxybenzyl) -3-methyl-1H-pyrazolo [4,3-b] pyridin-7-amine and (2-oxo-1,2-dihydropyridine-3 -yl) boronic acid were prepared in a similar manner.

Preparation of 5- (2-ethoxypyridin-3-yl) -1 -isopropyl-3-methyl-1 H-pyrazolo [4,3-b] pyridin-7-amine

A solution of 5- (2-ethoxypyridin-3-yl) -1-isopropyl-N- (4-methoxybenzyl) -3-methyl-1H

- 67 037544 pyrazolo [4,3-b] pyridin-7-amine (1.25 g, 2.90 mmol) in TFA (15 ml) at 60 ° C for 18 h. The mixture was concentrated and the residue was dissolved in ethyl acetate ( 200 ml). The resulting mixture was washed with saturated aqueous NaHCO ₃ (30 ml), brine (20 ml), dried over Na ₂ SO ₄ and concentrated. The crude mixture was purified by flash chromatography using petroleum ether: ethyl acetate = 3: 1 to 2: 1 to give 5- (2-ethoxypyridin-3-yl) -1-isopropyl-3-methyl-1Hpyrαzolo [4, 3-b] pyridin-7-amine (900 mg, 96% yield).

The following connections:

1- (sec-butyl) -5- (2-ethoxypyridin-3-yl) -1H-pyrazolo [4,3-b] pyridin-7-amine, enantiomer 1, obtained from (+) - 5,7-dibromo -1- (sec-butyl) -1H-pyrazolo [4,3-b] pyridine;

1- (sec-butyl) -5- (2-ethoxypyridin-3-yl) -1H-pyrαzolo [4,3-b] pyridin-7-amine, enantiomer 2, obtained from (-) - 5,7-dibromo -1- (sec-butyl) -1H-pyrαzolo [4,3-b] pyridine;

1- (sec-butyl) -5- (2-ethoxypyridin-3-yl) -3-methyl-1H-pyrαzolo [4,3-b] pyridin-7-amine, enantiomer 1, obtained from (+) - 5 , 7-dibromo-1- (sec-butyl) -3-methyl-1H-pyrαzolo [4,3-b] pyridine;

1- (sec-butyl) -5- (2-ethoxypyridin-3-yl) -3-methyl-1H-pyrαzolo [4,3-b] pyridin-7-amine, enantiomer 2, obtained from (-) - 5 , 7-dibromo-1- (sec-butyl) -3-methyl-1H-pyrαzolo [4,3-b] pyridine;

-isopropyl-5- (2-methoxypyridin-3-yl) -3 -methyl-1 H-pyrαzolo [4,3 -b] pyridin-7-amine

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derived from 1-isopropyl-N> (4-methoxybenzyl) -5- (2-methoxypyridin-3-yl) -3-methyl-Spirazolo [4,3-0] pyridin-7-amine;

5- (2- (dimethylamino) pyridin-3-yl) -1 -isopropyl-3-methyl-1 H-pyrazolo [4,3-b] pyridin-7-amine,

derived from 5- (2- (dimethylamino) pyridin-3-yl) -1-isopropyl-N- (4-methoxybenzyl) -3-methyl-1Hpyrazolo [4.3-0] pyridin-7-amine;

3- (7-amino-1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridin-5-yl) pyridin-2 (1H) -one

obtained from 3- (1-isopropyl-7 - ((4-methoxybenzyl) amino) -3-methyl-1H-pyrazolo [4,3-b] pyridin-5yl) pyridin-2 (1H) -one was prepared in a similar way ...

Obtaining ethyl 3-methyl-1,2,4-oxadiazole-5-carboxylate

To a solution of ethyl 2-chloro-2-oxoacetate (1 g, 13.5 mmol) and pyridine (4.27 g, 54 mmol, 4.36 ml) in dichloromethane (40 ml) was added at 15-20 ° С N '-hydroxyacetimidamide (2.40 g, 17.5 mmol, 1.96 ml). The solution was stirred at 50 ° C for 14 h. The reaction mixture was cooled and quenched with saturated aqueous NH ₄ Cl (30 ml). The aqueous phase was extracted with dichloromethane (2x50 ml).

The organic phases were combined, washed with saturated aqueous NaHCO ₃ (50 ml), dried over MgSO ₄ , filtered and concentrated under reduced pressure to give ethyl 3methyl 1,2,4-oxadiazole-5-carboxylate (2.80 g, yield 44%).

Obtaining (3-methyl-1,2,4-oxadiazol-5-yl) methanol

To a solution of ethyl 3-methyl-1,2,4-oxadiazole-5-carboxylate (2.10 g, 13.5 mmol) in THF (10 ml) and ethanol (10 ml) was added NaBH ₄ (1.02 g , 26.9 mmol) at 0 ° C. The mixture was stirred at 0 ° C for 1 h. The mixture was quenched with saturated aqueous NH ₄ Cl and concentrated in vacuo. The residue was dissolved in dichloromethane (50 ml) and filtered; the filtrate was dried over Na ₂ SO ₄ and concentrated in vacuo to give (3-methyl-1,2,4-oxadiazol-5-yl) methanol (800 mg, 52% yield).

Obtaining 3-methyl-1,2,4-oxadiazole-5-carbaldehyde

Cool a solution of oxalyl chloride (267 mg, 2.10 mmol, 184 μl) in dry dichloromethane (5 ml) to -78 ° C and then add DMSO (219 mg, 2.80 mmol). The mixture was stirred at -78 ° C for 15 minutes. A solution of (3-methyl-1,2,4-oxadiazol-5-yl) methanol (80 mg, 0.70 mmol) in dichloromethane (0.5 ml) was added

- 69 037544 at -78 ° C. The mixture was stirred at -78 ° C for 1 hour. Then triethylamine (0.58 ml, 4.2 mmol) was added at -78 ° C. The mixture was heated to 20 ° C and stirred at 20 ° C for 1 hour. The mixture was poured into

1n. aqueous HCl solution (5 ml). The mixture was extracted with dichloromethane (20 ml x 2). The combined organic layers were washed with H ₂ O (20 ml), dried over Na ₂ SO ₄ , filtered and concentrated to give 3-methyl-1,2,4-oxadiazole-5-carbaldehyde (80 mg).

¹ H NMR (chloroform-d 400 MHz) δ 9.97 (s, 1H), 2.55 (s, 3H).

Preparation of 1-methyl-1H-1,2,4-triazol-3 -karbaldegida ^<0H

IN ^ N N ^ N

To a mixture of (1-methyl-1H-1,2,4-triazol-3-yl) methanol (400 mg, 3.54 mmol) and iodobenzenediacetate (1.25 g, 3.89 mmol) in dichloromethane (10 ml) TEMPO ((2,2,6,6-tetramethylpiperidin-1-yl) oxyl) (56 mg, 354 μmol) was added. The mixture was stirred at 15-20 ° C for 2 hours. The mixture was concentrated in vacuo. The residue was purified by silica gel chromatography (petroleum ether: ethyl acetate = 1: 2) to give 1-methyl-1H-1,2,4-triazole-3-carbaldehyde (300 mg, 2.70 mmol, 76% yield).

¹ H NMR (chloroform-d 400 MHz) δ 10.01 (s, 1H), 8.19 (s, 1H), 4.06 (s, 3H).

Obtaining ethyl 2- (2-acetylhydrazinyl) -2-oxoacetate

To a solution of acetohydrazide (5 g, 67 mmol) in dichloromethane (150 ml) was added N-ethoxycarbonyl-2ethoxy-1,2-dihydroquinoline (16.7 g, 67 mmol). The mixture was stirred at 15 ° C for 10 minutes. Then ethyl 2-chloro-2-oxoacetate (9.22 g, 67.5 mmol, 7.56 ml) was added dropwise to the mixture. The mixture was stirred at 15 ° C for 16 hours. The mixture was washed with H 2 O (100 ml) and extracted with dichloromethane (100 ml x 3). The combined organic phases were dried over Na ₂ SO ₄ and concentrated in vacuo. The residue was purified by column chromatography (SiO ₂ , petroleum ether: ethyl acetate = 1: 0 to 0: 1) to give ethyl 2- (2-acetylhydrazinyl) -2-oxoacetate (9.30 g, 79% yield).

Preparation of ethyl 5-methyl- 1,3,4-thiadiazole-2-carboxylate

Oh oh

Ο ^ ΝΗ О NN

To a solution of ethyl 2- (2-acetylhydrazinyl) -2-oxoacetate (3 g, 17 mmol) in THF (100 mL) was added Lawesson's reagent (7.66 g, 19 mmol). The mixture was stirred at 75 ° C. for 3 hours. The mixture was diluted with ethyl acetate (500 ml) and about 40 g of decolorizing charcoal was added. The mixture was stirred at 18 ° C for 16 hours. The mixture was filtered. The filtrate was concentrated in vacuo. The residue was purified by column chromatography (SiO ₂ , petroleum ether: ethyl acetate = 3: 7) to give ethyl 5-methyl1,3,4-thiadiazole-2-carboxylate (921 mg, 28% yield).

Obtaining 5-methyl-1,3,4-thiadiazole-2-carbaldehyde

To a solution of ethyl 5-methyl-1,3,4-thiadiazole-2-carboxylate (400 mg, 2.32 mmol) in dry THF (5 ml) was added DIBAL-H (diisobutylaluminum hydride) (1M in toluene, 6.97 ml). The mixture was stirred at -40 ° C for 2 hours. The mixture was quenched with saturated aqueous NH ₄ Cl (5 ml) and filtered. The solution was extracted with dichloromethane (15 ml x 3). The combined organic phases were dried over Na ₂ SO ₄ and concentrated in vacuo. The residue was purified by preparative TLC (petroleum ether: ethyl acetate = 1: 1) to give 5-methyl-1,3,4-thiadiazole-2-carbaldehyde (123 mg, 41% yield).

¹ H NMR (chloroform-d 400 MHz) δ 10.19 (s, 1H), 2.92 (s, 3H).

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Obtaining (5-methylthiophen-3-yl) methanol

LiAlH4 (120 mg, 3.17 mmol) was slowly added to a solution of 5-methylthiophene-3-carboxylic acid (300 mg, 2.11 mmol) in THF (10 ml) at 0 ° C. The mixture was stirred at 20 ° C for 2 hours. Water (0.3 ml) was added at 0 ° C with quenching the reaction mixture followed by the addition of 15% aqueous NaOH solution (0.3 ml). Ethyl acetate (50 ml) was added to the mixture, the mixture was filtered and the residue was washed with ethyl acetate (20 ml x 2). The combined filtrates were dried over Na ₂ SO ₄ and concentrated to give (5-methylthiophen-3-yl) methanol (270 mg).

Obtaining (5-methyloxazol-2-yl) methanol

To the reaction mixture of ethyl 5-methyloxazole-2-carboxylate (500 mg, 3.22 mmol) in ethanol (10 ml) was added NaBH4 (609 mg, 16.10 mmol) with stirring at 20 ° C. The resulting solution was then stirred at 20 ° C. for 3 hours. The reaction mixture was quenched with water (50 ml), then concentrated under reduced pressure to remove ethanol. The residue was extracted with ethyl acetate (50 ml x 3). The combined organic layers were washed with brine (10 ml), dried over Na ₂ SO ₄ , concentrated to give (5-methyloxazol-2-yl) methanol (364 mg).

Obtaining 5-methylthiophene-3-carbaldehyde

To a solution of (5-methylthiophen-3-yl) methanol (270 mg, 2.11 mmol) in dichloromethane (10 ml) was added Dess-Martin reagent (1,1,1-triacetoxy-1,1-dihydro-1,2 -benziodoxol-3 (1H) -one) (1.07 g, 2.53 mmol). The mixture was stirred at 20 ° C for 1 h. The mixture was filtered and the residue was washed with dichloromethane (30 ml), the combined organic layers were concentrated. The crude mixture was purified by flash chromatography using petroleum ether: ethyl acetate = 5: 1 to give 5-methylthiophene-3carbaldehyde (180 mg, 1.43 mmol, 68% yield).

¹ H NMR (chloroform-d 400 MHz) δ 9.81 (s, 1H), 7.89 (s, 1H), 7.20 (s, 1H), 2.51 (s, 3H).

The following compounds were prepared in a similar manner:

5-methyloxazole-2-carbaldehyde from (5-methyloxazol-2-yl) methanol;

3-methylisoxazole-5-carbaldehyde from (3-methylisoxazol-5-yl) methanol;

Iazole-3-carbaldehyde 5-methyl-1,2,4-oxade from (5-methyl-1,2,4-oxadiazol-3-yl) methanol;

1,5-dimethyl-1 H-pyrazole-3-carbaldehyde from (1,5-dimethyl-1 H-pyrazol-3-yl) methanol.

Obtaining 1 - ((1-aminoethyl) thio) -3-chloropropan-2-one

A solution of ethanethioamide (1 g, 13.3 mmol) in acetone (7 ml) was added dropwise to a solution of 1,3 dichloropropan-2-one (1.69 g, 13.3 mmol, 1.66 ml) in acetone (5 ml ) at 20 ° C and stirred at 20 ° C for 12 hours. The mixture was filtered and the filter cake was washed with acetone (10 ml x 3) to give 1 ((1-aminoethyl) thio) -3-chloropropan-2-one.

Obtaining 4- (chloromethyl) -2-methylthiazole

Stir a mixture of 1 - ((1-aminoethyl) thio) -3-chloropropan-2-one (3 g, 17.9 mmol) in ethanol (30 ml) at 80 ° C for 2 h. The mixture was concentrated in vacuo to give 4- (chloromethyl) -2-methylthiazole (2.9 g).

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Preparation of 2 - ((2-methylthiazol-4-yl) methyl) isoindoline-1,3-dione

To a mixture of 4- (chloromethyl) -2-methylthiazole (2.80 g, 19.0 mmol) and isoindoline-1,3-dione in anhydrous DMF (30 ml) was added K2CO3 (1.31 g, 9.49 mmol) ... The mixture was stirred at 100 ° C for 0.5 h. The mixture was diluted with water (50 ml), extracted with ethyl acetate (50 ml x 2). The organic layer was washed with water (30 ml), brine (30 ml), dried with Na ₂ SO ₄ and concentrated in vacuo. The residue was purified by silica gel chromatography (petroleum ether: ethyl acetate = 10: 1 to 2: 1) to give 2 - ((2-methylthiazol-4-yl) methyl) isoindoline-1,3-dione (3.29 g ).

Obtaining (2-methylthiazol-4-yl) methanamine

Stirred a mixture of 2 - ((2-methylthiazol-4-yl) methyl) isoindoline-1,3-dione (1 g, 3.87 mmol) and hydrazine hydrate (291 mg, 5.81 mmol, 282 μL) in ethanol ( 10 ml) at 20 ° C for 0.5 h. The mixture was concentrated in vacuo. The residue was purified by silica gel chromatography (dichloromethane: methanol = 0: 1 to 10: 1) to give (2-methylthiazol-4-yl) methanamine (330 mg).

Obtaining benzyl (cyanomethyl) carbamate

Stirred a mixture of 2-aminoacetonitrile hydrochloride (5 g, 54.0 mmol), NaHCO ₃ (18.16 g, 216 mmol) and dioxane (50 ml) in H2O (100 ml) at 0 ° C. Then a solution of benzyl chloroformate (11.06 g, 64.8 mmol, 9.22 ml) in toluene (10 ml) was added at 0 ° C and stirred at 20 ° C for 12 h. The mixture was poured into water (100 ml) and the aqueous phase was extracted with ethyl acetate (100 ml x 3). The combined organic phases were washed with brine (100 ml), dried with anhydrous Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by silica gel chromatography to give benzyl (cyanomethyl) carbamate (1.70 g).

¹ H NMR (chloroform-d 400 MHz): 7.40-7.31 (m, 5H), 5.35-5.13 (m, 3H), 4.16-4.12 (m, 2H).

Obtaining benzyl - ((2H-tetrazol-5-yl) methyl) carbamate

Stirred a mixture of benzyl (cyanomethyl) carbamate (200 mg, 1.05 mmol), sodium azide (250 mg, 3.85 mmol) zinc dibromide (118 mg, 525 mmol) and isopropyl alcohol (2 ml) in H2O (4 ml) at 100 ° C for 24 h. The mixture was poured into water (50 ml) and KHSO ₄ (aq.) was added until pH 2. The aqueous phase was extracted with ethyl acetate (20 ml x 3). The combined organic phases were washed with brine (10 ml), dried with anhydrous Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (petroleum ether / ethyl acetate = 10/1 to 3/1) to give benzyl - ((2H-temrazol-5-yl) methyl) carbamate (200 mg).

Obtaining benzyl - ((2-methyl-2H-tetrazol-5-yl) methyl) carbamate

To a mixture of benzyl - ((2H-tetrazol-5-yl) methyl) carbamate (1 g, 4.29 mmol) and K ₂ CO ₃ (1.19 g, 8.58 mmol) in DMF (20 ml) was added CH3I (0.91 g, 6.4 mmol) at 0 ° C and the reaction mixture was stirred at 30 ° C for 12 h. The mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified using

72 037544 chromatography on silica gel (petroleum ether / ethyl acetate = 10/1 to 3/1) to give benzyl - ((2methyl-2H-tetrazol-5-yl) methyl) carbamate (400 mg).

Obtaining (2-methyl-2H-tetrazol-5-yl) methanamine

Pd / C (10%, wet) (10 mg) was added to a solution of benzyl - ((2-methyl-2H-tetrazol-5-yl) methyl) carbamate (250 mg, 1.0 mmol) in MeOH (10 ml) in an atmosphere of N ₂ . The suspension was degassed in vacuo and purged several times with H ₂ . The mixture was stirred under an atmosphere of H ₂ (15 psi) at 25 ° C for 12 hours. The mixture was filtered and the filtrate was concentrated in vacuo to give (2-methyl-2H-tetrazol-5-yl) methanamine (120 mg, crude) ...

Obtaining m-tolylmethanamine hydrochloride

Stirred a mixture of 3-methylbenzaldehyde (500 mg, 4.16 mmol, 490.20 μl) in NH ₃ / MeOH / MeOH (7M, 1 ml) at 80 ° C for 14 h. Then NaBH ₄ (315 mg, 8 , 32 mmol) and the reaction mixture was stirred at 20 ° C for 1 h. The mixture was diluted with water (20 ml) and was extracted with ethyl acetate (20 ml x 2). The organic layers were washed with water (10 ml), brine (10 ml), dried with Na ₂ SO ₄ and concentrated in vacuo. The residue was purified by preparative HPLC to give m-tolylmethanamine (370 mg) as the HCl salt.

Obtaining p-tolylmethanol

A solution of methyl 4methyl benzoate (11 g, 73.3 mmol) in anhydrous THF (50 ml) was added to a suspension of LiAlH ₄ (5.56 g, 147 mmol) in anhydrous THF (100 ml) and the resulting mixture was stirred at 0 ° C for _{1 h. The reaction mixture was quenched by adding H 2} O (5 ml), 15% aqueous NaOH solution (5 ml) and H 2 O (8 ml) at 0 ° C, 8 g of anhydrous Na ₂ SO ₄ were added and the reaction mixture was filtered. The filter cake was washed with additional THF (80 ml x 3). The combined organic layers were concentrated to give p-tolylmethanol (8.30 g, 93% yield).

¹ H NMR (chloroform-d 400 MHz) δ 7.26 (d, J = 8.0 Hz, 2H), 7.18 (d, J = 7.6 Hz, 2H), 4.65 (d, J = 5.2 Hz, 2H), 2.36 (s, 3H).

Obtaining 1 - (bromomethyl) -4-methylbenzene

To a solution of p-tolylmethanol (8.30 g, 68 mmol) in dichloromethane (200 ml) was added tribromophosphane (20.2 g, 74.7 mmol). The mixture was stirred at 0 ° C for 1 h. The reaction mixture was poured into H2O (10 ml) and extracted with dichloromethane (25 ml). The organic phase was separated, washed with brine (10 ml), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated to give 1 (bromomethyl) -4-methylbenzene (12.5 g, 99% yield).

1H NMR (chloroform-d 400 MHz) δ 7.29 (d, J = 7.6 Hz, 2H), 7.16 (d, J = 7.6 Hz, 2H), 4.50 (s, 2H) , 2.36 (s, 3H).

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Preparation of 2- (4-methylbenzyl) isoindoline-1,3-dione

To a solution of 1- (bromomethyl) -4-methylbenzene (5 g, 27 mmol) in DMF (30 ml) was added 1,3-dioxoisoindoline-2-idol potassium (7.51 g, 40.5 mmol). The mixture was stirred at 100 ° C for 14 hours. The reaction mixture was concentrated under reduced pressure to remove DMF. The residue was purified by column chromatography (SiO ₂ , petroleum ether: ethyl acetate = 0 to 20%) to give 2 (4-methylbenzyl) isoindoline-1,3-dione (5.50 g, 81% yield).

Ή NMR (chloroform-d 400 MHz) δ 7.85 (d, J = 3.2 Hz, 2H), 7.84 (d, J = 3.2 Hz, 2H), 7.34 (d, J = 7.6 Hz, 2H), 7.13 (d, J = 8.0 Hz, 2H), 4.82 (s, 2H), 2.32 (s, 3H).

Obtaining p-tolylmethanamine

Stirred a mixture of 2- (4-methylbenzyl) isoindoline-1,3-dione (1 g, 3.8 mmol) and hydrazine hydrate (752 mg, 15 mmol, 730 μl) in MeOH (10 ml) at 20 ° С for 3 h. The mixture was concentrated in vacuo. The residue was purified by silica gel chromatography (dichloromethane: methanol (with 5% ammonia in water) = 0: 1 to 5: 1) to give p-tolylmethanamine (160 mg).

Preparation of ethyl 5-methyl-1,2,4-oxadiazole-3-carboxylate

To a solution of hydroxylamine hydrochloride (1.71 g, 24.6 mmol) in acetic acid (10 ml) were added ethyl cyanoformate (2.00 g, 20.18 mmol, 1.98 ml, 1.00 eq.) And NaOAc (2 , 02 g, 24.62 mmol, 1.22 eq.) At room temperature and the reaction mixture was stirred for 0.5 h. Acetic anhydride (3.25 ml, 34.7 mmol) was added to the reaction mixture at room temperature and the reaction mixture stirred for 0.5 h. Then the resulting mixture was stirred at 100 ° C for 12 h. The mixture was cooled to room temperature and the acetic acid was removed in vacuo. Ethyl acetate (25 ml) and water (5 ml) were added to the reaction mixture. The solution was neutralized with K ₂ CO ₃ (aq) to give a pH of 7. The aqueous phase was extracted with ethyl acetate (5 ml x 3). The combined organic phases were washed with brine (10 ml), dried with anhydrous Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by preparative HPLC to give ethyl 5-methyl-1,2,4-oxadiazole 3-carboxylate (1.40 g).

Obtaining (5-methyl-1,2,4-oxadiazol-3-yl) methanol

_{NaBH 4} (290 mg, 7.68 mmol) was added to a solution of 5-methyl-1,2,4-oxadiazole-3-carboxylate (400 mg, 2.56 mmol) in THF (4 ml) and ethanol (4 ml) at 0 ° C. The reaction mixture was stirred at 0 ° C for 1 h. The reaction mixture was quenched with NH4Cl and the mixture was concentrated in vacuo. The residue was purified through silica gel chromatography (petroleum ether: ethyl acetate = 1/0 to 1/1) to give (5-methyl-1,2,4-oxadiazol-3-yl) methanol (250 mg).

Obtaining 5-methyl-1,2,4-oxadiazole-3-carbaldehyde

A solution of (5-methyl-1,2,4-oxadiazol-3-yl) methanol (250 mg, 2.19 mmol) and periodinane was stirred

Dess-Martin (1.39 g, 3.29 mmol) in dichloromethane (5 ml) at room temperature for 12 h.

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The mixture was filtered and the filtrate was concentrated in vacuo to give 5-methyl-1,2,4-oxadiazole-3-carbaldehyde (300 mg).

Preparation of methyl- (tert-butoxycarbonyl) glycinate

To a solution of methyl glycinate (20 g, 159.30 mmol) in dioxane (120 ml) and water (80 ml) was added Na ₂ CO ₃ (33.77 g, 318.60 mmol) at 0 ° C, Boc _{2 was added dropwise} O (43.9 ml, 191 mmol) at room temperature. The mixture was stirred at room temperature for 18 hours. The mixture was concentrated, water (200 ml) was added and the mixture was extracted with ethyl acetate (100 ml x 3). The organic layer was washed with water (50 ml x 2) and brine (50 ml x 2), dried with anhydrous Na ₂ SO ₄ , filtered, concentrated to give methyl (tert-butoxycarbonyl) glycinate (30 g) which was used directly at the next stage.

Obtaining tert-butyl- (2-hydrazinyl-2-oxoethyl) carbamate

A mixture of methyl- (tert-butoxycarbonyl) glycinate (10 g, 52.9 mmol) and hydrazine hydrate (4.37 ml, 89.85 mmol) in methanol (60 ml) and water (15 ml) was stirred at room temperature for 48 h. The mixture was concentrated to give tert-butyl (2-hydrazinyl-2-oxoethyl) carbamate (10 g).

Preparation of tert-butyl - ((1,3,4-oxadiazol-2-yl) methyl) carbamate

To a solution of tert-butyl (2-hydrazinyl-2-oxoethyl) carbamate (5.00 g, 26.4 mmol) in trimethoxymethane (50 ml) was added 4-methylbenzenesulfonic acid (45.5 mg, 0.26 mmol). The mixture was stirred at 80 ° C for 4 hours. The mixture was concentrated. The crude mixture was purified by flash chromatography using petroleum ether: ethyl acetate = 3: 1 to give tert-butyl - ((1,3,4oxadiazol-2-yl) methyl) carbamate (850 mg).

Preparation of (1,3,4-oxadiazol-2-yl) methanamine hydrobromide

A solution of tert-butyl - ((1,3,4-oxadiazol-2-yl) methyl) carbamate (450 mg, 2.26 mmol, 1.00 eq.) In 35% hydrobromic acid in acetic acid (5 ml) was stirred at room temperature for 2 hours. The mixture was concentrated to give (1,3,4-oxadiazol-2-yl) methanamine hydrobromide (406 mg).

Preparation of methyl 1,2,4-oxadiazole-3-carboxylate

To a solution of ethyl 2-amino-2- (hydroxyimino) acetate (1.90 g, 14.4 mmol) in triethoxymethane (9.58 ml, 57.5 mmol) was added BF ₃ .Et ₂ O (0.089 ml, 0 , 72 mmol). The mixture was heated at 90 ° C for 2 hours. The mixture was concentrated and the residue was dissolved in dichloromethane (30 ml). The organic layer was washed with 2N. HCl (aq.) (20 ml), saturated aqueous NaHCO ₃ (20 ml), water (20 ml), brine (20 ml) and dried over Na ₂ SO ₄ , filtered and concentrated to give methyl-1,2 , 4oxadiazole-3-carboxylate (1.60 g).

Obtaining (1,2,4-oxadiazol-3-yl) methanol

To a cooled (0 ° C) solution of methyl 1,2,4-oxadiazole-3-carboxylate (300 mg, 2.11 mmol) in ethanol (2 ml) and THF (2 ml) was added NaBH4 (239 mg, 6, 33 mmol). The mixture was stirred at 0 ° C for 1 h. Saturated aqueous NH4Cl solution (5 ml) was added, the mixture was concentrated and the residue was dissolved in 10% methanol in dichloromethane (20 ml). The mixture was filtered and the filtrate was concentrated. The residue was purified by flash chromatography on silica gel (10 to ~ 100% ethyl acetate in petroleum ether) to give (1,2,4-oxadiazol-3-yl) methanol (40 mg).

Obtaining 1,2,4-oxadiazole-3-carbaldehyde

To a cooled (0 ° C) solution of (1,2,4-oxadiazol-3-yl) methanol (40 mg, 0.40 mmol) in dichloromethane (5 ml) was added Dess-Martin periodin (254 mg, 0.60 mmol ). The mixture was stirred at room temperature for 1 hour. The mixture was filtered and the filtrate was concentrated to give 1,2,4oxadiazole-3-carbaldehyde (39 mg).

Obtaining ethyl- (5-methyl-1H-1,2,4-triazol-3-yl) methanol

To a mixture of ethyl 5-methyl-1H-1,2,4-triazole-3-carboxylate (200 mg, 1.29 mmol) in THF (5 ml) was added LiAlH4 (245 mg, 6.45 mmol) at 0 ° C in an atmosphere of N2. The mixture was stirred at 30 ° C for 1 h. The mixture was filtered and washed with methanol, concentrated with triazol-3-yl) methanol (350 mg).

Obtaining 5-methyl-1H-1,2,4-triazole-3-carbaldehyde in vacuo to obtain (5-methyl-1H-1,2,4-

To a mixture of (5-methyl-1H-1,2,4-triazol-3-yl) methanol (350 mg, 3.09 mmol) in dichloromethane (10 ml) and acetonitrile (10 ml) was added Dess-Martin periodinane (2 , 62 g, 6.19 mmol). The mixture was stirred at 30 ° C for 14 hours. The mixture was filtered and washed with petroleum ether and ethyl acetate and concentrated in vacuo to give 5-methyl-1H-1,2,4-triazole-3-carbaldehyde (90 mg).

Obtaining 4-bromo-6-chloro-2-methylpyridin-3-amine

To an ice-cold solution of 6-chloro-2-methylpyridin-3-amine (12 g, 84 mmol) and AcOH (5.1 g, 84 mmol) in MeOH (198 g, 250 ml) was added dropwise bromine (13.5 g , 84 mmol). The resulting solution was stirred at ice bath temperature overnight, after which the resulting solution was concentrated in vacuo. The resulting residue was dissolved in EtOAc and washed sequentially with saturated aqueous NaHCO ₃ , 10% aqueous Na ₂ S ₂ O ₃ , brine and dried (Na ₂ SO ₄ ). The solvent was removed in vacuo and the resulting crude material was purified by flash chromatography to give 4-bromo-6-chloro-2-methylpyridin-3-amine (12.6 g).

¹ H NMR (500 MHz, chloroform-d) δ 7.30 (s, 1H), 4.04 (brs, 2H), 2.46 (s, 3H).

Preparation of 7-bromo-5-chloro-1H-pyrazolo [4,3-b] pyridine

Isopentyl nitrite (3.97 g, 33.9 mmol) was added dropwise to an ice-cold suspension of 4-bromo-6-chloro-2methylpyridin-3-amine (5 g, 22.6 mmol), KOAc (4.43 g, 45, 2 mmol) and AcOH (44.1 g, 734 mmol) in toluene (125 ml) under an inert atmosphere. A reflux condenser was inserted and the reaction mixture was heated at 30 ° C for 4 h after which most of the solvent was removed in vacuo. The resulting residue was dissolved in ethyl acetate and washed carefully with saturated aqueous NaHCO ₃ solution to achieve a pH of 8-9. The organic layer was washed with brine, dried (Na ₂ SO ₄ ) and concentrated to give the crude material, which was purified by flash chromatography (SiO ₂ ) to give 7-bromo-5-chloro-1H-pyrazolo [4,3-b] pyridine (2.3 g, 44% yield).

1 H NMR (500 MHz, chloroform-d) δ 10.61 (brs, 1H), 8.35 (s, 1H), 7.60 (s, 1H).

Preparation of 7-bromo-5-chloro-1- (oxetan-3-yl) -1H-pyrazolo [4,3-b] pyridine

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Added dropwise diisopropyl azodicarboxylate (979 mg, 4.84 mmol) to an ice-cold solution of 7 bromo-5-chloro-1H-pyrazolo [4,3-b] pyridine (250 mg, 1.08 mmol), triphenylphosphine (1.27 g, 4.84 mmol) and oxetan-3-ol (319 mg, 4.30 mmol) in THF (10 ml) under an inert atmosphere. Allow the ice bath to warm to room temperature and continue stirring at room temperature overnight. Most of the solvent was removed in vacuo and the resulting crude material was purified by flash chromatography to give 7-bromo-5-chloro-1- (oxetane-3-ul) -1Hpyrazolo [4.3-0] pyridine (130 mg, yield 38%).

1H NMR (chloroform-d, 500 MHz) δ 8.31 (s, 1H), 7.56 (s, 1H), 6.48 (p, J = 6.9 Hz, 1H), 5.35 (t , J = 6.5 Hz, 2H), 5.11 (t, J = 7.1 Hz, 2H).

Preparation of 3- (1,3-dioxolan-2-yl) pyridine

To a solution of nicotinaldehyde (1 g, 9.34 mmol) in toluene (20 ml) was added toluene-4-sulfonic acid (1.93 g, 11 mmol) and stirred at 120 ° C for 0.5 h. Ethane was added. 1,2-diol (637 mg, 10 mmol) and the resulting solution was stirred at 120 ° C for 15 hours. The solution was quenched with saturated aqueous NaHCO ₃ (60 ml) and the aqueous phase was extracted with DCM (30 ml x 3). The combined organic phases were washed with brine, dried with Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (petroleum ether: ethyl acetate = 10: 1 to 1: 1) to give 3- (1,3-dioxolan-2-yl) pyridine (1.30 g, 92% yield).

¹ H NMR (chloroform-d, 400 MHz) δ 8.70 (d, J = 2.0 Hz, 1H), 8.61-8.60 (m, 1H), 7.79-7.77 (m , 1H), 7.327.29 (m, 1H), 5.84 (s, 1H), 4.12-4.01 (m, 4H).

Preparation of 5- (1,3-dioxolan-2-yl) -1-methylpyridin-2 (1H) -one

Dimethyl sulfate (1 g, 7.9 mmol) was slowly added dropwise to 3- (1,3-dioxolan-2-yl) pyridine (1.20 g, 7.94 mmol) and stirred at 100 ° C for 1 h The resulting solution was dissolved in H ₂ O (4 ml) and an aqueous solution of K ₃ [Fe (CN) 6] (6.27 g) in H ₂ O (24 ml) was added with stirring and cooling. KOH (3.56 g) was added slowly while maintaining the temperature at 5 ° C. After the addition of DCM (12 ml), the solution was stirred at 20 ° С for 0.5 h, after which additional portions of K ₃ [Fe (CN) ₆ ] (3.1 g) in H2O (11 ml) and KOH (1 , 8 g) at 20 ° C and stirred at 20 ° C for 12 h. The aqueous phase was extracted with ethyl acetate (30 ml x 3). The combined organic phases were washed with brine, dried with Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by preparative HPLC to give 5- (1,3-dioxolan-2-yl) -1-methylpyridin-2 (1H) one (250 mg).

Obtaining 1-methyl-6-oxo-1,6-dihydropyridine-3-carbaldehyde

A solution of 5- (1,3-dioxolan-2-yl) -1-methylpyridin-2 (1Н) -one (250 mg, 1.38 mmol) in 3% aqueous HCl solution (5 ml) was stirred at 100 ° С in for 3 h. The solution was extracted with DCM (10 ml x 3). The combined organic phases were washed with brine, dried with Na ₂ SO ₄ , filtered and concentrated in vacuo to give 1-methyl-6-oxo-1,6-dihydropyridine-3carbaldehyde (150 mg).

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Getting 6- (difluoromethyl) nicotinaldehyde

To a solution of 5-bromo-2- (difluoromethyl) pyridine (400 mg, 1.92 mmol) in THF (2 ml) at 0 ° C was added dropwise a complex of isopropyl magnesium chloride and lithium chloride (1.3 M, 2.96 ml) ... The reaction mixture was allowed to stir at room temperature for 2 h, then DMF (703 mg, 9.62 mmol) was added at 0 ° C and the reaction mixture was stirred for an additional 12 h at room temperature. The reaction mixture was quenched with 2M HCl (aq) and basified with 1M NaOH (aq) until pH 7. The organic layer was separated and the aqueous layer was extracted with dichloromethane. The combined organic layers were dried over Na ₂ SO ₄ and concentrated. The residue was purified by column chromatography (SiO ₂ , petroleum ether / ethyl acetate = 1/0 to 10: 1) to give 6- (difluoromethyl) nicotinaldehyde (130 mg).

Preparation of methyl 5-methoxypyrazine-2-carboxylate

_{SOCl 2} (927 mg, 7.79 mmol) was added to a solution of 5-methoxypyrazine-2-carboxylic acid (1 g, 6.49 mmol) in MeOH (20 ml) at 15 ° C. The mixture was heated under reflux at 60 ° C for 2 hours to give a brown solution. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was diluted with dichloromethane (20 ml) and the pH was adjusted to 8 with NaHCO ₃ (aq, 50 ml). The mixture was extracted with dichloromethane (100 ml x 3). The combined organic layers were washed with brine (100 ml), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give methyl 5-methoxypyrazine-2-carboxylate (1.02 g).

Obtaining (5-methoxypyrazin-2-yl) methanol

To a solution of methyl 5-methoxypyrazine-2-carboxylate (200 mg, 1.19 mmol) in THF (0.1 ml) and MeOH (4 ml) was added NaBH4 (225 mg, 5.95 mmol). The mixture was stirred at 15 ° C for 16 h. The mixture was quenched with water (5 ml), then diluted with additional water (15 ml), extracted with ethyl acetate (2x25 ml), then with 20% 2-propanol in dichloromethane (25 ml). The combined organic extracts were dried over anhydrous Na ₂ SO ₄ , filtered and concentrated to give (5methoxypyrazin-2-yl) methanol (122 mg).

Preparation of 5-methoxypyrazine-2-carbaldehyde

To a solution of (5-methoxypyrazin-2-yl) methanol (115 mg, 0.82 mmol) in dichloromethane (3 ml) was added MnO ₂ (714 mg, 8.21 mmol) at 15 ° C. The reaction mixture was heated under reflux at 50 ° C for 18 h. The reaction mixture was cooled to 20 ° C, filtered through celite and washed with dichloromethane (100 ml). The filtrate was concentrated to give 5-methoxypyrazine-2-carbaldehyde (45 mg).

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Preparation of 4-ethyloxazolidin-2-one

ABOUT

Et ₃ N (1.14 g, 11.2 mmol) in an argon atmosphere. The reaction mixture was stirred at room temperature for 12 hours. The mixture was concentrated and the residue was purified by column chromatography (SiO ₂ , petroleum ether: ethyl acetate = 10: 1 to 5: 1) to give 4-ethyloxazolidin-2one (800 mg).

Preparation of 5-bromo-1 -isopropyl-3-methyl-1 H-pyrazolo [4,3-b] pyridine-7-carbaldehyde

A solution of i-PrMgCl-LiCl (1.3M, 3.6 ml) in THF was added dropwise to a mixture of 5,7-dibromo-1-isopropyl3-methylpyrazolo [4,3-b] pyridine (1.3 g, 3, 9 mmol) in THF (25 ml) at 0 ° C. The mixture was stirred at room temperature for 30 minutes. The mixture was then cooled back to 0 ° C and DMF (1.4 g, 19.5 mmol, 1.5 mL) was added and the resulting mixture was stirred at room temperature for another 2.5 h. NH ₄ Cl (aq, 2 ml) with quenching of the reaction mixture, then water (20 ml) was added and the mixture was extracted with ethyl acetate (20 ml x 3). The combined organic layer was washed with brine (10 ml), dried over Na ₂ SO ₄ and concentrated. The crude mixture was purified by flash chromatography using petroleum ether: ethyl acetate = 30: 1 to ~ 20: 1 to give 5brom-1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine-7 -carbaldehyde (800 mg).

Preparation of N - ((5-bromo-1 -isopropyl-3-methyl-1 H-πyrazolo [4,3-b] pyridin-7-yl) methyl) -5-methoxypyridine-3-amine

Ti (i-PrO) ₄ (101 mg, 0.35 mmol) and 5-methoxypyridin-3-amine (44 mg, 0.35 mmol). The mixture was stirred at 80 ° C for 14 h. After the reaction mixture was cooled to room temperature, EtOH (3 ml) was added followed by the addition of NaBH4 (35 mg, 0.9 mmol). The mixture was stirred at room temperature for 15 minutes. Water (0.5 ml) was added to quench the reaction mixture at 0 ° C and the resulting mixture was stirred at room temperature for 10 min, then filtered and the residue was washed with ethyl acetate (30 ml x 3). The combined organic layers were dried and concentrated. The crude product, N - [(5-6pom-1isopropyl-3-methylpyrazolo [4,3-b] pyridin-7-yl) methyl] -5-methoxypyridin-3-amine (69 mg) was used in the next step without additional cleaning.

N - ((5-bromo-1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridin-7-yl) methyl) -1-methyl-1H-1,2,4triazol-3-amine was prepared in a similar manner from 5-bromo-1-isonronyl-3-methylpyrazolo [4,3-b] nyridine-7carbaldehyde and 1-methyl-1,2,4-triazol-3-amine.

Preparation of 5- (2-ethoxypyridin-3-yl) -1-isopropyl-3-methyl-1H-πyrazolo [4,3-b] pyridine-7-carbaldehyde

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Stirred a mixture of 5-bromo-1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine-7-carbaldehyde (0.56 g, 1.98 mmol), (2-ethoxy-3-pyridyl) boronic acid (497 mg, 2.98 mmol), Pd (dppf) Cl ₂ (145 mg, 0.2 mmol), Cs ₂ CO ₃ (1.94 g, 5.95 mmol) in dioxane (8 ml), water (2 ml) at 100 ° C for 2 h. The mixture was concentrated under reduced pressure. The residue was extracted with ethyl acetate (30 ml x 2). The combined organic layers were washed with brine (20 ml), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO ₂ , petroleum ether / ethyl acetate = 10: 1 to 3: 1) to give 5- (2ethoxypyridin-3-yl) -1-isopropyl-3-methyl-1H-pyrazolo [4, 3-b] pyridine-7-carbaldehyde (0.55 g).

Preparation of 5- (2-ethoxynyridin-3-yl) -7-ethynyl-1-isopropyl-3-methyl-1H-pyrazolo [4,3-L] pyridine

A mixture of 5- (2-ethoxypyridin-3-yl) -1-isopropyl-3-methyl-III-pyrazolo [4,3-L] pyridine7-carbaldehyde (0.55 g, 1.70 mmol), 1-diazo -1-dimethoxyphosphorylpropan-2-one (423 mg, 2.20 mmol) and Cs ₂ CO ₃ (1.66 g, 5.09 mmol) in MeOH (7 ml) at room temperature for 2 h. The mixture was concentrated at reduced pressure and extracted with DCM (20 ml x 2). The combined organic layers were washed with brine (20 ml), dried over Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give crude 5- (2-ethoxypyridin-3-yl) -7-ethynyl-1isopropyl-3-methyl-1H -pyrazolo [4,3-b] pyridine (0.5 g).

Preparation of tert-butyl - ((6-chloropyrazin-2-yl) methyl) carbamate

To a suspension of Raney-Ni (307 mg, 3.59 mmol) in EtOH (20 ml) were added 6-chloropyrazine-2carbonitrile (1.00 g, 7.17 mmol) and tert-butoxycarboyl tert-butyl carbonate (1.72 d, 7.88 mmol), then the reaction mixture was stirred at room temperature under an atmosphere of H ₂ (45 psi) for 16 hours. The reaction mixture was filtered through celite and the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by flash chromatography on silica gel (elution gradient ethyl acetate / petroleum ether, 0 to ~ 10%) to give tert-butyl N - [(6 chloropyrazin-2-yl) methyl] carbamate (1.05 g) ...

Preparation of tert-butyl - ((6-methoxypyrazin-2-yl) methyl) carbamate

Sodium methoxide (443 mg, 8.21 mmol) was added to an ice-cold solution of tert-butyl-N - [(6-chloropyrazin-2-yl) methyl] carbamate (500 mg, 2.05 mmol) in MeOH (10 ml), then the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure. The residue was diluted with water (100 ml) and was extracted with ethyl acetate (100 ml x 3). The combined organic layers were washed with saturated aqueous NH ₄ Cl (100 ml x 2), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash chromatography on silica gel (eluting with ethyl acetate / petroleum ether, 0 to ~ 16%) to give tert-butyl N - [(6-methoxypyrazine-2yl) methyl] carbamate (300 mg).

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Preparation of (6-methoxypyrazin-2-yl) methanamine hydrochloride

A solution of tert-butyl-N - [(6-methoxypyrαzin-2-yl) methyl] carbamate (350 mg, 1.46 mmol) in 4N HCI was stirred. HCl / dioxane (10 ml) at room temperature for 2 hours. The reaction mixture was concentrated under pressure to give (6-methoxypyrazin-2-yl) methanamine hydrochloride. The crude product was used directly without further purification.

The following compound was prepared in a similar manner:

(3-methoxypyrazin-2-yl) methanamine hydrochloride.

Obtaining (4-methoxy-3-pyridyl) methanamine

Raney-Ni (30 mg, 10%) was added to a solution of 4-methoxypyridine-3-carbonitrile (200 mg, 1.49 mmol), 25% ammonia in water (0.23 ml) and MeOH (5 ml), the reaction mixture stirred at room temperature for 4 hours under an atmosphere of H2 (45 psi). The reaction mixture was filtered to remove the catalyst and the filter cake was washed with MeOH (10 ml x 3), the filtrate was concentrated in vacuo to give the crude product (4-methoxy-3pyridyl) methanamine (150 mg).

Preparation of 6-methylheptyl-3 - ((5-bromo-1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine-7yl) thio) propanoate

A solution of 5,7-dibromo-1-isonropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine (150 mg, 0.45 mmol), 6-methylheptyl-3-mercaptopropanoate (124 mg, 0, 57 mmol), DIPEA (116 mg, 157 μl, 0.90 mmol) in NMP (2 ml) at RT. in an inert atmosphere for 15 min, after which it was placed in an oil bath at 50 ° C and stirred overnight. Partitioned between water (25 ml) and pentane: ethyl acetate (1: 1) solution (50 ml). Aq. the layer was extracted with fresh pentane: ethyl acetate (1: 1) (20 ml). United org. the layers were dried (Na ₂ SO ₄ ) and concentrated. The crude material was purified by flash chromatography using heptane: ethyl acetate 1: 0 to 0: 1 to give 6-methylheptyl-3 ((5-bromo-1-isopropyl-3-methyl-1H-pyrazolo [4.3 -b] pyridin-7-yl) thio) propanoate (194 mg).

Preparation of 6-methylheptyl-3 - ((5- (2-ethoxypyridin-3-yl) -1-isopropyl-3-methyl-1H-pyrαzolo [4,3b] pyridin-7-yl) thio) propanoate

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A suspension of 6-methylheptyl-3 - ((5-bromo-1-isopropyl-3-methyl-1H-pyrazolo [4,3 b] pyridin-7-yl) thio) propanoate (194 mg, 0.41 mmol) was degassed, 2-ethoxy-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine (123 mg, 0.50 mmol), PdCl ₂ (dppf) -CH ₂ Cl ₂ (84 mg, 0.10 mmol), K ₂ CO ₃ (85 mg, 0.62 mmol) in 1,4-dioxane (5.5 ml) and water (0.3 ml) by bubbling nitrogen for 3 min and then stirred at 105 ° C for 4 hours. Most of the solvent was removed in vacuo. The resulting residue was taken up in ethyl acetate (25 ml) and filtered through a thin pad of celite, which was rinsed with ethyl acetate (10 ml x 2). The combined filtrates were washed with brine (20 ml), dried (Na ₂ SO ₄ ) and concentrated. The crude material was purified by flash chromatography with heptane: ethyl acetate 1: 0 to 0: 1 to give 6-methylheptyl-3 - ((5- (2ethoxypyridin-3-yl) -1 -isopropyl-3-methyl-1 H -pyrazolo [4,3-b] pyridin-7-yl) thio) propanoate (128 mg).

