CN109952304A - 一类抑制并降解cdk的化合物 - Google Patents

一类抑制并降解cdk的化合物 Download PDF

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CN109952304A
CN109952304A CN201880004082.3A CN201880004082A CN109952304A CN 109952304 A CN109952304 A CN 109952304A CN 201880004082 A CN201880004082 A CN 201880004082A CN 109952304 A CN109952304 A CN 109952304A
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CN109952304B (zh
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舒永志
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Shanghai Meizer Pharmaceuticals Co ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • 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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

本发明提供了一类抑制并降解CDK的化合物，具体地，本发明提供了一种如下式I所示的化合物；其中，各基团的定义如说明书中所述。本发明的化合物具有很好的周期蛋白依赖性激酶CDK抑制活性，可以用于制备治疗CDK活性相关的疾病的药物。

Description

PCT国内申请，说明书已公开。

Claims (10)

  1. PCT国内申请，权利要求书已公开。
CN201880004082.3A 2017-09-17 2018-09-14 一类抑制并降解cdk的化合物 Active CN109952304B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN201710837228X 2017-09-17
CN201710837228.XA CN109516989B (zh) 2017-09-17 2017-09-17 一类抑制并降解cdk的化合物
PCT/CN2018/105713 WO2019052535A1 (zh) 2017-09-17 2018-09-14 一类抑制并降解cdk的化合物

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CN109952304A true CN109952304A (zh) 2019-06-28
CN109952304B CN109952304B (zh) 2021-08-24

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CN (2) CN109516989B (zh)
WO (1) WO2019052535A1 (zh)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109422733A (zh) * 2017-09-03 2019-03-05 上海美志医药科技有限公司 一类抑制并降解酪氨酸蛋白激酶alk的化合物
EP3728228A1 (en) 2017-12-22 2020-10-28 Ravenna Pharmaceuticals, Inc. Aminopyridine derivatives as phosphatidylinositol phosphate kinase inhibitors
US20210340140A1 (en) * 2018-07-23 2021-11-04 Dana-Farber Cancer Institute, Inc. Degradation of cyclin-dependent kinase 4/6 (cdk4/6) by conjugation of cdk4/6 inhibitors with e3 ligase ligand and methods of use
TW202112767A (zh) 2019-06-17 2021-04-01 美商佩特拉製藥公司 作為磷脂酸肌醇磷酸激酶抑制劑之胺基吡啶衍生物
CN110305126A (zh) * 2019-06-19 2019-10-08 浙江省医学科学院 一种基于crbn配体诱导cdk4/6降解的化合物及其制备方法、药物组合物和应用
CA3186548A1 (en) * 2020-07-21 2022-01-27 Song Hee Lee Compound for androgen receptor degradation, and pharmaceutical use thereof
WO2023177451A1 (en) * 2022-03-18 2023-09-21 EnhancedBio Inc. Compounds and methods for the targeted degradation of cyclin dependent kinases
TW202406904A (zh) * 2022-04-25 2024-02-16 大陸商上海岸闊醫藥科技有限公司 Ｃｄｋ抑制劑、醫藥組成物及其治療應用
WO2024125581A2 (zh) * 2022-12-16 2024-06-20 上海岸阔医药科技有限公司 化合物及其用途

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014063061A1 (en) * 2012-10-19 2014-04-24 Dana-Farber Cancer Institute, Inc. Hydrophobically tagged small molecules as inducers of protein degradation
WO2016015605A1 (en) * 2014-07-26 2016-02-04 Sunshine Lake Pharma Co., Ltd. Compounds as cdk small-molecule inhibitors and uses thereof
WO2017185031A1 (en) * 2016-04-22 2017-10-26 Dana-Farber Cancer Institute, Inc. Degradation of cyclin-dependent kinase 4/6 (cdk4/6) by conjugation of cdk4/6 inhibitors with e3 ligase ligand and methods of use
WO2018106870A1 (en) * 2016-12-08 2018-06-14 Icahn School Of Medicine At Mount Sinai Compositions and methods for treating cdk4/6-mediated cancer

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014063061A1 (en) * 2012-10-19 2014-04-24 Dana-Farber Cancer Institute, Inc. Hydrophobically tagged small molecules as inducers of protein degradation
WO2016015605A1 (en) * 2014-07-26 2016-02-04 Sunshine Lake Pharma Co., Ltd. Compounds as cdk small-molecule inhibitors and uses thereof
WO2017185031A1 (en) * 2016-04-22 2017-10-26 Dana-Farber Cancer Institute, Inc. Degradation of cyclin-dependent kinase 4/6 (cdk4/6) by conjugation of cdk4/6 inhibitors with e3 ligase ligand and methods of use
WO2018106870A1 (en) * 2016-12-08 2018-06-14 Icahn School Of Medicine At Mount Sinai Compositions and methods for treating cdk4/6-mediated cancer

Also Published As

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US20200216450A1 (en) 2020-07-09
US11236090B2 (en) 2022-02-01
CN109952304B (zh) 2021-08-24
WO2019052535A1 (zh) 2019-03-21
CN109516989A (zh) 2019-03-26
CN109516989B (zh) 2021-12-31

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