AU2010238289B2 - Bicyclic heterocyclyl derivatives as FGFR kinase inhibitors for therapeutic use - Google Patents
Bicyclic heterocyclyl derivatives as FGFR kinase inhibitors for therapeutic use Download PDFInfo
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- AU2010238289B2 AU2010238289B2 AU2010238289A AU2010238289A AU2010238289B2 AU 2010238289 B2 AU2010238289 B2 AU 2010238289B2 AU 2010238289 A AU2010238289 A AU 2010238289A AU 2010238289 A AU2010238289 A AU 2010238289A AU 2010238289 B2 AU2010238289 B2 AU 2010238289B2
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- 125000002618 bicyclic heterocycle group Chemical group 0.000 title abstract description 3
- 108091008794 FGF receptors Proteins 0.000 title description 82
- 230000001225 therapeutic effect Effects 0.000 title description 11
- 102000052178 fibroblast growth factor receptor activity proteins Human genes 0.000 title description 6
- 229940043355 kinase inhibitor Drugs 0.000 title description 4
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 364
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 69
- 201000010099 disease Diseases 0.000 claims abstract description 63
- 201000011510 cancer Diseases 0.000 claims abstract description 51
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 173
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 122
- -1 C=N Chemical group 0.000 claims description 110
- 125000000623 heterocyclic group Chemical group 0.000 claims description 103
- 238000006243 chemical reaction Methods 0.000 claims description 99
- 229910052739 hydrogen Inorganic materials 0.000 claims description 98
- 239000001257 hydrogen Substances 0.000 claims description 97
- 238000000034 method Methods 0.000 claims description 97
- 229910052757 nitrogen Inorganic materials 0.000 claims description 71
- 125000003118 aryl group Chemical group 0.000 claims description 54
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 53
- 238000002360 preparation method Methods 0.000 claims description 52
- 125000003545 alkoxy group Chemical group 0.000 claims description 47
- 150000003839 salts Chemical class 0.000 claims description 46
- 125000004122 cyclic group Chemical group 0.000 claims description 38
- 239000003814 drug Substances 0.000 claims description 36
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 35
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 34
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 34
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 32
- 150000002431 hydrogen Chemical class 0.000 claims description 31
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 29
- 239000012453 solvate Substances 0.000 claims description 29
- 229910052736 halogen Inorganic materials 0.000 claims description 27
- 238000011321 prophylaxis Methods 0.000 claims description 26
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 24
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 23
- 230000008569 process Effects 0.000 claims description 22
- 229910052799 carbon Inorganic materials 0.000 claims description 21
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 21
- 150000002367 halogens Chemical class 0.000 claims description 20
- 150000001299 aldehydes Chemical class 0.000 claims description 18
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 14
- 150000001412 amines Chemical class 0.000 claims description 14
- 150000002576 ketones Chemical class 0.000 claims description 14
- 150000001204 N-oxides Chemical class 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 125000002950 monocyclic group Chemical group 0.000 claims description 12
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- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
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- 125000006239 protecting group Chemical group 0.000 claims description 8
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 7
- 125000006553 (C3-C8) cycloalkenyl group Chemical group 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
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- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 4
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- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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| GB0906472.6 | 2009-04-15 | ||
| PCT/GB2010/050617 WO2010119284A1 (en) | 2009-04-15 | 2010-04-15 | Bicyclic heterocyclyl derivatives as fgfr kinase inhibitors for therapeutic use |
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| AU2010238289B2 true AU2010238289B2 (en) | 2015-12-03 |
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| AU2010238289A Ceased AU2010238289B2 (en) | 2009-04-15 | 2010-04-15 | Bicyclic heterocyclyl derivatives as FGFR kinase inhibitors for therapeutic use |
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| CA2672213C (en) | 2006-12-22 | 2016-02-16 | Astex Therapeutics Limited | Bicyclic amine derivatives as protein tyrosine kinase inhibitors |
| US8895745B2 (en) | 2006-12-22 | 2014-11-25 | Astex Therapeutics Limited | Bicyclic heterocyclic compounds as FGFR inhibitors |
| GB0720041D0 (en) | 2007-10-12 | 2007-11-21 | Astex Therapeutics Ltd | New Compounds |
| GB0720038D0 (en) | 2007-10-12 | 2007-11-21 | Astex Therapeutics Ltd | New compounds |
| GB0810902D0 (en) | 2008-06-13 | 2008-07-23 | Astex Therapeutics Ltd | New compounds |
| GB0906472D0 (en) | 2009-04-15 | 2009-05-20 | Astex Therapeutics Ltd | New compounds |
