CN115943144A - 一种作为pak4激酶抑制剂的化合物及其制备方法和应用 - Google Patents

一种作为pak4激酶抑制剂的化合物及其制备方法和应用 Download PDF

Info

Publication number
CN115943144A
CN115943144A CN202180036486.2A CN202180036486A CN115943144A CN 115943144 A CN115943144 A CN 115943144A CN 202180036486 A CN202180036486 A CN 202180036486A CN 115943144 A CN115943144 A CN 115943144A
Authority
CN
China
Prior art keywords
substituted
unsubstituted
group
alkyl
amino
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202180036486.2A
Other languages
English (en)
Inventor
杨茂
刘冠锋
李红波
刘龙飞
原晨光
李英富
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shenzhen Haibowei Pharmaceutical Co ltd
Chengdu Haibowei Pharmaceutical Co ltd
Original Assignee
Shenzhen Haibowei Pharmaceutical Co ltd
Chengdu Haibowei Pharmaceutical Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from CN202011631465.9A external-priority patent/CN114075175A/zh
Application filed by Shenzhen Haibowei Pharmaceutical Co ltd, Chengdu Haibowei Pharmaceutical Co ltd filed Critical Shenzhen Haibowei Pharmaceutical Co ltd
Publication of CN115943144A publication Critical patent/CN115943144A/zh
Pending legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/517—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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • 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
    • A61K31/69—Boron compounds
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C07D405/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • 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
    • C07D471/08—Bridged 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
    • 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
    • C07D487/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic System
    • C07F5/02—Boron compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

本发明提供了一种作为PAK4抑制剂的化合物，具有式I所示结构或其互变异构体、内消旋体、外消旋体、对映异构体、非对映异构体或其混合物形式、药学上可接受的水合物、溶剂化物或盐。试验结果表明，本发明制备的化合物对于PAK4激酶具有较高的抑制活性和选择性，同时其肝微粒体稳定性及大鼠PK也得到了一定的提升。

Description

PCT国内申请，说明书已公开。

Claims (16)

  1. PCT国内申请，权利要求书已公开。
CN202180036486.2A 2020-08-14 2021-08-09 一种作为pak4激酶抑制剂的化合物及其制备方法和应用 Pending CN115943144A (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
CN2020108194481 2020-08-14
CN202010819448 2020-08-14
CN202011631465.9A CN114075175A (zh) 2020-08-14 2020-12-31 一种作为pak4激酶抑制剂的化合物及其制备方法和应用
CN2020116314659 2020-12-31
PCT/CN2021/111472 WO2022033420A1 (zh) 2020-08-14 2021-08-09 一种作为pak4激酶抑制剂的化合物及其制备方法和应用

Publications (1)

Publication Number Publication Date
CN115943144A true CN115943144A (zh) 2023-04-07

Family

ID=80246914

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202180036486.2A Pending CN115943144A (zh) 2020-08-14 2021-08-09 一种作为pak4激酶抑制剂的化合物及其制备方法和应用

Country Status (2)

Country Link
CN (1) CN115943144A (zh)
WO (1) WO2022033420A1 (zh)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009053694A1 (en) * 2007-10-24 2009-04-30 Cancer Research Technology Limited Therapeutic oxy-phenyl-aryl compounds and their use
WO2010081881A1 (en) * 2009-01-15 2010-07-22 Universität Leipzig Aurora kinase inhibitors compounds.
JP2013032343A (ja) * 2011-06-29 2013-02-14 Otsuka Pharmaceut Co Ltd 治療用化合物、及び関連する使用の方法
CN103068821A (zh) * 2010-08-13 2013-04-24 詹森药业有限公司 作为脯氨酰羟化酶抑制剂的4-氨基喹唑啉-2-基-1-吡唑-4-羧酸化合物
CN103703001A (zh) * 2011-06-29 2014-04-02 大塚制药株式会社 喹唑啉作为治疗化合物及相关使用方法
CN108239071A (zh) * 2016-12-27 2018-07-03 沈阳药科大学 酰胺及硫代酰胺类衍生物及其制备方法和应用
CN111072640A (zh) * 2019-12-26 2020-04-28 沈阳药科大学 喹唑啉类衍生物及其制备方法和应用

