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
- Publication number
- 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
- Authority
- CN
- China
- Prior art keywords
- methyl
- indol
- dihydro
- isoindol
- hydroxy
- 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.)
- Active
Links
Classifications
-
- 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
-
- 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
-
- 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
Landscapes
- 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 | 2019-02-26 | ||
| EP19159299.7 | 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 (https=) |
| EP (1) | EP3931188B1 (https=) |
| JP (1) | JP7426398B2 (https=) |
| CN (1) | CN113474340B (https=) |
| WO (1) | WO2020173935A1 (https=) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019195609A2 (en) | 2018-04-04 | 2019-10-10 | Arvinas Operations, Inc. | Modulators of proteolysis and associated methods of use |
| EP4143196A4 (en) | 2020-04-29 | 2024-04-17 | Relay Therapeutics, Inc. | PI3K-A INHIBITORS AND METHODS OF USE THEREOF |
| CA3194067A1 (en) | 2020-09-15 | 2022-03-24 | Revolution Medicines, Inc. | Ras inhibitors |
| GB202104609D0 (en) | 2021-03-31 | 2021-05-12 | Sevenless Therapeutics Ltd | New Treatments for Pain |
| EP4313151A1 (en) | 2021-03-31 | 2024-02-07 | Sevenless Therapeutics Limited | Sos1 inhibitors and ras inhibitors for use in the treatment of 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 |
| EP4416131A4 (en) * | 2021-10-15 | 2025-07-30 | 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 |
| CN119212994A (zh) | 2021-12-17 | 2024-12-27 | 建新公司 | 作为shp2抑制剂的吡唑并吡嗪化合物 |
| EP4227307A1 (en) | 2022-02-11 | 2023-08-16 | Genzyme Corporation | Pyrazolopyrazine compounds as shp2 inhibitors |
| EP4473970A4 (en) | 2022-03-31 | 2026-01-21 | Eisai R&D Man Co Ltd | PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF TUMORS |
| WO2023240263A1 (en) | 2022-06-10 | 2023-12-14 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
| EP4598538A1 (en) | 2022-10-05 | 2025-08-13 | Sevenless Therapeutics Limited | New treatments for pain |
| US12448399B2 (en) | 2023-01-26 | 2025-10-21 | Arvinas Operations, Inc. | Cereblon-based KRAS degrading PROTACs and uses related thereto |
| AU2023439518A1 (en) | 2023-04-06 | 2025-08-28 | Eisai R&D Management Co., Ltd. | Pharmaceutical composition for treating tumors |
| CR20250420A (es) | 2023-04-07 | 2025-11-20 | Revolution Medicines Inc | Inhibidores macrocíclicos de ras |
| AR132338A1 (es) | 2023-04-07 | 2025-06-18 | Revolution Medicines Inc | Inhibidores de ras |
| CN121100123A (zh) | 2023-04-14 | 2025-12-09 | 锐新医药公司 | Ras抑制剂的结晶形式 |
| CN121464140A (zh) | 2023-04-14 | 2026-02-03 | 锐新医药公司 | Ras抑制剂的结晶形式、含有其的组合物及其使用方法 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA200901212A1 (ru) * | 2007-03-29 | 2010-04-30 | Новартис Аг | 3-имидазолилиндолы, предназначенные для лечения пролиферативных заболеваний |
| CA2904393A1 (en) | 2013-03-15 | 2014-09-25 | Araxes Pharma Llc | Covalent inhibitors of kras g12c |
| EP3055290B1 (en) | 2013-10-10 | 2019-10-02 | Araxes Pharma LLC | Inhibitors of kras g12c |
| JP2017528498A (ja) | 2014-09-25 | 2017-09-28 | 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インヒビター |
