CA3036594C - Alkynyl-substituted heterocyclic compound, preparation method thereof and medical use thereof - Google Patents
Alkynyl-substituted heterocyclic compound, preparation method thereof and medical use thereof Download PDFInfo
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- CA3036594C CA3036594C CA3036594A CA3036594A CA3036594C CA 3036594 C CA3036594 C CA 3036594C CA 3036594 A CA3036594 A CA 3036594A CA 3036594 A CA3036594 A CA 3036594A CA 3036594 C CA3036594 C CA 3036594C
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- Prior art keywords
- alkyl
- mmol
- pyrazole
- cancer
- compound
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- 125000000623 heterocyclic group Chemical group 0.000 claims description 48
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- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 18
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- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
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Classifications
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- 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
- C07D403/02—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
- C07D403/04—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 directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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- A61K31/415—1,2-Diazoles
- A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
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- 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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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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- A61P35/00—Antineoplastic agents
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- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/44—Oxygen and nitrogen or sulfur and nitrogen atoms
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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
- C07D401/02—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 containing two hetero rings
- C07D401/04—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 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D401/02—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 containing two hetero rings
- C07D401/06—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 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D403/02—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
- C07D403/06—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 carbon chain containing only aliphatic carbon atoms
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- 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
- 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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| CN201610833890.3 | 2016-09-19 | ||
| PCT/CN2017/072570 WO2018049781A1 (zh) | 2016-09-19 | 2017-01-25 | 炔代杂环化合物、其制备方法及其在医药学上的应用 |
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| WO2020120673A1 (en) * | 2018-12-13 | 2020-06-18 | Intervet International B.V. | Process for preparing 1-[(3r,4s)-4-cyanotetrahydropyran-3-yl]-3-[(2-fluoro-6-methoxy-4-pyridyl)amino]p yrazole-4-carboxamide |
| EP3898615A1 (en) | 2018-12-19 | 2021-10-27 | Array Biopharma, Inc. | 7-((3,5-dimethoxyphenyl)amino)quinoxaline derivatives as fgfr inhibitors for treating cancer |
| AU2020242287A1 (en) | 2019-03-21 | 2021-09-02 | INSERM (Institut National de la Santé et de la Recherche Médicale) | A Dbait molecule in combination with kinase inhibitor for the treatment of cancer |
| KR20220098759A (ko) | 2019-11-08 | 2022-07-12 | 인쎄름 (엥스띠뛰 나씨오날 드 라 쌍떼 에 드 라 흐쉐르슈 메디깔) | 키나제 억제제에 대해 내성을 획득한 암의 치료 방법 |
| AU2020412067A1 (en) * | 2019-12-26 | 2022-08-11 | Beijing Innocare Pharma Tech Co., Ltd. | Crystalline forms of (S) -1- (1-acryloylpyrrolidin-3-yl) -3- ( (3, 5-dimethoxyphenyl) ethynyl) -5- (methylamino) -1H-pyrazole-4-carboxamide |
| WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
| CN116057045A (zh) * | 2020-06-05 | 2023-05-02 | 金耐特生物制药公司 | 成纤维细胞生长因子受体激酶抑制剂 |
| CN116096707A (zh) * | 2020-06-05 | 2023-05-09 | 金耐特生物制药公司 | 成纤维细胞生长因子受体激酶的抑制剂 |
