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WO2018153545A1 - Dérivés de méthanone pipéridine ayant une activité multimodale contre la douleur - Google Patents

Dérivés de méthanone pipéridine ayant une activité multimodale contre la douleur Download PDF

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Publication number
WO2018153545A1
WO2018153545A1 PCT/EP2018/000078 EP2018000078W WO2018153545A1 WO 2018153545 A1 WO2018153545 A1 WO 2018153545A1 EP 2018000078 W EP2018000078 W EP 2018000078W WO 2018153545 A1 WO2018153545 A1 WO 2018153545A1
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substituted
unsubstituted
alkyl
compound
alkynyl
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Carmen ALMANSA-ROSALES
Monica Garcia-Lopez
Ute Christmann
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Esteve Pharmaceuticals SA
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Laboratorios del Dr Esteve SA
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

Definitions

  • the present invention relates to compounds having dual pharmacological activity towards both the sigma ( ⁇ ) receptor, and the ⁇ -opioid receptor (MOR or mu-opioid receptor) and more particularly to piperidine methanone derivatives having this pharmacological activity, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.
  • NSAIDs non-steroidal anti-inflammatory drugs
  • opioid agonists opioid agonists
  • calcium channel blockers and antidepressants
  • antidepressants but they are much less than optimal regarding their safety ratio. All of them show limited efficacy and a range of secondary effects that preclude their use, especially in chronic settings.
  • MOR ⁇ -opioid receptor
  • MOR agonists are not optimal for the treatment of chronic pain as indicated by the diminished effectiveness of morphine against chronic pain conditions. This is especially proven for the chronic pain conditions of neuropathic or inflammatory origin, in comparison to its high potency against acute pain.
  • the finding that chronic pain can lead to MOR down-regulation may offer a molecular basis for the relative lack of efficacy of morphine in long-term treatment settings [Dickenson, A.H., Suzuki, R. Opioids in neuropathic pain: Clues from animal studies. Eur J Pain 9, 113-6 (2005)].
  • prolonged treatment with morphine may result in tolerance to its analgesic effects, most likely due to treatment-induced MOR down-regulation, internalization and other regulatory mechanisms.
  • long-term treatment can result in substantial increases in dosing in order to maintain a clinically satisfactory pain relief, but the narrow therapeutic window of MOR agonists finally results in unacceptable side effects and poor patient compliance.
  • the sigma- 1 ( ⁇ ) receptor was discovered 35 years ago and initially assigned to a new subtype of the opioid family, but later on and based on the studies of the enantiomers of SKF-10,047, its independent nature was established.
  • the first link of the ⁇ 1 receptor to analgesia was established by Chien and Pasternak [Chien CC, Pasternak GW. Sigma antagonists potentiate opioid analgesia in rats. Neurosci. Lett. 190, 137-9 (1995)], who described it as an endogenous anti-opioid system, based on the finding that ⁇ 1 receptor agonists counteracted opioid receptor mediated analgesia, while ⁇ receptor antagonists, such as haloperidol, potentiated it.
  • capsaicin did not induce mechanical hypersensitivity, both phases of formalin-induced pain were reduced, and cold and mechanical hypersensitivity were strongly attenuated after partial sciatic nerve ligation or after treatment with paclitaxel, which are models of neuropathic pain. Many of these actions were confirmed by the use of ⁇ 1 receptor antagonists and led to the advancement of one compound, S1 RA, into clinical trials for the treatment of different pain states.
  • Compound S1 RA exerted a substantial reduction of neuropathic pain and anhedonic state following nerve injury (i.e., neuropathic pain conditions) and, as demonstrated in an operant self-administration model, the nerve- injured mice, but not sham-operated mice, acquired the operant responding to obtain it (presumably to get pain relief), indicating that ⁇ 1 receptor antagonism relieves neuropathic pain and also address some of the comorbidities (i.e., anhedonia, a core symptom in depression) related to pain states.
  • nerve injury i.e., neuropathic pain conditions
  • ⁇ 1 receptor antagonism relieves neuropathic pain and also address some of the comorbidities (i.e., anhedonia, a core symptom in depression) related to pain states.
  • therapies are a common clinical practice and many efforts are directed to assess the best combination of available drugs in clinical studies [Mao J, Gold MS, Backonja M. Combination drug therapy for chronic pain: a call for more clinical studies. J. Pain 12, 157-166 (2011)].
  • opioids are among the most potent analgesics but they are also responsible for various adverse effects which seriously limit their use.
  • the technical problem can therefore be formulated as finding compounds that have an alternative or improved pharmacological activity in the treatment of pain.
  • the present invention offers a solution by combining in a single compound binding to two different receptors relevant for the treatment of pain. This was mainly achieved by providing the compounds according to the invention that bind both to the ⁇ -opioid receptor and to the ⁇ 1 receptor.
  • the main object of the invention is in one aspect directed to piperidine methanone derivatives having a dual activity binding to the ⁇ 1 receptor and the ⁇ -opioid receptor for use in the treatment of pain.
  • the compound has a binding expressed as Kj which is preferably ⁇ 1000 nM for both receptors, more preferably ⁇ 500 nM, even more preferably ⁇ 100 nM.
  • R 1 , R 2 , R 3 , R 4 , 4 ,. R 4 ,,, R 4 ' " , X, Y, W, m, n, q and r are as defined below in the detailed description.
  • a further object of the invention refers to the processes for preparation of compounds of general formula (I).
  • a still further object of the invention refers to the use of some intermediate compounds for the preparation of a compound of general formula (I). It is also an object of the invention a pharmaceutical composition comprising a compound of formula (I).
  • the invention is directed to a family of structurally distinct to piperidine methanone derivatives which have a dual pharmacological activity towards both the sigma ( ⁇ ) receptor and the ⁇ -opioid receptor, thus solving the above problem of identifying alternative or improved pain treatments by offering such dual compounds.
  • the invention is directed to compounds having a dual activity binding to the ⁇ 1 receptor and the ⁇ -opioid receptor for use in the treatment of pain.
  • the compound has a binding expressed as K, which is preferably ⁇ 1000 nM for both receptors, more preferably ⁇ 500 nM, even more preferably ⁇ 100 nM.
  • the applicant has surprisingly found that the problem of providing a new effective and alternative for treating pain and pain related disorders can be solved by using a multimodal balanced analgesic approach combining two different synergistic activities in a single drug (i.e., dual ligands which are bifunctional and bind to ⁇ -opioid receptor and to ⁇ 1 receptor), thereby enhancing the opioid analgesia through the ⁇ 1 activation without increasing the undesirable side effects.
  • a dual compound that possess binding to both the ⁇ -opioid receptor and to the ⁇ receptor shows a highly valuable therapeutic potential by achieving an outstanding analgesia (enhanced in respect to the potency of the opioid component alone) with a reduced side-effect profile (safety margin increased compared to that of the opioid component alone) versus existing opioid therapies.
  • the dual compounds according to the present invention would show one or more the following functionalities: ⁇ 1 receptor antagonism and ⁇ -opioid receptor agonism. It has to be noted, though, that both functionalities “antagonism” and “agonism” are also sub-divided in their effect into subfunctionalities like partial agonism or inverse agonism. Accordingly, the functionalities of the dual compound should be considered within a relatively broad bandwidth.
  • An antagonist on one of the named receptors blocks or dampens agonist-mediated responses.
  • Known subfunctionalities are neutral antagonists or inverse agonists.
  • An agonist on one of the named receptors increases the activity of the receptor above its basal level.
  • Known subfunctionalities are full agonists, or partial agonists.
  • the two mechanisms complement each other since MOR agonists are only marginally effective in the treatment of neuropathic pain, while ⁇ 1 receptor antagonists show outstanding effects in preclinical neuropathic pain models.
  • the ⁇ 1 receptor component adds unique analgesic actions in opioid-resistant pain.
  • the dual approach has clear advantages over MOR agonists in the treatment of chronic pain as lower and better tolerated doses would be needed based on the potentiation of analgesia but not of the adverse events of MOR agonists.
  • a further advantage of using designed multiple ligands is a lower risk of drug-drug interactions compared to cocktails or multi-component drugs, thus involving simpler pharmacokinetics and less variability among patients.
  • W is -CH- or nitrogen
  • R 1 is selected from substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl;
  • R 2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl,
  • R 3 is selected from hydrogen, substituted or unsubstituted C 1 - ⁇ alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, -C(0)R 5 , -S(0) 2 R 5 and - C(0)NR 5 R 5 -; wherein R 5 and R 5 - are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl , substituted or unsubsti
  • R 4 and R 4 are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, R 4 and R 4 , may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl; alternatively R 4 and R 4 , may form together with the carbon atom to which they are attached a carbonyl group; R 4 , and F are independently selected from hydrogen, substituted or unsubstituted C 1- ⁇ alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, R 4 ,, and R 4 ,,,, may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl.
  • These compounds according to the invention are optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • these compounds according to the invention are optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.
  • the following proviso applies: when Y is -0-, then m is 1 or 2.
  • the compound according to the invention of general Formula (I) is a compound of general Formula (I , )
  • R 1 , R2, R3, R4, R 4 ,,, R 4 ,,, R 4 ,,,,, X, W, m, n, q and r are as defined below in the detailed description; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.
  • the compound according to the invention of general Formula (I) is a compound of general Formula (la')
  • R 1 , R 2 , R 3 , R 4 , R 4 ,. R 4 ,,, R 4 ' " , X, W, m, q and r are as defined below in the detailed description; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.
  • the compound according to the invention of general Formula (I) is a compound of general Formula (I 2 ')
  • R2, R3, R4, R 4 ,,, R 4 ,,, R 4 ,,,,,,,, X, W, m, n, q and r are as defined below in the detailed description, and wherein R 3 and R 3 - are independently selected from halogen, -R 14 , -OR 11 , -NO2, -NR 11 R 1 r, -NR 11 C(0)R 1 r, -NR 11 S(0)2R 1 r, - S(0) 2 NR 11 R 1 r, -NR 11 C(0)NR,rR 1 r, -SR 11 , -S(0)R 11 , -S(0) 2 R 11 , -CN, haloalkyl, haloalkoxy, -C(0)OR 11 , -C(0)NR 11 R 1 r, -OCH2CH2OR11, -NR 11 S(0)2NR 1 rR 1 r and -C(CH 3 )20R 11 ; and R11, R 14 ,
  • diastereomers a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.
  • the compound according to the invention of general Formula (I) is a compound of general Formula (I 3 ')
  • R2, R3, R4, R 4 ,, Re, R4-, X, W, m, q and r are as defined below in the detailed description, and wherein R 3 and R 3 - are independently selected from halogen, -R 11 , -OR 11 , -NO2, -NR 11 R 1 r, -NR 11 C(0)R 1 r, -NR 11 S(0) 2 R 1 r, - S(0) 2 NR 11 R 1 r, -NR 11 C(0)NR 1 rR 11 ,, -SR 11 , -S(0)R 11 , -S(0) 2 R 11 , -CN, haloalkyl, haloalkoxy, -C(0)OR 11 , -C(0)NR 11 R 1 r, -OCH2CH2OR11, -NR 11 S(0) 2 NR 11 R 11 - and -C(CH 3 )20R 11 ; and R11, R 11 and R 11 - are independently selected from hydrogen, unsubstitute
  • stereoisomers optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.
  • the compound according to the invention of general Formula (I) is a compound of general Formula (I 4 ')
  • the compound according to the invention of general Formula (I) is a compound of general Formula (l Sa ')
  • R2, R3, R 4 ,, R 4 ,,,,,, X, m, q and r are as defined below in the detailed description, and whereRin 6 andR 6 - are independently selected from halogen, - R 11 , -OR11, -NO2, -NR 11 R 11 ,, -NR 11 C(0)R 1 r, -NR 11 S(0) 2 R 1 r, -S(0) 2 NR 11 R 1 r, - NR 11 C(0)NR 11 R 11 ", -SR 11 , -S(0)R 11 , S(0) 2 R 11 , -CN, haloalkyl, haloalkoxy, -
  • the compound according to the invention of general Formula (I) is a compound of general Formula (l 5b ')
  • R2, R3, R 4 ,,, R 4 ,,,,,, X, m, q and r are as defined below in the detailed description, andR 6 andR 6 - are independently selected from halogen, -R 11 , - OR11, -NO2, -NR 11 R 1 r, -NR 11 C(0)R 1 r, -NR 11 S(0) 2 R 11 ,, -S(0) 2 NR 1 ,R 1 r, - NR 11 C(0)NR 11 ,R 1 r, -SR 11 , -S(0)R 11 , S(0) 2 R 11 , -CN, haloalkyl, haloalkoxy, - C(0)OR 11 , -C(0)NR 11 R 1 r, -OCH2CH2OR11, -NR 11 S(0) 2 NR 11 R 1 r and - C(CH 3 )20R 11 ; and R11, R 11 ,,and R 11 , are independently selected from hydrogen, unsubstitute
  • diastereomers a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.
