CA2494100A1 - Pyrazole compositions useful as inhibitors of gsk-3 - Google Patents

Pyrazole compositions useful as inhibitors of gsk-3 Download PDF

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Publication number
CA2494100A1
CA2494100A1 CA002494100A CA2494100A CA2494100A1 CA 2494100 A1 CA2494100 A1 CA 2494100A1 CA 002494100 A CA002494100 A CA 002494100A CA 2494100 A CA2494100 A CA 2494100A CA 2494100 A1 CA2494100 A1 CA 2494100A1
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disease
agent
disorder
compound according
treating
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CA2494100C (en
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Cornelia J. Forster
Larry C. Park
Marion W. Wannamaker
Yung-Mae Yao
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Vertex Pharmaceuticals Inc
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    • C07D403/12—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 chain containing hetero atoms as chain links
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    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
    • 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
    • C07D403/14—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 three or more hetero rings
    • 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

Abstract

The present invention provides a compound of formula (I) or a pharmaceutical ly acceptable derivative thereof. These compounds are inhibitors of protein kinases, particularly inhibitors of GSK3 mammalian protein kinase. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of utilizing those compounds and compositions in the treatment of various protein kinase mediated disorders.< /SDOAB>

Claims (23)

1. A compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein:
W is nitrogen or CH;
R1 is selected from hydrogen or fluorine; and R y is a C1-4 aliphatic group, optionally substituted with N(R2)2 or a 5-6 membered saturated ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein:
each R2 is independently selected from hydrogen or a C1-3 aliphatic group optionally substituted with OH, N(R3)2, or a 5-6 membered saturated ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and wherein:
each R3 is independently selected from hydrogen or a C1-3 aliphatic group;
provided that:
when R1 is hydrogen and W is CH, then R y is other than methyl.
2. The compound of claim 1, wherein R y is a C1-4 aliphatic group.
3. The compound of claim 2, wherein R y is selected from methyl, ethyl, cyclopropyl, tert-butyl, or isopropyl.
4. The compound according to claim 3, wherein R y is selected from methyl, cyclopropyl, or tert-butyl.
5. The compound according to claim 1, wherein W is nitrogen.
6. The compound according to claim 1, wherein W is CH.
7. The compound according to claim 1, wherein R1 is hydrogen.
8. The compound according to claim 1, wherein R1 is fluorine.
9. The compound according to claim 1, wherein R y is a C1-4 aliphatic group substituted with a 6-membered saturated ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
10. The compound according to claim 9, wherein R y is a C1-4 aliphatic group substituted with a morpholinyl, piperidinyl, or piperazinyl ring
11. The compound according to claim 1, wherein R y is a C1-4 aliphatic group substituted with N(R2)2.
12. A compound selected from the group consisting of:

13. A pharmaceutically acceptable composition comprising a compound according to claim 1, and a pharmaceutically acceptable carrier, adjuvent, or vehicle.
14. The composition according to claim 13, additionally comprising an additional therapeutic agent selected from a treatment for Alzheimer's Disease (AD), a treatment for Parkinson's Disease, an agent for treating Multiple Sclerosis (MS), a treatment for asthma, an anti-inflammatory agent, an immunomodulatory or immunosuppressive agent, a neurotrophic factor, an agent for treating stroke, an agent for treating cardiovascular disease, an antidepressant, an anti-psychotic agent, or an agent for treating diabetes.
15. A method of inhibiting GSK3 kinase activity in a biological sample, comprising the step of contacting said biological sample with:
a) a composition according to claim 13; or b) a compound according to claim 1.
16. A method of GSK3 kinase activity in a patient, comprising the step of administering to said patient:
a) a composition according to claim 13; or b) a compound according to claim 1.
17. A method of treating an autoimmune disease, an inflammatory disease, a metabolic disorder, a psychiatric disorder, diabetes, an angiogenic disorder, tauopothy, a neurological or neurodegenerative disorder, a spinal cord injury, glaucoma, baldness, or a cardiovascular disease, in a patient in need thereof, comprising administering to said patient a composition according to claim 13.
