OA12929A - Pyrazole derivatives as transforming growth (TGF) inhibitors. - Google Patents
Pyrazole derivatives as transforming growth (TGF) inhibitors. Download PDFInfo
- Publication number
- OA12929A OA12929A OA1200500078A OA1200500078A OA12929A OA 12929 A OA12929 A OA 12929A OA 1200500078 A OA1200500078 A OA 1200500078A OA 1200500078 A OA1200500078 A OA 1200500078A OA 12929 A OA12929 A OA 12929A
- Authority
- OA
- OAPI
- Prior art keywords
- alkyl
- cio
- phenyl
- cycloalkyl
- heteroaryl
- Prior art date
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- 239000003112 inhibitor Substances 0.000 title abstract description 9
- 150000003217 pyrazoles Chemical class 0.000 title abstract description 3
- 230000001131 transforming effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 156
- -1 derivatives thereof Chemical class 0.000 claims abstract description 61
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 18
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- 125000000217 alkyl group Chemical group 0.000 claims description 130
- 125000003545 alkoxy group Chemical group 0.000 claims description 42
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 32
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 125000001072 heteroaryl group Chemical group 0.000 claims description 23
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 21
- 125000000623 heterocyclic group Chemical group 0.000 claims description 19
- 239000000651 prodrug Substances 0.000 claims description 19
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- 125000003282 alkyl amino group Chemical group 0.000 claims description 18
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 12
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 11
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- 125000003118 aryl group Chemical group 0.000 claims description 9
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- 241001465754 Metazoa Species 0.000 claims description 7
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 7
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
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Classifications
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- 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
- C07D405/14—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 three or more hetero rings
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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
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- Hematology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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| EA200500377A1 (ru) * | 2002-09-18 | 2005-08-25 | Пфайзер Продактс Инк. | Пиразольные производные как ингибиторы трансформирующего фактора роста (tgf) |
| AU2003263404A1 (en) | 2002-09-18 | 2004-04-08 | Pfizer Products Inc. | Novel imidazole compounds as transforming growth factor (tgf) inhibitors |
| CL2004000234A1 (es) * | 2003-02-12 | 2005-04-15 | Biogen Idec Inc | Compuestos derivados 3-(piridin-2-il)-4-heteroaril-pirazol sustituidos, antagonistas de aik5 y/o aik4; composicion farmaceutica y uso del compuesto en el tratamiento de desordenes fibroticos como esclerodermia, lupus nefritico, cicatrizacion de herid |
| PA8595001A1 (es) * | 2003-03-04 | 2004-09-28 | Pfizer Prod Inc | Nuevos compuestos heteroaromaticos condensados que son inhibidores del factor de crecimiento transforante (tgf) |
| GB0313915D0 (en) * | 2003-06-16 | 2003-07-23 | Smithkline Beecham Corp | Compounds |
| AU2005280167A1 (en) * | 2004-08-31 | 2006-03-09 | Biogen Idec Ma Inc. | Pyrimidinylpyrazoles as TGF-beta inhibitors |
| US20070275968A1 (en) * | 2004-09-07 | 2007-11-29 | Hitoshi Kurata | Substituted Biphenyl Derivative |
