KR102546748B1 - 스테로이드 FXR 조절인자를 제조하기 위한 중간체로서의 6α-알킬-3,7-다이온 스테로이드 - Google Patents

스테로이드 FXR 조절인자를 제조하기 위한 중간체로서의 6α-알킬-3,7-다이온 스테로이드 Download PDF

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KR102546748B1
KR102546748B1 KR1020177016857A KR20177016857A KR102546748B1 KR 102546748 B1 KR102546748 B1 KR 102546748B1 KR 1020177016857 A KR1020177016857 A KR 1020177016857A KR 20177016857 A KR20177016857 A KR 20177016857A KR 102546748 B1 KR102546748 B1 KR 102546748B1
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KR20170104453A (ko
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알렉산더 웨이머스-윌슨
조피아 콤스타
제임스 보델
로라 월리스
리스 배철러
칼 오터
이안 데이비스
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엔제트피 유케이 리미티드
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Priority claimed from GBGB1505676.5A external-priority patent/GB201505676D0/en
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    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
    • C07J9/005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
    • C07J71/0005—Oxygen-containing hetero ring
    • C07J71/001—Oxiranes

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Steroid Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
KR1020177016857A 2014-11-19 2015-11-19 스테로이드 FXR 조절인자를 제조하기 위한 중간체로서의 6α-알킬-3,7-다이온 스테로이드 Active KR102546748B1 (ko)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
GBGB1420593.4A GB201420593D0 (en) 2014-11-19 2014-11-19 Compounds
GB1420593.4 2014-11-19
GBGB1420594.2A GB201420594D0 (en) 2014-11-19 2014-11-19 Compounds
GB1420594.2 2014-11-19
GBGB1505676.5A GB201505676D0 (en) 2015-04-01 2015-04-01 Compounds
GB1505676.5 2015-04-01
PCT/GB2015/053518 WO2016079519A1 (en) 2014-11-19 2015-11-19 6.alpha.-alkyl-3,7-dione steroids as intermediates for the production of steroidal fxr modulators

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KR20170104453A KR20170104453A (ko) 2017-09-15
KR102546748B1 true KR102546748B1 (ko) 2023-06-22

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US (1) US10538550B2 (https=)
EP (1) EP3221333B1 (https=)
JP (1) JP6735748B2 (https=)
KR (1) KR102546748B1 (https=)
CN (1) CN107108688B (https=)
CA (1) CA2968305A1 (https=)
DK (1) DK3221333T3 (https=)
EA (1) EA034739B1 (https=)
ES (1) ES2748692T3 (https=)
MX (1) MX375865B (https=)
PL (1) PL3221333T3 (https=)
TW (1) TWI686401B (https=)
WO (1) WO2016079519A1 (https=)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10131688B2 (en) 2014-11-19 2018-11-20 NZP UK Limited 5.beta.-6-alkyl-7-hydroxy-3-one steroids as intermediates for the production of steroidal FXR modulators
KR102526631B1 (ko) 2014-11-19 2023-04-27 엔제트피 유케이 리미티드 스테로이드 fxr 조절인자를 제조하기 위한 중간체로서의 6-알킬-7-하이드록시-4-엔-3-온 스테로이드
TWI688571B (zh) 2014-11-19 2020-03-21 英商Ｎｚｐ英國有限公司 化合物（四）
WO2017111979A1 (en) * 2015-12-22 2017-06-29 Intercept Pharmaceuticals, Inc. Polymorphic crystalline forms of obeticholic acid
GB201608779D0 (en) * 2016-05-18 2016-06-29 Dextra Lab Ltd Methods and compounds
GB201608776D0 (en) 2016-05-18 2016-06-29 Dextra Lab Ltd Methods and compounds
GB201608777D0 (en) 2016-05-18 2016-06-29 Dextra Lab Ltd Compounds
EP3431486A1 (en) 2017-07-18 2019-01-23 Bionice, S.L.U. Process and intermediates for the synthesis of obeticholic acid and derivatives thereof
GB201812382D0 (en) 2018-07-30 2018-09-12 Nzp Uk Ltd Compounds
US12186329B2 (en) 2018-08-23 2025-01-07 President And Fellows Of Harvard College Compositions and methods related to cholic acid 7-sulfate as a treatment for diabetes
CN111138509B (zh) * 2018-11-02 2022-12-06 东莞东阳光药物研发有限公司 奥贝胆酸的制备方法
EP3890745B1 (en) * 2018-12-04 2025-11-19 President and Fellows of Harvard College Synthetic derivatives of cholic acid 7-sulfate and uses thereof
KR20250171471A (ko) 2019-05-10 2025-12-08 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 장 박테리아 담즙산 대사의 소분자 조정제

