TW202144332A - 法尼醇x(farnesoid x)受體促效劑之結晶形式 - Google Patents
法尼醇x(farnesoid x)受體促效劑之結晶形式 Download PDFInfo
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- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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| US6645980B1 (en) | 2000-05-25 | 2003-11-11 | Sepracor Inc. | Heterocyclic analgesic compounds and methods of use thereof |
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| WO2004046162A2 (en) | 2002-11-14 | 2004-06-03 | The Scripps Research Institute | Non-steroidal fxr agonists |
| US7647217B2 (en) | 2002-11-15 | 2010-01-12 | The Salk Institute For Biological Studies | Structure of the farnesoid X receptor ligand binding domain and methods of use therefor |
| US20050143449A1 (en) | 2002-11-15 | 2005-06-30 | The Salk Institute For Biological Studies | Non-steroidal farnesoid X receptor modulators and methods for the use thereof |
| GB0309781D0 (en) | 2003-04-29 | 2003-06-04 | Glaxo Group Ltd | Compounds |
| US7759348B2 (en) | 2003-07-30 | 2010-07-20 | Xenon Pharmaceuticals Inc. | Pyridazine derivatives and their use as therapeutic agents |
| EP1648874B1 (en) | 2003-07-30 | 2011-10-05 | Xenon Pharmaceuticals Inc. | Piperazine derivatives and their use as therapeutic agents |
| US7754711B2 (en) | 2003-07-30 | 2010-07-13 | Xenon Pharmaceuticals Inc. | Pyridazine derivatives and their use as therapeutic agents |
| WO2005058822A1 (en) | 2003-12-17 | 2005-06-30 | Actelion Pharmaceuticals Ltd | Substituted amino-cycloalkanes |
| CN1914205A (zh) | 2003-12-19 | 2007-02-14 | 葛兰素集团有限公司 | 吡唑并[3,4－b]吡啶化合物及其作为磷酸二酯酶抑制剂的用途 |
| PL1734970T3 (pl) | 2004-03-12 | 2015-05-29 | Intercept Pharmaceuticals Inc | Leczenie zwłóknienia z zastosowaniem ligandów FXR |
| WO2005097760A1 (en) | 2004-03-26 | 2005-10-20 | Rigel Pharmaceuticals, Inc. | Heterocyclic anti-viral compounds comprising metabolizable moieties and their uses |
| WO2005113522A1 (en) | 2004-05-07 | 2005-12-01 | Janssen Pharmaceutica, N.V. | Azole carboxamide inhibitors of bacterial type iii protein secretion systems |
| JP2006199656A (ja) | 2005-01-24 | 2006-08-03 | Kowa Co | アミド基を有する環状アミン化合物 |
| MY144229A (en) | 2006-01-26 | 2011-08-15 | Xenon Pharmaceuticals Inc | Pyridazine derivatives and their use as therapeutic agents |
| 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 |
| EP2001851A2 (en) | 2006-03-28 | 2008-12-17 | Novartis AG | Amide derivatives and their application for the treament of g protein related diseases |
| US20080081824A1 (en) | 2006-09-29 | 2008-04-03 | Bristol-Myers Squibb Company | Substituted piperidines as modulators of chemokine receptor activity |
| WO2008065500A2 (en) | 2006-11-30 | 2008-06-05 | Pfizer Products Inc. | Heteroaryl amides as type i glycine transport inhibitors |
| EP2234977A4 (en) | 2007-12-19 | 2011-04-13 | Boehringer Ingelheim Int | VIRAL POLYMERASE INHIBITORS |
| US20090270418A1 (en) | 2008-01-09 | 2009-10-29 | Marianne Sloss | Pyrazole pyrazine amine compounds as kinase inhibitors, compositions thereof and methods of treatment therewith |
| US20100029657A1 (en) | 2008-02-29 | 2010-02-04 | Wyeth | Bridged, Bicyclic Heterocyclic or Spiro Bicyclic Heterocyclic Derivatives of Pyrazolo[1, 5-A]Pyrimidines, Methods for Preparation and Uses Thereof |