18. The method according to claim 17, wherein said disease, disorder, or condition is selected from allergy, asthma, diabetes, Alzheimer's disease, Huntington's disease, Parkinson's disease, AIDS-associated dementia, amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), multiple sclerosis (MS), an injury due to head trauma, schizophrenia, anxiety, bipolar disorder, tauopothy, a spinal cord or peripheral nerve injury, myocardial infarction, cardiomyocyte hypertrophy, glaucoma, attention deficit disorder (ADD), depression, a sleep disorder, reperfusion/ischemia, stroke, an angiogenic disorder, or baldness,
19. The method according to claim 18, wherein said disease, disorder, or condition is stroke.
20. The method according to claim 18, wherein said disease, disorder, or condition is Alzheimer's disease.
21. The method according to claim 17, wherein said disorder is a neurological or neurodegenerative disorder.
22. A method of decreasing sperm motility in a male patient comprising administering to said patient a composition according to claim 13.
23. The method according to claim 17, comprising the additional step of administering to said patient an additional therapeutic agent selected from a treatment for Alzheimer's Disease (AD), a treatment for Parkinson's Disease, an agent for treating Multiple Sclerosis (MS), a treatment for asthma, an anti-inflammatory agent, an immunomodulatory or immunosuppressive agent, a neurotrophic factor, an agent for treating stroke, an agent for treating cardiovascular disease, an antidepressant, an anti-psychotic agent, or an agent for treating diabetes, wherein:
said additional therapeutic agent is appropriate for the disease being treated; and said additional therapeutic agent is administered together with said composition as a single dosage form or separately from said composition as part of a multiple dosage form.
CA2494100A 2002-08-02 2003-07-31 Pyrazole compositions useful as inhibitors of gsk-3 Expired - Fee Related CA2494100C (en)

Applications Claiming Priority (3)

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US40096702P 2002-08-02 2002-08-02
US60/400,967 2002-08-02
PCT/US2003/023950 WO2004013140A1 (en) 2002-08-02 2003-07-31 Pyrazole compositions useful as inhibitors of gsk-3

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CA2494100A1 true CA2494100A1 (en) 2004-02-12
CA2494100C CA2494100C (en) 2011-10-11

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US (2) US7491730B2 (en)
EP (1) EP1532145B1 (en)
JP (3) JP4733388B2 (en)
KR (1) KR20050032105A (en)
CN (2) CN1319968C (en)
AR (1) AR040773A1 (en)
AT (1) ATE339419T1 (en)
AU (2) AU2003257078B2 (en)
BR (1) BR0313176A (en)
CA (1) CA2494100C (en)
CO (1) CO5700772A2 (en)
DE (1) DE60308387T2 (en)
DK (1) DK1532145T3 (en)
EA (1) EA200500299A1 (en)
EC (1) ECSP055640A (en)
ES (1) ES2273043T3 (en)
HK (1) HK1081186A1 (en)
IL (1) IL166620A (en)
MX (1) MXPA05001367A (en)
NO (1) NO20051100L (en)
NZ (2) NZ538426A (en)
PL (1) PL374967A1 (en)
PT (1) PT1532145E (en)
TW (1) TWI324157B (en)
WO (1) WO2004013140A1 (en)
ZA (1) ZA200501124B (en)

Families Citing this family (63)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6660731B2 (en) 2000-09-15 2003-12-09 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
EP1317449B1 (en) 2000-09-15 2006-05-31 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
ATE340172T1 (en) 2000-12-21 2006-10-15 Vertex Pharma PYRAZOLE COMPOUNDS AS PROTEIN KINASE INHIBITORS
US20040009981A1 (en) 2002-03-15 2004-01-15 David Bebbington Compositions useful as inhibitors of protein kinases
MY141867A (en) 2002-06-20 2010-07-16 Vertex Pharma Substituted pyrimidines useful as protein kinase inhibitors
ES2273043T3 (en) * 2002-08-02 2007-05-01 Vertex Pharmaceuticals Incorporated PIRAZOL COMPOSITIONS USEFUL AS INHIBITORS OF GSK-3.
