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CN109071468A - 一种杂环化合物及其制备方法和用途 - Google Patents

一种杂环化合物及其制备方法和用途 Download PDF

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Publication number
CN109071468A
CN109071468A CN201880001611.4A CN201880001611A CN109071468A CN 109071468 A CN109071468 A CN 109071468A CN 201880001611 A CN201880001611 A CN 201880001611A CN 109071468 A CN109071468 A CN 109071468A
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China
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compound
alkyl
base
halogenated
isoxazole
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CN201880001611.4A
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CN109071468B (zh
Inventor
刘钢
于华
杨定菊
何婷
康熙伟
蔡家强
刘金明
吴勇勇
曾宏
宋宏梅
苏东海
周信
谭玉婷
王利春
王晶翼
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Sichuan Kelun Biotech Biopharmaceutical Co Ltd
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Sichuan Kelun Biotech Biopharmaceutical Co Ltd
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    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A61K31/422—Oxazoles not condensed and containing further 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4245—Oxadiazoles
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • 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
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Urology & Nephrology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

本发明公开了类法尼醇X受体(FXR)激动剂化合物及其制备方法和用途。具体地，本发明提供一种含有杂环的FXR激动剂化合物，以及其立体异构体、互变异构体、多晶型物、溶剂化物(如水合物)、药学可接受的盐、酯、代谢物、N‑氧化物以及其化学保护的形式和前药。本发明还提供所述化合物的制备方法、包含所述化合物的药物组合物和药盒以及它们用于治疗由FXR介导的疾病或病症的用途。

Description

PCT国内申请，说明书已公开。

Claims (17)

  1. PCT国内申请，权利要求书已公开。
CN201880001611.4A 2017-01-20 2018-01-12 一种杂环化合物及其制备方法和用途 Active CN109071468B (zh)

Applications Claiming Priority (3)

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CN2017100469094 2017-01-20
CN201710046909 2017-01-20
PCT/CN2018/072398 WO2018133730A1 (zh) 2017-01-20 2018-01-12 一种杂环化合物及其制备方法和用途

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113412261A (zh) * 2019-04-08 2021-09-17 四川科伦博泰生物医药股份有限公司 苯并咪唑化合物、其制备方法及其用途
WO2023090858A1 (ko) * 2021-11-17 2023-05-25 일동제약(주) 아이속사졸 유도체의 제조 방법 및 그의 중간체

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EP3277286B1 (en) 2015-03-31 2021-04-21 Enanta Pharmaceuticals, Inc. Bile acid derivatives as fxr/tgr5 agonists and methods of use thereof
TW201808283A (zh) 2016-08-05 2018-03-16 廣東東陽光藥業有限公司 含氮三環化合物及其在藥物中的應用
US10450306B2 (en) 2016-10-04 2019-10-22 Enanta Pharmaceuticals, Inc. Isoxazole analogs as FXR agonists and methods of use thereof
US10597391B2 (en) 2016-10-26 2020-03-24 Enanta Pharmaceuticals, Inc. Urea-containing isoxazole derivatives as FXR agonists and methods of use thereof
US10689391B2 (en) 2017-12-12 2020-06-23 Enanta Pharmaceuticals, Inc. Isoxazole analogs as FXR agonists and methods of use thereof
CN110128432B (zh) 2018-02-02 2021-03-02 广东东阳光药业有限公司 含氮三环化合物及其在药物中的应用
WO2019160813A1 (en) 2018-02-14 2019-08-22 Enanta Pharmaceuticals, Inc. Isoxazole derivatives as fxr agonists and methods of use thereof
EP3886854A4 (en) 2018-11-30 2022-07-06 Nuvation Bio Inc. PYRROLE AND PYRAZOLE COMPOUNDS AND METHODS OF USE THERE
WO2020231917A1 (en) 2019-05-13 2020-11-19 Enanta Pharmaceuticals, Inc. Isoxazole derivatives as fxr agonists and methods of use thereof
EP4003350A1 (en) 2019-07-23 2022-06-01 Novartis AG Treatment comprising fxr agonists
CA3142905A1 (en) 2019-07-23 2021-01-28 Novartis Ag Combination treatment of liver diseases using fxr agonists
AU2020341135A1 (en) 2019-09-03 2022-04-07 Novartis Ag Treatment of liver disease or disorder comprising ActRII receptor antagonists
CN114401745A (zh) 2019-09-19 2022-04-26 诺华股份有限公司 包含fxr激动剂的治疗
WO2021064575A1 (en) 2019-09-30 2021-04-08 Novartis Ag Treatment comprising the use of fxr agonists
KR20220119424A (ko) 2019-12-20 2022-08-29 노파르티스 아게 인테그린 억제제를 사용한 간 질환의 조합 치료
WO2022101853A1 (en) 2020-11-16 2022-05-19 Novartis Ag Method of determining liver fibrosis

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CN101511813A (zh) * 2006-08-29 2009-08-19 菲尼克斯药品股份公司 杂环fxr结合化合物
CN102548974A (zh) * 2009-08-19 2012-07-04 菲尼克斯药品股份公司 新型fxr(nr1h4)结合和活性调节化合物
CN103702719A (zh) * 2011-07-13 2014-04-02 菲尼克斯药品股份公司 新型fxr（nr1h4）结合及活性调节化合物
WO2016096116A1 (en) * 2014-12-17 2016-06-23 Gilead Sciences, Inc. Novel fxr (nr1h4) modulating compounds

Patent Citations (5)

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CN101511813A (zh) * 2006-08-29 2009-08-19 菲尼克斯药品股份公司 杂环fxr结合化合物
CN102548974A (zh) * 2009-08-19 2012-07-04 菲尼克斯药品股份公司 新型fxr(nr1h4)结合和活性调节化合物
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113412261A (zh) * 2019-04-08 2021-09-17 四川科伦博泰生物医药股份有限公司 苯并咪唑化合物、其制备方法及其用途
WO2023090858A1 (ko) * 2021-11-17 2023-05-25 일동제약(주) 아이속사졸 유도체의 제조 방법 및 그의 중간체

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WO2018133730A1 (zh) 2018-07-26

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