CN114096544B - Kras g12c抑制剂及其用途 - Google Patents
Kras g12c抑制剂及其用途Info
- Publication number
- CN114096544B CN114096544B CN202080052231.0A CN202080052231A CN114096544B CN 114096544 B CN114096544 B CN 114096544B CN 202080052231 A CN202080052231 A CN 202080052231A CN 114096544 B CN114096544 B CN 114096544B
- Authority
- CN
- China
- Prior art keywords
- mmol
- compound
- mixture
- alkyl
- spiro
- 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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Classifications
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/527—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim spiro-condensed
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- 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
- C07D471/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/10—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962850289P | 2019-05-20 | 2019-05-20 | |
| US62/850289 | 2019-05-20 | ||
| PCT/US2020/033816 WO2020236940A1 (en) | 2019-05-20 | 2020-05-20 | Kras g12c inhibitors and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114096544A CN114096544A (zh) | 2022-02-25 |
| CN114096544B true CN114096544B (zh) | 2025-08-12 |
Family
ID=73458223
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202080052231.0A Active CN114096544B (zh) | 2019-05-20 | 2020-05-20 | Kras g12c抑制剂及其用途 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US20220227738A1 (enExample) |
| EP (1) | EP3972978A4 (enExample) |
| JP (1) | JP7502337B2 (enExample) |
| KR (1) | KR20220038289A (enExample) |
| CN (1) | CN114096544B (enExample) |
| AU (1) | AU2020279253A1 (enExample) |
| BR (1) | BR112021023359A2 (enExample) |
| CA (1) | CA3141604A1 (enExample) |
| IL (1) | IL288200A (enExample) |
| MX (1) | MX2021014177A (enExample) |
| SG (1) | SG11202112790SA (enExample) |
| WO (1) | WO2020236940A1 (enExample) |
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019217307A1 (en) | 2018-05-07 | 2019-11-14 | Mirati Therapeutics, Inc. | Kras g12c inhibitors |
| CA3112043A1 (en) | 2018-09-10 | 2020-03-19 | Mirati Therapeutics, Inc. | Combination therapies |
| AU2019338207B2 (en) | 2018-09-10 | 2025-01-02 | Mirati Therapeutics, Inc. | Combination therapies |
| SMT202500028T1 (it) | 2018-09-10 | 2025-03-12 | Mirati Therapeutics Inc | Terapie combinate |
| US12208099B2 (en) | 2018-09-10 | 2025-01-28 | Mirati Therapeutics, Inc. | Combination therapies |
| WO2020085504A1 (ja) | 2018-10-26 | 2020-04-30 | 大鵬薬品工業株式会社 | 光照射ザンドマイヤー反応を用いたクロロアゾールカルボキシレート誘導体の製造方法 |
| US12377101B2 (en) | 2018-12-05 | 2025-08-05 | Mirati Therapeutics, Inc. | Combination therapies |
| WO2020146613A1 (en) | 2019-01-10 | 2020-07-16 | Mirati Therapeutics, Inc. | Kras g12c inhibitors |
| CN114615981B (zh) | 2019-08-29 | 2024-04-12 | 米拉蒂治疗股份有限公司 | Kras g12d抑制剂 |
| CN114761012B (zh) | 2019-09-24 | 2025-03-21 | 米拉蒂治疗股份有限公司 | 组合疗法 |
| MD4051678T2 (en) | 2019-10-28 | 2026-07-31 | Merck Sharp & Dohme Llc | Small molecule inhibitors of the KRAS G12C mutant |
| WO2021085653A1 (en) | 2019-10-31 | 2021-05-06 | Taiho Pharmaceutical Co., Ltd. | 4-aminobut-2-enamide derivatives and salts thereof |
| WO2021093758A1 (zh) * | 2019-11-15 | 2021-05-20 | 四川海思科制药有限公司 | 一种嘧啶并环衍生物及其在医药上的应用 |
| EP4067343A4 (en) | 2019-11-29 | 2024-01-03 | Taiho Pharmaceutical Co., Ltd. | NEW PHENOLIC COMPOUND OR SALT THEREOF |
| PH12022551513A1 (en) | 2019-12-20 | 2023-04-24 | Mirati Therapeutics Inc | Sos1 inhibitors |
| WO2021139748A1 (en) * | 2020-01-08 | 2021-07-15 | Ascentage Pharma (Suzhou) Co., Ltd. | Spirocyclic tetrahydroquinazolines |
