CN102548974B - 新型fxr(nr1h4)结合和活性调节化合物 - Google Patents

新型fxr(nr1h4)结合和活性调节化合物 Download PDF

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CN102548974B
CN102548974B CN201080037300.7A CN201080037300A CN102548974B CN 102548974 B CN102548974 B CN 102548974B CN 201080037300 A CN201080037300 A CN 201080037300A CN 102548974 B CN102548974 B CN 102548974B
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cyclopropyl
compound
phenyl
dichlorophenyl
mmol
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CN102548974A (zh
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克洛·克伦默泽
乌尔里希·阿贝尔
C·斯蒂奈克
O·金策尔
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Gilead Sciences Inc
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Phenex Pharmaceuticals AG
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CN201080037300.7A 2009-08-19 2010-08-19 新型fxr(nr1h4)结合和活性调节化合物 Active CN102548974B (zh)

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Application Number Priority Date Filing Date Title
US23511709P 2009-08-19 2009-08-19
EP09010676.6 2009-08-19
EP09010676A EP2289883A1 (en) 2009-08-19 2009-08-19 Novel FXR (NR1H4) binding and activity modulating compounds
US61/235,117 2009-08-19
PCT/EP2010/005093 WO2011020615A1 (en) 2009-08-19 2010-08-19 Novel fxr (nr1h4 ) binding and activity modulating compounds

