CA2989167A1 - Tgr5 modulators and methods of use thereof - Google Patents

Tgr5 modulators and methods of use thereof Download PDF

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Publication number
CA2989167A1
CA2989167A1 CA2989167A CA2989167A CA2989167A1 CA 2989167 A1 CA2989167 A1 CA 2989167A1 CA 2989167 A CA2989167 A CA 2989167A CA 2989167 A CA2989167 A CA 2989167A CA 2989167 A1 CA2989167 A1 CA 2989167A1
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CA
Canada
Prior art keywords
mmol
compound
reduced pressure
under reduced
solution
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.)
Abandoned
Application number
CA2989167A
Other languages
English (en)
French (fr)
Inventor
Roberto Pellicciari
Antimo GIOIELLO
Antonio Macchiarulo
Francoise Perron-Sierra
Klaus Seedorf
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.)
Intercept Pharmaceuticals Inc
Original Assignee
Les Laboratoires Servier SAS
Intercept Pharmaceuticals 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 Les Laboratoires Servier SAS, Intercept Pharmaceuticals Inc filed Critical Les Laboratoires Servier SAS
Publication of CA2989167A1 publication Critical patent/CA2989167A1/en
Abandoned legal-status Critical Current

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    • 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
    • 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
    • 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
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • 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
    • A61P3/04—Anorexiants; Antiobesity agents
    • 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
    • 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
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
    • C07J31/006—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring the nitrogen atom being directly linked to the cyclopenta(a)hydro phenanthrene skeleton
    • C07J41/0016—Oximes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
    • C07J41/0055—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
    • C07J41/0055—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives
    • C07J41/0061—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives one of the carbon atoms being part of an amide group
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
    • C07J41/0094—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 containing nitrile radicals, including thiocyanide radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
    • C07J43/003—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
    • 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
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Toxicology (AREA)
  • Immunology (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Urology & Nephrology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Transplantation (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Steroid Compounds (AREA)
CA2989167A 2015-06-19 2016-06-16 Tgr5 modulators and methods of use thereof Abandoned CA2989167A1 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201562182081P 2015-06-19 2015-06-19
US62/182,081 2015-06-19
EP15305976.1 2015-06-24
EP15305976 2015-06-24
PCT/US2016/037812 WO2016205475A2 (en) 2015-06-19 2016-06-16 Tgr5 modulators and methods of use thereof

Publications (1)

Publication Number Publication Date
CA2989167A1 true CA2989167A1 (en) 2016-12-22

Family

ID=53489911

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2989167A Abandoned CA2989167A1 (en) 2015-06-19 2016-06-16 Tgr5 modulators and methods of use thereof

Country Status (14)

Country Link
EP (1) EP3310801B1 (https=)
JP (1) JP6861703B2 (https=)
KR (1) KR20180043247A (https=)
CN (1) CN107771180B (https=)
AU (1) AU2016280806B2 (https=)
CA (1) CA2989167A1 (https=)
IL (1) IL256085B (https=)
MX (1) MX380972B (https=)
PL (1) PL3310801T3 (https=)
PT (1) PT3310801T (https=)
SI (1) SI3310801T1 (https=)
TW (1) TW201700447A (https=)
UY (1) UY36738A (https=)
WO (1) WO2016205475A2 (https=)