| WO2010001869A1 (ja) | 2008-06-30 | 2010-01-07 | 武田薬品工業株式会社 | ４置換ベンゼン化合物およびその用途 |
| JP2010077109A (ja) | 2008-08-28 | 2010-04-08 | Takeda Chem Ind Ltd | 複素環化合物およびその用途 |
| JP2012516885A (ja) | 2009-02-04 | 2012-07-26 | ファイザー・インク | ４−アミノ−７，８−ジヒドロピリド［４，３−ｄ］ピリミジン−５（６Ｈ）−オン誘導体 |
| CA2767089A1 (en) | 2009-07-15 | 2011-01-20 | Abbott Laboratories | Pyrrolopyridine inhibitors of kinases |
| EP2454243A2 (en) | 2009-07-15 | 2012-05-23 | Merck Serono SA | Tetrazole derivatives |
| FR2963005B1 (fr) | 2010-07-23 | 2012-08-17 | Sanofi Aventis | Derives d'oxadiazoles et de pyridazines, leur preparation et leur application en therapeutique |
| WO2012087521A1 (en) | 2010-12-20 | 2012-06-28 | Irm Llc | Compositions and methods for modulating farnesoid x receptors |
| KR101834362B1 (ko) | 2011-03-18 | 2018-03-05 | 바이엘 인텔렉쳐 프로퍼티 게엠베하 | N-(3-카바모일페닐)-1h-피라졸-5-카복사미드 유도체 및 동물 해충을 구제하기 위한 그의 용도 |
| ME02754B (me) | 2011-03-23 | 2018-01-20 | Trevena Inc | Ligandi opioidnih receptora i postupci njihove upotrebe i pripreme |
| EP2545964A1 (en) | 2011-07-13 | 2013-01-16 | Phenex Pharmaceuticals AG | Novel FXR (NR1H4) binding and activity modulating compounds |
| EP2732871A4 (en) | 2011-07-13 | 2015-03-04 | M Tech Co Ltd | PROCESS FOR PRODUCING MICROPARTICLES WITH CONTROLLED CRYSTALLITE DIAMETER |
| WO2013037482A1 (en) | 2011-09-15 | 2013-03-21 | Phenex Pharmaceuticals Ag | Farnesoid x receptor agonists for cancer treatment and prevention |
| RU2543485C2 (ru) | 2013-02-26 | 2015-03-10 | Андрей Александрович Иващенко | Гетероциклические агонисты рецепторов желчных кислот tgr5, фармацевтическая композиция, способы их получения и применения |
| DK3043865T3 (da) | 2013-09-11 | 2021-02-01 | Univ Claude Bernard Lyon | Fremgangsmåder og farmaceutiske sammensætningr til behandlingen af hepatitis b-virusinfektion |
| GB201316824D0 (en) | 2013-09-23 | 2013-11-06 | R & D Vernalis Ltd | New Chemical Entities |
| US20150258052A1 (en) | 2014-03-13 | 2015-09-17 | Salk Institute For Biological Studies | Methods of using fexaramine and agents that increase sympathetic nervous system activity to promote browning of white adipose tissue |
| KR20160132111A (ko) | 2014-03-13 | 2016-11-16 | 더 솔크 인스티튜트 포 바이올로지칼 스터디즈 | Fxr 작용제와 제조방법 및 용도 |
| US10301268B2 (en) | 2014-03-13 | 2019-05-28 | The Salk Institute For Biological Studies | Analogs of fexaramine and methods of making and using |
| US10077268B2 (en) | 2014-03-13 | 2018-09-18 | Salk Institute For Biological Studies | FXR agonists and methods for making and using |
| EP3116851B1 (en) | 2014-03-13 | 2023-07-26 | Salk Institute for Biological Studies | Analogs of fexaramine and methods of making and using |
| US20180116993A1 (en) | 2015-01-22 | 2018-05-03 | Xiamen University | Modulators of farnesoid x receptor and methods for the use thereof |
| AU2016233579A1 (en) | 2015-03-13 | 2017-10-12 | Salk Institute For Biological Studies | Treating latent autoimmune diabetes of adults with farnesoid X receptor agonists to activate intestinal receptors |
| WO2017018751A1 (ko) | 2015-07-24 | 2017-02-02 | 동국대학교 산학협력단 | Blt 저해 활성을 갖는 신규 화합물 및 이를 유효성분으로 포함하는 염증성 질환 예방 또는 치료용 조성물 |
