CN113474340B - 作为ras抑制剂的新型异吲哚啉酮取代的吲哚和衍生物 - Google Patents
作为ras抑制剂的新型异吲哚啉酮取代的吲哚和衍生物 Download PDFInfo
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- CN113474340B CN113474340B CN202080016480.4A CN202080016480A CN113474340B CN 113474340 B CN113474340 B CN 113474340B CN 202080016480 A CN202080016480 A CN 202080016480A CN 113474340 B CN113474340 B CN 113474340B
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- methyl
- indol
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- isoindol
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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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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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
- C07D401/12—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 chain containing hetero atoms as chain links
-
- 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
- C07D401/14—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 three or more hetero rings
-
- 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
-
- 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
- C07D405/02—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 two hetero rings
- C07D405/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D405/02—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 two hetero rings
- C07D405/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D405/02—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 two hetero rings
- C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
-
- 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
-
- 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
- C07D487/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP19159299.7 | 2019-02-26 | ||
| EP19159299 | 2019-02-26 | ||
| PCT/EP2020/054897 WO2020173935A1 (en) | 2019-02-26 | 2020-02-25 | New isoindolinone substituted indoles and derivatives as ras inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113474340A CN113474340A (zh) | 2021-10-01 |
| CN113474340B true CN113474340B (zh) | 2024-07-23 |
Family
ID=65598476
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202080016480.4A Active CN113474340B (zh) | 2019-02-26 | 2020-02-25 | 作为ras抑制剂的新型异吲哚啉酮取代的吲哚和衍生物 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US12281099B2 (enExample) |
| EP (1) | EP3931188B1 (enExample) |
| JP (1) | JP7426398B2 (enExample) |
| CN (1) | CN113474340B (enExample) |
| WO (1) | WO2020173935A1 (enExample) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112020020307A2 (pt) | 2018-04-04 | 2021-01-12 | Arvinas Operations, Inc. | Moduladores de proteólise e métodos de uso associados |
| AU2021263914B2 (en) | 2020-04-29 | 2026-07-23 | D.E. Shaw Research, Llc | PI3K-α inhibitors and methods of use thereof |
| IL301298A (en) | 2020-09-15 | 2023-05-01 | Revolution Medicines Inc | Indole derivatives as RAS inhibitors in cancer therapy |
| EP4313151A1 (en) | 2021-03-31 | 2024-02-07 | Sevenless Therapeutics Limited | Sos1 inhibitors and ras inhibitors for use in the treatment of pain |
| GB202104609D0 (en) | 2021-03-31 | 2021-05-12 | Sevenless Therapeutics Ltd | New Treatments for Pain |
| CN115232108B (zh) | 2021-04-23 | 2025-04-18 | 领泰生物医药(绍兴)有限公司 | Sos1降解剂及其制备方法和应用 |
| AR127308A1 (es) | 2021-10-08 | 2024-01-10 | Revolution Medicines Inc | Inhibidores ras |
| WO2023060362A1 (en) * | 2021-10-15 | 2023-04-20 | Genetolead Inc. | Ras inhibitors, compositions and methods of use thereof |
| TW202334136A (zh) * | 2021-11-03 | 2023-09-01 | 美商傳達治療有限公司 | PI3Kα抑制劑及其製造與使用方法 |
| WO2023114973A1 (en) | 2021-12-17 | 2023-06-22 | Shure Acquisition Holdings, Inc. | Adaptive acoustic echo cancellation for a stereo audio signal |
| TW202340214A (zh) | 2021-12-17 | 2023-10-16 | 美商健臻公司 | 做為shp2抑制劑之吡唑并吡𠯤化合物 |