  • the compound according to the invention of general Formula (I) is a compound of general Formula (l 6a ')
  • R2, R3, R 4 ,, R 4 ,,,,,, m, q and r are as defined below in the detailed description, and whereRin 6 andR 6 - are independently selected from halogen, - R 11 , -OR11, -N0 2l -NR 11 R 1 r, -NR 11 C(0)R 1 r, -NR 11 S(0) 2 R 11 -, -S(0) 2 NR 11 R,v, - NR 11 C(0)NR 11 ,R 11 --, -SR 11 , -S(0)R 11 , S(0) 2 R 11 , -CN, haloalkyl, haloalkoxy, - C(0)OR 11 , -C(0)NR 11 R 1 r, -OCH 2 CH 2 OR 11 , -NR 11 S(0) 2 NR 11 ,R 11 - and - C(CH 3 ) 2 OR 11 ; and R11, R 1 r and R 11 - are independently selected from hydrogen, unsubstituted C
  • stereoisomers optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.
  • the compound according to the invention of general Formula (I) is a compound of general Formula (l eb ')
  • R2, R3, R 4 ,,, R 4 ,,,,,, m, q and r are as defined below in the detailed description, and whereiRn 6 andR 6 - are independently selected from halogen, - R 11 , -OR11, -NO2, -NR 11 R 1 r, -NR 11 C(0)R 1 r, -NR 11 S(0) 2 R 11 ,, -S(0) 2 NR 11 R 1 r, - NR 11 C(0)NR 1 rR 1 v, -SR 11 , -S(0)R 11 , S(0) 2 R 14 ,, -CN, haloalkyl, haloalkoxy, - C(0)OR 11 , -C(0)NR 11 R 11 ,, -OCH2CH 2 OR 11 , -NR 11 S(0) 2 NR 11 ,R 14 ' " and - C(CH 3 ) 2 OR 11 ; and R11, R 11 - and R 11 , are independently selected from hydrogen, unsubsti
  • stereoisomers optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.
  • the compound according to the invention of general Formula (I) is a compound of general Formula (I 7 ')
  • R 1 . R2, R3, R 4 ,-, R 4 ,,,,, X, Y, W, m, n, q and r are as defined below in the detailed description, optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.
  • the compound according to the invention of general Formula (I) is a compound of general Formula (I 8 ')
  • stereoisomers optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof.
  • alkyl is understood as meaning saturated, linear or branched hydrocarbons, which may be unsubstituted or substituted once or several times. It encompasses e.g. -CH 3 and -CH2-CH3.
  • C 1 -2-alkyl represents C1- or C2-alkyl
  • C 1 -3-alkyl represents C1-, C2- or C3-alkyl
  • C 1 -4-alkyl represents C1-, C2-, C3- or C4-alkyl
  • C 1 -5-alkyl represents C1-, C2-, C3-, C4-, or C5-alkyl
  • C 1-6 -alkyl represents C1-, C2-, C3-, C4-, C5- or C6-alkyl
  • C 1 -7-alkyl represents C1-, C2-, C3-, C4- , C5-, C6- or C7-alkyl
  • C 1-6 -alkyl represents C1-
  • the alkyl radicals are preferably methyl, ethyl, propyl, methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1 ,1-dimethylpropyl, 1 ,2-dimethylpropyl, 2,2-dimethylpropyl, hexyl, 1- methylpentyl, if substituted also CHF 2 , CF 3 or CH2OH etc.
  • alkyl is understood in the context of this invention as C 1-6 alkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, or octyl; preferably is C 1-6 alkyl like methyl, ethyl, propyl, butyl, pentyl, or hexyl; more preferably is C 1 -4alkyl like methyl, ethyl, propyl or butyl.
  • the alkenyl radicals are preferably vinyl (ethenyl), allyl (2-propenyl).
  • alkenyl is C 2 -io-alkenyl or C 2- 8-alkenyl like ethylene, propylene, butylene, pentylene, hexylene, heptylene or octylene; or is C 2-6 - alkenyl like ethylene, propylene, butylene, pentylene, or hexylene; or is C 2- 4-alkenyl, like ethylene, propylene, or butylenes.
  • Alkynyl is understood as meaning unsaturated, linear or branched hydrocarbons, which may be unsubstituted or substituted once or several times. It encompasses groups like e.g.
  • alkynyl in the context of this invention is C 2- 10- alkynyl or C 2-6 -alkynyl like ethyne, propyne, butyene, pentyne, hexyne, heptyne, or octyne; or is C 2-6 -alkynyl like ethyne, propyne, butyene, pentyne, or hexyne; or is C 2- 4- alkynyl like ethyne, propyne, butyene, pentyne, or hexyne.
  • alkyl also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl
  • substituted in the context of this invention is understood as meaning replacement of at least one hydrogen radical on a carbon atom by halogen (F, CI, Br, I), -NRcRc-, -SR C , -S(0)R c , -S(0) 2 R c , -OR c , - C(0)ORc, -CN, -C(0)NRcRc ⁇ haloalkyl, haloalkoxy or -OC 1-6 alkyl, being R c represented by R 11 , R12, R 1 3, (being R 6 - represented by R 1 r, R12', R 13 '; being R c - represented by R 11 ,,, R 1 2", R 13 "; ) wherein R 1 to R 1 r are as defined
  • alkyl also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl
  • alkenyl, alkynyl or O-alkyl substituted is understood in the context of this invention that any alkyl (also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl), alkenyl, alkynyl or O-alkyl which, if substituted, is substituted with one or more of halogen (F, CI, Br, I), -OR c , -CN, -SR c ,-S(0)R c , -S(0) 2 R c .
  • halogen F, CI, Br, I
  • haloalkyl, haloalkoxy, -NR C R C , or -OC 1-6 alkyl being R c represented by R 11 , R12, R 13 , (being Rc- represented by R1 1 -, R 12 ,, R 1 3'; being Rc n represented by R 11 ,, R 1 2"i R 13 ";), wherein R 1 to R 14 ,,are as defined in the description, and wherein when different radicals R 1 to R 14 ,, are present simultaneously in Formula I, they may be identical or different.
  • More than one replacement on the same molecule and also on the same carbon atom is possible with the same or different substituents.
  • This includes for example 3 hydrogens being replaced on the same C atom, as in the case of CF 3 , or at different places of the same molecule, as in the case of e.g. -CH(OH)-CH CH-CHCI 2 .
  • haloalkyl is understood as meaning an alkyl being substituted once or several times by a halogen (selected from F, CI, Br, I). It encompasses e.g. -CH 2 CI, -CH 2 F, -CHCI 2 , -CHF 2 , -CCI3, -CF 3 and -CH2-CHCI2.
  • haloalkyl is understood in the context of this invention as haloge 11 , substituted C 1 -4-alkyl representing halogen substituted C1-, C2-, C3- or C4-alkyl.
  • the halogen-substituted alkyl radicals are thus preferably methyl, ethyl, propyl, and butyl.
  • Preferred examples include -CH 2 CI, -CH 2 F, -CHCI2, -CHF 2 , and -CF 3 .
  • haloalkoxy is understood as meaning an -O-alkyl being substituted once or several times by a halogen (selected from F, CI, Br, I). It encompasses e.g. -OCH2CI, -OCH2F, -OCHCI2, -OCHF2, -OCCI 3l -OCF3 and - OCH 2 -CHCI2.
  • haloalkyl is understood in the context of this invention as halogen-substituted -OC 1 -4 -alkyl representing halogen substituted C1-, C2-, C3- or C4- alkoxy.
  • the halogen-substituted alkyl radicals are thus preferably O-methyl, O-ethyl, O-propyl, and O-butyl.
  • Preferred examples include -OCH2CI, -OCH 2 F, -OCHCI 2l - OCHF2, and -OCF3.
  • cycloalkyl is understood as meaning saturated and unsaturated (but not aromatic) cyclic hydrocarbons (without a heteroatom in the ring), which can be unsubstituted or once or several times substituted.
  • C3-4- cycloalkyl represents C3- or C4-cycloalkyl
  • C3-s-cycloalkyl represents C3-, C4- or C5- cycloalkyl
  • C 3 ⁇ 6 -cycloalkyl represents C3-, C4-, C5- or C6-cycloalkyl
  • C3-7-cycloalkyl represents C3-, C4-, C5-, C6- or C7-cycloalkyl
  • C 3- 8-cycloalkyl represents C3-, C4-, C5- , C6-, C7- or C8-cycloalkyl
  • C 4 ,5-cycloalkyl represents C4- or C5-cycloalkyl, C4-6- cycloal
  • Examples are cyclopropyl, 2-methylcyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclopentylmethyl, cyclohexyl, cycloheptyl, cyclooctyl, and also adamantly.
  • cycloalkyl is C 3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; or is C 3 -7cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; or is C 3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, especially cyclopentyl or cyclohexyl.
  • Aryl is understood as meaning 5 to 18 membered mono or polycyclic ring systems with at least one aromatic ring but without heteroatoms even in only one of the rings. Examples are phenyl, naphthyl, fluoranthenyl, fluorenyl, tetralinyl, indanyl, 9H-fluorenyl or anthracenyl radicals, which can be unsubstituted or once or several times substituted. Most preferably aryl is understood in the context of this invention as phenyl, naphthyl or anthracenyl, preferably is phenyl.
  • a heterocyclyl radical or group (also called heterocyclyl hereinafter) is understood as meaning 5 to 18 membered mono or poly heterocyclic ring systems, with at least one saturated or unsaturated ring which contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring.
  • a heterocyclic group can also be substituted once or several times.
  • Examples include non-aromatic heterocyclyls such as tetrahydropyran, oxazepane, morpholine, piperidine, pyrrolidine as well as heteroaryls such as furan, benzofuran, thiophene, benzothiophene, pyrrole, pyridine, pyrimidine, pyrazine, quinoline, isoquinoline, phthalazine, thiazole, benzothiazole, indole, benzotriazole, carbazole and quinazoline.
  • non-aromatic heterocyclyls such as tetrahydropyran, oxazepane, morpholine, piperidine, pyrrolidine as well as heteroaryls such as furan, benzofuran, thiophene, benzothiophene, pyrrole, pyridine, pyrimidine, pyrazine, quinoline, isoquinoline, phthalazine, thiazole,
  • heterocyclyls as understood herein include heteroaryls and non- aromatic heterocyclyls.
  • the heteroaryl (being equivalent to heteroaromatic radicals or aromatic heterocyclyls) is an aromatic 5 to 18 membered mono or polycyclic heterocyclic ring system of one or more rings of which at least one aromatic 5 to 18 membered ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is an aromatic 5 to 18 membered mono or polycyclic heterocyclic ring system of one or two rings of which at least one aromatic ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from furan, benzofuran, thiophene, benzothiophene, pyrrole, pyridine, pyrimidine, pyrazine, quinoline, isoquinoline, phthalazine, benzothiazole, indole, benzotriazole, carbazole, quinazoline, thiazole, imidazole, pyrazole, o
  • the non-aromatic heterocyclyl is a 5 to 18 membered mono or polycyclic heterocyclic ring system of one or more rings of which at least one ring - with this (or these) ring(s) then not being aromatic - contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a 5 to 18 membered mono or polycyclic heterocyclic ring system of one or two rings of which one or both rings - with this one or two rings then not being aromatic - contain/s one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably is selected from oxazepam, pyrrolidine, piperidine, piperazine, tetrahydropyran, morpholine, indoline, oxopyrrolidine, benzodioxane, oxetane, especially is benzodioxane, morpholine, tetra
  • heterocyclyl is defined as a 5 to 18 membered mono or polycyclic heterocyclic ring system of one or more saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring.
  • it is a 5 to 18 membered mono or polycyclic heterocyclic ring system of one or two saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring.
  • heterocyclyls include oxetane, oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1 ,2,5-thiadiazole, indole, benzotriazole, benzoxazole, oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole and qui
  • oxopyrrolidine is understood as meaning pyrrolidin-2- one.
  • aromatic heterocyclyls heteroaryls
  • non-aromatic heterocyclyls aryls and cycloalkyls
  • the ring system is defined first as an aromatic heterocyclyl (heteroaryl) if at least one aromatic ring contains a heteroatom. If no aromatic ring contains a heteroatom, then the ring system is defined as a non-aromatic heterocyclyl if at least one non-aromatic ring contains a heteroatom.
  • the ring system is defined as an aryl if it contains at least one aryl cycle. If no aryl is present, then the ring system is defined as a cycloalkyl if at least one non-aromatic cyclic hydrocarbon is present.
  • alkylaryl is understood as meaning an aryl group (see above) being connected to another atom through a C 1-6 -alkyl (see above) which may be branched or linear and is unsubstituted or substituted once or several times.
  • alkylaryl is understood as meaning an aryl group (see above) being connected to another atom through 1 to 4 (-CH 2 -) groups.
  • alkylaryl is benzyl (i.e. -CH 2 -phenyl).
  • alkylheterocyclyl is understood as meaning an heterocyclyl group (see above) being connected to another atom through a C 1-6 -alkyl (see above) which may be branched or linear and is unsubstituted or substituted once or several times.
  • alkylheterocyclyl is understood as meaning a heterocyclyl group (see above) being connected to another atom through 1 to 4 (-CH2-) groups.
  • alkylheterocyclyl is -CH 2 -pyridine.