| WO2006044509A2 (en) * | 2004-10-15 | 2006-04-27 | Biogen Idec Ma Inc. | Methods of treating vascular injuries |
| TW200639163A (en) | 2005-02-04 | 2006-11-16 | Genentech Inc | RAF inhibitor compounds and methods |
| WO2007070866A2 (en) * | 2005-12-16 | 2007-06-21 | Alcon, Inc. | Control of intraocular pressure using alk5 modulation agents |
| GEP20115239B (en) | 2006-10-31 | 2011-06-10 | Pfizer Prod Inc | Pyrazoline compounds as mineralocorticoid receptor antagonists |
| JP4792126B2 (ja) | 2007-08-01 | 2011-10-12 | ファイザー・インク | ピラゾール化合物およびＲａｆ阻害剤としてのその使用 |
| WO2015103355A1 (en) | 2014-01-01 | 2015-07-09 | Medivation Technologies, Inc. | Compounds and methods of use |
| ES2918924T3 (es) | 2015-04-01 | 2022-07-21 | Rigel Pharmaceuticals Inc | Inhibidores de TGF-beta |
| EP3313420B1 (en) | 2015-06-25 | 2024-03-13 | The Children's Medical Center Corporation | Methods and compositions relating to hematopoietic stem cell expansion, enrichment, and maintenance |
| WO2017161001A1 (en) | 2016-03-15 | 2017-09-21 | Children's Medical Center Corporation | Methods and compositions relating to hematopoietic stem cell expansion |
| JP6954932B2 (ja) * | 2016-06-13 | 2021-10-27 | ジェンフリート セラピューティクス（シャンハイ）インコーポレイテッド | ＴＧＦ−βＲＩ阻害剤としてのベンゾトリアゾール由来のα、β−不飽和アミド系化合物 |
| US11266647B2 (en) * | 2016-10-26 | 2022-03-08 | Icahn School Of Medicine At Mount Sinai | Method for increasing cell proliferation in pancreatic beta cells, treatment method, and composition |
| AU2017357333A1 (en) | 2016-11-14 | 2019-05-02 | Jiangsu Hengrui Medicine Co., Ltd. | 3,4-bipyridyl pyrazole derivative, and preparation method therefor and medical application thereof |
| CA3084581A1 (en) | 2017-11-20 | 2019-05-23 | Icahn School Of Medicine At Mount Sinai | Kinase inhibitor compounds and compositions and methods of use |
| AU2018383853B2 (en) * | 2017-12-13 | 2021-06-03 | Genfleet Therapeutics (Shanghai) Inc. | Crystal form and salt form of TGF-βRI inhibitor and preparation method therefor |
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| WO2020003219A1 (en) * | 2018-06-29 | 2020-01-02 | Oat & Iil India Laboratories Private Limited | Substituted pyrazole derivatives as insecticides and fungicides |
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| EP3894401A2 (en) | 2018-12-11 | 2021-10-20 | Theravance Biopharma R&D IP, LLC | Naphthyridine and quinoline derivatives useful as alk5 inhibitors |
| CN110467601B (zh) * | 2019-08-29 | 2021-07-02 | 杭州市西溪医院 | 一种吡唑联吡啶酮类化合物、中间体及其制备方法及应用 |
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| US4925857A (en) * | 1989-03-22 | 1990-05-15 | Sterling Drug Inc. | Pyridinyl-1H-pyrazole-1-alkanamides as antiarrhythmic agents |
| JP3734180B2 (ja) * | 1994-12-28 | 2006-01-11 | エーザイ株式会社 | 新規ピラゾール誘導体 |
| EP0983260A2 (en) | 1997-05-22 | 2000-03-08 | G.D. Searle & Co. | 3(5)-HETEROARYL SUBSTITUTED PYRAZOLES AS p38 KINASE INHIBITORS |
| CA2288787A1 (en) | 1997-05-22 | 1998-11-26 | G.D. Searle And Co. | Pyrazole derivatives as p38 kinase inhibitors |
| US6514977B1 (en) | 1997-05-22 | 2003-02-04 | G.D. Searle & Company | Substituted pyrazoles 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 |
| EP1349851A4 (en) | 2000-11-16 | 2004-09-08 | Smithkline Beecham Corp | COMPOUNDS |
| GB0027987D0 (en) | 2000-11-16 | 2001-01-03 | Smithkline Beecham Plc | Compounds |
| GB0100762D0 (en) | 2001-01-11 | 2001-02-21 | Smithkline Beecham Plc | Novel use |
| EP1363904A1 (en) * | 2001-02-02 | 2003-11-26 | Glaxo Group Limited | Pyrazoles as tgf inhibitors |
| WO2002066462A1 (en) * | 2001-02-02 | 2002-08-29 | Glaxo Group Limited | Pyrazole derivatives against tgf overexpression |
| GB0102672D0 (en) * | 2001-02-02 | 2001-03-21 | Glaxo Group Ltd | Compounds |
| WO2002072576A1 (en) | 2001-03-09 | 2002-09-19 | Pfizer Products Inc. | Benzimidazole anti-inflammatory compounds |
