KR20190057129A - Ppar 작용제 화합물의 결정형 및 염 형태 - Google Patents
Ppar 작용제 화합물의 결정형 및 염 형태 Download PDFInfo
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- KR20190057129A KR20190057129A KR1020197012668A KR20197012668A KR20190057129A KR 20190057129 A KR20190057129 A KR 20190057129A KR 1020197012668 A KR1020197012668 A KR 1020197012668A KR 20197012668 A KR20197012668 A KR 20197012668A KR 20190057129 A KR20190057129 A KR 20190057129A
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| CN109843857B (zh) | 2016-10-05 | 2023-01-06 | 米托布里奇公司 | Ppar激动剂化合物的结晶和盐形式 |
| CN111356451A (zh) | 2017-10-10 | 2020-06-30 | 奥尔德拉医疗公司 | 炎性病症的治疗 |
| CN112714762A (zh) * | 2018-08-06 | 2021-04-27 | 奥尔德拉医疗公司 | 多晶型化合物及其用途 |
| JP7397491B2 (ja) * | 2018-10-23 | 2023-12-13 | 国立研究開発法人科学技術振興機構 | ＰＰＡＲδ活性化剤 |
| US12098132B2 (en) | 2019-05-02 | 2024-09-24 | Aldeyra Therapeutics, Inc. | Process for preparation of aldehyde scavenger and intermediates |
| CN113784954A (zh) | 2019-05-02 | 2021-12-10 | 奥尔德拉医疗公司 | 多晶型化合物和其用途 |
| WO2021231792A1 (en) | 2020-05-13 | 2021-11-18 | Aldeyra Therapeutics, Inc. | Pharmaceutical formulations and uses thereof |
| WO2022256540A1 (en) | 2021-06-02 | 2022-12-08 | Astellas Pharma Inc. | Methods of use of ppar agonist compounds and pharmaceutical compositions thereof |
| WO2023147309A1 (en) | 2022-01-25 | 2023-08-03 | Reneo Pharmaceuticals, Inc. | Use of ppar-delta agonists in the treatment of disease |
| WO2025207099A1 (en) * | 2024-03-28 | 2025-10-02 | Astellas Pharma Inc. | Ppar-delta inhibitors for preventing post-operative atrial fibrillation |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060241157A1 (en) | 2003-01-06 | 2006-10-26 | Conner Scott E | Heterocyclic ppar modulators |
| EP1671633A1 (en) | 2004-12-17 | 2006-06-21 | Sanofi-Aventis Deutschland GmbH | Use of PPAR agonists for the treatment of congestive heart failure |
| CN101141957A (zh) * | 2005-02-03 | 2008-03-12 | Irm责任有限公司 | 作为ppar调节剂的化合物和组合物 |
| CN101296892A (zh) * | 2005-09-07 | 2008-10-29 | 普莱希科公司 | Ppar活性化合物 |
| DE102006023336A1 (de) | 2006-05-18 | 2007-11-22 | Merck Patent Gmbh | 1,5-Diphenyl-pyrazole II |
| FR2940289B1 (fr) * | 2008-12-23 | 2014-09-12 | Biopharmed | Derives de la classe des hydroxyquinoleines aminees pour le traitement du cancer du pancreas |
| CN102727489A (zh) * | 2012-07-18 | 2012-10-17 | 西南大学 | 5-芳(杂环)亚甲基噻唑烷-2，4-二酮在制备ppar激动剂中的应用 |
| US20170305894A1 (en) * | 2014-10-08 | 2017-10-26 | Mitobridge, Inc. | Ppar agonists, compounds, pharmaceutical compositions, and methods of use thereof |
| AU2016333963C1 (en) * | 2015-10-07 | 2021-05-27 | The Salk Institute For Biological Studies | PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof |
| US11358954B2 (en) | 2016-04-13 | 2022-06-14 | Mitobridge, Inc. | PPAR agonists, compounds, pharmaceutical compositions, and methods of use thereof |
| CN109843857B (zh) | 2016-10-05 | 2023-01-06 | 米托布里奇公司 | Ppar激动剂化合物的结晶和盐形式 |
| UA124019C2 (uk) * | 2016-10-05 | 2021-07-07 | Мітобрідж, Інк. | Спосіб лікування гострого пошкодження нирок |
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