  • alkylcycloalkyl is understood as meaning an cycloalkyl group (see above) being connected to another atom through a C 1-6 -alkyl (see above) which may be branched or linear and is unsubstituted or substituted once or several times.
  • alkylcycloalkyl is understood as meaning a cycloalkyl group (see above) being connected to another atom through 1 to 4 (-CH2-) groups.
  • alkylcycloalkyl is -CHjrcyclopropyl.
  • the aryl is a monocyclic aryl. More preferably the aryl is a 5, 6 or 7 membered monocyclic aryl. Even more preferably the aryl is a 5 or 6 membered monocyclic aryl.
  • the heteroaryl is a monocyclic heteroaryl. More preferably the heteroaryl is a 5, 6 or 7 membered monocyclic heteroaryl. Even more preferably the heteroaryl is a 5 or 6 membered monocyclic heteroaryl.
  • the non-aromatic heterocyclyl is a monocyclic non-aromatic heterocyclyl. More preferably the non-aromatic heterocyclyl is a 4, 5, 6 or 7 membered monocyclic non-aromatic heterocyclyl. Even more preferably the non-aromatic heterocyclyl is a 5 or 6 membered monocyclic non-aromatic heterocyclyl.
  • the cycloalkyl is a monocyclic cycloalkyl. More preferably the cycloalkyl is a 3, 4, 5, 6, 7 or 8 membered monocyclic cycloalkyl. Even more preferably the cycloalkyl is a 3, 4, 5 or 6 membered monocyclic cycloalkyl.
  • aryl including alkyl-aryl
  • cycloalkyl including alkyl-cycloalkyl
  • heterocyclyl including alkyl-heterocyclyl
  • aryl including alkyl-aryl
  • cycloalkyl including alkyl- cycloalkyl
  • heterocyclyl including alkyl-heterocyclyl
  • cycloalkyl including alkyl-cycloalkyl
  • heterocyclyl including alkylheterocyclyl
  • non-aromatic heterocyclyl including non-aromatic alkyl-heterocyclyl
  • substituted is also understood - unless defined otherwise - as meaning substitution of the ring-system of the cycloalkyl or alkyl-cycloalkyl; non- aromatic heterocyclyl or non aromatic alkyl-heterocyclyl with (leading to a spiro
  • cycloalkyl including alkyl-cycloalkyl
  • heterocyclyl including alkylheterocyclyl
  • non-aromatic heterocyclyl including non-aromatic alkyl-heterocyclyl
  • cycloalkyl including alkyl-cycloalkyl
  • heterocyclyl including alkylheterocyclyl
  • non-aromatic heterocyclyl including non-aromatic alkyl-heterocyclyl
  • a ring system is a system consisting of at least one ring of connected atoms but including also systems in which two or more rings of connected atoms are joined with "joined'' meaning that the respective rings are sharing one (like a spiro structure), two or more atoms being a member or members of both joined rings.
  • leaving group means a molecular fragment that departs with a pair of electrons in heterolytic bond cleavage.
  • Leaving groups can be anions or neutral molecules. Common anionic leaving groups are halides such as CI—, Br-, and I-, and sulfonate esters, such as tosylate (TsO-) or mesylate.
  • salt is to be understood as meaning any form of the active compound used according to the invention in which it assumes an ionic form or is charged and is coupled with a counter-ion (a cation or anion) or is in solution. By this are also to be understood complexes of the active compound with other molecules and ions, in particular complexes via ionic interactions.
  • physiologically acceptable salt means in the context of this invention any salt that is physiologically tolerated (most of the time meaning not being toxic- especially not caused by the counter-ion) if used appropriately for a treatment especially if used on or applied to humans and/or mammals.
  • physiologically acceptable salts can be formed with cations or bases and in the context of this invention is understood as meaning salts of at least one of the compounds used according to the invention - usually a (deprotonated) acid - as an anion with at least one, preferably inorganic, cation which is physiologically tolerated - especially if used on humans and/or mammals.
  • the salts of the alkali metals and alkaline earth metals are particularly preferred, and also those with NH 4 , but in particular (mono)- or (di)sodium, (mono)- or (di)potassium, magnesium or calcium salts.
  • Physiologically acceptable salts can also be formed with anions or acids and in the context of this invention is understood as meaning salts of at least one of the compounds used according to the invention as the cation with at least one anion which are physiologically tolerated - especially if used on humans and/or mammals.
  • the salt formed with a physiologically tolerated acid that is to say salts of the particular active compound with inorganic or organic acids which are physiologically tolerated - especially if used on humans and/or mammals.
  • physiologically tolerated salts of particular acids are salts of: hydrochloric acid, hydrobromic acid, sulfuric acid, methanesulfonic acid, formic acid, acetic acid, oxalic acid, succinic acid, malic acid, tartaric acid, mandelic acid, fumaric acid, lactic acid or citric acid.
  • the compounds of the invention may be present in crystalline form or in the form of free compounds like a free base or acid. Any compound that is a solvate of a compound according to the invention like a compound according to general formula I defined above is understood to be also covered by the scope of the invention. Methods of solvation are generally known within the art. Suitable solvates are pharmaceutically acceptable solvates.
  • the term "solvate" according to this invention is to be understood as meaning any form of the active compound according to the invention in which this compound has attached to it via non- covalent binding another molecule (most likely a polar solvent). Especially preferred examples include hydrates and alcoholates, like methanolates or ethanolates.
  • prodrug is used in its broadest sense and encompasses those derivatives that are converted in vivo to the compounds of the invention. Such derivatives would readily occur to those skilled in the art, and include, depending on the functional groups present in the molecule and without limitation, the following derivatives of the present compounds: esters, amino acid esters, phosphate esters, metal salts sulfonate esters, carbamates, and amides. Examples of well-known methods of producing a prodrug of a given acting compound are known to those skilled in the art and can be found e.g. in Krogsgaard-Larsen et al. "Textbook of Drug design and Discovery” Taylor & Francis (April 2002).
  • the compounds of the invention are also meant to include compounds which differ only in the presence of one or more isotopically enriched atoms.
  • compounds having the present structures except for the replacement of a hydrogen by a deuterium or tritium, or the replacement of a carbon by 13 C- or 14 C-enriched carbon or of a nitrogen by 15 N-enriched nitrogen are within the scope of this invention.
  • the compounds of formula (I) as well as their salts or solvates of the compounds are preferably in pharmaceutically acceptable or substantially pure form.
  • pharmaceutically acceptable form is meant, inter alia, having a pharmaceutically acceptable level of purity excluding normal pharmaceutical additives such as diluents and carriers, and including no material considered toxic at normal dosage levels.
  • Purity levels for the drug substance are preferably above 50%, more preferably above 70%, most preferably above 90%. In a preferred embodiment it is above 95% of the compound of formula (I), or of its salts. This applies also to its solvates or prodrugs.
  • n 0, 1 , 2 or 3
  • q 0, 1 , 2 or 3
  • X is a bond or -0-
  • W is -CH- or nitrogen
  • R 1 is selected from substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein said cycloalkyl, aryl or heterocyclyl in R 1 if substituted, is substituted with one or more substituent/s selected from halogen, -R 11 , -OR 11 , -NO2, -NR 14 ,R 11 ,, NR 11 C(0)R 11 ,, -NR 11 S(0) 2 R 11 ,, -S(0) 2 NR 11 R 1 r, -NR 11 C(0)NR 1 rR 1r , -SR 11 , - S(0)R 11 , -S(0) 2 R 11 , --
  • alkyl, alkenyl or alkynyl in R 1 if substituted, is substituted with one or more substituent/s selected from -OR 11 , halogen, -CN, haloalkyl, haloalkoxy and -
  • R 11 , R 11 , and R 11 - are independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl and unsubstituted C 2-6 alkynyl;
  • R 2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl, wherein said cycloalkyl, aryl or heterocyclyl in R 2 , if substituted, is substituted with one or more substituent/s selected from halogen, -R 12 , -OR12, -N0 2 , -NR 12 R 12 -, - NR 12 C(0)R 12 -, -NR 12 S(0) 2 R 12 ', -S(0) 2 NR 12 R 12 -, -NR 12 C(0)NR 12 R 12 -, -SR i2 , -S(0)R 12 ,
  • R 3 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, -C(0)R 5 , -S(0) 2 R 5 and - C(0)NR 5 R 5 -; wherein R 5 and R 5 - are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2- S alkenyl and substituted or unsubstituted C 2-6 alkynyl , substituted or unsubstitute
  • R4 and R 4 are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, R4 and R 4 ', may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl; alternatively R4 and R 4 may form together with the carbon atom to which they are attached a carbonyl group; R 4 ,, and FV-are independently selected from hydrogen, substituted or unsubstituted C 1- ⁇ alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, R4 " and R 4 ,, may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl;
  • the aryl, heterocyclyl or cycloalkyl also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, other than those defined in R 1 or R 2 , if substituted, is substituted with one or more substituent/s selected from halogen, -R14, -OR14, -NO2, -NRMRW, -NR 14 C(0)R 14 ,, - NR 14 S(0) 2 R 14 ,, -S(0) 2 NR 14 R 14 ,, - NR 14 C(0)NR 14 -R 14 ,,, -SR, 4 , -S(0)R 14 , S(0) 2 R 14 , -CN, haloalkyl, haloalkoxy, -C(0)OR 14 , -C(0)NR 14 R 14 , -OCH 2 CH 2 OR 14 , -NR 14 S(0) 2 NR 14 R 14 ,, and -C(CH 3 ) 2 OR 14 ;
  • R 14 , R 4' , and R 14 are independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl, unsubstituted C 2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;
  • These preferred compounds according to the invention are optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound according to the invention of general Formula (I) is a compound wherein m is 0, 1 or 2; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound according to the invention of general Formula (I) is a compound wherein r is 0, 1 or 2; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound according to the invention of general Formula (I) is a compound wherein n is 0, 1 , 2 or 3; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound according to the invention of general Formula (I) is a compound wherein q is 0, 1, 2 or 3; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound according to the invention of general Formula (I) is a compound wherein
  • X is a bond or -0-; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound according to the invention of general f Formula (I) is a compound wherein
  • W is -CH- or nitrogen; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound according to the invention of general Formula (I) is a compound wherein
  • Y is a bond or -0-; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • W is nitrogen; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound according to the invention of general Formula (I) is a compound wherein R 1 is selected from substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound according to the invention of general Formula (I) is a compound wherein R 1 is substituted or unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound according to the invention of general Formula (I) is a compound wherein
  • R 2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound according to the invention of general Formula (I) is a compound wherein
  • R 2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound according to the invention of general Formula (I) is a compound wherein
  • R 2 is selected from substituted or unsubstituted C 1-6 alkyl and substituted or unsubstituted aryl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • R 3 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, -C(0)R 5 , -S(0) 2 R 5 and - C(0)NR 5 R 5 -; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers,
  • R 3 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, -C(0)R 5 , -S(0) 2 R 5 and - C(0)NR 5 R 5 -; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solv
  • R 3 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, -C(0)R 5 , -S(0)2R 5 and - C(0)NR 5 R 5 -; wherein R 5 and R 2 , are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl , substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl;
  • R 3 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted alkylaryl, -C(0)R 5 , -S(0) 2 R 5 and -C(0)NR 5 R 5 ; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • R 3 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted alkylaryl, -C(0)R 5 , -S(0) 2 R 5 and -C(0)NR 5 R 5 -; wherein R 5 and R 5' are independently selected from hydrogen, substituted or unsubstituted C 1 _s alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl , substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl; preferably R 5 and R are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl; more preferably R 5 and R 5
  • stereoisomers optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • R 4 and R 4 are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound according to the invention of general Formula (I) is a compound wherein R 4 and R 4 , are both hydrogen; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound according to the invention of general Formula (I) is a compound wherein R 4 and R 4 , form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • R 4 and R 4 form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a
  • R 4 ,, and R 4 are independently selected from hydrogen, substituted or unsubstituted C 1- 6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • R 4 , and R - are independently selected from hydrogen and substituted or unsubstituted C 1-6 alkyl, optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • R 4 , and Ft*- form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • R 5 and R 5' are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl , substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • R 5 and R 5 - are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • R 5 and R 5 - are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl and substituted or unsubstituted aryl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • R 11 , R 11 ,,and R 11 - are independently selected from hydrogen, unsubstituted C 1 -6 alkyl, unsubstituted C 2-6 alkenyl and unsubstituted C 2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • R 1 2, R 12 ,and R 1 r are independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl and unsubstituted C 2-6 alkynyl ; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • R 1 3 and R 1 r are independently selected from hydrogen, unsubstituted C 1 - 6 alkyl, unsubstituted C 2-6 alkenyl, and unsubstituted C 2-6 alkynyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • R 14 , R 14 , and R 14 are independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl, unsubstituted C 2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • r 0, 1 or 2;
  • n 0, 1 , 2 or 3;
  • q 0, 1 , 2 or 3;
  • X is a bond or-O-;
  • Y is a bond or -0-
  • W is -CH- or nitrogen
  • R 1 is selected from substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein the C 1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C 2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C 2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne
  • R 2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein the C 1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably the C1-3 alkyl is isopropyl or isobutyl; and/or the C 2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C 2-6 -alkynyl is preferably selected from ethyn
  • R 4 and R 4 are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; wherein the C1 -6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl and/or the C 2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C 2- 8 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or
  • R 4 and R 4 form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl; wherein the cycloalkyl is C3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C3.7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C 3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; and/or
  • R 4 , and f are independently selected from hydrogen, substituted or unsubstituted C 1- ⁇ alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; wherein the C1-8 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; more preferably the C 1-6 alkyl is methyl; and/or the C 2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C 2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or