| US10428064B2 (en) | 2015-04-15 | 2019-10-01 | Araxes Pharma Llc | Fused-tricyclic inhibitors of KRAS and methods of use thereof |
| WO2017015562A1 (en) | 2015-07-22 | 2017-01-26 | Araxes Pharma Llc | Substituted quinazoline compounds and their use as inhibitors of g12c mutant kras, hras and/or nras proteins |
| HUE068392T2 (hu) | 2015-10-21 | 2024-12-28 | Otsuka Pharma Co Ltd | Benzolaktám vegyületek mint fehérje kináz gátlók |
| WO2018064510A1 (en) | 2016-09-29 | 2018-04-05 | Araxes Pharma Llc | Inhibitors of kras g12c mutant proteins |
| EP3523289A1 (en) * | 2016-10-07 | 2019-08-14 | Araxes Pharma LLC | Heterocyclic compounds as inhibitors of ras and methods of use thereof |
| CN110366550A (zh) | 2016-12-22 | 2019-10-22 | 美国安进公司 | 作为用于治疗肺癌、胰腺癌或结直肠癌的KRAS G12C抑制剂的苯并异噻唑、异噻唑并[3,4-b]吡啶、喹唑啉、酞嗪、吡啶并[2,3-d]哒嗪和吡啶并[2,3-d]嘧啶衍生物 |
| WO2018140513A1 (en) | 2017-01-26 | 2018-08-02 | 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 WO PCT/EP2020/054897 patent/WO2020173935A1/en not_active Ceased
- 2020-02-25 JP JP2021549575A patent/JP7426398B2/ja active Active
- 2020-02-25 EP EP20707599.5A patent/EP3931188B1/en active Active
- 2020-02-25 US US17/430,011 patent/US12281099B2/en active Active
- 2020-02-25 CN CN202080016480.4A patent/CN113474340B/zh 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 |
|---|---|
| EP3931188A1 (en) | 2022-01-05 |
| US12281099B2 (en) | 2025-04-22 |
| JP2022523201A (ja) | 2022-04-21 |
| WO2020173935A1 (en) | 2020-09-03 |
| JP7426398B2 (ja) | 2024-02-01 |
| EP3931188B1 (en) | 2023-08-30 |
| US20220144810A1 (en) | 2022-05-12 |
| CN113474340A (zh) | 2021-10-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN113474340B (zh) | 作为ras抑制剂的新型异吲哚啉酮取代的吲哚和衍生物 | |
| CN112996800B (zh) | 作为smarca2和/或smarca4的降解剂的新型蛋白水解靶向嵌合体（protac）及其衍生物 | |
| CN116234806B (zh) | 用于治疗癌症的环状2-氨基-3-氰基噻吩及其衍生物 | |
| TWI634112B (zh) | Ｃｏｔ調節劑及其使用方法 | |
| CN118613485A (zh) | 用于治疗癌症的环状2-氨基-3-氰基噻吩及衍生物 | |
| CN111372932A (zh) | 作为sos1抑制剂的新颖苄氨基取代吡啶并嘧啶酮及衍生物 | |
| CN115052881A (zh) | 作为HER2抑制剂的[1,3]二嗪并[5,4-d]嘧啶 | |
| CN110167928A (zh) | 作为sos1抑制剂的新型经苄基氨基取代的喹唑啉和衍生物 | |
| CN114375202A (zh) | 抗癌组合疗法 | |
| CN114409656B (zh) | Pim激酶抑制剂 | |
| CN103124730A (zh) | 杂环炔苯类化合物及其药用组合物和应用 | |
| US11304929B2 (en) | Tosylacetate based compounds and derivatives thereof as PHGDH inhibitors | |
| WO2013143466A1 (zh) | 作为欧若拉激酶抑制剂的取代嘧啶衍生物 | |
| CN110191709A (zh) | 可用作吲哚胺2,3-双加氧酶和/或色氨酸双加氧酶抑制剂的化合物 | |
| CN108026067A (zh) | 作为cot调节剂的6-氨基-喹啉-3-腈 | |
| CN109071548A (zh) | 可用于治疗尤其是癌症的吡咯并咪唑衍生物或其类似物 | |
| CN118019741A (zh) | 作为smarca降解剂的新型四氢喹啉和包含它们的蛋白水解靶向嵌合体（protac） | |
| EP2867233A1 (en) | 3-(PYRAZOLYL)-1H-PYRROLO[2,3-b]PYRIDINE DERIVATIVES AS KINASE INHIBITORS | |
| RU2807277C2 (ru) | Соединения пиримидина и содержащие их фармацевтические композиции для предупреждения или лечения рака | |
| WO2024240256A1 (zh) | 作为激酶抑制剂的多环化合物及其制备方法和用途 | |
| KR20240054994A (ko) | AhR 시그널링의 조절에 유용한 화합물 | |
| HK1200449B (en) | Substituted benzylindazoles for use as bub1 kinase inhibitors in the treatment of hyperproliferative diseases | |
| HK1200449A1 (en) | Substituted benzylindazoles for use as bub1 kinase inhibitors in the treatment of hyperproliferative diseases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |