ES3013592T3 - Kras g12d inhibitors - Google Patents
Kras g12d inhibitors Download PDFInfo
- Publication number
- ES3013592T3 ES3013592T3 ES22714667T ES22714667T ES3013592T3 ES 3013592 T3 ES3013592 T3 ES 3013592T3 ES 22714667 T ES22714667 T ES 22714667T ES 22714667 T ES22714667 T ES 22714667T ES 3013592 T3 ES3013592 T3 ES 3013592T3
- Authority
- ES
- Spain
- Prior art keywords
- mmol
- alkyl
- fluoro
- methoxy
- methyl
- 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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- 239000003112 inhibitor Substances 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 200
- 125000000217 alkyl group Chemical group 0.000 claims description 107
- 239000001257 hydrogen Substances 0.000 claims description 72
- 229910052739 hydrogen Inorganic materials 0.000 claims description 72
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 61
- 150000003839 salts Chemical class 0.000 claims description 56
- 125000005843 halogen group Chemical group 0.000 claims description 50
- 229920006395 saturated elastomer Polymers 0.000 claims description 48
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 39
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 38
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 38
- 229910052757 nitrogen Inorganic materials 0.000 claims description 31
- 125000001188 haloalkyl group Chemical group 0.000 claims description 30
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 19
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 16
- 125000003118 aryl group Chemical group 0.000 claims description 15
- 125000002619 bicyclic group Chemical group 0.000 claims description 14
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- 239000011737 fluorine Substances 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
- 125000001624 naphthyl group Chemical group 0.000 claims description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
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- 125000001153 fluoro group Chemical group F* 0.000 claims description 8
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- 150000002431 hydrogen Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 229910052717 sulfur Chemical group 0.000 claims description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 3
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- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 2
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- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 2
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- 238000000034 method Methods 0.000 abstract description 115
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- YCIBDOZDBNMZFF-GPANFISMSA-N tert-butyl 3-[7-bromo-6-chloro-8-fluoro-2-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]quinazolin-4-yl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CC(C)(C)OC(N(C(CC1)C2)C1CN2C(C1=CC(Cl)=C2Br)=NC(OC[C@H]3N(C)CCC3)=NC1=C2F)=O YCIBDOZDBNMZFF-GPANFISMSA-N 0.000 description 1
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Classifications
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- 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
- C07D487/08—Bridged systems
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07D471/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (5)
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|---|---|---|---|
| US202163160431P | 2021-03-12 | 2021-03-12 | |
| US202163173021P | 2021-04-09 | 2021-04-09 | |
| US202163220386P | 2021-07-09 | 2021-07-09 | |
| US202163236497P | 2021-08-24 | 2021-08-24 | |
| PCT/US2022/020239 WO2022192794A1 (en) | 2021-03-12 | 2022-03-14 | Kras g12d inhibitors |
Publications (1)
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| ES3013592T3 true ES3013592T3 (en) | 2025-04-14 |
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| JP (1) | JP2024510606A (https=) |
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| IL (1) | IL305568A (https=) |
| MX (1) | MX2023010430A (https=) |
| WO (1) | WO2022192794A1 (https=) |
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| KR20210006356A (ko) | 2018-04-04 | 2021-01-18 | 아비나스 오퍼레이션스, 인코포레이티드 | 단백질분해 조절제 및 연관된 사용 방법 |
| US20230365563A1 (en) * | 2020-09-30 | 2023-11-16 | Shanghai Pharmaceuticals Holding Co., Ltd. | Quinazoline compound and application thereof |
| CN115181106B (zh) * | 2021-04-07 | 2024-04-05 | 药雅科技(上海)有限公司 | 喹唑啉类krasg12d突变蛋白抑制剂的制备及其应用 |
| JP2024517695A (ja) * | 2021-04-29 | 2024-04-23 | アムジエン・インコーポレーテツド | 複素環式化合物及び使用方法 |
| WO2023278600A1 (en) * | 2021-06-30 | 2023-01-05 | Dana-Farber Cancer Institute, Inc. | Small molecule inhibitors of kras g12d mutant |
| WO2023114733A1 (en) * | 2021-12-13 | 2023-06-22 | Quanta Therapeutics, Inc. | Kras modulators and uses thereof |
| MX2024008849A (es) | 2022-01-21 | 2024-07-25 | Usynova Pharmaceuticals Ltd | Compuestos de benzopirimidina y uso de estos. |
| CN118556063A (zh) * | 2022-01-21 | 2024-08-27 | 上海湃隆生物科技有限公司 | 杂环类化合物、药物组合物及其应用 |