  • R 4 ,, and f form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl; wherein the cycloalkyl is C3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C34 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; and/or
  • R 5 and R 5 - are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl , substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl; wherein the C1-5 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably the C 1-6 alkyl is methyl or ethyl; and/or the C 2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C 2-6 -alkynyl is preferably selected from
  • R 6 and R 6 - are independently selected from halogen, -R 11 , -OR 11 , -N0 2 , -NRHRH-, - NR 11 C(0)R 1 r, -NR 11 S(0) 2 R 1 r, -S(0) 2 NR 11 R 1 r, -NR 11 C(0)NR 11 R 1 r, -SR 11 , -S(0)R 11 , - S(0) 2 R 11 , -CN, haloalkyl, haloalkoxy, -C(0)OR 11 , -C(0)NR 11 R 1 r, -OCH 2 CH 2 ORu, - NR 11 S(0) 2 NR 11 -R 11 - and -C(CH 3 ) 2 OR 11 ; wherein
  • the alkyl is C 1-6 alkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl;
  • R 11 , R 11 ,,and R 11 are independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl and unsubstituted C 2-6 alkynyl; wherein the C 1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C 2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C 2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne;
  • R12, R 1 2' and R 1 are independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl and unsubstituted C 2-6 alkynyl ;
  • the C1 -6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, preferably, C 1-6 alkyl is ethyl ; and/or the C 2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C 2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne;
  • R 1 3 and R 1 are independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl, and unsubstituted C 2-6 alkynyl; wherein the C 1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl;
  • the C 2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C 2- 8 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or
  • R 14 , R 14 , and R1 4 are independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl, unsubstituted C 2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; wherein the C1 -6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C 2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C 2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, iso
  • cycloalkyl like cyclopropyi, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C3-7 cycloalkyl like cyclopropyi, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C34 cycloalkyl like cyclopropyi, cyclobutyl, cyclopentyl or cyclohexyl; and/or the aryl is selected from phenyl, naphthyl , or anthracene; preferably is naphthyl and phenyl; and/or the heterocyclyl is a heterocyclic ring system of one or more saturated or unsaturated rings of which at least one ring contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is
  • stereoisomers optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound, wherein in R 1 as defined in any of the embodiments of the present invention, the C 1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C 2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C 2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or the cycloalkyl is C3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexy
  • the compound is a compound, wherein in R 2 as defined in any of the embodiments of the present invention, the C 1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably the C 1-6 alkyl is isopropyl or isobutyl; and/or the C 2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C 2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or the cycloalkyl is C3-8 cycloalkyl like cycloprop
  • the compound is a compound, wherein in R 6 as defined in any of the embodiments of the present invention, the alkyl is C 1-6 alkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; more preferably the alkyl is methyl or ethyl; and/or the C 1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, more preferably the C 1-6 alkyl is methyl; and/or the C 2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C2-6 -alkynyl is preferably selected from ethyn
  • the compound is a compound, wherein in R 4 and R 4 , as defined in any of the embodiments of the present invention, the C 1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl
  • the C 2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C 2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound, wherein in R 4 and as defined in any of the embodiments of the present invention, the cycloalkyl is C 3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C3 -6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantio
  • the compound is a compound, wherein in R « and R 4 , as defined in any of the embodiments of the present invention,
  • R4 and R 4 form together with the carbon atom to which they are attached a carbonyl group; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound, wherein in R 4 ,, and R 4 ,,, as defined in any of the embodiments of the present invention, the C 1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; more preferably the C 1-6 alkyl is methyl;
  • the C 2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C 2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound, wherein in R 4 , and R 4 ,,, as defined in any of the embodiments of the present invention, the cycloalkyl is C3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or cyclooctyl; preferably is C3-7 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl; more preferably from C 3-6 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers
  • the compound is a compound, wherein in R 5 and R5 as defined in any of the
  • the C1 -6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyi, isopropyl, or 2-methylpropyl, more preferably the C 1 -6 alkyl is methyl or ethyl; and/or the C 2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C 2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or the cycloalkyl is C3-8 cycloalkyl like cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,
  • stereoisomers optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound, wherein in R 6 and R 6 - as defined in any of the
  • the alkyl is C 1-6 alkyl like methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl;
  • stereoisomers optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound, wherein in R 11 , R 1 r and R 11 , as defined in any of the embodiments of the present invention, the C 1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C 2- 8 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C 2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of
  • the compound is a compound, wherein in R1 2 , R 12 , and R12- as defined in any of the embodiments of the present invention,
  • the C 1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl, preferably, C 1-6 alkyl is ethyl ; and/or the C 2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C 2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio
  • the compound is a compound, wherein in R 13 and R 13 - as defined in any of the embodiments of the present invention,
  • the C 1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl;
  • the C 2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C 2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound, wherein in R14, R 14 , and R1 4 ,, as defined in any of the embodiments of the present invention, the C1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, or 2-methylpropyl; and/or the C 2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or the C 2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; and/or the cycloalkyl is C 3 - 8 cycloalkyl like cyclopropyl, cyclobutyl,
  • stereoisomers optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound, wherein m is 0, 1 or 2; preferably m is 1 or 2; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound, wherein r is 0, 1 or 2; preferably r is 0 or 1 ; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound, wherein n is 0, 1 , 2 or 3; preferably n is 0; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound, wherein q is 0, 1 , 2 or 3; preferably q is 0 or 1 ; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound, wherein
  • Y is a bond or -0-; preferably, Y is a bond; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound, wherein Y is a bond or -0-; preferably, Y is -0-; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound, wherein
  • W is -CH- or nitrogen; preferably W is nitrogen; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound, wherein
  • W is -CH- or nitrogen; preferably W is -CH-; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound of Formula (I , )
  • R 1 is selected from substituted or unsubstituted C1 -6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl;
  • R 2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl;
  • R 3 is selected from hydrogen, substituted or unsubstituted C 1 - ⁇ alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocycl
  • R 4 ,, and R 4 are independently selected from hydrogen, substituted or unsubstituted C 1 - 6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2 . e alkynyl; alternatively, R 4 ,, and R 4 ,,, may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl;
  • stereoisomers optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • R 1 is selected from substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein said cycloalkyl, aryl or heterocyclyl in R 1 if substituted, is substituted with one or more substituent/s selected from halogen, -R 11 , -OR 11 , -N0 2 , -NR 11 R 1 r, - NR 11 C(0)R 11 ,, -
  • alkyl, alkenyl or alkynyl in R 1 if substituted, is substituted with one or more substituent/s selected from -OR 11 , halogen, -CN, haloalkyl, haloalkoxy and - NRuR 11 ,; wherein R 11 , R 11 ,and R 11 - are independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl and unsubstituted C 2-6 alkynyl;
  • R 2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein said cycloalkyl, aryl or heterocyclyl in R 2 , if substituted, is substituted with one or more substituent/s selected from halogen, -R 12 , -OR12, -N0 2 , -NR 12 R 12 -, - NR 12 C(0)R 12 -, -NR 12 S(0) 2 R 12 ', -S(0) 2 NR 12 R 12 -, -NR 12 C(0)NR 12 R 12 -, -SR 12 , -S(0)R 12 , S(0) 2 R 12l -CN, haloalkyl,
  • alkyl, alkenyl or alkynyl in R 2 if substituted, is substituted with one or more substituent/s selected from -OR12, halogen, -CN, haloalkyl, haloalkoxy, - NR 12 R 12 ,,; wherein R 12 , R 12 ' and R 12 - are independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl and unsubstituted C 2-6 alkynyl ; R 3 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2 -e alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted al
  • R4 and R 4 are independently selected from hydrogen, substituted or unsubstituted C1 -6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, R4 and R4' may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl; alternatively R and R 4 - may form together with the carbon atom to which they are attached a carbonyl group;
  • R 4 ,' and R 4 are independently selected from hydrogen, substituted or unsubstituted C 1- ⁇ alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, R 4 , and R 4 " may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl; the alkyl, alkenyl or alkynyl, other than those defined in R 1 or R 2l if substituted, is substituted with one or more substituent/s selected from -OR 13 , halogen, -CN, haloalkyl, haloalkoxy and -NR 13 R 13 -; wherein R 13 and R 13 - are independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl, and unsubstituted C 2-6 alkynyl;
  • the aryl, heterocyclyl or cycloalkyl also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, other than those defined in R 1 or R2, if substituted, is substituted with one or more substituent s selected from halogen, -R14, -OR14, -N0 2 , -NR14R1 4 ,, -NR 14 C(0)R 14 ', - NR 14 S(0) 2 R 14 ,, -S(0) 2 NR 14 R 14 ,, - NR 14 C(0)NR 14 R 14 ,,, -SR14 , -S(0)R 14 , -S(0) 2 R, 4 , -CN, haloalkyl, haloalkoxy, -C(0)OR 14 , -C(0)NR 14 R 14 ,, -OCH 2 CH 2 OR 14 , -NR 14 S(0) 2 NR 14 R 14 ,, and -C(CH 3 ) 2 OR 14 ;
  • R 14 , R 14 , and R 14 are independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl, unsubstituted C 2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;
  • stereoisomers optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound of Formula (la') wherein m is 0, 1 or 2; r is 0, 1 or 2; q is 0, 1 , 2 or 3;
  • X is a bond or -0-
  • R2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl;
  • R3 is selected from hydrogen, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, -C(0)R 5 , -S(0) 2 R5 and - C(0)NR 5 R 5 -; wherein R 5 and R 5 - are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl , substituted or unsubstitute
  • R 4 ,, and R4 ' " are independently selected from hydrogen, substituted or unsubstituted C 1 - 6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, R*- and R 4 - may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl;
  • the compound is a compound of Formula (la')
  • R 1 is selected from substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein said cycloalkyl, aryl or heterocyclyl in R 1 if substituted, is substituted with one or more substituent/s selected from halogen, -R 11 , -OR 11 , -NO2, -NR 11 R 11 ,, NR 11 C(0)R 1 r, -NR 11 S(0) 2 R 11 ,, -S(0) 2
  • alkyl, alkenyl or alkynyl in R 1 if substituted, is substituted with one or more substituent/s selected from -OR 11 , halogen, -CN, haloalkyl, haloalkoxy and -
  • R 11 , R 11 , and R 11 - are independently selected from hydrogen, unsubstituted C1 -6 alkyl, unsubstituted C 2-6 alkenyl and unsubstituted C 2-6 alkynyl;
  • R 2 is selected from hydrogen, substituted or unsubstitutedC 1 -6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein said cycloalkyl, aryl or heterocyclyl in R 2 , if substituted, is substituted with one or more substituent/s selected from halogen, -R 12 , -OR12, -NO2, -NR 12 R 12 -,
  • alkyl, alkenyl or alkynyl in R 2 if substituted, is substituted with one or more substituent/s selected from -OR12, halogen, -CN, haloalkyl, haloalkoxy, - NR 12 R 12 ,,; wherein R12, R 12 - and R 12 - are independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl and unsubstituted C 2-6 alkynyl ;
  • R 3 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, -C(0)R 5 , -S(0) 2 R5 and - C(0)NR 5 R 5 ; wherein R 5 and R 5 - are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl , substituted or unsubstituted
  • R 4 and R 4 are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, R and R4 may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl; alternatively R 4 and R 4 , may form together with the carbon atom to which they are attached a carbonyl group;
  • R4" and R 4 are independently selected from hydrogen, substituted or unsubstituted C 1- 6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, R 4 ,, and R 4 - may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl;
  • the aryl, heterocyclyl or cycloalkyl also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, other than those defined in R 1 or R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R14, -OR14, -NO2, -NR14R14', NR 14 C(0)R 14 ,, - NR 14 S(0) 2 R 14 ,, -S(0) 2 NR 14 R 14 ,, - NR 14 C(0)NR 14 R 14 ,,, -SR14 , -S(0)R 14 , S(0) 2 R 14 , -CN, haloalkyl, haloalkoxy, -C(0)OR 14 , -C(0)NR 14 R 14 ,, -OCH 2 CH 2 OR 14 , -NR 14 S(0) 2 NR 14 R 14 , and C(CH 3 ) 2 OR 14 ;
  • R14, R 14 and R 14 - are independently selected from hydrogen, unsubstituted C1 -6 alkyl, unsubstituted C 2-6 alkenyl, unsubstituted C 2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;
  • stereoisomers optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound of Formula (I 2 ')
  • R2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl;
  • R3 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted
  • R 4 ,, and R4 - are independently selected from hydrogen, substituted or unsubstituted C 1 - 6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, R 4 ,, and R4 """ may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl;
  • the compound is a compound of Formula (I 2 ')
  • X is a bond or -0-; W is -CH- or nitrogen;
  • R 2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein said cycloalkyl, aryl or heterocyclyl in R 2 , if substituted, is substituted with one or more substituent s selected from halogen, -R12, -OR12, -NO2, -NR12R12', - NR 12 C(0)R 1 2-, -NR 12 S(0) 2 R 1 2-, -S(0) 2 NR 12 R 1 2-, -NR 12 C(0)NR 12 R 1 2,,, -SR 12 , -S(0)R 12 ,
  • R 3 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, -C(0)R 5 , -S(0) 2 R 5 and - C(0)NR 5 R 5 -; wherein R5 and R 5' are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl , substituted or unsubstituted