Preparation of ethyl 5- (hydroxymethyl) isoxazole-3-carboxylate

In a solution of prop-2-yn-1-ol (500 mg, 0.52 ml, 8.92 mmol) and ethyl 2-nitroacetate (2.26 g, 1.88 ml, 16.95 mmol) in EtOH ( 15 ml) was added DABCO (1.0 g, 8.92 mmol). The mixture was stirred at 80 ° C for 72 hours while heating with microwave radiation. The mixture was concentrated and directly purified by flash chromatography with heptane: ethyl acetate = 1: 0 to 0: 1 to give ethyl 5- (hydroxymethyl) isoxazole-3-carboxylate (400 mg).

Preparation of ethyl 5- (fluoromethyl) isoxazole-3-carboxylate

To a solution of ethyl 5- (hydroxymethyl) isoxazole-3-carboxylate (50.0 mg, 0.29 mmol) in DCM (2 ml) was added diethylaminosulfur trifluoride (70.6 mg, 0.06 ml, 0.44 mmol) ... The mixture was stirred at 40 ° C for 1 h. Water (3 ml) was added and the mixture was extracted with ethyl acetate (5 ml x 3). The combined organic layers were washed with brine (5 ml), dried over Na ₂ SO ₄ and concentrated. The crude mixture was purified by flash chromatography with heptane: ethyl acetate = 1: 0 to 0: 1 to give ethyl 5- (fluoromethyl) isoxazole-3-carboxylate (41.0 mg).

Obtaining (5- (fluoromethyl) isoxazol-3-yl) methanol

To a solution of ethyl 5- (fluoromethyl) isoxazole-3-carboxylate (50.0 mg, 0.29 mmol) in THF (4 ml) at 0 ° С was added lithium aluminum hydride (0.43 ml, 0.43 mmol, 1M in THF). The mixture was stirred at 0 ° C for 1 hour. A semi-saturated sodium potassium tartrate solution (5 ml) was added and the mixture was thoroughly stirred for 30 minutes. The mixture was then extracted with ethyl acetate (10 ml x 3). The combined organic layers were washed with brine (10 ml), dried over Na ₂ SO ₄ and concentrated. The crude mixture was purified by flash chromatography using heptane: ethyl acetate = 1: 0 to 0: 1 to give (5- (fluoromethyl) isoxazol-3-yl) methanol (29.0 mg).

Getting 3 - (bromomethyl) -5 - (fluoromethyl) isoxazole

To a solution of (5- (fluoromethyl) isoxazol-3-yl) methanol (17.0 mg 0.13 mmol) in MeCN (2 ml) was added triphenylphosphine (68 mg, 0.26 mmol), 2,6-lutidine (13 , 9 mg, 0.015 ml, 0.13 mmol) and CBr ₄ (86 mg, 0.26 mmol). The reaction mixture was stirred at room temperature for 1 h. The mixture was concentrated and directly purified by flash chromatography with heptane: ethyl acetate = 1: 0 to 0: 1 to give 3- (bromomethyl) -5- (fluoromethyl) isoxazole (With 12 mg).

Obtaining ethyl 5- (bromomethyl) isoxazole-3-carboxylate

To a solution of ethyl 5- (hydroxymethyl) isoxazole-3-carboxylate (50 mg, 0.29 mmol) in MeCN (2 ml), triphenylphosphine (153 mg, 0.58 mmol), 2,6-lutidine (31.3 mg, 0.034 ml, 0.29 mmol) and CBr ₄ (194 mg, 0.58 mmol). The reaction mixture was stirred at room temperature for 1.5 hours. The mixture

- 82,037544 was concentrated and directly purified by flash chromatography using heptane: ethyl acetate = 1: 0 to 0: 1 to give ethyl 5- (bromomethyl) isoxazole-3-carboxylate (68 mg).

Obtaining (5- (bromomethyl) isoxazol-3-yl) methanol

To a solution of ethyl 5- (bromomethyl) isoxazole-3-carboxylate (26 mg, 0.11 mmol) in THF (1 ml) at 0 ° C was added diisopropylaluminum hydride (0.12 ml, 0.12 mmol, 1 M in THF ). The mixture was stirred at 0 ° C for 2 hours. An additional 0.12 mmol of diisopropylaluminum hydride solution was added and the mixture was stirred for an additional 1 hour. 3 drops of 4M HCl (aq.) Were added followed by the addition of a half-saturated sodium potassium tartrate solution (5 ml ). The mixture was thoroughly mixed for 30 minutes. The mixture was then extracted with ethyl acetate (10 ml x 3). The combined organic layers were washed with brine (10 ml), dried over Na ₂ SO ₄ and concentrated to give (5- (bromomethyl) isoxazole-3yl) methanol (21.3 mg, 0.11 mmol).

Preparation of 5- (bromomethyl) -3- (fluoromethyl) isoxazole

To a solution of (5- (bromomethyl) isoxazol-3-yl) methanol in DCM (1 ml) was added diethylaminosulfur trifluoride (70.6 mg, 0.06 ml, 0.44 mmol). The mixture was stirred at 40 ° C for 1 h. Water (3 ml) was added and the mixture was extracted with ethyl acetate (5 ml x 3). The combined organic layers were washed with brine (5 ml), dried over Na ₂ SO ₄ and concentrated. The crude mixture was purified by flash chromatography with heptane: ethyl acetate = 1: 0 to 0: 1 to give 5 (bromomethyl) -3- (fluoromethyl) isoxazole (7.0 mg, 0.04 mmol).

Preparation of methyl 1- (difluoromethyl) -1H-pyrazole-4-carboxylate

To a solution of 1- (difluoromethyl) -1H-pyrazole-4-carboxylic acid (100 mg, 0.62 mmol) in DCM (4 ml) was added (diazomethyl) trimethylsilane (0.62 ml, 1.23 mmol, 2M in hexane ). The mixture was stirred at room temperature for 2 hours. Acetic acid (0.2 ml) was added and the mixture was coevaporated with toluene (2x20 ml) to give methyl 1- (difluoromethyl) -1H-pyrazole-4-carboxylate (99.0 mg, 0.56 mmol).

Obtaining (1- (difluoromethyl) -1H-pyrazol-4-yl) methanol

To a solution of methyl 1- (difluoromethyl) -1H-pyrazole-4-carboxylate (120 mg, 0.68 mmol) in THF (4 ml) at 0 ° C was added lithium aluminum hydride (1.0 ml, 1.0 mmol, 1M in THF). The mixture was stirred at 0 ° C for 1 hour. A semi-saturated sodium potassium tartrate solution (5 ml) was added and the mixture was thoroughly stirred for 30 minutes. The mixture was then extracted with ethyl acetate (10 ml x 3). The combined organic layers were washed with brine (10 ml), dried over Na ₂ SO ₄ and concentrated. The crude mixture was purified by flash chromatography with heptane: ethyl acetate = 1: 0 to 0: 1 to give (1- (difluoromethyl) -1H-pyrazol-4-yl) methanol (101 mg, 0.68 mmol).

Obtaining 4- (bromomethyl) -1 - (difluoromethyl) -1 H-pyrazole

To a solution of (1- (difluoromethyl) -1H-pyrazol-4-yl) methanol (30 mg, 0.20 mmol) in MeCN (1.5 ml) was added triphenylphosphine (106 mg, 0.41 mmol), 2.6 β-lutidine (21.7 mg, 23.6 μL, 0.20 mmol) and CBr ₄ (134 mg, 0.41 mmol). The reaction mixture was stirred at room temperature for 1 hour. The mixture was concentrated and directly purified by flash chromatography using hepta-83 037544 on: ethyl acetate = 1: 0 to 0: 1 to give 4- (bromomethyl) -1- ( difluoromethyl) -1H-pyrazole (29 mg).

Preparation of N - ((1 - (difluoromethyl) -1 H-pyrazol-4-yl) methyl) -5- (2-ethoxypyridin-3-yl) -1 -isopropyl N- (4-methoxybenzyl) -3-methyl-1H -pyrαzolo [4,3-b] pyridin-7-amine

To a suspension of NaH (3.79 mg, 0.095 mmol, 60% w / w) in THF (1 ml) at 0 ° C was added 5- (2ethoxypyridin-3-yl) -1-isopropyl-N- (4- methoxybenzyl) -3-methyl-1H-pyrazolo [4,3-b] pyridin-7-amine (20.5 mg, 0.05 mmol). The mixture was stirred at 0 ° C for 15 min before adding 4- (bromomethyl) 1- (difluoromethyl) -1H-pyrazole (10 mg, 0.05 mmol) in THF (1 ml). The reaction mixture was allowed to slowly warm to room temperature and stirred for 2 hours. Water (5 ml) was added and the mixture was extracted with ethyl acetate (5 ml x 3). The combined organic layers were washed with brine (10 ml), dried over Na ₂ SO ₄ and concentrated. The crude mixture was purified by flash chromatography with heptane: ethyl acetate = 1: 0 to 0: 1 to give N - ((1 (difluoromethyl) -1H-pyrαzol-4-yl) methyl) -5- (2-ethoxypyridine -3-yl) -1-isopropyl-N- (4-methoxybenzyl) -3methyl-1H-pyrazolo [4,3-b] pyridin-7-amine (23 mg, 0.04 mmol).

The following examples:

5- (2-ethoxypyridin-3-yl) -N - ((5- (fluoromethyl) isoxazol-3-yl) methyl) -1-isonropyl-N- (4-methoxybenzyl) -3-methyl-1H-pyrazolo [ 4,3-b] pyridin-7-amine

obtained from 5- (2-ethoxypyridin-3-yl) -1-isonropyl-N- (4-methoxybenzyl) -3-methyl-1Hpyrazolo [4,3-b] pyridin-7-amine and 3- (bromomethyl) - 5- (fluoromethyl) isoxazole;

5- (2-ethoxypyridin-3-yl) -N - ((3- (fluoromethyl) isoxαzol-5-yl) methyl) -1-isonropyl-N- (4-methoxybenzyl) -3-methyl-1H-pyrazolo [ 4,3-b] pyridin-7-amine

obtained from 5- (2-ethoxypyridin-3-yl) -1-isonropyl-N- (4-methoxybenzyl) -3-methyl-1Hpyrazolo [4,3-b] pyridin-7-amine and 5- (bromomethyl) - 3- (fluoromethyl) isoxazole was prepared in a similar manner.

Obtaining (2-oxo-1,2-dihydropyridin-3-yl) boronic acid

To a solution of 3-bromopyridin-2 (1H) -one (3.3 g, 19 mmol) in THF (200 ml) cooled to -78 ° C was added TMEDA (tetramethylethylenediamine) (6.6 g, 57 mmol ) over 15 min followed by the addition of n-BuLi (in hexane, 2.5 M, 23 ml). The resulting mixture was stirred for 15 min at -78 ° C and then warmed to room temperature. The reaction mixture was cooled to 0 ° C and added

84 037544 Trimethyl borate (3.9 g, 38 mmol) was dropwise over 30 min. After the addition was complete, the reaction mixture was warmed to room temperature and stirred for 15 h. The mixture was then cooled to 0 ° C and a small amount of ice was added followed by the addition of HCl (aq., 100 ml,

2M). The THF was removed under reduced pressure and the aqueous solution was washed twice with dichloromethane (50 ml x 2). Concentrated aqueous NaOH was added slowly until a pH of 5 was reached and a precipitate formed. The mixture was cooled to 0 ° C and stirred for 10 minutes. The solid was collected by filtration, washed with cold water and dried under vacuum to give (2oxo-1,2-dihydropyridin-3-yl) boronic acid.

Preparation of 2- (trifluoromethyl) pyridine-3-carbonitrile

Zn (CN) 2 (572 mg, 4.87 mmol) and Pd (PPh ₃ ) ₄ (1 d, 0.885 mmol), then the reaction mixture was stirred at 140 ° C for 1 h under microwave heating. The reaction mixture was cooled to room temperature, filtered through celite and washed with ethyl acetate (100 ml). The reaction mixture was extracted with ethyl acetate (100 ml x 2) and the organic layers were washed with water (100 x 3 ml), brine (100 ml), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give a residue. The residue was purified by silica gel flash chromatography (petroleum ether / ethyl acetate) to give 2- (trifluoromethyl) pyridine-3-carbonitrile.

Obtaining (2- (trifluoromethyl) pyridin-3-yl) methanamine

N _F F Ψ Raney Ni, NH3.H2O F < ^{NH2 F} ХЗ MeOH ^F UJ

To a solution of Raney-Ni (50 mg, 0.581 mmol) in MeOH (20 ml), 2- (trifluoromethyl) pyridine-3carbonitrile (500 mg, 2.91 mmol) and NH _3. Water (6M, 5 ml) were added, then the reaction the mixture was stirred at 30 ° C. for 2 hours. The reaction mixture was concentrated under reduced pressure to give a precipitate. HCl (2M, 2 ml) and water (10 ml) were added to the residue. The resulting solution was lyophilized. The crude product was used in the next step without further purification.

Preparation of tert-butyl - ((5-methoxypyrimidin-2-yl) methyl) carbamate

A mixture of 5-methoxypyrimidine-2-carbonitrile (100 mg, 0.74 mmol) and Boc ₂ O (194 mg, 0.89 mmol) and MeOH (5 ml) was added to Raney-Ni (30 mg, 10%), reaction the mixture was stirred at room temperature for 2 hours under an atmosphere of H ₂ (45 psi). The reaction mixture was filtered to remove the catalyst and the filter cake was washed with MeOH (10 ml x 3) and the filtrate was concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (0 to ~ 10% ethyl acetate in petroleum ether) to give tert-butyl - ((5-methoxypyrimidin-2yl) methyl) carbamate.

Preparation of (5-methoxypyrimidin-2-yl) methanamine hydrochloride

A mixture of tert-butyl - ((5-methoxypyrimidin-2-yl) methyl) carbamate (100 mg, 0.42 mmol) and dichloromethane (5 ml) and HCl / dioxane (4M, 2 ml) was stirred at room temperature for 0 , 5 h. Water (10 ml) was added to the reaction mixture and the solution was concentrated in vacuo to give an organic phase and the aqueous phase was lyophilized to give the crude product. The crude product was obtained, which is (5-methoxypyrimidin-2-yl) methanamine.

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Preparation of 4-methoxypyrimidine-2-carbonitrile

Cl

Pd (dppf) CI ₂

Zn (CN) ₂

NMP

CN

Absorbed 2-chloro-4-methoxypyrimidine (600 mg, 4.15 mmol) and Zn (CN) ₂ (292 mg, 2.49 mmol) and Pd (dppf) Cl ₂ (607 mg, 0.83 mmol) in a test tube for microwave processing with NMP (3 ml). The closed tube was heated at 140 ° C for 1 hour using microwave radiation. The reaction mixture was cooled to room temperature, filtered through celite and washed with ethyl acetate (20 ml). The reaction mixture was extracted with ethyl acetate (20 ml x 3) and the organic layers were washed with water (20 x 3 ml), brine (20 ml), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give a residue. The residue was purified by silica gel flash chromatography (petroleum ether / ethyl acetate) to give 4-methoxypyrimidine-2carbonitrile.

Preparation of tert-butyl-N - [(4-methoxypyrimidin-2-yl) methyl] carbamate

Vos ₂ O,

CN

Ni Raney, H

EtOH

ABOUT

To a solution of Raney-Ni (25 mg, 0.296 mmol) in EtOH (5 ml) was added 4-methoxypyrimidine-2carbonitrile (200 mg, 1.48 mmol) and Boc ₂ O (355 mg, 1.63 mmol, 0.374 ml) in N ₂ atmosphere, then the reaction mixture was stirred at room temperature under H 2 atmosphere (45 psi) for 2 hours. The reaction mixture was filtered through celite and concentrated under reduced pressure to give a residue. The residue was purified by silica gel flash chromatography (petroleum ether / ethyl acetate) to give tert-butyl N - [(4-methoxypyrimidin-2-yl) methyl] carbamate.

Preparation of (4-methoxypyrimidin-2-yl) methanamine hydrobromide

NHBoc NH ₂ HBr

HBr / H ₂ O 1

N ^ N --- N ^ N ΐ j ΐ JJ

I I

Stir a solution of tert-butyl-N - [(4-methoxypyrimidin-2-yl) methyl] carbamate (100 mg, 0.418 mmol) in HBr / water (3 ml) at room temperature for 1 h. The reaction mixture was concentrated under reduced pressure with obtaining a precipitate. The crude product was used in the next step without further purification.

Preparation of 6-methoxypyrimidine-4-carbonitrile

To a solution of 4-chloro-6-methoxypyrimidine (1 g, 6.92 mmol) in DMF (10 ml) was added Pd (PPh ₃ ) ₄ (2 g,

1.38 mmol) and Zn (CN) ₂ (487 mg, 4.15 mmol). The reaction mixture was stirred at 80 ° C for 16 hours. The reaction mixture was cooled to room temperature, filtered through celite and washed with dichloromethane (100 ml). The reaction mixture was extracted with dichloromethane (100 ml x 3) and the organic layers were washed with water (100 x 3 ml) and brine (50 ml), dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure to give a residue. The residue was purified by silica gel flash chromatography (petroleum ether / ethyl acetate) to give 6methoxypyrimidine-4-carbonitrile.

Preparation of tert-butyl-N - ((6-methoxypyrimidin-4-yl) methyl) carbamate

To a solution of Raney-Ni (25 mg, 0.296 mmol) in EtOH (5 ml), 6-methoxypyrimidine-4carbonitrile (200 mg, 1.48 mmol) and Boc ₂ O (355 mg, 1.63 mmol, 0.374 ml) were added, then the reaction mixture was stirred at room temperature under an atmosphere of H ₂ (45 psi) for 2 hours. The reaction mixture was filtered through celite and washed with EtOH (20 ml x 2), the filtered was concentrated under reduced pressure with the receipt of the remainder. The residue was purified by silica gel flash chromatography (petroleum ether / ethyl acetate) to give tert-butyl N - [(6methoxypyrimidin-4-yl) methyl] carbamate.

Obtaining (6-methoxypyrimidin-4-yl) methanamine

NHBoc r ^ N ------ 1

JJ HC1 / dioxane

O N

'2

Stir a solution of tert-butyl N - [(6-methoxypyrimidin-4-yl) methyl] carbamate (240 mg, 1.00 mmol) in HCl / dioxane (10 ml) at room temperature for 2 h. reduced pressure to obtain a precipitate. The residue was used in the next step without further purification.

Obtaining 3-bromopicolinaldehyde

To a solution of 2,3-dibromopyridine (5 g, 21.11 mmol) in toluene (50 ml) was added t-BuLi (1.3 M, 19.50 ml) dropwise at -78 ° C under N2 atmosphere. The resulting mixture was stirred at -78 ° C for 2 hours. DMF (1.9 g, 25.33 mmol) was added dropwise at -78 ° C. The mixture was stirred at -78 ° C for an additional 2 hours. The solution was quenched with NH4Cl (aq, 1 ml) at -78 ° C and the mixture was concentrated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10/1 to 1/1) to give 3-bromopicolinaldehyde.

Obtaining 3-bromo-2- (difluoromethyl) pyridine

O Br F Br

DAST-F

To a solution of 3-bromopicolinaldehyde (1.3 g, 6.99 mmol) in dichloromethane (30 ml) was added diethylaminosulfur trifluoride (2.25 g, 13.98 mmol) at 0 ° C. The reaction mixture was stirred at 0 ° C for 2 h under N ₂ . The solution was quenched with NaHCO ₃ (aq. 15 ml) at 0 ° C. The aqueous phase was extracted with dichloromethane (10 ml x 3). The combined organic phases were washed with brine (15 ml x 1), dried with anhydrous Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (petroleum ether / ethyl acetate = 1/0 to 10/1) to give 3-bromo-2- (difluoromethyl) pyridine.

Obtaining 2- (difluoromethyl) nicotinonitrile

To a mixture of 3-bromo-2- (difluoromethyl) pyridine (600 mg, 2.88 mmol) and Zn (CN) ₂ (373 mg, 3.17 mmol) in NMP (10 ml) was added Pd (PPh ₃ ) ₄ ( 333 mg, 0.29 mmol). The reaction mixture was heated with microwave radiation at 140 ° C for 1 hour. The reaction mixture was poured into ethyl acetate (50 ml). The mixture was washed with water (20 ml x 3) and brine (15 ml x 1), dried over Na ₂ SO ₄ and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (petroleum ether / ethyl acetate = 1/0 to 2/1) to give 2- (difluoromethyl) nicotinonitrile.

Preparation of tert-butyl - ((2- (difluoromethyl) pyridin-3-yl) methyl) carbamate

A mixture of 2- (difluoromethyl) nicotinonitrile (0.4 g, 2.60 mmol), (Boc) ₂ O (680 mg, 3.11 mmol) and Raney-Ni (22 mg, 0.26 mmol) in MeOH ( 20 ml) at 30 ° C for 2 hours under an atmosphere of H ₂ (40 psi). The mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by silica gel chromatography (petroleum ether / ethyl acetate = 1/0 to 3/1) to give tert-butyl - ((2- (difluoromethyl) pyridin-3-yl) methyl) carbamate.

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Preparation of (2- (difluoromethyl) pyridin-3-yl) methanamine hydrochloride

To a solution of tert-butyl - ((2- (difluoromethyl) pyridin-3-yl) methyl) carbamate (0.6 g, 2.32 mmol) in dichloromethane (5 ml) was added HCl / dioxane (4M, 1 ml) at 0 ° C. The reaction mixture was stirred at room temperature for 12 hours. The mixture was concentrated in vacuo to give (2 (difluoromethyl) pyridin-3-yl) methanamine hydrochloride.

Obtaining 3-bromo-2-ethoxypyridine

To a mixture of 3-bromo-2-chloropyridine (200 mg, 1 mmol) in EtOH (5 ml) was added t-BuOK (233 mg, 2 mmol). The mixture was stirred at 80 ° C for 12 hours. The reaction mixture was filtered and the filtrate was concentrated in vacuo to give the crude product. The residue was purified by silica gel flash chromatography (0 to ~ 40% ethyl acetate in petroleum ether) to give 3-bromo-2ethoxypyridine.

Obtaining 2-ethoxynicotinonitrile

Zn (CN) 2 (244 mg, 2.1 mmol) and Pd (dppf) Cl ₂ (127 mg, 0.17 mmol). The mixture was degassed with N2 and heated at 140 ° C. with microwave for 1 hour. The mixture was cooled to room temperature and filtered through celite. The filter cake was washed with ethyl acetate (30 ml). The filtrate was washed with water (20 ml x 2) and brine (20 ml), dried over Na ₂ SO ₄ , filtered and concentrated. The residue was purified by silica gel flash chromatography (0 to ~ 20% ethyl acetate in petroleum ether) to give 2-ethoxy-nicotinonitrile.

Preparation of tert-butyl - ((2-ethoxypyridin-3-yl) methyl) carbamate

To a solution of Raney-Ni (24 mg, 0.28 mmol) in EtOH (5 ml) were added 2-ethoxynicotinonitrile (210 mg, 1.4 mmol) and Boc ₂ O (371 mg, 1.7 mmol). The reaction mixture was stirred at room temperature under an atmosphere of H ₂ (45 psi) for 2 h. The reaction mixture was filtered through celite and washed with EtOH (20 ml x 2), then the filtrate was concentrated under reduced pressure to give a residue. The residue was purified by preparative HPLC to give tert-butyl - ((2ethoxypyridin-3-yl) methyl) carbamate.

Obtaining (2-ethoxypyridin-3-yl) methanamine

Stir a solution of tert-butyl - ((2-ethoxypyridin-3-yl) methyl) carbamate (85 mg, 0.34 mmol) in HCl / dioxane (4M, 2 ml) at room temperature for 12 hours. The reaction mixture was concentrated at reduced pressure to give 2-ethoxypyridin-3-yl) methanamine.

Obtaining 3-methoxypyridine-4-carbonitrile

- 88 037544

Dissolve 3-chloropyridine-4-carbonitrile (250 mg, 1.80 mmol) in DMF (5 ml) and cool to ice bath temperature. _{CH 3} ONa (194.95 mg, 3.61 mmol) was added slowly and the reaction mixture was stirred at room temperature for 2 h under N2. Water (20 ml) and ethyl acetate (20 ml) were added to the reaction mixture. The aqueous phase was extracted with ethyl acetate (20 ml x 2). The organic phases were combined and dried over anhydrous Na ₂ SO ₄ (5 g), filtered and concentrated in vacuo to give the product 3-methoxypyridine-4-carbonitrile.

Obtaining (3-methoxy-4-pyridyl) methanamine

A mixture of 3-methoxypyridine-4-carbonitrile (200 mg, 1.49 mmol), NH3 in water (314 mg, 2.24 mmol, 25%) and Raney-Ni (30 mg) in MeOH (5 ml) was stirred at room temperature. temperature for 3 hours in an atmosphere of 1H (45 psi). The reaction mixture was filtered to remove the catalyst and the filter cake was washed with MeOH (10 ml x 3). The filtrate was concentrated in vacuo. The residue was dissolved in 1M HCl (30 ml) and the solution was lyophilized to give (3-methoxy-4pyridyl) methanamine hydrochloride (296 mg). Stir a mixture of (3-methoxy-4-pyridyl) methanamine hydrochloride (100 mg, 0.57 mmol), Ambersep 900 (OH) and metal exchange resin (150 mg) in MeCN (5 ml) at room temperature for 0.5 h Using a universal indicator paper, it was shown that the pH of the solution was 9-10. The reaction mixture was filtered to remove the gum, and the filtrate was dried over anhydrous Na ₂ SO ₄ , filtered and concentrated in vacuo to give (3-methoxy4-pyridyl) methanamine.

Preparation of methyl 4-methoxypyrimidine-5-carboxylate

Br ^with

N ^ N TEA, Pd (dppf) CI ₂ Νς ^ Ν

Triethylamine (1.07 g, 10.58 mmol) and Pd (dppf) Cl ₂ (774 mg, 1, 06 mmol). The suspension was degassed and flushed several times with CO. The mixture was heated at 80 ° C under a CO atmosphere (50 psi) for 16 hours. The mixture was filtered through celite and the filtrate was concentrated. The residue was purified by silica gel flash chromatography (petroleum ether / ethyl acetate) to give methyl 4-methoxypyrimidine 5-carboxylate.

Obtaining (4-methoxypyrimidin-5-yl) methanol

_{LiAlH 4} (169 mg, 4.46 mmol) was added to a solution of methyl 4-methoxypyrimidine-5-carboxylate (250 mg, 1.49 mmol) in THF (5 ml) at -40 ° C. The mixture was stirred at -40 ° C for 0.5 h. Water (0.5 ml) and 15% NaOH (0.5 ml) were added. The mixture was extracted with ethyl acetate (20 ml x 2). The combined organic layer was washed with water (10 ml), dried over Na ₂ SO ₄ , filtered and concentrated. The residue was purified by silica gel flash chromatography (petroleum ether / ethyl acetate) to give (4-methoxypyrimidin-5-yl) methanol.

Preparation of 5- (bromomethyl) -4-methoxypyrimidine

To a solution of (4-methoxypyrimidin-5-yl) methanol (50 mg, 0.36 mmol) in dry dichloromethane (2 ml) was added PBr ₃ (144 mg, 0.53 mmol) at 0 ° C. The mixture was stirred at 0 ° C for 0.5 h. The mixture was concentrated and ice water (5 g) was added. The aqueous layer was extracted with ethyl acetate (20 ml x 2). The organic layer was dried over Na ₂ SO ₄ , filtered and concentrated to give 5 (bromomethyl) -4-methoxypyrimidine (70 mg, crude).

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Obtaining 3-bromo-2- (ethoxy-d ₅ ) pyridine

D

NaH (60% dispersion in oil) (227 mg, 5.68 mmol) was suspended in THF (13 ml) and cooled to ice bath temperature. A solution of ethanol-d ₆ (296 mg, 5.68 mmol) in THF (1.2 ml) was added dropwise. The resulting suspension was stirred at ice bath temperature for 10 min, after which the cooling bath was removed and stirring continued for 0.5 h. The resulting mixture was cooled again to ice bath temperature and a solution of 3-bromo-2-fluoropyridine (500 mg , 2.84 mmol) in THF (1.2 mL). After stirring for 15 min at ice bath temperature, cooling was discontinued and stirring continued for an additional 45 min at room temperature, after which a reflux condenser was inserted and the mixture was heated to 65 ° C for 10 h. The mixture was cooled back to ice bath temperature and quenched with a few drops of water. Most of the solvent was removed in vacuo. The resulting residue was partitioned between ethyl acetate (25 ml) and brine (10 ml). The organic layer was dried (Na ₂ SO ₄ ) and concentrated. The residue was purified by silica gel flash chromatography (heptane / ethyl acetate) to give 3 bromo-2- (ethoxy-d ₅ ) pyridine.

The following connections:

D

3-bromo-2- (ethoxy-2,2,2-d ₃ ) pyridine, derived from 3-bromo-2-fluoropyridine and ethanol-2,2,2-d ₃ ;

3-bromo-2- (ethoxy-1,1-d ₃ ) pyridine, prepared from 3-bromo-2-fluoropyridine and ethanol (1,1-d ₂ ), was prepared in a similar manner.

Preparation of 2- (ethoxy-d ₅ ) -3- (4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl) pyridine

A suspension of 3-bromo-2- (ethoxy-d ₅ ) pyridine (152 mg, 0.73 mmol), 4,4,4 ', 4', 5.5,5 ', 5'octamethyl-2,2' was degassed -bi (1,3,2-dioxaborolane) (242 mg, 0.95 mmol), PdCl ₂ (dppf) -CH ₂ Cl ₂ (120 mg, 0.15 mmol) and KOAc (216 mg, 2.20 mmol ) in 1,4-dioxane (2.5 ml) by bubbling N2 through the suspension for approx. 3 min, after which it was heated to 110 ° C for 4.5 h. The resulting suspension was diluted with ethyl acetate (10 ml) and filtered through a thin pad of celite, which was rinsed with ethyl acetate (2x10 ml). Most of the solvent was removed in vacuo. The resulting residue was taken up in ethyl acetate (50 ml) and washed with brine (30 ml). The organic layer was dried (Na ₂ SO ₄ ), filtered and concentrated. Purification by flash chromatography on silica gel (eluting from heptane to ethyl acetate) gave 2- (ethoxy-d ₅ ) -3- (4,4,5,5-tetramethyl-1,3,2-dioxaboran-2- yl) pyridine.

The following connections:

D

2- (ethoxy-2,2,2-d ₃ ) -3- (4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl) pyridine obtained from 3-bromo-2 ( ethoxy-2,2,2-d ₃ ) pyridine;

- 90 037544

2- (ethoxy-1,1-d ₂ ) -3- (4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl) pyridine, obtained from 3-bromo-2 (ethoxy- 1,1-d ₂ ) pyridine was prepared in a similar manner.

Preparation of 2'-ethoxy-6-methyl- [2,3'-bipyridine] -5-amine

N2 was bubbled through a mixture of 6-bromo-2-methylpyridin-3-amine (2.5 g, 13.4 mmol), 2-ethoxy-3 (4,4,5,5-tetramethyl-1,3,2-dioxaborolane -2-yl) pyridine (5.0 g, 20.1 mmol), PdCl ₂ (dppf) -CH ₂ Cl ₂ (2.18 g, 2.67 mmol) and potassium carbonate (3.69 g, 26, 7 mmol) in 1,4-dioxane (126 ml) and water (12 ml) for 10 min. A reflux condenser was inserted and the reaction mixture was heated at 105 ° C for 2.5 h under an inert atmosphere after which most of the solvent was removed in vacuo. The resulting residue was taken up in ethyl acetate (150 ml) and filtered through a thin pad of celite, which was rinsed with ethyl acetate (2x50 ml). Concentration and purification by flash chromatography on silica gel (elution from heptane to heptane / dichloromethane (1: 1) to (1: 1: 1.5)) gave 2'-ethoxy-6-methyl- [2,3 '-bipyridine] -5-amine.

Preparation of 4-chloro-2'-ethoxy-6-methyl- [2,3'-bipyridine] -5-amine heptane / dichloromethane / ethyl acetate

Stirred a solution of 2'-ethoxy-6-methyl- [2,3'-bipyridine] -5-amine (7.40 g, 22.6 mmol) and N-chlorosuccinimide (3.77 g, 28.2 mmol) in NMP ( 104 ml) at room temperature for 15 minutes under an inert atmosphere. A reflux condenser was inserted and the solution was heated to 80 ° C for 3.5 h, after which it was allowed to cool to room temperature and partitioned between ethyl acetate (300 ml) and saturated aqueous NaHCO ₃ solution (3x200 ml). The combined aqueous layers were extracted with ethyl acetate (50 ml). The combined organic layers were further washed with brine (2x100 ml), dried (Na ₂ SO ₄ ) and concentrated. The residue was purified by silica gel flash chromatography (heptane / ethyl acetate) to give 4-chloro-2'-ethoxy-6-methyl- [2,3'bipyridine] -5-amine.

Preparation of 7-chloro-5- (2-ethoxypyridin-3-yl) -1H-pyrazolo [4,3-b] pyridine

A suspension of 4-chloro-2'-ethoxy-6-methyl- [2,3'-bipyridine] -5-amine (4.01 g, 12.2 mmol) and potassium acetate (2.98 g, 30.4 mmol) in toluene (84 ml) and acetic acid (28 ml) at ice bath temperature for 5 min under an inert atmosphere. Isopentyl nitrite (2.71 g, 23.11 mmol) was added dropwise over 5 min. After stirring at ice bath temperature for 10 min, a reflux condenser was inserted and the mixture was heated to 35 ° C for 2.5 h. Most of the solvent was removed in vacuo. The resulting residue was suspended in ethyl acetate (350 ml) and washed with saturated aqueous NaHCO ₃ (2x250 ml), brine (200 ml), dried (Na ₂ SO ₄ ) and concentrated. The residue was purified by silica gel flash chromatography (heptane / ethyl acetate) to give 7-chloro-5- (2-ethoxypyridin-3-yl) -1H-pyrazolo [4,3-b] pyridine.

Preparation of 7-chloro-5- (2-ethoxypyridin-3-yl) -3-iodo-1H-pyrazolo [4,3-b] pyridine

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A solution of 7-chloro-5- (2-ethoxynyridin-3-yl) -1H-nyrazolo [4,3-b] nyridine (1.0 g, 3.64 mmol) and N-iodosuccinimide (1.11 g, 4.91 mmol) in DMF (50.0 ml) at room temperature for 15 min under an inert atmosphere, after which a reflux condenser was inserted and stirring continued at 35 ° C for 11 h. The solution was diluted with ethyl acetate (350 ml) and washed 10% aqueous Na ₂ S ₂ O ₃ (100 ml), 1/2-saturated aqueous NaHCO ₃ (2x150 ml) and brine (50 ml). The organic layer was dried (Na ₂ SO ₄ ) and concentrated to give 7-chloro-5- (2ethoxypyridin-3-yl) -3-iodo-1H-pyrazolo [4,3-b] pyridine, which was used without further purification.

Preparation of 7-chloro-5- (2-ethoxypyridin-3-yl) -3-iodo-1-isopropyl-1H-pyrazolo [4,3-b] pyridine

A solution of diisopropyl azodicarboxylate (1.59 g, 7.86 mmol) in THF (3.0 ml) was added dropwise to an ice-cold solution of 7-chloro-5- (2-ethoxypyridin-3-yl) -3-iodo-1H-pyrazolo [4,3-b] pyridine (1.0 g, 2.25 mmol), isopropanol (0.60 ml, 7.86 mmol) and triphenylphosphine (2.06 g, 7.86 mmol) in THF (25 ml ) in an inert atmosphere. After stirring at ice bath temperature for 0.5 h, the solution was allowed to warm to room temperature and stirring continued for 4.5 h. Most of the solvent was removed in vacuo and the resulting residue was dissolved in ethyl acetate (150 ml) and washed with saturated aqueous NaHCO ₃ (150 ml), brine (100 ml), dried (Na ₂ SO ₄ ) and concentrated. Purification by flash chromatography on silica gel (gradient elution from heptane to ethyl acetate) gave 7-chloro-5- (2-ethoxypyridin-3-yl) -3-iodo-1-isopropyl 1 H-pyrazolo [4,3-b ] pyridine.

Preparation of 7-chloro-5- (2-ethoxypyridin-3-yl) -1-isopropyl-3-vinyl-1H-pyrazolo [4,3-b] pyridine

N2 was bubbled through a suspension of 7-chloro-5- (2-ethoxypyridin-3-yl) -3-iodo-1-isopropyl-Spirazolo [4,3-b] pyridine (10 mg, 0.023 mmol), tributyl (vinyl) stannane (9.9 μl, 0.034 mmol), bis (triphenylphosphine) palladium (P) dichloride (4 mg, 5.7 μmol) in 1,4-dioxane (0.30 ml) for 2 min. The mixture was stirred at 105 ° C for 6.5 h, after which additional tributyl (vinyl) stannane (5.0 μl, 0.017 mmol), bis (triphenylphosphine) palladium (II) dichloride (1.6 mg, 2, 3 μmol) and 1,4-dioxane (0.15 ml). The mixture was degassed by bubbling N2 for 2 min and heated again to 105 ° C for 5 h. Most of the solvent was removed in vacuo. The resulting residue was dissolved in ethyl acetate (20 ml), washed with brine (10 ml) and dried (Na ₂ SO ₄ ). Concentration in vacuo gave a residue which was purified by flash chromatography on silica gel (gradient elution from heptane to ethyl acetate) to give 7-chloro-5 (2-ethoxypyridin-3-yl) -1-isopropyl-3-vinyl-1H-pyrazolo [4,3-b] pyridine.

Preparation of 1- (7-chloro-5- (2-ethoxypyridin-3-yl) -1-isopropyl-1H-pyrazolo [4,3-b] pyridin-3-yl) ethan1,2-diol

A mixture of 7-chloro-5- (2-ethoxypyridin-3-yl) -1-isopropyl-3-vinyl-1H-pyrazolo [4,3b] pyridine (10 mg, 0.03 mmol), osmium tetroxide (in the form 2.5 wt% in 2-methyl-2-propanol) (37 μL, 2.9 μmol), N-methylmorpholine (as 50% aqueous solution) (14 mg, 0.06 mmol) in THF (0, 29 ml) and water (0.10 ml) at room temperature for 24 hours. The reaction mixture was quenched at room temperature with 10% aqueous Na2S2O ₃ solution (0.2 ml) and the resulting mixture was stirred for 5 minutes, diluted with brine (0.3 ml) and extracted with ethyl acetate (2x5 ml). The combined organic layers were dried (Na ₂ SO ₄ ) and concentrated to give crude 1- (7-chloro-5- (2ethoxypyridin-3-yl) -1-isopropyl-1H-pyrazolo [4,3-b] pyridin-3-yl ) ethane-1,2-diol, which was used without further purification.

Preparation of 7-chloro-5- (2-ethoxypyridin-3-yl) -1-isopropyl-1H-pyrazolo [4,3-b] pyridine-3-carbaldehyde

is he

A mixture of 1- (7-chloro-5- (2-ethoxypyridin-3-yl) -1-isopropyl-1H-pyrazolo [4,3-L] pyridin3-yl) ethane-1,2-diol (9.0 mg, 0.024 mmol) and sodium periodate (7.7 mg, 0.04 mmol) in THF (0.25 ml) and water (55 μl) at room temperature for 40 min, after which sodium periodate (10.0 mg, 0.05 mmol) and 3 drops of water. After stirring for an additional 15 minutes, the resulting suspension was diluted with ethyl acetate (5 ml) and stirred for 3 minutes. The mixture was filtered through a thin pad of celite, which was rinsed with ethyl acetate (2x5 ml). The combined filtrates were washed with brine (5 ml), dried (Na ₂ SO ₄ ) and concentrated to give 7-chloro-5- (2ethoxypyridin-3-yl) -1-isopropyl-1H-pyrazolo [4,3-b] pyridine -3-carbaldehyde, which was used without additional purification.

Preparation of (7-chloro-5- (2-ethoxypyridin-3-yl) -1-isopropyl-1H-pyrazolo [4,3-L] pyridin-3yl) methanol

_{NaBH 4} (2.0 mg, 0.05 mmol) was added to an ice-cold solution of 7-chloro-5- (2-ethoxypyridin-3-yl) -1isopropyl-1H-pyrαzolo [4,3-b] pyridine-3-carbaldehyde (4.0 mg, 0.01 mmol) in methanol (0.1 ml) under an inert atmosphere. After stirring for 5 minutes at ice bath temperature, the solution was allowed to warm to room temperature and stirring continued for 1 hour, cooled again to ice bath temperature and quenched with a few drops of water. Most of the solvent was removed in vacuo. The resulting residue was partitioned between ethyl acetate (15 ml) and brine (10 ml). The aqueous layer was back extracted with ethyl acetate (5 ml). The combined organic layers were dried (Na ₂ SO ₄ ) and concentrated. The residue was purified by flash chromatography on silica gel (heptane / ethyl acetate) to give (7-chloro-5- (2-ethoxypyridin-3-yl) -1isopropyl-1H-pyrazolo [4,3-b] pyridin-3-yl) methanol ...

Preparation of 7-chloro-5- (2-ethoxypyridin-3-yl) -3- (fluoro methyl) -1-isopropyl-1H-pyrαzolo [4,3-b] pyridine

Diethylaminosulfur trifluoride (5 μl, 0.04 mmol) was added to ice-cold solution (7-chloro-5- (2ethoxypyridin-3-yl) -1-isopropyl-1H-pyrazolo [4,3-b] pyridin-3-yl) methanol (4.0 mg, 0.01 mmol) in CHCl ₃ (0.2 ml). The reaction vessel was closed and the solution was stirred at 0 ° C for 5 min, after which the cooling bath was removed and stirring was continued at room temperature for 12 h. The solution was diluted with ethyl acetate (25 ml) and washed with saturated aqueous NaHCO3 solution (2x15 ml), brine solution (10 ml), dried (Na ₂ SO ₄ ) and concentrated. The residue was purified by flash chromatography on silica gel (heptane / ethyl acetate) to give 7-chloro-5- (2ethoxypyridin-3-yl) -3- (fluoromethyl) -1-isopropyl-1H-pyrazolo [4,3-b] pyridine.

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Preparation of 7-chloro-3- (difluoromethyl) -5- (2-ethoxypyridin-3-yl) -1-isopropyl-1H-pyrazolo [4,3b] pyridine

A solution of 7-chloro-5- (2-ethoxypyridin-3-yl) -1-isopropyl-1H-pyrazolo [4,3-b] pyridine3-carbaldehyde (5.0 mg, 0.01 mmol) and diethylaminosulfur trifluoride ( 10 μl, 0.08 mmol) in dichloromethane (0.15 ml) at room temperature for 4.5 h under an inert atmosphere. The mixture was diluted with ethyl acetate (20 ml) and washed with saturated aqueous NaHCO ₃ (10 ml) and brine (10 ml). The organic layer was dried (Na ₂ SO ₄ ) and concentrated. The residue was purified by silica gel flash chromatography (heptane / ethyl acetate) to give 7-chloro-3- (difluoromethyl) -5- (2ethoxypyridin-3-yl) -1-isopropyl-1H-pyrazolo [4,3-b] pyridine.

Compounds of the present invention

Example 1: 5- (2-ethoxypyridin-3-yl) -1-isopropyl-3-methyl-N - ((5-methyl-1,3,4-oxadiazol-2yl) methyl) -1 H-pyrazolo [4 , 3-b] pyridin-7-amine

To a solution of 5,7-dichloro-1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine (100 mg, 0.41 mmol) in NMP (2 ml) was added CsF (187 mg, 1, 23 mmol, 45 μl) and (5-methyl-1,3,4-oxadiazol-2-yl) methanamine hydrochloride (74 mg, 0.49 mmol). The mixture was stirred at 100 ° C for 18 hours. Water (30 ml) was added and the mixture was extracted with ethyl acetate (30 ml x 3). The combined organic layers were washed with brine (20 ml), dried over Na ₂ SO ₄ and concentrated. The crude mixture was purified by preparative HPLC to give 5-chloro-1-isopropyl-3-methyl-N - ((5-methyl-1,3,4-oxadiazol-2yl) methyl) -1H-pyrazolo [4,3- b] pyridin-7-amine (50 mg).

Into a solution of 5-chloro-1-isopropyl-3-methyl-N - ((5-methyl-1,3,4-oxadiazol-2-yl) methyl) -1H-pyrαzolo [4,3b] pyridin-7-amine (50 mg, 70 μmol) and (2-ethoxypyridin-3-yl) boronic acid (21 mg, 0.13 mmol) in dioxane (2 ml) and H2O (0.7 ml) CS ₂ CO ₃ (57 mg , 175 μmol) and Pd (1,1'bis (diphenylphosphino) ferrocene) O ₂ (10 mg, 14 μmol). The mixture was purged with nitrogen for 3 min, then stirred at 100 ° C for 30 min under microwave irradiation. Water (30 ml) was added and the mixture was extracted with ethyl acetate (30 ml x 3). The combined organic layers were washed with brine (20 ml), dried over Na ₂ SO ₄ and concentrated. The crude mixture was purified twice by preparative TLC with dichloromethane: methanol = 20: 1, then the crude product was further purified by preparative HPLC to give 5- (2-ethoxypyridin-3-yl) -1isopropyl-3-methyl-N- ( (5-methyl-1,3,4-oxadiazol-2-yl) methyl) -1H-pyrαzolo [4,3-b] pyridin-7-amine (6.1 mg).

¹ H NMR (chloroform-d, 400 MHz) δ 8.28-8.26 (m, 1H), 8.19-8.18 (m, 1H), 7.23 (s, 1H), 7.05 -7.02 (m, 1H), 5.27 (brs, 1H), 4.96-4.90 (m, 1H), 4.71 (d, J = 1.2Hz, 2H), 4, 53-4.48 (m, 2H), 2.65 (s, 3H), 2.57 (s, 3H), 1.66 (d, J = 6.4 Hz, 6H), 1.43 (t , J = 6.8 Hz, 3H).

LC-MS (mass / charge) 408.2 (MH +); tR = 2.08 min (method B).

The following examples were prepared in a similar manner.

Example 2. 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(5-methylthiazol-2-yl) methyl] pyrαzolo [4,3-b] pyridin-7-amine

derived from (5-methylthiazol-2-yl) methanamine dihydrochloride and 5,7-dichloro-1-isopropyl-3- 94 037544 methyl-1H-pyrazolo [4,3-b] pyridine;

1H NMR (DMSO-d6, 500 MHz) δ 8.21 - 8.14 (m, 2H), 7.42 (d, J = 1.4 Hz, 1H), 7.21 (t, J = 5, 6 Hz, 1H), 7.11 7.05 (m, 2H), 5.23 (hept, J = 6.4 Hz, 1H), 4.75 (d J = 5.5 Hz, 2H), 4 , 31 (q, J = 7.0 Hz, 2H), 2.48 (s, 3H), 2.35 (s, 3H), 1.50 (d, J = 6.4 Hz, 6H), 1 , 24 (t, J = 7.1 Hz, 3H).

LC-MS (mass / charge) 423 (MH +); tR = 0.61 min (method D).