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Families Citing this family (80)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CU24152B1 (es) * 2010-12-20 2016-02-29 Irm Llc 1,2 oxazol-8-azabiciclo[3,2,1]octano 8 il como moduladores de fxr
EP2545964A1 (en) 2011-07-13 2013-01-16 Phenex Pharmaceuticals AG Novel FXR (NR1H4) binding and activity modulating compounds
IL253437A0 (en) * 2011-07-13 2017-09-28 Gilead Sciences Inc New compounds modulate fxr (nr1h4) activity and bind
WO2013037482A1 (en) 2011-09-15 2013-03-21 Phenex Pharmaceuticals Ag Farnesoid x receptor agonists for cancer treatment and prevention
JP6224097B2 (ja) 2012-06-26 2017-11-01 サニオナ・エイピイエス フェニルトリアゾール誘導体及びｇａｂａａ受受容体複合体を調節するための該フェニルトリアゾール誘導体の使用
WO2014001278A1 (en) 2012-06-26 2014-01-03 Aniona Aps A phenyl triazole derivative and its use for modulating the gabaa receptor complex
JP6223443B2 (ja) 2012-06-26 2017-11-01 サニオナ・エイピイエス フェニルトリアゾール誘導体及びｇａｂａａ受容体複合体を調節するための該フェニルトリアゾール誘導体の使用
WO2014001280A1 (en) 2012-06-26 2014-01-03 Aniona Aps A phenyl triazole derivative and its use for modulating the gabaa receptor complex
WO2014001279A1 (en) 2012-06-26 2014-01-03 Aniona Aps A phenyl triazole derivative and its use for modulating the gabaa receptor complex
JO3215B1 (ar) 2012-08-09 2018-03-08 Phenex Pharmaceuticals Ag حلقات غير متجانسة بها 5 ذرات تحتوي على النيتروجين بها استبدال بكربوكساميد أو سلفوناميد كمعدلات لمستقبل نووي غير محمي RORy
CN102976946A (zh) * 2012-12-13 2013-03-20 烟台泰和新材料股份有限公司 合成间苯二甲酸二甲酯的方法
CN103232378B (zh) * 2013-04-27 2015-11-18 国家海洋局第三海洋研究所 一种含6-溴吲哚满二酮的荔枝螺提取物及制备方法与其抗癌应用
LT3043865T (lt) 2013-09-11 2021-04-26 Institut National De La Santé Et De La Recherche Médicale (Inserm) Hepatito b viruso infekcijos gydymo būdai ir farmacinė kompozicija
MX2017003933A (es) 2014-09-24 2017-06-30 Gilead Sciences Inc Metodos de tratamiento de la enfermedad hepatica.
EP3006939A1 (en) 2014-10-06 2016-04-13 Gilead Sciences, Inc. Histidine-rich Glycoprotein as a marker for hepatic Farnesoid X receptor activation
US10208081B2 (en) 2014-11-26 2019-02-19 Enanta Pharmaceuticals, Inc. Bile acid derivatives as FXR/TGR5 agonists and methods of use thereof
EP3034501A1 (en) 2014-12-17 2016-06-22 Gilead Sciences, Inc. Hydroxy containing FXR (NR1H4) modulating compounds
EP3034499A1 (en) 2014-12-17 2016-06-22 Gilead Sciences, Inc. Novel FXR (NR1H4) modulating compounds
ES2905872T3 (es) 2015-02-06 2022-04-12 Intercept Pharmaceuticals Inc Composiciones farmacéuticas para terapia combinada
TWI698430B (zh) 2015-02-13 2020-07-11 南北兄弟藥業投資有限公司 三環化合物及其在藥物中的應用
NZ735126A (en) 2015-03-31 2022-10-28 Enanta Pharm Inc Bile acid derivatives as fxr/tgr5 agonists and methods of use thereof
CN107613986A (zh) 2015-04-07 2018-01-19 英特塞普特医药品公司 用于组合疗法的药物组合物
CN106995416A (zh) * 2016-01-26 2017-08-01 上海翰森生物医药科技有限公司 Fxr激动剂及其制备方法和应用
WO2017128896A1 (zh) * 2016-01-26 2017-08-03 江苏豪森药业集团有限公司 Fxr激动剂及其制备方法和应用
CN107021957A (zh) * 2016-02-01 2017-08-08 山东轩竹医药科技有限公司 Fxr受体激动剂
JPWO2017170434A1 (ja) 2016-03-28 2019-01-31 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アゴニストとａｒｂの組み合わせ医薬
WO2017189652A1 (en) 2016-04-26 2017-11-02 Enanta Pharmaceuticals, Inc. Isoxazole derivatives as fxr agonists and methods of use thereof
WO2017189663A1 (en) 2016-04-26 2017-11-02 Enanta Pharmaceuticals, Inc. Isoxazole derivatives as fxr agonists and methods of use thereof
US10080742B2 (en) 2016-04-26 2018-09-25 Enanta Pharmaceuticals, Inc. Isoxazole derivatives as FXR agonists and methods of use thereof
US10149835B2 (en) 2016-05-18 2018-12-11 Elmore Patent Law Group, P.C. Isoxazole derivatives as FXR agonists and methods of use thereof
WO2017201152A1 (en) * 2016-05-18 2017-11-23 Enanta Pharmaceuticals, Inc. Isoxazole derivatives as fxr agonists and methods of use thereof
WO2017201150A1 (en) * 2016-05-18 2017-11-23 Enanta Pharmaceuticals, Inc. Isoxazole analogs as fxr agonists and methods of use thereof
AR108711A1 (es) * 2016-06-13 2018-09-19 Gilead Sciences Inc Compuestos moduladores de fxr (nr1h4)
CA3252823A1 (en) 2016-06-13 2025-02-25 Gilead Sciences Inc Fxr (nr1h4) modulating compounds
SI3730487T1 (sl) * 2016-06-13 2022-08-31 Gilead Sciences, Inc. Azetidinski derivati kot modulatorji FXR (NR1H4)
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
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
EP3954684A1 (en) 2016-08-23 2022-02-16 Ardelyx, Inc. Process for the preparation of hormone receptor modulators for treating metabolic conditions and disorders
WO2018039384A1 (en) 2016-08-23 2018-03-01 Ardelyx, Inc. Isoxazolyl-carbonyloxy azabicyclo[3.2.1]octanyl compounds as fxr activators