| WO2022042613A1 (zh) * | 2020-08-27 | 2022-03-03 | 上海和誉生物医药科技有限公司 | 一种1h-吡唑-4-酰胺衍生物，其制备方法和应用 |
| CA3204407A1 (en) * | 2021-01-12 | 2022-07-21 | Yucheng PANG | Process for preparing (s)-1-(1-acryloylpyrrolidin-3-yl)-3-((3,5-dimethoxyphenyl) ethynyl)-5-(methylamino)-1h-pyrazole-4-carboxamide |
| CN115433190B (zh) * | 2021-06-02 | 2024-09-20 | 药雅科技(上海)有限公司 | 不可逆杂环化合物fgfr抑制剂的制备方法和用途 |
| CN114853739B (zh) * | 2021-02-03 | 2023-09-22 | 药雅科技(上海)有限公司 | 一种炔代吡嗪类fgfr抑制剂及其制备方法和用途 |
| CN115043832B (zh) * | 2021-03-08 | 2023-08-22 | 药雅科技(上海)有限公司 | 一种fgfr抑制剂炔代杂环类化合物及其制备方法和用途 |
| JP2024539723A (ja) * | 2021-11-03 | 2024-10-29 | ベイジン・イノケア・ファーマ・テク・カンパニー・リミテッド | （ｓ）－１－（１－アクリロイルピロリジン－３－イル）－３－（（３，５－ジメトキシフェニル）エチニル）－５－（メチルアミノ）－１ｈ－ピラゾール－４－カルボキサミドを含む非晶質固体分散体 |
| CA3238193A1 (en) * | 2021-11-16 | 2023-05-25 | Jisong Cui | Method for treating head and neck cancer |
| KR20240119095A (ko) * | 2021-12-08 | 2024-08-06 | 킨네이트 바이오파마 인크. | Fgfr 저해제의 고체 상태 형태 |
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| EP4444713A4 (en) * | 2021-12-08 | 2025-08-06 | Kinnate Biopharma Inc | CANCER TREATMENT WITH AN FGFR KINASE INHIBITOR |
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| KR101124245B1 (ko) | 2002-06-27 | 2012-07-02 | 노보 노르디스크 에이/에스 | 치료제로서 아릴 카르보닐 유도체 |
| CN1508130A (zh) | 2002-12-18 | 2004-06-30 | 中国科学院大连化学物理研究所 | N-苯基-n’-嘧啶基取代脲类衍生物的合成方法 |
| US7150894B2 (en) * | 2003-05-01 | 2006-12-19 | Kraft Foods Holdings, Inc. | Acid whey texture system |
| ATE400567T1 (de) | 2004-06-23 | 2008-07-15 | Lilly Co Eli | Kinaseinhibitoren |
| FR2889526B1 (fr) | 2005-08-04 | 2012-02-17 | Aventis Pharma Sa | 7-aza-indazoles substitues, compositions les contenant, procede de fabrication et utilisation |
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| FR2908409B1 (fr) | 2006-11-10 | 2009-01-09 | Sanofi Aventis Sa | Pyrazoles substituees,compositions les contenant,procede de fabrication et utilisation |
| CN101611014B (zh) * | 2006-12-21 | 2012-05-30 | 阿斯利康(瑞典)有限公司 | 用作fgfr抑制剂的酰氨基吡唑类化合物 |
| US7737149B2 (en) * | 2006-12-21 | 2010-06-15 | Astrazeneca Ab | N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-yl]-4-(3,5-dimethylpiperazin-1-yl)benzamide and salts thereof |
| DK2959900T3 (en) | 2008-06-16 | 2017-06-26 | Univ Tennessee Res Found | CONNECTION TO TREATMENT OF CANCER |
| FR2947546B1 (fr) | 2009-07-03 | 2011-07-01 | Sanofi Aventis | Derives de pyrazoles, leur preparation et leur application en therapeutique |
| GB2474748B (en) * | 2009-10-01 | 2011-10-12 | Amira Pharmaceuticals Inc | Polycyclic compounds as lysophosphatidic acid receptor antagonists |
| CN102883607B (zh) * | 2010-03-01 | 2015-07-22 | Gtx公司 | 用于治疗癌的化合物 |
| JP6016915B2 (ja) * | 2011-07-28 | 2016-10-26 | ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ | キナーゼ阻害剤として活性なアルキニル置換ピリミジニルピロール |
| WO2013024427A1 (en) | 2011-08-16 | 2013-02-21 | Glenmark Pharmaceuticals S.A. | Novel urea derivatives as tec kinase inhibitors and uses thereof |
| CN103848810A (zh) * | 2012-11-30 | 2014-06-11 | 北京赛林泰医药技术有限公司 | 鲁顿酪氨酸激酶抑制剂 |
| PT3023100T (pt) * | 2013-07-18 | 2019-05-29 | Taiho Pharmaceutical Co Ltd | Fármaco antitumoral para administração intermitente de inibidor de fgfr |
| ES2819398T3 (es) * | 2013-07-18 | 2021-04-15 | Taiho Pharmaceutical Co Ltd | Agente terapéutico para el cáncer resistente al inhibidor de FGFR |
| AU2014338549B2 (en) | 2013-10-25 | 2017-05-25 | Novartis Ag | Ring-fused bicyclic pyridyl derivatives as FGFR4 inhibitors |
| JP6695353B2 (ja) | 2015-03-25 | 2020-05-20 | ノバルティス アーゲー | Ｆｇｆｒ４阻害剤としてのホルミル化ｎ−複素環式誘導体 |
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| WO2018049781A1 (zh) | 2018-03-22 |
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| JP6906811B2 (ja) | 2021-07-21 |
| AU2017327954B2 (en) | 2022-02-03 |
| AU2017327954A1 (en) | 2019-05-02 |
| EP3517535A4 (en) | 2020-02-26 |
| US11059805B2 (en) | 2021-07-13 |
| US10710981B2 (en) | 2020-07-14 |
| RU2729069C1 (ru) | 2020-08-04 |
| MX390747B (es) | 2025-03-21 |
| KR20190052113A (ko) | 2019-05-15 |
| US11572353B2 (en) | 2023-02-07 |
| US20210332027A1 (en) | 2021-10-28 |
| CN107840842A (zh) | 2018-03-27 |
| SG10202102822RA (en) | 2021-05-28 |
| CA3036594A1 (en) | 2018-03-22 |
| KR102783517B1 (ko) | 2025-03-19 |
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