Example 3. 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(5-methylisoxazol-3-yl) methyl] pyrazolo [4,3-b] pyridine-7-amine

prepared from (5-methylisoxazol-3-yl) methanamine and 5,7-dichloro-1-isopropyl-3-methyl-1Hpyrazolo [4,3-b] pyridine;

¹ H NMR (chloroform-d, 500 MHz) δ 8.28 (d, J = 7.3 Hz, 1H), 8.29 - 8.17 (m, 1H), 7.29 (s, 1H), 7.04 (m, 1H), 6.07 (s, 1H), 5.19 (brs, 1H), 4.90 (hept, J = 6.4Hz, 1H), 4.59 (d, J = 5.2 Hz, 2H), 4.50 (q, J = 7.0 Hz, 2H), 2.67 (s, 3H), 2.47 (s, 3H), 1.66 (d, J = 6.1, 6H), 1.43 (q, J = 7.1 Hz, 3H).

LC-MS (mass / charge) 407.3 (MH +); tR = 0.54 min (method E).

Example 4. 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(2-methyloxazol-5-yl) methyl] pyrazolo [4,3-b] pyridine-7-amine

derived from (2-methyloxazol-5-yl) methanamine and 5,7-dichloro-1-isopropyl-3-methyl-1Hpyrazolo [4,3-b] pyridine;

1H NMR (DMSO-d6, 600 MHz) δ 8.21 - 8.15 (m, 2H), 7.14 (s, 1H), 7.09 (dd, J = 7.3, 4.8 Hz, 1H), 6.90 (s, 1H), 6.82 (t, J = 5.7 Hz, 1H), 5.16 (hept, J = 6.4 Hz, 1H), 4.55 (d, J = 5.5 Hz, 2H), 4.39 (q, J = 7.0 Hz, 2H), 2.47 (s, 3H), 2.37 (s, 3H), 1.45 (d, J = 6.4 Hz, 6H), 1.26 (t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 407.1 (MH +); tR = 0.53 min (method D).

Example 5. 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(2-methyltriazol-4-yl) methyl] pyrazolo [4,3-b] pyridine-7-amine

prepared from (2-methyl-2H-1,2,3-triazol-4-yl) methanamine and 5,7-dichloro-1-isopropyl-3-methyl-1Hpyrazolo [4,3-b] pyridine;

1H NMR (DMSO-d6, 600 MHz) δ 8.21-8.15 (m, 2H), 7.64 (s, 1H), 7.10-7.08 (m, 2H), 6.88 ( t, J = 5.6 Hz, 1H), 5.19 (hept, J = 6.3 Hz, 1H), 4.59 (d, J = 5.1 Hz, 2H), 4.34 (q, J = 7.0 Hz, 2H), 4.11 (s, 3H), 2.48 (s, 3H), 1.48 (d, J = 5.7 Hz, 6H), 1.28 - 1, 20 (t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 407.1 (MH +); tR = 0.55 min (method D).

Example 6. 5 - (2-Ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-N - [(1 -methyltriazol-4-yl) methyl] pyrazolo [4,3-b] pyridine-7-amine

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derived from (1-methyl-1H-1,2,3-triazol-4-yl) methanamine and 5,7-dichloro-1-isopropyl-3-methyl-1Hpyrazolo [4,3-b] pyridine;

1H NMR (DMSO-d6, 600 MHz) δ 8.21 - 8.14 (m, 2H), 7.90 (s, 1H), 7.13 (s, 1H), 7.08 (dd, J = 7.3, 4.9 Hz, 1H), 6.88 (t, J = 5.7 Hz, 1H), 5.18 (hept, J = 6.4 Hz, 1H), 4.59 (d, J = 5.6 Hz, 2H), 4.34 (q, J = 7.0 Hz, 2H), 3.98 (s, 3H), 2.47 (s, 3H), 1.47 (d, J = 6.3 Hz, 6H), 1.25 (t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 407.3 (MH +); tR = 0.45 min (method E).

Example 7. 5- (2-Ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-N- (1 H-pyrazol-4-ylmethyl) pyrazolo [4,3 b] pyridin-7-amine

derived from (1H-pyrazol-4-yl) methanamine hydrochloride and 5,7-dichloro-1-isopropyl-3-methyl-1Hpyrazolo [4,3-b] pyridine;

1H NMR (chloroform-d, 600 MHz) δ 8.27 (dd, J = 7.3, 2.0 Hz, 1H), 8.18 (dd, J = 4.8, 1.9 Hz, 1H) , 7.69 (s, 2H), 7.25 (s, 1H), 7.03 (dd, J = 7.3, 4.9Hz, 1H), 4.76 (hept, J = 6.4 Hz, 1H), 4.55 (brds, 1H), 4.46 (m, 4H), 2.63 (s, 3H), 1.59 (d, J = 6.5 Hz, 6H), 1, 39 (t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 392.1 (MH +); tR = 0.50 min (method D).

Example 8 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(2-methyltetrazol-5-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine

derived from (2-methyl-2H-tetrazol-5-yl) methanamine and 5,7-dibromo-1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine;

1H NMR (chloroform-d, 400 MHz) δ 8.27 (dd, J = 7.2, 2.0 Hz, 1H), 8.18 (dd, J = 5.2, 2.0 Hz, 1H) , 7.26 (s, 1H), 7.04-7.01 (m, 1H), 5.33-5.31 (m, 1H), 4.96-4.93 (m, 1H), 4 , 80 (d, J = 5.2 Hz, 2H), 4.50 (q, J = 6.8 Hz, 2H), 4.39 (s, 3H), 2.65 (s, 3H), 1 , 67 (d, J = 6.4 Hz, 6H), 1.44 (t, J = 6.8 Hz, 3H).

LC-MS (mass / charge) 408.1 (MH +); tR = 1.96 min (method C).

Example 9. 5- (2-Ethoxypyridin-3-yl) -1-isopropyl-3-methyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) 1H-pyrazolo [4,3-b ] pyridin-7-amine

derived from (1-methyl-1H-pyrazol-4-yl) methanamine and 5,7-dibromo-1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine;

¹ H NMR (DMSO-d ₆ , 400 MHz): δ 8.18-8.16 (m, 2H), 7.60 (s, 1H), 7.41 (s, 1H), 7.10-7 , 06 (m, 2H), 6.686.65 (m, 1H), 5.19-5.12 (m, 1H), 4.39-4.34 (m, 4H), 3.77 (s, 3H ), 2.46 (s, 3H), 1.15 (d, J = 6.4 Hz, 6H), 1.25 (t,

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J = 7.2 Hz, 3H).

LC-MS (mass / charge) 406.1 (MH +); tR = 2.50 min (method B).

Example 10 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(3-methylisoxazol-5-yl) methyl] pyrazolo [4,3-b] pyridine-7-amine

derived from (3-methylisoxazol-5-yl) methanamine and 5,7-dichloro-1-isopropyl-3-methyl-1Hpyrazolo [4,3-b] pyridine;

Ή NMR (chloroform-d, 400 MHz) δ 8.28-8.26 (m, 1H), 8.15-8.18 (m, 1H), 7.20 (s, 1H), 7.04- 7.00 (m, 1H), 6.10 (s, 1H), 4.87 (brs, 2H), 4.66-4.65 (m, 2H), 4.45 (q, J = 7, 2 Hz, 2H), 2.64 (s, 3H), 2.29 (s, 3H), 1.63 (d, J = 6.8 Hz, 6H), 1.36 (t, J = 7, 2 Hz, 3H).

LC-MS (mass / charge) 407.1 (MH +); tR = 2.05 min (method C).

Example 11 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(2-methylthiazol-4-yl) methyl] pyrazolo [4,3-b] pyridine-7-amine

derived from (2-methylthiazol-4-yl) methanamine and 5,7-dibromo-1-isopropyl-3-methyl-1Hpyrazolo [4,3-b] pyridine;

¹ H NMR (chloroform-d, 400 MHz) δ 8.26 (dd, JJJ = 7.6, 2.0 Hz, 1H), 8.17 (dd, J = 4.8, 2.0 Hz, 1H ), 7.18 (s, 1H), 7.05-7.01 (m, 2H), 5.40-5.27 (m, 1H), 4.96-4.90 (m, 1H), 4.59 (d, J = 5.2 Hz, 2H), 4.46 (q, J = 7.2 Hz, 2H), 2.75 (s, 3H), 2.65 (s, 3H), 1.65 (d, J = 6.4 Hz, 6H), 1.38 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 423 (MH +); tR = 1.90 min (method A).

Example 12. 1-Cyclopropyl-5- (2-ethoxy-3-pyridyl) -3-methyl-N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridine-7-amine

derived from (1-methyl-1H-pyrazol-4-yl) methanamine and 5,7-dibromo-1-cyclopropyl-3-methyl-1Hpyrazolo [4,3-b] pyridine;

1H NMR (chloroform-d, 400 MHz): δ 8.26-8.23 (m, 1H), 8.19-8.17 (m, 1H), 7.57 (s, 1H), 7.44 (s, 1H), 7.16 (s, 1H), 7.04-7.01 (m, 1H), 5.64 (brs, 1H), 4.50-4.45 (m, 2H), 4.39 (d, J = 4.4 Hz, 2H), 3.93 (s, 3H), 3.72 3.70 (m, 1h), 2.61 (s, 3H), 1.46 - 1.38 (m, 5H), 1.16 -1.11 (m, 2H).

LC-MS (mass / charge) 404.1 (MH +); tR = 1.88 min (method C).

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Example 13.

B] pyridine-7-amine

- (2-Ethoxy-3-pyridyl) -N - [(1-methylpyrazol-4-yl) methyl] -1 -propylpyrazolo [4,3-

derived from (1-methyl-1H-pyrazol-4-yl) methanamine dihydrochloride and 5,7-dibromo-1-propyl-Spirazolo [4,3-b] pyridine;

1H NMR (chloroform-d, 400 MHz) δ 8.16 - 8.11 (m, 2H), 8.04 (s, 1H), 7.49 (s, 1H), 7.37 (s, 1H) , 7,17 (s,

1H), 6.97 - 6.94 (m, 1H), 4.42 - 4.32 (m, 7H), 3.86 (s, 3H), 1.85 (q, J = 7.2 Hz , 2H), 1.33 (t, J = 7.2 Hz, 3H), 0.86 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 392.2 (MH +); tR = 1.87 min (method C).

Example 14. 5- (2-Ethoxypyridin-3-yl) -N - ((1 -methyl-1 H-pyrazol-4-yl) methyl) -1 - (oxetan-3-yl) -1Hpyrazolo [4.3 -B] pyridin-7-amine

derived from (1-methyl-1H-nyrazol-4-yl) methanamine and 7-bromo-5-chloro-1- (oxetan-3-yl) -1H pyrazolo [4,3-b] pyridine;

1H NMR (methanol-d4, 600 MHz) δ 8.18 - 8.14 (m, 2H), 7.95 (dd, J = 7.3, 2.0 Hz, 1H), 7.62 (s, 1H), 7.51 (s, 1H), 7.08-7.04 (m, 2H), 6.24-6.17 (m, 1H), 5.24-5.18 (m, 2H) , 5.15 -5.08 (m, 2H), 4.45 (s, 2H), 4.38 (q, J = 7.0 Hz, 2H), 3.85 (s, 3H), 1, 26 (t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 406.2 (MH +); tR = 0.41 min (method D).

Example 15. 5- (2-Ethoxypyridin-3-yl) -1-methyl-N- (1- (1-methyl-1H-pyrazol-4-yl) ethyl) -1Hpyrazolo [4,3-b] pyridine- 7-amine (racemic)

prepared from 1- (1-methyl-1H-pyrazol-4-yl) ethan-1-amine and 7-bromo-5-chloro-1-methyl-1Hpyrazolo [4,3-b] pyridine;

1H NMR (chloroform-d, 500 MHz) δ 8.24 - 8.17 (m, 2H), 8.09 (s, 1H), 7.54 (s, 1H), 7.39 (s, 1H) , 7.17 (s, 1H), 7.03 (dd, J = 7.3, 5.1 Hz, 1H), 4.84 (m, 1H), 4.73 (d, J = 5.9 Hz, 1H), 4.54 - 4.37 (m, 2H), 4.35 (s, 3H), 3.91 (s, 3H), 1.72 (d, J = 7.0 Hz 3H) , 1.36 (t, J = 6.5 Hz, 3H).

LC-MS (mass / charge) 378.2 (MH +); tR = 0.44 min (method D).

Example 16. 5- (2-Ethoxypyridin-3-yl) -1 -methyl-N - ((1-methyl-1 H-pyrazol-4-yl) methyl) -1 H-pyrazolo [4,3-b] pyridine-7-amine

- 98 037544 prepared from (1-methyl-1H-pyrazol-4-yl) methanamine and 5,7-dibromo-1-methyl-1H-pyrazolo [4,3-b] pyridine;

1H NMR (methanol-d ₄ , 400 MHz) δ 8.15 - 8.14 (m, 1H), 7.93-7.92 (m, 2H), 7.60 (s, 1H), 7.50 (s, 1H), 7.038 (dd, J = 4.8Hz, J = 6.8Hz, 1H), 6.94 (s, 1H), 4.46 (s, 2H), 4.40-4 , 34 (m, 6H), 3.83 (s, 3H), 1.25 (t, J = 6.8 Hz, 3H).

LC-MS (mass / charge) 364.1 (MH +); tR = 1.71 min (method C).

Example 17 5 - (2-Ethoxy-3-pyridyl) -1 -isopropyl-N - [(1-methylimidazol-2-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine

derived from (1-methyl-1H-imidazol-2-yl) methanamine and 5,7-dibromo-1-isonropyl-1H-pyrazolo [4,3-b] pyridine;

Ή NMR (DMSO-d ₆ , 600 MHz) δ 8.19 (dd, J = 4.9, 2.0 Hz, 1H), 8.09-8.12 (m, 2H), 7.35 (s , 1H), 7.13 - 7.05 (m, 2H), 6.83 - 6.76 (m, 2H), 5.25 (hept, J = 6.5 Hz, 1H), 4.56 ( d, J = 4.9 Hz, 2H), 4.42 (q, J = 7.0 Hz, 2H), 3.71 (s, 3H), 1.51 (d, J = 6.4 Hz, 6H), 1.38 (t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 392.1 (MH +); tR = 0.35 min (method D).

Example 18 5 - (2-Ethoxypyridin-3-yl) -1 -isopropyl-N - ((1-methyl-1 H-pyrazol-5-yl) methyl) -1Hpyrazolo [4,3-b] pyridine-7 -amine at NH \ '

Γχ ^Ν prepared from (1-methyl-1H-pyrazol-5-yl) methanamine dihydrochloride and 5,7-dibromo-1-isopropyl 1H-pyrazolo [4,3-b] pyridine;

Ή NMR (DMSO-d6, 600 MHz) δ 8.20 - 8.12 (m, 3H), 7.33 (d, J = 1.8 Hz, 1H), 7.14 (s, 1H), 7 , 08 (dd, J = 7.4, 4.8 Hz, 1H), 6.89 (t, J = 5.4 Hz, 1H), 6.19 (d, J = 1.8 Hz, 1H) , 5.29 (hept, J = 6.5 Hz, 1H), 4.59 (d, J = 5.3 Hz, 2H), 4.36 (q, J = 7.0 Hz, 2H), 3 , 88 (s, 3H), 1.50 (d, J = 6.3 Hz, 6H), 1.24 (t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 392.1 (MH +); tR = 0.49 min (method D).

Example 19 5 - (2-Ethoxypyridin-3-yl) -1 -isopropyl-N - ((1-methyl-1 H-pyrazol-3-yl) methyl) -1Hπyrazolo [4,3-L] πyridine-7 -amine

prepared from (1-methyl-1H-nyrazol-3-yl) methanamine and 5,7-dibromo-1-isopropyl-1H-pyrazolo [4.3b] pyridine;

1H NMR (DMSO-d6, 600 MHz) δ 8.19 - 8.13 (m, 2H), 8.09 (s, 1H), 7.59 (d, J = 2.2 Hz, 1H), 7 , 14 (s, 1H), 7.07 (dd, J = 7.4, 4.8 Hz, 1H), 6.85 (t, J = 5.7 Hz, 1H), 6.17 (d, J = 2.1 Hz, 1H), 5.27 (hept, J = 6.4 Hz, 1H), 4.46 (d, J = 5.6 Hz, 2H), 4.36 (q, J = 7.0 Hz, 2H), 3.78 (s, 3H), 1.50 (d, J = 6.3 Hz, 6H), 1.29 (t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 392.1 (MH +); tR = 0.54 min (method D).

Example 20 5- (2-Ethoxy-3-pyridyl) -1 -isopropyl-N- (thiazol-2-ylmethyl) pyrazolo [4,3-b] pyridine-7amine

- 99 037544

derived from thiazol-2-ylmethanamine hydrochloride and 5,7-dibromo-1-isopropyl-1H-pyrazolo [4,3b] pyridine;

1H NMR (DMSO-d ₆ , 600 MHz). δ 8.18 - 8.13 (m, 3H), 7.78 (d, J = 3.3 Hz, 1H), 7.62 (d, J = 3.3 Hz, 1H), 7.32 ( t, J = 5.7 Hz, 1H), 7.12 (s, 1H), 7.06 (dd, J = 6.9, 5.4 Hz, 1H), 5.32 (hept, J = 6 , 5 Hz, 1H), 4.86 (d, J = 5.6 Hz, 2H), 4.29 (q, J = 7.0 Hz, 2H), 1.54 (d, J = 6.4 Hz, 6H), 1.21 (t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 395 (MH +); tR = 0.54 min (method D).

Example 21 5 - (2-Ethoxy-3-pyridyl) -1-isopropyl-N - [(1-methylimidazol-4-yl) methyl] pyrazolo [4,3b] pyridin-7-amine

prepared from (1-methyl-1H-imidazol-4-yl) methanamine and 5,7-dibromo-1-isopropyl-1H-pyrazolo [4,3-b] pyridine;

1H NMR (DMSO-d6, 600 MHz) δ 8.19 - 8.13 (m, 2H), 8.09 (s, 1H), 7.52 (s, 1H), 7.15 (s, 1H) , 7.07 (dd, J = 7.3, 4.9 Hz, 1H), 6.96 (s, 1H), 6.76 (t, J = 5.5 Hz, 1H), 5.25 ( hept, J = 6.5 Hz, 1H), 4.40 (d, J = 5.4 Hz, 2H), 4.35 (q, J = 7.0 Hz, 2H), 3.57 (s, 3H), 1.50 (d, J = 6.3 Hz, 6H), 1.27 (t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 392.1 (MH +); tR = 0.39 min (method D).

Example 22 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-N- (4-pyridylmethyl) pyrazolo [4,3-b] pyridine-7amine

derived from pyridin-4-ylmethanamine and 5,7-dibromo-1-isopropyl-1H-pyrazolo [4,3-b] pyridine;

1H NMR (methanol-d4, 600 MHz) δ 8.52 - 8.48 (m, 2H), 8.11 (dd, J = 5.0, 1.9 Hz, 1H), 8.06 (s, 1H), 7.90 (dd, J = 7.4, 2.0 Hz, 1H), 7.51 - 7.47 (m, 2H), 7.01 (dd, J = 7.4, 4, 9 Hz, 1H), 6.74 (s, 1H), 5.28 (hept, J = 6.5 Hz, 1H), 4.72 (s, 2H), 4.19 (q, J = 7, 1 Hz, 2H), 1.64 (d, J = 6.4 Hz, 6H), 1.07 (t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 389.1 (MH +); tR = 0.38 min (method D).

Example 23 5- (2-Ethoxy-3-nyridyl) -1-isopropyl-N- (m-tolylmethyl) pyrazolo [4,3-b] pyridin-7-amine

derived from m-tolylmethanamine hydrochloride and 5,7-dibromo-1-isopropyl-1H-pyrazolo [4,3-b] pyridine;

1H NMR (chloroform-d, 400 MHz) δ 8.22-8.17 (m, 3H), 7.33-7.19 (m, 5H), 7.03-7.00 (m, 1H), 4.89 4.86 (m, 2H), 4.53 (d, J = 5.2 Hz, 2H), 4.42 (q, J = 7.2 Hz, 2H), 2.39 (s, 3H), 1.65 (d, J = 6.4 Hz, 6H), 1.33 (t, J = 7.2 Hz, 3H).

- 100 037544

LC-MS (mass / charge) 402.1 (MH +); t _R = 2.57 min (method F).

Example 24 5- (2-Ethoxy-3-nyridyl) -1-isopropyl-N- (p-tolylmethyl) pyrazolo [4,3-b] pyridin-7-amine

derived from p-tolylmethanamine and 5,7-dibromo-1-isopropyl-1H-pyrazolo [4,3-b] pyridine;

1H NMR (chloroform-d, 400 MHz) δ 8.23-8.17 (m, 3H), 7.34-7.32 (m, 2H), 7.24-7.22 (m, 3H), 7.03-7.00 (m, 1H), 4.89-4.74 (m, 2H), 4.52 (d, J = 4.8 Hz, 2H), 4.42 (q, J = 6.8 Hz, 2H), 2.39 (s, 3H), 1.65 (d, J = 6.8 Hz, 6H), 1.35 (t, J = 6.8 Hz, 3H).

LC-MS (mass / charge) 402.1 (MH ⁺ ); t _R = 2.17 min (method A).

Example 25 5 - (2-Ethoxy-3-nyridyl) -1-isopropyl-N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine

derived from (1-methyl-1H-nyrazol-4-yl) methanamine dihydrochloride and 5,7-dibromo-1-isopropyl 1H-pyrazolo [4,3-b] pyridine;

1H NMR (chloroform-d, 400 MHz) δ 8.22-8.16 (m, 3H), 7.57 (s, 1H), 7.44 (s, 1H), 7.24 (s, 1H) , 7.03-7.00 (m, 1H), 4.82-4.77 (m, 1H), 4.60 (brs, 1H), 4.46 (q, J = 7.2 Hz, 2H ), 4.39 (d, J = 4.8 Hz, 2H), 3.93 (s, 3H), 1.62 (d, J = 6.4 Hz, 6H), 1.39 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 392.2 (MH ⁺ ); t _R = 1.86 min (method C).

Example 26 5- (2-Ethoxy-3-pyridyl) -1-ethyl-N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4.3b] pyridin-7-amine

derived from (1-methyl-1H-nyrazol-4-yl) methanamine and 5,7-dibromo-1-ethyl-1H-pyrazolo [4,3-b] pyridine;

1H NMR (chloroform-d, 400 MHz) δ 8.22-8.11 (m, 3H), 7.56 (s, 1H), 7.43 (s, 1H), 7.23 (s, 1H) , 7.03 7.00 (m, 1H), 4.56 - 4.39 (m, 7H), 3.92 (s, 3H), 1.51 (t, J = 7.2 Hz, 3H) , 1.38 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 378.2 (MH ⁺ ); t _R = 1.79 min (method G).

Example 27 5- (2-Ethoxy-3-pyridyl) -3-methyl-N - [(1-methylpyrazol-4-yl) methyl] -1 - (oxetan-3 yl) pyrazolo [4,3-b] pyridine-7-amine

derived from (1-methyl-1H-pyrazol-4-yl) methanamine and 5,7-dibromo-3-methyl-1- (oxetan-3-yl) -1Hpyrazolo [4,3-b] pyridine;

- 101 037544

Ή NMR (chloroform-d, 400 MHz) δ 8.30-8.28 (m, 1H), 8.20-8.18 (m, 1H), 7.54 (s, 1H), 7.43 ( s, 1H), 7.32 (s, 1H), 7.05-7.02 (m, 1H), 5.85-5.75 (m, 1H), 5.55 (brs, 1H), 5 , 18-5.11 (m, 4H), 4.51-4.45 (m, 2H), 4.41 (d,

J = 4.8 Hz, 2H), 3.92 (s, 3H), 2.64 (s, 3H), 1.40 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 420.1 (MH ⁺ ); tR = 1.99 min (method B).

Example 28 5- (2-Ethoxy-3-pyridyl) -1,3-dimethyl-N - [(1-methylpyrazol-4-yl) methyl] nyrazolo [4,3-b] pyridin-7-amine

derived from (1-methyl-1H-pyrazol-4-yl) methanamine and 5,7-dichloro-1,3-dimethyl-1H-pyrazolo [4,3b] pyridine;

Ή NMR (chloroform-d, 400 MHz) δ 8.28-8.26 (m, 1H), 8.19-8.18 (m, 1H), 7.56 (s, 1H), 7.44 ( s, 1H), 7.21 (s, 1H), 7.04-7.01 (m, 1H), 4.63 (brs, 1H), 4.47 (q, J = 6.8 Hz, 2H ), 4.38 (d, J = 4.8 Hz, 2H), 4.23 (s, 3H), 3.92 (s, 3H), 2.62 (s, 3H), 1.39 (t , J = 7.2 Hz, 3H).

LC-MS (mass / charge) 378.2 (MH ⁺ ); tR = 1.93 min (method B).

Example 29. 5- (2-Ethoxypyridin-3-yl) -1-isopropyl-3-methyl-N - ((4-methylthiazol-2-yl) methyl) -1Hpyrazolo [4,3-b] pyridine-7- amine

In a solution of 5- (2-ethoxypuridin-3-yl) -1-isopropyl-3-methyl-III-pyrazolo [4,3-b] pyridin-7-amine (50 mg, 0.16 mmol) in THF (3 ml) Ti (i-PrO) ₄ (91 mg, 0.32 mmol, 95 μl) and 4-methylthiazole-2carbaldehyde (41 mg, 0.32 mmol, 35 μl) were added. The mixture was stirred at 50 ° C for 18 h. The reaction mixture was cooled to 0 ° C, then NaBH ₄ (30 mg, 0.80 mmol) was added slowly to the mixture and the reaction mixture was stirred at 0 ° C for 10 min. Water (2 ml) was added to quench the reaction, the resulting mixture was filtered and the residue was washed with ethyl acetate (20 ml x 2). The combined filtrates were washed with brine (10 ml), dried over Na ₂ SO ₄ and concentrated. The residue was purified by column chromatography (SiO ₂ , petroleum ether: ethyl acetate = 2: 1 to 1: 1), followed by purification by preparative HPLC to give 5- (2-ethoxypyridin-3-yl) -1-isopropyl-3 -methyl-N ((4-methylthiazol-2-yl) methyl) -1 H-pyrazolo [4,3-b] pyridin-7-amine (14 mg).

Ή NMR (chloroform-d, 400 MHz) δ 8.26-8.24 (m, 1H), 8.18-8.17 (m, 1H), 7.19 (s, 1H), 7.03- 7.00 (m, 1H), 6.87 (s, 1H), 5.01-4.95 (m, 1H), 4.82 (d, J = 4.8 Hz, 2H), 4.47 -4.42 (q, J = 7.2 Hz, 2H), 2.66 (s, 3H), 2.48 (s, 3H), 1.68 (d, J = 6.4 Hz, 6H) , 1.37 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 423.0 (MH ⁺ ); tR = 1.92 min (method C).

The following examples were prepared in a similar manner.

Example 30 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(3-methyl-1,2,4-oxadiazol-5yl) methyl] pyrazolo [4,3-b ] pyridin-7-amine

obtained from 3-methyl-1,2,4-oxadiazole-5-carbaldehyde and 5- (2-ethoxypyridin-3-yl) -1-isopropyl 3-methyl-1H-pyrazolo [4,3-b] pyridine-7- amine;

1H NMR (chloroform-d, 400 MHz) δ 8.27 (dd, J = 7.2, 2.0 Hz, 1H), 8.19-8.18 (m, 1H), 7.17 (s, 1H), 7.057.02 (m, 1H), 4.95 (brs, 1H), 4.76 (d J = 4.8 Hz, 2H), 4.49 (q, J = 6.8 Hz, 2H ), 2.65 (s, 3H), 2.44 (s, 3H), 1.67 (d,

- 102 037544

J = 6.4 Hz, 6H), 1.42 (t, J = 6.8 Hz, 3H).

LC-MS (mass / charge) 408.2 (MH +); tR = 2.31 min (method B).

Example 31. 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(1-methyl-1,2,4-triazol-3-yl) methyl] pyrazolo [4.3 -B] pyridin-7-amine

obtained from 1-methyl-1H-1,2,4-triazole-3-carbaldehyde and 5- (2-ethoxypyridin-3-yl) -1-isopropyl3-methyl-1H-pyrazolo [4,3-b] pyridine- 7-amine;

Ή NMR (chloroform-d, 400 MHz) δ 8.27 (dd, J = 1.6, 7.2 Hz, 1H), 8.18 (dd, J = 1.6, 4.8 Hz, 1H) , 8.05 (s, 1H), 7.22 (s, 1H), 7.04-7.01 (m, 1H), 5.50 (brs, 1H), 5.01-4.96 (m , 1H), 4.58 (d, J = 4.8 Hz, 2H), 4.50 (q, J = 7.2 Hz, 2H), 3.95 (s, 3H), 2.66 (s , 3H), 1.66 (d, J = 6.0 Hz, 6H), 1.45 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 407.1 (MH +); tR = 1.87 min (method C).

Example 32 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(2-methylthiazol-5-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine

prepared from 2-methylthiazole-5-carbaldehyde and 5- (2-ethoxypyridin-3-yl) -1-isopropyl-3-methyl1H-pyrazolo [4,3-b] pyridin-7-amine;

Ή NMR (chloroform-d, 400 MHz) δ 8.17-8.25 (m, 1H), 8.19-8.18 (m, 1H), 7.62 (s, 1H), 7.26 ( s, 1H), 7.05-7.02 (m, 1H), 4.83-4.80 (m, 1H), 4.70 (s, 2H), 4.48 (q, J = 7, 2 Hz, 2H), 2.71 (s, 3H), 2.65 (s, 3H), 1.62 (d, J = 6.4 Hz, 6H), 1.40 (t, J = 7, 2 Hz, 3H).

LC-MS (mass / charge) 423 (MH +); tR = 1.80 min (method A).

Example 3 3.5- (2-Ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-N - [(5-methyl-1, 3,4-thiadiazol-2yl) methyl] pyrazolo [4.3 - b] pyridin-7-amine

obtained from 5-methyl-1,3,4-thiadiazole-2-carbaldehyde and 5- (2-ethoxypyridin-3-yl) -1-isopropyl3-methyl-1H-pyrazolo [4,3-b] pyridine-7- amine;

¹ H NMR (chloroform-d, 400 MHz) δ 8.32-8.29 (m, 1H), 8.22-8.20 (m, 1H), 7.30 (s, 1H), 7.07 -7.04 (m, 1H), 5.51 (brs, 1H), 4.97 (d, J = 5.2 Hz, 2H), 4.57-4.48 (m, 2H), 2, 82 (s, 3H), 2.69 (s, 3H), 1.69 (d, J = 6.4 Hz, 6H), 1.42 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 424 (MH +); tR = 2.14 min (method B).

Example 3 4. 5- (2-Ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-N - [(5-methyl-3-thienyl) methyl] pyrazolo [4,3-b] pyridine-7- amine

- 103 037544

derived from 5-methylthiophene-3-carbaldehyde and 5- (2-ethoxypyridin-3-yl) -1-isopropyl-3-methyl1 H-pyrazolo [4,3-b] pyridin-7-amine;

1H NMR (chloroform-d, 400 MHz) δ 8.28-8.26 (m, 1H), 8.18-8.17 (m, 1H), 7.22 (s, 1H), 7.04- 7.01 (m, 2H), 6.80 (s, 1H), 4.84-4.77 (m, 1H), 4.66 (brs, 1H), 4.48-4.43 (m, 4H), 2.65 (s, 3H), 2.51 (s, 3H), 1.62 (d, J = 6.8 Hz, 6H), 1.38 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 422 (MH +); tR = 2.21 min. (method H).

Example 3 5. 5- (2-Ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-N - [(4-methyl-2-thienyl) methyl] pyrazolo [4,3-b] pyridine-7- amine '. NH) -

And obtained from 4-methylthiophene-2-carbaldehyde and 5- (2-ethoxypyridin-3-yl) -1-isopropyl-3-methyl1H-pyrazolo [4,3-b] pyridin-7-amine;

Ή NMR (chloroform-d, 400 MHz) δ 8.27 (dd, J = 7.6, 1.6 Hz, 1H), 8.18 (dd, J = 4.8, 2.0 Hz, 1H) , 7.26 (s, 1H), 7.04-7.01 (m, 1H), 6.92 (s, 1H), 6.87 (s, 1H), 4.86-4.81 (m , 1H), 4.72 (brs, 1H), 4.66-4.65 (m, 2H), 4.47 (q, J = 7.2 Hz, 2H), 2.65 (s, 3H) , 2.27 (s, 3H), 1.62 (d, J = 6.4 Hz, 6H), 1.39 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 422.1 (MH +); tR = 1.78 min (method I).

Example 36 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(5-methyl-2-thienyl) methyl] pyrazolo [4,3-b] pyridin-7-amine

derived from 5-methylthiophene-2-carbaldehyde and 5- (2-ethoxypyridin-3-yl) -1-isopropyl-3-methyl1H-pyrazolo [4,3-b] pyridin-7-amine;

Ή NMR (chloroform-d, 400 MHz) δ 8.28-8.25 (m, 1H), 8.18-8.17 (m, 1H), 7.25 (s, 1H), 7.04- 7.01 (m, 1H), 6.90-6.89 (m, 1H), 6.67-6.66 (s, 1H), 4.86-4.81 (m, 1H), 4, 72 (brs, 1H), 4.63-4.62 (m, 2H), 4.48 (q, J = 6.8 Hz, 2H), 2.65 (s, 3H), 2.49 (s , 3H), 1.62 (d, J = 6.4 Hz, 6H), 1.39 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 422 (MH +); tR = 1.78 min (method I).

Example 37. 5- (2-Ethoxy-3-πyridyl) -1-isopropyl-3-methyl-N - [(2-methyloxazol-4-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine

derived from 2-methyloxazole-4-carbaldehyde and 5- (2-ethoxypyridin-3-yl) -1-isopropyl-3-methyl1H-πyrazolo [4,3-b] πyridin-7-amine;

- 104 037544

1H NMR (chloroform-d, 400 MHz) δ 8.26-8.24 (m, 1H), 8.17-8.16 (m, 1H), 7.53 (s, 1H), 7.17 ( s, 1H),

7.03-7.00 (m, 1H), 5.01 (brs, 1H), 4.88-4.83 (m, 1H), 4.49-4.44 (m, 2H), 4, 39 (d, J = 5.2 Hz, 2H), 2.64 (s, 3H),

2.48 (s, 3H), 1.62 (d, J = 6.8 Hz, 6H), 1.38 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 407.1 (MH +); tR = 2.03 min (method C).

Example 38 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl - # - [(5-methyloxazol-2-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine

derived from 5-methyloxazole-2-carbaldehyde and 5- (2-ethoxypyridin-3-yl) -1-isopropyl-3-methyl1H-pyrazolo [4,3-b] pyridin-7-amine;

1H NMR (chloroform-d, 400 MHz) δ 8.27-8.25 (m, 1H), 8.19-8.17 (m, 1H), 7.17 (s, 1H), 7.04- 7.01 (m, 1H), 6.75 (s, 1H), 5.41 (brs, 1H), 4.99-4.95 (m, 1H), 4.55 (d, J = 4, 8 Hz, 2H), 4.49 (q, J = 7.2 Hz, 2H), 2.65 (s, 3H), 2.35 (s, 3H), 1.67 (d, J = 6, 4 Hz, 6H), 1.44 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 407.1 (MH +); tR = 2.06 min (method C).

Example 39 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl - # - (1H-pyrazol-3-ylmethyl) pyrazolo [4,3b] pyridin-7-amine ίΓ ^ Ι /

Ν. J '.ΝΗ} -

ΗΝ - obtained from 1H-pyrazole-3-carbaldehyde and 5- (2-ethoxypyridin-3-yl) -1-isopropyl-3-methyl-1Hpyrazolo [4,3-b] pyridin-7-amine;

1H NMR (chloroform-d, 400 MHz) δ 8.25-8.23 (m, 1H), 8.18-8.16 (m, 1H), 7.58 (d, J = 2.4 Hz, 1H), 7.19 (s, 1H), 7.03-7.00 (m, 1H), 6.35 (d, J = 2.4Hz, 1H), 5.31 (brs, 1H), 4.93-4.87 (m, 1H), 4.57 (d, J = 4.8 Hz, 2H), 4.50 -4.45 (m, 2H), 2.65 (s, 3H) , 1.63 (d, J = 6.4 Hz, 6H), 1.41 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 392.1 (MH +); tR = 1.92 min (method C).

Example 40 5- (2-Ethoxy-3-pyridyl) - # - (1 H-imidazol-4-ylmethyl) -1 -isopropyl-3-methylpyrazolo [4,3 b] pyridin-7-amine

prepared from 1H-imidazole-4-carbaldehyde and 5- (2-ethoxypyridin-3-yl) -1-isopropyl-3-methyl-1Hpyrazolo [4,3-b] pyridin-7-amine;

1H NMR (chloroform-d, 400 MHz) δ 8.24-8.22 (m, 1H), 8.17-8.15 (m, 1H), 7.65 (m, 1H), 7.19 ( m, 1H), 7.03-7.00 (m, 2H), 5.27 (brs, 1H), 4.92-4.86 (m, 1H), 4.49-4.44 (m, 4H), 2.64 (s, 3H), 1.61 (d, J = 6.4 Hz, 6H), 1.40 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 392.1 (MH +); tR = 1.52 min (method C).

Example 41 # -benzyl-5- (2-ethoxy-3-pyridyl) -1-isopropylpyrazolo [4,3-b] pyridin-7-amine

- 105 037544

derived from benzaldehyde and 5- (2-ethoxypyridin-3-yl) -1-isopropyl-1H-pyrazolo [4,3b] pyridine-7-amine;

1H NMR (DMSO-d ₆ , 600 MHz) δ 8.16-8.07 (m, 3H), 7.43-7.38 (m, 2H), 7.35 (dd, J = 8.4, 7.0 Hz, 2H), 7.27 - 7.21 (m, 1H), 7.04 (dd, J = 7.4, 4.9 Hz, 2H), 6.96 (s, 1H), 5.34 (hept, J = 6.4 Hz, 1H), 4.58 (d, J = 5.6 Hz, 2H), 4.23 (q, J = 7.0 Hz, 2H), 1, 56 - 1.45 (d, J = 6.4 Hz, 6H), 1.13 (t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 388 (MH +); tR = 0.66 min (method D).

Example 42 5- (2-Ethoxy-3-pyridyl) -1 -isopropyl-N - [(3-methylisoxazol-5-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine

derived from 3-methylisoxazole-5-carbaldehyde and 5- (2-ethoxypyridin-3-yl) -1-isopropyl-Spirazolo [4,3-b] pyridin-7-amine;

1H NMR (DMSO-d ₆ , 600 MHz) δ 8.25 - 8.17 (m, 3H), 7.16 - 7.11 (m, 2H), 7.08 (t, J = 5.8 Hz , 1H), 6.31 (s, 1H), 5.31 (hept, J = 6.5 Hz, 1H), 4.71 (d, J = 5.7 Hz, 2H), 4.40 (q , J = 7.0 Hz, 2H), 2.23 (s, 3H), 1.56 (d, J = 6.5 Hz, 6H), 1.29 (t, J = 7.0 Hz, 3H ).

LC-MS (mass / charge) 393.1 (MH +); tR = 0.55 min (method D).

Example 43 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-N - [(5-methyl-1,2,4-oxadiazol-3-yl) methyl] pyrazolo [4,3-b] pyridine -7-amine

prepared from 5-methyl-1,2,4-oxadiazole-3-carbaldehyde and 5- (2-ethoxypyridin-3-yl) -1-isopropyl1H-pyrazolo [4,3-b] pyridin-7-amine;

1H NMR (DMSO-d ₆ , 600 MHz) δ 8.20 - 8.10 (m, 3H), 7.13 (s, 1H), 7.08 (dd, J = 7.4, 4.9 Hz , 1H), 7.00 (t, J = 5.9 Hz, 1H), 5.26 (hept, J = 6.4 Hz, 1H), 4.66 (d, J = 5.8 Hz, 2H ), 4.36 (q, J = 7.0 Hz, 2H), 2.56 (s, 3H), 1.50 (d, J = 6.4 Hz, 6H), 1.28 (t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 394 (MH +); tR = 0.54 min (method D).

Example 44. N - [(1,5-dimethylpyrazol-3-yl) methyl] -5- (2-ethoxy-3-pyridyl) -1 -isopropylpyrazolo [4,3b] pyridin-7-amine

- 106 037544 prepared from 1,5-dimethyl-1H-pyrazole-3-carbaldehyde and 5- (2-ethoxypyridin-3-yl) -1-isopropyl 1H-pyrazolo [4,3-b] pyridin-7-amine;

1H NMR (methanol-d, 600 MHz) δ 8.17 (dd, J = 5.0, 2.0 Hz, 1H), 8.04 (s, 1H), 7.94 (dd, J = 7, 3, 1.9 Hz, 1H), 7.07 (dd, J = 7.3, 4.9 Hz, 1H), 6.98 (s, 1H), 6.07 (s, 1H), 5, 22 (hept, J = 6.4 Hz, 1H), 4.53 (d, J = 1.5 Hz, 2H), 4.39 (q, J = 7.0 Hz, 2H), 3.75 ( s, 3H), 2.26 (s, 3H), 1.63 (d, J = 6.5 Hz, 6H), 1.30 (t, J = 7.1 Hz, 3H).

LC-MS (mass / charge) 406.1 (MH +); tR = 0.60 min (method D).

Example 45. 3- (1-Isopropyl-3-methyl-7 - (((1-methyl-1 H-pyrazol-4-yl) methyl) amino) -1 H-pyrazolo [4,3 b] pyridine-5 -yl) -1-methylpyridin-2 (1H) -one derived from 1-methyl-6-oxo-1,6-dihydropyridine-3-carbaldehyde and 5- (2-ethoxypyridin-3-yl) -1isopropyl-3- methyl-1H-pyrazolo [4,3-b] pyridin-7-amine;

¹ H NMR (chloroform-d, 400 MHz) 8.28-8.26 (m, 1H), 8.19-8.18 (m, 1H), 7.44-7.42 (m, 1H), 7.35 (d, J = 2.0 Hz, 1H), 7.19 (s, 1H), 7.05-7.02 (m, 1H), 6.66 (d, J = 9.6 Hz , 1H), 4.82-4.76 (m, 1H), 4.56 (brs, 1H), 4.474.42 (m, 2H), 4.29 (d, J = 5.2 Hz, 2H) , 3.56 (s, 3H), 2.65 (s, 3H), 1.62 (d, J = 6.4 Hz, 6H), 1.35 (t, J = 7.2 Hz, 3H) ...

LC-MS (mass / charge) 433.1 (MH +); tR = 1.86 min (method C).

Example 46.5- (2-Ethoxypyridin-3-yl) -1-isopropyl-3-methyl-N - ((2-methyl-1H-imidazol-4-yl) methyl) 1H-pyrazolo [4,3-b ] pyridin-7-amine obtained from 2-methyl-1H-imidazole-4-carbaldehyde and 5- (2-ethoxypyridin-3-yl) -1-isopropyl-3methyl-1H-pyrazolo [4,3-b] pyridine- 7-amine;

1H NMR (chloroform-d, 400 MHz) 8.25-8.23 (m, 1H), 8.17-8.15 (m, 1H), 7.19 (s, 1H), 7.02-6 , 99 (m, 1H), 6.89 (s, 1H), 5.19 (brs, 1H), 4.90-4.85 (m, 1H), 4.49-4.41 (m, 4H ), 2.63 (s, 3H), 2.43 (s, 3H), 1.61 (d, J = 6.8 Hz, 6H), 1.40 (t, J = 7.2 Hz, 3H ).

LC-MS (mass / charge) 406.1 (MH +); tR = 1.60 min (method C).

Example 47.5- (2-Ethoxypyridin-3-yl) -1-isopropyl-3-methyl-N - ((5-methyl-1H-pyrazol-3-yl) methyl) 1H-pyrazolo [4,3-b ] pyridin-7-amine obtained from 5-methyl-1H-pyrazole-3-carbaldehyde and 5- (2-ethoxypyridin-3-yl) -1-isopropyl-3methyl-1H-pyrazolo [4,3-b] pyridine- 7-amine;

1H NMR (chloroform-d, 400 MHz) δ 8.27-8.25 (m, 1H), 8.19-8.17 (m, 1H), 7.20 (s, 1H), 7.04- 7.01 (m, 1H), 6.08 (s, 1H), 5.29 (brs, 1H), 4.94-4.87 (m, 1H), 4.51-4.46 (m, 4H), 2.65 (s, 3H), 2.35 (s, 3H), 1.63 (d, J = 6.8 Hz, 6H), 1.42 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 406.1 (MH +); tR = 1.90 min (method B).

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Example 48 5- (2-Ethoxypyridin-3-yl) -1-ethyl-3-methyl-N - ((1-methyl-1 H-pyrazol-4-yl) methyl) -1Hpyrazolo [4,3-b ] pyridin-7-amine

obtained using the same procedure as described for example 1, from (1-methyl-1Hpyrazol-4-yl) methanamine and 5,7-dibromo-1-ethyl-3-methyl-1H-pyrazolo [4,3 - B] pyridine;

Ή NMR (chloroform-d, 400 MHz) δ 8.28-8.26 (m, 1H), 8.19-8.17 (m, 1H), 7.56 (s, 1H), 7.43 ( s, 1H), 7.23 (s, 1H), 7.04-7.01 (m, 1H), 4.53 (brs, 1H), 4.50-4.45 (m, 4H), 4 , 40 (d, J = 4.8 Hz, 2H), 3.92 (s, 3H), 2.63 (s, 3H), 1.47 (t, J = 7.2 Hz, 3H), 1 , 39 (t, J = 7.2 Hz, 3H).

LC-MS: LC-MS (mass / charge) 392.1 (MH ⁺ ); tR = 1.72 min (method F).

Example 49. 3- (1-Isopropyl-3-methyl-7 - (((1-methyl-1 H-pyrazol-4-yl) methyl) amino) -1 H-pyrazolo [4.3b] pyridine-5 - yl) -1-methylpyridin-2 (1H) -one

A mixture of 5-bromo-1 -isopropyl-3-methyl-N - ((1-methyl-1 H-pyrazol-4-yl) methyl) - 1Hpyrazolo [4,3-b] pyridin-7-amine (60 mg , 0.17 mmol), 3-bromo-1-methylpyridin-2 (1H) -one (62 mg, 0.33 mmol), [1,1'-bis (diphenylphosphino) ferrocene] palladium (P) dichloride (24 mg, 33 mmol), CS ₂ CO ₃ (108 mg, 0.33 mmol) and 4,4,4 ', 4', 5.5,5 ', 5'-octamethyl-2,2'-bi (1 , 3,2-dioxaborolane) (84 mg, 0.33 mmol) in dioxane (3 ml) and purged 3 times with N2, and then the mixture was stirred at 100 ° C for 1 h while heating with microwave radiation. Then added water (30 ml) and the mixture was extracted with ethyl acetate (30 ml x 3). The combined organic layers were washed with brine (20 ml), dried over Na ₂ SO ₄ and concentrated. The crude product was purified by preparative HPLC to give 3- (1-isopropyl-3-methyl-7 - (((1-methyl-1 H-pyrazol-4-yl) methyl) amino) -1 H-pyrazolo [4, 3b] pyridin-5-yl) -1-methylpyridin-2 (1H) -one.

¹ H NMR (chloroform-d, 400 MHz) δ 8.45-8.42 (m, 1H), 7.82-7.80 (m, 1H), 7.56-7.54 (m, 2H) , 7.44-7.43 (m, 1H), 6.43-6.41 (m, 1H), 4.84-4.82 (m, 1H), 4.48 (s, 2H), 3 , 92 (s, 3H), 3.68 (s, 3H), 2.63 (s, 3H) 1.57 (d, J = 6.8 Hz, 6H).