KR102205368B1 (ko) * 2016-09-14 2021-01-20 노파르티스 아게 Fxr 작용제의 신규 요법
KR20180036522A (ko) * 2016-09-30 2018-04-09 (주)나노믹스 스틸벤 유도체 및 그 제조 방법
CA3039124A1 (en) 2016-10-04 2018-04-12 Enanta Pharmaceuticals, Inc. Isoxazole analogs as fxr agonists and methods of use thereof
CN107973790A (zh) * 2016-10-22 2018-05-01 合帕吉恩治疗公司 杂环fxr调节剂
US10597391B2 (en) 2016-10-26 2020-03-24 Enanta Pharmaceuticals, Inc. Urea-containing isoxazole derivatives as FXR agonists and methods of use thereof
CN106588804B (zh) * 2016-12-09 2018-11-09 都创(上海)医药科技有限公司 一种作为类法尼醇x受体(fxr)的化合物的制备方法
WO2018133730A1 (zh) * 2017-01-20 2018-07-26 四川科伦博泰生物医药股份有限公司 一种杂环化合物及其制备方法和用途
CA3051776A1 (en) 2017-02-21 2018-08-30 Genfit Combination of a ppar and fxr agonist for the treatment of liver disorders
JP6906626B2 (ja) 2017-03-28 2021-07-21 ギリアード サイエンシーズ， インコーポレイテッド 肝疾患を処置するための治療的組み合わせ
EP3600293A1 (en) 2017-03-30 2020-02-05 Institut National de la Sante et de la Recherche Medicale (INSERM) Methods and pharmaceutical compositions for reducing persistence and expression of episomal viruses
CA3058754A1 (en) 2017-04-07 2018-10-11 Enanta Pharmaceuticals, Inc. Process for preparation of sulfonyl carbamate bile acid derivatives
WO2018190643A1 (en) * 2017-04-12 2018-10-18 Il Dong Pharmaceutical Co., Ltd. An isoxazole derivatives as nuclear receptor agonists and used thereof
RS62711B1 (sr) * 2017-04-12 2022-01-31 Il Dong Pharma Derivati izoksazola kao agonisti nuklearnih receptora i njihova upotreba
AU2018272359B2 (en) 2017-05-26 2022-03-03 Cspc Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd. Lactam compound as FXR receptor agonist
CN110944997B (zh) 2017-07-06 2021-04-09 轩竹生物科技有限公司 Fxr受体激动剂
EP3681881B1 (en) * 2017-09-14 2022-11-02 Ardelyx, Inc. Hormone receptor modulators for treating metabolic mutagenic and fibrotic conditions and disorders
CN111630051B (zh) 2017-11-01 2023-12-26 百时美施贵宝公司 作为法尼醇x受体调节剂的烯烃螺环化合物
KR102732404B1 (ko) 2017-11-01 2024-11-19 브리스톨-마이어스 스큅 컴퍼니 파르네소이드 x 수용체 조정제로서의 알켄 화합물
US11370785B2 (en) 2017-11-01 2022-06-28 Bristol-Myers Squibb Company Multicyclic compounds as farnesoid X receptor modulators
WO2019118571A1 (en) 2017-12-12 2019-06-20 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
US10829486B2 (en) 2018-02-14 2020-11-10 Enanta Pharmacueticals, Inc. Isoxazole derivatives as FXR agonists and methods of use thereof
AU2019263176B2 (en) * 2018-04-30 2025-02-27 The Trustees Of Indiana University Compounds for modulating DDAH and ADMA levels, as well as methods of using thereof to treat disease
BR102019014802A2 (pt) 2018-07-20 2020-02-04 Boehringer Ingelheim Int difluorometil-fenil triazóis
IL280520B2 (en) 2018-08-08 2023-11-01 Inorbit Therapeutics Ab Compounds useful in paranoid X receptor modulation and methods of making and using them
US11225473B2 (en) 2019-01-15 2022-01-18 Gilead Sciences, Inc. FXR (NR1H4) modulating compounds
CA3128416A1 (en) 2019-01-31 2020-08-06 The National Institutes of Pharmaceutical R&D Co., Ltd. Aromatic ring or heteroaromatic ring compounds, preparation method therefor and medical use thereof
EP3927683A1 (en) 2019-02-19 2021-12-29 Gilead Sciences, Inc. Solid forms of fxr agonists
US11555032B2 (en) 2019-05-13 2023-01-17 Enanta Pharmaceuticals, Inc. Isoxazole derivatives as FXR agonists and methods of use thereof
WO2020243590A1 (en) 2019-05-30 2020-12-03 Intercept Pharmaceuticals, Inc. Pharmaceutical compositions comprising a fxr agonist and a fibrate for use in the treatment of cholestatic liver disease
WO2021009332A1 (en) 2019-07-18 2021-01-21 Enyo Pharma Method for decreasing adverse-effects of interferon
CA3159163A1 (en) 2020-01-15 2021-07-22 Raphael Darteil Use of fxr agonists for treating an infection by hepatitis d virus
US11478533B2 (en) 2020-04-27 2022-10-25 Novo Nordisk A/S Semaglutide for use in medicine
CN113754541B (zh) * 2020-06-02 2025-01-03 深圳湾实验室 靶向eb病毒核抗原蛋白的小分子抑制剂、制备方法及其应用
CN114656460B (zh) 2020-12-22 2025-01-10 江苏天士力帝益药业有限公司 一种新型吡嗪结构fxr激动剂、制备方法及应用
CA3204800A1 (en) 2021-01-14 2022-07-21 Raphael Darteil Synergistic effect of a fxr agonist and ifn for the treatment of hbv infection
US20240216364A1 (en) 2021-04-28 2024-07-04 Enyo Pharma Strong potentiation of tlr3 agonists effects using fxr agonists as a combined treatment
WO2023090858A1 (ko) * 2021-11-17 2023-05-25 일동제약(주) 아이속사졸 유도체의 제조 방법 및 그의 중간체
KR102740618B1 (ko) * 2021-11-17 2024-12-10 유노비아 주식회사 아이속사졸 유도체의 제조 방법 및 그의 중간체
WO2023090859A1 (ko) * 2021-11-17 2023-05-25 일동제약(주) 아이속사졸 유도체의 제조 방법 및 그의 신규한 중간체
WO2024005586A1 (ko) * 2022-06-30 2024-01-04 일동제약(주) 아이속사졸 유도체 또는 이의 염의 신규한 결정형

