AU2003263431A1 - 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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- AU2003263431A1 AU2003263431A1 AU2003263431A AU2003263431A AU2003263431A1 AU 2003263431 A1 AU2003263431 A1 AU 2003263431A1 AU 2003263431 A AU2003263431 A AU 2003263431A AU 2003263431 A AU2003263431 A AU 2003263431A AU 2003263431 A1 AU2003263431 A1 AU 2003263431A1
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- Prior art keywords
- alkyl
- compound
- phenyl
- alkoxy
- cycloalkyl
- Prior art date
- Legal status (The legal status 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 status listed.)
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- 102000009618 Transforming Growth Factors Human genes 0.000 title description 18
- 108010009583 Transforming Growth Factors Proteins 0.000 title description 18
- 239000003112 inhibitor Substances 0.000 title description 10
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 title description 5
- 150000002545 isoxazoles Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 144
- 125000000217 alkyl group Chemical group 0.000 claims description 91
- -1 hydroxy, oxo, mercapto Chemical class 0.000 claims description 62
- 150000003839 salts Chemical class 0.000 claims description 36
- 125000003545 alkoxy group Chemical group 0.000 claims description 32
- 238000000034 method Methods 0.000 claims description 22
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- 201000010099 disease Diseases 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
- 239000000651 prodrug Substances 0.000 claims description 20
- 229940002612 prodrug Drugs 0.000 claims description 20
- 125000000623 heterocyclic group Chemical group 0.000 claims description 17
- 125000001072 heteroaryl group Chemical group 0.000 claims description 16
- 125000000753 cycloalkyl 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
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 125000000304 alkynyl group Chemical group 0.000 claims description 12
- 241001465754 Metazoa Species 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 125000003282 alkyl amino group Chemical group 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 8
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 5
- 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
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 5
- 125000003368 amide group Chemical group 0.000 claims description 5
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- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
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- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 3
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
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Classifications
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- 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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- A61P3/00—Drugs for disorders of the metabolism
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- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
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- 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
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- 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)
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- 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 (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41213102P | 2002-09-18 | 2002-09-18 | |
| US60/412,131 | 2002-09-18 | ||
| US48458003P | 2003-07-02 | 2003-07-02 | |
| US60/484,580 | 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)
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| AU2003263431A1 true AU2003263431A1 (en) | 2004-04-08 |
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| AU2003263431A Abandoned AU2003263431A1 (en) | 2002-09-18 | 2003-09-12 | Novel isothiazole and isoxazole compounds as transforming growth factor (tgf) inhibitors |
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| EP (1) | EP1542995A1 (https=) |
| JP (1) | JP2006506443A (https=) |
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| CN (1) | CN1681809A (https=) |
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| AR (1) | AR041275A1 (https=) |
| AU (1) | AU2003263431A1 (https=) |