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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
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
US10538550B2 (en) 2014-11-19 2020-01-21 NZP UK Limited 6.alpha.-alkyl-3,7-dione 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
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
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
MX2017010376A (es) 2015-02-11 2017-12-20 Enanta Pharm Inc Análogos de ácido biliar como agonistas de fxr/tgr5 y métodos para el uso de los mismos.
CA2981503C (en) 2015-03-31 2023-09-19 Enanta Pharmaceuticals, Inc. Bile acid derivatives as fxr/tgr5 agonists and methods of use thereof
CN111116699B (zh) * 2015-04-28 2023-02-28 江苏豪森药业集团有限公司 胆酸衍生物及其制备方法和医药用途
US10800807B2 (en) 2015-06-19 2020-10-13 Intercept Pharmaceuticals, Inc. TGR5 modulators and methods of use thereof
US20170196893A1 (en) * 2016-01-07 2017-07-13 The Board Of Trustees Of The Leland Stanford Junior University Treatment of inflammatory demyelinating disease with agonists of farnesoid x receptor
US10323060B2 (en) 2016-02-23 2019-06-18 Enanta Pharmaceuticals, Inc. Benzoic acid derivatives of bile acid as FXR/TGR5 agonists and methods of use thereof
WO2017147174A1 (en) 2016-02-23 2017-08-31 Enanta Pharmaceuticals, Inc. Heteroaryl containing bile acid analogs as fxr/tgr5 agonists and methods of use thereof
GB201608777D0 (en) 2016-05-18 2016-06-29 Dextra Lab Ltd Compounds
CA3045023A1 (en) 2016-11-29 2018-06-07 Enanta Pharmaceuticals, Inc. Process for preparation of sulfonylurea bile acid derivatives
US10472386B2 (en) 2017-02-14 2019-11-12 Enanta Pharmaceuticals, Inc. Bile acid derivatives as FXR agonists and methods of use thereof
CA3058754A1 (en) 2017-04-07 2018-10-11 Enanta Pharmaceuticals, Inc. Process for preparation of sulfonyl carbamate bile acid derivatives
CN109134572A (zh) * 2017-06-19 2019-01-04 中国科学院上海药物研究所 胆酸衍生物及其制备方法和用途
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
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
CN112334476B (zh) * 2019-09-09 2022-03-15 邦泰生物工程(深圳)有限公司 一种合成鹅去氧胆酸的方法及其应用
KR20220150270A (ko) 2019-10-07 2022-11-10 칼리오페, 인크. Gpr119 효능제
TW202140440A (zh) 2020-02-28 2021-11-01 美商克力歐普股份有限公司 Gpr40激動劑
CN112300237A (zh) * 2020-04-13 2021-02-02 苏州恩泰新材料科技有限公司 海豹胆酸的制备方法及其应用
CN112341512A (zh) * 2020-04-13 2021-02-09 苏州恩泰新材料科技有限公司 由海豹胆酸制备鹅去氧胆酸的方法
WO2021236617A1 (en) 2020-05-19 2021-11-25 Kallyope, Inc. Ampk activators
CN116390925A (zh) 2020-06-26 2023-07-04 卡尔优普公司 Ampk活化剂
CN114276402B (zh) * 2022-01-05 2023-11-14 厦门大学 一种甾体衍生物及其在制备抗肿瘤药物中的应用
CN120271652B (zh) * 2025-05-27 2025-10-03 华南理工大学 噁二唑-甾体化合物、药物组合物和用途

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AU2008209566C1 (en) * 2007-01-19 2013-02-14 Intercept Pharmaceuticals, Inc. 23-substituted bile acids as TGR5 modulators and methods of use thereof
EP1947108A1 (en) * 2007-01-19 2008-07-23 Intercept Pharmaceuticals, Inc. TGR5 modulators and methods of use thereof
ES2663948T3 (es) * 2008-11-19 2018-04-17 Intercept Pharmaceuticals, Inc. Moduladores de TGR5 y método de uso de los mismos
SG11201610789SA (en) * 2014-06-25 2017-01-27 3M Innovative Properties Co Pressure sensitive adhesive composition including ultraviolet light-absorbing oligomer
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
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
US10208081B2 (en) * 2014-11-26 2019-02-19 Enanta Pharmaceuticals, Inc. Bile acid derivatives as FXR/TGR5 agonists and methods of use thereof
CN111116699B (zh) * 2015-04-28 2023-02-28 江苏豪森药业集团有限公司 胆酸衍生物及其制备方法和医药用途
TW201704251A (zh) * 2015-04-29 2017-02-01 正大天晴藥業集團股份有限公司 鵝去氧膽酸衍生物

Also Published As

Publication number Publication date
AU2016280806A1 (en) 2018-01-04
IL256085A (en) 2018-02-28
EP3310801B1 (en) 2021-04-07
AU2016280806B2 (en) 2021-01-28
PL3310801T3 (pl) 2021-11-22
SI3310801T1 (sl) 2021-10-29
TW201700447A (zh) 2017-01-01
JP2018518537A (ja) 2018-07-12
IL256085B (en) 2021-02-28
CN107771180A (zh) 2018-03-06
PT3310801T (pt) 2021-06-18
EP3310801A2 (en) 2018-04-25
WO2016205475A3 (en) 2017-02-23
UY36738A (es) 2017-01-31
WO2016205475A2 (en) 2016-12-22
MX2017016611A (es) 2018-05-15
JP6861703B2 (ja) 2021-04-21
CN107771180B (zh) 2021-03-23
KR20180043247A (ko) 2018-04-27
MX380972B (es) 2025-03-12

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Effective date: 20210510

FZDE Discontinued

Effective date: 20240130