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
Prior art keywords
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)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (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)

Country Link
US (2) US9540415B2 (https=)
EP (1) EP3027637B1 (https=)
JP (1) JP6556129B2 (https=)
CN (2) CN105593237B (https=)
AU (1) AU2014296023B2 (https=)
BR (1) BR112016002268B1 (https=)
CA (1) CA2920017C (https=)
NZ (1) NZ716568A (https=)
WO (1) WO2015017813A2 (https=)

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
SMT202000070T1 (it) * 2014-05-29 2020-03-13 Bar Pharmaceuticals S R L Derivati del colano per l'uso del trattamento e/o la prevenzione di malattie mediate da fxr e tgr5/gpbar1
SG11201703717SA (en) 2014-11-06 2017-06-29 Enanta Pharm Inc Bile acid analogs an fxr/tgr5 agonists and methods of use thereof
EP3223823A4 (en) 2014-11-26 2018-10-17 Enanta Pharmaceuticals, Inc. Bile acid analogs 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
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
EP3256134A4 (en) 2015-02-11 2018-10-03 Enanta Pharmaceuticals, Inc. Bile acid analogs as fxr/tgr5 agonists and methods of use thereof
WO2016161003A1 (en) 2015-03-31 2016-10-06 Enanta Phamraceuticals, Inc. Bile acid derivatives as fxr/tgr5 agonists and methods of use thereof
JP2018519246A (ja) * 2015-04-28 2018-07-19 ジエンス ハンセン ファーマセウティカル グループ カンパニー リミテッド コール酸誘導体、及びその製造方法及び医薬用途
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
CA3252823A1 (en) 2016-06-13 2025-02-25 Gilead Sciences, Inc. Substituted tert-butyl-3-(2-chloro-phenyl)-3-hydroxyazetidine-1-carboxylate compounds
MX385718B (es) 2016-06-13 2025-03-18 Gilead Sciences Inc Compuestos moduladores de fxr (nr1h4).
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
CN110121347A (zh) 2016-11-29 2019-08-13 英安塔制药有限公司 制备磺酰脲胆汁酸衍生物的方法
US10472386B2 (en) 2017-02-14 2019-11-12 Enanta Pharmaceuticals, Inc. Bile acid derivatives as FXR agonists and methods of use thereof
PT3600309T (pt) 2017-03-28 2022-10-03 Gilead Sciences Inc Combinações terapêuticas para o tratamento de doenças hepáticas
BR112019020780A2 (pt) 2017-04-07 2020-04-28 Enanta Pharm Inc processo para preparação de derivados de ácido biliar de carbamato de sulfonila
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
EP3911647B1 (en) 2019-01-15 2023-12-13 Gilead Sciences, Inc. Isoxazole compound as fxr agonist and pharmaceutical compositions comprising same
CA3233305A1 (en) 2019-02-19 2020-08-27 Gilead Sciences, Inc. Solid forms of fxr agonists
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
WO1987002367A2 (en) 1985-10-18 1987-04-23 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
JP2008509912A (ja) 2004-08-10 2008-04-03 エグゼリクシス， インコーポレイテッド 医薬品としての複素環化合物
CN101395170A (zh) * 2006-02-14 2009-03-25 英特塞普特药品公司 用于预防或治疗fxr介导的疾病或状态的作为fxr配体的胆汁酸衍生物
US7932244B2 (en) * 2006-06-27 2011-04-26 Intercept Pharmaceuticals, Inc. Bile acid derivatives as FXR ligands for the prevention or treatment of FXR-mediated diseases or conditions
WO2011022838A1 (en) 2009-08-25 2011-03-03 British Columbia Cancer Agency Branch Polyhydroxylated bile acids for treatment of biliary disorders
US20110071100A1 (en) * 2008-05-05 2011-03-24 Tiltan Pharma Ltd. Sulfobetaines for cancer, obesity, macular degeneration, neurodegenerative diseases
WO2010014836A2 (en) 2008-07-30 2010-02-04 Intercept Pharmaceuticals, Inc. Tgr5 modulators and methods of use thereof
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

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

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