| GB0906470D0 (en) | 2009-04-15 | 2009-05-20 | Astex Therapeutics Ltd | New compounds |
| WO2012088266A2 (en) | 2010-12-22 | 2012-06-28 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of fgfr3 |
| KR20140078710A (ko) | 2011-09-30 | 2014-06-25 | 온코디자인 에스.에이. | 거대고리 flt3 키나제 억제제 |
| UA111382C2 (uk) | 2011-10-10 | 2016-04-25 | Оріон Корпорейшн | Інгібітори протеїнкінази |
| HUE042374T2 (hu) | 2012-06-13 | 2019-06-28 | Incyte Holdings Corp | Szubsztituált triciklusos vegyületek mint FGFR inhibitorok |
| US9388185B2 (en) | 2012-08-10 | 2016-07-12 | Incyte Holdings Corporation | Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors |
| US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
| AR094812A1 (es) | 2013-02-20 | 2015-08-26 | Eisai R&D Man Co Ltd | Derivado de piridina monocíclico como inhibidor del fgfr |
| US9834520B2 (en) | 2013-03-14 | 2017-12-05 | Takeda Pharmaceutical Company Limited | Heterocyclic compound |
| TWI628176B (zh) * | 2013-04-04 | 2018-07-01 | 奧利安公司 | 蛋白質激酶抑制劑 |
| KR102469849B1 (ko) | 2013-04-19 | 2022-11-23 | 인사이트 홀딩스 코포레이션 | Fgfr 저해제로서 이환식 헤테로사이클 |
| AU2014338549B2 (en) | 2013-10-25 | 2017-05-25 | Novartis Ag | Ring-fused bicyclic pyridyl derivatives as FGFR4 inhibitors |
| AR098145A1 (es) * | 2013-10-25 | 2016-05-04 | Novartis Ag | Compuestos derivados de piridilo bicíclicos fusionados como inhibidores de fgfr4 |
| KR102344105B1 (ko) | 2014-08-18 | 2021-12-29 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 모노시클릭 피리딘 유도체의 염 및 이의 결정 |
| EP3200786B1 (en) * | 2014-10-03 | 2019-08-28 | Novartis AG | Use of ring-fused bicyclic pyridyl derivatives as fgfr4 inhibitors |
| US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
| AU2016219822B2 (en) | 2015-02-20 | 2020-07-09 | Incyte Holdings Corporation | Bicyclic heterocycles as FGFR inhibitors |
| WO2016134294A1 (en) | 2015-02-20 | 2016-08-25 | Incyte Corporation | Bicyclic heterocycles as fgfr4 inhibitors |
| CN114984013A (zh) | 2015-03-25 | 2022-09-02 | 国立癌症研究中心 | 胆管癌治疗剂 |
| US9802917B2 (en) | 2015-03-25 | 2017-10-31 | Novartis Ag | Particles of N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-formyl-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide |
| SG10201913989QA (en) | 2015-10-16 | 2020-03-30 | Abbvie Inc | PROCESSES FOR THE PREPARATION OF (3S,4R)-3-ETHYL-4-(3H-IMIDAZO[1,2-a]PYRROLO[2,3-e]-PYRAZIN-8-YL)-N-(2,2,2-TRIFLUOROETHYL)PYRROLIDINE-1-CARBOXAMIDE AND SOLID STATE FORMS THEREOF |
| US11773106B2 (en) | 2015-10-16 | 2023-10-03 | Abbvie Inc. | Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof |
| US11365198B2 (en) | 2015-10-16 | 2022-06-21 | Abbvie Inc. | Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof |
| US10550126B2 (en) | 2015-10-16 | 2020-02-04 | Abbvie Inc. | Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-A]pyrrolo[2,3-e]-pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof |
| US12365689B2 (en) | 2015-10-16 | 2025-07-22 | Abbvie Inc. | Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-n-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof |
| WO2017104739A1 (ja) | 2015-12-17 | 2017-06-22 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 乳がん治療剤 |
| EP3498707A4 (en) * | 2016-08-12 | 2020-04-08 | Jiangsu Hansoh Pharmaceutical Group Co., Ltd. | FGFR4 INHIBITOR, PREPARATION METHOD THEREOF AND USE THEREOF |
| AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
| SG11202007591RA (en) | 2018-03-28 | 2020-09-29 | Eisai R&D Man Co Ltd | Therapeutic agent for hepatocellular carcinoma |
| EP3788046B1 (en) | 2018-05-04 | 2025-12-10 | Incyte Corporation | Salts of an fgfr inhibitor |
| EP4309737A3 (en) | 2018-05-04 | 2024-03-27 | Incyte Corporation | Solid forms of an fgfr inhibitor and processes for preparing the same |
| KR102878873B1 (ko) | 2019-02-14 | 2025-10-31 | 브리진 바이오사이언시스, 인코포레이티드 | 암 치료를 위한 fgfr 억제제 |
| US11628162B2 (en) | 2019-03-08 | 2023-04-18 | Incyte Corporation | Methods of treating cancer with an FGFR inhibitor |
| US11591329B2 (en) | 2019-07-09 | 2023-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| WO2021018047A1 (zh) | 2019-07-26 | 2021-02-04 | 南京明德新药研发有限公司 | 作为fgfr和vegfr双重抑制剂的吡啶衍生物 |
| US12122767B2 (en) | 2019-10-01 | 2024-10-22 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| WO2021076602A1 (en) | 2019-10-14 | 2021-04-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| WO2021076728A1 (en) | 2019-10-16 | 2021-04-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| JP7720840B2 (ja) | 2019-12-04 | 2025-08-08 | インサイト・コーポレイション | Fgfr阻害剤としての三環式複素環 |
| KR20220131900A (ko) | 2019-12-04 | 2022-09-29 | 인사이트 코포레이션 | Fgfr 억제제의 유도체 |
| US12012409B2 (en) | 2020-01-15 | 2024-06-18 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| EP4286382A4 (en) * | 2021-01-26 | 2025-01-08 | CGeneTech (Suzhou, China) Co., Ltd. | CRYSTAL FORM OF A METHYLPYRAZOLE-SUBSTITUTED PYRIDOIMIDAZOLE COMPOUND AND METHOD FOR PREPARING THE SAME |
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| WO2008078091A1 (en) * | 2006-12-22 | 2008-07-03 | Astex Therapeutics Limited | Bicyclic heterocyclic compounds as fgfr inhibitors |
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| HUE028138T2 (en) | 2016-12-28 |
| GB0906472D0 (en) | 2009-05-20 |
| JP5718897B2 (ja) | 2015-05-13 |
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| CY1118061T1 (el) | 2017-06-28 |
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| US8481531B2 (en) | 2013-07-09 |
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| PL2419427T3 (pl) | 2016-12-30 |
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