AU2014296023B2 - Inhibitors of the farnesoid X receptor and uses in medicine - Google Patents

Inhibitors of the farnesoid X receptor and uses in medicine Download PDF

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Publication number
AU2014296023B2
AU2014296023B2 AU2014296023A AU2014296023A AU2014296023B2 AU 2014296023 B2 AU2014296023 B2 AU 2014296023B2 AU 2014296023 A AU2014296023 A AU 2014296023A AU 2014296023 A AU2014296023 A AU 2014296023A AU 2014296023 B2 AU2014296023 B2 AU 2014296023B2
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AU
Australia
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mice
fxr
mca
weeks
gly
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AU2014296023A
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AU2014296023A1 (en
Inventor
Shantu Amin
Dhimant Desai
Frank J. Gonzalez
Changtao Jiang
Fei Li
James B. Mitchell
Andrew D. PATTERSON
Cen XIE
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Penn State Research Foundation
US Department of Health and Human Services
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Penn State Research Foundation
Government of the United States of America
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    • 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
    • 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
    • A61P3/04—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
    • 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
    • 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
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
    • A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
    • 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
    • C07J41/0033—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
    • C07J41/0066—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 a carbon atom forming part of an amide group
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Diabetes (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Child & Adolescent Psychology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Steroid Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
AU2014296023A 2013-08-01 2014-08-01 Inhibitors of the farnesoid X receptor and uses in medicine Ceased AU2014296023B2 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201361861109P 2013-08-01 2013-08-01
US61/861,109 2013-08-01
US201462004436P 2014-05-29 2014-05-29
US62/004,436 2014-05-29
PCT/US2014/049460 WO2015017813A2 (en) 2013-08-01 2014-08-01 Inhibitors of the farnesoid x receptor and uses in medicine

Publications (2)

Publication Number Publication Date
AU2014296023A1 AU2014296023A1 (en) 2016-02-25
AU2014296023B2 true AU2014296023B2 (en) 2020-02-06

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
AU2014296023A Ceased AU2014296023B2 (en) 2013-08-01 2014-08-01 Inhibitors of the farnesoid X receptor and uses in medicine

Country Status (9)

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US (2) US9540415B2 (enExample)
EP (1) EP3027637B1 (enExample)
JP (1) JP6556129B2 (enExample)
CN (2) CN110437297B9 (enExample)
AU (1) AU2014296023B2 (enExample)
BR (1) BR112016002268B1 (enExample)
CA (1) CA2920017C (enExample)
NZ (1) NZ716568A (enExample)
WO (1) WO2015017813A2 (enExample)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2545964A1 (en) 2011-07-13 2013-01-16 Phenex Pharmaceuticals AG Novel FXR (NR1H4) binding and activity modulating compounds
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
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
US10208081B2 (en) 2014-11-26 2019-02-19 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
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
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
CA2968836C (en) 2016-06-13 2025-09-02 Gilead Sciences, Inc. FXR MODULATING COMPOUNDS (NR1H4)
NZ748641A (en) 2016-06-13 2020-04-24 Gilead Sciences Inc Fxr (nr1h4) modulating compounds
IT201600068742A1 (it) * 2016-07-01 2018-01-01 Bar Pharmaceuticals Soc A Responsabilita Limitata Derivati dell'acido iodesossicolico e loro uso
CN106237332A (zh) * 2016-08-11 2016-12-21 河南大学 核受体fxr在肝癌干细胞靶向治疗中的应用
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
SI4122464T1 (sl) 2017-03-28 2024-07-31 Gilead Sciences, Inc. Terapevtske kombinacije za zdravljenje bolezni jeter
CA3058754A1 (en) 2017-04-07 2018-10-11 Enanta Pharmaceuticals, Inc. Process for preparation of sulfonyl carbamate bile acid derivatives
US11028111B2 (en) 2017-12-19 2021-06-08 Xi' An Biocare Pharma Ltd. Compound for treating metabolic diseases and preparation method and use thereof
IT201800005598A1 (it) 2018-05-22 2019-11-22 Ossadiazoli come antagonisti del recettore fxr
PT3911647T (pt) 2019-01-15 2024-03-04 Gilead Sciences Inc Composto de isoxazole como agonista de fxr e composições farmacêuticas que o contenham
JP2022519906A (ja) 2019-02-19 2022-03-25 ギリアード サイエンシーズ， インコーポレイテッド Ｆｘｒアゴニストの固体形態
CN112409435B (zh) * 2019-08-23 2023-07-18 深圳云合医药科技合伙企业(有限合伙) 胆汁酸衍生物及其组合物和应用
US20220378766A1 (en) * 2021-05-25 2022-12-01 Louis Habash Modulating expression level of a gene encoding an uncoupling protein by treating a human subject with a nitroxide
US20230128120A1 (en) * 2021-10-21 2023-04-27 University Of Washington Omega muricholic acid as a pregnane x receptor ligand for treating hepato-intestinal diseases