WO2004072029A2 (en) 2003-02-06 2004-08-26 Vertex Pharmaceuticals Incorporated Pyrazolopyridazines useful as inhibitors of protein kinases
WO2006007864A1 (en) * 2004-07-17 2006-01-26 Max Planck Geselllschaft Zur Förderung Der Wissenschaft Treating neurodegenerative conditions
WO2006031852A1 (en) 2004-09-13 2006-03-23 Amgen Inc. Vanilloid receptor ligands and their use in treatments
US8771754B2 (en) * 2004-09-17 2014-07-08 Vanderbilt University Use of GSK3 inhibitors in combination with radiation therapies
CA2619517A1 (en) 2005-08-18 2007-02-22 Michael Mortimore Pyrazine kinase inhibitors
EP1928437A2 (en) 2005-08-26 2008-06-11 Braincells, Inc. Neurogenesis by muscarinic receptor modulation
EP2258358A3 (en) 2005-08-26 2011-09-07 Braincells, Inc. Neurogenesis with acetylcholinesterase inhibitor
JP2009512711A (en) 2005-10-21 2009-03-26 ブレインセルス，インコーポレイティド Regulation of neurogenesis by PDE inhibition
EP1942879A1 (en) 2005-10-31 2008-07-16 Braincells, Inc. Gaba receptor mediated modulation of neurogenesis
TW200734327A (en) 2005-11-03 2007-09-16 Vertex Pharma Aminopyrimidines useful as kinase inhibitors
CN104650077A (en) 2006-01-17 2015-05-27 沃泰克斯药物股份有限公司 Azaindoles useful as inhibitors of janus kinases
US20100216734A1 (en) 2006-03-08 2010-08-26 Braincells, Inc. Modulation of neurogenesis by nootropic agents
CA2651813A1 (en) 2006-05-09 2007-11-22 Braincells, Inc. Neurogenesis by modulating angiotensin
US20100184806A1 (en) 2006-09-19 2010-07-22 Braincells, Inc. Modulation of neurogenesis by ppar agents
BRPI0717937A2 (en) 2006-10-31 2013-12-03 Pfizer Prod Inc PIRAZONE COMPOUNDS AS ANTAGONISTS OF THE MINERALOCORTICIDE RECEPTOR
DE602007004750D1 (en) * 2006-11-02 2010-03-25 Vertex Pharma AS INHIBITORS OF PROTEIN KINASES SUITABLE AMINOPYRIDINES AND AMINOPYRIMIDINES
DE602007007985D1 (en) 2006-12-19 2010-09-02 Vertex Pharma AS INHIBITORS OF PROTEIN KINASES SUITABLE AMINO-PRIMIDINES
EP2124951B1 (en) 2006-12-21 2014-05-21 Vertex Pharmaceuticals Inc. 5-cyan0-4- (pyrrolo[2, 3b]pyridine-3-yl) -pyrimidine derivatives useful as protein kinase inhibitors
US8802638B1 (en) 2007-01-25 2014-08-12 University Of South Florida Flavonoid treatment of glycogen synthase kinase-based disease
JP2010518014A (en) * 2007-01-31 2010-05-27 バーテックス ファーマシューティカルズ インコーポレイテッド 2-Aminopyridine derivatives useful as kinase inhibitors
AU2008226457B2 (en) * 2007-03-09 2014-03-20 Vertex Pharmaceuticals Incorporated Aminopyrimidines useful as inhibitors of protein kinases
CA2680029A1 (en) 2007-03-09 2008-09-18 Vertex Pharmaceuticals Incorporated Aminopyrimidines useful as inhibitors of protein kinases
NZ579483A (en) 2007-03-09 2012-07-27 Vertex Pharma Aminopyridines useful as inhibitors of protein kinases
CA2683785A1 (en) 2007-04-13 2008-10-23 Vertex Pharmaceuticals Incorporated Aminopyrimidines useful as kinase inhibitors
AU2008247594A1 (en) 2007-05-02 2008-11-13 Vertex Pharmaceuticals Incorporated Aminopyrimidines useful as kinase inhibitors
MX2009011810A (en) 2007-05-02 2010-01-14 Vertex Pharma Thiazoles and pyrazoles useful as kinase inhibitors.
