HRP20050246A2 - Novel isothiazole and isoxazole compounds as transforming growth factor (tgf) inhibitors - Google Patents
Novel isothiazole and isoxazole compounds as transforming growth factor (tgf) inhibitors Download PDFInfo
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- HRP20050246A2 HRP20050246A2 HR20050246A HRP20050246A HRP20050246A2 HR P20050246 A2 HRP20050246 A2 HR P20050246A2 HR 20050246 A HR20050246 A HR 20050246A HR P20050246 A HRP20050246 A HR P20050246A HR P20050246 A2 HRP20050246 A2 HR P20050246A2
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- alkyl
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- phenyl
- amino
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- 102000009618 Transforming Growth Factors Human genes 0.000 title description 16
- 108010009583 Transforming Growth Factors Proteins 0.000 title description 16
- 239000003112 inhibitor Substances 0.000 title description 8
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 title description 4
- 150000002545 isoxazoles Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 140
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 77
- -1 cyano, nitro, carbamoyl Chemical group 0.000 claims description 60
- 150000003839 salts Chemical class 0.000 claims description 32
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 25
- 229910052736 halogen Inorganic materials 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 24
- 150000002367 halogens Chemical class 0.000 claims description 22
- 239000000651 prodrug Substances 0.000 claims description 21
- 229940002612 prodrug Drugs 0.000 claims description 21
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 20
- 201000010099 disease Diseases 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 241001465754 Metazoa Species 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 8
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 7
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 7
- 125000000172 C5-C10 aryl group Chemical group 0.000 claims description 7
- 125000000304 alkynyl group Chemical group 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 5
- 125000003368 amide group Chemical group 0.000 claims description 5
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- 206010028980 Neoplasm Diseases 0.000 claims description 4
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 4
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- 125000003367 polycyclic group Chemical group 0.000 claims description 4
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 3
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- 201000011510 cancer Diseases 0.000 claims description 3
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 3
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- 125000001475 halogen functional group Chemical group 0.000 claims 1
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
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- XINQFOMFQFGGCQ-UHFFFAOYSA-L (2-dodecoxy-2-oxoethyl)-[6-[(2-dodecoxy-2-oxoethyl)-dimethylazaniumyl]hexyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCOC(=O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(=O)OCCCCCCCCCCCC XINQFOMFQFGGCQ-UHFFFAOYSA-L 0.000 description 5
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- 108091000080 Phosphotransferase Proteins 0.000 description 5
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- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
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Classifications
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Obesity (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Cardiology (AREA)
- Pulmonology (AREA)
- Oncology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US41213102P | 2002-09-18 | 2002-09-18 | |
US48458003P | 2003-07-02 | 2003-07-02 | |
PCT/IB2003/004005 WO2004026865A1 (en) | 2002-09-18 | 2003-09-12 | Novel isothiazole and isoxazole compounds as transforming growth factor (tgf) inhibitors |
Publications (1)
Publication Number | Publication Date |
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HRP20050246A2 true HRP20050246A2 (en) | 2005-10-31 |
