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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 PDF

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CN114829362A
CN114829362A CN202080069976.8A CN202080069976A CN114829362A CN 114829362 A CN114829362 A CN 114829362A CN 202080069976 A CN202080069976 A CN 202080069976A CN 114829362 A CN114829362 A CN 114829362A
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deuterium
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阳安乐
易韬
王志
张德伟
沈欢
胡凯
王浩
何权鸿
余攀
杨旭东
胡晓
王燕
杨奇
苏忠海
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Chengdu Beite Pharmaceutical Co ltd
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    • A—HUMAN NECESSITIES
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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
    • A61K31/435—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
    • A61K31/437—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 five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • 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
    • A61K31/435—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
    • 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
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring 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
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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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
    • C07D471/04—Ortho-condensed systems
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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
    • 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
    • C07D495/04—Ortho-condensed 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

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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)

  1. PCT国内申请，权利要求书已公开。
CN202080069976.8A 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 Pending CN114829362A (zh)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
CN2019112582167 2019-12-10
CN201911258216 2019-12-10
CN202010585854 2020-06-24
CN2020105858546 2020-06-24
CN2020111972727 2020-10-31
CN202011197272 2020-10-31
CN2020112054239 2020-11-02
CN202011205423 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)

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CN114829362A true CN114829362A (zh) 2022-07-29

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CN (1) CN114829362A (zh)
TW (1) TW202130641A (zh)
WO (1) WO2021115286A1 (zh)

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CN116209438A (zh) 2020-09-03 2023-06-02 锐新医药公司 使用sos1抑制剂治疗具有shp2突变的恶性疾病
EP4214209A1 (en) 2020-09-15 2023-07-26 Revolution Medicines, Inc. Indole derivatives as ras inhibitors in the treatment of cancer
CN117500811A (zh) 2021-05-05 2024-02-02 锐新医药公司 共价ras抑制剂及其用途
AR125787A1 (es) 2021-05-05 2023-08-16 Revolution Medicines Inc Inhibidores de ras
JP2024517847A (ja) 2021-05-05 2024-04-23 レボリューション メディシンズ インコーポレイテッド Ｒａｓ阻害剤
AU2022309195A1 (en) 2021-07-09 2024-01-25 Kanaph Therapeutics Inc. Shp2 inhibitor and use thereof
JP2024532374A (ja) 2021-09-01 2024-09-05 ノバルティス アーゲー Ｔｅａｄ阻害剤を含む医薬品組み合わせ物及び癌の治療のためのその使用
AR127308A1 (es) 2021-10-08 2024-01-10 Revolution Medicines Inc Inhibidores ras
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
CN114920759B (zh) * 2022-05-18 2024-09-10 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
WO2024175081A1 (zh) * 2023-02-24 2024-08-29 深圳真实生物医药科技有限公司 Shp2抑制剂化合物及其应用
WO2024206858A1 (en) 2023-03-30 2024-10-03 Revolution Medicines, Inc. Compositions for inducing ras gtp hydrolysis and uses thereof
WO2024211663A1 (en) 2023-04-07 2024-10-10 Revolution Medicines, Inc. Condensed macrocyclic compounds as ras inhibitors
WO2024211712A1 (en) 2023-04-07 2024-10-10 Revolution Medicines, Inc. Condensed macrocyclic compounds as ras inhibitors
TW202446388A (zh) 2023-04-14 2024-12-01 美商銳新醫藥公司 Ｒａｓ抑制劑之結晶形式、含有其之組合物及其使用方法
US20240352038A1 (en) 2023-04-14 2024-10-24 Revolution Medicines, Inc. Crystalline forms of ras inhibitors, compositions containing the same, and methods of use thereof
WO2024229406A1 (en) 2023-05-04 2024-11-07 Revolution Medicines, Inc. Combination therapy for a ras related disease or disorder
US20250049810A1 (en) 2023-08-07 2025-02-13 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder

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