US8648069B2 (en) 2007-06-08 2014-02-11 Abbvie Inc. 5-substituted indazoles as kinase inhibitors
KR20100032886A (en) * 2007-06-08 2010-03-26 아보트 러보러터리즈 5-heteroaryl substituted indazoles as kinase inhibitors
CA2694499A1 (en) * 2007-07-31 2009-02-05 Vertex Pharmaceuticals Incorporated Process for preparing 5-fluoro-1h-pyrazolo [3, 4-b] pyridin-3-amine and derivatives thereof
KR20090031122A (en) * 2007-09-21 2009-03-25 주식회사 중외제약 Compounds containing indazole frameworks, preparing method thereof and pharmaceutical composition containing thereof
JP5587206B2 (en) 2007-12-19 2014-09-10 バーテックス ファーマシューティカルズ インコーポレイテッド Pyrazolo [1,5-a] pyrimidines useful as JAK2 inhibitors
WO2009145814A2 (en) * 2008-03-10 2009-12-03 Vertex Pharmaceuticals Incorporated Pyrimidines and pyridines useful as inhibitors of protein kinases
US8263547B2 (en) 2008-05-28 2012-09-11 Massachusetts Institute Of Technology DISC-1 pathway activators in the control of neurogenesis
US20100216805A1 (en) 2009-02-25 2010-08-26 Braincells, Inc. Modulation of neurogenesis using d-cycloserine combinations
US9265764B2 (en) * 2009-02-27 2016-02-23 Massachusetts Institute Of Technology Uses of chemicals to modulate GSK-3 signaling for treatment of bipolar disorder and other brain disorders
KR20100101055A (en) * 2009-03-07 2010-09-16 주식회사 메디젠텍 Composition for treating or preventing nuclear export of gsk3- mediated disease including compound for inhibiting nuclear export of gsk3
BRPI1011993A2 (en) 2009-06-17 2021-07-06 Vertex Pharmaceuticals Incorporated replication inhibitors of the influenza virus, their use, method of preparation and pharmaceutical composition that comprises them
US20110118275A1 (en) * 2009-11-13 2011-05-19 Astrazeneca Ab OXAZOLO[4,5-c]PYRIDINE SUBSTITUTED PYRAZINE
US8592485B2 (en) * 2010-06-17 2013-11-26 Healthpartners Research Foundation Methods and pharmaceutical compositions for treating the animal central nervous system for psychiatric disorders
KR20120063283A (en) * 2010-12-07 2012-06-15 제일약품주식회사 Novel pyrazolopyridine derivatives or pharmaceutically acceptable salts thereof, process for the preparation thereof and pharmaceutical composition comprising the same
CA2822057A1 (en) 2010-12-16 2012-06-21 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
UA118010C2 (en) 2011-08-01 2018-11-12 Вертекс Фармасьютікалз Інкорпорейтед INFLUENCES OF INFLUENZA VIRUS REPLICATION
EP2671885A1 (en) * 2012-06-05 2013-12-11 Ares Trading S.A. Imidazo-oxadiazole and Imidazo-thiadiazole derivatives
US8992951B2 (en) 2013-01-09 2015-03-31 Sapna Life Sciences Corporation Formulations, procedures, methods and combinations thereof for reducing or preventing the development, or the risk of development, of neuropathology as a result of trauma
