CN113677682A - 作为XIa因子抑制剂的大环衍生物 - Google Patents

作为XIa因子抑制剂的大环衍生物 Download PDF

Info

Publication number
CN113677682A
CN113677682A CN202080028108.5A CN202080028108A CN113677682A CN 113677682 A CN113677682 A CN 113677682A CN 202080028108 A CN202080028108 A CN 202080028108A CN 113677682 A CN113677682 A CN 113677682A
Authority
CN
China
Prior art keywords
compound
isomer
pharmaceutically acceptable
acceptable salt
added
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.)
Granted
Application number
CN202080028108.5A
Other languages
English (en)
Other versions
CN113677682B (zh
Inventor
蔡亚仙
颜小兵
王廷
吴成德
丁照中
陈曙辉
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.)
China Resources Biomedical Co ltd
Original Assignee
Medshine Discovery Inc
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
Application filed by Medshine Discovery Inc filed Critical Medshine Discovery Inc
Publication of CN113677682A publication Critical patent/CN113677682A/zh
Application granted granted Critical
Publication of CN113677682B publication Critical patent/CN113677682B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • C07D471/12—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 three hetero rings
    • C07D471/18—Bridged systems
    • 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
    • A61K31/435—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
    • A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Epidemiology (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

一类大环衍生物、其制备方法及含有该衍生物的药物组合物，以及它们作为治疗剂，特别是作为XIa因子抑制剂和在治疗和预防血栓栓塞等疾病的药物中的用途，具体公开了式(I)所示化合物、其异构体及其药学上可接受的盐。

Description

PCT国内申请，说明书已公开。

Claims (24)

  1. PCT国内申请，权利要求书已公开。
CN202080028108.5A 2019-04-16 2020-04-15 作为XIa因子抑制剂的大环衍生物 Active CN113677682B (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
CN2019103033584 2019-04-16
CN201910303358 2019-04-16
CN2020102007782 2020-03-20
CN202010200778 2020-03-20
PCT/CN2020/084932 WO2020211781A1 (zh) 2019-04-16 2020-04-15 作为XIa因子抑制剂的大环衍生物

Publications (2)

Publication Number Publication Date
CN113677682A true CN113677682A (zh) 2021-11-19
CN113677682B CN113677682B (zh) 2023-05-30

Family

ID=72837025

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202080028108.5A Active CN113677682B (zh) 2019-04-16 2020-04-15 作为XIa因子抑制剂的大环衍生物

Country Status (8)

Country Link
US (1) US20220204508A1 (zh)
EP (1) EP3957638A4 (zh)
JP (1) JP7270770B2 (zh)
KR (1) KR20220002966A (zh)
CN (1) CN113677682B (zh)
AU (1) AU2020257911B2 (zh)
CA (1) CA3136861A1 (zh)
WO (1) WO2020211781A1 (zh)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3953334B1 (en) * 2019-04-11 2023-11-22 Bristol-Myers Squibb Company Novel synthetic options towards the manufacture of (6r,10s)-10- {4-[5-chloro-2-(4-chloro-1h-1,2,3-triazol-1-yl)phenyl]-6-oxo-1(6h)- pyrimidinyl}- 1-(difluoromethyl)-6-methyl-1,4,7,8,9,10-hexahydro-11,15 -(metheno)pyrazolo [4,3-b] [1,7] diazacyclotetradecin-5(6h)-one

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016053455A1 (en) * 2014-10-01 2016-04-07 Bristol-Myers Squibb Company Pyrimidinones as factor xia inhibitors
CN105980384A (zh) * 2014-01-31 2016-09-28 百时美施贵宝公司 作为因子xia抑制剂的具有杂环p2＇基团的大环化合物
CN106459051A (zh) * 2014-01-31 2017-02-22 百时美施贵宝公司 含杂环基团的大环fxia抑制剂

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8940720B2 (en) 2010-02-11 2015-01-27 Bristol-Myers Squibb Company Macrocycles as factor XIa inhibitors
TW201311689A (zh) 2011-08-05 2013-03-16 必治妥美雅史谷比公司 作為因子ｘｉａ抑制劑之新穎巨環化合物
TW201319068A (zh) 2011-08-05 2013-05-16 必治妥美雅史谷比公司 作為ｘｉａ因子抑制劑之環狀ｐ１接合劑
CA2880898A1 (en) 2012-08-03 2014-02-06 Bristol-Myers Squibb Company Dihydropyridone p1 as factor xia inhibitors
RS55975B1 (sr) 2012-08-03 2017-09-29 Bristol Myers Squibb Co Dihidropiridon p1 kao inhibitori xia faktora
US10344039B2 (en) 2015-10-29 2019-07-09 Merck Sharp & Dohme Corp. Macrocyclic spirocarbamate derivatives as factor XIa inhibitors, pharmaceutically acceptable compositions and their use
MX2018005045A (es) 2015-10-29 2018-08-01 Merck Sharp & Dohme Inhibidores de factor xia.
WO2018133793A1 (zh) 2017-01-18 2018-07-26 广东东阳光药业有限公司 凝血因子XIa抑制剂及其用途