| AU2023218370B2 (en) | 2022-02-09 | 2024-11-28 | Quanta Therapeutics, Inc. | Kras modulators and uses thereof |
| CN119136806A (zh) | 2022-03-08 | 2024-12-13 | 锐新医药公司 | 用于治疗免疫难治性肺癌的方法 |
| CN118344386A (zh) * | 2023-01-13 | 2024-07-16 | 苏州泽璟生物制药股份有限公司 | 取代桥环类抑制剂及其制备方法和应用 |
| IL317601A (en) | 2022-05-25 | 2025-02-01 | Quanta Therapeutics Inc | Pyrimidine-based modulators and their uses |
| WO2023240263A1 (en) | 2022-06-10 | 2023-12-14 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
| TW202416976A (zh) * | 2022-09-16 | 2024-05-01 | 大陸商南京明德新藥研發有限公司 | 含六氫螺環［環丙烷—１，２＇—吡咯𠯤］的化合物 |
| WO2024061365A1 (zh) * | 2022-09-22 | 2024-03-28 | 成都奥睿药业有限公司 | 嘧啶并环类化合物及其制备方法与用途 |
| AU2023349002A1 (en) * | 2022-09-30 | 2025-05-15 | Trasveda Ltd. | Compounds with anti-kras mutant tumor activity |
| EP4631942A1 (en) | 2022-10-21 | 2025-10-15 | Leadingtac Pharmaceutical (Shaoxing) Co., Ltd. | Pan-kras degrading agent, and preparation method therefor and use thereof |
| JP2025536369A (ja) | 2022-10-21 | 2025-11-05 | リーディングタック ファーマシューティカル（シャオシン）カンパニー，リミテッド | Ｋｒａｓ ｇ１２ｄ分解剤及びその製造方法並びに応用 |
| CN117263959A (zh) * | 2022-10-24 | 2023-12-22 | 药雅科技(上海)有限公司 | 芳香类kras突变蛋白抑制剂的制备及其应用 |
| WO2024092420A1 (zh) * | 2022-10-31 | 2024-05-10 | 上海皓元医药股份有限公司 | 一种((2R,7aS)-2-氟六氢-1H-吡咯嗪-7a-基)甲醇的制备方法 |
| CN121419983A (zh) | 2023-01-26 | 2026-01-27 | 阿尔维纳斯运营股份有限公司 | 基于小脑蛋白的kras降解protac及其相关用途 |
| WO2024186680A1 (en) * | 2023-03-03 | 2024-09-12 | Frontier Medicines Corporation | Methods for preparing pyrrolizidine compounds |
| WO2024192424A1 (en) | 2023-03-15 | 2024-09-19 | Quanta Therapeutics, Inc. | Kras modulators and uses thereof |
| EP4687905A1 (en) | 2023-03-30 | 2026-02-11 | Revolution Medicines, Inc. | Compositions for inducing ras gtp hydrolysis and uses thereof |
| KR20260005904A (ko) | 2023-04-07 | 2026-01-12 | 레볼루션 메디슨즈, 인크. | 매크로사이클릭 ras 억제제 |
| CN121263418A (zh) | 2023-04-07 | 2026-01-02 | 锐新医药公司 | 大环ras抑制剂 |
| WO2024215862A2 (en) * | 2023-04-12 | 2024-10-17 | Board Of Regents, The University Of Texas System | Heterocyclic compounds as nras inhibitors |
| KR20250172857A (ko) | 2023-04-14 | 2025-12-09 | 레볼루션 메디슨즈, 인크. | Ras 억제제의 결정형 |
| AU2024252105A1 (en) | 2023-04-14 | 2025-10-16 | Revolution Medicines, Inc. | Crystalline forms of ras inhibitors, compositions containing the same, and methods of use thereof |
| CN121419984A (zh) * | 2023-04-26 | 2026-01-27 | 珃诺生物医药科技(杭州)有限公司 | Kras（g12d）的二氮杂双环辛烷抑制剂及用途 |
| AU2024265078A1 (en) | 2023-05-04 | 2025-12-11 | Revolution Medicines, Inc. | Combination therapy for a ras related disease or disorder |
| WO2024230707A1 (zh) * | 2023-05-07 | 2024-11-14 | 上海医药集团股份有限公司 | 一种喹唑啉类化合物及其应用 |
| IL326136A (en) | 2023-08-07 | 2026-03-01 | Revolution Medicines Inc | RMC-6291 for use in the treatment of a disease or disorder associated with the RAS protein |
| AU2024337913A1 (en) | 2023-09-08 | 2026-03-26 | Gilead Sciences, Inc. | Pyrimidine-containing polycyclic derivatives as kras g12d modulating compounds |
| US20250114339A1 (en) | 2023-10-09 | 2025-04-10 | Incyte Corporation | Combination therapy comprising a kras g12d inhibitor and an egfr inhibitor |
| AU2024357850A1 (en) | 2023-10-09 | 2026-04-23 | Incyte Corporation | Combination therapy using a kras g12d inhibitor and pd-1 inhibitor or pd-l1 inhibitor |
| US20250154171A1 (en) | 2023-10-12 | 2025-05-15 | Revolution Medicines, Inc. | Ras inhibitors |
| KR102738924B1 (ko) * | 2023-12-26 | 2024-12-06 | 주식회사 베노바이오 | Kras g12d 변이가 존재하는 암 치료를 위한 신규한 화합물 및 이를 이용한 암의 예방 또는 치료용 조성물 |
| WO2025171296A1 (en) | 2024-02-09 | 2025-08-14 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025240847A1 (en) | 2024-05-17 | 2025-11-20 | Revolution Medicines, Inc. | Ras inhibitors |
| US20250375445A1 (en) | 2024-06-07 | 2025-12-11 | Revolution Medicines, Inc. | Methods of treating a ras protein-related disease or disorder |
| WO2025265060A1 (en) | 2024-06-21 | 2025-12-26 | Revolution Medicines, Inc. | Therapeutic compositions and methods for managing treatment-related effects |
| WO2026006747A1 (en) | 2024-06-28 | 2026-01-02 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2026015825A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Use of ras inhibitor for treating pancreatic cancer |
| WO2026015796A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
| WO2026015790A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
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| WO2022002102A1 (en) * | 2020-06-30 | 2022-01-06 | InventisBio Co., Ltd. | Quinazoline compounds, preparation methods and uses thereof |
| US20230081426A1 (en) * | 2020-09-18 | 2023-03-16 | Plexxikon Inc. | Compounds and methods for kras modulation and indications therefor |
| BR112023015976A2 (pt) * | 2021-02-09 | 2023-12-12 | Medshine Discovery Inc | Compostos de anel aromático de pirimidina |
| AU2022224511A1 (en) * | 2021-02-16 | 2023-08-10 | Lawrence Livermore National Security, Llc | Compositions and methods for inhibition of ras |
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| EP4305038B1 (en) | 2025-01-29 |
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