LC-MS (mass / charge) 392.1 (MH ⁺ ); t _R = 1.76 min (method B).

Example 50: 5- (2-Ethoxypyridin-3-yl) -1-isopropyl-3-methyl-N - ((4-methyloxαzol-2-yl) methyl) -1Hpyrazolo [4,3-L] pyridine-7- amine-2,2,2-trifluoroacetate

obtained using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1 -isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridin-7-amine and 4 -methyloxazole-2carbaldehyde.

1H NMR (DMSO-d ₆ , 600 MHz) δ 8.37 (dd, J = 4.9, 1.9 Hz, 1H), 8.03 (dd, J = 7.5, 1.9 Hz, 1H ), 7.81 (s, 1H), 7.22 (dd, J = 7.5, 4.9 Hz, 1H), 7.11 (s, 1H), 6.64 (bds, 1H), 5 , 29 (p, J = 6.3 Hz, 1H), 4.91 (d, J = 5.6 Hz, 2H), 4.37 (q, J = 7.0 Hz, 2H), 2.54 (s, 3H), 2.03 (s, 3H), 1.50 (d, J = 6.3 Hz, 6H), 1.26 (t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 407.4 (MH ⁺ ); t _R = 0.52 min (method E).

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Example 51. X - ((1,2-dimethyl-III-imidazol-4-yl) methyl) -5- (2-ethoxypyridin-3-yl) -1-isopropyl-3methyl-1 H-pyrazolo [4.3 -b] pyridin-7-amine-2,2,2-trifluoroacetate

obtained using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridin-7-amine and 1, 2-dimethylimidazole 4-carbaldehyde.

¹ H NMR (DMSO-d ₆ , 600 MHz) δ 8.35 (s, 1H), 8.05 (s, 1H), 7.61 (s, 1H), 7.23-7.17 (m, 1H), 7.09 (s, 1H), 6.66 (bds, 1H), 5.30 (m, 1H), 4.85 (m, 2H), 4.36 (q, J = 7.0 Hz, 2H), 3.77 (s, 3H), 2.58 (s, 3H), 2.53 (s, 3H), 1.50 (d, J = 6.3 Hz, 6H), 1, 19 (t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 420.4 (MH +); tR = 0.33 min (method E).

Example 52 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-X - [(5-methyl-1,2,4-oxadiazol-3yl) methyl] pyrazolo [4,3-b ] pyridin-7-amine

prepared using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1 -isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridin-7-amine and 5 -methyl-1,2,4oxadiazole-3 -carbaldehyde.

¹ H NMR (chloroform-d, 400 MHz) δ 8.27-8.25 (m, 1H), 8.19-8.18 (m, 1H), 7.23 (s, 1H), 7.04 -7.01 (m, 1H), 5.23 (brs, 1H), 4.94-4.91 (m, 1H), 4.63 (d, J = 5.2 Hz, 2H), 4, 52-4.47 (m, 2H), 2.65 (s, 3H), 2.64 (s, 3H), 1.66 (d, J = 6.4 Hz, 6H), 1.44 (t , J = 6.8 Hz, 3H).

LC-MS (mass / charge) 408.4 (MH ⁺ ); tR = 0.49 min (method E).

Example 53 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N- (1,2,4-oxadiazol-3-ylmethyl) pyrazolo [4,3-b] pyridine-7- amine

prepared using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1 -isopropyl-3-methyl-1 H-pyrazolo [4,3-b] pyridin-7-amine and 1 , 2,4-oxadiazole-3 carbaldehyde.

¹ H NMR (chloroform-d, 400 MHz) δ 8.78 (s, 1H), 8.27-8.25 (m, 1H), 8.19-8.17 (m, 1H), 7.25 (s, 1H), 7.04-7.01 (m, 1H), 5.25 (brs, 1H), 4.96-4.90 (m, 1H), 4.74 (d, J = 4 , 4 Hz, 2H), 4.52-4.47 (m, 2H), 2.65 (s, 3H), 1.66 (d, J = 6.4 Hz, 6H), 1.43 (t , J = 7.2 Hz, 3H).

LC-MS (mass / charge) 394.4 (MH ⁺ ); tR = 0.47 min (method E).

Example 54. X - [(1,5-dimethylpyrazol-3-yl) methyl] -5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methylpyrazolo [4,3-b] pyridine-7- amine

- 109 037544

prepared using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] nyridin-7-amine and 1, 5-dimethylpyrazole-3carbaldehyde.

1H NMR (chloroform-d, 400 MHz) δ 8.26 (dd, J = 2.0, 7.6 Hz, 1H), 8.18 (dd, J = 2.0, 8.4 Hz, 1H) , 7.18 (s, 1H), 7.03 (dd, J = 5.2, 7.6 Hz, 1H), 6.03 (s, 1H), 5.29 (brs, 1H), 4, 95-4.88 (m, 1H), 4.51-4.44 (m, 4H), 3.79 (s, 3H), 2.65 (s, 3H), 2.29 (s, 3H) , 1.64 (d, J = 6.8 Hz, 6H), 1.42 (t, J = 7.6 Hz, 3H).

LC-MS (mass / charge) 420.4 (MH +); tR = 0.53 min (method E).

Example 55. 5 - (2-Ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-N - [(5-methyl-1H-1,2,4-triazol-3 yl) methyl] pyrazolo [4, 3-b] pyridin-7-amine

obtained using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1 -isopropyl-3-methyl-1H-pyrazolo [4,3-b] nyridin-7-amine and 5- methyl 1H-1,2,4triazole-3-carbaldehyde.

1H NMR (chloroform-d, 400 MHz) δ 8.23 (dd, J = 2.0, 7.6 Hz, 1H), 8.17 (dd, J = 2.0, 5.2 Hz, 1H) , 7.19 (s, 1H), 7.01 (dd, J = 5.2, 7.6 Hz, 1H), 5.70 (brs, 1H), 5.00 (brs, 1H), 4, 61 (br s, 2H), 4.48 (q, J = 7.2 Hz, 2H), 2.64 (s, 3H), 2.48 (s, 3H), 1.65 (d, J = 6.4 Hz, 6H), 1.43 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 407.1 (MH +); tR = 1.86 min (method C).

Example 56 5 - (2-Ethoxy-3-pyridyl) -1 -isopropyl-N - [(1-methyl-1,2,4-triazol-3-yl) methyl] pyrazolo [4,3-b] pyridine -7-amine

prepared using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1 -isopropyl-1H-pyrazolo [4,3-b] pyridin-7-amine and 1-methyl-1 , 2,4-triazole-3carbaldehyde.

¹ H NMR (chloroform-d, 400 MHz) δ 8.24-8.17 (m, 3H), 8.06 (s, 1H), 7.23 (s, 1H), 7.04-7.01 (m, 1H), 5.61 (brs, 1H), 5.08-5.01 (m, 1H), 4.60 (d, J = 4.4 Hz, 2H), 4.50 (q, J = 7.2 Hz, 2H), 3.95 (s, 3H), 1.70 (d, J = 6.4 Hz, 6H), 1.46 (t, J = 7.2 Hz, 3H) ...

LC-MS (mass / charge) 393.4 (MH +); tR = 0.41 min (method E).

Example 57 5 - (2-Ethoxy-3-pyridyl) -1 -isopropyl-N- (1 H-nyrazol-3-ylmethyl) pyrazolo [4,3b] pyridin-7-amine

- 110 037544

prepared using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1-isopropyl-1H-pyrazolo [4,3-b] pyridin-7-amine and 1H-pyrazole-3- carbaldehyde.

1H NMR (chloroform-d, 400 MHz) δ 8.23 - 8.17 (m, 3H), 7.61 (d, J = 2.4 Hz, 1H), 7.22 (s, 1H), 7 , 04-7.01 (m, 1H), 6.38 (d, J = 2.4 Hz, 1H), 5.46 (brs, 1H), 5.02-4.95 (m, 1H), 4.59 (d, J = 4.4 Hz, 2H), 4.49 (q, J = 7.2 Hz, 2H), 1.67 (d, J = 6.8 Hz, 6H), 1, 43 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 378.3 (MH ⁺ ); tR = 0.43 min (method E).

Example 5 8. 5- (2-Ethoxypyridin-3-yl) -1 -isopropyl-3-methyl-N - ((1-methyl-1 H-imidazol-4-yl) methyl) 1H-pyrazolo [4.3 -b] pyridin-7-amine-2,2,2-trifluoroacetate

obtained using the same procedure as described for example 1, from 5,7-dichloro-1 isopropyl-3-methyl-1 H-pyrazolo [4,3-b] pyridine and (1-methyl-1 H-imidazole- 4-yl) methanamine.

1H NMR (DMSO-d ₆ , 600 MHz) δ 8.99 (s, 1H), 8.55 (bds, 1H), 8.39 (dd, J = 5.0, 1.9 Hz, 1H), 8.02 (dd, J = 7.4, 1.9 Hz, 1H), 7.67 (s, 1H), 7.23 (dd, J = 7.4, 5.0 Hz, 1H), 7 , 04 (s, 1H), 5.29 (p, J = 6.4 Hz, 1H), 4.91 (d, J = 5.8 Hz, 2H), 4.36 (t, J = 7, 0 Hz, 2H), 3.82 (s, 3H), 2.55 (s, 3H), 1.51 (d, J = 6.4 Hz, 6H), 1.21 (t, J = 7, 0 Hz, hey).

LC-MS (mass / charge) 406.4 (MH +); t _R = 0.34 min (method E).

Example 59. 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N- (1,3,4-oxadiazol-2-ylmethyl) pyrazolo [4,3-b] pyridine-7- amine

prepared using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine and (1,3,4-oxadiazol-2-yl ) methanamine hydrobromide.

1H NMR (chloroform-d, 400 MHz) δ 8.42-8.37 (m, 2H), 8.24-8.22 (m, 1H), 7.88 (s, 1H), 7.10- 7.08 (m, 2H), 4.86-4.79 (m, 1H), 4.52 (d, J = 7.2 Hz, 2H), 4.33 (s, 2H), 2.71 (s, 3H), 1.55 (d, J = 6.8 Hz, 6H), 1.45 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 394.3 (MH ⁺ ); t _R = 0.61 min (method E).

Example 60. 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(1-methylpyrαzol-3-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 1, from 5,7-dichloro-1-isopropyl-3-methyl-1 H-pyrazolo [4,3-b] pyridine and (1-methyl-1 H-pyrazole-3 -yl) methanamine;

- 111 037544

1H NMR (chloroform-d, 400 MHz) δ 8.27-8.25 (m, 1H), 8.18-8.17 (m, 1H), 7.37 (d, J = 2.0Hz, 1H), 7.20 (s, 1H), 7.04-7.01 (m, 1H), 6.26 (d, J = 2.0 Hz, 1H), 5.25 (brs, 1H), 4.95-4.88 (m, 1H), 4.51-4.46 (m, 4H), 3.93 (s,

3H), 2.65 (s, 3H), 1.64 (d, J = 6.4 Hz, 6H), 1.42 (t, J = 6.8 Hz, 3H).

LC-MS (mass / charge) 406.4 (MH +); tR = 0.50 min (method E).

Example 61 5- (1,3-Dimethylpyrazol-4-yl) -1 -isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridine-7 -amine

obtained using the same procedure as described for example 1, from 5-chloro-1isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridine-7- amine and 1,3-dimethyl-4 (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrazole.

1H NMR (chloroform-d, 400 MHz): δ 7.75 (s, 1H), 7.55 (s, 1H), 7.40 (s, 1H), 6.56 (s, 1H), 4, 74-4.67 (m, 1H), 4.54 (brs, 1H), 4.37 (d, J = 4.8 Hz, 2H), 3.92 (s, 3H), 3.87 (s , 3H), 2.60 (s, 3H), 2.50 (s, 3H), 1.56 (d, J = 6.4Hz, 6H).

LC-MS (mass / charge) 379.4 (MH +); tR = 0.38 min (method E).

Example 62 1-Isopropyl-5- (2-methoxy-3-pyridyl) -3-methyl-N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine

obtained using the same procedure as described for example 1, from 5-chloro-1isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridine-7- amine and (2-methoxy-3pyridyl) boronic acid.

1H NMR (chloroform-d, 400 MHz) δ 8.21 - 8.17 (m, 2H), 7.57 (s, 1H), 7.45 (s, 1H), 7.08-7.04 ( m, 2H), 4.79 - 4.73 (m, 1H), 4.57 (brs, 1H), 4.39 (d, J = 4.8 Hz, 2H), 3.99 (s, 3H ), 3.93 (s, 3H), 2.64 (s, 3H), 1.59 (d, J = 6.4 Hz, 6H).

LC-MS (mass / charge) 392.4 (MH +); tR = 0.43 min (method E).

Example 63 1-Isopropyl-5- (2-methoxyphenyl) -3-methyl-N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine

n-ν / obtained using the same procedure as described for example 1, from 5-chloro-1isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine and (2-methoxyphenyl) boronic acid.

1H NMR (chloroform-d, 400 MHz) δ 7.74 (dd, J = 1.8, 7.4 Hz, 1H), 7.56 (s, 1H), 7.43 (s, 1H), 7 , 40-7.31 (m, 1H), 7.13-7.05 (m, 1H), 7.00 (d, J = 8.0 Hz, 1H), 6.94 (s, 1H), 4.82 -4.72 (m, 1H), 4.53 (brs, 1H), 4.36 (d, J = 4.8 Hz, 2H), 3.92 (s, 3H), 3.82 (s, 3H), 2.65 (s, 3H), 1.59 (d, J = 6.8 Hz, 6H).

LC-MS (mass / charge) 391.1 (MH +); tR = 0.47 min (method E).

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Example 64 1-Isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] -5-phenylpyrazolo [4,3-b] pyridin-7-amine

NH A NN obtained using the same procedure as described for example 1, from 5-chloro-1isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridine -7-amine and phenylboronic acid.

1H NMR (chloroform-d, 400 MHz) δ 8.00-7.99 (m, 2H), 7.58 (s, 1H), 7.49-7.43 (m, 3H), 7.41 - 7.37 (m, 1H), 6.88 (s, 1H), 4.79-4.69 (m, 1H), 4.56 (brs, 1H), 4.43 (d, J = 4, 8 Hz, 2H), 3.93 (s, 3H), 2.67 (s, 3H), 1.59 (d, J = 6.4 Hz, 6H).

LC-MS (mass / charge) 361.3 (MH +); tR = 0.45 min (method E).

Example 65. 1-Isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] -5- (2-methyl-3-thienyl) pyrazolo [4,3-b] pyridine-7-amine

NH

A N-N /

obtained using the same procedure as described for example 1, from 5-chloro-1isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridine-7- amine and 4,4,5,5-tetramethyl-2- (2-methyl-3-thienyl) -1,3,2-dioxaborolane.

1H NMR (chloroform-d, 400 MHz) δ 7.55 (s, 1H), 7.40 (s, 1H), 7.26 (d, JJJ = 4.8 Hz, 1H), 7.08 (d , JJJ = 5.2 Hz, 1H), 6.60 (brs, 1H), 4.77-4.72 (m, 1H), 4.57 (brs, 1H), 4.36 (d, J = 4.4 Hz, 2H), 3.92 (s, 3H), 2.66 (s, 3H), 2.62 (s, 3H), 1.58 (d, J = 6.4 Hz, 6H) ...

LC-MS (mass / charge) 381.0 (MH +); tR = 2.06 min (method F).

Example 66 5- (1,5-Dimethylpyrazol-4-yl) -1-isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridine-7 -amine

obtained using the same procedure as described for example 1, from 5-chloro-1isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridine-7- amine and 1,5-dimethyl-4 (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrazole.

1H NMR (DMSO-d6, 400 MHz) δ 7.74 (s, 1H), 7.64 (s, 1H), 7.44 (s, 1H), 6.57 (brs, 1H), 6.57 (s, 1H), 5.135.07 (m, 1H), 4.38 (d, J = 5.2 Hz, 2H), 3.76 (s, 3H), 3.75 (s, 3H), 2 , 56 (s, 3H), 2.41 (s, 3H), 1.42 (d, J = 6.4Hz, 6H).

LC-MS (mass / charge) 379.4 (MH +); tR = 0.38 min (method E).

Example 67. 5- (2-Ethoxy-3-pyridyl) -3-methyl-1- [1-methylpropyl] -N - [(1-methylpyrazol-3-yl) methyl] pyrazolo [4,3-b] pyridine -7-amine, enantiomer 2

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obtained using the same procedure as described for example 1, from 1- (sec-butyl) -5 (2-ethoxyπpyridin-3-yl) -3-methyl-1H-pyrazolo [4,3-b] pyridine-7- amine, enantiomer 2, (2-ethoxy-3pyridyl) boronic acid and (1-methyl-1H-π-pyrazol-3-yl) methanamine.

¹ H NMR (chloroform-d, 400 MHz) δ 8.27 (dd, J = 1.6, 7.2 Hz, 1H), 8.17 (dd, J = 1.6, 4.8 Hz, 1H ), 7.37 (d, J = 2.0 Hz, 1H), 7.21 (s, 1H), 7.02 (dd, J = 4.8, 7.6 Hz, 1H), 6.25 (d, J = 2.0 Hz, 1H), 5.24 (brs, 1H), 4.65-4.60 (m, 1H), 4.51-4.46 (m, 4H), 3, 92 (s, 3H), 2.65 (s, 3H), 2.22 - 2.15 (m, 1H), 1.92 - 1.85 (m, 1H), 1.62 (d, J = 6.4 Hz, 3H), 1.43 (t, J = 6.8 Hz, 3H), 0.92 (t, J = 7.6 Hz, 3H).

LC-MS (mass / charge) 420.1 (MH ⁺ ); t _R = 1.87 (method A).

Example 68. 3-Methyl- 1- [1-methylpropyl] -N - [(2-methyltetrazol-5-yl) methyl] -5- (2-propoxy-3pyridyl) pyrazolo [4,3-b] pyridine-7 -amine, enantiomer 2

obtained using the same procedure as described for example 1, from 1- (sec-butyl) -5 (2-ethoxypyridin-3-yl) -3-methyl-1H-pyrazolo [4,3-b] pyridine-7 -amine, enantiomer 2 and (2-methyl-2Htetrazol-5-yl) methanamine.

Ή NMR (chloroform-d, 400 MHz) δ 8.27 (dd, J = 7.50, 1.98 Hz, 1H), 8.19 (dd, J = 5.07, 1.98 Hz, 1H) , 7.25 (s, 1H), 7.03 (dd, J = 7.39, 4.96 Hz, 1H), 5.29 (s, 1H), 4.78 (d, J = 5.07 Hz, 2H), 4.61 - 4.68 (m, 1H), 4.37 - 4.41 (m, 5H), 2.66 (s, 3H), 2.18 (s, 1H), 1 , 80 - 1.96 (m, 3H), 1.65 (d, J = 6.62 Hz, 3H), 1.06 (t, J = 7.39 Hz, 3H), 0.92 (t, J = 7.39 Hz, 3H).

LC-MS (mass / charge) 436.1 (MH ⁺ ); tR = 1.97 (method A).

Example 69. 5- (2-Ethoxy-3-pyridyl) -1- [1-methylpropyl] -N - [(1-methylπyrazol-4-yl) methyl] πyrazolo [4,3-b] nyridin-7-amine , enantiomer 1

obtained using the same procedure as described for example 1, from 1- (sec-butyl) -5 (2-ethoxypyridin-3-yl) -1H-nyrazolo [4,3-b] nyridin-7-amine, enantiomer 1, (2-ethoxy-3-pyridyl) boronic acid and (1-methyl-1H-pyrazol-4-yl) methanamine.

Ή NMR (chloroform-d, 400 MHz) δ 8.18-8.14 (m, 2H), 8.11 (s, 1H), 7.59 (s, 1H), 7.40 (s, 1H) , 7.11-7.07 (m, 2H), 6.73-6.72 (m, 1H), 5.01-4.96 (m, 1H), 4.39-4.33 (m, 4H), 3.77 (s, 3H), 2.00-1.97 (m, 1H), 1.81-1.79 (m, 1H), 1.49 (d, J = 6.8Hz , 3H), 1.25 (t, J = 6.8 Hz, 3H), 0.73 (t, J = 7.2 Hz, 3H).

SFC-MS: tR = 4.72 min, ee% = 97.51.

LC-MS (mass / charge) 406.1 (MH ⁺ ); tR = 2.09 (method A).

Example 70 5- (2-Ethoxy-3-pyridyl) -1- [1-methylpropyl] -N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine , enantiomer 2

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obtained using the same procedure as described for example 1, from 1- (sec-butyl) -5 (2-ethoxypyridin-3-yl) -1H-pyrazolo [4,3-b] pyridin-7-amine, enantiomer 2, (2-ethoxy-3-pyridyl) boronic acid and (1-methyl-1H-pyrazol-4-yl) methanamine.

¹ H NMR (chloroform-d, 400 MHz) δ 8.17-8.14 (m, 2H), 8.11 (s, 1H), 7.59 (s, 1H), 7.40 (s, 1H ), 7.11-7.06 (m, 2H), 6.74-6.71 (m, 1H), 5.01-4.97 (m, 1H), 4.39-4.33 (m , 4H), 3.77 (s, 3H), 2.00-1.95 (m, 1H), 1.82-1.77 (m, 1H), 1.49 (d, J = 6.4 Hz, 3H), 1.25 (t, J = 6.8 Hz, 3H), 0.73 (t, J = 7.2 Hz, 3H).

SFC-MS: tR = 4.48 min, ee% = 95.47. LC-MS (mass / charge) 406.1 (MH ⁺ ); tR = 2.01 (method A).

Example 71 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-N - [(4-methylthiazol-5-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine

obtained using the same procedure as described for example 1, from 5,7-dibromo-1isopropyl-1H-pyrazolo [4,3-b] pyridine, 2-ethoxy-3- (4,4,5,5-tetramethyl -1,3,2-dioxaborolan-2yl) pyridine and (4-methylthiazol-5-yl) methanamine dihydrochloride.

¹ H NMR (DMSO-d ₆ , 600 MHz) δ 8.84 (s, 1H), 8.17 (dd, J = 4.9, 1.9 Hz, 1H), 8.14-8.08 ( m, 2H), 7.07 (dd, J = 7.3, 4.7Hz, 2H), 7.02 (s, 1H), 5.26 (hept, J = 6.4Hz, 1H), 4.67 (d, J = 5.3 Hz, 2H), 4.34 (q, J = 7.0 Hz, 2H), 2.44 (s, 3H), 1.50 (d, J = 6 , 3 Hz, 6H), 1.21 (t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 409.5 (MH ⁺ ); tR = 0.51 (method D).

Example 72 5- [[5- (2-Ethoxy-3-pyridyl) -1 -isopropyl-3-methylpyrazolo [4,3-b] pyridin-7-yl] oxymethyl] -2-methyloxazole

obtained using the same procedure as described for example 1, from 5,7-dibromo-1isopropyl-1H-pyrazolo [4,3-b] pyridine, 2-ethoxy-3- (4,4,5,5-tetramethyl -1,3,2-dioxaborolan-2-yl) pyridine and (2-methyloxazol-5-yl) methanol.

¹ H NMR (DMSO-d ₆ , 600 MHz) δ 8.24 (dd, J = 4.9, 2.0 Hz, 1H), 8.18 (dd, J = 7.3, 2.0 Hz, 1H), 7.65 (s, 1H), 7.28 (s, 1H), 7.14 (dd, J = 7.4, 4.9Hz, 1H), 5.45 (s, 2H), 5.11 (hept, J = 6.7 Hz, 1H), 4.45 (q, J = 7.0 Hz, 2H), 2.51 (s, 3H), 2.43 (s, 3H), 1.44 (d, J = 6.6 Hz, 6H), 1.36 (t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 408.6 (MH ⁺ ); tR = 0.64 (method D).

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Example 73. 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N- (pyrimidin-4-ylmethyl) pyrazolo [4,3b] pyridin-7-amine

prepared using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methylpyrαzolo [4,3-b] pyridine, (2-ethoxy-3-pyridyl) boronic acid and pyrimidine-4ylmethanamine.

¹ H NMR (400 MHz, chloroform-d) δ 9.28 (s, 1H), 8.76 (d, J = 5.3 Hz, 1H), 8.27 (brd, J = 7.5 Hz, 1H), 8.19 (brd, J = 3.3 Hz, 1H), 7.45 (brs, 1H), 7.11 (s, 1H), 7.04 (dd, J = 5.0, 6 , 9 Hz, 1H), 6.30 (weak br s, 1H), 5.11 (m, 1H), 4.68 (m, 2H), 4.46 (q, J = 7.1 Hz, 2H ), 2.68 (s, 3H), 1.72 (d, J = 6.6 Hz, 6H), 1.39 (t, J = 7.1 Hz, 3H).

LC-MS (mass / charge) 404.1 (MH +); tR = 1.89 (method C).

Example 74. 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N- (pyrimidin-2-ylmethyl) pyrazolo [4,3b] pyridin-7-amine

prepared using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methylpyrαzolo [4,3-b] pyridine, (2-ethoxy-3-pyridyl) boronic acid and pyrimidin-2 ylmethanamine ...

Ή NMR (chloroform-d, 400 MHz) δ 8.83 (d, J = 4.8 Hz, 2H), 8.28 (dd, J = 2.0, 7.2 Hz, 1H), 8.19 (dd, J = 2.0, 4.8 Hz, 1H), 7.34-7.31 (m, 1H), 7.19 (s, 1H), 7.03 (dd, J = 5.2 , 7.6 Hz, 1H), 6.45 (brs, 1H), 5.17-5.10 (m, 1H), 4.74 (d, J = 4.0 Hz, 2H), 4.50 (q, J = 6.8 Hz, 2H), 2.67 (s, 3H), 1.72 (d, J = 6.4 Hz, 6H), 1.46 (t, J = 6.8 Hz , 3H).

LC-MS (mass / charge) 404 (MH +); t _R = 2.20 (method B).

Example 75 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(4-methylpyrimidin-2-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methylpyrαzolo [4,3-b] pyridine, (2-ethoxy-3-pyridyl) boronic acid and (4-methylpyrimidine -2-yl) methanamine.

¹ H NMR (chloroform-d, 400 MHz) δ 8.65 (d, J = 5.2 Hz, 1H), 8.25 (dd, J = 2.0, 7.2 Hz, 1H), 8, 18 (dd, J = 2.0, 5.2 Hz, 1H), 7.18-7.15 (m, 2H), 7.03 (dd, J = 5.2, 7.2 Hz, 1H) , 6.57 (brs, 1H), 5.21-5.15 (m, 1H), 4.68 (d, J = 4.0 Hz, 2H), 4.50 (q, J = 7.2 Hz, 2H), 2.67 (s, 3H), 2.61 (s, 3H), 1.73 (d, J = 6.4 Hz, 6H), 1.46 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 418.1 (MH +); t _R = 2.2 (method C).

Example 76. 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N- (pyrazin-2-ylmethyl) pyrazolo [4,3b] pyridin-7-amine

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prepared using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methylpyrazolo [4,3-b] pyridine, (2-ethoxy-3-pyridyl) boronic acid and pyrazin-2 ylmethanamine ...

Ή NMR (chloroform-d, 400 MHz) δ 8.73 (d, J = 1.6 Hz, 1H), 8.63 (dd, J = 2.4, 1.6 Hz, 1H), 8.59 (d, J = 2.4 Hz, 1H), 8.26 (dd, J = 2, 7.6 Hz, 1H), 8.18 (dd, J = 2, 4.8 Hz, 1H), 7 , 18 (s, 1H), 7.05-7.02 (m, 1H), 6.10 (brs, 1H), 5.06-5.03 (m, 1H), 4.7 (d, J = 4.0 Hz, 2H), 4.48 (q, J = 7.2 Hz, 2H), 2.67 (s, 3H), 1.69 (d, J = 6.4 Hz, 6H), 1.42 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 404.1 (MH +); tR = 2.19 (method B).

Example 77 5- (2-Ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-N - [[2- (trifluoromethyl) -3-pyridyl] methyl] pyrazolo [4,3-b] pyridine-7 -amine

prepared using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methylpyrazolo [4,3-b] pyridine, (2-ethoxy-3-pyridyl) boronic acid and (2- ( trifluoromethyl) pyridin-3-yl) methanamine.

¹ H NMR (chloroform-d, 400 MHz) δ 8.67-8.66 (m, 1H), 8.26-8.23 (m, 1H), 8.16-8.13 (m, 1H) , 7.99-7.98 (m, 1H), 7.52-7.49 (m, 1H), 7.06 (s, 1H), 7.02-6.99 (m, 1H), 4 , 94-4.87 (m, 4H), 4.34-4.29 (m, 2H), 2.66 (s, 3H), 1.66 (d, J = 6.4 Hz, 6H), 1.17 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 471 (MH +); tR = 2.1 (method A).

Example 78 4- [[[5- (2-Ethoxy-3-pyridyl) -1 -isopropyl-3-methylpyrazolo [4,3-L] pyridin-7 yl] amino] methyl] -1 -methylpyridine-2- is he

prepared using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methylpyrazolo [4,3-b] pyridine, (2-ethoxy-3-pyridyl) boronic acid and 4- (aminomethyl ) 1-methylpyridin-2 (1 H) -one.

1H NMR (chloroform-d, 400 MHz) δ 8.23 (dd, J = 1.6, 5.6 Hz, 1H), 8.16 (dd, J = 2.0, 5.2 Hz, 1H) , 7.29 (d, J = 6.8 Hz, 1H), 7.04-7.01 (m, 2H), 6.61 (s, 1H), 6.21 (d, J = 6.8 Hz, 1H), 4.89 (m, 1H), 4.44-4.39 (m, 4H), 3.54 (s, 3H), 2.65 (s, 3H), 1.66 (d , J = 6.4 Hz, 6H), 1.33 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 433.1 (MH +); tR = 1.88 (method B).

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Example 79. 5- (2- (Ethylamino) pyridin-3-yl) -1-isopropyl-3-methyl-N ((1-methyl-N-pyrazol-4yl) methyl) -1 H-pyrαzolo [4.3 -B] pyridine-7-amine

obtained using the same procedure as described for example 1, from 5-bromo-1isopropyl-3-methyl-N - ((1-methyl-1H-pyrαzol-4-yl) methyl) -1H-pyrαzolo [4,3 -b] pyridin-7-amine and N-ethyl3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridin-2-amine.

¹ H NMR (chloroform-d, 600 MHz) δ 9.34 - 9.27 (m, 1H), 8.16 (dd, J = 4.9, 1.8 Hz, 1H), 7.77 (dd , J = 7.6, 1.8 Hz, 1H), 7.57 (s, 1H), 7.42 (s, 1H), 6.80 (s, 1H), 6.58 (dd, J = 7.5, 4.9 Hz, 1H), 4.72 (hept, J = 6.6 Hz, 1H), 4.57 (t, J = 5.0 Hz, 1H), 4.41 (d, J = 4.7 Hz, 2H), 3.93 (s, 3H), 3.57 (qd, J = 7.2, 4.6 Hz, 2H), 2.61 (s, 3H), 1, 59 (d, J = 6.5 Hz, 6H), 1.37 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 405.6 (MH +); tR = 0.45 min (method D).

Example 81 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-N - [(4-methoxy-2-pyridyl) methyl] -3-methylpyrαzolo [4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methylpyrαzolo [4,3-b] pyridine, (2-ethoxy-3-pyridyl) boronic acid and (4methoxypyridine-2 -yl) methanamine.

¹ H NMR (chloroform-d, 400 MHz) δ 8.45 (d, J = 2.4 Hz, 1H), 8.26 (d, J = 7.2 Hz, 1H), 8.18 (d, J = 4.4 Hz, 1H), 7.12 (s, 1H), 7.03 (dd, J = 5.2, 6.8 Hz, 1H), 6.87-6.81 (m, 2H ), 6.54-6.49 (m, 1H), 5.13-5.06 (m, 1H), 4.574.55 (m, 2H), 4.50-4.45 (m, 2H), 3.89 (s, 3H), 2.67 (s, 3H), 1.69 (d, J = 6.4 Hz, 6H), 1.42 (t, J = 1.6 Hz, 3H).

LC-MS (mass / charge) 433.1 (MH +); t _R = 2.32 (method B).

Example 82 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-N - [(6-methoxypyrαzin-2-yl) methyl] -3-methylpyrazolo [4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methylpyrazolo [4,3-b] pyridine, (2-ethoxy-3-pyridyl) boronic acid and (6methoxypyrazine-2 -yl) methanamine hydrochloride.

¹ H NMR (chloroform-d, 400 MHz) δ 8.25-8.27 (m, 2H), 8.23 (s, 1H), 8.18-8.19 (m, 1H), 7.21 (s, 1H), 7.03 (dd, J = 5.2, 7.6Hz 1H), 5.72-5.74 (m, 1H), 4.99-5.06 (s, 1H) , 4.60 (d, J = 4.4 Hz 2H), 4.45-4.51 (m, 2H), 4.03 (s, 3H), 2.66 (s, 3H), 1.67 (d, J = 6.4 Hz, 6H), 1.42 (t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 434.1 (MH +); t _R = 1.86 (method a).

Example 83 5- (2-Ethoxy-3-pyridyl) -N - [(5-fluoropyrimidin-2-yl) methyl] -1-isopropyl-3-methylpyrazolo [4,3-b] pyridin-7-amine

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prepared using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methylpyrαzolo [4,3-b] pyridine, (2-ethoxy-3-pyridyl) boronic acid and (5fluoropyrimidine-2 -yl) methanamine.

¹ H NMR (chloroform-d, 400 MHz) δ 8.70 (s, 2H), 8.27 (dd, J = 2.0, 6.0 Hz, 1H), 8.20 (d, J = 2 , 8 Hz, 1H), 7.18 (s, 1H), 7.04 (dd, J = 4.8, 7.2 Hz, 1H), 6.25 (brs, 1H), 5.13-5 , 06 (m, 1H), 4.75 (d, J = 4.4 Hz, 2H), 4.50 (q, J = 7.2 Hz, 2H), 3.69 (s, 3H), 1 , 71 (d, J = 6.8 Hz, 6H), 1.46 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 422.1 (MH +); tR = 2.2 (method C).

Example 84 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(2-methyl-3-pyridyl) methyl] pyrazolo [4,3 - b] pyridin-7-amine

D ⁴ ] /

HS n I .NH A 'prepared using the same procedure as described for example 1 from 5,7-dichloro-1-isopropyl-3-methylpyrazolo [4,3-b] pyridine, (2-ethoxy-3-pyridyl) boronic acid and (2methylpyridin-3-yl) methanamine.

¹ H NMR (chloroform-d, 400 MHz): δ = 8.50 (d, J = 5.2 Hz, 1H), 8.26 (d, J = 7.2 Hz, 1H), 8.16 ( d, J = 5.2 Hz, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.19 - 7.16 (m, 1H), 7.14 (s, 1H), 7.03 - 7.00 (m, 1H), 4.83 - 4.78 (m, 1H), 4.68 (brs, 1H), 4.54 (d, J = 5.2 Hz, 2H) , 4.36 (q, J = 7.2 Hz, 2H), 2.66 (s, 6H), 1.62 (d, J = 6.4 Hz, 6H), 1.25 (t, J = 6.8 Hz, 3H).

LC-MS (mass / charge) 417.1 (MH +); tR = 1.33 (method A).

Example 85 5- (2-Ethoxy-3-pyridyl) -N - [(2-fluoro-3-pyridyl) methyl] -1-isopropyl-3-methylpyrαzolo [4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methylpyrαzolo [4,3-b] pyridine, (2-ethoxy-3-pyridyl) boronic acid and (2-fluoropyridine -3-yl) methanamine.

¹ H NMR (chloroform-d, 400 MHz): δ 8.26-8.14 (m, 1H), 8.19-8.15 (m, 2H), 7.90-7.80 (m, 1H ), 7.22-7.19 (m, 1H), 7.13 (s, 1H), 7.03-7.00 (m, 1H), 5.00-4.80 (m, 2H), 4.67-4.66 (m, 2H), 4.37 (q, J = 7.2 Hz, 2H), 2.65 (s, 3H), 1.65 (d, J = 6.8 Hz , 6H), 1.33 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 421.1 (MH +); tR = 1.8 (method A).

Example 86 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-N - [(2-methoxy-3-pyridyl) methyl] -3-methylpyrαzolo [4,3-b] pyridin-7-amine

- 119 037544

obtained using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methylpyrazolo [4,3-b] pyridine, (2-ethoxy-3-pyridyl) boronic acid and (2methoxypyridine-3 -yl) methanamine.

1H NMR (chloroform-d, 400 MHz): δ 8.26-8.23 (m, 1H), 8.16-8.13 (m, 2H), 7.62-7.61 (m, 1H) , 7.15 (s, 1H), 7.03-7.00 (m, 1H), 6.92-6.89 (m, 1H), 5.13-5.11 (m, 1H), 4 , 93-4.90 (m, 1H), 4.53-4.52 (m, 2H), 4.41 (q, J = 7.2 Hz, 2H), 4.04 (s, 3H), 2.65 (s, 3H), 1.65 (d, J = 6.8 Hz, 6H), 1.33 (t, J = 7.2 Hz, 3H, chloroform-d, 400 MHz).

LC-MS (mass / charge) 433 (MH ⁺ ); tR = 2.04 (method A).

Example 87 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(6-methyl-3-pyridyl) methyl] pyrazolo [4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methylpyrazolo [4,3-b] pyridine, (2-ethoxy-3-pyridyl) boronic acid and (6methylpyridine-3 -yl) methanamine.

1H NMR (chloroform-d, 400 MHz): δ = 8.60 (s, 1H), 8.25 (brd, J = 7.7 Hz, 1H), 8.17 (brd, J = 4.6 Hz , 1H), 7.66 (brd, J = 8.4 Hz, 1H), 7.20 - 7.17 (m, 1H), 7.20 (brd, J = 11.5 Hz, 1H), 7 , 06 - 6.99 (m, 1H), 4.82 (s, 1H), 4.71 (s, 1H), 4.55 (br s, 2H), 4.42 (q, J = 7, 1 Hz, 2H), 2.65 (s, 3H), 2.59 (s, 3H), 1.62 (d, J = 6.4 Hz, 6H), 1.33 (t, J = 7, 1 Hz, 3H).

LC-MS (mass / charge) 417.1 (MH +); t _R = 1.36 (method A).

Example 88 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-N - [(2-methoxyphenyl) methyl] -3-methylpyrazolo [4,3b] pyridin-7-amine

prepared using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methylpyrazolo [4,3-b] pyridine, (2-ethoxy-3-pyridyl) boronic acid and (2-methoxyphenyl ) methanamine.

1H NMR (400 MHz, chloroform-d,) δ = 8.24 (d, J = 7.3 Hz, 1H), 8.18 - 8.13 (m, 1H), 7.37 - 7.30 ( m, 2H), 7.23 (s, 1H), 7.03 - 6.94 (m, 3H), 5.08 (brs, 1H), 4.89 - 4.81 (m, 1H), 4 , 53 (d, J = 5.3 Hz, 2H), 4.45 (q, J = 6.9 Hz, 2H), 3.90 (s, 3H), 2.64 (s, 3H), 1 , 62 (d, J = 6.6 Hz, 6H), 1.38 (t, J = 7.1 Hz, 3H).

LC-MS (mass / charge) 432.1 (MH +); t _R = 2.19 (method A).

Example 89 5- (2-Ethoxy-3-pyridyl) -N - [(2-fluorophenyl) methyl] -1-isopropyl-3-methylpyrazolo [4,3b] pyridin-7-amine

prepared using the same procedure as described for example 1, from 5,7-dichloro-1-120 037544 isopropyl-3-methylpyrazolo [4,3-b] pyridine, (2-ethoxy-3-pyridyl) boronic acid and (2fluorophenyl) methanamine.

1H NMR (chloroform-d, 400 MHz): δ = 8.26-8.24 (m, 1H), 8.18-8.17 (m, 1H), 7.44 (br s, J = 7, 7 Hz, 1H),

7.34-7.32 (m, 1H), 7.20 (s, 1H), 7.18-7.14 (m, 2H), 7.03-7.02 (m, 1H), 4, 89-4.85 (m, 2H), 4.65-4.64 (m, 2H),

4.42 (q, J = 7.2 Hz, 2H), 2.65 (s, 3H), 1.64 (d, J = 6.4 Hz, 6H), 1.33 (t, J = 6 , 8 Hz, 3H).

LC-MS (mass / charge) 420 (MH ⁺ ); tR = 2.14 (method A).

Example 90 5 - (2-Ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-N - [[2- (trifluoromethyl) phenyl] methyl] pyrazolo [4,3-b] pyridine-7-amine

prepared using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methylpyrazolo [4,3-b] pyridine, (2-ethoxy-3-pyridyl) boronic acid and (2 (trifluoromethyl ) phenyl) methanamine.

1H NMR (chloroform-d, 400 MHz): δ 8.34-8.22 (m, 1H), 8.17-8.15 (m, 1H), 7.75 (d, J = 7.6 Hz , 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.55 (t, J = 6.4 Hz, 1H), 7.45 (t, J = 7.6 Hz, 1H ), 7.11 (s, 1H), 7.03-6.99 (m, 1H), 4.91-4.86 (m, 1H), 4.82 (br s, 2H), 4.35 (q, J = 7.2 Hz, 2H), 2.66 (s, 3H), 1.62 (d, J = 6.4 Hz, 6H), 1.23 (t, J = 6.8 Hz , 3H).

LC-MS (mass / charge) 470 (MH ⁺ ); tR = 1.87 (method I).

Example 91 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-N - [(3-methoxypyrazin-2-yl) methyl] -3-methylpyrazolo [4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methylpyrazolo [4,3-b] pyridine, (2-ethoxy-3-pyridyl) boronic acid and (3-methoxypyrazine -2-yl) methanamine hydrochloride.

1H NMR (chloroform-d, 400 MHz): δ 8.34-8.32 (m, 1H), 8.20-8.12 (m, 3H), 7.30 (s, 1H), 7.04 (dd, J = 7.6, 4.8Hz, 1H), 6.53 (brs, 1H), 5.14-5.08 (m, 1H), 4.58 (d, J = 4.0Hz 2H), 4.52 (q, J = 7.2 Hz, 2H), 4.08 (s, 3H), 2.67 (s, 3H), 1.71 (d, J = 6.8 Hz, 6H), 1.51 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 434.1 (MH +); t _R = 2.01 (method A).

Example 92 5- (2-Ethoxy-3-pyridyl) -1 -isopropyl-N - [(4-methoxy-3-pyridyl) methyl] -3-methylpyrazolo [4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methylpyrazolo [4,3-b] pyridine, (2-ethoxy-3-pyridyl) boronic acid and (4-methoxy -3pyridyl) methanamine.

1H NMR (chloroform-d, 400 MHz) δ = 8.53 - 8.50 (m, 2H), 8.24 (dd, J = 1.6, 7.2 Hz, 1H), 8.17 (dd , J = 2.8, 4.8 Hz, 1H), 7.23 (s, 1H), 7.05 - 7.00 (m, 1H), 6.89 (d, J = 6.0 Hz, 1H), 4.95 (brs, 1H), 4.87 - 4.81 (m, 1H), 4.54 (d, J = 6.4 Hz, 2H), 4.47 (q, J = 7 , 8 Hz, 2H), 3.95 (s, 3H), 2.65 (s, 3H), 1.62 (d, J = 6.4 Hz, 6H), 1.39 (t, J = 7 , 8 Hz, 3H).

LC-MS (mass / charge) 433.1 (MH +); t _R = 1.39 (method A).

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Example 93 1-Isopropyl-3-methyl - # - [(2-methyltetrazol-5-yl) methyl] -5- (2-propoxy-3-pyridyl) pyrazolo [4,3-b] nyridin-7-amine

prepared using the same procedure as described for example 1, from 5,7-dichloro-1isopronyl-3-methylpyrazolo [4,3-b] nyridine, (2-propoxy-3-pyridyl) boronic acid and (2-methyl -2Ntetrazol-5-yl) methanamine.

1H NMR (chloroform-d, 400 MHz): δ = 8.26-8.19 (m, 2H), 7.22 (s, 1H), 7.06-7.03 (m, 1H), 5, 48 (br. S, 1H), 4.99-4.91 (m, 1H), 4.81 (d, J = 3.2 Hz, 2H), 4.41-4.38 (m, 5H) , 2.65 (s, 3H), 1.88-1.82 (m, 2H), 1.67 (d, J = 6.4 Hz, 6H), 1.06 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 422.1 (MH +); tR = 2.04 (method C).

Example 94. 1-Isopropyl-3-methyl - # - [(1-methylpyrazol-4-yl) methyl] -5- (2-propoxy-3-pyridyl) pyrazolo [4,3-b] nyridin-7-amine

obtained using the same procedure as described for example 1, from 5,7-dichloro-1isopronyl-3-methylpyrazolo [4,3-b] nyridine, 2-propoxy-3- (4,4,5,5-tetramethyl -1,3,2-dioxaborolane-2yl) pyridine and (1-methyl-1H-pyrazol-4-yl) methanamine.

1H NMR (chloroform-d, 400 MHz): δ 8.26 (dd, J = 2.0, 7.6 Hz, 1H), 8.18 (dd, J = 5.2 Hz, 1H), 7, 57 (s, 1H), 7.44 (s, 1H), 7.22 (s, 1H), 7.03 (dd, J = 4.8, 7.2 Hz, 1H), 4.84 - 4 , 67 (m, 1H), 4.48 (brs, 1H), 4.40-4.33 (m, 4H), 3.94 (s, 3H), 2.65 (s, 3H), 1, 89 - 1.74 (m, 2H), 1.59 (d, J = 6.8 Hz, 6H), 1.03 (t, J = 7.6 Hz, 3H).

LC-MS (mass / charge) 420.4 (MH +); tR = 0.59 (method D).

Example 95 1-Isopropyl-5- (2-methoxy-3-pyridyl) - # - [(2-methoxy-3-pyridyl) methyl] -3-methylpyrazolo [4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 1, from 5,7-dibromo-1isopropyl-3-methyl-1H-πyrazolo [4,3-b] pyridine, (2-methoxypyridin-3-yl) boronic acid and (2methoxypyridin-3-yl) methanamine.

¹ H NMR (chloroform-d, 400 MHz): d 8.20-8.18 (m, 1H), 8.16-8.14 (m, 2H), 7.64-7.62 (m, 1H ), 7.04-7.03 (m, 1H), 6.97 (s, 1H), 6.93-6.92 (m, 1H), 5.24-5.21 (m, 1H), 4.93-4.87 (m, 1H), 4.51 (d, J = 5.6 Hz, 2H), 4.04 (s, 3H), 3.89 (s, 3H), 2.64 (s, 3H), 1.65 (d, J = 6.4Hz, 6H).

LC-MS (mass / charge) 419.1 (MH +); tR = 1.82 (method A).

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Example 96 1-Isopropyl-5- (2-methoxy-3-pyridyl) -N - [(6-methoxy-3-pyridyl) methyl] -3-methylpyrazolo [4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 1, from 5,7-dibromo-1isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine, (2-methoxypyridin-3-yl) boronic acid and (6methoxy-3-pyridyl) methanamine.

