EA038632B1 - 7,11-дигидрокси-6-этил-5-холан-24-овая кислота и фармацевтические композиции на ее основе для лечения или предупреждения заболевания или состояния, опосредованных фарнезоидным х-рецептором (fxr) - Google Patents
7,11-дигидрокси-6-этил-5-холан-24-овая кислота и фармацевтические композиции на ее основе для лечения или предупреждения заболевания или состояния, опосредованных фарнезоидным х-рецептором (fxr) Download PDFInfo
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- EA038632B1 EA038632B1 EA201892007A EA201892007A EA038632B1 EA 038632 B1 EA038632 B1 EA 038632B1 EA 201892007 A EA201892007 A EA 201892007A EA 201892007 A EA201892007 A EA 201892007A EA 038632 B1 EA038632 B1 EA 038632B1
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- Eurasian Patent Office
- Prior art keywords
- disease
- compound
- present
- liver
- fxr
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Landscapes
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| CA2966885A1 (en) | 2014-11-06 | 2016-05-12 | Enanta Pharmaceuticals, Inc. | Bile acid analogs an fxr/tgr5 agonists and methods of use thereof |
| HK1244708A1 (zh) | 2014-11-26 | 2018-08-17 | 英安塔制药有限公司 | 作爲fxr/tgr5激动剂的胆汁酸类似物及其使用方法 |
| WO2016086115A1 (en) | 2014-11-26 | 2016-06-02 | 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 |
| RU2017130466A (ru) | 2015-02-11 | 2019-03-12 | Энанта Фармасьютикалс, Инк. | Аналоги желчной кислоты в качестве агонистов fxr/tgr5 и способы их применения |
| NZ735126A (en) | 2015-03-31 | 2022-10-28 | Enanta Pharm Inc | Bile acid derivatives as fxr/tgr5 agonists and methods of use thereof |
| TN2018000106A1 (en) | 2015-10-07 | 2019-10-04 | Intercept Pharmaceuticals Inc | Farnesoid x receptor modulators |
| WO2017147159A1 (en) | 2016-02-23 | 2017-08-31 | Enanta Pharmaceuticals, Inc. | Deuterated bile acid derivatives as fxr/tgr5 agonists and methods of use thereof |
| 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 |
| US10323061B2 (en) | 2016-02-23 | 2019-06-18 | Enanta Pharmaceuticals, Inc. | Heteroaryl containing bile acid analogs as FXR/TGR5 agonists and methods of use thereof |
| ES2874682T3 (es) | 2016-03-11 | 2021-11-05 | Intercept Pharmaceuticals Inc | Derivados de 3-desoxi y composiciones farmacéuticas de los mismos |
| WO2018102418A1 (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 |
| GB201812382D0 (en) | 2018-07-30 | 2018-09-12 | Nzp Uk Ltd | Compounds |
| AU2022208190A1 (en) * | 2021-01-14 | 2023-07-06 | Enyo Pharma | Method for treating chronic kidney diseases |
| WO2023288123A1 (en) | 2021-07-16 | 2023-01-19 | Interecept Pharmaceuticals, Inc. | Methods and intermediates for the preparation of 3.alpha.,7.alpha.,11.beta.-trihydroxy-6.alpha.-ethyl-5.beta.-cholan-24-oic acid |
| AU2023257308A1 (en) * | 2022-04-21 | 2024-10-10 | Intercept Pharmaceuticals, Inc. | Uses of farnesoid x receptor agonists |
| WO2024097247A1 (en) * | 2022-10-31 | 2024-05-10 | Intercept Pharmaceuticals, Inc. | Uses of farnesoid x receptor agonists |
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| US20130261317A1 (en) * | 2010-09-27 | 2013-10-03 | Kythera Biopharmaceuticals, Inc. | Methods for preparing synthetic bile acids and compositions comprising the same |
| US20140371190A1 (en) * | 2013-05-14 | 2014-12-18 | TES Pharma SrI. | Farnesoid X receptor modulators |
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| PT1734970E (pt) * | 2004-03-12 | 2015-03-11 | Intercept Pharmaceuticals Inc | Tratamento de fibrose utilizando ligandos de rfx |
| KR101922164B1 (ko) | 2011-12-29 | 2019-02-13 | 노보 노르디스크 에이/에스 | 비-단백질원 아미노산을 포함하는 디펩티드 |
| ES2938874T3 (es) * | 2014-05-29 | 2023-04-17 | Bar Pharmaceuticals S R L | Derivados de colano para su uso en el tratamiento y/o prevención de enfermedades mediadas por FXR y TGR5/GPBAR1 |
| BR112018002499A2 (pt) | 2015-08-07 | 2018-09-18 | Intercept Pharmaceuticals Inc | método de preparação de um composto da fórmula (a) ou um seu sal, solvato ou conjugado de aminoácido farmaceuticamente aceitável, composto produzido pelo método e composição farmacêutica |
| ES2874682T3 (es) | 2016-03-11 | 2021-11-05 | Intercept Pharmaceuticals Inc | Derivados de 3-desoxi y composiciones farmacéuticas de los mismos |
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2017
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130261317A1 (en) * | 2010-09-27 | 2013-10-03 | Kythera Biopharmaceuticals, Inc. | Methods for preparing synthetic bile acids and compositions comprising the same |
| US20140371190A1 (en) * | 2013-05-14 | 2014-12-18 | TES Pharma SrI. | Farnesoid X receptor modulators |
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