| EP4227307A1 (en) | 2022-02-11 | 2023-08-16 | Genzyme Corporation | Pyrazolopyrazine compounds as shp2 inhibitors |
| CA3244999A1 (en) | 2022-03-31 | 2025-06-13 | Eisai R&D Management Co., Ltd. | Pharmaceutical composition for treating tumors |
| EP4536364A1 (en) | 2022-06-10 | 2025-04-16 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
| EP4598538A1 (en) | 2022-10-05 | 2025-08-13 | Sevenless Therapeutics Limited | New treatments for pain |
| PE20260006A1 (es) | 2023-01-26 | 2026-01-06 | Arvinas Operations Inc | Protacs degradadores de kras basados en cereblon y usos relacionados con los mismos |
| KR20250166103A (ko) | 2023-04-06 | 2025-11-27 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 종양 치료용 약제학적 조성물 |
| CN121487951A (zh) | 2023-04-07 | 2026-02-06 | 锐新医药公司 | 大环ras抑制剂 |
| WO2024211712A1 (en) | 2023-04-07 | 2024-10-10 | Revolution Medicines, Inc. | Condensed macrocyclic compounds as ras inhibitors |
| AU2024251341A1 (en) | 2023-04-14 | 2025-10-16 | Revolution Medicines, Inc. | Crystalline forms of a ras inhibitor |
| EP4695261A1 (en) | 2023-04-14 | 2026-02-18 | Revolution Medicines, Inc. | Crystalline forms of ras inhibitors, compositions containing the same, and methods of use thereof |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI0810082A2 (pt) * | 2007-03-29 | 2014-10-21 | Novartis Ag | 3-imidazolil-indóis para o tratamento de doenças proliferativas |
| TW201524952A (zh) | 2013-03-15 | 2015-07-01 | Araxes Pharma Llc | Ｋｒａｓ ｇ１２ｃ之共價抑制劑 |
| MX380928B (es) | 2013-10-10 | 2025-03-12 | Araxes Pharma Llc | Inhibidores de kras g12c. |
| US9862701B2 (en) | 2014-09-25 | 2018-01-09 | Araxes Pharma Llc | Inhibitors of KRAS G12C mutant proteins |
| ES2856880T3 (es) | 2015-04-15 | 2021-09-28 | Araxes Pharma Llc | Inhibidores tricíclicos condensados de KRAS y métodos de uso de los mismos |
| JP6869947B2 (ja) | 2015-07-22 | 2021-05-12 | アラクセス ファーマ エルエルシー | 置換キナゾリン化合物ならびにそのｇ１２ｃ変異ｋｒａｓ、ｈｒａｓおよび／またはｎｒａｓタンパク質の阻害剤としての使用 |
| WO2017068412A1 (en) * | 2015-10-21 | 2017-04-27 | Otsuka Pharmaceutical Co., Ltd. | Benzolactam compounds as protein kinase inhibitors |
| JP2019529484A (ja) | 2016-09-29 | 2019-10-17 | アラクセス ファーマ エルエルシー | Ｋｒａｓ ｇ１２ｃ変異体タンパク質の阻害剤 |
| US10377743B2 (en) * | 2016-10-07 | 2019-08-13 | Araxes Pharma Llc | Inhibitors of RAS and methods of use thereof |
| CR20190338A (es) | 2016-12-22 | 2019-09-09 | Amgen Inc | Inhibidores de kras g12c y métodos para su uso |
| EP3573971A1 (en) * | 2017-01-26 | 2019-12-04 | Araxes Pharma LLC | 1-(3-(6-(3-hydroxynaphthalen-1-yl)benzofuran-2-yl)azetidin-1yl)prop-2-en-1-one derivatives and similar compounds as kras g12c modulators for treating cancer |
| US11136308B2 (en) | 2017-01-26 | 2021-10-05 | Araxes Pharma Llc | Substituted quinazoline and quinazolinone compounds and methods of use thereof |
| WO2021148581A1 (en) * | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
-
2020
- 2020-02-25 EP EP20707599.5A patent/EP3931188B1/en active Active
- 2020-02-25 CN CN202080016480.4A patent/CN113474340B/zh active Active
- 2020-02-25 WO PCT/EP2020/054897 patent/WO2020173935A1/en not_active Ceased
- 2020-02-25 JP JP2021549575A patent/JP7426398B2/ja active Active
- 2020-02-25 US US17/430,011 patent/US12281099B2/en active Active
Non-Patent Citations (2)
| Title |
|---|
| Drugging an undruggable pocket on KRAS;Dirk Kesslera等;PNAS;第116卷(第32期);15823-15829 * |
| The small molecule BI-2852 induces a nonfunctional dimer of KRAS;Timothy H. Trana等;PNAS;第117卷(第7期);3363-3364 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113474340A (zh) | 2021-10-01 |
| WO2020173935A1 (en) | 2020-09-03 |
| EP3931188B1 (en) | 2023-08-30 |
| JP7426398B2 (ja) | 2024-02-01 |
| US20220144810A1 (en) | 2022-05-12 |
| US12281099B2 (en) | 2025-04-22 |
| EP3931188A1 (en) | 2022-01-05 |
| JP2022523201A (ja) | 2022-04-21 |
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