| BR (1) | BR0314286A (https=) |
| CA (1) | CA2499332A1 (https=) |
| CO (1) | CO5550458A2 (https=) |
| EA (1) | EA200500286A1 (https=) |
| EC (1) | ECSP055685A (https=) |
| HR (1) | HRP20050246A2 (https=) |
| IS (1) | IS7695A (https=) |
| MA (1) | MA27444A1 (https=) |
| MX (1) | MXPA05002378A (https=) |
| NO (1) | NO20051852L (https=) |
| OA (1) | OA12925A (https=) |
| PA (1) | PA8583101A1 (https=) |
| PE (1) | PE20050076A1 (https=) |
| PL (1) | PL375973A1 (https=) |
| TW (1) | TW200410954A (https=) |
| UY (1) | UY27983A1 (https=) |
| WO (1) | WO2004026865A1 (https=) |
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| MXPA05002981A (es) | 2002-09-18 | 2005-06-22 | Pfizer Prod Inc | Nuevos compuestos de imidazol como inhibidores del factor de crecimiento transformante (tgf). |
| AU2003256003A1 (en) | 2002-09-18 | 2004-04-08 | Pfizer Products Inc. | Novel oxazole and thiazole compounds as transforming growth factor (TGF) inhibitors |
| CA2496295C (en) | 2002-09-18 | 2010-11-23 | Michael John Munchhof | Novels pyrazole compounds as transforming growth factor (tgf) inhibitors |
| PA8595001A1 (es) * | 2003-03-04 | 2004-09-28 | Pfizer Prod Inc | Nuevos compuestos heteroaromaticos condensados que son inhibidores del factor de crecimiento transforante (tgf) |
| AU2005286647A1 (en) | 2004-09-20 | 2006-03-30 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-CoA desaturase inhibitors |
| CN101084211A (zh) | 2004-09-20 | 2007-12-05 | 泽农医药公司 | 杂环衍生物及其作为治疗剂的用途 |
| MX2007003318A (es) | 2004-09-20 | 2007-05-18 | Xenon Pharmaceuticals Inc | Derivados heterociclicos y su uso como agentes terapeuticos. |
| BRPI0515500A (pt) | 2004-09-20 | 2008-07-29 | Xenon Pharmaceuticals Inc | derivados piridazina para inibição de estearoil-coa-desaturase |
| MX2007003332A (es) | 2004-09-20 | 2007-06-05 | Xenon Pharmaceuticals Inc | Derivados heterociclicos y su uso como inhibidores de estearoil-coa-desaturasa. |
| AU2005286728A1 (en) | 2004-09-20 | 2006-03-30 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as mediators of stearoyl-CoA desaturase |
| BRPI0515482A (pt) | 2004-09-20 | 2008-07-22 | Xenon Pharmaceuticals Inc | derivados heterocìclicos e seus usos como agentes terapêuticos |
| MX2007009888A (es) | 2005-02-17 | 2007-10-16 | Synta Pharmaceuticals Corp | Compuestos para el tratamiento de trastornos proliferativos. |
| CA2618646A1 (en) | 2005-06-03 | 2007-11-15 | Xenon Pharmaceuticals Inc. | Aminothiazole derivatives as human stearoyl-coa desaturase inhibitors |
| CN101330914A (zh) * | 2005-12-16 | 2008-12-24 | 爱尔康公司 | 使用alk5调节剂控制眼内压 |
| 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 |
| PL2970890T3 (pl) | 2013-03-14 | 2020-11-16 | The Brigham And Women's Hospital, Inc. | Kompozycje i sposoby ekspansji i hodowli nabłonkowych komórek macierzystych |
| PL3089971T3 (pl) | 2014-01-01 | 2021-01-25 | Medivation Technologies Llc | Związki i sposoby ich zastosowania |
| EP3189134A1 (en) | 2014-09-03 | 2017-07-12 | The Brigham and Women's Hospital, Inc. | Compositions, systems, and methods for generating inner ear hair cells for treatment of hearing loss |
| US10669528B2 (en) | 2015-06-25 | 2020-06-02 | Children's Medical Center Corporation | Methods and compositions relating to hematopoietic stem cell expansion, enrichment, and maintenance |
| US11021687B2 (en) | 2016-01-08 | 2021-06-01 | The Brigham And Women's Hospital, Inc. | Production of differentiated enteroendocrine cells and insulin producing cells |
| 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 |
| EP4049665B1 (en) | 2016-03-15 | 2025-03-12 | The Children's Medical Center Corporation | Methods and compositions relating to hematopoietic stem cell expansion |
| EP3562827A1 (en) | 2016-12-30 | 2019-11-06 | Frequency Therapeutics, Inc. | 1h-pyrrole-2,5-dione compounds and methods of using them to induce self-renewal of stem/progenitor supporting cells |
| CN112135613A (zh) | 2018-03-20 | 2020-12-25 | 西奈山伊坎医学院 | 激酶抑制剂化合物和组合物及使用方法 |
| US20210254006A1 (en) | 2018-06-06 | 2021-08-19 | Ideaya Biosciences, Inc. | Methods of culturing and/or expanding stem cells and/or lineage committed progenitor cells using lactam compounds |
| JP2021533788A (ja) | 2018-08-17 | 2021-12-09 | 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 | Ｊａｇ−１を上方制御することにより有毛細胞を生成するための組成物及び方法 |
