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WO2004058265A1 - Bibliotheques de composes de derives de pyrazine 2,3-substitues pouvant se fixer aux recepteurs couples a la proteine g - Google Patents

Bibliotheques de composes de derives de pyrazine 2,3-substitues pouvant se fixer aux recepteurs couples a la proteine g Download PDF

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Publication number
WO2004058265A1
WO2004058265A1 PCT/GB2003/005668 GB0305668W WO2004058265A1 WO 2004058265 A1 WO2004058265 A1 WO 2004058265A1 GB 0305668 W GB0305668 W GB 0305668W WO 2004058265 A1 WO2004058265 A1 WO 2004058265A1
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WIPO (PCT)
Prior art keywords
list
compounds
formula
attachment
point
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PCT/GB2003/005668
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English (en)
Inventor
Graham Peter Jones
David Hardy
Jacqueline Anne Macritchie
Martin John Slater
Original Assignee
Biofocus Plc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GB0230195A external-priority patent/GB0230195D0/en
Application filed by Biofocus Plc filed Critical Biofocus Plc
Priority to PCT/GB2003/005668 priority Critical patent/WO2004058265A1/fr
Priority to AU2003290346A priority patent/AU2003290346A1/en
Publication of WO2004058265A1 publication Critical patent/WO2004058265A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4747—Quinolines; Isoquinolines spiro-condensed
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D241/20—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/10—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings
    • 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
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00—Libraries per se, e.g. arrays, mixtures
    • C40B40/04—Libraries containing only organic compounds
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B50/00—Methods of creating libraries, e.g. combinatorial synthesis
    • C40B50/08—Liquid phase synthesis, i.e. wherein all library building blocks are in liquid phase or in solution during library creation; Particular methods of cleavage from the liquid support