HUE057521T2 (en) 2013-03-14 2022-05-28 Brigham & Womens Hospital Inc Compositions and methods for epithelial stem cell expansion and culture
PT3068776T (en) 2013-11-13 2019-08-26 Vertex Pharma Inhibitors of influenza viruses replication
PT3068782T (en) 2013-11-13 2018-10-08 Vertex Pharma Methods of preparing inhibitors of influenza viruses replication
WO2015155738A2 (en) 2014-04-09 2015-10-15 Christopher Rudd Use of gsk-3 inhibitors or activators which modulate pd-1 or t-bet expression to modulate t cell immunity
KR101731624B1 (en) 2014-07-01 2017-05-04 광주과학기술원 Compositions for inducing a cell re-programming
AU2015311816B2 (en) 2014-09-03 2019-04-04 Massachusetts Institute Of Technology Compositions, systems, and methods for generating inner ear hair cells for treatment of hearing loss
WO2016183116A1 (en) 2015-05-13 2016-11-17 Vertex Pharmaceuticals Incorporated Methods of preparing inhibitors of influenza viruses replication
MA42422A (en) 2015-05-13 2018-05-23 Vertex Pharma INHIBITORS OF INFLUENZA VIRUS REPLICATION
CN108779437A (en) 2016-01-08 2018-11-09 麻省理工学院 The preparation of the enteroendocrine cell and insulin-producing cells of differentiation
CN107151235B (en) * 2016-03-04 2019-12-13 上海市计划生育科学研究所 Use of thiadiazolidinedionyl GSK3 inhibitors for modulating sperm motility
US11331313B2 (en) 2017-05-22 2022-05-17 Whitehead Institute For Biomedical Research KCC2 expression enhancing compounds and uses thereof
CN112334473B (en) * 2018-09-14 2022-05-27 江苏恒瑞医药股份有限公司 Crystal form of heteroaryl [4,3-c ] pyrimidine-5-amine derivative and preparation method thereof
JP2022520671A (en) 2019-02-08 2022-03-31 フリークエンシー・セラピューティクス・インコーポレイテッド Valproic acid compounds and WNT agonists for the treatment of ear disorders

Family Cites Families (81)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3133081A (en) 1964-05-12 J-aminoindazole derivatives
US3935183A (en) 1970-01-26 1976-01-27 Imperial Chemical Industries Limited Indazole-azo phenyl compounds
BE754242A (en) 1970-07-15 1971-02-01 Geigy Ag J R DIAMINO-S-TRIAZINES AND DINITRO-S-TRIAZINES
US3998951A (en) 1974-03-13 1976-12-21 Fmc Corporation Substituted 2-arylquinazolines as fungicides
DE2458965C3 (en) 1974-12-13 1979-10-11 Bayer Ag, 5090 Leverkusen 3-Amino-indazole-N-carboxylic acid derivatives, process for their preparation and pharmaceuticals containing them
MA18829A1 (en) 1979-05-18 1980-12-31 Ciba Geigy Ag PYRIMIDINE DERIVATIVES, METHODS FOR THEIR PREPARATION, PHARMACEUTICAL COMPOSITIONS CONTAINING THESE COMPOUNDS AND THEIR THERAPEUTIC USE
DOP1981004033A (en) 1980-12-23 1990-12-29 Ciba Geigy Ag PROCEDURE TO PROTECT CROP PLANTS FROM PHYTOTOXIC ACTION OF HERBICIDES.