| US12702658B2 (en) | 2020-04-24 | 2026-08-11 | Taiho Pharmaceutical Co., Ltd. | Anticancer combination therapy with N-(1-acryloyl-azetidin-3-yl)-2-((1H-indazol-3-yl)amino)methyl)-1H-imidazole-5-carboxamide inhibitor of KRAS-G12C |
| WO2021215544A1 (en) | 2020-04-24 | 2021-10-28 | Taiho Pharmaceutical Co., Ltd. | Kras g12d protein inhibitors |
| CN116034106B (zh) | 2020-06-02 | 2025-11-04 | 勃林格殷格翰国际有限公司 | 用于治疗癌症的环状2-氨基-3-氰基噻吩及衍生物 |
| US12655160B2 (en) | 2020-08-04 | 2026-06-16 | Mirati Therapeutics, Inc. | KRAS G12D inhibitors |
| WO2022040469A1 (en) * | 2020-08-19 | 2022-02-24 | The Trustees Of The Stevens Institute Of Technology | Spiro compounds as kras inhibitors |
| EP4210833A4 (en) | 2020-09-11 | 2024-09-11 | Mirati Therapeutics, Inc. | CRYSTALLINE FORMS OF A KRAS G12C INHIBITOR |
| EP4216951B1 (en) | 2020-09-22 | 2026-04-01 | Mirati Therapeutics, Inc. | Kras g12d inhibitors |
| WO2022066805A1 (en) | 2020-09-23 | 2022-03-31 | Erasca, Inc. | Tricyclic pyridones and pyrimidones |
| WO2022109487A1 (en) | 2020-11-23 | 2022-05-27 | Merck Sharp & Dohme Corp. | Spirocyclic-substituted 6,7-dihydro-pyrano[2,3-d]pyrimidine inhibitors of kras g12c mutant |
| EP4262807A4 (en) | 2020-12-15 | 2025-04-23 | Mirati Therapeutics, Inc. | Azachinazoline pan-KRAS inhibitors |
| WO2022133038A1 (en) | 2020-12-16 | 2022-06-23 | Mirati Therapeutics, Inc. | Tetrahydropyridopyrimidine pan-kras inhibitors |
| US20230107642A1 (en) | 2020-12-18 | 2023-04-06 | Erasca, Inc. | Tricyclic pyridones and pyrimidones |
| CN114685502A (zh) * | 2020-12-25 | 2022-07-01 | 由理生物医药（上海）有限公司 | 作为kras-g12c抑制剂的螺环类化合物 |
| CN114805311B (zh) * | 2021-01-21 | 2024-10-29 | 苏州亚盛药业有限公司 | 螺环茚 |
| US20240219403A1 (en) * | 2021-04-09 | 2024-07-04 | Memorial Sloan-Kettering Cancer Center | Methods for inhibiting kras oncoprotein through enhanced gtpase activity |
| WO2022240971A2 (en) * | 2021-05-11 | 2022-11-17 | 1200 Pharma Llc | Kras g12d inhibitors and uses thereof |
| WO2022266206A1 (en) | 2021-06-16 | 2022-12-22 | Erasca, Inc. | Kras inhibitor conjugates |
| US20240374571A1 (en) | 2021-09-01 | 2024-11-14 | Novartis Ag | Pharmaceutical combinations comprising a tead inhibitor and uses thereof for the treatment of cancers |
| CA3237274A1 (en) * | 2021-11-09 | 2023-05-19 | 1200 Pharma Llc | Select kras g12c inhibitors and uses thereof |
| TW202337432A (zh) * | 2021-12-01 | 2023-10-01 | 德商百靈佳殷格翰國際股份有限公司 | 用於治療癌症之環狀2-胺基-3-氰基噻吩及衍生物 |
| CR20240233A (es) | 2021-12-01 | 2024-07-17 | Univ Vanderbilt | Tiofenos 2-amino-3-ciano anulados y derivados para el tratamiento del cáncer |
| CA3243798A1 (en) | 2022-02-09 | 2023-08-17 | Quanta Therapeutics, Inc. | Kras Modulators and Their Uses |
| WO2023230190A1 (en) | 2022-05-25 | 2023-11-30 | Quanta Therapeutics, Inc. | Pyrimidine based modulators and uses thereof |
| KR20250109197A (ko) | 2022-11-21 | 2025-07-16 | 트리라인 바이오사이언시스, 인크. | 스피로환식 디하이드로피라노피리미딘 KRas 억제제 |
| EP4680609A1 (en) | 2023-03-15 | 2026-01-21 | Quanta Therapeutics, Inc. | Kras modulators and uses thereof |
| KR20260054710A (ko) | 2023-08-17 | 2026-04-22 | 트리라인 바이오사이언시스, 인크. | 스피로시클릭 디히드로피라노피리미딘 KRas 저해제 |
| WO2025064848A1 (en) | 2023-09-21 | 2025-03-27 | Treeline Biosciences, Inc. | Spirocyclic dihydropyranopyridine kras inhibitors |
| KR20260096846A (ko) | 2023-10-20 | 2026-06-24 | 머크 샤프 앤드 돔 엘엘씨 | Kras 단백질의 소분자 억제제 |
| WO2025237091A1 (zh) * | 2024-05-17 | 2025-11-20 | 中山优理生物医药有限公司 | 螺环类化合物的制备方法及其中间体 |