¹ H NMR (chloroform-d, 400 MHz): δ 8.26 (d, J = 1.6 Hz, 1H), 8.16-8.21 (m, 2H), 7.67 (dd, J = 2.4, 8.4 Hz, 1H), 7.02-7.07 (m, 2H), 6.80 (d, J = 8.8 Hz, 1H), 4.76-4.82 (m , 1H), 4.69 (brs, 1H), 4.47 (d, J = 5.2 Hz, 2H), 3.96 (s, 3H), 3.94 (s, 3H), 2.65 (s, 3H), 1.61 (d, J = 6.4Hz, 6H).

LC-MS (mass / charge) 419 (MH +); t _R = 1.83 (method A).

Example 97 5- (2-Isopropoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 29, from 5- (2isopropoxypyridin-3-yl) -1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridin-7-amine and 1- methyl 1Hpyrazole-4-carbaldehyde.

¹ H NMR (600 MHz, DMSO) δ 8.21-8.09 (m, 2H), 7.58 (d, J = 9.7 Hz, 1H), 7.38 (s, 1H), 7, 08 (s, 1H), 7.06 (dd, J = 7.3, 4.9 Hz, 1H), 6.67 (t, J = 5.5 Hz, 1H), 5.44 - 5.33 (m, 1H), 5.16 (dt, J = 12.7, 6.4 Hz, 1H), 4.36 (d, J = 5.5 Hz, 2H), 3.76 (s, 3H) , 2.46 (s, 3H), 1.45 (d, J = 6.4 Hz, 6H), 1.23 (d, J = 6.2 Hz, 6H).

LC-MS (mass / charge) 420.4 (MH +); t _R = 0.52 (method E).

Example 98. 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N- (1H-1,2,4-triazol-3-ylmethyl) pyrazolo [4,3-b] pyridine- 7-amine

prepared using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1 -isopropyl-3-methyl-1H-pyrazolo [4,3-0] pyridin-7-amine and 1H -1,2,4-triazole-3 carbaldehyde.

¹ H NMR (chloroform-d, 400 MHz): δ 8.21-8.17 (m, 2H), 8.12 (s, 1H), 7.15 (s, 1H), 7.02-6, 99 (m, 1H), 5.60 (brs, 1H), 4.99-4.93 (m, 1H), 4.65 (s, 2H), 4.46 (q, J = 7.2 Hz , 2H), 2.65 (s, 3H), 1.65 (d, J = 6.4 Hz, 6H), 1.39 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 393.1 (MH +); t _R = 2.3 (method C).

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Example 99. 5- (2-Ethoxy-3-nyridyl) -1-isopropyl-3-methyl-N- (2H-tetrazol-5-ylmethyl) pyrazolo [4.3b] pyridin-7-amine

HN-N prepared using the same procedure as described for example 29 from 5- (2ethoxypyridin-3-yl) -1-isopropyl-3-methyl-N-pyrazolo [4,3-b] pyridin-7-amine and 2H-tetrazole-5carbaldehyde.

1H NMR (DMSO-d6 400 MHz): δ 8.17-8.13 (m, 2H), 7.09-7.05 (m, 1H), 6.99 (s, 1H), 6.91 ( br. s, 1H), 5.20-5.14 (m, 1H), 4.79 (d, J = 5.2 Hz, 2H), 4.30 (q, J = 6.8 Hz, 2H ), 2.47 (s, 3H), 1.49 (d, J = 6.4 Hz, 6H), 1.22 (t, J = 6.8 Hz, 3H).

LC-MS (mass / charge) 394 (MH ⁺ ); tR = 1.77 (method C).

Example 100 5- (2-Ethoxy-3-nyridyl) -1-isopropyl-3-methyl-N- (2-nyridylmethyl) pyrazolo [4.3b] pyRidin-7-amine

prepared using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridin-7-amine and picolinaldehyde.

Ή NMR (chloroform-d, 400 MHz): δ 8.66-8.64 (m, 1H), 8.26 (dd, J = 2.0, 7.2 Hz, 1H), 8.18 (dd , J = 2.0.4.8 Hz, 1H), 7.77-7.72 (m, 1H), 7.38-7.36 (m, 1H), 7.30-7.28 (m , 1H), 7.14 (s, 1H), 7.03 (dd, J = 4.8, 7.2 Hz, 1H), 6.53 (brs, 1H), 5.15-5.08 ( m, 1H), 4.62 (d, J = 4.0 Hz, 2H), 4.48 (q, J = 6.8 Hz, 2H), 2.67 (s, 3H), 1.70 ( d, J = 6.8 Hz, 6H), 1.42 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 403.1 (MH ⁺ ); tR = 2.15 (method A).

Example 101 5- (2-Ethoxy-3-pyrigyl) -1-isopropyl-3-methyl-N - [(6-methyl-2-pyrigyl) methyl] pyrazolo [4,3-b] pyridin-7-amine

obtained using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridin-7-amine and 6- methylpicolinaldehyde.

¹ H NMR (chloroform-d, 400 MHz): δ 8.27-8.26 (m, 1H), 8.19-8.18 (m, 1H), 7.66-7.62 (m, 1H ), 7.18-7.14 (m, 2H), 7.11 (s, 1H), 7.04 (dd, J = 4.8, 7.2 Hz, 1H), 6.84 (brs, 1H), 5.22-5.19 (m, 1H), 4.57 (d, J = 3.6 Hz, 2H), 4.49 (q, J = 6.8 Hz, 2H), 2, 68 (s, 3H), 2.61 (s, 3H), 1.73 (d, J = 6.4 Hz, 6H), 1.43 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 417.1 (MH ⁺ ); tR = 2.04 (method A).

Example 102 5- (2-Ethoxy-3-pyridyl) -1 -isopropyl-N - [(6-methoxy-2-nyridyl) methyl] -3-methylpyrazolo [4,3-b] pyridin-7-amine

- 124 037544 prepared using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1 -isopropyl-3-methyl-1 H-pyrazolo [4,3-b] pyridine-7 - amine and 6-methoxypicolinaldehyde.

Ή NMR (chloroform-d, 400 MHz): δ 8.28-8.26 (m, 1H), 8.19-8.18 (m, 1H), 7.65-7.61 (m, 1H) , 7.17 (s, 1H), 7.05-7.02 (m, 1H), 6.96-6.94 (m, 1H), 6.75-6.72 (m, 1H), 6 , 17 (brs, 1H), 5.11-5.08 (m, 1H), 4.55-4.46 (m, 4H), 4.01 (s, 3H), 2.67 (s, 3H ), 1.66 (d, J = 6.0 Hz, 6H), 1.43 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 433.1 (MH +); tR = 2.47 (method A).

Example 103. 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(2-methyl-4-pyridyl) methyl] pyrazolo [4,3-b] pyridine-7-amine । NH

X) prepared using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1 -isopropyl-3-methyl-1 H-pyrazolo [4,3-b] pyridine-7-amine and 2-methylisonicotinaldehyde.

1H NMR (chloroform-d, 400 MHz): δ 8.50 (d, J = 5.2 Hz, 1H), 8.22 (dd, J = 2.0, 7.2 Hz, 1H), 8, 15 (dd, J = 2.0, 4.2 Hz, 1H), 7.20 (s, 1H), 7.15 (d, J = 5.2 Hz, 1H), 7.03 (s, 1H ), 7.00 (dd, J = 5.2, 7.6 Hz, 1H), 4.91-4.86 (m, 2H), 4.57 (d, J = 5.2 Hz, 2H) , 4.32 (q, J = 7.2 Hz, 2H), 2.66 (s, 3H), 2.57 (s, 3H), 1.67 (d, J = 6.4 Hz, 6H) , 1.21 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 417.1 (MH ⁺ ); tR = 1.53 (method A).

Example 104. 5 - (2-Ethoxy-3-pyridyl) -1 -isopropyl-N - [(2-methoxy-4-pyridyl) methyl] -3-methylpyrazolo [4,3-b] pyridine-7-amine) __ (X i lT ^ ^N

I .NH xe o ^a n ^ obtained using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1 -isopropyl-3-methyl-1 H-pyrazolo [4,3-b ] pyridine-7-amine and 2-methoxyisonicotinaldehyde.

¹ H NMR (chloroform-d, 400 MHz): δ 8.22 (d, J = 7.6 Hz, 1H), 8.18-8.14 (m, 2H), 7.04 (s, 1H) , 7 (dd, J = 5.2, 7.6 Hz 1H), 6.92 (d, J = 5.2 Hz 1H), 6.79 (s, 1H), 4.89-4.86 ( m, 2H), 4.56 (d, J = 5.2 Hz, 2H), 4.34 (q, J = 7.2 Hz, 2H), 3.94 (s, 3H), 2.66 ( s, 3H), 1.66 (d, J = 6.8 Hz, 6H), 1.24 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 433.1 (MH ⁺ ); tR = 1.94 (method A).

Example 105. 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(2-methylpyrimidin-4-yl) methyl] pyrazolo [4,3-b] pyridine-7-amine

prepared using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1 -isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridin-7-amine and 2 -methylpyrimidine-4 carbaldehyde.

1H NMR (chloroform-d, 400 MHz): δ 8.65 (d, J = 5.2 Hz, 1H), 8.26 (dd, J = 2.0, 7.6 Hz, 1H), 8, 18 (dd, J = 2.0, 7.6 Hz, 1H), 7.20 (d, J = 5.2 Hz, 1H), 7.09 (s, 1H), 7.05-7.02 (m, 1H), 6.45 (brs, 1H), 5.16-5.13 (m, 1H), 4.59 (d, J = 4.0 Hz, 2H), 4.46 (q, J = 7.2 Hz, 2H), 2.81 (s, 3H), 2.67 (s, 3H), 1.73 (d, J = 6.4 Hz, 6H), 1.40 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 418.1 (MH ⁺ ); t _R = 1.96 (method C).

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Example 106 5 - (2-Ethoxy-3-pyridyl) -1 -isopropyl-N - [(5-methoxy-3-pyridyl) methyl] -3-methylpyrazolo [4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridin-7-amine and 5- methoxy-nicotinaldehyde.

¹ H NMR (chloroform-d, 400 MHz): δ 8.24 (s, 1H), 8.19-8.18 (m, 1H), 8.14-8.12 (m, 2H), 7, 38 (s, 1H), 7.10-7.03 (m, 1H), 7.02-6.97 (m, 1H), 6.94 (s, 1H), 5.27-5.21 ( m, 1H), 4.58 (d, J = 4.8 Hz, 2H), 4.24 (q, J = 7.2 Hz, 2H), 3.78 (s, 3H), 2.46 ( s, 3H), 1.48 (d, J = 6.0 Hz, 6H), 1.10 (t, J = 6.8 Hz, 3H).

LC-MS (mass / charge) 433.1 (MH +); tR = 1.63 (method A).

Example 107. 5- (2-Ethoxy-3-pyridyl) -1-isonropyl-3-methyl-N - [[6- (trifluoromethyl) -2-pyridyl] methyl] pyrazolo [4,3-b] pyridine-7 -amine

obtained using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridin-7-amine and 6 - (trifluoromethyl) picolinaldehyde.

Ή NMR (chloroform-d, 400 MHz): δ 8.27 (dd, J = 2.0, 7.2 Hz, 1H), 8.18 (dd, J = 4.8, 2.0 Hz 1H) , 8.00-7.95 (m, 1H), 7.71 (d, J = 7.6 Hz, 1H), 7.59 (d, J = 7.6 Hz, 1H), 7.13 ( s, 1H), 7.04 (dd, J = 7.2, 4.8 Hz, 1H), 6.68 (brs, 1H), 5.19-5.16 (m, 1H), 4.70 (d, J = 3.6 Hz, 2H), 4.49 (q, J = 7.2 Hz, 2H), 2.67 (s, 3H), 1.71 (d, J = 6.4 Hz , 6H), 1.44 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 471 (MH +); tR = 2.34 (method A).

Example 108 3 - [[[5- (2-Ethoxy-3-pyridyl) -1 -isopropyl-3-methylpyrazolo [4,3-b] pyridin-7-yl] amino] methyl] -1-methylpyridin-2 -is he

obtained using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridin-7-amine and 1- methyl 2-oxo-1,2-dihydropyridine-3-carbaldehyde.

1H NMR (chloroform-d, 400 MHz): δ 8.31-8.24 (m, 1H), 8.19-8.17 (m, 1H), 7.50-7.42 (m, 1H) , 7.30-7.28 (m, 1H), 7.15 (s, 1H), 7.05-7.02 (m, 1H), 6.21-6.17 (m, 1H), 5 , 06-4.95 (m, 1H), 4.51-4.45 (m, 4H), 3.59 (s, 3H), 2.65 (s, 3H), 1.64 (d, J = 6.8 Hz, 6H), 1.40 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 433 (MH +); tR = 1.93 (method C).

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Example 109 5- (2-Ethoxy-3-pyridyl) -N - [(1-ethylpyrαzol-4-yl) methyl] -1-isopropyl-3-methylpyrazolo [4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 29, from 5- (2 ethoxypyridin-3-yl) -1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridin-7-amine and 1 -ethyl-1H-pyrazole-4carbaldehyde.

1H NMR (chloroform-d, 400 MHz): δ 8.28 (dd, J = 7.6, 2.0 Hz, 1H), 8.18 (dd, J = 4.8, 1.6 Hz, 1H ), 7.59 (s, 1H), 7.48 (s, 1H), 7.25 (s, 1H), 7.03 (dd, J = 7.6, 5.2 Hz, 1H), 4 , 77-4.50 (m, 1H), 4.52-4.45 (m, 3H), 4.39 (d, J = 4.8 Hz, 2H), 4.2 (q, J = 7 , 2 Hz, 2H), 2.65 (s, 3H), 1.59 (d, J = 6.8 Hz, 6H), 1.52 (t, J = 7.2 Hz, 3H), 1, 40 (t, J = 6.8 Hz, 3H).

LC-MS (mass / charge) 420.1 (MH ⁺ ); tR = 2.13 (method F).

Example 110 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(1-propylpyrαzol-4-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine

obtained using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1-isopropyl-3-methyl-1H-pyrαzolo [4,3-b] pyridin-7-amine and 1- propyl-1H-pyrazole4-carbaldehyde.

1H NMR (chloroform-d, 400 MHz): δ 8.27 (dd, J = 2.0, 7.2 Hz, 1H), 8.18 (dd, J = 2.0, 5.2 Hz, 1H ), 7.59 (s, 1H), 7.45 (s, 1H), 7.24 (s, 1h), 7.03 (dd, J = 4.8, 7.2 Hz, 1H), 4 , 77-4.74 (m, 1H), 4.48 (q, J = 7.2 Hz, 3H), 4.39 (d, J = 4.4 Hz, 2H), 4.09 (t, J = 7.2 Hz, 2H), 2.65 (s, 3H), 1.94-1.88 (m, 2H), 1.59 (d, J = 6.4 Hz, 6H), 1, 4 (t, J = 6.8 Hz, 3H), 0.93 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 434.1 (MH ⁺ ); t _R = 1.89 (method A).

Example 111 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-N - [(6-methoxy-3-pyridyl) methyl] -3-methylpyrazolo [4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1-isopropyl-3-methyl-1H-pyrαzolo [4,3-b] pyridin-7-amine and 6- methoxy-nicotinaldehyde.

¹ H NMR (chloroform-d, 400 MHz): δ 8.30-8.24 (m, 2H), 8.20-8.15 (m, 1H), 7.67 (d, J = 8.0 Hz, 1H), 7.21 (s, 1H), 7.04-7.01 (m, 1H), 6.80 (d, J = 8.0 Hz, 1H), 4.80 (dd, J = 4.8, 6.4 Hz, 1H), 4.65 (brs, 1H), 4.49-4.42 (m, 4H), 3.96 (s, 3H), 2.66 (s, 3H), 1.59 (d, J = 4.8 Hz, 6H), 1.40-1.34 (m, 3H).

LC-MS (mass / charge) 433.1 (MH ⁺ ); tR = 2.33 (method F).

Example 112 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-N - [(5-methoxy-2-pyridyl) methyl] -3-methylpyr

- 127 037544 ash [4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1-isopropyl-3-methyl-1H-nyrazolo [4,3-b] pyridin-7-amine and 5- methoxypicolinaldehyde.

1H NMR (chloroform-d, 400 MHz): δ 8.33 (d, J = 1.6 Hz, 1H), 8.26 (dd, J = 2.0, 7.6 Hz, 1H), 8, 18 (dd, J = 2.0, 4.8 Hz, 1H), 7.31-7.28 (m, 2H), 7.13 (s, 1H), 7.03 (dd, J = 7, 2, 7.6 Hz, 1H), 6.36 (s, 1H), 5.11-5.05 (m, 1H), 4.56 (d, J = 4.4 Hz, 2H), 4, 48 (q, J = 7.2 Hz, 2H), 3.91 (s, 3H), 2.66 (s, 3H), 1.69 (d, J = 7.2 Hz, 6H), 1, 42 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 433.1 (MH +); tR = 2.14 (method A).

Example 113 5- (2-Ethoxy-3-pyrigyl) -3-methyl-N - [(2-methylthiazol-4-yl) methyl] -1- (oxetane-3yl) pyrazolo [4,3-b] pyridine -7-amine

obtained using the same procedure as described for example 1, from 5,7-dibromo-3methyl-1- (oxetan-3-yl) pyrazolo [4,3-b] pyridine, (2-ethoxy-3-pyridyl) boronic acid and (2methylthiazol-4-yl) methanamine.

1H NMR (chloroform-d, 400 MHz) δ 8.26 (dd, J = 1.6, 7.2 Hz 1H), 8.18 (dd, J = 2.0, 4.8 Hz 1H), 7 , 24 (s, 1H), 7.05-7.02 (m, 2H), 5.94-5.85 (m, 2H), 5.28-5.25 (m, 2H), 5.20 -5.16 (m, 2H), 4.57 (d, J = 5.2 Hz, 2H), 4.46 (q, J = 7.2 Hz, 2H), 2.76 (s, 3H) , 2.66 (s, 3H), 1.39 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 437.4 (MH +); tR = 0.46 min (method E).

Example 114 5- (2-Ethoxy-3-nyridyl) -1-isopropyl-N - [(5-methoxypyrazin-2-yl) methyl] -3-methylpyrazolo [4,3-b] pyridin-7-amine

obtained using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1-isopropyl-3-methyl-1H-nyrazolo [4,3-b] pyridin-7-amine and 5 - methoxypyrazine-2carbaldehyde.

¹ H NMR (400 MHz, chloroform-d,): δ 8.24-8.28 (m, 2H), 8.16-8.23 (m, 2H), 7.18 (s, 1H), 7 , 04 (brt, J = 5.84 Hz, 1H), 5.80 (brs, 1H), 4.93-5.06 (m, 1H), 4.60 (brd, J = 3.75 Hz, 2H), 4.48 (q, J = 6.69 Hz, 2H), 4.00 (s, 3H), 2.66 (s, 3H), 1.66 (brd, J = 6.39 Hz, 6H), 1.41 (t, J = 6.95 Hz, 3H).

LC-MS (mass / charge) 434.1 (MH +); tR = 1.99 (method A).

Example 115 5- (2-Ethoxy-3-nirigyl) -1-isopropyl-3-methyl-N- (3-nyridylmethyl) pyrazolo [4,3b] pyrigin-7-amine

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prepared using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1-isopropyl-3-methyl-1H-nyrazolo [4,3-b] pyridin-7-amine and nicotinaldehyde.

1H NMR (chloroform-d, 400 MHz): δ = 8.73 (s, 1H), 8.61 (d, J = 3.6 Hz, 1H), 8.24 (d, J = 6.0 Hz , 1H), 8.16 (dd, J = 1.6, 4.4 Hz, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.36 - 7.33 (m, 1H), 7.18 (s, 1H), 7.01 (dd, J = 4.8, 7.6 Hz, 1H), 4.82 (s, 1H), 4.75 (s, 1H), 4.60 (d, J = 5.2 Hz, 2H), 4.40 (q, J = 6.8 Hz, 2H), 2.65 (s, 3H), 1.62 (d, J = 6 , 4 Hz, 6H), 1.30 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 403.1 (MH ⁺ ); tR = 1.41 (method A).

Example 116 5- (2-Ethoxy-3-nyridyl) -N - [(6-fluoro-3-nyridyl) methyl] -1-isopropyl-3-methylpyrazolo [4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1-isopropyl-3-methyl-1H-nyrazolo [4,3-b] pyridin-7-amine and 6- fluoronicotinaldehyde.

¹ H NMR (chloroform-d, 400 MHz): δ 8.33 (s, 1H), 8.26-8.24 (m, 1H), 8.18-8.17 (m, 1H), 7, 88-7.86 (m, 1H), 7.17 (s, 1H), 7.04-6.98 (m, 2H), 4.83-4.82 (m, 1H), 4.74- 4.72 (m, 1H), 4.59-4.58 (m, 2H), 4.41 (q, J = 6.8 Hz, 2H), 2.66 (s, 3H), 1.63 (d, J = 6.8 Hz, 6H), 1.31 (t, J = 6.8 Hz, 3H).

LC-MS (mass / charge) 421 (MH ⁺ ); t _R = 1.89 (method A).

Example 117 N - [[6- (difluoromethyl) -3-nyridyl] methyl] -5- (2-ethoxy-3-nyridyl) -1-isopropyl-3methylpyrazolo [4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1-isopropyl-3-methyl-1H-nyrazolo [4,3-b] pyridin-7-amine and 6- (difluoromethyl) nicotinaldehyde.

1H NMR (chloroform-d, 400 MHz): δ 8.76 (s, 1H), 8.24 (dd, J = 7.2, 2.0 Hz, 1H), 8.16 (dd, J = 5 , 2, 2.0 Hz, 1H), 7.92 (d, J = 8.0, 1H), 7.68 (d, J = 8.2 Hz, 1H), 7.13 (s, 1H) , 7.01 (dd, J = 7.2, 4.8 Hz, 1H), 6.67 (t, J = 55.2 Hz, 1H), 4.87 - 4.83 (m, 2H), 4.68 (d, J = 5.2 Hz, 2H), 4.35 (q, J = 6.8 Hz, 2H), 2.66 (s, 3H), 1.65 (d, J = 6 , 8 Hz, 6H), 1.24 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 453.1 (MH ⁺ ); tR = 1.92 (method A).

Example 118 5- (2-Ethoxy-3-nyridyl) -1-isopropyl-N - [(3-methoxy-2-nyridyl) methyl] -3-methylpyrazolo [4,3-b] pyridin-7-amine

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prepared using the same procedure as described for example 29, from 5- (2ethoxypyridin-3-yl) -1 -isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridin-7-amine and 3 -methoxypicolinaldehyde.

1H NMR (chloroform-d, 400 MHz): δ 8.33 (dd, J = 2.0, 7.2 Hz, 1H), 8.23 (dd, J = 1.2, 4.8 Hz, 1H ), 8.19 (dd, J = 2.0, 5.2 Hz, 1H), 7.28-7.30 (m, 2H), 7.22-7.24 (m, 1H), 7, 04 (dd, J = 4.8, 7.2 Hz, 1H), 6.96 (brs, 1H), 5.12-5.21 (m, 1H), 4.57 (d, J = 4, 0 Hz, 2H), 4.52 (q, J = 6.8 Hz, 2H), 3.94 (s, 3H), 2.68 (s, 3H), 1.72 (d, J = 6, 4 Hz, 6H), 1.51 (t, 7 = 7.0 Hz, 3H).

LC-MS (mass / charge) 433.1 (MH +); tR = 2.08 (method A).

Example 119 5- (2-Ethoxy-3-pyridyl) -3-methyl-1- [1-methylpropyl] -N- (1H-pyrazol-3-ylmethyl) pyrazolo [4,3-b] pyridine-7- amine, enantiomer 1

prepared using the same procedure as described for example 29, from 1- (sec-butyl) 5- (2-ethoxypyridin-3-yl) -3-methyl-1H-pyrazolo [4,3-b] pyridine-7 -amine, enantiomer 1 and 1H-pyrazole-3carbaldehyde.

1H NMR (chloroform-d, 400 MHz): δ 8.26 (dd, J = 2.0, 7.6 Hz, 1H), 8.18 (dd, J = 2.0, 4.2 Hz, 1H ), 7.60 (d, J = 2.4 Hz, 1H), 7.22 (s, 1H), 7.03 (dd, J = 4.8, 7.2 Hz, 1H), 6.36 (d, J = 2.4 Hz, 1H), 5.29 (br. s, 1H), 4.64-4.60 (m, 1H), 4.57 (d, J = 4.8 Hz, 2H), 4.48 (q, J = 6.8 Hz, 2H), 2.66 (s, 3H), 2.22-2.14 (m, 1H), 1.90-1.85 (m , 1H), l, 61 (d, J = 6.4 Hz, 3H), 1.43 (t, J = 6.8 Hz, 3H), 0.89 (t, J = 7.6 Hz, 3H ).

LC-MS (mass / charge) 406.1 (MH ⁺ ); t _R = 2.25 (method A).

Example 120 5- (2-Ethoxy-3-pyridyl) -3-methyl-1- [1-methylpropyl] -N- (1H-pyrazol-3-ylmethyl) pyrazolo [4,3-b] pyridine-7- amine, enantiomer 2

prepared using the same procedure as described for example 29, from 1- (sec-butyl) 5- (2-ethoxypyridin-3-yl) -3-methyl-1H-pyrazolo [4,3-b] pyridine-7 -amine, enantiomer 2 and 1H-pyrazole-3carbaldehyde.

1H NMR (chloroform-d, 400 MHz): δ 8.26 (dd, J = 2.0, 7.2 Hz, 1H), 8.18 (dd, J = 2.0, 4.2 Hz, 1H ), 7.60 (d, J = 2.4 Hz, 1H), 7.22 (s, 1H), 7.03 (dd, J = 4.8, 7.2 Hz, 1H), 6.36 (d, J = 2.4 Hz, 1H), 5.28 (br. s, 1H), 4.64-4.60 (m, 1H), 4.57 (d, J = 4.8 Hz, 2H), 4.48 (q, J = 6.8 Hz, 2H), 2.66 (s, 3H), 2.22-2.14 (m, 1H), 1.92-1.86 (m , 1H), 1.62 (d, J = 6.8 Hz, 3H), 1.43 (t, J = 6.8 Hz, 3H), 0.89 (t, J = 7.2 Hz, 3H ).

LC-MS (mass / charge) 406.1 (MH ⁺ ); tR = 2.22 (method A).

Example 121 5 - (2-Ethoxy-3-pyridyl) -3-methyl-1- [1-methylpropyl] -N - [(1-methyl-1,2,4-triazol-3yl) methyl] pyrazolo [4 , 3-b] pyridin-7-amine, enantiomer 1

- 130 037544 prepared using the same procedure as described for example 29, from 1- (sec-butyl) 5- (2-ethoxypyridin-3-yl) -3-methyl-1H-pyrazolo [4,3-b] pyridine -7-amine, enantiomer 1 and 1-methyl-1H1,2,4-triazole-3-carbaldehyde.

¹ H NMR (chloroform-d, 400 MHz): δ 8.27 (dd, J = 2.0, 7.2 Hz, 1H), 8.18 (dd, J = 2.0, 5.2 Hz, 1H), 8.05 (s, 1H), 7.20 (s, 1H), 7.03 (dd, J = 4.8, 7.2 Hz, 1H), 5.49 (br. S, 1H ), 4.69-4.65 (m, 1H), 4.57 (d, J = 4.8 Hz, 2H), 4.49 (q, J = 6.8 Hz, 2H), 3.95 (s, 3H), 2.66 (s, 3H), 2.21-2.16 (m, 1H), 1.94-1.91 (m, 1H), 1.64 (d, J = 6 , 4 Hz, 3H), 1.45 (t, J = 7.2 Hz, 3H), 0.93 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 421.1 (MH ⁺ ); tR = 2.26 (method C).

Example 122. 5- (2-Ethoxy-3-pyridyl) -3-methyl-1- [1-methylpropyl] -N - [(1-methyl-1,2,4-triazol-3yl) methyl] pyrazolo [4 , 3-b] pyridin-7-amine, enantiomer 2

prepared using the same procedure as described for example 29, from 1- (sec-butyl) 5- (2-ethoxypyridin-3-yl) -3-methyl-1H-pyrazolo [4,3-b] pyridine-7 -amine, enantiomer 2 and 1-methyl-1H1,2,4-triazole-3-carbaldehyde.

¹ H NMR (chloroform-d, 400 MHz): δ 8.26 (dd, J = 2.0, 7.2 Hz, 1H), 8.18 (dd, J = 2.0, 5.2 Hz, 1H), 8.05 (s, 1H), 7.21 (s, 1H), 7.03 (dd, J = 4.8, 7.2 Hz, 1H), 5.49 (br. S, 1H ), 4.68-4.65 (m, 1H), 4.57 (d, J = 4.8 Hz, 2H), 4.49 (q, J = 6.8 Hz, 2H), 3.95 (s, 3H), 2.65 (s, 3H), 2.21-2.16 (m, 1H), 1.94-1.89 (m, 1H), 1.64 (d, J = 6 , 8 Hz, 3H), 1.45 (t, J = 6.8 Hz, 3H), 0.93 (t, J = 7.6 Hz, 3H).

LC-MS (mass / charge) 421.1 (MH ⁺ ); t _R = 2.29 (method C).

Example 123. 5- (2-Ethoxy-3-pyridyl) -3-methyl-N - [(5-methyl-1,3,4-oxadiazol-2-yl) methyl] -1- [1methylpropyl] pyrazolo [4 , 3-b] pyridin-7-amine, enantiomer 1

obtained using the same procedure as described for example 29, from 1- (sec-butyl) 5- (2-ethoxypyridin-3-yl) -3-methyl-1H-pyrazolo [4,3-b] pyridine-7 -amine, enantiomer 1 and 5-methyl-1,3,4oxadiazole-2-carbaldehyde.

1H NMR (chloroform-d, 400 MHz): δ 8.30-8.28 (m, 1H), 8.21-8.20 (m, 1H), 7.25 (s, 1H), 7.06 -7.01 (m, 1H), 5.28-5.20 (m, 1H), 4.76-4.64 (m, 3H), 4.51 (q, J = 7.2 Hz, 2H ), 2.66 (s, 3H), 2.58 (s, 3H), 2.23-2.18 (m, 1H), 1.94-1.91 (m, 1H), 1.65 ( d, J = 6.4 Hz, 3H), 1.45 (t, J = 6.8 Hz, 3H), 0.91 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 422.1 (MH +); t _R = 2.22 (method C).

Example 124 5- (2-Ethoxy-3-pyridyl) -3-methyl-N - [(5-methyl-1,3,4-oxadiazol-2-yl) methyl] -1- [1methylpropyl] pyrazolo [4 , 3-b] pyridin-7-amine, enantiomer 2

obtained using the same procedure as described for example 29, from 1- (sec-butyl) 5- (2-ethoxypyridin-3-yl) -3-methyl-1H-pyrazolo [4,3-b] pyridine-7 -amine, enantiomer 2 and 5-methyl-1,3,4oxadiazole-2-carbaldehyde.

1H NMR (chloroform-d, 400 MHz): δ 8.30-8.28 (m, 1H), 8.20-8.19 (m, 1H), 7.25 (s, 1H), 7.06 -7.02 (m, 1H), 5.20-5.18 (m, 1H), 4.73-4.71 (m, 2H), 4.63-4.61 (m, 1H), 4 , 51 (q, J = 7.2 Hz, 2H), 2.66 (s, 3H), 2.58 (s,

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3H), 2.23-2.16 (m, 1H), 1.94-1.90 (m, 1H), 1.65 (d, J = 6.4Hz, 3H), 1.44 (t , J = 6.8 Hz, 3H), 0.91 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 422.1 (MH ⁺ ); tR = 2.17 (method C).

Example 125 5- (2-Ethoxy-3-pyridyl) - # - [(5-methoxy-3-pyridyl) methyl] -3-methyl-1- [1-methylpropyl] pyrazolo [4,3-b] pyridine -7-amine, enantiomer 2

prepared using the same procedure as described for example 29, from 1- (sec-butyl) 5- (2-ethoxypyridin-3-yl) -3-methyl-1H-pyrazolo [4,3-b] pyridine-7 -amine, enantiomer 2 and 5 of methoxy nicotinaldehyde.

¹ H NMR (DMSO-d6 400 MHz): δ = 8.21 (s, 1H), 8.16 (d, J = 2.8 Hz, 1H), 8.13 (s, 1H), 8.12 - 8.09 (m, 1H), 7.33-7.32 (m, 1H), 7.05-7.02 (m, 1H), 6.93 (s, 1H), 6.91 (s , 1H), 4.96-4.93 (m, 1H), 4.57-4.56 (m, 2H), 4.254.20 (m, 2H), 3.75 (s, 3H), 2, 44 (s, 3H), 1.98 - 1.74 (m, 2H), 1.48 (d, J = 6.4 Hz, 3H), 1.08 (t, J = 7.0 Hz, 3H ), 0.73 (t, J = 7.6 Hz, 3H).

LC-MS (mass / charge) 447.1 (MH ⁺ ); t _R = 1.62 (method A).

Example 126 5- (2-Ethoxy-3-pyridyl) - # - [(2-methoxy-4-pyridyl) methyl] -3-methyl-1- [1-methylpropyl] pyrazolo [4,3-b] pyridine -7-amine, enantiomer 2

prepared using the same procedure as described for example 29, from 1- (sec-butyl) 5- (2-ethoxypyridin-3-yl) -3-methyl-1H-pyrazolo [4,3-b] pyridine-7 -amine, enantiomer 2 and 2methoxyisonicotinaldehyde.

1H NMR (chloroform-d, 400 MHz): δ = 8.24 (dd, J = 2.0, 7.6 Hz, 1H), 8.17 (d, J = 5.6 Hz, 1H), 8 , 15 (dd, J = 1.6, 4.8 Hz, 1H), 7.07 (s, 1H), 7.00 (dd, J = 5.2, 7.6 Hz, 1H), 6, 91 (d, J = 4.0 Hz, 1H), 6.78 (s, 1H), 4.80 (brs, 1H), 4.55 (d, J = 5.6 Hz, 3H), 4, 35 (q, J = 6.8 Hz, 2H), 3.94 (s, 3H), 2.66 (s, 3H), 2.26 - 2.15 (m, 1H), 1.95 - 1 , 85 (m, 1H), 1.64 (d, J = 6.4 Hz, 3H), 1.25 (t, J = 6.8 Hz, 3H), 0.90 (t, J = 7, 6 Hz, 3H).

LC-MS (mass / charge) 447.1 (MH ⁺ ); t _R = 1.96 (method A).

Example 127 5- (2-Ethoxy-3-pyridyl) -3-methyl-1- [1-methylpropyl] - # - [(2-methyltetrazol-5-yl) methyl] pyrazolo [4,3-b] pyridine -7-amine, enantiomer 2

obtained using the same procedure as described for example 29, from 1- (sec-butyl) 5- (2-ethoxypyridin-3-yl) -3-methyl-1H-pyrazolo [4,3-b] pyridine-7 -amine, enantiomer 2 and 2-methyl-2Htetrazole-5-carbaldehyde.

1H NMR (chloroform-d, 400 MHz): δ 8.28 (dd, J = 7.6, 2.0 Hz, 1H), 8.18 (dd, J = 5.2, 2.0 Hz, 1H ), 7.27 (s, 1H), 7.05-7.02 (m, 1H), 5.31-5.28 (m, 1H), 4.79 (d, J = 5.2 Hz, 2H), 4.67-4.62 (m, 1H), 4.50 (q, J = 6.8 Hz, 2H), 4.39 (s, 3H), 2.67 (s, 3H), 2.24-2.17 (m, 1H), 1.95-1.88 (m, 1H), 1.65 (d, J = 6.8 Hz, 3H), 1.45 (t, J = 7.2 Hz, 3H), 0.92 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 422.1 (MH ⁺ ); tR = 2.03 (method C).

- 132 037544

Example 128 5- (2-Ethoxy-3-pyridyl) -3-methyl-N - [(5-methyl-1,2,4-oxadiazol-3-yl) methyl] -1- [1methylpropyl] pyrazolo [4 , 3-b] pyridin-7-amine, enantiomer 2

prepared using the same procedure as described for example 29, from 1 - (sec-butyl) 5- (2-ethoxypyridin-3-yl) -3-methyl-1H-pyrazolo [4,3-b] pyridine-7 -amine, enantiomer 2 and 5-methyl-1,2,4oxadiazole-3-carbaldehyde.

Ή NMR (chloroform-d, 400 MHz): δ 8.26 (dd, J = 2.0, 7.2 Hz, 1H), 8.18 (dd, J = 2.0, 4.2 Hz, 1H ), 7.24 (s, 1H), 7.03 (dd, J = 4.4, 7.2 Hz, 1H), 5.17 (br. S, 1H), 4.65-4.60 ( m, 3H), 4.50 (q, J = 7.2 Hz, 2H), 2.65 (s, 3H), 2.64 (s, 3H), 2.23-2.16 (m, 1H ), 1.93-1.90 (m, 1H), 1.64 (d, J = 6.4 Hz, 3H), 1.44 (t, J = 6.8 Hz, 3H), 0.92 (t, J = 7.6 Hz, 3H).

LC-MS (mass / charge) 422.1 (MH +); tR = 2.05 (method C).

Example 129 5- (2-Ethoxy-3-pyridyl) -3-methyl-N - [(2-methyloxazol-4-yl) methyl] -1- [1-methylpropyl] pyrazolo [4,3-b] pyridine -7-amine, enantiomer 2

prepared using the same procedure as described for example 29, from 1- (sec-butyl) 5- (2-ethoxypyridin-3-yl) -3-methyl-1H-pyrazolo [4,3-b] pyridine-7 -amine, enantiomer 2 and 2methyloxazole-4-carbaldehyde.

¹ H NMR (chloroform-d, 400 MHz): δ = 8.27 (dd, J = 2.0, 7.2 Hz, 1H), 8.18 (dd, J = 2.0, 5.2 Hz , 1H), 7.54 (s, 1H), 7.18 (s, 1H), 7.03 (dd, J = 4.8, 7.2 Hz, 1H), 5.11 - 4.91 ( m, 1H), 4.61 - 4.55 (m, 1H), 4.48 (q, J = 7.2 Hz, 2H), 4.40 (d, J = 4.8 Hz, 2H), 2.65 (s, 3H), 2.49 (s, 3H), 2.21 - 2.14 (m, 1H), 1.92 - 1.85 (m, 1H), 1.63 (s, 3H), 1.40 (t, J = 7.2 Hz, 3H), 0.89 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 421.1 (MH +); tR = 1.9 (method A).

Example 130 5- (2-Ethoxy-3-pyridyl) -N- (1 H-imidazol-4-ylmethyl) -3 -methyl-1- [1-methylpropyl] pyrazolo [4,3-b] pyridine-7 -amine, enantiomer 2

prepared using the same procedure as described for example 29, from 1- (sec-butyl) 5- (2-ethoxypyridin-3-yl) -3-methyl-1H-pyrazolo [4,3-b] pyridine-7 -amine, enantiomer 2 and 1H-imidazole-4carbaldehyde.

1H NMR (chloroform-d, 400 MHz): δ = 8.25 (dd, J = 2.0, 7.2 Hz, 1H), 8.17 (dd, J = 2.0, 4.8 Hz, 1H), 7.67 (d, J = 1.2 Hz, 1H), 7.21 (s, 1H), 7.03 (s, 1H), 7.02-7.00 (m, 1H), 5.57 - 5.08 (m, 1H), 4.63 - 4.60 (m, 1H), 4.504.51 (m, 4H), 2.64 (s, 3H), 2.18-2, 12 (m, 1H), 1.90 - 1.85 (m, 1H), 1.61 (d, J = 6.4 Hz, 3H), 1.41 (t, J = 7.2 Hz, 3H ), 0.87 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 406.1 (MH +); tR = 1.35 (method A).

Example 131 5- (2-Ethoxy-3-pyridyl) -3-methyl-1- [1-methylpropyl] -N - [(5-methyl-1H-pyrazol-3yl) methyl] pyrazolo [4,3-b ] pyridin-7-amine, enantiomer 2

- 133 037544

prepared using the same procedure as described for example 29, from 1- (sec-butyl) 5- (2-ethoxypyridin-3-yl) -3-methyl-1H-pyrazolo [4,3-b] pyridine-7 -amine, enantiomer 2 and 5-methyl-1Hpyrazole-3-carbaldehyde.

1H NMR (chloroform-d, 400 MHz): δ = 8.27 (dd, J = 2.0, 7.2 Hz, 1H), 8.18 (dd, J = 2.0, 4.8 Hz, 1H), 7.20 (s, 1H), 7.04-7.01 (m, 1H), 6.08 (s, 1H), 5.28 (brs, 1H), 4.61-4.58 (m, 1H), 4.51 - 4.46 (m, 4H), 2.65 (s, 3H), 2.35 (s, 3H), 2.21 - 2.14 (m, 1H), 1.91 - 1.85 (m, 1H), 1.62 (d, J = 6.8 Hz, 3H), 1.43 (t, J = 6.8 Hz, 3H), 0.89 (t , J = 7.6 Hz, 3H).

LC-MS (mass / charge) 420.1 (MH +); tR = 1.85 (method A).

Example 132 5- (2-Ethoxy-3-pyridyl) -3-methyl-N - [(1-methylimidazol-4-yl) methyl] -1- [1-methylpropyl] pyrazolo [4,3-b] pyridine -7-amine, enantiomer 2

obtained using the same procedure as described for example 29, from 1- (sec-butyl) 5- (2-ethoxypyridin-3-yl) -3-methyl-1H-pyrazolo [4,3-b] pyridine-7 -amine, enantiomer 2 and 1-methyl-Shimidazole-4-carbaldehyde.

1H NMR (chloroform-d, 400 MHz): δ = 8.28 (dd, J = 2.0, 7.6 Hz, 1H), 8.17 (dd, J = 2.0, 4.8 Hz, 1H), 7.45 (s, 1H), 7.20 (s, 1H), 7.04-7.01 (m, 1H), 6.88 (s, 1H), 5.25 (brs, 1H ), 4.61 - 4.58 (m, 1H), 4.48 (q, J = 6.8 Hz, 2H), 4.42 (d, J = 4.8 Hz, 2H), 3.70 (s, 3H), 2.65 (s, 3H), 2.18-2.13 (m, 1H), 1.89-1.85 (m, 1H), 1.60 (d, J = 6 , 8 Hz, 3H), 1.42 (t, J = 6.8 Hz, 3H), 0.88 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 420.1 (MH +); tR = 1.38 (method A).

Example 133. 5- (2-Ethoxy-3-pyridyl) -3-methyl-N [(2-methyloxazol-5-yl) methyl] -1- [1-methylpropyl] pyrazolo [4,3-b] pyridine- 7-amine, enantiomer 2

prepared using the same procedure as described for example 29, from 1- (sec-butyl) 5- (2-ethoxypyridin-3-yl) -3-methyl-1H-pyrazolo [4,3-b] pyridine-7 -amine, enantiomer 2 and 2methyloxazole-5-carbaldehyde.

¹ H NMR (chloroform-d, 400 MHz): δ = 8.27 (dd, J = 2.0, 7.6 Hz, 1H), 8.18 (dd, J = 2.0, 4.8 Hz , 1H), 7.25 (s, 1H), 7.03 (dd, J = 4.8, 7.6 Hz, 1H), 6.94 (s, 1H), 4.62 (brd, J = 4.8 Hz, 1H), 4.55 - 4.46 (m, 5H), 2.65 (s, 3H), 2.47 (s, 3H), 2.21 - 2.13 (m, 1H ), 1.91 - 1.84 (m, 1H), 1.62 (d, J = 6.8 Hz, 3H), 1.41 (t, J = 6.8 Hz, 3H), 0.87 (t, J = 7.6 Hz, 3H).

LC-MS (mass / charge) 421.1 (MH +); tR = 1.81 (method A).

Example 134. 3-Methyl-1- [1-methylpropyl] -N - [(1-methyl-1,2,4-triazol-3-yl) methyl] -5 - (2-propoxy-3 pyridyl) pyrazolo [ 4,3-b] pyridin-7-amine, enantiomer 2

- 134 037544

prepared using the same procedure as described for example 29, from 1- (sec-butyl) 5- (2-ethoxypyridin-3-yl) -3-methyl-1H-pyrazolo [4,3-b] pyridine-7 -amine, enantiomer 2 and 1-methyl-III-1,2,4-triazole-3-carbaldehyde.

1H NMR (chloroform-d, 400 MHz): δ 8.27-8.25 (m, 1H), 8.19-8.17 (m, 1H), 8.06 (s, 1H), 7.19 (s, 1H), 7.04-7.01 (m, 1H), 5.50-5.48 (m, 1H), 4.71-4.66 (m, 1H), 4.56 (d , J = 2.2 Hz, 2H), 4.39 (t, J = 6.8 Hz, 2H), 3.96 (s, 3H), 2.66 (s, 3H), 2.24-2 , 18 (m, 1H), 1.91-1.83 (m, 3H), 1.65 (d, J = 3.2 Hz, 3H), 1.06 (t, J = 7.2 Hz, 3H), 0.94 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 435.1 (MH ⁺ ); tR = 2.05 (method C).

Example 135. 3-Methyl-1- [1-methylpropyl] -5- (2-propoxy-3-pyridyl) -N- (1H-pyrazol-3-ylmethyl) pyrazolo [4,3-L] pyridine-7- amine, enantiomer 2 /

Ν. .N. J

JXX> d ^ NH

HN - obtained using the same procedure as described for example 29, from 1- (sec-butyl) 5- (2-ethoxypyridin-3-yl) -3-methyl-1H-pyrazolo [4,3-b] pyridine -7-amine, enantiomer 2, and 1H-pyrazole-3carbaldehyde.

¹ H NMR (chloroform-d, 400 MHz): δ 12.66 (s, 1H), 8.16-8.11 (m, 2H), 7.57 (s, 1H), 7.10-7, 06 (m, 2H), 6.71 (t, J = 6.0 Hz, 1H), 6.15-6.14 (m, 1H), 4.93-4.91 (m, 1H), 4 , 50 (d, J = 5.6 Hz, 2H), 4.26 (t, J = 6.8 Hz, 2H), 2.45 (s, 3H), 2.00-1.92 (m, 1H), 1.76-1.67 (m, 3H), 1.47 (d, J = 6.4 Hz, 3H), 0.94 (t, J = 7.2 Hz, 3H), 0, 73 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 420.1 (MH ⁺ ); tR = 2.1 (method C).

Example 136 5- (2-Ethoxy-3-pyridyl) -1- [1-methylpropyl] -N- (1H-pyrazol-3-ylmethyl) pyrazolo [4.3b] pyridin-7-amine, enantiomer 1

obtained using the same procedure as described for example 29, from 1 - (sec-butyl) 5- (2-ethoxypyridin-3-yl) -1H-pyrazolo [4,3-b] pyridin-7-amine, enantiomer 1 and 1H-pyrazole-3carbaldehyde.

1H NMR (chloroform-d, 400 MHz): δ 8.24-8.19 (m, 3H), 7.62 (d, J = 2.0 Hz, 1H), 7.23 (s, 1H), 7.04-7.01 (m, 1H), 6.37 (d, J = 2.4 Hz, 1H), 5.45 (s, 1H), 4.71-4.67 (m, 1H) , 4.59 (d, J = 4.8 Hz, 2H), 4.49 (q, J = 6.8 Hz, 2H), 2.25-2.18 (m, 1H), 1.94- 1.90 (m, 1H), 1.66 (d, J = 6.4 Hz, 3H), 1.44 (t, J = 7.2 Hz, 3H), 0.9 (t, J = 7 , 2 Hz, 3H).