Citations (15)

* 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
WO2003015771A1 (en) * 2001-08-13 2003-02-27 Lion Bioscience Ag Fxr nr1h4 nuclear receptor binding compounds
WO2003080803A2 (en) * 2002-03-21 2003-10-02 Smithkline Beecham Corporation Methods of using farnesoid x receptor (fxr) agonists
WO2004048349A1 (en) * 2002-11-22 2004-06-10 Smithkline Beecham Corporation Farnesoid x receptor agonists
WO2004087076A2 (en) * 2003-03-31 2004-10-14 The Rockefeller University Methods for inhibiting adipogenesis and for treating type 2 diabetes
WO2007076260A2 (en) * 2005-12-19 2007-07-05 Smithkline Beecham Corporation Farnesoid x receptor agonists
WO2007092751A2 (en) * 2006-02-03 2007-08-16 Eli Lilly And Company Compounds and methods for modulating fx-receptors
WO2007140174A2 (en) * 2006-05-24 2007-12-06 Eli Lilly And Company Compounds and methods for modulating fxr
WO2007140183A1 (en) * 2006-05-24 2007-12-06 Eli Lilly And Company Fxr agonists
WO2008025540A1 (en) * 2006-08-29 2008-03-06 Phenex Pharmaceuticals Ag Heterocyclic fxr binding compounds
WO2008025539A1 (en) * 2006-08-29 2008-03-06 Phenex Pharmaceuticals Ag Heterocyclic fxr binding compounds
WO2008051942A2 (en) * 2006-10-24 2008-05-02 Smithkline Beecham Corporation Farnesoid x receptor agonists
WO2008157270A1 (en) * 2007-06-13 2008-12-24 Smithkline Beecham Corporation Farnesoid x receptor agonists
WO2009005998A1 (en) * 2007-07-02 2009-01-08 Smithkline Beecham Corporation Farnesoid x receptor agonists
WO2009012125A1 (en) * 2007-07-16 2009-01-22 Eli Lilly And Company Compounds and methods for modulating fxr

Patent Citations (15)

* 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
WO2003015771A1 (en) * 2001-08-13 2003-02-27 Lion Bioscience Ag Fxr nr1h4 nuclear receptor binding compounds
WO2003080803A2 (en) * 2002-03-21 2003-10-02 Smithkline Beecham Corporation Methods of using farnesoid x receptor (fxr) agonists
WO2004048349A1 (en) * 2002-11-22 2004-06-10 Smithkline Beecham Corporation Farnesoid x receptor agonists
WO2004087076A2 (en) * 2003-03-31 2004-10-14 The Rockefeller University Methods for inhibiting adipogenesis and for treating type 2 diabetes
WO2007076260A2 (en) * 2005-12-19 2007-07-05 Smithkline Beecham Corporation Farnesoid x receptor agonists
WO2007092751A2 (en) * 2006-02-03 2007-08-16 Eli Lilly And Company Compounds and methods for modulating fx-receptors
WO2007140174A2 (en) * 2006-05-24 2007-12-06 Eli Lilly And Company Compounds and methods for modulating fxr
WO2007140183A1 (en) * 2006-05-24 2007-12-06 Eli Lilly And Company Fxr agonists
WO2008025540A1 (en) * 2006-08-29 2008-03-06 Phenex Pharmaceuticals Ag Heterocyclic fxr binding compounds
WO2008025539A1 (en) * 2006-08-29 2008-03-06 Phenex Pharmaceuticals Ag Heterocyclic fxr binding compounds
WO2008051942A2 (en) * 2006-10-24 2008-05-02 Smithkline Beecham Corporation Farnesoid x receptor agonists
WO2008157270A1 (en) * 2007-06-13 2008-12-24 Smithkline Beecham Corporation Farnesoid x receptor agonists
WO2009005998A1 (en) * 2007-07-02 2009-01-08 Smithkline Beecham Corporation Farnesoid x receptor agonists
WO2009012125A1 (en) * 2007-07-16 2009-01-22 Eli Lilly And Company Compounds and methods for modulating fxr

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
"Conformationally constrained farnesoid X receptor (FXR) agonists:Naphthoic acid-based analogs of GW 4064";Adwoa Akwabi-Ameyaw等;《Bioorganic & Medicinal Chemistry Letters》;20080628;第18卷;第4339–4343页 *

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