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006122977A2 (en) 2005-05-19 2006-11-23 Erregierre S.P.A. PROCESS FOR PREPARING 3α(β)-7α(β)-DIHYDROXY-6α(β)-ALKYL-5β-CHOLANIC ACID

Family Cites Families (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2624748A (en) 1950-09-09 1953-01-06 Upjohn Co Bisnorchola-4, 6-dien-3-one-22-al
US4289872A (en) 1979-04-06 1981-09-15 Allied Corporation Macromolecular highly branched homogeneous compound based on lysine units
US5229490A (en) 1987-05-06 1993-07-20 The Rockefeller University Multiple antigen peptide system
WO1993021259A1 (en) 1992-04-14 1993-10-28 Cornell Research Foundation Inc. Dendritic based macromolecules and method of production
AU6392894A (en) 1993-02-26 1994-09-14 Magainin Pharmaceuticals, Inc. Chemical synthesis of squalamine
US5643575A (en) 1993-10-27 1997-07-01 Enzon, Inc. Non-antigenic branched polymer conjugates
US5932462A (en) 1995-01-10 1999-08-03 Shearwater Polymers, Inc. Multiarmed, monofunctional, polymer for coupling to molecules and surfaces
AU2002308295B2 (en) * 2001-03-12 2007-08-23 Intercept Pharmaceuticals, Inc. Steroids as agonists for FXR
US20090062256A1 (en) 2001-06-01 2009-03-05 Bristol-Myers Squibb Pharma Company LACTAMS SUBSTITUTED BY CYCLIC SUCCINATES AS INHIBITORS OF Abeta PROTEIN PRODUCTION
EP1446438A2 (en) 2001-11-07 2004-08-18 Nektar Therapeutics Al, Corporation Branched polymers and their conjugates
EP1568706A1 (en) 2004-02-26 2005-08-31 Intercept Pharmaceuticals, Inc. Novel steroid agonist for FXR
JP2007210888A (ja) * 2006-01-12 2007-08-23 Mitsubishi Chemicals Corp ステロイド化合物の製造方法
JP2010517931A (ja) 2006-02-14 2010-05-27 インターセプト ファーマシューティカルズ， インコーポレイテッド Ｆｘｒ媒介性の疾患または状態の予防または治療用のｆｘｒリガンドとしての胆汁酸誘導体
PT2040713E (pt) 2006-06-27 2014-10-13 Intercept Pharmaceuticals Inc Para a prevenção ou o tratamento de doenças ou estados clínicos mediados por fxr
AU2008209566C1 (en) 2007-01-19 2013-02-14 Intercept Pharmaceuticals, Inc. 23-substituted bile acids as TGR5 modulators and methods of use thereof
EA020310B1 (ru) 2008-07-30 2014-10-30 Интерсепт Фармасьютикалз, Инк. Модуляторы рецептора tgr5 и их применение
CN102282157B (zh) 2008-11-19 2017-02-22 英特塞普特医药品公司 G蛋白偶联受体5(tgr5)调节剂及其使用方法
ES2663948T3 (es) 2008-11-19 2018-04-17 Intercept Pharmaceuticals, Inc. Moduladores de TGR5 y método de uso de los mismos
US8829213B2 (en) 2009-07-29 2014-09-09 The University Of Chicago Liver X receptor agonists
NZ734451A (en) 2012-06-19 2018-12-21 Intercept Pharmaceuticals Inc Preparation, uses and solid forms of obeticholic acid
AU2013334122B2 (en) 2012-10-26 2017-11-02 Intercept Pharmaceuticals, Inc. Process for preparing bile acid derivatives
SG11201503697TA (en) 2012-11-28 2015-06-29 Intercept Pharmaceuticals Inc Treatment of pulmonary disease
US20140206657A1 (en) * 2013-01-18 2014-07-24 City Of Hope Bile acid analog tgr5 agonists
CA2912139C (en) 2013-05-14 2021-04-20 Roberto Pellicciari 11-hydroxyl-derivatives of bile acids and amino acid conjugates thereof as farnesoid x receptor modulators
JP2016521683A (ja) 2013-05-24 2016-07-25 ネステク ソシエテ アノニム 過敏性腸症候群の診断を予測するための経路特異的なアッセイ
WO2015183794A1 (en) 2014-05-27 2015-12-03 City Of Hope Tgr5 agonist complexes for treating diabetes and cancer
US10407462B2 (en) 2014-05-29 2019-09-10 Bar Pharmaceuticals S.R.L. Cholane derivatives for use in the treatment and/or prevention of FXR and TGR5/GPBAR1 mediated diseases
WO2016073767A1 (en) 2014-11-06 2016-05-12 Enanta Pharmaceuticals, Inc. Bile acid analogs an fxr/tgr5 agonists and methods of use thereof
KR102526631B1 (ko) 2014-11-19 2023-04-27 엔제트피 유케이 리미티드 스테로이드 fxr 조절인자를 제조하기 위한 중간체로서의 6-알킬-7-하이드록시-4-엔-3-온 스테로이드
TWI688571B (zh) 2014-11-19 2020-03-21 英商Ｎｚｐ英國有限公司 化合物（四）
US10131688B2 (en) 2014-11-19 2018-11-20 NZP UK Limited 5.beta.-6-alkyl-7-hydroxy-3-one steroids as intermediates for the production of steroidal FXR modulators
US10208081B2 (en) 2014-11-26 2019-02-19 Enanta Pharmaceuticals, Inc. Bile acid derivatives as FXR/TGR5 agonists and methods of use thereof
WO2016086134A1 (en) 2014-11-26 2016-06-02 Enanta Pharmaceuticals, Inc. Bile acid derivatives as fxr/tgr5 agonists and methods of use thereof
JP2017535570A (ja) 2014-11-26 2017-11-30 エナンタ ファーマシューティカルズ インコーポレイテッド Ｆｘｒ／ｔｇｒ５アゴニストとしての胆汁酸類似体およびその使用方法
US11578097B2 (en) 2014-11-26 2023-02-14 Enanta Pharmaceuticals, Inc. Tetrazole derivatives of bile acids as FXR/TGR5 agonists and methods of use thereof
CN106279328A (zh) 2015-05-20 2017-01-04 重庆药友制药有限责任公司 一种制备6α-烷基鹅去氧胆酸的方法
EP3310801B1 (en) 2015-06-19 2021-04-07 Intercept Pharmaceuticals, Inc. Tgr5 modulators and methods of use thereof
CN106397522A (zh) 2015-07-31 2017-02-15 中国人民解放军军事医学科学院毒物药物研究所 3,7‑二（叔丁基二甲基硅基氧基）‑6‑烯‑5β‑胆烷‑24‑酸甲酯
CN106478759A (zh) 2015-08-31 2017-03-08 陕西合成药业股份有限公司 奥贝胆酸衍生物及其制备方法和用途
CN106478756A (zh) 2015-09-02 2017-03-08 中美华世通生物医药科技（武汉）有限公司 Oca-e单晶及其制备方法和用途
CN106518946A (zh) 2015-09-10 2017-03-22 上海迪诺医药科技有限公司 磺酰脲衍生物、其药物组合物及应用