| US11617745B2 (en) | 2018-08-17 | 2023-04-04 | Frequency Therapeutics, Inc. | Compositions and methods for generating hair cells by downregulating FOXO |
| WO2020142485A1 (en) | 2018-12-31 | 2020-07-09 | Icahn School Of Medicine At Mount Sinai | Kinase inhibitor compounds and compositions and methods of use |
Family Cites Families (18)
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| JPS5095272A (https=) * | 1973-12-24 | 1975-07-29 | ||
| US6514977B1 (en) | 1997-05-22 | 2003-02-04 | G.D. Searle & Company | Substituted pyrazoles as p38 kinase inhibitors |
| IL132736A0 (en) | 1997-05-22 | 2001-03-19 | Searle & Co | 3(5)-Heteroaryl substituted pyrazoles as p38 kinase inhibitors |
| EP1019394A1 (en) | 1997-05-22 | 2000-07-19 | G.D. Searle & Co. | PYRAZOLE DERIVATIVES AS p38 KINASE INHIBITORS |
| DE60001229T2 (de) | 1999-04-09 | 2003-10-30 | Smithkline Beecham Corp., Philadelphia | Triarylimidazole |
| 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 |
| AU2002225730A1 (en) | 2000-11-16 | 2002-05-27 | Smith Kline Beecham Corporation | Compounds |
| GB0100762D0 (en) | 2001-01-11 | 2001-02-21 | Smithkline Beecham Plc | Novel use |
| ATE291020T1 (de) * | 2001-02-02 | 2005-04-15 | Smithkline Beecham Corp | Pyrazolderivate gegen tgf überexprimierung |
| GB0102672D0 (en) * | 2001-02-02 | 2001-03-21 | Glaxo Group Ltd | Compounds |
| GB0102668D0 (en) * | 2001-02-02 | 2001-03-21 | Glaxo Group Ltd | Compounds |
| JP2004521901A (ja) * | 2001-02-02 | 2004-07-22 | グラクソ グループ リミテッド | Ｔｇｆ阻害剤としてのピラゾール |
| 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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2003
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- 2003-09-12 EA EA200500286A patent/EA200500286A1/ru unknown
- 2003-09-12 OA OA1200500074A patent/OA12925A/en unknown
- 2003-09-12 AU AU2003263431A patent/AU2003263431A1/en not_active Abandoned
- 2003-09-12 BR BR0314286-8A patent/BR0314286A/pt not_active IP Right Cessation
- 2003-09-12 WO PCT/IB2003/004005 patent/WO2004026865A1/en not_active Ceased
- 2003-09-12 CA CA002499332A patent/CA2499332A1/en not_active Abandoned
- 2003-09-12 AP AP2005003262A patent/AP2005003262A0/xx unknown
- 2003-09-12 MX MXPA05002378A patent/MXPA05002378A/es active IP Right Grant
- 2003-09-12 KR KR1020057004662A patent/KR20050057441A/ko not_active Ceased
- 2003-09-12 PL PL03375973A patent/PL375973A1/xx not_active Application Discontinuation
- 2003-09-12 CN CNA038222043A patent/CN1681809A/zh active Pending
- 2003-09-12 JP JP2004568905A patent/JP2006506443A/ja not_active Withdrawn
- 2003-09-12 HR HR20050246A patent/HRP20050246A2/hr not_active Application Discontinuation
- 2003-09-15 TW TW092125380A patent/TW200410954A/zh unknown
- 2003-09-16 UY UY27983A patent/UY27983A1/es not_active Application Discontinuation
- 2003-09-16 AR ARP030103359A patent/AR041275A1/es unknown
- 2003-09-17 PA PA20038583101A patent/PA8583101A1/es unknown
- 2003-09-17 US US10/667,167 patent/US7030125B2/en not_active Expired - Fee Related
- 2003-09-17 PE PE2003000951A patent/PE20050076A1/es not_active Application Discontinuation
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2005
- 2005-02-14 IS IS7695A patent/IS7695A/is unknown
- 2005-03-17 EC EC2005005685A patent/ECSP055685A/es unknown
- 2005-03-18 CO CO05025189A patent/CO5550458A2/es not_active Application Discontinuation
- 2005-03-18 MA MA28158A patent/MA27444A1/fr unknown
- 2005-04-15 NO NO20051852A patent/NO20051852L/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2004026865A1 (en) | 2004-04-01 |
| NO20051852L (no) | 2005-06-16 |
| TW200410954A (en) | 2004-07-01 |
| MXPA05002378A (es) | 2005-05-23 |
| EA200500286A1 (ru) | 2005-08-25 |
| CA2499332A1 (en) | 2004-04-01 |
| AP2005003262A0 (en) | 2005-03-31 |
| PA8583101A1 (es) | 2004-04-23 |
| KR20050057441A (ko) | 2005-06-16 |
| HRP20050246A2 (en) | 2005-10-31 |
| PE20050076A1 (es) | 2005-03-26 |
| EP1542995A1 (en) | 2005-06-22 |
| UY27983A1 (es) | 2004-04-30 |
| CO5550458A2 (es) | 2005-08-31 |
| BR0314286A (pt) | 2005-08-02 |
| IS7695A (is) | 2005-02-14 |
| ECSP055685A (es) | 2005-05-30 |
| CN1681809A (zh) | 2005-10-12 |
| OA12925A (en) | 2006-10-13 |
| JP2006506443A (ja) | 2006-02-23 |
| MA27444A1 (fr) | 2005-07-01 |
| PL375973A1 (en) | 2005-12-12 |
| US7030125B2 (en) | 2006-04-18 |
| AR041275A1 (es) | 2005-05-11 |
| US20040116473A1 (en) | 2004-06-17 |
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