  • R 4 and R ' are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, R4 and R 4 , may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl; alternatively R4 and R 4' , may form together with the carbon atom to which they are attached a carbonyl group;
  • R 4 , and R4 ' " are independently selected from hydrogen, substituted or unsubstituted C 1 - ⁇ alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, R 4' , and R 4 , - may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl;
  • the aryl, heterocyclyl or cycloalkyl also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, other than those defined in R 1 or R2, if substituted, is substituted with one or more substituent s selected from halogen, -R 14 , -OR14, -NO2, -NR 14 R, 1 -r, -NR 14 C(0)R 14 ,, - NR 14 S(0) 2 R 14 ,, -S(0) 2 NR 14 R 14 ,, - NR, 4 C(0)NR 14 ,R 14 ,,, -SR i4 , -S(0)R 14 , -S(0) 2 R 14 , -CN, haloalkyl, haloalkoxy, -C(0)OR 14 , -C(0)NR 14 R 14 ,, -OCH 2 CH 2 OR 14 , -NR 14 S(0) 2 NR 14 R 14 , and -C(CH 3 ) 2 OR
  • R14, R 14 , and R14 ⁇ are independently selected from hydrogen, unsubstituted
  • C 1-6 alkyl unsubstituted C 2-6 alkenyl, unsubstituted C 2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound of Formula (I 3 ')
  • R 2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl;
  • R 3 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, -C(0)R 5 , -S(0) 2 R5 and - C(0)NR 5 R 5 -; wherein R 5 and R 5 - are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl , substituted or unsubstitute
  • R 4 , and R4 ' " are independently selected from hydrogen, substituted or unsubstituted C 1- ⁇ alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, R 4 ,, and R ⁇ "" may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound of Formula (I 3 ')
  • X is a bond or -0-
  • R 2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein said cycloalkyl, aryl or heterocyclyl in R 2 , if substituted, is substituted with one or more substituent/s selected from halogen, -R12, -OR12, -NO2, -NR12R12', - NR 12 C(0)R 1 2-, -NR 12 S(0) 2 R 1 2-, -S(0) 2 NR 12 R 1 2-, -NR 12 C(0)NR 12 R 1 2", -SR12, -S(0)R 12 ,
  • R3 is selected from hydrogen, substituted or unsubstituted O -6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, -C(0)R 5) -S(0) 2 R 5 and - C(0)NR 5 R 5 -; wherein R 5 and R 5 - are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl , substituted or unsubstituted
  • R 4 and R4 are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, R4 and R 4 - may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl; alternatively R 4 and R 4 , may form together with the carbon atom to which they are attached a carbonyl group; R4" and F are independently selected from hydrogen, substituted or unsubstituted C 1 - ⁇ alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, R 4 ,, and R4 ' " may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl; the alkyl, alkenyl or alkyn
  • stereoisomers optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound of Formula (I 4 ')
  • X is a bond or -0-
  • W is -CH- or nitrogen
  • R 2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein said cycloalkyl, aryl or heterocyclyl in R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R12, -OR12, -NO2, -NR12R12', - NR 12 C(0)R 1 2-, -NR 12 S(0)2R 12 ,, -S(0) 2 NR 12 R 1 2', -NR 12 C(0)NR 12 R 1 2", -SR 12 , -S(0)R 12 , -S(0) 2 R 1 2, -CN, haloalkyl, haloalkoxy,
  • R3 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, -C(0)R 5 , -S(0)2R 5 and - C(0)NR 5 R5-; wherein R5 and R 5 - are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl , substituted or unsubstituted
  • R 4 , and R-n are independently selected from hydrogen, substituted or unsubstituted C 1- 6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, R 4 , and R 4 ,- may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl;
  • R 13 and R 13 - are independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl, and unsubstituted C 2-6 alkynyl; the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, other than those defined in R 1 or R 2 , if substituted, is substituted with one or more substituent/s selected from halogen, -R 14 , -OR14, -NO2, -NR14R14', -NR 14 C(0)R 14 ,, - NR
  • R 14 , R 14 and R 14 are independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl, unsubstituted C 2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound of Formula (I 4 ')
  • R 2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein said cycloalkyl, aryl or heterocyclyl in R 2 , if substituted, is substituted with one or more substituent/s selected from halogen, -R 12> -OR 12 , -N0 2l -NR12R12', - NR 12 C(0)R,2-, -NR 12 S(0) 2 R 1 2-, -S(0) 2 NR 1 2R 12 -, -NR 12 C(0)NR 12 R 1 2,,, -SR12, -S(0)R 12 , -S(0) 2 R 12 , -CN, haloalkyl,
  • alkyl, alkenyl or alkynyl in R 2 if substituted, is substituted with one or more substituent/s selected from -OR 12 , halogen, -CN, haloalkyl, haloalkoxy, - NR 12 R 12 ,,; wherein R 12l R 12 , and R 12 - are independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl and unsubstituted C 2-6 alkynyl ;
  • R 3 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2 . 6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, -C(0) 5 , -S(0)2R 5 and - C(0)NR 5 R 5 -; wherein R 5 and R 5 - are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl , substituted or unsubstit
  • R 4 , and R4 - " are independently selected from hydrogen, substituted or unsubstituted C 1- ⁇ alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl; alternatively, R 4' , and R ⁇ " ⁇ may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl; the alkyl, alkenyl or alkynyl, other than those defined in R 1 or R2, if substituted, is substituted with one or more substituent/s selected from -OR 13 , halogen, -CN, haloalkyl, haloalkoxy and -NR 13 R 13 ; wherein R 13 and R 1 3- are independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl, and unsubstituted C 2-6 alkynyl; the aryl
  • stereoisomers optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound of Formula (I 58 ')
  • R 2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl;
  • R 3 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted d-o alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocycly
  • R4 - and R 4 are independently selected from hydrogen, substituted or unsubstituted C 1- ⁇ alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, R 4 ,, and R* " ⁇ " may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl;
  • stereoisomers optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound of Formula (I 58 ')
  • R 2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein said cycloalkyl, aryl or heterocyclyl in R 2 , if substituted, is substituted with one or more substituent/s selected from halogen, -R12, -OR 12 , -N0 2 , -NR12R12', NR 12 C(0)R 1 2-, -NR 1 2S(0) 2 R 1 2-, -S(0) 2 NR 12 R 1 2-, -NR 12 C(0)NR 12 R 1 2", -SR12, -S(0)R 12 , S(0) 2 R 1 2, -CN, haloalkyl, haloalkoxy,
  • R 5 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, -C(0)R 5 , -S(0) 2 R5 and - C(0)NR 5 R 5 '; wherein R 5 and R 5 - are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl , substituted or unsubstitute
  • R 4 ,, and R 4 are independently selected from hydrogen, substituted or unsubstituted O. ⁇ alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, R 4 ,, and R 4 " may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl;
  • R 13 and R 13 ' are independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl, and unsubstituted C 2-6 alkynyl; the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, other than those defined in R 1 or R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R14, -ORTM, -NO2, -NRMRM-, -NR 14 C(0)R 14 ,, - NR 14 S(0) 2
  • R 14 , R 14 ,,and R 14 - are independently selected from hydrogen, unsubstituted C1 -6 alkyl, unsubstituted C 2-6 alkenyl, unsubstituted C 2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;
  • stereoisomers optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound of Formula (l 5b ')
  • R 2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C2 -6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl;
  • R 3 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, -C(0)R 5 , -S(0) 2 R 5 and - C(0)NR 5 R 5 -; wherein R 5 and R 5' are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl , substituted or unsubstituted
  • Re and R 4 are independently selected from hydrogen, substituted or unsubstituted C 1- ⁇ alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, R4 "" and R 4 , may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound of Formula (l 5b ')
  • R2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein said cycloalkyl, aryl or heterocyclyl in R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R12, -OR12, -NO2, -NR12R17, -
  • alkyl, alkenyl or alkynyl in R 2 if substituted, is substituted with one or more substituent/s selected from -OR12, halogen, -CN, haloalkyl, haloalkoxy, - NR12R12"; wherein R12, R 1 2- and R12- are independently selected from hydrogen, unsubstituted C1 -6 alkyl, unsubstituted C 2-6 alkenyl and unsubstituted C 2- 3 alkynyl ;
  • R 3 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, -C(0)R 5 , -S(0) 2 R 5 and - C(0)NR 5 R 5 -; wherein R 5 and R 5 , are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl , substituted or unsubstitute
  • R4 " and R4 ' " are independently selected from hydrogen, substituted or unsubstituted C 1- ⁇ alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, R4 ' " and R4 ' " may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl;
  • R 13 is independently selected from hydrogen, unsubstituted C14 alkyl, unsubstituted C 2-6 alkenyl, and unsubstituted C 2-8 alkynyl;
  • the aryl, heterocyclyl or cycloalkyl also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, other than those defined in R 1 or R 2 , if substituted, is substituted with one or more substituent/s selected from halogen, -R 14 , -OR14, -N0 2 , -NR14R1 4 ,, -NR 14 C(0)R 14 ,, - NR 14 S(0) 2 R 14 ,, -S(0) 2 NR 14 R 14 ,, - NR 14 C(0)NR 14 R 14 ,,, -SR14 , -S(0)R 14 , S(0) 2 R 14 , -CN, haloalkyl, haloalkoxy, -C(0)OR 14 , -C(0)NR 14 R 14 ,, -OCH 2 CH 2 OR 14 , -NR 14 S(0) 2 NR 14 R 14 , and -C(CH 3 )20R 14 ;
  • R14, R 14 and R 14 are independently selected from hydrogen, unsubstituted C1 -6 alkyl, unsubstituted C 2-6 alkenyl, unsubstituted C 2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound of Formula (l 6a ')
  • R 2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl;
  • R 3 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylcyclo
  • R 4 , and R 4 - are independently selected from hydrogen, substituted or unsubstituted C 1 - ⁇ alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, R4 "- and Rc- may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl;
  • stereoisomers optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound of Formula (I 68 ')
  • R 2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein said cycloalkyl, aryl or heterocyclyl in R 2 , if substituted, is substituted with one or more substituent/s selected from halogen, -R 12 , -OR 12 , -N0 2l -NR 12 R 12 -, - NR 12 C(0)R 1 2', -NR 12 S(0) 2 R 1 2-, -S(0) 2 NR 12 R 12 -, -NR 12 C(0)NR 12 R 12 -, -SR 12 , -S(0)R 12 , S(0) 2 R 12 , -CN, haloalkyl,
  • R3 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, -C(0)R 5 , -S(0) 2 R 5 and - C(0)NR 5 R 5 ; wherein R5 and R 5 - are independently selected from hydrogen, substituted or unsubstituted C1-5 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl , substituted or unsubstituted
  • Re and Re- are independently selected from hydrogen, substituted or unsubstituted C 1 - 6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, Re and Re- may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl;
  • R 13 and R 1 are independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl, and unsubstituted C 2-6 alkynyl; the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, other than those defined in R 1 or R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R14, -OR14, -NO2, -NR 14 R 14 -, -NR 14 C(0)R 14 -, - NR 14 S(0)
  • R 14 , R 14 and R 14 are independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl, unsubstituted C 2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound of Formula (l 6b ')
  • R2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl;
  • R3 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, -C(0)R 5 , -S(0) 2 R 5 and - C(0)NR 5 R 5 -; wherein R5 and R 5' are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl , substituted or unsubstituted
  • R 4 , and R 4 are independently selected from hydrogen, substituted or unsubstituted C 1- ⁇ alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, Re and R4 - may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound of Formula (l 6b ')
  • R 2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein said cycloalkyl, aryl or heterocyclyl in R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R12, -OR12, -NO2, -NR12R12 , - NR 12 C(0)R 1 2-, -NR 12 S(0) 2 R 1 2-, -S(0)2NR 12 R 12 ', -NR 1 2C(0)NR 12 R 1 2", -SR12, -S(0)R 12 , -S(0) 2 R 1 2, -CN, haloalkyl, haloalkoxy, -
  • R 3 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, -C(0)R 5 , -S(0) 2 R 5 and - C(0)NR 5 R 5 -; wherein R5 and R 5 - are independently selected from hydrogen, substituted or unsubstituted C1 -6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl , substituted or unsubstit
  • R 4 ,, and R4 ' " are independently selected from hydrogen, substituted or unsubstituted C 1 - 6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, R 4 , and RA- may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl;
  • R 13 and R 1 are independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl, and unsubstituted C 2-8 alkynyl; the aryl, heterocyclyl or cycloalkyl, also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, other than those defined in R 1 or R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R 14> -OR14, -NO2, -NRHRM-, -NR 14 C(0)R 14 ,, - NR 14 S(0) 2 R
  • the compound is a compound of Formula (I 7 ')
  • R 1 is selected from substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl;
  • R 2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl;
  • R 3 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, -C(0)R 5 , -S(0) 2 R 5 and - C(0)NR 5 R 5 '; wherein R 5 and R 5 - are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C2-0 alkenyl and substituted or unsubstituted C 2-6 alkynyl , substituted or unsubstituted
  • stereoisomers optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound of Formula (I 7 ')
  • X is a bond or -0-
  • W is -CH- or nitrogen; Y is a bond or-O-; R 1 is selected from substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein said cycloalkyl, aryl or heterocyclyl in R 1 if substituted, is substituted with one or more substituent s selected from halogen, -R 11 , -OR 11 , -NO2, -NR 11 R 11 ,, - NR 11 C(0)R 1 r, -NR 1 ,S(0) 2 R 1 r, -S(0) 2 NR 11 R 1 r, -NR 1 ,C(0)NR 11 R 1 r, -SR 11 , - S(0)R 11
  • alkyl, alkenyl or alkynyl in R 1 if substituted, is substituted with one or more substituent s selected from -OR 11 , halogen, -CN, haloalkyl, haloalkoxy and - NR11R11"; wherein R 11 , R 11 ,,and R 11 , are independently selected from hydrogen, unsubstituted C1 -6 alkyl, unsubstituted C 2-6 alkenyl and unsubstituted C 2-6 alkynyl;
  • R 2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein said cycloalkyl, aryl or heterocyclyl in R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R12, -OR12, -N0 2 , -NR12R12', - NR 12 C(0)R 1 2-, -NR 12 S(0) 2 R 12 -, -S(0) 2 NR 12 R 12 -, -NR 12 C(0)NR 12 R 12 ,,, -SR 12 , -S(0)R 12 , -S(0) 2 R 12l -CN, haloalkyl, hal
  • alkyl, alkenyl or alkynyl in R 2 if substituted, is substituted with one or more substituent s selected from -OR12, halogen, -CN, haloalkyl, haloalkoxy, - NR 12 R 12 -; wherein R12, R12 and R 12 - are independently selected from hydrogen, unsubstituted C1 -6 alkyl, unsubstituted C 2-6 alkenyl and unsubstituted C 3-6 alkynyl ;
  • R3 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, -C(0)R 5 , -S(0) 2 R 5 and - C(0)NR 5 R 5 -; wherein R 5 and R 2 , are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl , substituted or unsubstitute
  • R 4 ,, and Re- are independently selected from hydrogen, substituted or unsubstituted C 1- 6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, RA- and R 4 """ may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl; the alkyl, alkenyl or alkynyl, other than those defined in R 1 or R 2
  • the aryl, heterocyclyl or cycloalkyl also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, other than those defined in R 1 or R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R14, -OR14, -N0 2 , -NR14R1 4 ,, -NR 14 C(0)R 14 ', - NR 14 S(0) 2 R 14 ,, -S(0) 2 NR 14 R 14 ,.