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006122977A2 (en) 2005-05-19 2006-11-23 Erregierre S.P.A. PROCESS FOR PREPARING 3α(β)-7α(β)-DIHYDROXY-6α(β)-ALKYL-5β-CHOLANIC ACID
JP2008540612A (ja) 2005-05-19 2008-11-20 エレジーレ ソシエタ ペル アチオニ ３α（β）−７α（β）−ジヒドロキシ−６α（β）−アルキル−５β−コラン酸の調製方法

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EP3221333A1 (en) 2017-09-27
WO2016079519A1 (en) 2016-05-26
EA034739B1 (ru) 2020-03-16
WO2016079519A9 (en) 2018-08-09
CA2968305A1 (en) 2016-05-26
TW201632538A (zh) 2016-09-16
MX375865B (es) 2025-03-07
HK1244287A1 (en) 2018-08-03
EP3221333B1 (en) 2019-07-24
CN107108688A (zh) 2017-08-29
CN107108688B (zh) 2019-10-29
US10538550B2 (en) 2020-01-21
DK3221333T3 (da) 2019-09-30
EA201790879A1 (ru) 2017-11-30
KR20170104453A (ko) 2017-09-15
ES2748692T3 (es) 2020-03-17
MX2017006565A (es) 2018-01-26
US20180340006A1 (en) 2018-11-29
JP6735748B2 (ja) 2020-08-05
JP2017538690A (ja) 2017-12-28
TWI686401B (zh) 2020-03-01
PL3221333T3 (pl) 2020-01-31

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