SE8102193L (en) 1981-04-06 1982-10-07 Pharmacia Ab THERAPEUTIC ACTIVE ORGANIC ASSOCIATION AND ITS USE
SE8102194L (en) 1981-04-06 1982-10-07 Pharmacia Ab THERAPEUTIC ACTIVE ORGANIC ASSOCIATION AND PHARMACEUTICAL PREPARATION INCLUDING THIS
JPS58124773A (en) * 1982-01-20 1983-07-25 Mitsui Toatsu Chem Inc 5-methylthiopyrimidine derivative, its preparation and fungicide for agricultural and horticultural purposes
JPS59173249U (en) 1983-05-07 1984-11-19 日本碍子株式会社 Open fuse cutout with built-in lightning arrester element
EP0136976A3 (en) 1983-08-23 1985-05-15 Ciba-Geigy Ag Use of phenyl pyrimidines as plant regulators
DE3725638A1 (en) 1987-08-03 1989-02-16 Bayer Ag NEW ARYLOXY (OR THIO) AMINOPYRIMIDINE
JPH0532662A (en) 1990-11-09 1993-02-09 Nissan Chem Ind Ltd Substituted pyrazole derivative and agricultural and horticultural fungicide
US5710158A (en) 1991-05-10 1998-01-20 Rhone-Poulenc Rorer Pharmaceuticals Inc. Aryl and heteroaryl quinazoline compounds which inhibit EGF and/or PDGF receptor tyrosine kinase
US5597920A (en) 1992-04-30 1997-01-28 Neurogen Corporation Gabaa receptor subtypes and methods for screening drug compounds using imidazoquinoxalines and pyrrolopyrimidines to bind to gabaa receptor subtypes
JPH0665237A (en) 1992-05-07 1994-03-08 Nissan Chem Ind Ltd Substituted pyrazole derivative and germicide for agriculture and horticulture
JP3588116B2 (en) 1993-10-01 2004-11-10 ノバルティス アクチェンゲゼルシャフト Pharmacologically active pyrimidineamine derivatives and process for their production
ATE262902T1 (en) 1994-11-10 2004-04-15 Millennium Pharm Inc USE OF PYRAZOLE COMPOUNDS TO TREAT GLOMERULONEPHRITIS, CANCER, ATHEROSCLERosis OR RESTENOSIS
IL117659A (en) 1995-04-13 2000-12-06 Dainippon Pharmaceutical Co Substituted 2-phenyl pyrimidino amino acetamide derivative process for preparing the same and a pharmaceutical composition containing same
AU726058B2 (en) 1995-09-01 2000-10-26 Signal Pharmaceuticals, Inc. Pyrimidine carboxylates and related compounds and methods for treating inflammatory conditions
GB9523675D0 (en) 1995-11-20 1996-01-24 Celltech Therapeutics Ltd Chemical compounds
US6716575B2 (en) 1995-12-18 2004-04-06 Sugen, Inc. Diagnosis and treatment of AUR1 and/or AUR2 related disorders
ID19609A (en) 1996-07-13 1998-07-23 Glaxo Group Ltd HETEROSICLIC COMPOUNDS
JPH10130150A (en) 1996-09-05 1998-05-19 Dainippon Pharmaceut Co Ltd Medicine comprising acetic acid amide derivative
GB9619284D0 (en) 1996-09-16 1996-10-30 Celltech Therapeutics Ltd Chemical compounds
CA2268098A1 (en) 1996-10-11 1998-04-23 Warner-Lambert Company Aspartate ester inhibitors of interleukin-1.beta. converting enzyme
CN1138472C (en) 1997-10-10 2004-02-18 西托维亚公司 Dipeptide apoptosis inhibitors and the use thereof
US6267952B1 (en) 1998-01-09 2001-07-31 Geltex Pharmaceuticals, Inc. Lipase inhibiting polymers
JP2000026421A (en) 1998-01-29 2000-01-25 Kumiai Chem Ind Co Ltd Diaryl sulfide derivative and pest controlling agent
CN1297447A (en) 1998-02-17 2001-05-30 图拉列克股份有限公司 Anti-viral pyrimidine derivs
EP1076563B1 (en) 1998-03-16 2005-05-11 Cytovia, Inc. Dipeptide caspase inhibitors and the use thereof
JP4533534B2 (en) * 1998-06-19 2010-09-01 ノバルティス バクシンズ アンド ダイアグノスティックス，インコーポレーテッド Inhibitor of glycogen synthase kinase 3
CA2339188A1 (en) 1998-08-21 2000-03-02 Dupont Pharmaceuticals Company Isoxazolo¬4,5-d|pyrimidines as crf antagonists
US6184226B1 (en) 1998-08-28 2001-02-06 Scios Inc. Quinazoline derivatives as inhibitors of P-38 α
ATE284387T1 (en) * 1998-10-08 2004-12-15 Smithkline Beecham Plc 3-(3-CHLORO-4-HYDROXYPHENYLAMINO)-4-(2-NITROPHENYL)-1H-PYRROL-2,5-DIONE AS A GLYCOGEN SYNTHASE KINASE-3 INHIBITOR (GSK-3)
GB9828640D0 (en) 1998-12-23 1999-02-17 Smithkline Beecham Plc Novel method and compounds
BR0009507A (en) 1999-03-30 2002-01-15 Novartis Ag Phthalazine derivatives for the treatment of inflammatory diseases
JP2003502424A (en) 1999-06-17 2003-01-21 シオノギ バイオリサーチ コーポレイション Inhibitor of IL-12 production
GB9914258D0 (en) 1999-06-18 1999-08-18 Celltech Therapeutics Ltd Chemical compounds
JP2003531103A (en) 1999-08-12 2003-10-21 バーテックス ファーマシューティカルズ インコーポレイテッド Inhibitors of c-JUNN-terminal kinase (JNK) and other protein kinases
JP2003511378A (en) 1999-10-07 2003-03-25 アムジエン・インコーポレーテツド Triazine kinase inhibitors
EA200200411A1 (en) 1999-11-30 2002-10-31 Пфайзер Продактс Инк. 2,4-DIAMINOPYRIMIDINE COMPOUNDS USEFUL AS IMMUNOSUPRESSORS
ES2269217T3 (en) 1999-12-02 2007-04-01 Osi Pharmaceuticals, Inc. SPECIFIC COMPOUNDS FOR ADENOSINE A1, A2A AND A3 RECEPTORS AND THEIR USES.
MY125768A (en) 1999-12-15 2006-08-30 Bristol Myers Squibb Co N-[5-[[[5-alkyl-2-oxazolyl]methyl]thio]-2-thiazolyl]-carboxamide inhibitors of cyclin dependent kinases
US6376489B1 (en) 1999-12-23 2002-04-23 Icos Corporation Cyclic AMP-specific phosphodiesterase inhibitors
US20020065270A1 (en) 1999-12-28 2002-05-30 Moriarty Kevin Joseph N-heterocyclic inhibitors of TNF-alpha expression
JP4783532B2 (en) 2000-02-05 2011-09-28 バーテックス ファーマシューティカルズ インコーポレイテッド Pyrazole compositions useful as inhibitors of ERK
EP1257546A1 (en) 2000-02-17 2002-11-20 Amgen Inc. Kinase inhibitors
GB0004890D0 (en) 2000-03-01 2000-04-19 Astrazeneca Uk Ltd Chemical compounds
AU2001249865A1 (en) * 2000-04-18 2001-10-30 Agouron Pharmaceuticals, Inc. Pyrazoles for inhibiting protein kinase
DE60133897D1 (en) 2000-06-28 2008-06-19 Astrazeneca Ab SUBSTITUTED CHINAZOLIN DERIVATIVES AND THEIR USE AS AURORA-2-KINASE INHIBITORS
US6660731B2 (en) 2000-09-15 2003-12-09 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
US6610677B2 (en) 2000-09-15 2003-08-26 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
US6613776B2 (en) 2000-09-15 2003-09-02 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
EP1317449B1 (en) 2000-09-15 2006-05-31 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
US7473691B2 (en) 2000-09-15 2009-01-06 Vertex Pharmaceuticals Incorporated Pyrazole compounds useful as protein kinase inhibitors
DE60122176T2 (en) 2000-09-15 2007-07-05 Vertex Pharmaceuticals Inc., Cambridge ISOXAZOLE AND ITS USE AS ERK INHIBITORS