| ATE402164T1 (de) * | 2001-04-26 | 2008-08-15 | Eisai R&D Man Co Ltd | Stickstoffhaltige verbindung mit kondensiertem ring und pyrazolylgruppe als substituent und medizinische zusammensetzung davon |
| AR039241A1 (es) | 2002-04-04 | 2005-02-16 | Biogen Inc | Heteroarilos trisustituidos y metodos para su produccion y uso de los mismos |
| AR040726A1 (es) | 2002-07-31 | 2005-04-20 | Smithkline Beecham Corp | Compuesto de 2- fenilpiridin-4-il-heterociclico, composicion farmaceutica que lo comprende y su uso para la fabricacion de un medicamento |
| EA200500377A1 (ru) * | 2002-09-18 | 2005-08-25 | Пфайзер Продактс Инк. | Пиразольные производные как ингибиторы трансформирующего фактора роста (tgf) |
| PL375973A1 (en) | 2002-09-18 | 2005-12-12 | Pfizer Products Inc. | Novel isothiazole and isoxazole compounds as transforming growth factor (tgf) inhibitors |
| AU2003263404A1 (en) | 2002-09-18 | 2004-04-08 | Pfizer Products Inc. | Novel imidazole compounds as transforming growth factor (tgf) inhibitors |
| AU2003260810A1 (en) | 2002-09-18 | 2004-04-08 | Pfizer Products Inc. | Triazole derivatives as transforming growth factor (tgf) inhibitors |
| DE60327443D1 (de) | 2002-09-18 | 2009-06-10 | Pfizer Prod Inc | Neue oxazolverbindungen als inhibitoren des transforming growth factor (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) |
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2003
- 2003-09-08 EA EA200500377A patent/EA200500377A1/ru unknown
- 2003-09-08 BR BR0314302-3A patent/BR0314302A/pt not_active IP Right Cessation
- 2003-09-08 EP EP09177298A patent/EP2165708A3/en not_active Withdrawn
- 2003-09-08 MX MXPA05002376A patent/MXPA05002376A/es active IP Right Grant
- 2003-09-08 WO PCT/IB2003/003933 patent/WO2004026306A2/en not_active Ceased
- 2003-09-08 OA OA1200500078A patent/OA12929A/en unknown
- 2003-09-08 HR HR20050247A patent/HRP20050247A2/hr not_active Application Discontinuation
- 2003-09-08 AU AU2003259475A patent/AU2003259475A1/en not_active Abandoned
- 2003-09-08 DE DE60330362T patent/DE60330362D1/de not_active Expired - Lifetime
- 2003-09-08 EP EP03797443A patent/EP1542684B1/en not_active Expired - Lifetime
- 2003-09-08 KR KR1020057004598A patent/KR20050044807A/ko not_active Ceased
- 2003-09-08 JP JP2004568904A patent/JP4519657B2/ja not_active Expired - Fee Related
- 2003-09-08 AT AT03797443T patent/ATE450258T1/de not_active IP Right Cessation
- 2003-09-08 CA CA2496295A patent/CA2496295C/en not_active Expired - Fee Related
- 2003-09-08 PL PL03375979A patent/PL375979A1/xx not_active Application Discontinuation
- 2003-09-08 AP AP2005003263A patent/AP2005003263A0/xx unknown
- 2003-09-08 CN CNA038222655A patent/CN1681501A/zh active Pending
- 2003-09-08 ES ES03797443T patent/ES2335099T3/es not_active Expired - Lifetime
- 2003-09-15 PE PE2003000940A patent/PE20040988A1/es not_active Application Discontinuation
- 2003-09-16 UY UY27985A patent/UY27985A1/es not_active Application Discontinuation
- 2003-09-16 AR ARP030103356A patent/AR041272A1/es unknown
- 2003-09-17 PA PA20038583201A patent/PA8583201A1/es unknown
- 2003-09-17 US US10/667,189 patent/US6958354B2/en not_active Expired - Fee Related
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2005
- 2005-02-16 NO NO20050838A patent/NO20050838L/no unknown
- 2005-02-17 IS IS7698A patent/IS7698A/is unknown
- 2005-03-16 CO CO05024529A patent/CO5550456A2/es not_active Application Discontinuation
- 2005-03-16 EC EC2005005679A patent/ECSP055679A/es unknown
- 2005-03-18 MA MA28154A patent/MA27440A1/fr unknown
- 2005-09-23 US US11/234,564 patent/US7151110B2/en not_active Expired - Fee Related
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2006
- 2006-11-08 US US11/557,638 patent/US7638537B2/en not_active Expired - Fee Related
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2009
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