Definitions

  • the present invention relates to compounds capable of binding to G-protein coupled receptors.
  • a library of compounds is provided for use in screening 10 programmes against GPCR targets as well as the individual compounds for use in hit to lead and lead optimisation projects and similar stages in the drug discovery process.
  • the method also provides methods for making compounds and 15 libraries.
  • Screening libraries are commonly collections of compounds from several sources. As a result, they typically contain compounds synthesised as a part of previous projects in the history of a company. With regard to drug discovery, these collections will be drug-like but are likely to be limited in scope and will be directed to certain areas of a particular project. It has been the common practice of many pharmaceutical companies in recent times to augment the collections by purchasing either single compounds from vendors or by contracting the synthesis of combinatorial libraries of compounds. The singly purchased compounds may have been selected to fill in areas of compound space poorly represented in the compound collections. Combinatorial libraries are typically synthesised around well-performing chemistries with some ' design based on producing ⁇ diversity' in compound space.
  • a complementary approach, and one that is increasingly preferred, is to screen focused libraries against the target of choice. Focused libraries are becoming of increasing importance in their ability to generate hits capable of rapid expansion in many areas including GPCRs . Such libraries are slightly more expensive to prepare but have attributes of reliability, reproducibility and provide a considerably higher hit rate: typically 10-100 fold and above compared with random screening. They are, however, very difficult to design and their efficiency relates directly to the amount of effort that has gone into the design. Using focused libraries, it is usually possible to get a number of hits in the low micromolar and below range. As there is a defined set of compounds there is the potential to observe indications of SAR in a chemical series and progress the chemistry efficiently.
  • GPCRs G-protein-coupled receptors
  • the rhodopsin receptor is somewhat unusual in its interactions with its ligand and is not used as a drug target. Nevertheless the overall three dimensional arrangement can be deduced from the X-ray and is in accordance with previous work based upon bacteriorhodopsin receptor which is not G-protein-coupled.
  • GPCRs are most often characterised by sequence homology as being comprised of several sub-families. Most attention currently is directed towards Family A receptors as being the most tractable class historically and also the one with the most potential targets.
  • Family A comprises about 300 receptors that are potential drug targets, approximately half of which have known ligands and the rest, the so-called orphan receptors.
  • the group of druggable receptors is composed essentially of two types: those whose natural ligand interacts wholly within the transmembrane domain, such as the aminergic, nucleotide-like, prostaglandin receptors, etc. and those peptide liganded receptors, which have a large part of their interactions in the extracellular region and which may insert a peptide loop or tail into the transmembrane region to effect signal transduction. Examples of this class are angiotensin, cholecystokinin and opioid receptors.
  • the focused library provided herein is designed to interact with a range of the family A receptors.
  • Each library is a defined set of compounds that will enhance the probability of finding a small molecule that will interact with one or more type of GPCR receptor.
  • focused libraries can be provided having compounds which will interact with aminergic GPCRs, and peptidic GPCRs requiring an obligatory positive charge in ligands, or other types or groups of GPCRs.
  • Focused libraries according to this invention can provide hit rates of 1-13% or more for the requisite predicted GPCRs from both amine- and peptide-liganded classes and with agonists and antagonists.
  • library means a group of compounds which are structurally related by virtue of a core chemical structure (or “scaffold”) but which differ from each other by virtue of permutation of specific substituent groups attached to the scaffold.
  • such a library will consist of or comprise a number of compounds, e.g. as many as about 100, 1000,2000, 3000 or indeed 10,000 compounds.
  • the number of compounds should be sufficient to provide an adequate diversity of related compounds without being so large as to be unduly complex/expensive to produce.
  • the substituent may appear in the compound exactly as shown (i.e. simply covalently bonded to the scaffold) or may be a derivative of the shown chemical formula of the substituent by virtue of use of a reactive group to couple the substituent to the scaffold.
  • the total number of permutations created by the permitted substituents may be a very large number, far greater in magnitude than the actual number of compounds in an actual library.
  • the number of possible compounds for any "virtual" library may well greatly exceed the number of synthesised compounds making up an embodiment of the "real” library.
  • the invention is intended to encompass libraries having all, and a number, which is less than all, of the permitted substitutions represented by compounds therein.
  • WO 03/00308 discloses a compound library suitable for use in identifying compounds which act on G-protein coupled receptors, also called 7TM receptors. This compound library may overlap with WO 03/00308, but is not identical to the compound library of the present invention. Where compounds per se are claimed by the present ' invention, generally any compounds specifically claimed in WO 03/00308 are hereby disclaimed per se.
  • Library 5 is designed to pick up interactions with receptors for a subset of peptidic receptors, especially those with recognition sites for amide and acidic ligands based around TM3 and TM6.
  • This group is represented by such receptors as Bombesin (BSR3) , Endothelin A, Neuromedin U and Neuropeptide Y amongst others.
  • BSR3 Bombesin
  • Endothelin A Endothelin A
  • Neuromedin U and Neuropeptide Y amongst others.
  • the presence of the amide-acid recognition site here is a consequence of the requirements for binding the natural ligands either with C-terminal regions or with the backbone of peptide loops .
  • the techniques used in designing this library have also provided the opportunity to design both agonists and antagonists for these receptors .
  • the invention provides a compound library comprising of a set of structurally related compounds of the following general formulae:
  • 3-chloroprazine-2-carbonitrile (1.39g (0.01 mol)) and 4- hydroxymethyl phenyl boronic acid (1.5g, 0.011 mol) were dissolved in dimethoxyethane (30ml) and potassium carbonate (3.8g) in water (15ml) added.
  • Triphenyl phosphine (0.39g) and Palladium (II) acetate 1(0. llg) were added and the mixture was stirred and heated to 90°C overnight, after cooling the reaction was diluted with ethyl acetate (30ml) , filtered through celite and the organic layer separated, dried and evaporated.
  • the reaction was cooled, added to water (800ml) and washed with ethyl acetate (2x250ml) .
  • the aqueous phase was acidified with citric acid and extracted with ethyl acetate (3x500ml) .
  • the organic extracts were combined, washed with brine (100ml) , dried over MgS0 and evaporated down.
  • Cyclopropane sulphonic acid (3-chloro pyrazin-2-yl) amide (2.42g, 0.008mmol) and 4-formyl benzene boronic acid (1.4g, 0.0093 mol) were dissolved in dimethoxy ethane (30ml) and potassium carbonate (3.2g in 15ml water) added.
  • Triphenyl phosphine (0.32g) and palladium (II) acetate (93mg) were added and the mixture stirred at 90°C overnight. The mixture was cooled and diluted with diethyl ether (60ml) . Water (50ml) was added and the cloudy solution was filtered through celite.
  • reaction was added to water (200ml) , acidified with AcOH (3ml) and extracted with ethyl acetate (4x50ml) .
  • the organic phases were combined, washed with water (2x100ml) , dried over magnesium sulphate and evaporated down.
  • Benzyl sulphonyl chloride 38mg, 0.2 mmol
  • Hunigs Base lml, 1.0M in dimethyl formamide 1.0 mmol
  • the aqueous phase was acidified with acetic acid (1.25ml) and extracted with ethyl acetate (2x40ml) .
  • the organic phases were combined, washed with water (40ml) , dried over magnesium sulphate and evaporated under reduced pressure.
  • the product was purified by flash chromatography using 30% ethyl acetate in petrol to give 165mg of 4-Chloro-N-phenyl-3, 4, 5, 6- tetrahydro-2H- [1,2' ] bipyazinyl-3' -yl) benzenesulphonamide .
  • the Gilson 215 was used as both auto-sampler and fraction collector.
  • the gradient used was 95% water / 5% acetonitrile (each containing 0.1% formic acid) for 1.5 min to 95% acetonitrile over 6 min then held at 95% acetonitrile for 3.0 min.
  • the solvent mixture was then returned to the initial conditions over 0.25 min.
  • the column was re- equilibrated over 2.5 minutes prior to the next injection.
  • the purification was controlled by Unipoint software, triggering a threshold collection value monitoring at 240 nm. Collected fractions were analysed by LCMS . The fractions that contained the desired product were concentrated by vacuum centrifugation and the resultant residue dried by freeze-drying.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biochemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Molecular Biology (AREA)
  • Structural Engineering (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