SFC: tR = 4.729 min, ee% = 97.49%. LC-MS (mass / charge) 392 (MH ⁺ ); tR = 2.23 (method A).

Example 137. 5- (2-Ethoxy-3-nyridyl) -1- [1-methylpropyl] -N- (1H-nyrazol-3-ylmethyl) pyrazolo [4.3b] pyridin-7-amine, enantiomer 2

- 135 037544

obtained using the same procedure as described for example 29, from 1- (sec-butyl) 5- (2-ethoxypyridin-3-yl) -1H-pyrazolo [4,3-b] pyridin-7-amine, enantiomer 2 and 1H-pyrazole-3carbaldehyde.

1H NMR (chloroform-d, 400 MHz): δ 8.24-8.18 (m, 3H), 7.61 (d, J = 2.4 Hz, 1H), 7.23 (s, 1H), 7.04-7.01 (m, 1H), 6.37 (d, J = 2.4 Hz, 1H), 5.44 (s, 1H), 4.71-4.67 (m, 1H) , 4.59 (d, J = 4.8 Hz, 2H), 4.49 (q, J = 6.8 Hz, 2H), 2.25-2.18 (m, 1H), 1.96- 1.90 (m, 1H), 1.66 (d, J = 6.8 Hz, 3H), 1.43 (t, J = 7.2 Hz, 3H), 0.9 (t, J = 7 , 2 Hz, 3H).

SFC: tR = 4.453 min, ee% = 94.84%. LC-MS (mass / charge) 392.1 (MH ⁺ ); tR = 2.23 (method A).

Example 138. 5- (2-Ethoxy-3-pyridyl) -N - [(5-methyl-1,3,4-oxadiazol-2-yl) methyl] -1- [1-methylpropyl] pyrazolo [4.3 -b] pyridin-7-amine, enantiomer 1

prepared using the same procedure as described for example 29, from 1- (sec-butyl) 5- (2-ethoxypyridin-3-yl) -1H-pyrazolo [4,3-b] pyridin-7-amine, enantiomer 1 and 5-methyl-1,3,4oxadiazole-2-carbaldehyde.

¹ H NMR (chloroform-d, 400 MHz): δ 8.24-8.20 (m, 3H), 7.25 (s, 1H), 7.03 (dd, J = 4.8, 7.2 Hz, 1H), 5.37 (brs, 1H), 4.73-4.69 (m, 3H), 4.51 (q, J = 7.2 Hz, 2H), 2.58 (s, 3H ), 2.27-2.19 (m, 1H), 1.97-1.93 (m, 1H), 1.68 (d, J = 6.4Hz, 3H), 1.44 (t, J = 7.2 Hz, 3H), 0.92 (t, J = 7.2 Hz, 3H).

SFC-MS: tR = 4.24 min, ee% = 98.70%. LC-MS (mass / charge) 408 (MH ⁺ ); tR = 2.4 (method C).

Example 139. 5- (2-Ethoxy-3-pyridyl) -N - [(5-methyl-1,3,4-oxadiazol-2-yl) methyl] -1- [1-methylpropyl] pyrazolo [4.3 -b] pyridin-7-amine, enantiomer 2

prepared using the same procedure as described for example 29, from 1- (sec-butyl) 5- (2-ethoxypyridin-3-yl) -1H-pyrazolo [4,3-b] pyridin-7-amine, enantiomer 2 and 5-methyl-1,3,4oxadiazole-2-carbaldehyde.

1H NMR (chloroform-d, 400 MHz): δ 8.25-8.20 (m, 3H), 7.25 (s, 1H), 7.03 (dd, J = 4.8, 7.2 Hz , 1H), 5.31 (brs, 1H), 4.73-4.68 (m, 3H), 4.51 (q, J = 7.2 Hz, 2H), 2.59 (s, 3H) , 2.27-2.20 (m, 1H), 1.97-1.94 (m, 1H), 1.68 (d, J = 6.4 Hz, 3H), 1.45 (t, J = 7.2 Hz, 3H), 0.92 (t, J = 7.2 Hz, 3H).

SFC-MS: tR = 3.997 min, ee% = 97.68%. LC-MS (mass / charge) 408.1 (MH ⁺ ); tR = 2.4 (method C).

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Example 140. 5- (2-Ethoxy-3-pyridyl) -1- [1-methylpropyl] -N - [(1-methyl-1,2,4-triazol-3-yl) methyl] pyrazolo [4.3 -B] pyridin-7-amine, enantiomer 1

obtained using the same procedure as described for example 29, from 1- (sec-butyl) 5- (2-ethoxypyridin-3-yl) -1H-pyrazolo [4,3-b] pyridin-7-amine, enantiomer 1 and 1-methyl-1H-1,2,4triazole-3-carbaldehyde.

¹ H NMR (chloroform-d, 400 MHz): δ 8.25-8.19 (m, 3H), 8.07 (s, 1H), 7.23 (s, 1H), 7.03 (dd, J = 4.8, 7.2 Hz, 1H), 5.61 (brs, 1H), 4.79-4.74 (m, 1H), 4.59 (d, J = 4.8 Hz, 2H ), 4.50 (q, J = 7.2 Hz, 2H), 3.96 (s, 3H), 2.272.22 (m, 1H), 1.98-1.93 (m, 1H), 1 , 68 (d, J = 6.8 Hz, 3H), 1.46 (t, J = 7.2 Hz, 3H), 0.95 (t, J = 7.2 Hz, 3H).

SFC-MS: tR = 4.97 min, ee% = 98.60%. LC-MS (mass / charge) 407 (MH ⁺ ); tR = 2.44 (method C).

Example 141 5- (2-Ethoxy-3-pyridyl) -1- [1-methylpropyl] -N - [(1-methyl-1,2,4-triazol-3-yl) methyl] pyrazolo [4.3 -B] pyridin-7-amine, enantiomer 2

obtained using the same procedure as described for example 29, from 1- (sec-butyl) 5- (2-ethoxypyridin-3-yl) -1H-pyrazolo [4,3-b] pyridin-7-amine, enantiomer 2 and 1-methyl-1H-1,2,4triazole-3-carbaldehyde.

¹ H NMR (chloroform-d, 400 MHz): δ 8.24-8.19 (m, 3H), 8.07 (s, 1H), 7.23 (s, 1H), 7.03 (dd, J = 4.8, 7.2 Hz, 1H), 5.60 (brs, 1H), 4.78-4.73 (m, 1H), 4.59 (d, J = 4.8 Hz, 2H ), 4.50 (q, J = 7.2 Hz, 2H), 3.96 (s, 3H), 2.272.22 (m, 1H), 1.98-1.93 (m, 1H), 1 , 68 (d, J = 6.8 Hz, 3H), 1.46 (t, J = 7.2 Hz, 3H), 0.95 (t, J = 7.2 Hz, 3H).

SFC-MS: tR = 4.66 min, ee% = 96.90%. LC-MS (mass / charge) 407.1 (MH ⁺ ); tR = 2.44 (method C).

Example 142. 1-Isopropyl-3-methyl-N - [(1-methylimidazol-4-yl) methyl] -5- (2-propoxy-3-pyridyl) pyrazolo [4,3-L] pyridin-7-amine

prepared using the same procedure as described for example 29, from 1-isopropyl-3methyl-5- (2-propoxypyridin-3-yl) -1H-pyrazolo [4,3-b] pyridin-7-amine and 1- methyl 1H-imidazole-4carbaldehyde.

¹ H NMR (chloroform-d, 400 MHz): δ 8.28-8.26 (m, 1H), 8.20-8.18 (m, 1H), 7.46 (s, 1H), 7, 18 (s, 1H), 7.05-7.02 (m, 1H), 6.91 (s, 1H), 5.43 (brs, 1H), 4.94-4.90 (m, 1H) , 4.45-4.44 (m, 2H), 4.38 (t, J = 6.8 Hz, 2H), 3.70 (s, 3H), 2.65 (s, 3H), 1, 87-1.78 (m, 2H), 1.62 (d, J = 6.8 Hz, 6H), 1.05 (t, J = 7.6 Hz, 3H).

LC-MS (mass / charge) 420.1 (MH ⁺ ); tR = 1.75 (method C).

- 137 037544

Example 143 1-Isopropyl-3-methyl-5- (2-propoxy-3-pyridyl) -N- (1H-pyrazol-3-ylmethyl) pyrazolo

[4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 29, from 1-isopropyl-3methyl-5- (2-propoxypyridin-3-yl) -1 H-pyrazolo [4,3-b] pyridin-7-amine and 1 H-pyrazole-3-carbaldehyde.

1H NMR (chloroform-d, 400 MHz): δ 8.25-8.23 (m, 1H), 8.19-8.17 (m, 1H), 7.61 (d, J = 1.2Hz , 1H), 7.18 (s, 1H), 7.05-7.01 (m, 1H), 6.36 (d, J = 1.2 Hz, 1H), 5.40 (brs, 1H) , 4.96-4.90 (m, 1H), 4.58 (d, J = 2.4 Hz, 2H), 4.38 (t, J = 7.2 Hz, 2H), 2.65 ( s, 3H), 1.86-1.82 (m, 2H), 1.64 (d, J = 3.2 Hz, 6H), 1.05 (t, J = 7.6 Hz, 3H).

LC-MS (mass / charge) 406.1 (MH +); tR = 1.83 (method A).

Example 144. 5- (2-Ethoxy-3-pyridyl) -3-methyl-1- [1-methylpropyl] -N- (1H-1,2,4-triazol-3-ylmethyl) pyrazolo [4,3- b] pyridin-7-amine, enantiomer 2

prepared using the same procedure as described for example 29, from 1- (sec-butyl) 5- (2-ethoxypyridin-3-yl) -3-methyl-1H-pyrazolo [4,3-b] pyridine-7 -amine, enantiomer 2 and 1 - ((2 (trimethylsilyl) ethoxy) methyl) -1H-1,2,4-triazole-3-carbaldehyde followed by TFA deprotection.

1H NMR (chloroform-d, 400 MHz): δ 11.58 (brs, 1H), 8.25 (d, J = 2.0 Hz, 1H), 8.23-8.17 (m, 2H), 7.19 (s, 1H), 7.01 (dd, J = 4.8, 7.2 Hz, 1H), 5.51 (brs, 1H), 4.69-4.66 (m, 3H) , 4.48 (q, J = 7.2 Hz, 2H), 2.66 (s, 3H), 2.22-2.16 (m, 1H), 1.93-1.89 (m, 1H ), 1.64 (d, J = 6.8 Hz, 3H), 1.42 (t, J = 6.8 Hz, 3H), 0.91 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 407.1 (MH ⁺ ); tR = 1.91 (method C) [a] D ²⁰ -3.40 (c = 1.0, DCM).

Example 145. 1-Isopropyl-3-methyl-N - [(1-methyl-1,2,4-triazol-3-yl) methyl] -5- (2-propoxy-3 pyridyl) pyrazolo [4,3- b] pyridin-7-amine

prepared using the same procedure as described for example 29, from 1-isopropyl-3methyl-5- (2-propoxypyridin-3-yl) -1H-pyrazolo [4,3-b] pyridin-7-amine and carbaldehyde.

1H-1,2,4-triazole-31H NMR (chloroform-d, 400 MHz): δ = 8.26-8.23 (m, 1H), 8.19-8.17 (m, 1H), 8 , 06 (s, lH), 7.18 (s, 1H), 7.04-7.01 (m, 1H), 5.52-5.51 (m, 1H), 5.01-4.95 (m, 1H), 4.57 (d, J = 4.8 Hz, 2H), 4.38 (t, J = 6.8 Hz, 2H), 3.95 (s, 3H), 2.65 (s, 3H), 1.90-1.81 (m, 2H), 1.66 (d, J = 6.4 Hz, 6H), 1.05 (t, J = 7.6 Hz, 3H) ...

LC-MS (mass / charge) 421.1 (MH +); tR = 2.1 (method B).

Example 146. 1-Isopropyl-3-methyl-5- (2-propoxy-3-pyridyl) -N- (1H-1,2,4-triazol-3-ylmethyl) pyrazolo [4,3-b] pyridine- 7-amine

obtained using the same procedure as described for example 29, from 1-isopropyl-3-138 037544 methyl-5- (2-propoxypyridin-3-yl) -1H-purazolo [4,3-b] pyrudin-7- amine and 1 - ((2- (trimethylsilyl) ethoxy) methyl) -1H-1,2,4-triazole-3-carbaldehyde followed by TFA deprotection.

¹ H NMR (chloroform-d, 400 MHz): δ 8.20-8.17 (m, 2H), 8.14 (s, 1H), 7.14 (s, 1H), 7.03 (dd, J = 4.2, 7.6 Hz, 1H), 5.59 (brs, 1H), 5.00-4.94 (m, 1H), 4.64 (s, 2H), 4.36 (t , J = 6.8 Hz, 2H), 2.65 (s, 3H), 1.85-1.76 (m, 2H), 1.65 (d, J = 6.8 Hz, 6H), 1 , 01 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 407.1 (MH +); tR = 1.91 (method C).

Example 147. 1-Isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] -5-thiazol-2-ylpyrazolo [4,3b] pyridin-7-amine

In a solution of 5-bromo-1 -isopropyl-3-methyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) -1 H-pyrazolo [4.3b] pyridin-7-amine (50 mg , 0.14 mmol) in DMF (2 ml), 2- (tributylstannyl) thiazole (103 mg, 0.28 mmol) and Pd (PPh ₃ ) ₄ (16 mg, 0.013 mmol) were added. The mixture was bubbled with N ₂ and heated at 80 ° C for 2 h. The mixture was cooled to room temperature, ethyl acetate (20 ml) and water (10 ml) were added. The organic layer was washed with water (10 ml x 2), brine (10 ml), dried over Na ₂ SO ₄ , filtered and concentrated. The crude material was purified by preparative TLC (SiO ₂ , ethyl acetate) to give 1-isopropyl-3-methyl-N - ((1-methyl-1H-purazol-4-yl) methyl) -5- (thiazol-2-yl ) -1Hpyrazolo [4,3-b] pyridin-7-amine (10 mg).

¹ H NMR (chloroform-d, 400 MHz): δ 7.88 (d, J = 3.2 Hz, 1H), 7.58 (s, 1H), 7.46 (s, 2H), 7.40 (d, J = 3.2 Hz, 1H), 4.75-4.68 (m, 1H), 4.54 (brs, 1H), 4.46 (d, J = 4.8 Hz, 2H) , 3.94 (s, 3H), 2.65 (s, 3H), 1.58 (d, J = 6.8 Hz, 6H).

LC-MS (mass / charge) 368 (MH +); tR = 1.91 (method C).

Example 148 1-Isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] -5- (5-methylthiazol-2-yl) pyrazolo [4,3-b] pyridin-7-amine

obtained using the same procedure as described for example 147, from 5-bromo-1isopropyl-3-methyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) -1H-pyrazolo [4.3 -b] pyridin-7-amine and 5methyl-2- (tributylstannyl) thiazole.

¹ H NMR (600 MHz, DMSO-d ₆ ) δ 7.62 (s, 1H), 7.56 (s, 1H), 7.43 (s, 1H), 7.20 (s, 1H), 6 , 86 (t, J = 5.6 Hz, 1H), 5.16 (m, 1H), 4.41 (d, J = 5.5 Hz, 2H), 3.77 (s, 3H), 2 , 47 (s, 3H), 2.45 (s, 3H), 1.44 (d, J = 6.3 Hz, 6H).

LC-MS (mass / charge) 382.3 (MH +); tR = 0.51 (method D).

Example 149 1-Isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] -5- (4-methylthiazol-2-yl) pyrazolo [4,3-b] pyridin-7-amine

obtained using the same procedure as described for example 147, from 5-bromo-1isopropyl-3-methyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) -1H-pyrazolo [4.3 -b] puridine-7-amine and 4-methyl2- (tributylstannyl) thiazole.

¹ H NMR (500 MHz, chloroform-d) δ 7.60 (s, 1H), 7.47 (s, 1H), 7.45 (s, 1H), 6.96 (s, 1H), 4, 73 (m, 1H),

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4.53 (s, 1H), 4.49 (s, 2H), 3.96 (s, 3H), 2.65 (s, 3H), 2.55 (s, 3H), 1.59 (d , J = 6.4 Hz, 6H).

LC-MS (mass / charge) 382.4 (MH +); tR = 0.51 (method D).

Example 150. 3- [1-Isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3-b] pyridin-5-yl] -5-methyloxazolidin-2-one

A mixture of 5-bromo-1-isopropyl-3-methyl-X - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3b] pyridin-7-amine (20 mg, 0.06 mmol), 5 -methyloxazolidin-2-one (7 mg, 0.07 mmol), Pd ₂ (dba) ₃ (5 mg, 0.006 mmol), Xantphos (10 mg, 0.02 mmol), CS ₂ CO ₃ (25 mg, 0 , 08 mmol) in dioxane (2 ml) at 85 ° C for 12 h. The mixture was concentrated to give a residue. The residue was purified by preparative HPLC to give 3- [1-isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3b] pyridin-5-yl] -5-methyloxazolidine- 2-one (15 mg).

¹ H NMR (chloroform-d, 400 MHz): δ = 7.59 (s, 1H), 7.55 (s, 2H), 4.80 (brd, J = 6.8 Hz, 1H), 4, 74 - 4.64 (m, 1H), 4.63 - 4.56 (m, 1H), 4.47 (dd, J = 8.4, 10.4 Hz, 1H), 4.39 (d, J = 5.0 Hz, 2H), 3.98 - 3.93 (m, 1H), 3.92 (s, 3H), 2.51 (s, 3H), 1.58 (s, 3H), 1.55 (d, J = 6.3 Hz, 6H).

LC-MS (mass / charge) 384.1 (MH +); tR = 1.9 (method C).

Example 151 3- [1-Isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4.3b] pyridin-5-yl] oxazolidin-2-one

obtained using the same procedure as described for example 150, from 5-bromo-1isopropyl-3-methyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) -1H-pyrazolo [4.3 -b] pyridin-7-amine and oxazolidin-2-one.

¹ H NMR (600 MHz, DMSO-d6) δ 7.65 (s, 1H), 7.45 (s, 1H), 7.41 (s, 1H), 6.78 (t, J = 5.7 Hz, 1H), 5.09 (m, 1H), 4.41 (m, 2H), 4.28 (d, J = 5.6 Hz, 2H), 4.19 (m, 2H), 3, 77 (s, 3H), 2.36 (s, 3H), 1.40 (d, J = 6.3Hz, 6H).

LC-MS (mass / charge) 370.2 (MH +); tR = 1.51 (method J).

Example 152 1- [1-Isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3-b] pyridin-5-yl] azetidin-2-one

obtained using the same procedure as described for example 150, from 5-bromo-1isopropyl-3-methyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) -1H-pyrazolo [4.3 -b] pyridin-7-amine and azetidin-2-one.

1H NMR (600 MHz, DMSO-d6) δ 7.64 (s, 1H), 7.45 (s, 1H), 6.94 (s, 1H), 6.81 (t, J = 5.6 Hz , 1H), 5.07 (m, 1H), 4.27 (d, J = 5.5 Hz, 2H), 3.77 (s, 3H), 3.66 (s, 2H), 3.04 (t, J = 4.5 Hz, 2H), 2.35 (s, 3H), 1.40 (d, J = 6.3 Hz, 6H).

LC-MS (mass / charge) 354.2 (MH +); tR = 1.46 (method K).

Example 153. 1-tert-Butyl-3- [1-isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3-b] pyridin-5-yl] imidazolidine- 2nd

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obtained using the same procedure as described for example 150, from 5-bromo-1isopropyl-3-methyl - # - ((1-methyl-1H-pyrαzol-4-yl) methyl) -1H-pyrαzolo [4,3 -B] pyridin-7-amine and 1- (tert-butyl) imidazolidin-2-one.

1H NMR (500 MHz, chloroform-d) δ 7.71 (s, 1H), 7.61 (s, 1H), 7.48 (s, 1H), 6.52 (t, J = 5.6 Hz , 1H), 5.104.94 (m, 1H), 4.25 (d J = 5.6 Hz, 2H), 3.91-3.82 (m, 2H), 3.77 (s, 3H), 3.44 (t, J = 7.9 Hz, 2H), 2.34 (s, 3H), 1.481.23 (m, 15H).

LC-MS (mass / charge) 425.2 (MH +); tR = 1.64 (method K).

Example 154 1- [1-Isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3-L] pyridin-5-yl] pyrrolidin-2-one

obtained using the same procedure as described for example 150, from 5-bromo-1isopropyl-3-methyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) -1H-pyrazolo [4.3 -B] pyridin-7-amine and pyrrolidin-2-one.

¹ H NMR (600 MHz, DMSO-d6) δ 7.68 (s, 1H), 7.67 (s, 1H), 7.47 (s, 1H), 6.70 (t, J = 5.7 Hz, 1H), 5.08 (m, 1H), 4.26 (d, J = 5.6 Hz, 2H), 4.06 - 3.96 (m, 2H), 3.77 (s, 3H ), 2.56 (t, J = 8.0 Hz, 2H), 2.36 (s, 3H), 2.06 - 1.94 (m, 2H), 1.39 (d, J = 6, 3 Hz, 6H).

LC-MS (mass / charge) 368.2 (MH ⁺ ); tR = 1.39 (method K).

Example

155. 3- [1-Isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4.3

b] pyridin-5-yl] -4-methyloxazolidin-2-one

obtained using the same procedure as described for example 150, from 5-bromo-1isopropyl-3-methyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) -1H-pyrazolo [4.3 -B] pyridin-7-amine and 4methyloxazolidin-2-one.

1H NMR (chloroform-d, 400 MHz): δ = 7.55 (d, J = 2.4 Hz, 2H), 7.45 (s, 1H), 5.14 -5.03 (m, 1H) , 4.73 4.64 (m, 1H), 4.62 - 4.51 (m, 2H), 4.38 (dd, J = 5.0, 9.6 Hz, 2H), 4.07 ( dd, J = 4.5, 8.3 Hz, 1H), 3.92 (s, 3H), 2.51 (s, 3H), 1.56 (dd, J = 1.7, 6.5 Hz , 6H), 1.52 (d, J = 6.2 Hz, 3H).

LC-MS (mass / charge) 384.1 (MH ⁺ ); tR = 2 (method B).

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Example 156 4-Ethyl-3- [1-isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4.3b] pyridin-5-yl] oxazolidin-2-one

obtained using the same procedure as described for example 150, from 5-bromo-1isopropyl-3-methyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) -1H-pyrazolo [4.3 -b] pyridin-7-amine and 4ethyloxazolidin-2-one.

Ή NMR (chloroform-d, 400 MHz): δ 7.55 (d, J = 2.0 Hz, 2H), 7.46 (s, 1H), 5.1 - 4.98 (m, 1H), 4.70-4.66 (m, 1H), 4.57-4.55 (m, 1H), 4.51 (t, J = 8.8 Hz, 1H), 4.40-4.36 ( m, 2H), 4.21 - 4.18 (m, 1H), 3.92 (s, 3H), 2.50 (s, 3H), 2.02 - 1.79 (m, 2H), 1 , 55 (d, J = 4.8 Hz, 6H), 0.93 (t, J = 7.6 Hz, 3H).

LC-MS (mass / charge) 398.1 (MH +); tR = 1.99 (method C).

Example 157 N - [[5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methylpyrazolo [4,3-b] pyridin-7-yl] methyl] 5-methoxypyridin-3-amine

A mixture of N - [(5-bromo-1-isopropyl-3-methyl-pyrazolo [4,3-b] pyridin-7-yl) methyl] -5methoxypyridin-3-amine (69 mg, 0.18 mmol) was degassed, (2-ethoxy-3-pyridyl) boronic acid (59 mg, 0.35 mmol), Pd (dppf) Cl ₂ (26 mg, 0.03 mmol), CS2CO3 (115 mg, 0.35 mmol) in dioxane ( 3 ml) and water (1 ml) and purged 3 times with N2 and then the mixture was stirred at 100 ° C for 2 h under N2 atmosphere. Water (20 ml) was added and the mixture was extracted with ethyl acetate (30 ml x 3). The combined organic layers were washed with brine (20 ml), dried over Na ₂ SO ₄ and concentrated. The crude mixture was purified by preparative HPLC to give N - [[5- (2-ethoxy-3-pyridyl) -1-isopropyl3-methylpyrazolo [4,3-b] pyridin-7-yl] methyl] -5-methoxypyridine- 3-amine (48.16 mg).

¹ H NMR (chloroform-d, 400 MHz): δ 8.27 (dd, J = 2.0, 7.6 Hz, 1H), 8.18 (dd, J = 2.0, 4.8 Hz, 1H), 8.00 (s, 1H), 7.81-7.80 (m, 2H), 7.05-7.02 (m, 1H), 6.49-6.48 (m, 1H) , 4.90-4.87 (m, 1H), 4.74 (d, J = 5.6 Hz, 2H), 4.40 (q, J = 7.2 Hz, 2H), 4.18- 4.16 (m, 1H), 3.83 (s, 3H), 2.72 (s, 3H), 1.58 (d, J = 7.2 Hz, 6H). 1.27 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 433.1 (MH +); tR = 1.88 (method A).

Example 158 N - [[5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methylpyrazolo [4,3-b] pyridin-7-yl] methyl] 1 -methyl-1,2,4 -triazole-3-amine

obtained using the same procedure as described for example 157, from N - [(5-6pom-1isopropyl-3-methylpyrazolo [4,3-b] pyridin-7-yl) methyl] -1-methyl-1,2 , 4-triazol-3-amine and (2-ethoxy-3-pyridyl) boronic acid.

1H NMR (chloroform-d, 400 MHz): δ 8.24 (dd, J = 2.0, 7.6 Hz, 1H), 8.18 (dd, J = 2.0, 5.2 Hz, 1H ), 7.99 (s, 1H), 7.67 (s, 1H), 7.03 (dd, J = 4.8, 7.2 Hz, 1H), 5.01-4.98 (m, 1H), 4.91 (d, J = 6.0 Hz, 2H), 4.56 (t, J = 6.0 Hz, 1H), 4.45 (q, J = 7.2 Hz, 2H) , 3.77 (s, 3H), 2.70 (s, 3H), 1.58 (d, J = 6.4 Hz, 6H), 1.34 (t, J = 7.2 Hz, 3H) ...

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LC-MS (mass / charge) 407.1 (MH +); tR = 2.17 (method C).

Example 159 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-7- [2- (5-methoxy-3-pyridyl) ethyl] -3-methylpyrazolo [4,3F] pyridine

A mixture of 5- (2-ethoxypyridin-3-yl) -7-ethynyl-1-isopropyl-3-methyl-1 H-pyrazolo [4,3b] pyridine (0.05 g, 0.6 mmol), 3- iodine-5-methoxypyridine (37 mg, 0.16 mmol), CuI (3 mg, 0.016 mmol), Pd (dppf) Cl ₂ (11 mg, 0.016 mmol) and Et ₃ N (79 mg, 0.78 mmol) in dioxane (3 ml) at 100 ° C under N ₂ for 4 hours. The mixture was treated with 4 more batches (each using the same procedure and the same amount of starting material). The mixture was concentrated and extracted with ethyl acetate (20 ml x 2), dried over Na ₂ SO ₄ and concentrated to give a residue. The mixture was purified by column chromatography (SiO ₂ , petroleum ether / ethyl acetate = 10/1 about 1/1) to give 5- (2ethoxypyridin-3-yl) -1-isopropyl-7 - ((5-methoxypyridine-3- yl) ethynyl) -3-methyl-1H-pyrazolo [4,3-b] pyridine (0.025 g).

A mixture of 5- (2-ethoxypyridin-3-yl) -1-isopropyl-7 - ((5-methoxypyridin-3-yl) ethynyl) -3methyl-1H-pyrazolo [4,3-b] pyridine (0.02 g, 0.047 mmol), Pd / C (0.005 g, 0.047 mmol, 10%), H2 (15 psi) in ethyl acetate (2 ml) at room temperature for 0.25 h. The mixture was filtered and the filtrate was concentrated with the receipt of the remainder. The residue was purified by preparative HPLC to give 5- (2-ethoxypyridin-3-yl) -1 -isopropyl-7- (2- (5-methoxypyridin-3-yl) ethyl) -3-methyl-1Hpyrazolo [4.3 -b] pyridine (7 mg).

¹ H NMR (chloroform-d, 400 MHz): δ = 8.27 - 8.24 (m, 1H), 8.24 - 8.14 (m, 3H), 7.79 (s, 1H), 7 , 05 (dd, J = 4.8, 7.2 Hz, 1H), 6.96 (t, J = 2.0 Hz, 1H), 4.98 - 4.79 (m, 1H), 4, 48 (q, J = 7.2 Hz, 2H), 3.81 (s, 3H), 3.43 - 3.29 (m, 2H), 3.18 - 3.01 (m, 2H), 2 , 70 (s, 3H), 1.59 (d, J = 6.8 Hz, 6H), 1.41 (t, J = 6.8 Hz, 3H).

LC-MS (mass / charge) 432.1 (MH +); tR = 1.97 (method A).

Example 160. 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-7- [2- (1-methyl-1,2,4-triazol-3-yl) ethyl] pyrazolo [4 , 3-b] pyridine

prepared using the same procedure as described for example 159, from 5- (2ethoxypyridin-3-yl) -7-ethynyl-1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine and added 3 bromine -1-methyl-III-1,2,4-triazole.

1H NMR (chloroform-d, 400 MHz): δ 8.23 (dd, J = 2.0, 7.6 Hz, 1H), 8.19 (dd, J = 1.6, 4.4 Hz, 1H ), 7.99 (s, 1H), 7.81 (s, 1H), 7.04 (dd, J = 4.2, 7.6 Hz, 1H), 5.11-5.04 (m, 1H), 4.48 (q, J = 7.2 Hz, 2H), 3.90 (s, 3H), 3.553.51 (m, 2H), 3.23-3.18 (m, 2H), 2.70 (s, 3H), 1.61 (d, J = 6.8 Hz, 6H), 1.43 (t, J = 6.8 Hz, 3H).

LC-MS (mass / charge) 406.1 (MH '); tR = 2.3 (method C).

Example 161 5- (2-Ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-N - [(2-methyl-1,2,4-triazol-3 yl) methyl] pyrazolo [4.3 - b] pyridin-7-amine.

Example 162 5 - (2-Ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-N - [(4-methyl-1,2,4-triazol-3 yl) methyl] pyrazolo [4.3 - b] pyridin-7-amine.

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N = / N = / N = /

CS2CO3 (16.6 mg, 0.051 mmol) and iodomethane (510 μL, 0.051 mmol, 100 mM, THF) were added to N ((4H-1,2,4-triazol-3-yl) methyl) -5- (2 -ethoxypyridin-3-yl) -1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine-7-amine (20 mg, 0.051 mmol) in THF (1.3 ml). The reaction mixture was stirred in a closed vessel at 80 ° C for 50 minutes. The reaction mixture was concentrated in vacuo. Added water. The mixture was extracted with ethyl acetate. The organic phase was washed with brine, dried over MgSO ₄ , filtered and concentrated in vacuo. The residue was purified by SFC to give 5- (2ethoxypyridin-3-yl) -1-isopropyl-3-methyl-N - ((1-methyl-1H-1,2,4-triazol-5-yl) methyl) - 1H-pyrazolo [4,3b] pyridin-7-amine (2 mg) and 5- (2-ethoxypyridin-3-yl) -1-isopropyl-3-methyl-N - ((4-methyl-4H-1, 2,4triazol-3-yl) methyl) -1H-pyrazolo [4,3-b] pyridin-7-amine (1 mg).

Example 161 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-N - [(2-methyl-1,2,4-triazol-3 yl) methyl] pyrazolo [4,3- b] pyridin-7-amine:

¹ H NMR (600 MHz, chloroform-d) δ 8.28 (dt, J = 7.3, 1.4 Hz, 1H), 8.19 (dd, J = 4.9, 1.9 Hz, 1H ), 7.92 (s, 1H), 7.17 (s, 1H), 7.05 (dd, J = 7.3, 4.9 Hz, 1H), 5.72 (s, 1H), 4 , 98 (hept, J = 6.6 Hz, 1H), 4.56 (d, J = 4.1 Hz, 2H), 4.49 (q, J = 7.0 Hz, 2H), 3.95 (s, 3H), 2.66 (s, 3H), 1.66 (d, J = 6.5 Hz, 6H), 1.44 (t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 407.4 (MH +); tR = 0.51 (method D).

Example 162 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(4-methyl-1,2,4-triazol-3yl) methyl] pyrazolo [4,3-b ] pyridin-7-amine:

1H NMR (600 MHz, DMSO-d6) δ 8.43 (s, 1H), 8.19 (dd, J = 4.9, 1.9 Hz, 1H), 8.12 (dd, J = 7, 3, 2.0 Hz, 1H), 7.32 (s, 1H), 7.09 (dd, J = 7.4, 4.8 Hz, 1H), 6.80 (t, J = 5.2 Hz, 1H), 5.17 (hept, J = 6.8 Hz, 1H), 4.67 (d, J = 5.0 Hz, 2H), 4.42 (q, J = 7.0 Hz, 2H), 3.71 (s, 3H), 2.46 (s, 3H), 1.45 (d, J = 6.3 Hz, 6H), 1.36 (t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 407.4 (MH +); tR = 0.49 (method D).

Example 163 5- (2-Ethoxy-3-pyridyl) -3 -methyl-N - [(1-methyl-1,2,4-triazol-3-yl) methyl] -1 - (oxetan-3 yl) pyrazolo [4,3-b] pyridin-7-amine

A suspension of 5- (2-ethoxypyridin-3-yl) -3-methyl-N - ((1-methyl-1H-1,2,4-triazol-3-yl) methyl) 1H-pyrazolo [4,3- b] pyridin-7-amine (80 mg, 0.22 mmol, prepared using the same procedure as described for example 29, from 5- (2-ethoxypyridin-3-yl) -3-methyl-1H-pyrazolo [ 4,3-b] pyridine-7amine and 1-methyl-1,2,4-triazole-3-carbaldehyde), 3-iodoxetane (81 mg, 0.44 mmol) and t-BuOK (215 mg, 1.91 mmol) in DMF (2 ml) to 120 ° C for 34 h. The reaction mixture was cooled to room temperature and concentrated in vacuo. The residue was purified twice by preparative HPLC to give 5- (2-ethoxy-3-pyridyl) -3-methyl-N - [(1-methyl-1,2,4-triazol-3-yl) methyl] -1- (oxetane-3yl) pyrazolo [4,3-b] pyridin-7-amine (8 mg).

1H NMR (chloroform-d, 400 MHz) δ 8.28 (dd, J = 2.2, 7.4 Hz, 1H), 8.19 (dd, J = 2.0, 4.8 Hz, 1H) , 8.06 (s, 1H), 7.26 (s, 1H), 7.03 (dd, J = 4.8, 7.4 Hz, 1H), 5.97-5.93 (m, 1H ), 5.34 (t, J = 6.4 Hz, 2H), 5.19 (t, J = 7.2 Hz, 2H), 4.57 (d, J = 5.2 Hz, 2H), 4.49 (q, J = 6.8 Hz, 2H), 3.96 (s, 3H), 2.67 (s, 3H), 1.44 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 421.1 (MH +); tR = 2.04 (method B).

Example 164 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylsulfanyl] pyrazolo [4,3-b] pyridine

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KOtBu (6.9 mg, 0.06 mmol) was added to a solution of 6-methylheptyl-3 - ((5- (2-ethoxypyridin-3-yl) -1isopropyl-3-methyl-1H-pyrazolo [4,3 -b ] pyridin-7-yl) thio) propanoate (21 mg, 0.04 mmol) in DMF (0.59 ml) at RT. The resulting mixture was stirred at rt. over 50 min, after which 4- (chloromethyl) -1-methyl-1H-pyrazole (13.4 mg, 0.06 mmol) was added in one portion. After stirring at rt. over 6 hours the mixture was cooled to ice bath temperature, quenched with a few drops of water and stirred without a cooling bath for 5 minutes. Partitioned between ethyl acetate (40 ml) and water (2x15 ml). Org. the layer was further washed with brine (10 ml). United org. the layers were dried (Na ₂ SO ₄ ) and concentrated. The crude material was purified by flash chromatography using heptane: ethyl acetate, 1: 0 to 0: 1, to give 5- (2-ethoxypyridin-3-yl) -1isopropyl-3-methyl-7 - (((1-methyl- 1H-pyrazol-4-yl) methyl) thio) -1H-pyrazolo [4,3-b] pyridine (8 mg).

Ή NMR (DMSO-d6 600 MHz): δ 8.28 - 8.22 (m, 2H), 7.94 (s, 1H), 7.76 (s, 1H), 7.47 (s, 1H) , 7.16 (dd, J = 7.3, 4.9 Hz, 1H), 5.33 (hept, J = 6.5 Hz, 1H), 4.44 (q, J = 7.0 Hz, 2H), 4.39 (s, 2H), 3.79 (s, 3H), 2.54 (s, 3H), 1.47 (d, J = 6.5 Hz, 6H), 1.34 ( t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 423.6 (MH ⁺ ); tR = 0.76 (method D).

Example 165. N - [[1 - (difluoromethyl) pyrazol-4-yl] methyl] -5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methylpyrazolo [4,3-b] pyridine-7- amine

In a solution of N - ((1- (difluoromethyl) -1 N-pyrazol-4-yl) methyl) -5- (2-ethoxypyridin-3-yl) -1-isopropyl-N (4-methoxybenzyl) -3-methyl -1H-pyrazolo [4,3-b] pyridin-7-amine (15 mg, 0.027 mmol) in DCM (0.5 ml) was added trifluoroacetic acid (0.5 ml). The mixture was stirred at room temperature for 1 h. Water (3 ml) was added and the mixture was poured into saturated aqueous NaHCO ₃ solution. The mixture was extracted with ethyl acetate (5 ml x 3). The combined organic layers were washed with brine (5 ml), dried over Na ₂ SO ₄ and concentrated. The crude mixture was purified by flash chromatography with heptane: ethyl acetate = 1: 0 to 0: 1 to give N - ((1- (difluoromethyl) -1Hpyrazol-4-yl) methyl) -5- (2-ethoxypyridine-3 -yl) -1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine-7amine (11 mg, 0.025 mmol, 93% yield).

Ή NMR (600 MHz, chloroform-d) δ 8.26 (dd, J = 7.4, 2.0 Hz, 1H), 8.17 (dd, J = 4.9, 2.0 Hz, 1H) , 7.84 (d, J = 2.7 Hz, 1H), 7.20 (s, 1H), 7.17 (t, J = 60.7 Hz, 1H), 7.02 (dd, J = 7.3, 4.9 Hz, 1H), 6.49 (d, J = 2.7 Hz, 1h), 5.24 (s, 1H), 4.91 (hept, J = 6.6 Hz, 1H), 4.57 (d, J = 4.8 Hz, 2H), 4.47 (q, J = 7.0 Hz, 2H), 2.65 (s, 3H), 1.65 (d, J = 6.5 Hz, 6H), 1.40 (t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 442.5 (MH ⁺ ); tR = 0.60 min (method D).

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Example 166 5- (2-Ethoxypyridin-3-yl) -N - ((5- (fluoromethyl) isoxazol-3-yl) methyl) -1-isopropyl-3methyl-1H-pyrazolo [4,3-b] pyridine -7-amine

obtained using the same procedure as described for Example 165, from 5- (2ethoxypyridin-3-yl) -N - ((5- (fluoromethyl) isoxazol-3-yl) methyl) -1-isopropyl-N- (4 -methoxybenzyl) -3methyl-1H-pyrazolo [4,3-b] pyridin-7-amine.

Ή NMR (600 MHz, chloroform-d) δ 8.27 (dd, J = 7.4, 2.0 Hz, 1H), 8.18 (dd, J = 4.9, 2.0 Hz, 1H) , 7.22 (s, 1H), 7.02 (dd, J = 7.4, 4.9 Hz, 1H), 6.47 (d, J = 2.6 Hz, 1H), 5.43 ( d, J = 47.3 Hz, 2H), 5.22 (s, 1H), 4.89 (hept, J = 6.6 Hz, 1H), 4.65 (d, J = 5.2 Hz, 2H), 4.47 (q, J = 7.0 Hz, 2H), 2.64 (s, 3H), 1.64 (d, J = 6.5 Hz, 6H), 1.39 (t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 425.6 (MH ⁺ ); tR = 0.57 min (method D).

Example 167 5- (2-Ethoxypyridin-3-yl) -N - ((3- (fluoromethyl) isoxazol-5-yl) methyl) -1-isopropyl-3methyl-1H-pyrazolo [4,3-b] pyridine -7-amine

obtained using the same procedure as described for example 165, from 5- (2ethoxypyridin-3-yl) -N - ((3- (fluoromethyl) isoxazol-5-yl) methyl) -1-isopropyl-N- (4 -methoxybenzyl) -3methyl-1H-pyrazolo [4,3-b] pyridin-7-amine.

¹ H NMR (600 MHz, chloroform-d) δ 8.28 (dd, J = 7.4, 2.0 Hz, 1H), 8.17 (dd, J = 4.9, 2.0 Hz, 1H ), 7.22 (s, 1H), 7.02 (dd, J = 7.4, 4.9 Hz, 1H), 6.41 (s, 1H), 5.44 (d, J = 46, 9 Hz, 2H), 4.90 (t, J = 5.9 Hz, 1H), 4.84 (hept, J = 6.6 Hz, 1H), 4.73 (d, J = 5.8 Hz , 2H), 4.45 (q, J = 7.0 Hz, 2H), 2.65 (s, 3H), 1.64 (d, J = 6.5 Hz, 6H), 1.35 (t , J = 7.0 Hz, 3H).

LC-MS (mass / charge) 425.6 (MH ⁺ ); tR = 0.55 minutes (method D).

Example 168 1-Isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] -5-oxazol-2-ylpyrazolo [4,3-b] pyridin-7-amine

obtained using the same procedure as described for example 147, from 5-bromo-1isopropyl-3-methyl-N - ((1-methyl-1 H-pyrazol-4-yl) methyl) -1 H-pyrazolo [4 , 3-b] pyridin-7-amine and tributyl (oxazol-2-yl) stannane.

¹ H NMR (chloroform-d, 400 MHz): δ 7.83 (s, 1H), 7.59 (s, 1H), 7.46 (s, 1H), 7.39 (s, 1H), 7 , 29 (s, 1H), 4.76-4.70 (m, 1H), 4.58 (brs, 1H), 4.44 (d, J = 4.2 Hz, 2H), 3.94 ( s, 3H), 2.69 (s, 3H), 1.59 (d, J = 6.4 Hz, 6H).

LC-MS (mass / charge) 352 (MH ⁺ ); tR = 1.75 minutes (method C).

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Example 169 1-Isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] -5- (3-methyltriazol-4-yl) pyrazolo [4,3-b] pyridin-7-amine

obtained using the same procedure as described for example 147, from 5-bromo-1isopropyl-3-methyl-N - ((1-methyl-1H-pyrαzol-4-yl) methyl) -1H-pyrαzolo [4.3 -b] pyridin-7-amine and 1-methyl5- (tributylstannyl) -1H-1,2,3-triazole.

Ή NMR (chloroform-d, 400 MHz): δ 7.93 (s, 1H), 7.57 (s, 1H), 7.45 (s, 1H), 6.70 (s, 1H), 4, 76-4.69 (m, 1H), 4.65 (brs, 1H), 4.48 (s, 3H), 4.39 (d, J = 4.4 Hz, 2H), 3.95 (s , 3H), 2.62 (s, 3H), 1.60 (d, J = 6.4Hz, 6H).

LC-MS (mass / charge) 366 (MH ⁺ ); tR = 1.69 min (method C).

Example 170. 1-Isopropyl-5- (2-methoxy-3-pyridyl) -3-methyl-N - [[2- (trifluoromethyl) -3-pyridyl] methyl] pyrazolo [4.3-0] pyridine-7 -amine

obtained using the same procedure as described for example 1, from [2 (trifluoromethyl) -3-pyridyl] methanamine, (2-methoxypyridin-3-yl) boronic acid and 5,7-dichloro-1isopropyl-3-methylpyrazolo [ 4,3-b] pyridine.

¹ H NMR (chloroform-d, 400 MHz): δ 8.67 (d, J = 4.0 Hz, 1H), 8.20 (dd, J = 1.2, 7.2 Hz, 1H), 8 , 15 (dd, J = 2.0, 4.8 Hz, 1H), 7.99 (d, J = 7.6 Hz, 1H), 7.50 (dd, J = 4.8, 8.0 Hz, 1H), 7.01 (dd, J = 5.2, 7.6 Hz, 1H), 6.90 (s, 1H), 5.07 (brs, 1H), 4.86-4.89 (m, 3H), 3.74 (s, 3H), 2.65 (s, 3H), 1.66 (d, J = 6.8 Hz, 6H).

LC-MS (mass / charge) 457 (MH ⁺ ); tR = 1.89 min (method A).

Example 171 3- [1-Isopropyl-7 - [(2-methoxy-3-pyridyl) methylamino] -3-methylpyrazolo [4.3b] pyridin-5-yl] -1 H-pyridin-2-one

prepared using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine, (2-methoxypyridin-3-yl) methanamine and ( 2-oxo-1,2-dihydropyridin-3-yl) boronic acid.

1H NMR (DMSO-d6, 400 MHz): δ 11.73 (brs, 1H), 8.27 (dd, J = 2.0, 7.2 Hz, 1H), 8.01 (d, J = 3 , 6 Hz, 1H), 7.57 (d, J = 6.4 Hz, 1H), 7.45-7.35 (m, 1H), 6.88 (dd, J = 4.2, 7, 2 Hz, 1H), 6.75-6.67 (m, 1H), 6.35-6.25 (m, 1h), 5.20-5.14 (m, 1H), 4.45-4 , 40 (m, 2H), 3.91 (s, 3H), 2.43 (s, 3H), 1.43 (d, J = 6.4Hz, 6H).

LC-MS (mass / charge) 405 (MH ⁺ ); tR = 1.95 min (method C).

Example 172 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-N - [(3-methoxy-4-pyridyl) methyl] -3-methylpyrazolo [4,3 - b] pyridin-7-amine

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prepared using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine, (3-methoxy-4-pyridyl) methanamine and ( 2-ethoxy-3pyridyl) boronic acid.

1H NMR (chloroform-d, 400 MHz): δ 8.32 (s, 1H), 8.26 (d, J = 4.8 Hz, 1H), 8.22 (d, J = 7.2 Hz, 1H), 8.14 (d, J = 4.2 Hz, 1H), 7.30-7.25 (m, 1H), 7.08 (s, 1H), 7.01 (dd, J = 4 , 8, 7.2 Hz, 1H), 5.02 (brs, 1H), 4.91-4.88 (m, 1H), 4.58 (d, J = 5.6 Hz, 2H), 4 , 35 (q, J = 7.2 Hz, 2H), 4.01 (s, 3H), 2.65 (s, 3H), 1.66 (d, J = 7.2 Hz, 6H), 1 , 26 (t, J = 7.2 Hz, 3H).

LC-MS (mass / charge) 433.1 (MH ⁺ ); tR = 1.47 min (method A).

Example 173 1-Isopropyl-5- (2-methoxy-3-pyridyl) -3-methyl-N - [(2-methylthiazol-5-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine

obtained using the same procedure as described for example 29, from 1-isopropyl-5 (2-methoxypyridin-3-yl) -3-methyl-1H-pyrazolo [4,3-b] pyridin-7-amine and 2 -methylthiazole-5-carbaldehyde.

