CN114829362A - 一种可用作shp2抑制剂的含氮杂原子的六元并五元芳环衍生物 - Google Patents
一种可用作shp2抑制剂的含氮杂原子的六元并五元芳环衍生物 Download PDFInfo
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- 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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- 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
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- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P37/02—Immunomodulators
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- 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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- 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
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- 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
Abstract
提供一种如式(I)所示的具有抑制SHP2的活性的化合物、其制备方法,包含该化合物的组合物以及可用作SHP2抑制剂的用途及其制药用途;式(1)中,环A选自3~10元脂环、6~10元芳环、5~10元脂杂环、5~10元芳杂环,环B选自5~8元单杂环、6~12元双杂环、10~18元三杂环、14~20元四杂环,X1、X2、X3各自独立地选自C、N,X4、X5、X6、X7、X8各自独立地选自CR1、N、NR2,L选自共价键、S、CR3R4、NR0、S(O)2、S(O)、O。
Description
PCT国内申请,说明书已公开。
Claims (63)
- PCT国内申请,权利要求书已公开。
Applications Claiming Priority (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2019112582167 | 2019-12-10 | ||
CN201911258216 | 2019-12-10 | ||
CN2020105858546 | 2020-06-24 | ||
CN202010585854 | 2020-06-24 | ||
CN202011197272 | 2020-10-31 | ||
CN2020111972727 | 2020-10-31 | ||
CN202011205423 | 2020-11-02 | ||
CN2020112054239 | 2020-11-02 | ||
PCT/CN2020/134658 WO2021115286A1 (zh) | 2019-12-10 | 2020-12-08 | 一种可用作shp2抑制剂的含氮杂原子的六元并五元芳环衍生物 |
Publications (1)
Publication Number | Publication Date |
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CN114829362A true CN114829362A (zh) | 2022-07-29 |
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Application Number | Title | Priority Date | Filing Date |
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CN202080069976.8A Pending CN114829362A (zh) | 2019-12-10 | 2020-12-08 | 一种可用作shp2抑制剂的含氮杂原子的六元并五元芳环衍生物 |
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Country | Link |
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CN (1) | CN114829362A (zh) |
TW (1) | TW202130641A (zh) |
WO (1) | WO2021115286A1 (zh) |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MX2023002248A (es) | 2020-09-03 | 2023-05-16 | Revolution Medicines Inc | Uso de inhibidores de sos1 para tratar neoplasias malignas con mutaciones de shp2. |
CR20230165A (es) | 2020-09-15 | 2023-06-02 | Revolution Medicines Inc | Derivados indólicos como inhibidores de ras en el tratamiento del cáncer |
BR112023022819A2 (pt) | 2021-05-05 | 2024-01-16 | Revolution Medicines Inc | Compostos, composição farmacêutica, conjugados e métodos para tratar câncer em um sujeito, para tratar um distúrbio e para inibir uma proteína ras em uma célula |
CN117616031A (zh) | 2021-05-05 | 2024-02-27 | 锐新医药公司 | 用于治疗癌症的ras抑制剂 |
WO2022235866A1 (en) | 2021-05-05 | 2022-11-10 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
IL309984A (en) | 2021-07-09 | 2024-03-01 | Kanaph Therapeutics Inc | SHP2 inhibitor and use thereof |
CA3224341A1 (en) | 2021-09-01 | 2023-03-09 | Novartis Ag | Pharmaceutical combinations comprising a tead inhibitor and uses thereof for the treatment of cancers |
AR127308A1 (es) | 2021-10-08 | 2024-01-10 | Revolution Medicines Inc | Inhibidores ras |
WO2023172940A1 (en) | 2022-03-08 | 2023-09-14 | Revolution Medicines, Inc. | Methods for treating immune refractory lung cancer |
CN114920759A (zh) * | 2022-05-18 | 2022-08-19 | 江南大学 | 杂环-三氮唑并噻二唑杂环串联化合物、合成方法、药物组合物及用途 |
WO2023240263A1 (en) | 2022-06-10 | 2023-12-14 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