Family
ID=32033584
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR20050246A HRP20050246A2 (en) | 2002-09-18 | 2005-03-16 | Novel isothiazole and isoxazole compounds as transforming growth factor (tgf) inhibitors |
Country Status (25)
Country | Link |
---|---|
US (1) | US7030125B2 (hu) |
EP (1) | EP1542995A1 (hu) |
JP (1) | JP2006506443A (hu) |
KR (1) | KR20050057441A (hu) |
CN (1) | CN1681809A (hu) |
AP (1) | AP2005003262A0 (hu) |
AR (1) | AR041275A1 (hu) |
AU (1) | AU2003263431A1 (hu) |
BR (1) | BR0314286A (hu) |
CA (1) | CA2499332A1 (hu) |
CO (1) | CO5550458A2 (hu) |
EA (1) | EA200500286A1 (hu) |
EC (1) | ECSP055685A (hu) |
HR (1) | HRP20050246A2 (hu) |
IS (1) | IS7695A (hu) |
MA (1) | MA27444A1 (hu) |
MX (1) | MXPA05002378A (hu) |
NO (1) | NO20051852L (hu) |
OA (1) | OA12925A (hu) |
PA (1) | PA8583101A1 (hu) |
PE (1) | PE20050076A1 (hu) |
PL (1) | PL375973A1 (hu) |
TW (1) | TW200410954A (hu) |
UY (1) | UY27983A1 (hu) |
WO (1) | WO2004026865A1 (hu) |
Families Citing this family (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
OA12929A (en) * | 2002-09-18 | 2006-10-13 | Pfizer Prod Inc | Pyrazole derivatives as transforming growth (TGF) inhibitors. |
AU2003256003A1 (en) | 2002-09-18 | 2004-04-08 | Pfizer Products Inc. | Novel oxazole and thiazole compounds as transforming growth factor (TGF) inhibitors |
EA200500378A1 (ru) | 2002-09-18 | 2005-08-25 | Пфайзер Продактс Инк. | Новые соединения имидазола в качестве ингибиторов трансформирующего фактора роста (tgf) |
PA8595001A1 (es) | 2003-03-04 | 2004-09-28 | Pfizer Prod Inc | Nuevos compuestos heteroaromaticos condensados que son inhibidores del factor de crecimiento transforante (tgf) |
CA2580787A1 (en) | 2004-09-20 | 2006-03-30 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives for the treatment of diseases mediated by stearoyl-coa desaturase enzymes |
US7951805B2 (en) | 2004-09-20 | 2011-05-31 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as mediators of stearoyl-CoA desaturase |
CA2580856A1 (en) | 2004-09-20 | 2006-03-30 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-coa desaturase inhibitors |
CA2580762A1 (en) | 2004-09-20 | 2006-03-30 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as therapeutic agents |
BRPI0515482A (pt) | 2004-09-20 | 2008-07-22 | Xenon Pharmaceuticals Inc | derivados heterocìclicos e seus usos como agentes terapêuticos |
JP5149009B2 (ja) | 2004-09-20 | 2013-02-20 | ゼノン・ファーマシューティカルズ・インコーポレイテッド | ヒトステアロイル−CoAデサチュラーゼを阻害するためのピリダジン誘導体 |
EP1807085B1 (en) | 2004-09-20 | 2013-08-21 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-coa desaturase inhibitors |
SG164378A1 (en) | 2005-02-17 | 2010-09-29 | Synta Pharmaceuticals Corp | Compounds for the treatment of proliferative disorders |
CA2618646A1 (en) | 2005-06-03 | 2007-11-15 | Xenon Pharmaceuticals Inc. | Aminothiazole derivatives as human stearoyl-coa desaturase inhibitors |
CA2629432A1 (en) * | 2005-12-16 | 2007-06-21 | Alcon, Inc. | Control of intraocular pressure using alk5 modulation agents |
TWI453207B (zh) | 2008-09-08 | 2014-09-21 | Signal Pharm Llc | 胺基三唑并吡啶,其組合物及使用其之治療方法 |
LT2970890T (lt) | 2013-03-14 | 2020-07-10 | The Brigham And Women`S Hospital, Inc. | Kompozicijos ir būdai, skirti epitelinių kamieninių ląstelių padauginimui ir kultivavimui |
CA2935392C (en) | 2014-01-01 | 2022-07-26 | Medivation Technologies, Inc. | Amino pyridine derivatives for the treatment of conditions associated with excessive tgf.beta activity |
KR20230019500A (ko) | 2014-09-03 | 2023-02-08 | 더 브리검 앤드 우먼즈 하스피털, 인크. | 청력 손실의 치료를 위해 내이 털세포를 생성하기 위한 조성물, 시스템, 및 방법 |
WO2016210292A1 (en) | 2015-06-25 | 2016-12-29 | Children's Medical Center Corporation | Methods and compositions relating to hematopoietic stem cell expansion, enrichment, and maintenance |
CN108779437A (zh) | 2016-01-08 | 2018-11-09 | 麻省理工学院 | 分化的肠内分泌细胞和胰岛素产生细胞的制备 |
US10213511B2 (en) | 2016-03-02 | 2019-02-26 | Frequency Therapeutics, Inc. | Thermoreversible compositions for administration of therapeutic agents |
US10201540B2 (en) | 2016-03-02 | 2019-02-12 | Frequency Therapeutics, Inc. | Solubilized compositions for controlled proliferation of stem cells / generating inner ear hair cells using GSK3 inhibitors: I |