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000037077A1 (en) * 1998-12-23 2000-06-29 Glaxo Group Limited Assays for ligands for nuclear receptors

Family Cites Families (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4235871A (en) 1978-02-24 1980-11-25 Papahadjopoulos Demetrios P Method of encapsulating biologically active materials in lipid vesicles
US4501728A (en) 1983-01-06 1985-02-26 Technology Unlimited, Inc. Masking of liposomes from RES recognition
US5019369A (en) 1984-10-22 1991-05-28 Vestar, Inc. Method of targeting tumors in humans
US4917826A (en) 1985-10-18 1990-04-17 The Upjohn Company Cyclic hydrocarbons with an aminoalkyl sidechain
US4837028A (en) 1986-12-24 1989-06-06 Liposome Technology, Inc. Liposomes with enhanced circulation time
IT1222395B (it) * 1987-07-30 1990-09-05 Pierrel Spa Composizione farmaceutica per somministrazione intranasale comprendente l'ormone ghrh,un agonista colinergico e/o un sale biliare
IT1219733B (it) * 1988-06-28 1990-05-24 Istituto Chemioterapico Di Lod Derivato dell' acido ursodesossicolico
JPH0637392B2 (ja) * 1988-11-25 1994-05-18 健二 片桐 胆汁うっ滞改善剤
IT1229570B (it) 1989-04-17 1991-09-04 Giuliani Spa Derivati fluorurati di acidi biliari, loro preparazione e composizioni farmaceutiche che li contengono.
IT1264131B1 (it) * 1993-04-16 1996-09-16 D R Drug Research Srl Derivato dell'acido iodesossicolico
US6551623B1 (en) * 1993-09-09 2003-04-22 Lorus Therapeutics Inc. Immunomodulating compositions from bile
GB9320597D0 (en) * 1993-10-06 1993-11-24 Proteus Molecular Design Improvements in and realting to vaccines
IT1299270B1 (it) * 1998-05-15 2000-02-29 Moreno Paolini Acidi biliari come induttori del sistema citocromo p450-dipendente, in particolare ad attivita' anticolestatica
US20020132223A1 (en) * 1999-03-26 2002-09-19 City Of Hope Methods for modulating activity of the FXR nuclear receptor
WO2002094865A1 (en) * 2001-05-24 2002-11-28 Smithkline Beecham Corporation Nonhuman pregnane x receptor sequences for use in comparative pharmacology
US7595311B2 (en) 2002-05-24 2009-09-29 Exelixis, Inc. Azepinoindole derivatives as pharmaceutical agents
MX2007001539A (es) 2004-08-10 2007-04-23 Exelisis Inc Compuestos heterociclicos como agentes farmaceuticos.
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
WO2009136396A2 (en) * 2008-05-05 2009-11-12 Tiltan Pharma Ltd. Sulfobetaines for therapy
EA020310B1 (ru) * 2008-07-30 2014-10-30 Интерсепт Фармасьютикалз, Инк. Модуляторы рецептора tgr5 и их применение
CN101891791B (zh) * 2009-05-22 2012-10-03 中国科学院上海应用物理研究所 一种标记胆汁酸衍生物及其参照化合物、制备方法和应用
EP2470553B1 (en) * 2009-08-25 2024-06-19 Qing Bile Therapeutics Inc. Polyhydroxylated bile acids for treatment of biliary disorders

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000037077A1 (en) * 1998-12-23 2000-06-29 Glaxo Group Limited Assays for ligands for nuclear receptors

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
JIAQI DAI ET AL, "Impact of bile acids on the growth of human cholangiocarcinoma via FXR", JOURNAL OF HEMATOLOGY & ONCOLOGY, BIOMED CENTRAL LTD, LONDON UK, (2011-10-12), vol. 4, no. 1, doi:10.1186/1756-8722-4-41, ISSN 1756-8722, page 41 *
SAYIN, S.I. et al., Cell Metabolism (2013-02-05), vol. 17 no. 2, page 225-235, doi:10.1016/j.cmet.2013.01.003 *

Also Published As

Publication number Publication date
CN110437297B9 (zh) 2022-01-11
WO2015017813A2 (en) 2015-02-05
NZ716568A (en) 2021-07-30
CA2920017A1 (en) 2015-02-05
BR112016002268B1 (pt) 2022-11-01
CN105593237B (zh) 2019-06-04
CA2920017C (en) 2021-11-23
EP3027637A2 (en) 2016-06-08
BR112016002268A2 (pt) 2017-08-01
CN110437297A (zh) 2019-11-12
US20160159851A1 (en) 2016-06-09
US20170152283A1 (en) 2017-06-01
US9540415B2 (en) 2017-01-10
CN105593237A (zh) 2016-05-18
JP2016527277A (ja) 2016-09-08
EP3027637B1 (en) 2019-10-09
WO2015017813A3 (en) 2015-04-02
JP6556129B2 (ja) 2019-08-07
US10233209B2 (en) 2019-03-19
AU2014296023A1 (en) 2016-02-25
CN110437297B (zh) 2021-12-21

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