Citations (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2662163A1 (fr) * | 1990-05-16 | 1991-11-22 | Lipha | Nouvelles 8-amino-1,2,4-triazolo(4,3-a) pyrazines, procedes de preparation et medicaments les contenant. |
US6187777B1 (en) * | 1998-02-06 | 2001-02-13 | Amgen Inc. | Compounds and methods which modulate feeding behavior and related diseases |
CN1692115A (zh) * | 2002-12-26 | 2005-11-02 | 大正制药株式会社 | 环状氨基取代的吡咯并嘧啶和吡咯并吡啶衍生物 |
US20130053371A1 (en) * | 2010-01-22 | 2013-02-28 | Centro Nacional De Investigaciones Oncológicas (Cnio) | Inhibitors of pi3 kinase |
CN103328482A (zh) * | 2011-01-03 | 2013-09-25 | 韩美药品株式会社 | 用于调节g蛋白-偶联受体的新双环化合物 |
CN103415520A (zh) * | 2011-12-21 | 2013-11-27 | 江苏恒瑞医药股份有限公司 | 吡咯并六元杂芳环类衍生物、其制备方法及其在医药上的应用 |
US20150284398A1 (en) * | 2014-04-04 | 2015-10-08 | Duquesne University Of The Holy Spirit | Substituted Bicyclic Pyrimidine Compounds with Tubulin and Multiple Receptor Inhibition |
CN106488919A (zh) * | 2014-06-25 | 2017-03-08 | 武田药品工业株式会社 | 3‑取代的2‑氨基吲哚衍生物 |
CN107567452A (zh) * | 2015-04-29 | 2018-01-09 | 詹森药业有限公司 | 咪唑并哌嗪和吡唑并嘧啶以及它们作为ampa受体调节剂的用途 |
WO2019040102A1 (en) * | 2017-08-22 | 2019-02-28 | Gilead Sciences, Inc. | THERAPEUTIC HETEROCYCLIC COMPOUNDS |
US20190290649A1 (en) * | 2018-03-21 | 2019-09-26 | Synblia Therapeutics, Inc. | Shp2 inhibitors and uses thereof |
US20190307745A1 (en) * | 2016-09-22 | 2019-10-10 | Relay Therapeutics, Inc. | Shp2 phosphatase inhibitors and methods of use thereof |
CN110446709A (zh) * | 2017-01-23 | 2019-11-12 | 锐新医药公司 | 作为变构shp2抑制剂的二环化合物 |
-
2020
- 2020-12-08 WO PCT/CN2020/134658 patent/WO2021115286A1/zh active Application Filing
- 2020-12-08 CN CN202080069976.8A patent/CN114829362A/zh active Pending
- 2020-12-09 TW TW109143532A patent/TW202130641A/zh unknown
Patent Citations (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2662163A1 (fr) * | 1990-05-16 | 1991-11-22 | Lipha | Nouvelles 8-amino-1,2,4-triazolo(4,3-a) pyrazines, procedes de preparation et medicaments les contenant. |
US6187777B1 (en) * | 1998-02-06 | 2001-02-13 | Amgen Inc. | Compounds and methods which modulate feeding behavior and related diseases |
CN1692115A (zh) * | 2002-12-26 | 2005-11-02 | 大正制药株式会社 | 环状氨基取代的吡咯并嘧啶和吡咯并吡啶衍生物 |
US20130053371A1 (en) * | 2010-01-22 | 2013-02-28 | Centro Nacional De Investigaciones Oncológicas (Cnio) | Inhibitors of pi3 kinase |
CN103328482A (zh) * | 2011-01-03 | 2013-09-25 | 韩美药品株式会社 | 用于调节g蛋白-偶联受体的新双环化合物 |
CN103415520A (zh) * | 2011-12-21 | 2013-11-27 | 江苏恒瑞医药股份有限公司 | 吡咯并六元杂芳环类衍生物、其制备方法及其在医药上的应用 |
US20150284398A1 (en) * | 2014-04-04 | 2015-10-08 | Duquesne University Of The Holy Spirit | Substituted Bicyclic Pyrimidine Compounds with Tubulin and Multiple Receptor Inhibition |
CN106488919A (zh) * | 2014-06-25 | 2017-03-08 | 武田药品工业株式会社 | 3‑取代的2‑氨基吲哚衍生物 |
CN107567452A (zh) * | 2015-04-29 | 2018-01-09 | 詹森药业有限公司 | 咪唑并哌嗪和吡唑并嘧啶以及它们作为ampa受体调节剂的用途 |
US20190307745A1 (en) * | 2016-09-22 | 2019-10-10 | Relay Therapeutics, Inc. | Shp2 phosphatase inhibitors and methods of use thereof |
CN110446709A (zh) * | 2017-01-23 | 2019-11-12 | 锐新医药公司 | 作为变构shp2抑制剂的二环化合物 |
WO2019040102A1 (en) * | 2017-08-22 | 2019-02-28 | Gilead Sciences, Inc. | THERAPEUTIC HETEROCYCLIC COMPOUNDS |
US20190290649A1 (en) * | 2018-03-21 | 2019-09-26 | Synblia Therapeutics, Inc. | Shp2 inhibitors and uses thereof |
Non-Patent Citations (2)
Title |
---|
JEFFREY T. BAGDANOFF,等: "Optimization of Fused Bicyclic Allosteric SHP2 Inhibitors" * |
WANG, JIAN-XIN,等: "Palladium-Catalyzed Direct Heck Arylation of Dual π-Deficient/π-Excessive Heteroaromatics. Synthesis of C-5 Arylated Imidazo[1,5-a]pyrazines" * |
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TW202130641A (zh) | 2021-08-16 |
WO2021115286A1 (zh) | 2021-06-17 |
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