CN108290864A - 一种蛋白激酶抑制剂及其制备方法和医药用途 - Google Patents

一种蛋白激酶抑制剂及其制备方法和医药用途 Download PDF

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CN108290864A
CN108290864A CN201680064053.7A CN201680064053A CN108290864A CN 108290864 A CN108290864 A CN 108290864A CN 201680064053 A CN201680064053 A CN 201680064053A CN 108290864 A CN108290864 A CN 108290864A
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mesomer
enantiomter
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CN108290864B (zh
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尹磊
刘文剑
李恒
朱殿玺
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Gan and Lee Pharmaceuticals Co Ltd
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    • 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
    • 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
    • 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
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
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    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
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    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Steroid Compounds (AREA)

Abstract

本发明提供一种结构式I所示的化合物或其互变异构体、内消旋体、外消旋体、对映异构体、非对映异构体，氘代化合物，前药或其混合物形式，或结构式I所示的化合物、其互变异构体、内消旋体、外消旋体、对映异构体、非对映异构体，氘代化合物，前药或其混合物的药学上可以接受的盐或溶剂化物，其中R1～R7如文中定义。本发明还提供所述化合物的制备方法和医药用途。本发明所述的化合物活性优于或与目前处于III期临床试验的候选药物LY2835219相当，部分化合物表现出更好的选择性。而且优选的化合物口服吸收良好、血脑分布好，预示着本发明的化合物有希望被开发成新的治疗细胞增殖相关疾病的药物，尤其是脑瘤，为临床医生和患者提供新的选择。

Description

PCT国内申请，说明书已公开。

Claims (17)

  1. PCT国内申请，权利要求书已公开。
CN201680064053.7A 2015-11-30 2016-11-28 一种蛋白激酶抑制剂及其制备方法和医药用途 Active CN108290864B (zh)

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CN2015108566411 2015-11-30
PCT/CN2016/107455 WO2017092635A1 (zh) 2015-11-30 2016-11-28 一种蛋白激酶抑制剂及其制备方法和医药用途

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US (2) US11091476B2 (zh)
EP (1) EP3385262B1 (zh)
JP (2) JP6921101B2 (zh)
KR (1) KR20180083421A (zh)
CN (3) CN106810536A (zh)
AU (1) AU2016365366B2 (zh)
BR (1) BR112018010879A2 (zh)
CA (1) CA3002884A1 (zh)
CO (1) CO2018005854A2 (zh)
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ES (1) ES2928169T3 (zh)
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IL (1) IL259711B (zh)
MA (1) MA42341B2 (zh)
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CN114364668A (zh) * 2019-06-21 2022-04-15 甘李药业股份有限公司 Cdk4/6抑制剂、及其盐和中间体的制备方法
AR119184A1 (es) 2019-06-21 2021-12-01 Gan & Lee Pharmaceuticals Sales de un compuesto, formas cristalinas de las sales y método de preparación y uso de las mismas
CN116113628A (zh) * 2020-08-31 2023-05-12 甘李药业股份有限公司 一种含cdk4/6抑制剂的药物组合物
KR20230122096A (ko) * 2020-12-18 2023-08-22 프렐루드 테라퓨틱스, 인코포레이티드 Cdk 억제제 및 약제로서의 이의 용도
WO2022218247A1 (zh) * 2021-04-12 2022-10-20 甘李药业股份有限公司 作为cdk4/6抑制剂的氘代化合物
CN117337284A (zh) * 2021-05-17 2024-01-02 甘李药业股份有限公司 一种cdk4/6抑制剂的医药用途
WO2023040914A1 (zh) * 2021-09-14 2023-03-23 甘李药业股份有限公司 一种cdk4/6抑制剂的医药用途
WO2023116862A1 (zh) * 2021-12-24 2023-06-29 江苏恒瑞医药股份有限公司 氢化吲哚类化合物、其制备方法及其在医药上的应用
CN115093397B (zh) * 2022-06-07 2023-09-05 自贡市第三人民医院 一种用于治疗肿瘤的化合物、合成方法及应用
WO2024051717A1 (zh) * 2022-09-08 2024-03-14 上海深势唯思科技有限责任公司 作为plk1抑制剂的化合物及其制备方法和用途
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BR112018010879A2 (zh) 2018-11-21
UA124001C2 (uk) 2021-07-07
RU2018122864A3 (zh) 2020-03-17
US20200165239A1 (en) 2020-05-28
JP2021138737A (ja) 2021-09-16
ES2928169T3 (es) 2022-11-15
KR20180083421A (ko) 2018-07-20
CN106810536A (zh) 2017-06-09
HUE060152T2 (hu) 2023-02-28
CA3002884A1 (en) 2017-06-08
CN113956238B (zh) 2023-07-14
ZA201803531B (en) 2021-10-27
US11091476B2 (en) 2021-08-17
MX2018006370A (es) 2018-09-24
PT3385262T (pt) 2022-10-18
JP6921101B2 (ja) 2021-08-18
EP3385262A4 (en) 2019-06-19
RU2018122864A (ru) 2020-01-13
WO2017092635A1 (zh) 2017-06-08
PH12018550049A1 (en) 2018-10-29
US11787801B2 (en) 2023-10-17
IL259711B (en) 2022-08-01
IL259711A (en) 2018-07-31
US20210371418A1 (en) 2021-12-02
CN108290864B (zh) 2022-05-10
JP2019500413A (ja) 2019-01-10
EP3385262A1 (en) 2018-10-10
MA42341A1 (fr) 2018-06-29
AU2016365366A1 (en) 2018-05-17
DK3385262T3 (da) 2022-10-10
CO2018005854A2 (es) 2018-06-20
RU2749437C2 (ru) 2021-06-10
CN113956238A (zh) 2022-01-21
EP3385262B1 (en) 2022-07-13
MA42341B2 (fr) 2021-05-31
AU2016365366B2 (en) 2021-03-04

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