CN111741769A - 一种多功能化合物、其制备方法及其在医药上的应用 - Google Patents

一种多功能化合物、其制备方法及其在医药上的应用 Download PDF

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CN111741769A
CN111741769A CN201980014546.3A CN201980014546A CN111741769A CN 111741769 A CN111741769 A CN 111741769A CN 201980014546 A CN201980014546 A CN 201980014546A CN 111741769 A CN111741769 A CN 111741769A
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CN111741769B (zh
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蔡家强
李桂英
陈忠辉
宋帅
孙启正
王太津
韩晓军
王利春
王晶翼
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Sichuan Kelun Biotech Biopharmaceutical Co Ltd
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    • 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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    • 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
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
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    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/55—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C07D495/12—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 three hetero rings
    • C07D495/14—Ortho-condensed systems

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  • Health & Medical Sciences (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

一类新的安全有效的通式为I或II的化合物，所述化合物的立体异构体、互变异构体或其混合物，所述化合物药学上可接受的盐、共晶、多晶型物或溶剂合物，或者所述化合物的稳定同位素衍生物、代谢物或前药：
Figure DDA0002642358920000011

Description

PCT国内申请，说明书已公开。

Claims (35)

  1. PCT国内申请，权利要求书已公开。
CN201980014546.3A 2018-04-20 2019-04-10 一种多功能化合物、其制备方法及其在医药上的应用 Active CN111741769B (zh)

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CN201810357402 2018-04-20
CN2018103574025 2018-04-20
CN2018110123044 2018-08-31
CN201811012304 2018-08-31
PCT/CN2019/081988 WO2019201123A1 (zh) 2018-04-20 2019-04-10 一种多功能化合物、其制备方法及其在医药上的应用

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112457297A (zh) * 2020-11-24 2021-03-09 福建医科大学 一种parp蛋白降解剂及其制备方法与应用
CN114044775A (zh) * 2021-08-30 2022-02-15 杭州医学院 一种靶向泛素化诱导bcr-abl蛋白降解的化合物及其应用
CN114890989A (zh) * 2022-05-25 2022-08-12 佛山市晨康生物科技有限公司 一种含氮衍生物为Linker的HDAC8降解剂其制备方法和应用
CN117143114A (zh) * 2023-10-30 2023-12-01 深圳大学 一种BRD4和Src双靶点抑制剂及其制备方法与应用

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020069105A1 (en) * 2018-09-27 2020-04-02 Dana-Farber Cancer Institute, Inc. Degraders of wee1 kinase
EP4069229A4 (en) * 2019-12-05 2024-02-07 Viracta Subsidiary, Inc. SOLID STATE FORMS OF HDAC INHIBITOR
WO2021141662A1 (en) * 2020-01-10 2021-07-15 Massachusetts Institute Of Technology Proteolysis targeting chimeric molecules (protacs) with functional handles and uses thereof
CN113402520A (zh) * 2020-03-16 2021-09-17 中国科学院上海药物研究所 Wee1蛋白降解剂
CA3196385A1 (en) 2020-10-28 2022-05-05 Xiaohu Deng Hdac inhibitor solid state forms
GB202017717D0 (en) * 2020-11-10 2020-12-23 Univ Dundee Improved small molecules
CA3240051A1 (en) * 2021-12-30 2023-07-06 Beigene Switzerland Gmbh Degradation of bruton's tyrosine kinase (btk) by conjugation of btk inhibitors with e3 ligase ligand and methods of use
TW202340196A (zh) * 2021-12-31 2023-10-16 大陸商正大天晴藥業集團股份有限公司 含有雜環的化合物及其應用
CN115385859B (zh) * 2022-08-22 2024-03-08 西安交通大学 一种可细胞内自组装的蛋白降解剂及其制备方法和应用
CN115403561B (zh) * 2022-08-22 2024-03-08 西安交通大学 一种基于沙利度胺类似物的细胞内自组装蛋白降解剂及其制备方法和应用
WO2024056077A1 (en) * 2022-09-15 2024-03-21 Cullgen (Shanghai) , Inc. Modified proteins and protein binders and degraders