La présente invention concerne une bibliothèque de composés pouvant sélectionner des interactions avec des récepteurs pour un sous-ensemble de récepteurs peptidiques, en particulier ceux qui comprennent des sites de reconnaissance de ligands d'amides et d'acides basés autour de TM3 et TM6. La présence du site de reconnaissance amides-acides est une conséquence des exigences de liaison des ligands naturels soit à des régions C-terminal, soit au squelette de boucles peptidiques. La bibliothèque comprend ou est composée d'un ensemble de composés structurellement associés représentés par les formules générales suivantes: formule (A) formule (B) formule (C) formule (D1) formule (D2) formule (D3) formule (E) formule (F).
PCT/GB2003/005668 2002-12-24 2003-12-24 Bibliotheques de composes de derives de pyrazine 2,3-substitues pouvant se fixer aux recepteurs couples a la proteine g WO2004058265A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
PCT/GB2003/005668 WO2004058265A1 (fr) 2002-12-24 2003-12-24 Bibliotheques de composes de derives de pyrazine 2,3-substitues pouvant se fixer aux recepteurs couples a la proteine g
AU2003290346A AU2003290346A1 (en) 2002-12-24 2003-12-24 Compound libraries of 2,3-substituted pyrazine derivatives capable of binding to g-protein coupled receptors

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB0230195.0 2002-12-24
GB0230195A GB0230195D0 (en) 2002-12-24 2002-12-24 Compound Libraries
PCT/GB2003/005668 WO2004058265A1 (fr) 2002-12-24 2003-12-24 Bibliotheques de composes de derives de pyrazine 2,3-substitues pouvant se fixer aux recepteurs couples a la proteine g