  • R 14 , R 1 band R 14 - are independently selected from hydrogen, unsubstituted C1 -6 alkyl, unsubstituted C 2-6 alkenyl, unsubstituted C 2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;
  • stereoisomers optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound of Formula (l 8 ')
  • R 1 is selected from substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl;
  • R2 is selected from hydrogen, substituted or unsubstituted C1 -6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl;
  • R3 is selected from hydrogen, substituted or unsubstituted C1-5 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, -C(0)R 5 , -S(0) 2 R 5 and - C(0)NR 5 R 5 -; wherein R 5 and R 5 - are independently selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl , substituted or unsubstitute
  • R4" and R4 - are independently selected from hydrogen, substituted or unsubstituted C 1- ⁇ alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl; alternatively, R 4 ,, and R 4 , may form together with the carbon atom to which they are attached a substituted or unsubstituted cycloalkyl;
  • stereoisomers optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compound is a compound of Formula (I 8 ')
  • R 1 is selected from substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2- 8 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein said cycloalkyl, aryl or heterocyclyl in R 1 if substituted, is substituted with one or more substituent/s selected from halogen, -R 11 , -OR 11 , -N0 2 , -NR 11 R 1 r, -
  • alkyl, alkenyl or alkynyl in R 1 if substituted, is substituted with one or more substituent/s selected from -OR 11 , halogen, -CN, haloalkyl, haloalkoxy and - NR 11 R 11 ,,; wherein R 11 , R 11 ,,and R 11 ,,are independently selected from hydrogen, unsubstituted C1 -6 alkyl, unsubstituted C 2-6 alkenyl and unsubstituted C 2 -5 alkynyl; R 2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein said cycloalky
  • alkyl, alkenyl or alkynyl in R 2 if substituted, is substituted with one or more substituent s selected from -OR 12 , halogen, -CN, haloalkyl, haloalkoxy, - NR 12 R 12 ,,; wherein R 12 , R 12 , and R17- are independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl and unsubstituted C 2-6 alkynyl ;
  • R 3 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, -C(0)R 5l -S(0) 2 R 5 and - C(0)NR 5 R 5 -; wherein R 5 and R 5' are independently selected from hydrogen, substituted or unsubstituted C1-3 alkyl, substituted or unsubstituted C 2-6 alkenyl and substituted or unsubstituted C 2-6 alkynyl , substituted or unsubstituted cycl
  • R 13 is independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl, and unsubstituted C 2-6 alkynyl;
  • the aryl, heterocyclyl or cycloalkyl also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, other than those defined in R 1 or R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R14, -OR14, -NO2, -NRMRW, -NR 14 C(0)R 14 ,, - NR 14 S(0) 2 R 14 ,, -S(0) 2 NR 14 R 14 ,, - NR 14 C(0)NR 14 R 14 ,,, -SR14 , -S(0)R 14 , -S(0) 2 R 14 , -CN, haloalkyl, haloalkoxy, -C(0)OR 14 , -C(0)NR 14 R 14 ,, -OCH 2 CH 2 OR 14 , -NR 14 S(0) 2 NR 14 R 14 ,, and -C(CH 3 ) 2 OR 14 ;
  • R14, R 14 ,,and R 14 are independently selected from hydrogen, unsubstituted C1 -6 alkyl, unsubstituted C 2-6 alkenyl, unsubstituted C 2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;
  • the compound is a compound of Formula (I , ),
  • R 6 andR 6 - are independently selected from halogen, -R 11 , -OR 11 , -N0 2 , -NR 11 R 11 ", -NR 11 C(0)R 11 ,, -NR,iS(0) 2 R 1 r, -S(0) 2 NR 11 R 1 r, -NR 11 C(0)NR 11 R 1 r, -SR11 , -S(0)R 11 , -S(0) 2 R 11 , -CN, haloalkyl, haloalkoxy, -C(0)OR 11 , - C(0)NR 11 R 1 r, -OCH2CH2OR11, -NR 11 S(0) 2 NR 11 R 11 ⁇ and -C(CH 3 ) 2 OR 11 ; and R 11 , R 11 ,,and R 11 , are independently selected from hydrogen, unsubstituted C1-8 alkyl, unsubstituted C 2-6 alkenyl and unsubstituted C 2-6 alkynyl.
  • stereoisomers optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • n 1 or 2.
  • r is 0 or 1.
  • n 1
  • n 0.
  • q is 0 or 1.
  • Y is a bond
  • Y is -0-.
  • X is a bond or -0-.
  • W is nitrogen.
  • W is -CH-.
  • R 1 is a substituted or unsubstituted pyridine, preferably unsubstituted pyridine.
  • R 2 is substituted or unsubstituted group selected from isopropyl, isobutyl and phenyl, more preferably an unsubstituted group selected from isopropyl, isobutyl and phenyl.
  • R 3 is hydrogen or a substituted or unsubstituted group selected from methyl, 1- propiopyl, benzyl, acetyl, benzoyl, -S(0)2-methyl and -C(0)NH-methyl; preferably hydrogen or an unsubstituted group selected from methyl, 1 -propiopyl, benzyl, acetyl, benzoyl, -S(0)2-methyl and -C(0)NH-methyl.
  • R3 is hydrogen or a substituted or unsubstituted group selected from methyl, ethyl, 1- propiopyl, benzyl, acetyl, benzoyl, -S(0)2-methyl and -C(0)NH-methyl; preferably hydrogen or an unsubstituted group selected from methyl, 1 -propiopyl, benzyl, acetyl, benzoyl, -S(0)2-methyl and -C(0)NH-methyl.
  • R is hydrogen.
  • R4' is hydrogen.
  • R4' is hydrogen.
  • R 4 is hydrogen. In a preferred embodiment R4 - is hydrogen. In a preferred embodiment
  • R 4 is substituted or unsubstituted methyl, preferably unsubstituted methyl.
  • R4 ' " is substituted or unsubstituted methyl, preferably unsubstituted methyl.
  • R 4 and R 4 are both hydrogen.
  • R 4 and R 4 are both hydrogen.
  • R 4 , and R4 ' " are both hydrogen.
  • R 4 , and R4 ' " are both substituted or unsubstituted methyl; preferably R 4 , and R4 ' " are both unsubstituted methyl.
  • R 4 , and R4 ' " are both substituted or unsubstituted methyl; preferably R 4 , and R4 ' " are both unsubstituted methyl.
  • R 4 and R 4 are both hydrogen, while R 4 , and R4 ' " are both substituted or unsubstituted methyl; preferably while R4 ' " and R 4 , are both unsubstituted methyl.
  • R 4 ' " are both substituted or unsubstituted methyl; preferably while R4 ' " and R 4 , are both unsubstituted methyl.
  • R4, R ', 4 ,, and R4 " are all hydrogen.
  • R 5 is hydrogen or a substituted or unsubstituted group selected from methyl, ethyl and phenyl; preferably hydrogen or an unsubstituted group selected from methyl, ethyl and phenyl.
  • R 5 - is substituted or unsubstituted methyl, preferably unsubstituted methyl.
  • R 5 is hydrogen or a substituted or unsubstituted group selected from methyl, ethyl and phenyl; preferably hydrogen or an unsubstituted group selected from methyl, ethyl and phenyl, while R 5 - is substituted or unsubstituted methyl, preferably unsubstituted methyl.
  • R 6 andR 6 - are both hydrogen.
  • R11 is hydrogen. In a preferred embodiment R 1 2 is hydrogen. In a preferred embodiment R 14 is hydrogen.
  • the compounds of the general Formula (I) are selected from
  • stereoisomers optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compounds of the general Formula (I) are selected from
  • stereoisomers optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the compounds of the general Formula (I) are selected from
  • stereoisomers optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • R 1 is selected from substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein said cycloalkyl, aryl or heterocyclyl in R 1 if substituted, is substituted with one or more substituent s selected from halogen, -R 11 , -OR 11 , -N0 2 , -NR 11 R 11 ,, - NR 11 C(0)R 1 r, -NR 11 S(0) 2 R 1 r, -S(0) 2 NR 11 R 1 r, -NR 11 C(0)NR 11 R 1 r, -SR 11 , - S(0)R 11 , S(0) 2
  • alkyl, alkenyl or alkynyl in R 1 if substituted, is substituted with one or more substituent/s selected from -OR 11 , halogen, -CN, haloalkyl, haloalkoxy and -
  • R 11 , R 11 ,,and R 11 are independently selected from hydrogen, unsubstituted
  • R 2 is selected from hydrogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; wherein said cycloalkyl, aryl or heterocyclyl in f3 ⁇ 4, if substituted, is substituted with one or more substituent/s selected from halogen, -R12, -OR12, -NO2, -NR12R12, - NR 12 C(0)R 1 2-, -NR 12 S(0) 2 R 1 2-, -S(0) 2 NR 1 2R 1 2-, -NR 12 C(0)NR 12 R 1 2", -SR12, -S(0)R 12 , S(0) 2 R 1 2, -CN, haloalkyl, haloalkoxy, -
  • alkyl, alkenyl or alkynyl in R 2 if substituted, is substituted with one or more substituent s selected from -OR12, halogen, -CN, haloalkyl, haloalkoxy, - NR 12 R 1 2,,; wherein R12, R 12 and R 12 - are independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl and unsubstituted C 2-6 alkynyl ; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • substituent s selected from -OR12, halogen, -CN, haloalkyl, haloalk
  • the compound of general Formula (I), the alkyl, alkenyl or alkynyl, other than those defined in R 1 or R 2 , if substituted, is substituted with one or more substituent/s selected from -OR 13 , halogen, -CN, haloalkyl, haloalkoxy and -NR 13 R 13 ; wherein R 13 and R 1 3- are independently selected from hydrogen, unsubstituted C 1-6 alkyl, unsubstituted C 2-6 alkenyl, and unsubstituted C 2 .
