CN114787142A - 作为周期蛋白依赖性激酶9抑制剂的化合物及其应用 - Google Patents

作为周期蛋白依赖性激酶9抑制剂的化合物及其应用 Download PDF

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CN114787142A
CN114787142A CN202080085286.1A CN202080085286A CN114787142A CN 114787142 A CN114787142 A CN 114787142A CN 202080085286 A CN202080085286 A CN 202080085286A CN 114787142 A CN114787142 A CN 114787142A
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dichloromethane
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CN114787142B (zh
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王振玉
张颜
穆永钊
郭见桥
安会
高娜
张朝再
王佳
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CSPC Zhongqi Pharmaceutical Technology Shijiazhuang Co Ltd
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    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
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    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
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    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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    • 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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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    • 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
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    • C07—ORGANIC CHEMISTRY
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    • 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
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    • 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
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    • 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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  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Hematology (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

本发明提供一种式（I）所示的化合物或其可药用盐、其立体异构体、同位素衍生物或前药，其作为周期蛋白依赖性激酶9（CDK9）抑制剂，在治疗过度增殖性疾病方面具有优良的活性，细胞增殖的体外抑制以及体内抑瘤试验研究显示，这些化合物对MV4;11细胞及体内肿瘤模型具有较强的抑制作用，且选择性好，毒副作用低，作为新型抗肿瘤药具有较好的临床价值。

Description

PCT国内申请，说明书已公开。

Claims (12)

  1. PCT国内申请，权利要求书已公开。
CN202080085286.1A 2019-12-09 2020-12-09 作为周期蛋白依赖性激酶9抑制剂的化合物及其应用 Active CN114787142B (zh)

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CN2019112525751 2019-12-09
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PCT/CN2020/134966 WO2021115335A1 (zh) 2019-12-09 2020-12-09 作为周期蛋白依赖性激酶9抑制剂的化合物及其应用

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Cited By (2)

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CN115381823A (zh) * 2021-05-24 2022-11-25 石药集团中奇制药技术（石家庄）有限公司 一种周期蛋白依赖性激酶9抑制剂的用途
CN115381824A (zh) * 2021-05-24 2022-11-25 石药集团中奇制药技术（石家庄）有限公司 周期蛋白依赖性激酶9抑制剂的用途

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CN114786673A (zh) * 2019-09-11 2022-07-22 普莱鲁德疗法有限公司 Cdk抑制剂及其作为药物的用途
CN115448874B (zh) * 2021-06-09 2024-11-01 石药集团中奇制药技术（石家庄）有限公司 固体形式的周期蛋白依赖性激酶9抑制剂及其用途

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CN102471310A (zh) * 2009-09-04 2012-05-23 诺瓦提斯公司 用于治疗增生性疾病的联吡啶化合物
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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115381823A (zh) * 2021-05-24 2022-11-25 石药集团中奇制药技术（石家庄）有限公司 一种周期蛋白依赖性激酶9抑制剂的用途
CN115381824A (zh) * 2021-05-24 2022-11-25 石药集团中奇制药技术（石家庄）有限公司 周期蛋白依赖性激酶9抑制剂的用途
CN115381824B (zh) * 2021-05-24 2024-11-05 石药集团中奇制药技术（石家庄）有限公司 周期蛋白依赖性激酶9抑制剂的用途
CN115381823B (zh) * 2021-05-24 2024-11-05 石药集团中奇制药技术（石家庄）有限公司 一种周期蛋白依赖性激酶9抑制剂的用途

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KR20220113773A (ko) 2022-08-16
JP2023505850A (ja) 2023-02-13
AU2020401999A1 (en) 2022-07-14
EP4074699A4 (en) 2024-01-03
AU2020401999B2 (en) 2024-01-18
CA3161351A1 (en) 2021-06-17
WO2021115335A1 (zh) 2021-06-17
US20230102081A1 (en) 2023-03-30
CN114787142B (zh) 2024-08-02
EP4074699A1 (en) 2022-10-19

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