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105980384A (zh) * 2014-01-31 2016-09-28 百时美施贵宝公司 作为因子xia抑制剂的具有杂环p2＇基团的大环化合物
CN106459051A (zh) * 2014-01-31 2017-02-22 百时美施贵宝公司 含杂环基团的大环fxia抑制剂
WO2016053455A1 (en) * 2014-10-01 2016-04-07 Bristol-Myers Squibb Company Pyrimidinones as factor xia inhibitors

Also Published As

Publication number Publication date
KR20220002966A (ko) 2022-01-07
AU2020257911A1 (en) 2021-12-16
US20220204508A1 (en) 2022-06-30
CA3136861A1 (en) 2020-10-22
WO2020211781A1 (zh) 2020-10-22
AU2020257911B2 (en) 2023-01-05
EP3957638A4 (en) 2023-01-11
CN113677682B (zh) 2023-05-30
JP7270770B2 (ja) 2023-05-10
JP2022529959A (ja) 2022-06-27
EP3957638A1 (en) 2022-02-23

Similar Documents

Publication Publication Date Title
CN109415386B (zh) 硼酸衍生物及其治疗用途
TWI520965B (zh) 作為因子ｘｉａ抑制劑之巨環類
CN114174282A (zh) 作为甲状腺素受体-β激动剂的哒嗪酮类衍生物及其应用
TW201938556A (zh) 化合物及它們在治療癌症中之用途
TW202317097A (zh) 戊二醯亞胺類化合物與其應用
CN113677682A (zh) 作为XIa因子抑制剂的大环衍生物
CN113227051A (zh) 用于视网膜疾病的化合物
JP7292588B2 (ja) Ｃｃｒ２／ｃｃｒ５アンタゴニストとしてのヘテロシクロアルキル系化合物
CN114008047B (zh) 作为XIa因子抑制剂的大环衍生物
KR20220044573A (ko) (2-아세트아미딜)티오-베타-d-갈락토피라노시드 유도체
JP7275444B2 (ja) チエノ［２，３－ｃ］ピリダジン－４（１Ｈ）－オン系誘導体及びその使用
JP7227427B2 (ja) Ｓｇｌｔ２／ｄｐｐ４阻害剤及びその使用
CN112424189A (zh) 吡咯烷基脲衍生物及其在TrkA相关疾病的应用
TW202144358A (zh) 用作ret激酶抑制劑的化合物及其應用
WO2011024933A1 (ja) ３－（ビアリールオキシ）プロピオン酸誘導体
WO2024114677A1 (zh) 苯并螺环吲哚化合物的制备、应用及用途
CN115260195B (zh) Egfr降解剂
TWI839738B (zh) 含氮雜環化合物、其製備方法及應用
TW202246272A (zh) 吡唑並吡嗪三環類化合物及其應用
JPH04145085A (ja) スタウロスポリンのγ―ラクタム環誘導体とそのアンモニウム塩
KR960015088B1 (ko) 혈소판 활성인자에 길항작용을 하는 1,1-비스(히드록시메틸) 시클로알칸 화합물
CN117279923A (zh) 六元杂芳并脲环的衍生物及其应用
TW202233609A (zh) 2-羥環烷-1-胺甲醯基衍生物
TW202413366A (zh) 含氮雜環化合物作為泛素－特異性蛋白酶１抑制劑的製備方法、應用及其用途
TW202304924A (zh) 含氮雜環化合物、其製備方法及應用

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
REG Reference to a national code

Ref country code: HK

Ref legal event code: DE

Ref document number: 40056348

Country of ref document: HK

TA01 Transfer of patent application right
TA01 Transfer of patent application right

Effective date of registration: 20220801

Address after: 100018 building 7, yard 2, Middle North Third Ring Road, Chaoyang District, Beijing

Applicant after: China Resources biomedical Co.,Ltd.

Address before: 210032 room 218, business office building, No.9 Gaoxin Road, Jiangbei new district, Nanjing City, Jiangsu Province

Applicant before: Nanjing Mingde New Drug Development Co.,Ltd.

GR01 Patent grant
GR01 Patent grant