  • the cycloalkyl, aryl or heterocyclyl in R 1 if substituted is substituted with one or more substituent/s selected from halogen, -R 11 , -OR 11 , -N0 2 , -NR 11 R 11 , -NR 11 C(0)R 14 ,,, - NR 11 S(0) 2 R 1 r, -S(0) 2 NR 11 R 1 r, -NR 11 C(0)NR 11 R 1 r, -SR 11 , -S(0)R 11 , -S(0) 2 R 11 , -CN, haloalkyl, haloalkoxy, -C(0)OR 11 , -C(0)NR 11 R 1 r, -OCH 2 CH 2 OR 11 , -NR 11 S(0) 2 NR 11 R 1r and -C(CH 3 ) 2 OR 11 ; optionally in
  • the alkyl, alkenyl or alkynyl in R 1 if substituted, is substituted with one or more substituent s selected from -OR 11 , halogen, -CN, haloalkyl, haloalkoxy and -NR 11 R 11 ,; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the cycloalkyl, aryl or heterocyclyl in R2 if substituted, is substituted with one or more substituent/s selected from halogen, -R12, -OR12, -NO2, -NR12R17, -NR 12 C(0)R 12 ', -
  • the alkyl, alkenyl or alkynyl in R 2 if substituted, is substituted with one or more substituent/s selected from -OR12, halogen, -CN, haloalkyl, haloalkoxy, -NR12R12"; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the alkyl, alkenyl or alkynyl, other than those defined in R 1 or R2, if substituted, is substituted with one or more substituent/s selected from -OR 13 , halogen, -CN, haloalkyl, haloalkoxy and -NR 13 R1 ; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • the aryl, heterocyclyl or cycloalkyl also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl, other than those defined in R 1 or R2, if substituted, is substituted with one or more substituent/s selected from halogen, -R14, -OR , -NO2, -NRMRW, -NR 14 C(0)R 14 ,, - NR 14 S(0) 2 R 14 ,, -S(0) 2 NR 14 R 14 ,, -NR 14 C(0)NR 14 R 14 ,,, -SR14 , -S(0)R 14 , -S(0) 2 R 14 , -CN, haloalkyl, haloalkoxy, -C(0)OR 1 ,
  • the halogen is fluorine, chlorine, iodine or bromine; optionally in form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in form of a mixture of at least two of the stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof.
  • this invention is aimed at providing a compound or a chemically related series of compounds which act as dual ligands of the ⁇ 1 receptor and the ⁇ -opioid receptor it is a very preferred embodiment in which the compounds are selected which act as dual ligands of the ⁇ 1 receptor and the ⁇ -opioid receptor and especially compounds which have a binding expressed as K, which is preferably ⁇ 1000 nM for both receptors, more preferably ⁇ 500 nM, even more preferably ⁇ 100 nM.
  • the compounds of the invention represented by the above described Formula (I) may include enantiomers depending on the presence of chiral centres or isomers depending on the presence of multiple bonds (e.g. Z, E).
  • the single isomers, enantiomers or diastereoisomers and mixtures thereof fall within the scope of the present invention.
  • the processes are described below in the experimental part.
  • the starting materials are commercially available or can be prepared by conventional methods.
  • a preferred aspect of the invention is also a process for the production of a compound according to Formula (I), following scheme 1.
  • a preferred aspect of the invention is a process for the production of a compound according to Formula (I), wherein R 1 , R2, R3, R4, 4 ,, R 4 ,-, R4 ' " , R 5 , R 5 -, m, n, q, r, X, Y and W are as defined in the description, following scheme 1.
  • R 1 , R2, R3, R4, 4 ,, R 4 ,-, R4 ' " , R 5 , R 5 -, m, n, q, r, X, Y and W are as defined in the description, following scheme 1.
  • the expression "a compound according to Formula (I), wherein e.g. R 1 , etc. are as defined in the description” would (just like the expression "a compound of Formula (I) as defined in any one of claims e.g. 1 to 10" found in the claims) refer to "a compound according to Formula (I)", wherein the definitions of the respective substituents R 1 etc.
  • a preferred embodiment of the invention is a process for the production of a compound according to Formula (I),
  • ketone wherein Z is chlorine or bromine, P is Q, and Q is
  • a preferred embodiment of the invention is a process for the production of a compound according to Formula (I),
  • a preferred embodiment of the invention is a process for the production of a compound according to Formula (I),
  • a preferred embodiment of the invention is a process for the production of a compound according to Formula (I),
  • a reductive reagent in the presence of a reductive reagent, in a suitable solvent, at a suitable temperature, preferably in a microwave reactor, wherein Z is chlorine or bromine, P is Q, and Q is
  • R 1 , R 2 , Ra, Ro, R 4 ,, R 4 ,, R 4 ,-, m, n, q, r, X, W and Y have the meanings defined in the description.
  • a preferred embodiment of the invention is a process, wherein n is 0 and W is nitrogen, for the production of a compound of Formula (IVa) or (IVb) starting from a compound of Formula (II),
  • P is a protecting group PG such as Boc (tert-butoxycarbonyl), Teoc (2- (trimethylsilyl)ethoxycarbonyl) or benzyl, or P is Q, and Q is
  • a preferred embodiment of the invention is a process, for the production of a compound of Formula (VI) starting from a compound of Formula (IVa),
  • P is a protecting group PG such as Boc (tert-butoxycarbonyl), Teoc (2- (trimethylsilyl)ethoxycarbonyl) or benzyl
  • Z is chlorine or bromine
  • R 1 , R3, R4, R4', R 4 ,, R 4 ,,,, m, n, r and Y have the meanings defined in the description.
  • a preferred embodiment of the invention is a process for the production of a compound of Formula (VIII) starting from a compound of Formula (VI),
  • P is a protecting group PG such as Boc (tert-butoxycarbonyl), Teoc (2- (trimethylsilyl)ethoxycarbonyl) or benzyl, and wherein R 1 , R3, R4, R4; Rr, R 4 ", m, n, r and W have the meanings defined in the description.
  • protecting group PG such as Boc (tert-butoxycarbonyl), Teoc (2- (trimethylsilyl)ethoxycarbonyl) or benzyl
  • R 1 , R3, R4, R4; Rr, R 4 ", m, n, r and W have the meanings defined in the description.
  • a preferred embodiment of the invention is a process for the production of a compound of Formula (I) starting from a compound of Formula (VIII),
  • L is a leaving group such as halogen, mesylate, tosylate or inflate, and wherein R 1 , R2, R 3 , R4, R4 , R 4 ,,, R4 ", m, n, q, r, X, Y and W have the meanings defined in the description.
  • R 1 , R2, R 3 , R4, R4 , R 4 ,,, R4 ", m, n, q, r, X, Y and W have the meanings defined in the description.
  • P is a protecting group PG such as Boc (tert-butoxycarbonyl), Teoc (2- (trimethylsilyl)ethoxycarbonyl) or benzyl, and W has the meaning defined in the description, is used for the preparation of a compound of Formula (I).
  • PG such as Boc (tert-butoxycarbonyl), Teoc (2- (trimethylsilyl)ethoxycarbonyl) or benzyl
  • W has the meaning defined in the description, is used for the preparation of a compound of Formula (I).
  • P is a protecting group PG such as Boc (tert-butoxycarbonyl), Teoc (2- (trimethylsilyl)ethoxycarbonyl) or benzyl, and wherein R3, R 4 , R 4 ,, Re, Rv; m, r, n, W and Y have the meanings defined in the description, is used for the preparation of a compound of Formula (I).
  • PG such as Boc (tert-butoxycarbonyl), Teoc (2- (trimethylsilyl)ethoxycarbonyl) or benzyl
  • R3, R 4 , R 4 ,, Re, Rv; m, r, n, W and Y have the meanings defined in the description, is used for the preparation of a compound of Formula (I).
  • P is a protecting group PG such as Boc (tert-butoxycarbonyl), Teoc (2- (trimethylsilyl)ethoxycarbonyl) or benzyl, and wherein R 1 , R3, R4, R 4 ,, R 4 ,,, R-r, m, r, n, W and Y have the meanings defined in the description, is used for the preparation of a compound of Formula (I).
  • PG such as Boc (tert-butoxycarbonyl), Teoc (2- (trimethylsilyl)ethoxycarbonyl) or benzyl
  • R 1 , R3, R4, R 4 ,, R 4 ,,, R-r, m, r, n, W and Y have the meanings defined in the description, is used for the preparation of a compound of Formula (I).
  • R 2 , q and X have the meanings defined in the description.
  • R 1 , R 3 , R*. R 4 ,. R 4 ,, Re-, m, r, n, W and Y have the meanings defined in the description, is used for the preparation of a compound of Formula (I).
  • P is a protecting group PG such as Boc (tert-butoxycarbonyl), Teoc (2-(trimethylsilyl)ethoxycarbonyl) or benzyl or P is Q and Q is
  • PG such as Boc (tert-butoxycarbonyl), Teoc (2-(trimethylsilyl)ethoxycarbonyl) or benzyl or P is Q and Q is
  • R 1 , R 2 , R 3 , 4, R*-, Rr, R*-, m, r, n, q, W, X and Y have
  • reaction products may, if desired, be purified by conventional methods, such as crystallisation and chromatography.
  • these isomers may be separated by conventional techniques such as preparative chromatography. If there are chiral centres the compounds may be prepared in racemic form, or individual enantiomers may be prepared either by enantiospecific synthesis or by resolution.
  • One preferred pharmaceutically acceptable form of a compound of the invention is the crystalline form, including such form in pharmaceutical composition.
  • the additional ionic and solvent moieties must also be non-toxic.
  • the compounds of the invention may present different polymorphic forms, it is intended that the invention encompasses all such forms.
  • compositions which comprises a compound according to the invention as described above according to general formula I or a pharmaceutically acceptable salt or stereoisomer thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle.
  • the present invention thus provides pharmaceutical compositions comprising a compound of this invention, or a pharmaceutically acceptable salt or stereoisomers thereof together with a pharmaceutically acceptable carrier, adjuvant, or vehicle, for administration to a patient.
  • pharmaceutical compositions include any solid (tablets, pills, capsules, granules etc.) or liquid (solutions, suspensions or emulsions) composition for oral, topical or parenteral administration.
  • the pharmaceutical compositions are in oral form, either solid or liquid.
  • Suitable dose forms for oral administration may be tablets, capsules, or solutions and may contain conventional excipients known in the art such as binding agents, for example syrup, acacia, gelatine, sorbitol, tragacanth, or polyvinylpyrrolidone; fillers, for example lactose, sugar, maize starch, calcium phosphate, sorbitol or glycine; tabletting lubricants, for example magnesium stearate; disintegrants, for example starch, polyvinylpyrrolidone, sodium starch glycollate or microcrystalline cellulose; or pharmaceutically acceptable wetting agents such as sodium lauryl sulfate.
  • binding agents for example syrup, acacia, gelatine, sorbitol, tragacanth, or polyvinylpyrrolidone
  • fillers for example lactose, sugar, maize starch, calcium phosphate, sorbitol or gly
  • the solid oral compositions may be prepared by conventional methods of blending, filling or tabletting. Repeated blending operations may be used to distribute the active agent throughout those compositions employing large quantities of fillers. Such operations are conventional in the art.
  • the tablets may for example be prepared by wet or dry granulation and optionally coated according to methods well known in normal pharmaceutical practice, in particular with an enteric coating.
  • compositions may also be adapted for parenteral administration, such as sterile solutions, suspensions or lyophilized products in the appropriate unit dosage form.
  • Adequate excipients can be used, such as bulking agents, buffering agents or surfactants.
  • the mentioned formulations will be prepared using standard methods such as those described or referred to in the Spanish and US Pharmacopoeias and similar reference texts.
  • Administration of the compounds or compositions of the present invention may be by any suitable method, such as intravenous infusion, oral preparations, and intraperitoneal and intravenous administration. Oral administration is preferred because of the convenience for the patient and the chronic character of the diseases to be treated.
  • an effective administered amount of a compound of the invention will depend on the relative efficacy of the compound chosen, the severity of the disorder being treated and the weight of the sufferer.
  • active compounds will typically be administered once or more times a day for example 1 , 2, 3 or 4 times daily, with typical total daily doses in the range of from 0.1 to 1000 mg/kg/day.
  • the compounds and compositions of this invention may be used with other drugs to provide a combination therapy.
  • the other drugs may form part of the same composition, or be provided as a separate composition for administration at the same time or at different time.
  • Another aspect of the invention refers to the use of a compound of the invention or a pharmaceutically acceptable salt or isomer thereof in the manufacture of a medicament.
  • Another aspect of the invention refers to a compound of the invention according as described above according to general formula I, or a pharmaceutically acceptable salt or isomer thereof, for use as a medicament for the treatment of pain.
  • the pain is medium to severe pain, visceral pain, chronic pain, cancer pain, migraine, inflammatory pain, acute pain or neuropathic pain, allodynia or hyperalgesia. This may include mechanical allodynia or thermal hyperalgesia.
  • Another aspect of the invention refers to the use of a compound of the invention in the manufacture of a medicament for the treatment or prophylaxis of pain.
  • the pain is selected from medium to severe pain, visceral pain, chronic pain, cancer pain, migraine, inflammatory pain, acute pain or neuropathic pain, allodynia or hyperalgesia, also preferably including mechanical allodynia or thermal hyperalgesia.
  • Another aspect of this invention relates to a method of treating or preventing pain which method comprises administering to a patient in need of such a treatment a therapeutically effective amount of a compound as above defined or a pharmaceutical composition thereof.
  • pain syndromes that can be treated are medium to severe pain, visceral pain, chronic pain, cancer pain, migraine, inflammatory pain, acute pain or neuropathic pain, allodynia or hyperalgesia, whereas this could also include mechanical allodynia or thermal hyperalgesia.
  • L is a leaving group such as halogen, mesylate, tosylate or triflate and Z is chlorine or bromine
  • Q is the group indicated in a square in Scheme 1 and PG is a protecting group.
  • Step 1 The compounds of general formula IVa or IVb wherein n is 0 and W is nitrogen, are prepared by Strecker reaction of ketone derivatives of formula II with amino compounds of formula Ilia or 1Mb using a metal cyanide, preferably potassium cyanide, in the presence of an acid catalyst, in water at room temperature.
  • a metal cyanide preferably potassium cyanide
  • Step 2 Compounds of general formula Iva or IVb are treated with a lithium salt in situ generated from compounds of general formula V with nBuLi, in a suitable solvent, preferably in tetrahydrofuran, at a suitable temperature comprised between -78 °C and room temperature, preferably at room temperature.
  • a suitable solvent preferably in tetrahydrofuran
  • the obtained imine intermediate compound is hydrolized to ketone compounds of formula VI or I in the presence of an aqueous inorganic acid such as HCI.
  • Step 3 A compound of formula VIII is prepared by deprotection of a compound of formula VI. If the protecting group is benzyl the deprotection is carried out under hydrogenation conditions, with hydrogen at a pressure comprised between 1 and 10 bar, in the presence of Pd and in a suitable solvent such as methanol or ethanol, optionally in the presence of an acid such as acetic or hydrochloric acid, at a suitable temperature comprised between room temperature and the reflux temperature.
  • Alternative hydrogenation conditions involve the treatment with dichloroethyl formate as hydrogen source, in a suitable solvent such dichloroethane, at a suitable temperature comprised between room temperature and the reflux temperature, preferably at the reflux temperature.
  • Step 4 From deprotected compounds of general formula VIII, compounds of general formula I can be prepared by reaction with suitable reagents, such as those of formula Vlla-b, using different conditions depending on the reagent nature.
  • suitable reagents such as those of formula Vlla-b, using different conditions depending on the reagent nature.
  • the alkylation reaction with a compound of formula Vila is carried out in a suitable solvent, such as acetonitrile, dichloromethane, 1 ,4-dioxane, ethanol or dimethylformamide, preferably in acetonitrile, in the presence of an inorganic base such as K2CO3 or CS2CO3, or an organic base such as triethylamine or diisopropylethylamine, preferably K2CO3, at a suitable temperature comprised between room temperature and the reflux temperature, preferably heating, or alternatively, this reaction can be carried out in a microwave reactor. Additionally, an activating agent such as Nal or Kl can be used.
  • a suitable solvent such as acetonitrile, dichloromethane, 1 ,4-dioxane, ethanol or dimethylformamide, preferably in acetonitrile
  • an inorganic base such as K2CO3 or CS2CO3
  • an organic base such as triethylamine or di
  • the reductive amination with a compound of formula Vllb is carried out in the presence of a reductive reagent, preferably sodium triacetoxyborohydride, in a suitable solvent, preferably methanol, at a suitable temperature comprised between room temperature and the reflux temperature, preferably in a microwave reactor.
  • a reductive reagent preferably sodium triacetoxyborohydride
  • a suitable solvent preferably methanol
  • Steps 1 to 4 represents the general route for the
  • Suitable protecting groups such as for example Boc (tert-butoxycarbonyl), Teoc (2-(trimethylsilyl)ethoxycarbonyl) or benzyl for the protection of amino groups.
  • suitable protecting groups such as for example Boc (tert-butoxycarbonyl), Teoc (2-(trimethylsilyl)ethoxycarbonyl) or benzyl for the protection of amino groups.
  • Boc tert-butoxycarbonyl
  • Teoc (2-(trimethylsilyl)ethoxycarbonyl) or benzyl for the protection of amino groups.
  • the procedures for the introduction and removal of these protecting groups are well known in the art and can be found thoroughly described in the literature.
  • a compound of formula I that shows chirality can also be obtained by resolution of a racemic compound of formula I either by chiral preparative HPLC or by crystallization of a diastereomeric salt or co-crystal.
  • the resolution step can be carried out at a previous stage, using any suitable intermediate.
  • DIPEA ⁇ /,N-Diisopropylethylarnine
  • A Column Acquity UPLC BEH C18 2.1x50 mm, 1.7 pm; flow rate 0.61 mL/min; A: NH 4 HCO 3 10mM; B: ACN; Gradient: 0.3 min in 98% A, 98% A to 0% A in 2.7 min, 2 min in 0% A, 0% A to 98% A in 0.2 min, 0.55 min in 98% A
  • step a The crude imine obtained in step a (1.3 g, 3.2 mmol) was dissolved in THF (26 mL) and 3 N HCI (ca. 26 mL) was added. The reaction was stirred at rt overnight until full conversion was achieved (HPLC analysis). The mixture was made alkaline with 10% NaOH and extracted twice with AcOEt. The combined organic phases were dried over Na2SO-), filtered and concentrated to give a brown oil. The crude product was purified by flash chromatography on neutral alumina, eluents CH:AcOEt, gradient from 0 to 100% of AcOEt, to give the title compound (1 g, yield 74% over two steps).
  • Example 7 (3-(4-(2-lsopropoxyethyl)piperazin-1 -yl)-1 -methylpiperidin-3-yl)(pyridin-2- yl)methanone.
  • Example 10 1 -(3-(4-lsopentylpiperazin-1 -yl)-3-picolinoylpiperidin-1 -yl)ethanone.
  • Example 11 ((1-Benzoyl-3-(4-isopentylpiperazin-1-yl)piperidin-3-yl)(pyridin-2- yl)methanone.
  • Example 15 (4-(4-lsopentylpiperazin-1 -yl)-2,2-dimethylpiperidin-4-yl)(pyridin-2- yl)methanone.
  • step a The compound obtained in step a (62 mg, 0.16 mmol) was dissolved in DCM (4 mL) under nitrogen atmosphere at 0 °C and Dess-Martin periodinane (DMP, 1.1 mL, 0.32 mmol) was added. The reaction mixture was allowed to reach rt and stirred overnight. After that it was diluted with DCM and washed with 10% NaOH. The aqueous layer was extracted several times and the combined organic phases were dried over Na 2 S0 4 , filtered and concentrated.
  • DMP Dess-Martin periodinane
  • Example 17 (1 -Benzoyl-4-(4-isopentylpiperazin-1 -yl)-2,2-dimethylpiperidin-4- yl)(pyridin-2-yl)methanone.
  • Example 19 4-(4-lsopentylpiperazin-1-yl)-A/ l 2 l 2-trimethyl-4-picolinoylpiperidine-1- carboxamide.
  • step a 70 mg, 0.18 mmol was dissolved, under argon atmosphere, in MeOH (2 mL).
  • the suspension was stirred at rt overnight and then, more sodium triacetoxyborohydride was added and stirred for 24 h more.
  • the reaction mixture was slowly poured into sat aqueous solution of NaHC0 3 at 0 °C. The reaction was filtered, washed with water several times and dried to afford the title compound (61 mg, 74% purity, yield 62%).
  • step a) The compound obtained in step a) was oxidized using the procedure described in Ex 15 step b, to give the title compound.
  • Example 21 was prepared according to the procedure described in example 1 , using intermediate 1H as starting material.
  • transfected HEK-293 membranes and [ 3 H](+)-pentazocine (Perkin Elmer, NET-1056), as the radioligand, were used.
  • the assay was carried out with 7 ig of membrane suspension, 5 nM of [ 3 H](+)-pentazocine in either absence or presence of either buffer or 10 ⁇ Haloperidol for total and non-specific binding, respectively.
  • Binding buffer contained Tris-HCI 50 mM at pH 8. Plates were incubated at 37 °C for 120 minutes.
  • the reaction mix was then transferred to Multiscreen HTS, FC plates (Millipore), filtered and plates were washed 3 times with ice-cold 10 mM Tris-HCL (pH7.4). Filters were dried and counted at approximately 40% efficiency in a MicroBeta scintillation counter (Perkin-Elmer) using EcoScint liquid scintillation cocktail.
  • transfected HEK-293 membranes (7 ⁇ g) were incubated with 5 nM of [ 3 H](+)-pentazocine in assay buffer containing Tris-HCI 50 mM at pH 8. NBS (nonspecific binding) was measured by adding 10 ⁇ Haloperidol.
  • the binding of the test compound was measured at five different concentrations. Plates were incubated at 37 °C for 120 minutes. After the incubation period, the reaction mix was then transferred to Multiscreen HTS, FC plates (Millipore), filtered and plates were washed 3 times with ice-cold 10 mM Tris-HCL (pH7.4). Filters were dried and counted at approximately 40% efficiency in a MicroBeta scintillation counter (Perkin-Elmer) using EcoScint liquid scintillation cocktail.
  • Human u-opioid receptor radioligand assay To investigate binding properties of test compounds to human ⁇ -opioid receptor, transfected CHO-K1 cell membranes and [ 3 H]-DAMGO (Perkin Elmer, ES-542-C), as the radioligand, were used. The assay was carried out with 20 [ig of membrane suspension, 1 nM of [ 3 H]-DAMGO in either absence or presence of either buffer or 10 ⁇ Naloxone for total and non-specific binding, respectively. Binding buffer contained Tris-HCI 50 mM, MgCI2 5 mM at pH 7.4. Plates were incubated at 27°C for 60 minutes.
  • the reaction mix was then transferred to Multiscreen HTS, FC plates (Millipore), filtered and plates were washed 3 times with ice-cold 10 mM Tris- HCL (pH 7.4). Filters were dried and counted at approximately 40% efficiency in a MicroBeta scintillation counter (Perkin-Elmer) using EcoScint liquid scintillation cocktail.
  • transfected CHO-K1 cell membranes (20 ⁇ g) were incubated with 1 nM of [ 3 H]-DAMGO in assay buffer containing Tris-HCI 50 mM, MgCI2 5 mM at pH 7.4. NBS (non-specific binding) was measured by adding 10 ⁇ Naloxone.
  • the binding of the test compound was measured at five different concentrations. Plates were incubated at 27°C for 60 minutes. After the incubation period, the reaction mix was then transferred to Multiscreen HTS, FC plates (Millipore), filtered and plates were washed 3 times with ice-cold 10 mM Tris-HCL (pH 7.4). Filters were dried and counted at approximately 40% efficiency in a MicroBeta scintillation counter (Perkin-Elmer) using EcoScint liquid scintillation cocktail.
  • this invention is aimed at providing a compound or a chemically related series of compounds which act as dual ligands of the ⁇ 1 receptor and the ⁇ -opioid receptor it is a very preferred embodiment in which the compounds are selected which act as dual ligands of the ⁇ 1 receptor and the ⁇ -opioid receptor and especially compounds which have a binding expressed as K, which is preferably ⁇ 1000 nM for both receptors, more preferably ⁇ 500 nM, even more preferably ⁇ 100 nM.

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Abstract

La présente invention concerne des dérivés de méthanone pipéridine ayant une double activité pharmacologique à la fois envers le récepteur sigma (σ) et le récepteur µ-opioïde. L'invention concerne également des procédés de préparation de ces composés, des compositions pharmaceutiques les comprenant, ainsi que leur utilisation thérapeutique, en particulier pour traiter la douleur.
PCT/EP2018/000078 2017-02-27 2018-02-27 Dérivés de méthanone pipéridine ayant une activité multimodale contre la douleur Ceased WO2018153545A1 (fr)

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Citations (4)

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Publication number Priority date Publication date Assignee Title
WO2016078771A1 (fr) * 2014-11-21 2016-05-26 Laboratorios Del Dr. Esteve, S.A. Composés de 1,9-diazaspiro-undécane à activité multimodale contre la douleur
WO2016078770A1 (fr) * 2014-11-21 2016-05-26 Laboratorios Del Dr. Esteve, S.A. Composés de spiro-isoquinoline-1,4'-pipéridine à activité multimodale contre la douleur
WO2016173710A1 (fr) * 2015-04-28 2016-11-03 Laboratorios Del Dr. Esteve, S.A. Composés de spiro-isoquinoline-3,4'-pipéridine à activité contre la douleur
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WO2016078771A1 (fr) * 2014-11-21 2016-05-26 Laboratorios Del Dr. Esteve, S.A. Composés de 1,9-diazaspiro-undécane à activité multimodale contre la douleur
WO2016078770A1 (fr) * 2014-11-21 2016-05-26 Laboratorios Del Dr. Esteve, S.A. Composés de spiro-isoquinoline-1,4'-pipéridine à activité multimodale contre la douleur
WO2016173710A1 (fr) * 2015-04-28 2016-11-03 Laboratorios Del Dr. Esteve, S.A. Composés de spiro-isoquinoline-3,4'-pipéridine à activité contre la douleur
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