1H NMR (chloroform-d, 400 MHz): δ 8.20-8.18 (m, 2H), 7.64 (s, 1H), 7.12 (s, 1H), 7.07-7.04 (m, 1H), 4.88-4.77 (m, 2H), 4.77-4.68 (m, 2H), 4.00 (s, 3H), 2.72 (s, 3H), 2.65 (s, 3H), 1.62 (d, J = 6.8 Hz, 6H).

LC-MS (mass / charge) 409 (MH ⁺ ); tR = 1.66 min (method A).

Example 174 5- (2-Cyclopropoxypyridin-3-yl) -1 -isopropyl-N - ((2-methoxypyridin-3-yl) methyl) -3 methyl-1 H-pyrazolo [4,3-b] pyridine- 7-amine

prepared using the same procedure as described for example 1, from 5,7-dibromo-1isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine, (2-methoxypyridin-3-yl) methanamine and 2cyclopropoxy -3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine.

1H NMR (chloroform-d, 600 MHz) δ 8.23 (dd, J = 4.9, 2.0 Hz, 1H), 8.21 (dd, J = 7.4, 2.0 Hz, 1H) , 8.14 (dd, J = 5.0, 1.9 Hz, 1H), 7.59 (dd, J = 7.2, 1.8 Hz, 1H), 7.05 (dd, J = 7 , 4, 4.9 Hz, 1H), 6.97 (s, 1H), 6.90 (dd, J = 7.2, 5.0 Hz, 1H), 5.11 (t, J = 5, 8 Hz, 1H), 4.86 (hept, J = 6.5 Hz, 1H), 4.48 (d, J = 5.8 Hz, 2H), 4.39 - 4.34 (m, 1H) , 4.04 (s, 3H), 2.63 (s, 3H), 1.63 (d, J = 6.6 Hz, 6H), 0.79 - 0.76 (m, 2H), 0, 63 0.60 (m, 2H).

LC-MS (mass / charge) 445.5 (MH ⁺ ); t _R = 0.6 min (method D).

Example 175. 1-Isopropyl-N - ((2-methoxypyridin-3-yl) methyl) -3-methyl-5- (1-methyl-1 H-pyrazol-5 yl) -1 H-pyrazolo [4.3 -B] pyridin-7-amine

obtained using the same procedure as described for example 1, from 5,7-dibromo-1-148 037544 isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine, (2-methoxypyridin-3-yl ) methanamine and 1-methyl-5 (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-pyrazole.

1H NMR (chloroform-d, 600 MHz) δ 8.15 (dd, J = 5.1, 1.9 Hz, 1H), 7.60 (dd, J = 7.2, 1.8 Hz, 1H) , 7.48 (d, J = 1.9 Hz, 1H), 6.91 (dd, J = 7.2, 5.0 Hz, 1H), 6.64 (s, 1H), 6.44 ( d, J = 2.0 Hz, 1H), 5.22 (t, J = 5.9 Hz, 1H), 4.84 (hept, J = 6.6 Hz, 1H), 4.49 (d, J = 5.8 Hz, 2H), 4.22 (s, 3H), 4.04 (s, 3H), 2.60 (s, 3H), 1.63 (d, J = 6.5 Hz, 6H).

LC-MS (mass / charge) 392.5 (MH +); tR = 0.49 min (method D).

Example 176 5- (2-Ethoxy-3-pyridyl) -1 -isopropyl-N - [(5-methoxypyrimidin-2-yl) methyl] -3 methylpyrazolo [4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methyl-1H-pyrazolo [4,3-b] πyridine, (5-methoxypyrimidin-2-yl) methanamine and ( 2-ethoxy-3pyridyl) boronic acid.

Ή NMR (chloroform-d, 400 MHz): δ 8.48 (s, 2H), 8.27 (d, J = 7.6 Hz, 1H), 8.20 (d, J = 4.0 Hz, 1H), 7.16 (s, 1H), 7.04 (dd, J = 4.8, 6.8 Hz, 1H), 5.15-5.08 (m, 1H), 4.68 (d , J = 4.4 Hz, 2H), 4.50 (q, J = 7.2 Hz, 2H), 3.98 (s, 3H), 2.70 (s, 3H), 1.71 (d , J = 6.4 Hz, 6H), 1.45 (t, J = 6.8 Hz, 3H).

LC-MS (mass / charge) 434.1 (MH +); tR = 2.15 min (method C).

Example 177. 3- [1-Isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3-b] pyridin-5-yl] -S-pyridin-2-one

obtained using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methyl-1H-πyrazolo [4,3-b] πyridine, (1-methyl-1H-pyrazol-4-yl ) methanamine and (2-oxo-1,2-dihydropyridin-3-yl) boronic acid.

¹ H NMR (chloroform-d, 400 MHz): δ 8.22 (d, J = 6.8 Hz, 1H), 7.90-7.75 (m, 1H), 7.59 (s, 1H) , 7.57 (s, 1H), 7.26-7.20 (m, 1H), 6.65-6.63 (m, 1H), 5.47 (brs, 1H), 4.96-4 , 90 (m, 1H), 4.52 (d, J = 4.4 Hz, 2H), 3.92 (s, 3H), 2.60 (s, 3H), 1.59 (d, J = 6.4 Hz, 6H).

LC-MS (mass / charge) 378 (MH +); tR = 1.71 min (method C).

Example 178 N- [[2- (Difluoromethyl) -3-pyridyl] methyl] -5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3 methylpyrazolo [4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 1, from 5,7-dibromo-1isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine, (2- (difluoromethyl) pyridin-3-yl) methanamine and (2ethoxy-3-pyridyl) boronic acid.

1H NMR (chloroform-d, 400 MHz): δ 8.58 (d, J = 4.4 Hz, 1H), 8.24 (dd, J = 7.6, 2.0 Hz, 1H), 8, 14 (dd, J = 4.8, 2.0 Hz, 1H), 7.92 (d, J = 7.6 Hz, 1H), 7.42 (dd, J = 8.0, 5.2 Hz , 1H), 7.13 (s, 1H), 7.00 (dd, J = 7.2, 4.8 Hz, 1H), 6.80 (t, J = 54.8 Hz, 1H), 4 , 97 - 4.82 (m, 4H), 4.33 (q, J = 6.8 Hz, 2H), 2.66 (s, 3H), 1.64 (d, J = 6.4 Hz, 6H), 1.21 (t, J = 6.8 Hz, 3H)

LC-MS (mass / charge) 453.1 (MH +); tR = 1.98 min (method A).

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Example 179 5- (2-Ethoxy-3-pyridyl) -1 -isopropyl-N - [(6-methoxypyrimidin-4-yl) methyl] -3methylpyrazolo [4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine, (6-methoxypyrimidin-4-yl) methanamine and ( 2-ethoxy-3pyridyl) boronic acid.

Ή NMR (chloroform-d, 400 MHz): δ 8.82 (s, 1H), 8.25 (dd, J = 5.2, 7.2 Hz, 1H), 8.17 (dd, J = 2 , 0.2 Hz, 1H), 7.08 (s, 1H), 7.02 (dd, J = 4.8, 7.2 Hz, 1H), 6.78 (s, 1H), 6 , 01 (brs, 1H), 5.06-5.00 (m, 1H), 4.54 (d, J = 4.4 Hz, 2H), 4.43 (q, J = 6.8 Hz, 2H), 4.01 (s, 3H), 2.66 (s, 3H), 1.69 (d, J = 6.8 Hz, 6H), 1.36 (t, J = 6.8 Hz, 3H).

LC-MS (mass / charge) 434.1 (MH +); tR = 1.9 min (method A).

Example 180 5- (2- (Ethoxy-1,1-d ₂ ) pyridin-3-yl) -1 -isopropyl-N - ((2-methoxypyridin-3-yl) methyl) -3methyl-1 H-pyrazolo [4,3-b] pyridin-7-amine

obtained using the same procedure as described for example 1, from 5-bromo-1isopropyl-N - ((2-methoxypyridin-3-yl) methyl) -3-methyl-1H-pyrazolo [4,3-b] pyridine -7-amine and 2- (ethoxy1,1 -d ₂ ) -3- (4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl) pyridine.

Ή NMR (chloroform-d, 600 MHz) δ 8.24 (dd, J = 7.3, 2.0 Hz, 1H), 8.12-8.15 (m, 2H), 7.59 (ddt, J = 7.2, 1.8, 0.8 Hz, 1H), 7.14 (s, 1H), 6.99 (dd, J = 7.4, 4.9 Hz, 1H), 6.89 (dd, J = 7.2, 5.0 Hz, 1H), 5.10 (t, J = 5.8 Hz, 1H), 4.87 (hept, J = 6.6 Hz, 1H), 4 , 50 (d, J = 5.7 Hz, 2H), 4.03 (s, 3H), 2.64 (s, 3H), 1.63 (d, J = 6.5 Hz, 6H), 1 , 29 (s, 3H).

LC-MS (mass / charge) 435.6 (MH +); tR = 0.61 min (method D).

Example 181 5- (2- (Ethoxy-d ₅ ) pyridin-3-yl) -1 -isopropyl-N - ((2-methoxypyridin-3-yl) methyl) -3methyl-1 H-pyrazolo [4.3 -b] pyridin-7-amine

obtained using the same procedure as described for example 1, from 5-bromo-1isopropyl-N - ((2-methoxypyridin-3-yl) methyl) -3-methyl-1H-pyrazolo [4,3-b] pyridine -7-amine and 2- (ethoxyd ₅ ) -3- (4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl) pyridine.

Ή NMR (chloroform-d, 600 MHz) δ 8.24 (ddd, J = 7.4, 2.0, 0.7 Hz, 1H), 8.12-8.15 (m, 2H), 7, 61-7.56 (m, 1H), 7.14 (s, 1H), 7.02-6.96 (m, 1H), 6.89 (dd, J = 7.2, 5.0 Hz, 1H), 5.10 (t, J = 5.8 Hz, 1H), 4.87 (hept, J = 6.6 Hz, 1H), 4.50 (d, J = 5.7 Hz, 2H) , 4.03 (s, 3H), 2.64 (s, 3H), 1.63 (d, J = 6.5 Hz, 6H).

LC-MS (mass / charge) 438.6 (MH +); tR = 0.6 min (method D).

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Example 182.5- (2- (Ethoxy-2,2,2-d ₃ ) pyrudin-3-yl) -1-isopropyl-N - ((2-methoxypyrudin-3-yl) methyl) 3-methyl-1H -pyrazolo [4,3-b] pyrudin-7-amine

prepared using the same procedure as described for example 1, from 5-bromo-1isopropyl-N - ((2-methoxypyridin-3-yl) methyl) -3-methyl-1H-pyrazolo [4,3-b] pyrudine -7-amune and 2- (ethoxy2,2,2-d ₃ ) -3- (4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl) pyridine.

¹ H NMR (chloroform-d, 600 MHz) δ 8.24 (dd, J = 7.4, 2.0 Hz, 1H), 8.12-8.16 (m, 2H), 7.59 (ddd , J = 7.3, 1.9, 0.9 Hz, 1H), 7.14 (s, 1H), 6.99 (dd, J = 7.4, 4.9 Hz, 1H), 6, 89 (dd, J = 7.2, 5.0 Hz, 1H), 5.10 (t, J = 5.8 Hz, 1H), 4.87 (hept, J = 6.6 Hz, 1H), 4.50 (d, J = 5.7 Hz, 2H), 4.38 (s, 2H), 4.03 (s, 3H), 2.64 (s, 3H), 1.63 (d, J = 6.5 Hz, 6H).

LC-MS (mass / charge) 436.6 (MH +); tR = 0.6 min (method D).

Example 183. 1-Isopropyl-N - ((2-methoxypyridin-3-yl) methyl) -3-methyl-5- (2- (trifluoromethyl) pyridin-3-yl) -1 H-pyrazolo [4,3- b] pyridin-7-amine

obtained using the same procedure as described for example 1, from 5-bromo-1isopropyl-N - ((2-methoxypyridin-3-yl) methyl) -3-methyl-1H-nyrazolo [4,3-b] puridine -7-amine and (2 (trifluoromethyl) pyridin-3-yl) boronic acid.

¹ H NMR (chloroform-d, 600 MHz) δ 8.73 (dd, J = 4.7, 1.6 Hz, 1H), 8.13 (dd, J = 5.1, 1.9 Hz, 1H ), 7.94 (dd, J = 7.9, 1.6 Hz, 1H), 7.57 - 7.52 (m, 2H), 6.89 (dd, J = 7.2, 5.1 Hz, 1H), 6.49 (s, 1H), 5.29 (t, J = 5.8 Hz, 1H), 4.87 (hept, J = 6.6 Hz, 1H), 4.45 ( d, J = 5.8 Hz, 2H), 4.01 (s, 3H), 2.61 (s, 3H), 1.66 (d, J = 6.5 Hz, 6H).

LC-MS (mass / charge) 457.5 (MH +); tR = 0.56 min (method D).

Example 184. 3- (Difluoromethyl) -5- (2-ethoxypyridin-3-yl) -1 -isopropyl-N - ((1-methyl-1H-pyrazol-4yl) methyl) -1 H-pyrazolo [4.3 -b] pyridin-7-amine

A solution of 7-chloro-3- (difluoromethyl) -5- (2-ethoxypyridin-3-yl) -1 -isopropyl-1H-pyrazolo [4,3-b] pyridine (3.0 mg, 6.5 μmol) was placed , (1-methyl-1H-pyrazol-4-yl) methanamine (29.0 mg, 0.26 mmol) in NMP (0.22 ml) in a sealed vessel in an oil bath at 155 ° C and stirred for 16 h The mixture was partitioned between ethyl acetate (20 ml) and water (2x15 ml). The organic layer was washed with brine (10 ml), dried (Na ₂ SO ₄ ) and concentrated. Flash chromatography on silica gel (elution gradient from heptane to ethyl acetate) gave 3- (difluoromethyl) -5- (2-ethoxypyridin3-yl) -1-isopropyl-N - ((1-methyl-1H-pyrazole-4- yl) methyl) -1H-pyrazolo [4,3-b] pyridin-7-amine.

¹ H NMR (chloroform-d, 600 MHz) δ 8.33 (dd, J = 7.4, 2.0 Hz, 1H), 8.18 (dd, J = 4.9, 2.0 Hz, 1H ), 7.57 (s, 1H), 7.44 (s, 1H), 7.35 (s, 1H), 7.16 (t, J = 54.1 Hz, 1H), 7.03 (dd , J = 7.4, 4.9 Hz, 1H), 4.82 (hept, J = 6.5 Hz, 1H), 4.57 (t, J = 5.0 Hz, 1H), 4.47 (q, J = 7.0 Hz, 2H), 4.40 (d, J = 4.8 Hz, 2H), 3.93 (s, 3H), 1.64 (d, J = 6.5 Hz , 6H), 1.39 (t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 442.6 (MH +); tR = 0.55 min (method D).

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Example 185 1-Isonronyl-3-methyl-N - ((1-methyl-1H-nyrazol-4-yl) methyl) -5- (1H-1,2,4-triazol-1-yl) 1H-pyrazolo [4,3-b] pyridin-7-amine

A mixture of 5-bromo-1 -isopropyl-3-methyl-N - ((1-methyl-1 H-pyrazol-4-yl) methyl) - 1Hpyrazolo [4,3-L] pyridin-7-amine (50 mg , 0.14 mmol), 1H-1,2,4-triazole (19 mg, 0.28 mmol), CS2CO3 (135 mg, 0.41 mmol), N ₁ , N ₂ -dimethylethane-1,2-diamine (2 mg, 0.028 mmol), tetrabutylammonium diiodide and copper iodide (30 mg, 0.027 mmol) in dimethylacetamide (2 ml) at 110 ° C for 16 h in a sterile glove box. After filtration, the filtrate was concentrated and purified by preparative HPLC to give 1-isopropyl-3-methyl-N - ((1-methyl-1 H-pyrazol-4-yl) methyl) -5- (1H-1,2,4 -triazol-1-yl) -1Hpyrazolo [4,3-b] pyridin-7-amine.

1H NMR (chloroform-d, 400 MHz): δ 9.24 (s, 1H), 8.08 (s, 1H), 7.58 (s, 1H), 7.47 (s, 1H), 7, 13 (s, 1H), 4.76 - 4.73 (m, 1H), 4.73 - 4.64 (m, 1H), 4.45 (d, J = 4.8 Hz, 2H), 3 , 95 (s, 3H), 2.59 (s, 3H), 1.59 (d, J = 6.4Hz, 6H).

LC-MS: t _R = 1.88 min (method B), mass / charge = 352.1 [M + H] ⁺ .

Example 186. 3- [1-Isopropyl-3-methyl-7 - [(1-methyl-1,2,4-triazol-3-yl) methylamino] pyrazolo [4,3 -

b] pyridin-5-yl] -1 N-pyridin-2-one

obtained using the same procedure as described for example 29, from 3 - (7-amino-1isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridin-5-yl) pyridin-2 (1H) - she and 1-methyl-1H-1,2,4-triazole-3carbaldehyde.

Ή NMR (chloroform-d, 400 MHz): δ 8.24-8.22 (m, 1H), 8.05 (s, 1H), 8.02-7.98 (m, 1H), 7.21 (s, 1H), 6.79-6.74 (m, 1H), 6.00-5.94 (m, 1H), 5.03-4.97 (m, 1H), 4.70 (d , J = 4.4 Hz, 2H), 3.95 (s, 3H), 2.62 (s, 3H), 1.65 (d, J = 6.8 Hz, 6H).

LC-MS (mass / charge) 379.1 (MH +); t _R = 1.56 min (method B).

Example 187. 3- [1-Isopropyl-3-methyl-7- (yl] -1 H-pyridin-2-one

N-pyrazol-3-ylmethylamino) pyrazolo [4,3 -b] pyridine-5-

obtained using the same procedure as described for example 29, from 3- (7-amino-1isopropyl-3-methyl-1H-pyrazolo [4,3-b] πyridin-5-yl) πyridin-2 (1H) - she and 1H-nyrazole-3-carbaldehyde.

¹ H NMR (DMSO-d6, 400 MHz): δ 12.63 (brs, 1H), 11.73 (brs, 1H), 8.30-8.28 (m, 1H), 7.82-7, 47 (m, 3H), 6.62-6.51 (m, 1H), 6.32-6.21 (m, 2H), 5.16-5.13 (m, 1H), 4.57- 4.39 (m, 2H), 2.46 (s, 3H), 1.43 (d, J = 6.4Hz, 6H).

LC-MS (mass / charge) 364 (MH +); t _R = 1.79 min (method C).

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Example 188 5- [2- (Difluoromethoxy) -3-pyridyl] -1-isopropyl-N - [(2-methoxy-3-pyridyl) methyl] -3methylpyrazolo [4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 1, from 5,7-dibromo-1isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine, (2-methoxypyridin-3-yl) methanamine and ( 2- (difluoromethoxy) pyridin-3-yl) boronic acid.

1H NMR (chloroform-d, 600 MHz) δ 8.38 (dd, J = 7.5, 2.0 Hz, 1H), 8.19 (dd, J = 4.8, 2.0 Hz, 1H) , 8.12 (dd, J = 5.1, 1.9 Hz, 1H), 7.64 (dd, J = 7.2, 1.7 Hz, 1H), 7.60 (t, J = 73 , 1 Hz, 1H), 7.24 (dd, J = 7.5, 4.8 Hz, 1H), 7.05 (s, 1H), 6.90 (dd, J = 7.2, 5, 0 Hz, 1H), 5.27 (t, J = 6.0 Hz, 1H), 4.87 (hept, J = 6.5 Hz, 1H), 4.51 (d, J = 5.9 Hz , 2H), 4.03 (s, 3H), 2.62 (s, 3H), 1.64 (d, J = 6.6 Hz, 6H).

LC-MS (mass / charge) 455.6 (MH +); tR = 0.57 min (method D).

Example 189 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-N - [(4-methoxypyrimidin-2-yl) methyl] -3methylpyrazolo [4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine, (4-methoxypyrimidin-2-yl) methanamine and ( 2-ethoxy-3pyridyl) boronic acid.

1H NMR (chloroform-d, 400 MHz): δ 8.47 (d, J = 5.6 Hz, 1H), 8.26 (dd, J = 2.0, 7.6 Hz, 1H), 8, 19 (dd, J = 2.0, 4.8 Hz, 1H), 7.17 (s, 1H), 7.03 (dd, J = 4.8, 7.2 Hz, 1H), 6.71 (d, J = 6.0 Hz, 1H), 6.35 (brs, 1H), 5.16-5.10 (m, 1H), 4.62 (d, J = 4.4 Hz, 2H) , 4.50 (q, J = 6.8 Hz, 2H), 4.04 (s, 3H), 2.67 (s, 3H), 1.69 (d, J = 6.4 Hz, 6H) , 1.46 (t, J = 6.8 Hz, 3H).

LC-MS (mass / charge) 434.2 (MH +); tR = 1.75 min (method A).

Example 190 5- (2-Ethoxy-3-pyridyl) -1-isopropyl-N - [(4-methoxypyrimidin-5-yl) methyl] -3methylpyrazolo [4,3-b] pyridin-7-amine

obtained using the same procedure as described for example 165, from 5- (2ethoxypyridin-3-yl) -1-isopropyl-N- (4-methoxybenzyl) -3-methyl-1H-pyrazolo [4,3-b] pyridin-7-amine and 5- (bromomethyl) -4-methoxypyrimidine.

1H NMR (chloroform-d, 400 MHz): δ 8.77 (s, 1H), 8.49 (s, 1H), 8.24 (dd, J = 2.0, 7.2 Hz, 1H), 8.17 (dd, J = 2.0.4.8 Hz, 1H), 7.16 (s, 1H), 7.02 (dd, J = 4.8, 7.2 Hz, 1H), 4 , 97-4.94 (m, 1H), 4.88-4.84 (m, 1H), 4.52 (d, J = 5.6 Hz, 2H), 4.44 (q, J = 7 , 2 Hz, 2H), 4.09 (s, 3H), 2.65 (s, 3H), 1.64 (d, J = 6.8 Hz, 6H), 1.34 (t, J = 6 , 8 Hz, 3H).

LC-MS (mass / charge) 434.1 (MH +); tR = 1.57 min (method A).

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Example 191 5- (2-Ethoxy-3-pyridyl) -N - [(2-ethoxy-3-pyridyl) methyl] -1-isopropyl-3-methylpyrazolo

[4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyrugine, (2-ethoxypyridin-3-yl) methanamine and ( 2-ethoxy-3pyridyl) boronic acid.

1H NMR (chloroform-d, 400 MHz): δ 8.26-8.24 (m, 1H), 8.17-8.16 (m, 1H), 8.12-8.11 (m, 1H) , 7.60-7.59 (m, 1H), 7.17 (s, 1H), 7.03-7.00 (m, 1H), 6.88-6.87 (m, 1H), 5 , 08 (brs, 1H), 4.89-4.86 (m, 1H), 4.53-4.45 (m, 4H), 4.41 (q, J = 6.8 Hz, 2H), 2.65 (s, 3H), 1.64 (d, J = 6.4 Hz, 6H), 1.43 (t, J = 7.2 Hz, 3H), 1.32 (t, J = 7 , 2 Hz, 3H).

LC-MS (mass / charge) 447.2 (MH +); t _R = 1.9 min (method A).

Example 192 5- [2- (Dimethylamino) -3-pyridyl] -1-isopropyl-N - [(4-methoxyphenyl) methyl] -3methylpyr azolo [4,3-b] pyridine-7-amine

To a solution of NaH (183 mg, 4.59 mmol, 60% w / w) in THF (4 ml) was added 5- (2-fluoropyridin-3-yl) 1-isopropyl-N- (4-methoxybenzyl) - 3-methyl-1H-pyrazolo [4,3-b] pyridin-7-amine (310 mg, 0.77 mmol) at 0 ° C. Dimethylamine hydrochloride (156 mg, 1.91 mmol) was added and the resulting mixture was stirred at 70 ° C for 16 hours. Water (3 ml) was added and the mixture was poured into saturated aqueous NaHCO ₃ solution. The mixture was extracted with ethyl acetate (20 ml x 3). The combined organic layers were washed with brine (20 ml), dried over Na ₂ SO ₄ and concentrated. The crude mixture was purified by flash chromatography with heptane: ethyl acetate = 1: 0 to 0: 1 to give 5- (2 (dimethylamino) pyrugin-3-yl) -1-isopropyl-N- (4-methoxybenzyl) -3-methyl-1H-pyrazolo [4,3-b] pyrugin-7amine.

¹ H NMR (chloroform-d, 600 MHz) δ 8.19 (dd, J = 4.8, 1.9 Hz, 1H), 7.82 (dd, J = 7.4, 1.9 Hz, 1H ), 7.32 (d, J = 8.6 Hz, 2H), 6.93 (d, J = 8.7 Hz, 2H), 6.82 (dd, J = 7.4, 4.8 Hz , 1H), 6.79 (s, 1H), 4.87 - 4.83 (m, 1H), 4.83 - 4.79 (m, 1H), 4.42 (d, J = 5.1 Hz, 2H), 3.83 (s, 3H), 2.64 (s, 3H), 2.61 (s, 6H), 1.64 (d, J = 6.6 Hz, 6H).

LC-MS (mass / charge) 431.2 (MH +); t _R = 0.42 min (method D).

Example 193. 3- [1-Isopropyl-3-methyl-7 - [[2- (trifluoromethyl) -3-pyridyl] methylamino] pyrazolo [4,3-b] pyrudin-5-yl] -1H-pyrudin-2 -is he

prepared using the same procedure as described for example 1, from 5,7-dichloro-1isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine, (2- (trifluoromethyl) pyridin-3-yl) methanamine and (2-oxo1,2-dihydropyridin-3-yl) boronic acid.

1H NMR (chloroform-d, 400 MHz): δ 8.64 (d, J = 4.4 Hz, 1H), 8.08 (d, J = 8.0 Hz, 2H), 7.69 (m, 1H), 7.507.47 (m, 1H), 7.07 (m, 1H), 6.59-6.56 (m, 1H), 6.06 (brs, 1H), 5.08 (m, 1H ), 4.91 (s, 2H), 2.58 (s, 3H), 1.63 (d, J = 6.4 Hz, 6H).

LC-MS (mass / charge) 443 (MH +); t _R = 1.87 min (method C).

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Example 194 1-Isopropyl-3-methyl-5- (3-methylisoxαzol-4-yl) -N - [(1-methylpyrαzol-4-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine

obtained using the same procedure as described for example 1, from 5-bromo-1isopropyl-3-methyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) -1H-pyrazolo [4.3 -b] pyridin-7-amine and 3-methyl4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) isoxazole.

¹ H NMR (chloroform-d, 400 MHz): δ = 8.67 (s, 1H), 7.56 (s, 1H), 7.43 (s, 1H), 6.54 (s, 1H), 4.79 - 4.66 (m, 1H), 4.60 (brs, 1H), 4.38 (d, J = 4.8 Hz, 2H), 3.94 (s, 3H), 2.61 (s, 6H), 1.59 (d, J = 6.4 Hz, 6H).

LC-MS (mass / charge) 366.1 (MH +); tR = 1.61 min (method C).

Example 195 1 -Isopropyl-3-methyl-5- (1-methyl-1H-1,2,4-triαzol-5-yl) -N - ((1-methyl-1H-pyrαzol-4yl) methyl) - 1H-pyrazolo [4,3-b] pyridin-7-amine

A mixture of 5-bromo-1 -isopropyl-3-methyl-N - ((1-methyl-1 H-pyrazol-4-yl) methyl) - 1Hpyrazolo [4,3-b] pyridin-7-amine (0, 15 g, 0.41 mmol), 1-methyl-1H-1,2,4-triazole (103 mg, 1.24 mmol), Pd (OAc) ₂ (5 mg, 0.021 mmol), Ru-Phos (2 -dicyclohexylphosphino-2 ', 6'-diisopropoxybiphenyl) (19 mg, 0.041 mmol), K2CO3 (171 mg, 1.24 mmol) and 2,2-dimethylpropanoic acid (21 mg, 0.21 mmol) in xylene (15 ml ) at 140 ° С for 12 h in an N2 atmosphere. The mixture was concentrated in vacuo. The residue was purified by preparative TLC (SiO ₂ , ethyl acetate / MeOH = 10: 1) and preparative HPLC to give 1-isopropyl-3-methyl-5- (1-methyl-1H-1,2,4-triαzole-5- yl) -N - ((1-methyl-1H-pyrazol-4-yl) methyl) 1 H-pyrazolo [4,3-b] pyridin-7-amine.

¹ H NMR (chloroform-d; 400 MHz): δ 7.92 (s, 1H), 7.57 (s, 1H), 7.46 (s, 1H), 7.42 (s, 1H), 4 , 76-4.70 (m, 1H), 4.59-4.56 (m, 1H), 4.47 (s, 3H), 4.44 (d, J = 4.4Hz, 2H), 3.93 (s, 3H), 2.62 (s, 3H), 1.59 (d, J = 6.4Hz, 6H).

LC-MS (mass / charge) 366.1 (MH +); t _R = 1.72 min (method C).

Example 196 1-Isopropyl-3-methyl-5- (2-propoxy-3-pyridyl) -N- (1H-pyrazol-4-ylmethyl) pyrazolo [4,3-b] pyridin-7-amine

prepared using the same procedure as described for example 29, from 1-isopropyl-3methyl-5- (2-propoxypyridin-3-yl) -1H-pyrazolo [4,3-b] pyridin-7-amine and 1- trityl-1H-pyrazole-4carbaldehyde.

¹ H NMR (DMSO-d6, 400 MHz): δ 8.27 (dd, J = 7.2, 2.0 Hz, 1H), 8.18 (dd, J = 4.8, 2.0 Hz, 1H), 7.70 (s, 2H), 7.24 (s, 1H), 7.03 (dd, J = 7.6, 5.2 Hz, 1H), 4.82-4.72 (m , 1H), 4.52 (brs, 1H), 4.45 (d, J = 4.8 Hz, 2H), 4.37 (t, J = 6.4 Hz, 2H), 2.65 (s , 3H), 1.86-1.77 (m, 2H), 1.6 (d, J = 6.4 Hz, 6H), 1.04 (t, J = 7.6 Hz, 3H).

LC-MS (mass / charge) 406.1 (MH +); tR = 1.66 min (method A).

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Example 197 5- (2-Ethoxy-3-pyridyl) -N - [(2-methoxy-3-pyridyl) methyl] -3-methyl-1- (oxetane-3yl) pyrazolo [4,3-b] pyridine -7-amine

obtained using the same procedure as described for example 1, from 5,7-dibromo-3methyl-1- (oxetan-3-yl) pyrazolo [4,3-b] pyridine, (2-methoxy-3-pyridyl) methanamine and (2-ethoxy-3pyridyl) boronic acid.

¹ H NMR (chloroform-d, 400 MHz): δ 8.27 (dd, J = 2.0, 7.6 Hz, 1H), 8.19-8.16 (m, 1H), 8.15- 8.12 (m, 1H), 7.59 (d, J = 6.4Hz 1H), 7.23 (s, 1H), 7.04-7.01 (m, 1H), 6.91- 6.88 (m, 1H), 6.15 (brs, 1H), 5.90-5.86 (m, 1H), 5.26-5.22 (m, 2H), 5.18-5, 15 (m, 2H), 4.53 (d, J = 5.6 Hz, 2H), 4.42 (q, J = 6.8 Hz, 2H) 4.03 (s, 3H), 2.64 (s, 3H), 1.32 (t, J = 6.8 Hz, 3H).

LC-MS (mass / charge) 447 (MH +); tR = 1.89 min (method C).

Example 198.5 - (2- (Ethyl (methyl) amino) pyridin-3-yl) -1-isopropyl-N- (4-methoxybenzyl) -3-methyl1H-pyrazolo [4,3-b] pyrigin-7- amine

obtained using the same procedure as described for example 192, from 5- (2fluoropyridin-3-yl) -1 -isopropyl-N- (4-methoxybenzyl) -3 -methyl-1H-pyrazolo [4,3-b ] pyridine-7-amine and methylethanamine.

1H NMR (chloroform-d, 600 MHz) δ 8.20 (dd, J = 4.8, 1.9 Hz, 1H), 7.80 (dd, J = 7.4, 1.9 Hz, 1H) , 7.32 (d, J = 8.7 Hz, 2H), 6.93 (d, J = 8.6 Hz, 2H), 6.84 - 6.80 (m, 2H), 4.79 ( hept, J = 6.6 Hz, 1H), 4.72 (t, J = 5.2 Hz, 1H), 4.40 (d, J = 5.1 Hz, 2H), 3.83 (s, 3H), 3.08 (q, J = 7.0 Hz, 2H), 2.65 (s, 3H), 2.64 (s, 3H), 1.62 (d, J = 6.5 Hz, 6H), 0.93 (t, J = 7.0 Hz, 3H).

LC-MS (mass / charge) 445.6 (MH +); tR = 0.53 min (method D).

Example 199. 5- (2-Ethoxypyrigin-3-yl) -3- (fluoromethyl) -1-isopropyl-N - ((1-methyl-1H-pyrazol-4yl) methyl) - III-pyr azolo [4.3 -b] pyridine-7-amine

A solution of 7-chloro-5- (2-ethoxypyridin-3-yl) -3- (fluoromethyl) -1-isopropyl-1H-pyrazolo [4,3-b] pyridine (2.0 mg, 5.7 μmol), (1-methyl-1H-pyrazol-4-yl) methanamine (30.0 mg, 0.27 mmol) in NMP (0.2 ml) in a closed vessel was placed in an oil bath at 155 ° C. After 20 h, (1-methyl-1H-pyrazole-4yl) methanamine (30.0 mg, 0.27 mmol) was added and the solution was heated at 155 ° C for 15 h. The mixture was partitioned between ethyl acetate (25 ml) and water ( 3x20 ml). The organic layer was washed with brine (25 ml), dried (Na ₂ SO ₄ ) and concentrated. The residue was purified by flash chromatography on silica gel (heptane / ethyl acetate) to give 5- (2-ethoxypyridin-3-yl) -3- (fluoromethyl) -1-isopropyl-N - ((1methyl-1H-pyrazole-4- yl) methyl) -1H-pyrazolo [4,3-b] pyridin-7-amine.

Ή NMR (DMSO-d ₆ , 600 MHz) δ 8.21 - 8.15 (m, 2H), 7.61 (s, 1H), 7.42 (s, 1H), 7.14 (s, 1H ), 7.10 (dd, J = 7.4, 4.9 Hz, 1H), 6.84 (t, J = 5.6 Hz, 1H), 5.67 (d J = 49.2 Hz, 2H), 5.28 (hept, J = 6.4 Hz, 1H), 4.41 - 4.33 (m, 4H), 3.77 (s, 3H), 1.51 (d, J = 6 , 5 Hz, 6H), 1.24 (t, J = 6.9 Hz, 3H).

LC-MS (mass / charge) 424.6 (MH +); tR = 0.5 min (method D).

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Example 200. 1-Isopropyl-3-methyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) -5- (4-methyloxazol-5-yl) 1H-pyrazolo [4,3-b ] pyridin-7-amine

A mixture of 5-bromo-1-isopropyl-3-methyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) -1Hpyrazolo [4,3-b] pyridin-7-amine (0.15 g, 0.41 mmol), 4-methyloxazole (103 mg, 1.2 mmol), Pd (OAc) ₂ (5 mg, 0.021 mmol), Ru-Phos (19 mg, 0.041 mmol), K ₂ CO ₃ ( 171 mg, 1.2 mmol) and 2,2-dimethylpropane acid (17 mg, 0.17 mmol) in toluene (15 ml) at 110 ° С for 12 h. The mixture was concentrated in vacuo. The residue was purified by preparative TLC (SiO ₂ , petroleum ether / ethyl acetate = 0: 1) and preparative HPLC to give 1-isopropyl-3-methyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) -5- (4methyloxazol-5-yl) -1H-nyrazolo [4,3-b] pyridin-7-amine.

1H NMR (chloroform-d; 400 MHz): δ 7.85 (s, 1H), 7.58 (s, 1H), 7.45 (s, 1H), 6.84 (s, 1H), 4, 78-4.72 (m, 2H), 4.43 (d, J = 4.4 Hz, 2H), 3.94 (s, 3H), 2.68 (s, 3H), 2.62 (s , 3H), 1.58 (d, J = 6.4 Hz, 6H).

LC-MS (mass / charge) 366 (MH +); t _R = 1.6 min (method C).

Example 201 5- [2- (Dimethylamino) -3-pyridyl] -1-isopropyl-3-methyl-N - [(1-methylpyrazole-4yl) methyl] pyr azolo [4,3-b] pyridine-7 - amine

JL.N .___ / .NH) -

A NN ^ obtained using the same procedure as described for example 29, from 5- (2 (dimethylamino) pyridin-3-yl) -1-isopropyl-3-methyl-1H-pyrazolo [4,3-b] pyridine -7-amine and 1-methyl-1Hpyrazole-4-carbaldehyde.

1H NMR (Chloroform-d, 600 MHz) δ 8.22 (dd, J = 4.8, 1.9 Hz, 1H), 7.83 (dd, J = 7.3, 1.9 Hz, 1H) , 7.54 (s, 1H), 7.40 (s, 1H), 6.87-6.82 (m, 2H), 4.77 (hept, J = 6.6 Hz, 1H), 4, 58 (t, J = 4.7 Hz, 1H), 4.33 (d, J = 5.0 Hz, 2H), 3.93 (s, 3H), 2.73 (s, 6H), 2, 64 (s, 3H), 1.61 (d, J = 6.6 Hz, 6H).

LC-MS (mass / charge) 405.6 (MH +); t _R = 0.34 min (method D).

Example 202. 1-Isopropyl-3-methyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) -5- (4-methyloxazol-2-yl) 1H-pyrazolo [4,3-b ] pyridin-7-amine

A mixture of 5-bromo-1-isopropyl-3-methyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) -1Hpyrazolo [4,3-b] pyridin-7-amine (100 mg, 0.28 mmol), 4-methyloxazole (46 mg, 0.55 mmol), XPHOS-PdG3 ((2-dicyclohexylphosphino-2 ', 4', 6'-triisopropyl-1,1 '-biphenyl) [2- ( 2'-amino-1,1'-biphenyl)] palladium (P) methanesulfonate) (12 mg, 0.014 mmol), t-BuOK (93 mg, 0.83 mmol) in dimethylacetamide (5 ml) at 100 ° С in for 12 hours in an atmosphere of N2. The mixture was concentrated in vacuo. The residue was purified by preparative TLC (SiO ₂ , petroleum ether / ethyl acetate = 0: 1) and preparative HPLC to give 1-isopropyl-3-methyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) -5- (4-methyloxazol-2-yl) -1H-pyrazolo [4.3b] pyridin-7-amine.

1H NMR (chloroform-d; 400 MHz): δ 7.58 (s, 1H), 7.53 (s, 1H), 7.45 (s, 1H), 7.34 (s, 1H), 4, 77-4.67 (m, 1H), 4.58 (brs, 1H), 4.44 (d, J = 4.8 Hz, 2H), 3.94 (s, 3H), 2.68 (s , 3H), 2.29 (s, 3H), 1.58 (d, J = 6.8 Hz, 6H).

LC-MS (mass / charge) 366.1 (MH +); t _R = 1.74 min (method C).

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Example 203. 1-Isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] -5- (4-methyl-1,2,4-triazol-3yl) pyrazolo [4,3-b ] pyridin-7-amine <1 N / Ν '^ ί- νΊ IL £>

.NH A NN \ obtained using the same procedure as described for example 195, from 5-bromo-1isopropyl-3-methyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) -1H- pyrazolo [4,3-b] pyridin-7-amine and 4-methyl4H-1,2,4-triazole.

1H NMR (CDCl3 400 MHz): δ 8.18 (s, 1H), 7.56 (s, 1H), 7.55 (s, 1H), 7.48 (s, 1H), 4.78-4 , 71 (m, 1H), 4.60 (brs, 1H), 4.44 (d, J = 4.4 Hz, 2H), 4.23 (s, 3H), 3.93 (s, 3H) , 2.60 (s, 3H), 1.59 (d, J = 6.4Hz, 6H).

LC-MS (mass / charge) 366.1 (MH +); tR = 1.65 min (method B).

In vitro testing.

PDE1 inhibition assay.

Analyzes for PDE1A, PDE1B, and PDE1C were performed as follows: analyzes were performed with 60 μl samples containing a fixed amount of PDE1 enzyme (sufficient to convert 20-25% cyclic nucleotide substrate), buffer (50 mM HEPES with pH 7.6; 10 mM MgCl ₂ ; 0.02% Tween 20), 0.1 mg / ml BSA, 15 nM tritiated cAMP, and various amounts of inhibitors. Reactions were initiated by the addition of cyclic nucleotide substrate and allowed to react for 1 hour at room temperature, after which they were stopped by mixing with 20 μl (0.2 mg) of yttrium silicate SPA beads (PerkinElmer). The pellets were allowed to settle for 1 hour in the dark, after which the plates were counted on a Wallac 1450 Microbeta counting device. The measured signals were converted to activity relative to the non-inhibited control (100%), and IC ₅₀ values were calculated using XlFit (model 205, IDBS).