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104736569A (zh) * 2012-01-12 2015-06-24 耶鲁大学 通过e3泛素连接酶增强靶蛋白质及其他多肽降解的化合物和方法
CN106458993A (zh) * 2014-04-14 2017-02-22 阿尔维纳斯股份有限公司 基于酰亚胺的蛋白水解调节剂和相关使用方法
WO2017211924A1 (en) * 2016-06-10 2017-12-14 Glaxosmithkline Intellectual Property Development Limited Novel compounds
EP3268363A1 (en) * 2015-03-13 2018-01-17 The University of Dundee Derivatives of 1-[(cyclopentyl or 2-pyrrolidinyl)carbonylaminomethyl]-4-(1,3-thiazol-5-yl) benzene which are useful for the treatment of proliferative, autoimmune or inflammatory diseases
CN107698657A (zh) * 2017-09-26 2018-02-16 中国药科大学 基于vhl配体和bet抑制剂诱导bet降解的双功能分子及其制备和应用
CN107698575A (zh) * 2017-09-26 2018-02-16 中国药科大学 cereblon配体介导的新型BET蛋白降解的双功能分子及其制备和应用
WO2018033556A1 (en) * 2016-08-18 2018-02-22 Glaxosmithkline Intellectual Property Development Limited Novel compounds
WO2022101603A1 (en) * 2020-11-10 2022-05-19 University Of Dundee Improved small molecules

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20200108289A (ko) * 2018-01-10 2020-09-17 재단법인 생물기술개발중심 항체 프로탁 컨쥬게이트

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104736569A (zh) * 2012-01-12 2015-06-24 耶鲁大学 通过e3泛素连接酶增强靶蛋白质及其他多肽降解的化合物和方法
CN106458993A (zh) * 2014-04-14 2017-02-22 阿尔维纳斯股份有限公司 基于酰亚胺的蛋白水解调节剂和相关使用方法
EP3268363A1 (en) * 2015-03-13 2018-01-17 The University of Dundee Derivatives of 1-[(cyclopentyl or 2-pyrrolidinyl)carbonylaminomethyl]-4-(1,3-thiazol-5-yl) benzene which are useful for the treatment of proliferative, autoimmune or inflammatory diseases
WO2017211924A1 (en) * 2016-06-10 2017-12-14 Glaxosmithkline Intellectual Property Development Limited Novel compounds
WO2018033556A1 (en) * 2016-08-18 2018-02-22 Glaxosmithkline Intellectual Property Development Limited Novel compounds
CN107698657A (zh) * 2017-09-26 2018-02-16 中国药科大学 基于vhl配体和bet抑制剂诱导bet降解的双功能分子及其制备和应用
CN107698575A (zh) * 2017-09-26 2018-02-16 中国药科大学 cereblon配体介导的新型BET蛋白降解的双功能分子及其制备和应用
WO2022101603A1 (en) * 2020-11-10 2022-05-19 University Of Dundee Improved small molecules

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
SATOMI IMAIDE等: "Trivalent PROTACs enhance protein degradation through cooperativity and avidity", 《CHEMRXIV》 *
刘斌等: "基于E3泛素连接酶小分子配体的靶向蛋白降解嵌合体的研究进展", 《中国药学杂志》 *
徐鹏飞等: "诱导蛋白降解的小分子PROTACs的研究进展", 《中国新药杂志》 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112457297A (zh) * 2020-11-24 2021-03-09 福建医科大学 一种parp蛋白降解剂及其制备方法与应用
CN112457297B (zh) * 2020-11-24 2023-04-28 福建医科大学 一种parp蛋白降解剂及其制备方法与应用
CN114044775A (zh) * 2021-08-30 2022-02-15 杭州医学院 一种靶向泛素化诱导bcr-abl蛋白降解的化合物及其应用
CN114890989A (zh) * 2022-05-25 2022-08-12 佛山市晨康生物科技有限公司 一种含氮衍生物为Linker的HDAC8降解剂其制备方法和应用
CN114890989B (zh) * 2022-05-25 2024-03-22 广东晨康生物科技有限公司 一种含氮衍生物为Linker的HDAC8降解剂其制备方法和应用
CN117143114A (zh) * 2023-10-30 2023-12-01 深圳大学 一种BRD4和Src双靶点抑制剂及其制备方法与应用
CN117143114B (zh) * 2023-10-30 2024-02-20 深圳大学 一种BRD4和Src双靶点抑制剂及其制备方法与应用

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TW201943712A (zh) 2019-11-16

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