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Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004089905A1 (fr) * 2003-04-14 2004-10-21 Abbott Gmbh & Co. Kg Composes n-[(piperazinyl)hetaryl]arylsulfonamide dotes d'une affinite pour le recepteur de la dopamine d3
WO2006111560A3 (fr) * 2005-04-21 2007-05-03 Applied Research Systems Pyrazine sulfonamides 2,3 substituees
US7320979B2 (en) 2003-04-14 2008-01-22 Abbott Gmbh & Co. Kg. N-[(piperazinyl)hetaryl]arylsulfonamide compounds
JP2008526996A (ja) * 2005-01-14 2008-07-24 ケモセントリックス， インコーポレイテッド ヘテロアリールスルホンアミドおよびｃｃｒ２
WO2009147990A1 (fr) * 2008-06-02 2009-12-10 萬有製薬株式会社 Nouveau dérivé d'isoxazole
WO2012052420A1 (fr) 2010-10-20 2012-04-26 Merck Serono S.A. Geneva Procédé de préparation de n-(3-amino-quinoxalin-2-yl)-sulfonamides substitués et de leurs n-(3-chloro-quinoxalin-2-yl)sulfonamides intermédiaires
US8546408B2 (en) 2007-07-12 2013-10-01 Chemocentryx, Inc. Fused heteroaryl pyridyl and phenyl benzenesuflonamides as CCR2 modulators for the treatment of inflammation
CN106831556A (zh) * 2015-12-07 2017-06-13 成都海创药业有限公司 磺酰胺类化合物及其制备方法和作为尿酸盐转运体抑制剂类药物的用途
US10206912B2 (en) 2006-07-14 2019-02-19 Chemocentryx, Inc. Heteroaryl sulfonamides and CCR2/CCR9
US10758540B2 (en) 2017-10-11 2020-09-01 Chemocentryx, Inc. Treatment of focal segmental glomerulosclerosis with CCR2 antagonists
US10973809B2 (en) 2016-11-23 2021-04-13 Chemocentryx, Inc. Method of treating focal segmental glomerulosclerosis

Citations (5)

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Publication number Priority date Publication date Assignee Title
WO1996003424A1 (fr) * 1994-07-26 1996-02-08 The Scripps Research Institute Bibliotheques combinatoires de molecules et procedes de production des memes
WO1998054116A1 (fr) * 1997-05-28 1998-12-03 Cadus Pharmaceutical Corporation Synthese et utilisation de composes heteroaromatiques a base de thiophene et de pyrrole
WO2003003008A1 (fr) * 2001-06-29 2003-01-09 7Tm Pharma A/S Bibliotheques chimiques utiles aux procedes de decouvertes de medicaments
WO2003031406A2 (fr) * 2001-10-12 2003-04-17 Irm Llc Squelettes d'inhibiteurs de kinase et leurs methodes de preparation
WO2003066629A2 (fr) * 2002-02-06 2003-08-14 Vertex Pharmaceuticals Incorporated Composes heteroaryles utiles en tant qu'inhibiteurs de gsk-3

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996003424A1 (fr) * 1994-07-26 1996-02-08 The Scripps Research Institute Bibliotheques combinatoires de molecules et procedes de production des memes
WO1998054116A1 (fr) * 1997-05-28 1998-12-03 Cadus Pharmaceutical Corporation Synthese et utilisation de composes heteroaromatiques a base de thiophene et de pyrrole
WO2003003008A1 (fr) * 2001-06-29 2003-01-09 7Tm Pharma A/S Bibliotheques chimiques utiles aux procedes de decouvertes de medicaments
WO2003031406A2 (fr) * 2001-10-12 2003-04-17 Irm Llc Squelettes d'inhibiteurs de kinase et leurs methodes de preparation
WO2003066629A2 (fr) * 2002-02-06 2003-08-14 Vertex Pharmaceuticals Incorporated Composes heteroaryles utiles en tant qu'inhibiteurs de gsk-3

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Title
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; PALAMIDASSI, G.: "Pyrazine derivatives. VI", XP002277788, retrieved from STN Database accession no. 59:75305 *
FARMACO, EDIZIONE SCIENTIFICA (1963), 18(8), 557-65 *

Cited By (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004089905A1 (fr) * 2003-04-14 2004-10-21 Abbott Gmbh & Co. Kg Composes n-[(piperazinyl)hetaryl]arylsulfonamide dotes d'une affinite pour le recepteur de la dopamine d3
US7320979B2 (en) 2003-04-14 2008-01-22 Abbott Gmbh & Co. Kg. N-[(piperazinyl)hetaryl]arylsulfonamide compounds
US8476275B2 (en) * 2003-04-14 2013-07-02 Abbott Gmbh & Co. Kg N-[piperazinyl hetaryl]arylsufonamide compounds with affinity for the dopamine D3 receptor
EP2354126A1 (fr) * 2005-01-14 2011-08-10 ChemoCentryx, Inc. Sulfonamides d'hétéroarylamide et CCR2
JP2008526996A (ja) * 2005-01-14 2008-07-24 ケモセントリックス， インコーポレイテッド ヘテロアリールスルホンアミドおよびｃｃｒ２
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