US11260130B2 (en) | 2016-03-02 | 2022-03-01 | Frequency Therapeutics, Inc. | Solubilized compositions for controlled proliferation of stem cells / generating inner ear hair cells using a GSK3 inhibitor: IV |
DK3429603T3 (da) | 2016-03-15 | 2022-03-14 | Childrens Medical Center | Fremgangsmåder og sammensætninger vedrørende ekspansion af hæmatopoietiske stamceller |
JP7109446B2 (ja) | 2016-12-30 | 2022-07-29 | 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 | 幹細胞/前駆支持細胞の自己複製を誘導するための1h-ピロール-2,5-ジオン化合物およびその使用方法 |
US11866427B2 (en) | 2018-03-20 | 2024-01-09 | Icahn School Of Medicine At Mount Sinai | Kinase inhibitor compounds and compositions and methods of use |
WO2019236766A1 (en) | 2018-06-06 | 2019-12-12 | Ideaya Biosciences, Inc. | Methods of culturing and/or expanding stem cells and/or lineage committed progenitor cells using lactam compounds |
CN113195707A (zh) | 2018-08-17 | 2021-07-30 | 频率治疗公司 | 用于通过上调jag-1来生成毛细胞的组合物和方法 |
WO2020037326A1 (en) | 2018-08-17 | 2020-02-20 | Frequency Therapeutics, Inc. | Compositions and methods for generating hair cells by downregulating foxo |
EP3906233B1 (en) | 2018-12-31 | 2024-01-31 | Icahn School of Medicine at Mount Sinai | Kinase inhibitor compounds and compositions and methods of use |
Family Cites Families (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5095272A (hu) * | 1973-12-24 | 1975-07-29 | ||
US6514977B1 (en) | 1997-05-22 | 2003-02-04 | G.D. Searle & Company | Substituted pyrazoles as p38 kinase inhibitors |
AU7726898A (en) | 1997-05-22 | 1998-12-11 | G.D. Searle & Co. | Pyrazole derivatives as p38 kinase inhibitors |
JP2002502379A (ja) | 1997-05-22 | 2002-01-22 | ジー.ディー.サール アンド カンパニー | p38キナーゼインヒビターとしての3(5)−ヘテロアリール置換ピラゾール |
EP1169317B1 (en) | 1999-04-09 | 2003-01-15 | SmithKline Beecham Corporation | Triarylimidazoles |
CO5271680A1 (es) | 2000-02-21 | 2003-04-30 | Smithkline Beecham Corp | Compuestos |
GB0007405D0 (en) | 2000-03-27 | 2000-05-17 | Smithkline Beecham Corp | Compounds |
PE20020506A1 (es) | 2000-08-22 | 2002-07-09 | Glaxo Group Ltd | Derivados de pirazol fusionados como inhibidores de la proteina cinasa |
GB0027987D0 (en) * | 2000-11-16 | 2001-01-03 | Smithkline Beecham Plc | Compounds |
WO2002040468A1 (en) | 2000-11-16 | 2002-05-23 | Smithkline Beecham Corporation | Compounds |
GB0100762D0 (en) | 2001-01-11 | 2001-02-21 | Smithkline Beecham Plc | Novel use |
GB0102672D0 (en) * | 2001-02-02 | 2001-03-21 | Glaxo Group Ltd | Compounds |
WO2002066462A1 (en) * | 2001-02-02 | 2002-08-29 | Glaxo Group Limited | Pyrazole derivatives against tgf overexpression |
GB0102668D0 (en) * | 2001-02-02 | 2001-03-21 | Glaxo Group Ltd | Compounds |
WO2002062787A1 (en) * | 2001-02-02 | 2002-08-15 | Glaxo Group Limited | Pyrazoles as tgf inhibitors |
US6673818B2 (en) * | 2001-04-20 | 2004-01-06 | Pharmacia Corporation | Fluoro-substituted benzenesulfonyl compounds for the treatment of inflammation |
AR039241A1 (es) | 2002-04-04 | 2005-02-16 | Biogen Inc | Heteroarilos trisustituidos y metodos para su produccion y uso de los mismos |
EP1539748A1 (en) | 2002-07-31 | 2005-06-15 | Smithkline Beecham Corporation | 2-phenylpyridin-4-yl derivatives as alk5 inhibitors |
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PL375973A1 (en) | 2005-12-12 |
JP2006506443A (ja) | 2006-02-23 |
NO20051852L (no) | 2005-06-16 |
MXPA05002378A (es) | 2005-05-23 |
TW200410954A (en) | 2004-07-01 |
AR041275A1 (es) | 2005-05-11 |
ECSP055685A (es) | 2005-05-30 |
US20040116473A1 (en) | 2004-06-17 |
BR0314286A (pt) | 2005-08-02 |
KR20050057441A (ko) | 2005-06-16 |
IS7695A (is) | 2005-02-14 |
AU2003263431A1 (en) | 2004-04-08 |
WO2004026865A1 (en) | 2004-04-01 |
EA200500286A1 (ru) | 2005-08-25 |
MA27444A1 (fr) | 2005-07-01 |
OA12925A (en) | 2006-10-13 |
EP1542995A1 (en) | 2005-06-22 |
AP2005003262A0 (en) | 2005-03-31 |
UY27983A1 (es) | 2004-04-30 |
PE20050076A1 (es) | 2005-03-26 |
PA8583101A1 (es) | 2004-04-23 |
US7030125B2 (en) | 2006-04-18 |
CN1681809A (zh) | 2005-10-12 |
CA2499332A1 (en) | 2004-04-01 |
CO5550458A2 (es) | 2005-08-31 |
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