Claims (50)

CLAIM 1. Compound of formula (I) R1 R4 .N. J _X L R2 R3 (i), where L is selected from the group consisting of NH, CH ₂ , S and O; R1 is selected from the group consisting of hydrogen, linear or branched C ₁ -C ₅ alkyl, _{C 1 C 5} fluoroalkyl, and saturated monocyclic C ₃ -C ₅ cycloalkyl; R2 is selected from the group consisting of linear or branched C ₁ -C ₈ alkyl, saturated monocyclic C ₃ -C ₈ cycloalkyl, oxetanyl, tetrahydrofuranyl, and tetrahydropyranyl; all of which may optionally be substituted with one or more substituents selected from the group consisting of methyl, fluoro, hydroxy, cyano, and methoxy; R3 is methyl substituted with phenyl, pyridonyl, pyridinyl, pyrimidinyl or pyrazinyl, all of which may be optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, C ₁ -C ₃ alkyl, C ₁ -C ₃ fluoroalkyl, C1C ₃ fluoroalkoxy and C ₁ -C ₃ alkoxy; or R3 is methyl substituted with a 5-membered heteroaryl containing from 1 to 4 carbon atoms and one or more heteroatoms selected from oxygen, nitrogen and sulfur, which is optionally substituted with one or more substituents selected from halogen, cyano, C ₁ -C ₃ alkyl, C ₁ -C ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy and C ₁ -C ₃ alkoxy; or R3 is ethyl substituted with phenyl, pyridonyl, pyridinyl, pyrimidinyl or pyrazinyl, all of which may be optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, C ₁ -C ₃ alkyl, C ₁ -C ₃ fluoroalkyl, C1C ₃ fluoroalkoxy and C ₁ -C ₃ alkoxy; or R3 is ethyl substituted with a 5-membered heteroaryl containing from 1 to 4 carbon atoms and one or more heteroatoms selected from oxygen, nitrogen and sulfur, which is optionally substituted with one or more substituents selected from halogen, cyano, C ₁ -C ₃ alkyl, - 158 037544 C ₁ -C ₃ fluoroalkyl, _C1-C3 fluoroalkoxy and C1-C ₃ alkoxy; or L is CH2 and R3 is NH substituted with phenyl, pyridonyl, pyridinyl, pyrimidinyl, or pyrazinyl, all of which may optionally be substituted with one or more substituents selected from the group consisting of halogen, cyano, C ₁ C ₃ alkyl, C ₁ -C ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy and C ₁ -C ₃ alkoxy; or L is CH2 and R3 is NH substituted with 5-membered heteroaryl containing from 1 to 4 carbon atoms and one or more heteroatoms selected from oxygen, nitrogen and sulfur, which is optionally substituted with one or more substituents selected from halogen, cyano, C ₁ -C ₃ alkyl, C ₁ -C ₃ fluoroalkyl, C ₁ -C ₃ fluoroalkoxy and C ₁ -C ₃ alkoxy; R4 represents phenyl, pyridinyl or pyridonyl, all of which may be optionally substituted with one or more substituents selected from the group consisting of halogen, cyano, _C1-C4 alkyl, _C1-C4 fluoroalkyl, _C1-C4 deyterioalkila, C ₁ -C ₃ fluoroalkoxy, cyclopropyloxy, C ₁ -C ₃ alkoxy, C _{1 -C 3} deuterioalkoxy, and —NR5R6, where R5 and R6 are each independently selected from H, C ₁ C ₃ alkyl, and C ₁ -C ₃ deuterioalkyl; or R4 represents a 5-membered heteroaryl containing from 1 to 4 carbon atoms and one or more heteroatoms selected from oxygen, nitrogen and sulfur, which is optionally substituted by one or more substituents selected from halogen, cyano, _C1-C4 alkyl, C1 -C ₄ fluoroalkyl, _{C 1} C ₄ deuterioalkyl, C _{1 -C 3} fluoroalkoxy, cyclopropyloxy, C ₁ -C ₃ alkoxy, C ₁ -C ₃ deuterioalkoxy and -NR5R6, where each of R5 and R6 is independently selected from H, C ₁ -C ₃ alkyl and C ₁ -C ₃ deuterioalkyl; or R4 is a 4-, 5- or 6-membered saturated heterocycle containing from 1 to 3, 4 or 5 carbon atoms and one or more heteroatoms selected from oxygen, nitrogen and sulfur, which in all cases may be optionally substituted with one or more substituents selected from oxo, _C1-C4 alkyl and _C1-C4 fluoroalkyl; and its pharmaceutically acceptable salts. 2. A compound according to claim 1 of formula (Ib) R1 (lb), where R1 is selected from the group consisting of hydrogen, linear or branched C ₁ -C ₅ alkyl and saturated monocyclic C ₃ -C ₅ cycloalkyl; R2 is selected from the group consisting of linear or branched C ₁ -C ₈ alkyl, saturated monocyclic C 3 -C 8 cycloalkyl, oxetanyl, tetrahydrofuranyl, and tetrahydropyranyl; all of which may optionally be substituted with one or more substituents selected from the group consisting of methyl, fluoro, hydroxy, cyano, or methoxy; R3 is methyl substituted by phenyl or pyridinyl piridonilom, all of which may be optionally substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkyl, and methoxy; or R3 is methyl substituted with a 5-membered heteroaryl containing from 1 to 4 carbon atoms and one or more heteroatoms selected from oxygen, nitrogen and sulfur, which is optionally substituted with one or more substituents selected from C ₁ -C ₃ alkyl and C ₁ -C ₃ fluoroalkyl; or R3 is ethyl substituted with phenyl, pyridonyl or pyridinyl, all of which may be optionally substituted with one or more substituents selected from the group consisting of halogen, C ₁ -C ₃ alkyl and methoxy; or R3 is ethyl substituted with 5-membered heteroaryl containing from 1 to 4 carbon atoms and one or more heteroatoms selected from oxygen, nitrogen and sulfur, which is optionally substituted with one or more substituents selected from C ₁ -C ₃ alkyl and C ₁ -C ₃ fluoroalkyl; R4 represents phenyl, pyridinyl or pyridonyl, all of which may be optionally substituted with one or more substituents selected from the group consisting of halogen, C1S ₃ alkyl and C ₁ -C ₃ alkoxy; or R4 is 5-membered heteroaryl which is optionally substituted with one or more substituents selected from C ₁ -C ₃ alkyl and C ₁ -C ₃ fluoroalkyl; and its pharmaceutically acceptable salts. 3. A compound according to claim 1 wherein L is NH. 4. A compound according to any one of claims 1 to 3, wherein R2 is selected from the group consisting of linear or branched C1-C8 alkyl, saturated monocyclic C3-C8 cycloalkyl, oxetanyl, tetrahydrofuranyl and tetrahydropyranyl, all of which are unsubstituted. 5. A compound according to any one of claims 1 and 3-4, wherein R3 is methyl or ethyl substituted 159 037544 phenyl, pyridonyl, pyridinyl, pyrimidinyl or pyrazinyl, all of which may optionally be substituted with one or more of methyl. 6. A compound according to any one of claims 1-4, wherein R3 is methyl or ethyl substituted with a 5-membered heteroaryl containing from 1 to 4 carbon atoms and one or more heteroatoms selected from oxygen, nitrogen and sulfur, which is optionally substituted with one or several of methyl. 7. A compound according to any one of claims 1-6, wherein R4 is phenyl, pyridinyl or pyridonyl, all of which may be optionally substituted with one substituent selected from the group consisting of halogen, Cl-C ₃ alkyl and C ₁ -C ₃ alkoxy. 8. A compound according to any one of claims 1-6, wherein R4 is a 5-membered heteroaryl containing from 1 to 4 carbon atoms and one or more heteroatoms selected from oxygen, nitrogen and sulfur, which is optionally substituted with one or more substituents, selected from Cl-C ₃ alkyl and Ci-C ₃ fluoroalkyl. 9. A compound according to any one of claims 6 or 8, wherein said 5-membered heteroaryl is selected from thiazolyl, oxazolyl, isoxazolyl, triazolyl, pyrazolyl, tetrazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, and thiophenyl. 10. A compound according to any one of claims 1 and 3-6, wherein R4 is a 4-, 5- or 6-membered saturated heterocycle containing from 1 to 3, 4 or 5 carbon atoms and one or more heteroatoms selected from oxygen , nitrogen and sulfur, which in all cases may be optionally substituted with one substituent selected from oxo, C 1-C ₄ alkyl and C ₁ -C ₄ fluoroalkyl. 11. A compound according to any one of claims 1, 3-7 and 10, wherein R4 is a 4-, 5- or 6-membered saturated heterocycle selected from the group consisting of oxazolidin-2-one, azetidin-2-one, imidazolidin-2-one, pyrrolidin-2-one, imidazolidin-2,4-dione, oxazolidin-2,4-dione and piperidin-2-one. 12. A compound according to claim 1, wherein the compound is selected from the group consisting of 1) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(5-methyl-1,3,4-oxadiazol-2-yl) methyl] pyrazolo [4, 3-b] pyridine-7-amine; 2) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(5-methylthiazol-2-yl) methyl] pyrazolo [4,3- b] pyridin-7-amine; 3) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(5-methylisoxazol-3-yl) methyl] pyrazolo [4,3- b] pyridin-7-amine; 4) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-N - [(2-methyloxazol-5-yl) methyl] pyrazolo [4,3- b] pyridin-7-amine; 5) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(2-methyltriazol-4-yl) methyl] pyrazolo [4,3- b] pyridin-7-amine; 6) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(1-methyltriazol-4-yl) methyl] pyrazolo [4,3- b] pyridin-7-amine; 7) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N- (1H-pyrazol-4-ylmethyl) pyrazolo [4,3-b] pyridin7-amine; 8) 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-N - [(2-methyltetrazol-5-yl) methyl] pyrazolo [4,3- b] pyridin-7-amine; 9) 5- (2-ethoxypyridin-3-yl) -1-isopropyl-3-methyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) -1Hpyrazolo [4,3-b] pyridine -7 -amine; 10) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(3-methylisoxazol-5-yl) methyl] pyrazolo [4,3- b] pyridin-7-amine; 11) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(2-methylthiazol-4-yl) methyl] pyrazolo [4,3b] pyridin-7-amine; 12) 1-cyclopropyl-5- (2-ethoxy-3-pyridyl) -3-methyl-N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3b] pyridin-7-amine; 13) 5- (2-ethoxy-3-pyridyl) -N - [(1-methylpyrazol-4-yl) methyl] -1-propylpyrazolo [4,3-b] pyridine-7amine; 14) 5- (2-ethoxypyridin-3-yl) -N - ((1-methyl-1H-pyrazol-4-yl) methyl) -1 - (oxetan-3-yl) -1H-pyrazolo [4,3 -b] pyridine-7-amine; 15) 5- (2-ethoxypyridin-3-yl) -1-methyl-N- (1- (1-methyl-1H-pyrazol-4-yl) ethyl) -1H-pyrazolo [4,3-b] pyridine -7-amine (racemic); 15а) (R) -5- (2-ethoxypyridin-3-yl) -1-methyl-N- (1- (1-methyl-1H-pyrazol-4-yl) ethyl) -1H-pyrazolo [4,3b ] pyridin-7-amine; 15b) (S) -5- (2-ethoxypyridin-3-yl) -1-methyl-N- (1- (1-methyl-1H-pyrazol-4-yl) ethyl) -1H-pyrazolo [4,3b ] pyridin-7-amine; 16) 5- (2-ethoxypyridin-3-yl) -1-methyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) -1H-pyrazolo [4,3-b] pyridine-7 -amine; 17) 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-N - [(1-methylimidazol-2-yl) methyl] pyrazolo [4,3-b] pyridin7-amine; 18) 5- (2-ethoxypyridin-3-yl) -1 -isopropyl-N - ((1-methyl-1H-pyrazol-5-yl) methyl) -1H-pyrazolo [4,3- - 160 037544 b] pyridin-7-amine; 19) 5- (2-ethoxypyridin-3-yl) -1 -isopropyl-N - ((1-methyl-1H-pyrazol-3-yl) methyl) -1H-pyrazolo [4,3b] pyridin-7-amine ; 20) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-N- (thiazol-2-ylmethyl) pyrazolo [4,3-L] pyridine-7-amine; 21) 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-N - [(1-methylimidazol-4-yl) methyl] pyrazolo [4,3-b] pyridin7-amine; 22) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-N- (4-pyridylmethyl) pyrazolo [4,3-b] pyridin-7-amine; 23) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-N- (m-tolylmethyl) pyrazolo [4,3-b] pyridin-7-amine; 24) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-N- (p-tolylmethyl) pyrazolo [4,3-b] pyridin-7-amine; 25) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridine-7amine; 26) 5- (2-ethoxy-3-pyridyl) -1-ethyl-N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridine-7amine; 27) 5- (2-ethoxy-3-pyridyl) -3-methyl-N - [(1-methylpyrazol-4-yl) methyl] -1 - (oxetan-3-yl) pyrazolo [4,3b] pyridine- 7-amine; 28) 5- (2-ethoxy-3-pyridyl) -1,3-dimethyl-N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridine-7amine; 29) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-N - [(4-methylthiazol-2-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine; 30) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(3-methyl-1,2,4-oxαdiazol-5-yl) methyl] pyrazolo [4,3- b] pyridine-7-amine; 31) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-N - [(1-methyl-1,2,4-triazol-3-yl) methyl] pyrazolo [4,3- b] pyridine-7-amine; 32) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(2-methylthiazol-5-yl) methyl] pyrazolo [4,3b] pyridin-7-amine; 33) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(5-methyl-1,3,4-thiadiazol-2-yl) methyl] pyrazolo [4, 3-b] pyridine-7-amine; 34) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(5-methyl-3-thienyl) methyl] pyrazolo [4,3b] pyridin-7-amine; 35) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(4-methyl-2-thienyl) methyl] pyrazolo [4,3-b] pyridin-7-amine; 36) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(5-methyl-2-thienyl) methyl] pyrazolo [4,3-b] pyridin-7-amine; 37) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(2-methyloxazol-4-yl) methyl] pyrazolo [4,3- b] pyridin-7-amine; 38) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(5-methyloxazol-2-yl) methyl] pyrazolo [4,3- b] pyridin-7-amine; 3 9) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N- (1H-pyrazole-3-ylmethyl) pyrazolo [4,3- b] pyridin-7-amine; 40) 5- (2-ethoxy-3-pyridyl) -N- (1H-imidazol-4-ylmethyl) -1-isopropyl-3-methylpyrazolo [4,3- b] pyridin-7-amine; 41) N-benzyl-5 - (2-ethoxy-3-pyridyl) -1 -isopropylpyrazolo [4,3-b] pyridine-7-amine; 42) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-N - [(3-methylisoxazol-5-yl) methyl] pyrazolo [4,3-b] pyridin7-amine; 43) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-N - [(5-methyl-1,2,4-oxαdiazol-3-yl) methyl] pyrazolo [4,3b] pyridine-7- amine; 44) N - [(1,5-dimethylpyrazol-3-yl) methyl] -5- (2-ethoxy-3-pyridyl) -1 -isopropylpyrazolo [4,3-b] pyridin-7-amine; 45) 3- (1-isopropyl-3-methyl-7 - (((1-methyl-1H-pyrazol-4-yl) methyl) amino) -1H-pyrazolo [4,3-b] pyridin-5-yl ) -1 -methylpyridin-2 (1I) -one; 46) 5- (2-ethoxypyridin-3-yl) -1 -isopropyl-3-methyl-N - ((2-methyl-1H-imidazol-4-yl) methyl) -1H-pyrazolo [4,3-b ] pyridine-7-amine; 47) 5- (2-ethoxypyridin-3-yl) -1-isopropyl-3-methyl-N - ((5-methyl-1H-pyrazol-3-yl) methyl) -1Hpyrazolo [4,3-b] pyridine -7 -amine; 48) 5- (2-ethoxypyridin-3-yl) -1-ethyl-3-methyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) -1H-pyrazolo [4,3-b ] pyridine-7-amine; 49) 3- (1-isopropyl-3-methyl-7 - (((1-methyl-1H-pyrazol-4-yl) methyl) amino) -1H-pyrazolo [4,3-b] pyridin-5-yl ) -1 -methylpyridin-2 (1H) -one; 52) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(5-methyl-1,2,4-oxαdiazol-3-yl) methyl] pyrazolo [4, 3-b] pyridine-7-amine; 53) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N- (1,2,4-oxadiazol-3-ylmethyl) pyrazolo [4,3b] pyridin-7-amine; - 161 037544 54) N - [(1,5-dimethylpyrazol-3-yl) methyl] -5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methylpyrazolo [4,3b] pyridin-7-amine; 55) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(5-methyl-1H-1,2,4-triazol-3-yl) methyl] pyrazolo [4, 3-b] pyridine-7-amine; 56) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-N - [(1-methyl-1,2,4-triazol-3-yl) methyl] pyrazolo [4,3- b] pyridin-7-amine; 57) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-N- (1H-pyrazol-3-ylmethyl) pyrazolo [4,3-b] pyridin-7-amine; 58) 5- (2-ethoxypyridin-3-yl) -1 -isopropyl-3-methyl-N - ((1-methyl-1H-imidazol-4-yl) methyl) -1H-pyrazolo [4,3-b ] pyridine-7-amine-2,2,2-trifluoroacetate; 59) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N- (1,3,4-oxadiazol-2-ylmethyl) pyrazolo [4,3- b] pyridin-7-amine; 60) 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-N - [(1-methylpyrazol-3-yl) methyl] pyrazolo [4,3- b] pyridin-7-amine; 61) 5- (1,3-dimethylpyrazol-4-yl) -1 -isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridine-7 - amine; 62) 1 -isopropyl-5- (2-methoxy-3-pyridyl) -3-methyl-N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3- b] pyridin-7-amine; 63) 1 -isopropyl-5- (2-methoxyphenyl) -3-methyl-N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3- b] pyridin-7-amine; 64) 1 -isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] -5-phenylpyrazolo [4,3-b] pyridin-7-amine; 65) 1 -isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] -5 - (2-methyl-3-thienyl) pyrazolo [4,3-b] pyridin-7-amine; 66) 5- (1,5-dimethylpyrazol-4-yl) -1 -isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridine-7 - amine; 67а) (R) -5 - (2-ethoxy-3-pyridyl) -3 -methyl-1- [1-methylpropyl] -N - [(1-methylpyrazol-3-yl) methyl] pyrazolo [4,3- b] pyridine-7-amine; 67b) (S) -5 - (2-ethoxy-3-pyridyl) -3 -methyl-1- [1-methylpropyl] -N - [(1-methylpyrazol-3-yl) methyl] pyrazolo [4,3- b] pyridine-7-amine; 68а) (R) -3 -methyl-1- [1-methylpropyl] -N - [(2-methyltetrazol-5-yl) methyl] -5- (2-propoxy-3-pyridyl) pyrazolo [4,3- B] pyridine-7-amine; 68b) (S) -3-methyl-1- [1-methylpropyl] -N - [(2-methyltetrazol-5-yl) methyl] -5- (2-propoxy-3-pyridyl) pyrazolo [4,3- B] pyridine-7-amine; 70) (R) -5- (2-ethoxy-3-pyridyl) -1- [1-methylpropyl] -N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridine- 7-amine or (S) -5- (2-ethoxy-3-pyridyl) -1- [1-methylpropyl] -N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridine-7-amine; 71) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-N - [(4-methylmiazol-5-yl) methyl] pyrazolo [4,3-b] pyridine-7amine; 72) 5 - [[5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methylpyrazolo [4,3-b] pyridin-7-yl] oxymethyl] -2methyloxazole; 73) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N- (pyrimidin-4-ylmethyl) pyrazolo [4,3-b] pyridin-7-amine; 74) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N- (pyrimidin-2-ylmethyl) pyrazolo [4,3-b] pyridin-7-amine; 75) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(4-methylpyrimidin-2-yl) methyl] pyrazolo [4,3b] pyridin-7-amine; 76) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N- (pyrazin-2-ylmethyl) pyrazolo [4,3-b] pyridine-7amine; 77) 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-N - [[2- (trifluoromethyl) -3-pyridyl] methyl] pyrazolo [4,3-b] pyridine- 7 -amine; 78) 4 - [[[5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methylpyrazolo [4,3-b] pyridin-7-yl] amino] methyl] -1methylpyridin-2-one; 79) 5- (2- (ethylamino) pyridin-3-yl) -1-isopropyl-3-methyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) -1Hpyrazolo [4,3- B] pyridine-7-amine; 81) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-N - [(4-methoxy-2-pyridyl) methyl] -3-methylpyrazolo [4,3- b] pyridin-7-amine; 82) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-N - [(6-methoxypyrazin-2-yl) methyl] -3-methylpyrazolo [4,3- b] pyridin-7-amine; 83) 5- (2-ethoxy-3-pyridyl) -N - [(5-fluoropyrimidin-2-yl) methyl] -1 -isopropyl-3-methylpyrazolo [4,3- b] pyridin-7-amine; 84) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(2-methyl-3-pyridyl) methyl] pyrazolo [4,3-b] pi- - 162 037544 readin-7-amine; 85) 5- (2-ethoxy-3-pyridyl) -N - [(2-fluoro-3-pyridyl) methyl] -1-isopropyl-3-methylpyrazolo [4,3b] pyridin-7-amine; 86) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-N - [(2-methoxy-3-pyridyl) methyl] -3-methylpyrazolo [4,3b] pyridin-7-amine; 87) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(6-methyl-3-pyridyl) methyl] pyrazolo [4,3-b] pyridin-7-amine; 88) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-N - [(2-methoxyphenyl) methyl] -3-methylpyrazolo [4,3- b] pyridin-7-amine; 89) 5- (2-ethoxy-3-pyridyl) -N - [(2-fluorophenyl) methyl] -1-isopropyl-3-methylpyrazolo [4,3-b] pyridin7-amine; 90) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [[2- (trifluoromethyl) phenyl] methyl] pyrazolo [4,3b] pyridin-7-amine; 91) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-N - [(3-methoxypyrazin-2-yl) methyl] -3 -methylpyrazolo [4,3- b] pyridin-7-amine; 92) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-N - [(4-methoxy-3-pyridyl) methyl] -3-methylpyrazolo [4,3- b] pyridin-7-amine; 93) 1-isopropyl-3-methyl-N - [(2-methyltetrazol-5-yl) methyl] -5- (2-propoxy-3-pyridyl) pyrazolo [4,3b] pyridin-7-amine; 94) 1 -isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] -5- (2-propoxy-3-pyridyl) pyrazolo [4,3b] pyridin-7-amine; 95) 1 -isopropyl-5 - (2-methoxy-3-pyridyl) -N - [(2-methoxy-3-pyridyl) methyl] -3-methylpyrazolo [4,3- b] pyridin-7-amine; 96) 1 -isopropyl-5 - (2-methoxy-3-pyridyl) -N - [(6-methoxy-3-pyridyl) methyl] -3-methylpyrazolo [4,3- b] pyridin-7-amine; 97) 5 - (2-isopropoxy-3-pyridyl) -1 -isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridine-7-amine; 98) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N- (1H-1,2,4-triazol-3-ylmethyl) pyrazolo [4,3b] pyridin-7-amine ; 99) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-N- (2H-tetrazol-5-ylmethyl) pyrazolo [4,3- b] pyridin-7-amine; 100) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N- (2-pyridylmethyl) pyrazolo [4,3-b] pyridine-7amine; 101) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(6-methyl-2-pyridyl) methyl] pyrazolo [4,3-b] pyridin-7-amine; 102) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-N - [(6-methoxy-2-pyridyl) methyl] -3-methylpyrazolo [4,3- b] pyridin-7-amine; 103) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(2-methyl-4-pyridyl) methyl] pyrazolo [4,3-b] pyridin-7-amine; 104) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-N - [(2-methoxy-4-pyridyl) methyl] -3-methylpyrazolo [4,3- b] pyridin-7-amine; 105) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(2-methylpyrimidin-4-yl) methyl] pyrazolo [4,3b] pyridin-7-amine; 106) 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-N - [(5-methoxy-3-pyridyl) methyl] -3-methylpyrazolo [4,3- b] pyridin-7-amine; 107) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [[6- (trifluoromethyl) -2-pyridyl] methyl] pyrazolo [4,3-b] pyridine-7 - amine; 108) 3 - [[[5 - (2-ethoxy-3-pyridyl) -1-isopropyl-3-methylpyrazolo [4,3-b] pyridin-7-yl] amino] methyl] 1-methylpyridin-2-one ; 109) 5- (2-ethoxy-3-pyridyl) -N - [(1-ethylpyrazol-4-yl) methyl] -1-isopropyl-3-methylpyrazolo [4,3b] pyridin-7-amine; 110) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-N - [(1-propylpyrazol-4-yl) methyl] pyrazolo [4,3- b] pyridin-7-amine; 111) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-N - [(6-methoxy-3-pyridyl) methyl] -3-methylpyrazolo [4,3b] pyridin-7-amine; 112) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-N - [(5-methoxy-2-pyridyl) methyl] -3-methylpyrazolo [4,3b] pyridin-7-amine; 113) 5- (2-ethoxy-3-pyridyl) -3-methyl-N - [(2-methylthiazol-4-yl) methyl] -1 - (oxetan-3-yl) pyrazolo [4,3b] pyridine- 7-amine; 114) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-N - [(5-methoxypyrazin-2-yl) methyl] -3-methylpyrazolo [4,3b] pyridin-7-amine; 115) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-N- (3-pyridylmethyl) pyrazolo [4,3-b] pyridine-7 - - 163 037544 amines; 116) 5- (2-ethoxy-3-pyridyl) -N - [(6-fluoro-3-pyridyl) methyl] -1-isopropyl-3-methylpyrazolo [4,3- b] pyridin-7-amine; 117) N - [[6- (difluoromethyl) -3-pyridyl] methyl] -5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methylpyrazolo [4,3-b] pyridine-7-amine ; 118) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-N - [(3-methoxy-2-pyridyl) methyl] -3-methylpyrazolo [4,3- b] pyridin-7-amine; 120) (R) -5- (2-ethoxy-3-pyridyl) -3 -methyl-1- [1-methylpropyl] -N- (1H-pyrazol-3-ylmethyl) pyrazolo [4,3-b] pyridine -7 -amine or (S) -5 - (2-ethoxy-3-pyridyl) -3 -methyl-1- [1-methylpropyl] -N- (1H-pyrazol-3 ylmethyl) pyrazolo [4,3-b ] pyridine-7-amine; 122) (R) -5- (2-ethoxy-3-pyridyl) -3-methyl-1- [1-methylpropyl] -N - [(1-methyl-1,2,4-triazol-3-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine or (S) -5- (2-ethoxy-3-pyridyl) -3-methyl-1- [1-methylpropyl] -N - [(1methyl- 1,2,4-mriazol-3-yl) methyl] pyrazolo [4,3-b] pyridine-7-αmine; 124) (R) -5- (2-ethoxy-3-pyridyl) -3-methyl-N - [(5-methyl-1,3,4-oxαdiazol-2-yl) methyl] -1- [1- methylpropyl] pyrazolo [4,3-b] pyridin-7-amine or (S) -5- (2-ethoxy-3-pyridyl) -3-methyl-N - [(5-methyl-1,3,4oxadiazole- 2-yl) methyl] -1- [1-methylpropyl] pyrazolo [4,3-b] pyridin-7-amine; 125а) (R) -5- (2-ethoxy-3-pyridyl) -N - [(5-methoxy-3-pyridyl) methyl] -3-methyl-1- [1-methylnropyl] pyrazolo [4,3- b] pyridine-7-amine; 125b) (S) -5- (2-ethoxy-3-pyridyl) -N - [(5-methoxy-3-pyridyl) methyl] -3-methyl-1- [1-methylnropyl] pyrazolo [4,3- B] pyridin-7-amine; 126а) (R) -5- (2-ethoxy-3-pyridyl) -N - [(2-methoxy-4-pyridyl) methyl] -3-methyl-1- [1-methylnpropyl] pyrazolo [4,3- B] pyridin-7-amine; 126b) (S) -5- (2-ethoxy-3-pyridyl) -N - [(2-methoxy-4-pyridyl) methyl] -3-methyl-1- [1-methylnpropyl] pyrazolo [4,3- b] pyridine-7-amine; 127а) (R) -5- (2-ethoxy-3-pyridyl) -3-methyl-1- [1-methylpropyl] -N - [(2-methyltetrazol-5-yl) methyl] pyrazolo [4,3- b] pyridine-7-amine; 127b) (S) -5- (2-ethoxy-3-pyridyl) -3-methyl-1- [1-methylpropyl] -N - [(2-methyltetrazol-5-yl) methyl] pyrazolo [4,3- b] pyridine-7-amine; 128а) (R) -5- (2-ethoxy-3-pyridyl) -3-methyl-N - [(5-methyl-1,2,4-oxαdiazol-3-yl) methyl] -1- [1- methylpropyl] pyrazolo [4,3-b] pyridin-7-amine; 128b) (S) -5- (2-ethoxy-3-pyridyl) -3-methyl-N - [(5-methyl-1,2,4-oxadiazol-3-yl) methyl] -1- [1- methylpropyl] pyrazolo [4,3-b] pyridin-7-amine; 129а) (R) -5- (2-ethoxy-3-pyridyl) -3-methyl-N - [(2-methyloxazol-4-yl) methyl] -1- [1-methylpropyl] pyrazolo [4,3- B] pyridine-7-amine; 129b) (S) -5- (2-ethoxy-3-pyridyl) -3-methyl-N - [(2-methyloxazol-4-yl) methyl] -1- [1-methylpropyl] pyrazolo [4,3- B] pyridine-7-amine; 130а) (R) -5- (2-ethoxy-3-pyridyl) -N- (1H-imidazol-4-ylmethyl) -3 -methyl-1- [1-methylpropyl] pyrazolo [4,3-b] pyridine -7 -amine; 130b) (S) -5- (2-ethoxy-3-pyridyl) -N- (1H-imidazol-4-ylmethyl) -3 -methyl-1- [1-methylpropyl] pyrazolo [4,3-b] pyridine -7 -amine; 131а) (R) -5- (2-ethoxy-3-pyridyl) -3 -methyl-1- [1 -methylpropyl] -N - [(5-methyl-1H-pyrazol-3-yl) methyl] pyrazolo [ 4,3-b] pyridine-7-amine; 131b) (S) -5- (2-ethoxy-3-pyridyl) -3 -methyl-1- [1-methylpropyl] -N - [(5-methyl-1H-pyrazol-3-yl) methyl] pyrazolo [ 4,3-b] pyridine-7-amine; 132а) (R) -5- (2-ethoxy-3-pyridyl) -3-methyl-N - [(1-methylimidazol-4-yl) methyl] -1- [1-methylpropyl] pyrazolo | 4.3-b | purudin-7-amine; 132b) (S) -5- (2-ethoxy-3-pyridyl) -3-methyl-N - [(1-methylimidazol-4-yl) methyl] -1- [1-methylpropyl] pyrazolo | 4.3-b | purudin-7-amine; 133а) (R) -5- (2-ethoxy-3-pyridyl) -3-methyl-N - [(2-methyloxαzol-5-yl) methyl] -1- [1-methylpropyl] pyrazolo [4,3- B] pyridine-7-amine; 133b) (S) -5- (2-ethoxy-3-pyridyl) -3-methyl-N - [(2-methyloxαzol-5-yl) methyl] -1- [1-methylpropyl] pyrazolo [4,3- B] pyridine-7-amine; 134а) (R) -3-methyl-1- [1-methylnropyl] -N - [(1-methyl-1,2,4-mriαzol-3-yl) methyl] -5- (2-propoxy-3pyridyl) pyrazolo [4,3-b] pyridin-7-amine; 134b) (S) -3-methyl-1- [1-methylnpropyl] -N - [(1-methyl-1,2,4-mriazol-3-yl) methyl] -5- (2-propoxy-3pyridyl) pyrazolo [4,3-b] pyridin-7-amine; 135а) (R) -3 -methyl-1- [1-methylpropyl] -5- (2-propoxy-3-pyridyl) -N- (1H-pyrazol-3-ylmethyl) pyrazolo | 4.3-b | pyridin-7 -amine; 13 5b) (S) -3 -methyl-1- [1-methylpropyl] -5- (2-propoxy-3-pyridyl) -N- (1H-pyrazol-3-ylmethyl) pyrazolo | 4.3-b | purudin-7-amine; 137) (R) -5- (2-ethoxy-3-pyridyl) -1- [1-methylpropyl] -N- (1H-pyrazol-3-ylmethyl) pyrazolo [4,3- b] puridin-7-amine or (S) -5- (2-ethoxy-3-pyridyl) -1- [1-methylpropyl] -N- (1H-pyrazol-3-ylmethyl) pyra-164 037544 zolo [4 , 3-b] pyridine-7-amine; 139) (R) -5- (2-ethoxy-3-pyridyl) -N - [(5-methyl-1,3,4-oxadiazol-2-yl) methyl] -1- [1-methylpropyl] pyrazolo [ 4,3-b] pyridin-7-amine or (S) -5- (2-ethoxy-3-pyridyl) -N - [(5-methyl-1,3,4-oxadiazol-2-yl) methyl] -1 [1-methylpropyl] pyrazolo [4,3-b] pyridine-7-amine; 141) (R) -5- (2-ethoxy-3-pyridyl) -1- [1-methylpropyl] -N - [(1-methyl-1,2,4-triazol-3-yl) methyl] pyrazolo [ 4,3-b] pyridin-7-amine or (S) -5- (2-ethoxy-3-pyridyl) -1- [1-methylpropyl] -N - [(1-methyl-1,2,4triazole- 3-yl) methyl] pyrazolo [4,3-b] pyridin-7-amine; 142) 1 -isopropyl-3-methyl-N - [(1-methylimidazol-4-yl) methyl] -5 - (2-propoxy-3-pyridyl) pyrazolo [4,3-b] pyridine-7 - amine; 143) 1-isopropyl-3-methyl-5 - (2-propoxy-3-pyridyl) -N- (1H-pyrazol-3-ylmethyl) pyrazolo [4,3- b] pyridin-7-amine; 144а) (R) -5- (2-ethoxy-3-pyridyl) -3 -methyl-1- [1-methylpropyl] -N- (1H-1,2,4-triazol-3-ylmethyl) pyrazolo [4 , 3-b] pyridine-7-amine; 144b) (S) -5- (2-ethoxy-3-pyridyl) -3 -methyl-1- [1-methylpropyl] -N- (1H-1,2,4-triazol-3-ylmethyl) pyrazolo [4 , 3-b] pyridine-7-amine; 145) 1 -isopropyl-3-methyl-N - [(1-methyl-1,2,4-triazol-3-yl) methyl] -5 - (2-propoxy-3-pyridyl) pyrazolo [4, 3-b] pyridine-7-amine; 146) 1-isopropyl-3-methyl-5- (2-propoxy-3-pyridyl) -N- (1H-1,2,4-triazol-3-ylmethyl) pyrazolo [4,3b] pyridin-7-amine ; 147) 1 -isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] -5-thiazol-2-ylpyrazolo [4,3-b] pyridin7-amine; 148) 1-isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] -5- (5-methylthiazol-2-yl) pyrazolo [4,3- b] pyridin-7-amine; 149) 1-isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] -5- (4-methylthiazol-2-yl) pyrazolo [4,3- b] pyridin-7-amine; 150) 3- [1 -isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3-b] pyridin-5-yl] -5methyloxazolidin-2-one; 151) 3- [1 -isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3-b] pyridin-5-yl] oxazolidin-2-one; 152) 1- [1 -isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3-b] pyridin-5-yl] azetidin-2-one; 153) 1-tert-butyl-3 - [1-isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3- b] pyridin-5-yl] imidazolidin-2-one; 154) 1- [1 -isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3-b] pyridin-5-yl] pyrrolidin-2-one; 155) 3- [1-isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3-b] pyridin-5-yl] -4methyloxazolidin-2-one; 156) 4-ethyl-3 - [1-isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylamino] pyrazolo [4,3-L] pyridin5-yl] oxazolidin-2-one; 157) N - [[5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methylpyrazolo [4,3-b] pyridin-7-yl] methyl] -5methoxypyridine-3-amine; 158) N - [[5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methylpyrazolo [4,3-b] pyridin-7-yl] methyl] -1 -methyl1,2,4-triazole -3 -amine; 159) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-7- [2- (5-methoxy-3-pyridyl) ethyl] -3-methylpyrazolo [4,3b] pyridine; 160) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-7- [2- (1-methyl-1,2,4-triazol-3-yl) ethyl] pyrazolo [4, 3-b] pyridine; 161) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-N - [(2-methyl-1,2,4-triazol-3-yl) methyl] pyrazolo [4,3- b] pyridine-7-amine; 162) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-N - [(4-methyl-1,2,4-triazol-3-yl) methyl] pyrazolo [4,3- B] pyridine-7-amine; 163) 5- (2-ethoxy-3-pyridyl) -3-methyl-N - [(1-methyl-1,2,4-triazol-3-yl) methyl] -1- (oxetan-3-yl) pyrazolo [4,3-b] pyridine-7-amine; 164) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-7 - [(1-methylpyrazol-4-yl) methylsulfanyl] pyrazolo [4,3-b] pyridine; 165) N - [[l- (difluoromethyl) pyrazol-4-yl] methyl] -5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methylpyrazolo [4,3-b] pyridine-7 - amine; 166) 5 - (2-ethoxy-3-pyridyl) -N - [[5- (fluoromethyl) isoxazol-3-yl] methyl] -1 -isopropyl-3-methylpyrazolo [4,3-b] pyridine- 7 -amine; 167) 5 - (2-ethoxy-3-pyridyl) -N- [[3 - (fluoromethyl) isoxazol-5-yl] methyl] -1 -isopropyl-3-methylpyrazolo [4,3-b] pyridine- 7 -amine; 168) 1-isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] -5-oxazol-2-ylpyrazolo [4,3-b] pyridine- - 165 037544 7-amine; 169) 1-isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] -5- (3-methyltriazol-4-yl) pyrazolo [4,3- b] pyridin-7-amine; 170) 1 -isopropyl-5 - (2-methoxy-3-pyridyl) -3 -methyl-N - [[2- (trifluoromethyl) -3-pyridyl] methyl] pyrazolo [4,3-b] pyridine- 7 -amine; 171) 3- [1 -isopropyl-7 - [(2-methoxy-3-pyridyl) methylamino] -3-methylpyrazolo [4,3-b] pyridin-5-yl] 1H-pyridin-2-one; 172) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-N - [(3-methoxy-4-pyridyl) methyl] -3-methylpyrαzolo [4,3b] pyridin-7-amine; 173) 1-isopropyl-5- (2-methoxy-3-pyridyl) -3-methyl-N - [(2-methylmiazol-5-yl) methyl] pyrazolo [4,3b] pyridin-7-amine; 174) 5- (2-cyclopropoxypyridin-3-yl) -1-isopropyl-N - ((2-methoxypyridin-3-yl) methyl) -3-methyl1H-pyrazolo [4,3-b] pyridin-7-amine ; 175) 1 -isopropyl-N - ((2-methoxypyridin-3-yl) methyl) -3 -methyl-5- (1-methyl-1H-pyrazol-5-yl) -1H-pyrazolo [4,3-b ] pyridine-7-amine; 176) 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-N - [(5-methoxypyrimidin-2-yl) methyl] -3-methylpyrazolo [4,3-b] pyridine-7-amine ; 177) 3- [1-isopropyl-3-methyl-7 - [(1-methylnyrαzol-4-yl) methylamino] pyrαzolo [4,3-b] pyridin-5-yl] 1H-pyridin-2-one; 178) N - [[2- (difluoromethyl) -3-pyridyl] methyl] -5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methylpyrazolo [4,3-b] pyridine-7-amine ; 179) 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-N - [(6-methoxypyrimidin-4-yl) methyl] -3-methylpyrazolo [4,3-b] pyridine-7-amine ; 180) 5- (2- (ethoxy-1,1 -d ₂ ) pyridin-3-yl) -1 -isopropyl-N - ((2-methoxypyridin-3-yl) methyl) -3 -methyl- 1H-pyrazolo [4,3-b] pyridine-7-amine; 181) 5- (2- (ethoxy-d ₅ ) pyridin-3-yl) -1-isopropyl-N - ((2-methoxypyridin-3-yl) methyl) -3-methyl-1H-pyrazolo [4.3 -B] pyridine-7-amine; 182) 5- (2- (ethoxy-2,2,2-dh) pyridin-3-yl) -1 -isopropyl-N - ((2-methoxypyridin-3-yl) methyl) -3 -methyl1H-pyrazolo [ 4,3-b] pyridine-7-amine; 183) 1-isopropyl-N - ((2-methoxypyridin-3-yl) methyl) -3 -methyl-5- (2- (trifluoromethyl) pyridin-3-yl) 1H-pyrazolo [4,3-b] pyridine -7 -amine; 184) 3 - (difluoromethyl) -5 - (2-ethoxypyridin-3-yl) -1-isopropyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) 1H-pyrazolo [4,3- B] pyridine-7-amine; 185) 1-isopropyl-3-methyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) -5- (1H-1,2,4-triαzol-1-yl) -1Hpyrazolo [4 , 3-b] pyridine-7-amine; 186) 3- [1-isopropyl-3-methyl-7 - [(1-methyl-1,2,4-triazol-3-yl) methylamino] pyrazolo [4,3-b] pyridin5-yl] -1H- pyridin-2-one; 187) 3- [1-isopropyl-3-methyl-7- (1H-pyridin-3-ylmethylamino) pyrazolo [4,3-b] pyridin-5-yl] -1H-pyridin-2-one; 188) 5- [2- (difluoromethoxy) -3-pyridyl] -1 -isopropyl-N - [(2-methoxy-3-pyridyl) methyl] -3-methylpyrazolo [4,3-b] pyridine-7-amine ; 189) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-N - [(4-methoxypyrimidin-2-yl) methyl] -3-methylpyrazolo [4,3-b] pyridine-7-amine; 190) 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-N - [(4-methoxypyrimidin-5-yl) methyl] -3 -methylpyrazolo [4,3-b] pyridine-7-amine ; 191) 5- (2-ethoxy-3-pyridyl) -N - [(2-ethoxy-3-pyridyl) methyl] -1 -isopropyl-3-methylpyrazolo [4,3- b] pyridine-7-amine; 192) 5- [2- (dimethylamino) -3-pyridyl] -1 -isopropyl-N - [(4-methoxyphenyl) methyl] -3-methylpyrazolo [4,3-b] pyridine-7-amine; 193) 3- [1-isopropyl-3-methyl-7 - [[2- (trifluoromethyl) -3-pyridyl] methylamino] pyrazolo [4,3- b] pyridin-5-yl] -III-pyridin-2-one; 194) 1-isopropyl-3-methyl-5- (3-methylisoxazol-4-yl) -N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3b] pyridin-7-amine; 195) 1-isopropyl-3-methyl-5- (1-methyl-1H-1,2,4-triazol-5-yl) -N - ((1-methyl-1H-pyrαzol-4-yl) methyl) 1H-pyrazolo [4,3-b] pyridine-7-amine; 196) 1-isopropyl-3-methyl-5 - (2-propoxy-3-pyridyl) -N- (1H-pyrazol-4-ylmethyl) pyrazolo [4,3- b] puridine-7-αmine; 197) 5- (2-ethoxy-3-pyridyl) -N - [(2-methoxy-3-pyridyl) methyl] -3 -methyl-1 - (oxetane-3-yl) pyrazolo [4,3- B] pyridine-7-amine; 198) 5- (2- (ethyl (methyl) amino) pyridin-3-yl) -1-isopropyl-N- (4-methoxybenzyl) -3-methyl-1Hpyrazolo [4,3-b] pyridin-7-amine ; 199) 5- (2-ethoxypyridin-3-yl) -3 - (fluoromethyl) -1-isopropyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) - - 166 037544 1H-pyrazolo [4,3-b] pyridine-7-amine; 200) 1 -isopropyl-3-methyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) -5 - (4-methyloxazol-5-yl) -1Hpyrazolo [4,3-b] pyridine -7 -amine; 201) 5- [2- (dimethylamino) -3-pyridyl] -1 -isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] pyrazolo [4,3-b] pyridine-7 - amine; 202) 1-isopropyl-3-methyl-N - ((1-methyl-1H-pyrazol-4-yl) methyl) -5- (4-methyloxazol-2-yl) -1Hpyrazolo [4,3-b] pyridine -7 -amine; 203) 1-isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] -5- (4-methyl-1,2,4-triazol-3-yl) pyrazolo [4,3- b] pyridine-7-amine; and pharmaceutically acceptable salts of any of these compounds. 13. A compound according to claim 1, wherein the compound is selected from the group consisting of 6) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(1-methyltriazol-4-yl) methyl] pyrazolo [4.3b] pyridin-7-amine; 7) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N- (1H-pyrazol-4-ylmethyl) pyrazolo [4,3-b] pyridin7-amine; 21) 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-N - [(1-methylimidazol-4-yl) methyl] pyrazolo [4,3-b] pyridin7-amine; 29) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(4-methylthiazol-2-yl) methyl] pyrazolo [4,3- b] pyridin-7-amine; 32) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(2-methylthiazol-5-yl) methyl] pyrazolo [4,3- b] pyridin-7-amine; 3 9) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-N- (1H-pyrazol-3-ylmethyl) pyrazolo [4,3-b] pyridin-7-amine; 47) 5- (2-ethoxypyridin-3-yl) -1-isopropyl-3-methyl-N - ((5-methyl-1H-pyrazol-3-yl) methyl) -1H-pyrazolo [4,3-b ] pyridine-7-amine; 50) 5- (2-ethoxypyridin-3-yl) -1-isopropyl-3-methyl-N - ((4-methyloxazol-2-yl) methyl) -1H-pyrazolo [4,3-b] pyridine -7 -amine; 56) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-N - [(1-methyl- 1,2,4-triazol-3-yl) methyl] pyrazolo [4,3-b] pyridine- 7-amine; 57) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-N- (1H-pyrazole-3-ylmethyl) pyrazolo [4,3-b] pyridin-7-amine; 67а) (R) -5 - (2-ethoxy-3-pyridyl) -3 -methyl-1- [1-methylpropyl] -N - [(1-methylpyrazol-3-yl) methyl] pyrazolo [4,3- b] pyridine-7-amine; 67b) (S) -5 - (2-ethoxy-3-pyridyl) -3 -methyl-1- [1-methylpropyl] -N - [(1-methylpyrazol-3-yl) methyl] pyrazolo [4,3- b] pyridine-7-amine; 77) 5 - (2-ethoxy-3-pyridyl) -1 -isopropyl-3-methyl-N - [[2- (trifluoromethyl) -3-pyridyl] methyl] pyrazolo [4,3-b] pyridine- 7 -amine; 82) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-N - [(6-methoxypyrazin-2-yl) methyl] -3-methylpyrazolo [4,3- b] pyridin-7-amine; 85) 5- (2-ethoxy-3-pyridyl) -N - [(2-fluoro-3-pyridyl) methyl] -1-isopropyl-3-methylpyrazolo [4,3- b] pyridin-7-amine; 86) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-N - [(2-methoxy-3-pyridyl) methyl] -3-methylpyrazolo [4,3- b] pyridin-7-amine; 88) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-N - [(2-methoxyphenyl) methyl] -3-methylpyrazolo [4,3- b] pyridin-7-amine; 89) 5- (2-ethoxy-3-pyridyl) -N - [(2-fluorophenyl) methyl] -1-isopropyl-3-methylpyrazolo [4,3-b] pyridin7-amine; 90) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [[2- (trifluoromethyl) phenyl] methyl] pyrazolo [4,3b] pyridin-7-amine; 92) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-N - [(4-methoxy-3-pyridyl) methyl] -3-methylpyrazolo [4,3- b] pyridin-7-amine; 94) 1 -isopropyl-3-methyl-N - [(1-methylpyrazol-4-yl) methyl] -5- (2-propoxy-3-pyridyl) pyrazolo [4,3b] pyridin-7-amine; 100) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N- (2-pyridylmethyl) pyrazolo [4,3-b] pyridine-7amine; 101) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [(6-methyl-2-pyridyl) methyl] pyrazolo [4,3-b] pyridin-7-amine; 107) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-3-methyl-N - [[6- (trifluoromethyl) -2-pyridyl] methyl] pyrαzolo [4,3-b] pyridine-7 - amine; 111) 5- (2-ethoxy-3-pyridyl) -1-isopropyl-N - [(6-methoxy-3-pyridyl) methyl] -3-methylpyrazolo [4,3b] pyridin-7-amine; 113) 5- (2-ethoxy-3-pyridyl) -3-methyl-N - [(2-methylthiazol-4-yl) methyl] -1 - (oxetan-3-yl) pyrazolo [4,3- - 167 037544 b] pyridin-7-amine; 118) 5- (2-ethoxy-3-pyridyl) -1 -isopropyl-N - [(3-methoxy-2-pyridyl) methyl] -3-methylpyrazolo [4,3b] pyridin-7-amine; 120) (R) -5- (2-ethoxy-3-pyridyl) -3 -methyl-1- [1-methylpropyl] -N- (1H-pyrazole-3-ylmethyl) pyrazolo [4,3-b] pyridine -7-amine or (S) -5- (2-ethoxy-3-pyridyl) -3-methyl-1- [1-methylpropyl] -N- (1H-pyrazol-3ylmethyl) pyrazolo [4,3-b] pyridine-7-amine; 135а) (R) -3 -methyl-1- [1-methylpropyl] -5- (2-propoxy-3-pyridyl) -N- (1H-pyrazol-3-ylmethyl) pyrazolo [4,3-b] pyridine -7 -amine; 13 5b) (S) -3 -methyl-1- [1-methylpropyl] -5- (2-propoxy-3-pyridyl) -N- (1H-pyrazole-3-ylmethyl) pyrazolo [4,3- b] pyridine-7-amine; 137) (R) -5- (2-ethoxy-3-pyridyl) -1- [1-methylpropyl] -N- (1H-pyrazol-3-ylmethyl) pyrazolo [4,3- B] pyridin-7-amine or (S) -5- (2-ethoxy-3-pyridyl) -1- [1-methylpropyl] -N- (1H-pyrazol-3-ylmethyl) pyrazolo [4,3-b ] pyridine-7-amine; 141) (R) -5- (2-ethoxy-3-pyridyl) -1- [1-methylpropyl] -N - [(1-methyl-1,2,4-triazol-3-yl) methyl] pyrazolo [ 4,3-b] pyridin-7-amine or (S) -5- (2-ethoxy-3-pyridyl) -1- [1-methylpropyl] -N - [(1-methyl-1,2,4- triazol-3yl) methyl] pyrazolo [4,3-b] pyridine-7-amine; 180) 5- (2- (ethoxy-1,1 -d ₂ ) pyridin-3-yl) -1 -isopropyl-N - ((2-methoxypyridin-3-yl) methyl) -3 -methyl- 1H-pyrazolo [4,3-b] pyridine-7-amine; 181) 5- (2- (ethoxy-d ₅ ) pyridin-3-yl) -1-isopropyl-N - ((2-methoxypyridin-3-yl) methyl) -3-methyl-1H-pyrazolo [4.3 -B] pyridine-7-amine; 182) 5- (2- (ethoxy-2,2,2-dh) pyridin-3-yl) -1 -isopropyl-N - ((2-methoxypyridin-3-yl) methyl) -3 -methyl1Н-pyrazolo [ 4,3-b] pyridine-7-amine; 191) 5- (2-ethoxy-3-pyridyl) -N - [(2-ethoxy-3-pyridyl) methyl] -1 -isopropyl-3-methylpyrazolo [4,3- b] pyridin-7-amine; and pharmaceutically acceptable salts of any of these compounds. 14. Use of a compound according to any one of claims 1 to 13 for the treatment of a neurodegenerative disorder. 15. Use according to claim 14, wherein the neurodegenerative disorder is selected from the group consisting of Alzheimer's disease, Parkinson's disease and Hentington's disease. 16. Use of a compound according to any one of claims 1 to 13 for the treatment of a mental disorder. 17. Use according to claim 16, wherein the mental disorder is selected from the group consisting of attention deficit / hyperactivity disorder (ADHD), depression, anxiety, narcolepsy, cognitive impairment, cognitive impairment associated with schizophrenia (CIAS), or syndrome restless legs. 18. A pharmaceutical composition for the treatment of a neurodegenerative disorder, comprising a therapeutically effective amount of a compound according to any one of claims 1 to 13 and one or more of pharmaceutically acceptable carriers, diluents and excipients. 19. The pharmaceutical composition of claim 18, wherein the neurodegenerative disorder is selected from the group consisting of Alzheimer's disease, Parkinson's disease and Huntington's disease. 20. A pharmaceutical composition for the treatment of a mental disorder, comprising a therapeutically effective amount of a compound according to any one of claims 1 to 13 and one or more pharmaceutically acceptable carriers, diluents and excipients. 21. The pharmaceutical composition of claim 20, wherein the mental disorder is selected from the group consisting of attention deficit / hyperactivity disorder (ADHD), depression, anxiety, narcolepsy, cognitive impairment, cognitive impairment associated with schizophrenia (CIAS), or restless legs syndrome. 22. A method of treating a neurodegenerative disorder selected from the group consisting of Alzheimer's disease, Parkinson's disease and Huntington's disease, the method comprising administering a therapeutically effective amount of a compound according to any one of claims 1-13 to a patient in need thereof. 23. A method of treating a mental disorder selected from the group consisting of attention deficit / hyperactivity disorder (ADHD), depression, anxiety, narcolepsy, cognitive impairment, cognitive impairment associated with schizophrenia (CIAS), or restless legs syndrome, with this method comprises administering a therapeutically effective amount of a compound according to any one of claims 1 to 13 to a patient in need thereof.