AU2001293817A1 (en) 2000-09-20 2002-04-02 Merck Patent Gmbh 4-amino-quinazolines
WO2002047690A1 (en) 2000-12-12 2002-06-20 Cytovia, Inc. Substituted 2-aryl-4-arylaminopyrimidines and analogs as activators of caspases and inducers of apoptosis and the use thereof
DE10061863A1 (en) 2000-12-12 2002-06-13 Basf Ag Preparation of triethylenediamine, useful for making pharmaceuticals and polymers, by reacting ethylenediamine over specific zeolite catalyst
US6716851B2 (en) 2000-12-12 2004-04-06 Cytovia, Inc. Substituted 2-aryl-4-arylaminopyrimidines and analogs as activators or caspases and inducers of apoptosis and the use thereof
JP2004518662A (en) * 2000-12-19 2004-06-24 スミスクライン　ビーチャム　パブリック　リミテッド　カンパニー Pyrazolo [3,4-C] pyridines as GSK-3 inhibitors
ATE340172T1 (en) 2000-12-21 2006-10-15 Vertex Pharma PYRAZOLE COMPOUNDS AS PROTEIN KINASE INHIBITORS
MY130778A (en) 2001-02-09 2007-07-31 Vertex Pharma Heterocyclic inhibitiors of erk2 and uses thereof
DE60223790D1 (en) 2001-03-29 2008-01-10 Vertex Pharma HEMMER OF C-JUN TERMINAL KINASE (JNK) AND OTHER PROTEIN KINASE
MXPA03009378A (en) 2001-04-13 2004-01-29 Vertex Pharma Inhibitors of c-jun n-terminal kinases (jnk) and other protein kinases.
US20030096813A1 (en) 2001-04-20 2003-05-22 Jingrong Cao Compositions useful as inhibitors of GSK-3
WO2002092573A2 (en) 2001-05-16 2002-11-21 Vertex Pharmaceuticals Incorporated Heterocyclic substituted pyrazoles as inhibitors of src and other protein kinases
WO2002102800A1 (en) 2001-06-15 2002-12-27 Vertex Pharmaceuticals Incorporated 5-(2-aminopyrimidin-4-yl) benzisoxazoles as protein kinase inhibitors
US6689778B2 (en) 2001-07-03 2004-02-10 Vertex Pharmaceuticals Incorporated Inhibitors of Src and Lck protein kinases
EP1474147B1 (en) * 2001-12-07 2010-05-05 Vertex Pharmaceuticals Incorporated Pyrimidine-based compounds useful as gsk-3 inhibitors
US20040009981A1 (en) 2002-03-15 2004-01-15 David Bebbington Compositions useful as inhibitors of protein kinases
DE60332433D1 (en) 2002-03-15 2010-06-17 Vertex Pharma AZOLYLAMINOAZINE AS PROTEIN KINASE INHIBITOR
WO2003078423A1 (en) 2002-03-15 2003-09-25 Vertex Pharmaceuticals, Inc. Compositions useful as inhibitors of protein kinases
EP1485381B8 (en) 2002-03-15 2010-05-12 Vertex Pharmaceuticals Incorporated Azolylaminoazine as inhibitors of protein kinases
US20030207873A1 (en) 2002-04-10 2003-11-06 Edmund Harrington Inhibitors of Src and other protein kinases
AU2003237121A1 (en) 2002-04-26 2003-11-10 Vertex Pharmaceuticals Incorporated Pyrrole derivatives as inhibitors of erk2 and uses thereof
MY141867A (en) 2002-06-20 2010-07-16 Vertex Pharma Substituted pyrimidines useful as protein kinase inhibitors
JP4570955B2 (en) 2002-07-09 2010-10-27 バーテクス ファーマスーティカルズ インコーポレイテッド Imidazoles with protein kinase inhibitory activity
ES2273043T3 (en) 2002-08-02 2007-05-01 Vertex Pharmaceuticals Incorporated PIRAZOL COMPOSITIONS USEFUL AS INHIBITORS OF GSK-3.

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