| US10703712B2 (en) | 2015-09-16 | 2020-07-07 | Metacrine, Inc. | Farnesoid X receptor agonists and uses thereof |
| US10626081B2 (en) | 2015-09-16 | 2020-04-21 | Metacrine, Inc. | Farnesoid X receptor agonists and uses thereof |
| EP3350164A4 (en) | 2015-09-16 | 2019-03-27 | Metacrine, Inc. | FARNESOID-X RECEPTOR AGONISTS AND USES THEREOF |
| WO2017049177A1 (en) | 2015-09-16 | 2017-03-23 | Metacrine, Inc. | Farnesoid x receptor agonists and uses thereof |
| MX389514B (es) | 2015-10-01 | 2025-03-20 | Firmenich Incorporated | Compuestos útiles como moduladores de canal receptor 8 de potencial transitorio de melastatina (trpm8). |
| CN105477636B (zh) | 2015-10-16 | 2019-09-17 | 厦门大学 | 使用阿维菌素及其衍生物治疗代谢疾病的方法 |
| WO2017078928A1 (en) | 2015-11-06 | 2017-05-11 | Salk Institute For Biological Studies | Fxr agonists and methods for making and using |
| CN107126419B (zh) | 2016-02-26 | 2020-06-19 | 石药集团中诺药业（石家庄）有限公司 | 一种奥贝胆酸片剂及其制备方法 |
| WO2017170182A1 (ja) | 2016-03-31 | 2017-10-05 | 株式会社Adeka | 感光性組成物及び新規化合物 |
| WO2018170165A1 (en) | 2017-03-15 | 2018-09-20 | Metacrine, Inc. | Farnesoid x receptor agonists and uses thereof |
| JP7258763B2 (ja) * | 2017-03-15 | 2023-04-17 | メタクリン，インク． | ファルネソイドｘ受容体アゴニストおよびその使用 |
| US20200131129A1 (en) | 2017-03-15 | 2020-04-30 | Metacrine, Inc. | Farnesoid x receptor agonists and uses thereof |
| CA3055990A1 (en) * | 2017-03-15 | 2018-09-20 | Metacrine, Inc. | Farnesoid x receptor agonists and uses thereof |
| WO2018170167A1 (en) | 2017-03-15 | 2018-09-20 | Metacrine, Inc. | Farnesoid x receptor agonists and uses thereof |
| CZ2017298A3 (cs) | 2017-05-26 | 2018-12-05 | Zentiva, K.S. | Amorfní formy obeticholové kyseliny |
| WO2020060007A1 (ko) | 2018-09-17 | 2020-03-26 | 엘지전자 주식회사 | 5g 이동통신에서 pdu 세션을 핸들링하는 방법 및 무선 기기 |
| JP2022500393A (ja) * | 2018-09-18 | 2022-01-04 | メタクリン，インク． | ファルネソイドｘ受容体アゴニストおよびその使用 |
| WO2020061118A1 (en) | 2018-09-18 | 2020-03-26 | Metacrine, Inc. | Farnesoid x receptor agonists and uses thereof |
| EP3852749A4 (en) | 2018-09-18 | 2022-08-24 | Metacrine, Inc. | CRYSTALLINE FORMS OF A FARNESOID X RECEPTOR AGONIST |
| WO2020061116A1 (en) * | 2018-09-18 | 2020-03-26 | Metacrine, Inc. | Farnesoid x receptor agonists and uses thereof |
| EA202190661A1 (ru) | 2018-09-18 | 2021-08-13 | Метакрайн, Инк. | Агонисты фарнезоидного х-рецептора для лечения заболевания |
| CN113056264A (zh) | 2018-09-18 | 2021-06-29 | 梅塔科林公司 | 法尼醇x受体激动剂及其用途 |
| AU2019344903B2 (en) | 2018-09-18 | 2025-02-27 | Eli Lilly And Company | Farnesoid X receptor agonists and uses thereof |
| CN120732855A (zh) | 2020-03-18 | 2025-10-03 | 伊莱利利公司 | 用于治疗疾病的法尼醇x受体激动剂 |
| KR20220155356A (ko) | 2020-03-18 | 2022-11-22 | 메타크린, 인크. | 파르네소이드 x 수용체 효능제의 결정형 |
| WO2021188695A1 (en) | 2020-03-18 | 2021-09-23 | Metacrine, Inc. | Formulations of a farnesoid x receptor agonist |
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| IL296532A (en) | 2022-11-01 |
| US20230147756A1 (en) | 2023-05-11 |
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| JP2025121901A (ja) | 2025-08-20 |
| AR121596A1 (es) | 2022-06-22 |
| JP2023518399A (ja) | 2023-05-01 |
| BR112022018596A2 (pt) | 2023-03-07 |
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