| WO2025245127A1 (en) | 2024-05-21 | 2025-11-27 | Treeline Biosciences, Inc. | Spirocyclic dihydropyranopyrimidine kras inhibitors |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6011029A (en) * | 1996-02-26 | 2000-01-04 | Bristol-Myers Squibb Company | Inhibitors of farnesyl protein transferase |
| US6875751B2 (en) | 2000-06-15 | 2005-04-05 | Idenix Pharmaceuticals, Inc. | 3′-prodrugs of 2′-deoxy-β-L-nucleosides |
| US7964580B2 (en) | 2007-03-30 | 2011-06-21 | Pharmasset, Inc. | Nucleoside phosphoramidate prodrugs |
| WO2009047255A1 (en) * | 2007-10-09 | 2009-04-16 | Ucb Pharma, S.A. | Heterobicyclic compounds as histamine h4-receptor antagonists |
| MX380928B (es) | 2013-10-10 | 2025-03-12 | Araxes Pharma Llc | Inhibidores de kras g12c. |
| JO3556B1 (ar) * | 2014-09-18 | 2020-07-05 | Araxes Pharma Llc | علاجات مدمجة لمعالجة السرطان |
| AU2016245864C1 (en) * | 2015-04-10 | 2021-09-09 | Araxes Pharma Llc | Substituted quinazoline compounds and methods of use thereof |
| ES2863873T3 (es) * | 2016-05-18 | 2021-10-11 | Mirati Therapeutics Inc | Inhibidores de KRAS G12C |
| JOP20190186A1 (ar) * | 2017-02-02 | 2019-08-01 | Astellas Pharma Inc | مركب كينازولين |
| US20190134056A1 (en) * | 2017-03-10 | 2019-05-09 | The Trustees Of The Stevens Institute Of Technolog | K-ras mutations and antagonists |
| TW201906832A (zh) | 2017-05-25 | 2019-02-16 | 美商亞瑞克西斯製藥公司 | 用於癌症治療之化合物及其使用方法 |
| CN110869358A (zh) | 2017-05-25 | 2020-03-06 | 亚瑞克西斯制药公司 | Kras的共价抑制剂 |
| KR102736865B1 (ko) * | 2017-06-21 | 2024-12-03 | 샤이 테라퓨틱스 엘엘씨 | 암, 염증성 질환, 신경발달질환 및 섬유증 질환의 치료를 위하여 Ras 수퍼패밀리와 상호작용하는 화합물 |
| TW201942116A (zh) * | 2018-02-09 | 2019-11-01 | 美商輝瑞股份有限公司 | 作為抗癌劑之四氫喹唑啉衍生物 |
| WO2019232419A1 (en) * | 2018-06-01 | 2019-12-05 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
| AU2019284472B2 (en) * | 2018-06-11 | 2024-05-30 | Amgen Inc. | KRAS G12C inhibitors for treating cancer |
| CN112119075B (zh) * | 2018-08-16 | 2024-03-12 | 豪夫迈·罗氏有限公司 | 稠环化合物 |
| WO2021139748A1 (en) * | 2020-01-08 | 2021-07-15 | Ascentage Pharma (Suzhou) Co., Ltd. | Spirocyclic tetrahydroquinazolines |
| WO2022040469A1 (en) * | 2020-08-19 | 2022-02-24 | The Trustees Of The Stevens Institute Of Technology | Spiro compounds as kras inhibitors |
-
2020
- 2020-05-20 CA CA3141604A patent/CA3141604A1/en active Pending
- 2020-05-20 MX MX2021014177A patent/MX2021014177A/es unknown
- 2020-05-20 AU AU2020279253A patent/AU2020279253A1/en not_active Abandoned
- 2020-05-20 BR BR112021023359A patent/BR112021023359A2/pt not_active IP Right Cessation
- 2020-05-20 KR KR1020217041514A patent/KR20220038289A/ko not_active Ceased
- 2020-05-20 SG SG11202112790SA patent/SG11202112790SA/en unknown
- 2020-05-20 WO PCT/US2020/033816 patent/WO2020236940A1/en not_active Ceased
- 2020-05-20 US US17/612,972 patent/US20220227738A1/en active Pending
- 2020-05-20 JP JP2021568865A patent/JP7502337B2/ja active Active
- 2020-05-20 EP EP20810811.8A patent/EP3972978A4/en active Pending
- 2020-05-20 CN CN202080052231.0A patent/CN114096544B/zh active Active
-
2021
- 2021-11-17 IL IL288200A patent/IL288200A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US20220227738A1 (en) | 2022-07-21 |
| WO2020236940A1 (en) | 2020-11-26 |
| AU2020279253A1 (en) | 2021-12-16 |
| EP3972978A1 (en) | 2022-03-30 |
| JP2022533398A (ja) | 2022-07-22 |
| BR112021023359A2 (pt) | 2022-02-01 |
| JP7502337B2 (ja) | 2024-06-18 |
| MX2021014177A (es) | 2022-04-25 |
| CA3141604A1 (en) | 2020-11-26 |
| EP3972978A4 (en) | 2023-04-26 |
| KR20220038289A (ko) | 2022-03-28 |
| SG11202112790SA (en) | 2021-12-30 |
| IL288200A (en) | 2022-01-01 |
| CN114096544A (zh) | 2022-02-25 |
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