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009053694A1 (en) * 2007-10-24 2009-04-30 Cancer Research Technology Limited Therapeutic oxy-phenyl-aryl compounds and their use
WO2010081881A1 (en) * 2009-01-15 2010-07-22 Universität Leipzig Aurora kinase inhibitors compounds.
CN103068821A (zh) * 2010-08-13 2013-04-24 詹森药业有限公司 作为脯氨酰羟化酶抑制剂的4-氨基喹唑啉-2-基-1-吡唑-4-羧酸化合物
JP2013032343A (ja) * 2011-06-29 2013-02-14 Otsuka Pharmaceut Co Ltd 治療用化合物、及び関連する使用の方法
CN103703001A (zh) * 2011-06-29 2014-04-02 大塚制药株式会社 喹唑啉作为治疗化合物及相关使用方法
CN108239071A (zh) * 2016-12-27 2018-07-03 沈阳药科大学 酰胺及硫代酰胺类衍生物及其制备方法和应用
CN111072640A (zh) * 2019-12-26 2020-04-28 沈阳药科大学 喹唑啉类衍生物及其制备方法和应用

Also Published As

Publication number Publication date
WO2022033420A1 (zh) 2022-02-17

Similar Documents

Publication Publication Date Title
TWI766882B (zh) 新穎化合物類
RU2717238C2 (ru) Соединения 1-циано-пирролидинов в качестве ингибиторов USP30
IL266894A (en) (s)-4-(8-amino-3-(1-but-2-inoyl-pyrrolidin-2-yl)imidazo[5,1-a]pyrazin-1-yl)-n-(pyridin-2- l) Benzamide as btk inhibitors
TW202200562A (zh) 喹喔啉二酮衍生物作為kras g12c突變蛋白的不可逆抑制劑
BR112017003054B1 (pt) Compostos de aminopirimidinila e composição farmacêutica ou veterinária
CN105732637B (zh) 杂芳化合物及其在药物中的应用
TW202016094A (zh) 週期素依賴性激酶抑制劑
JP2017531679A (ja) キナーゼ阻害剤として有用なインドールカルボキシアミド
CN105566321B (zh) 杂芳化合物及其在药物中的应用
CN114867720A (zh) 杂芳基类衍生物及其制备方法和用途
CN102985417A (zh) 作为jak1抑制剂的哌啶-4-基氮杂环丁烷衍生物
EP3640247B1 (en) Syk inhibitor and use method therefor
WO2017071516A1 (zh) 一种蛋白激酶抑制剂及其制备方法和医药用途
US20220033380A1 (en) Poly-adp ribose polymerase (parp) inhibitors
CN115843297A (zh) 作为bcl-2抑制剂的化合物
CN116888108B (zh) 新型egfr降解剂
CN114075175A (zh) 一种作为pak4激酶抑制剂的化合物及其制备方法和应用
CN114258391A (zh) 吡咯化合物
BR122022001938B1 (pt) Composto derivado de amina heterocíclica, composição farmacêutica compreendendo o mesmo e uso do dito composto para prevenir ou tratar doenças autoimunes ou cânceres
WO2022140769A1 (en) Lactam (hetero)arylfusedpyrimidine derivatives as inhibitors of erbb2
WO2024082872A1 (zh) 一种pak4激酶抑制剂及其制备方法和用途
AU2022349569A1 (en) Pyridine derivative and use thereof
CN115943144A (zh) 一种作为pak4激酶抑制剂的化合物及其制备方法和应用
TW202233608A (zh) 一種作為ｐａｋ４激酶抑制劑的化合物及其製備方法和應用
CN114133394A (zh) 一种选择性针对细胞周期依赖性激酶12活性的化合物、制备方法及医药用途

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination