RU2674983C1 - Октагидро конденсированные азадекалиновые модуляторы глюкокортикоидного рецептора - Google Patents
Октагидро конденсированные азадекалиновые модуляторы глюкокортикоидного рецептора Download PDFInfo
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- RU2674983C1 RU2674983C1 RU2016123449A RU2016123449A RU2674983C1 RU 2674983 C1 RU2674983 C1 RU 2674983C1 RU 2016123449 A RU2016123449 A RU 2016123449A RU 2016123449 A RU2016123449 A RU 2016123449A RU 2674983 C1 RU2674983 C1 RU 2674983C1
- Authority
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- Russia
- Prior art keywords
- fluorophenyl
- pyrazolo
- sulfonyl
- octahydro
- isoquinolin
- Prior art date
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Classifications
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| US12433882B2 (en) | 2022-10-28 | 2025-10-07 | Corcept Therapeutics Incorporated | Treatments for amyotrophic lateral sclerosis using dazucorilant |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12226412B2 (en) | 2012-05-25 | 2025-02-18 | Corcept Therapeutics, Inc. | Heteroaryl-ketone fused azadecalin glucocorticoid receptor modulators |
| US8859774B2 (en) | 2012-05-25 | 2014-10-14 | Corcept Therapeutics, Inc. | Heteroaryl-ketone fused azadecalin glucocorticoid receptor modulators |
| BR112016011826B1 (pt) * | 2013-11-25 | 2022-09-27 | Corcept Therapeutics, Inc | Composto, composição farmacêutica e uso do referido composto |
| AU2016243625B2 (en) | 2015-03-30 | 2020-09-10 | Corcept Therapeutics, Inc. | Use of glucocorticoid receptor antagonists in combination with glucocorticoids to treat adrenal insufficiency |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0375210A1 (en) * | 1988-12-08 | 1990-06-27 | Lilly Industries Limited | Pyrazoloisoquinoline derivatives, process for their preparation and pharmaceutical compositions containing them |
| WO2005087769A1 (en) * | 2004-03-09 | 2005-09-22 | Corcept Therapeutics, Inc. | Fused ring azadecalin glucocorticoid receptor modulators |
| RU2381217C2 (ru) * | 2005-04-05 | 2010-02-10 | Ф.Хоффман-Ля Рош Аг | Пиразолы |
| US20120220565A1 (en) * | 2010-08-27 | 2012-08-30 | Corcept Therapeutics, Inc. | Pyridyl-amine fused azadecalin modulators |
Family Cites Families (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS322220B1 (enExample) | 1954-11-30 | 1957-04-11 | ||
| US4391904A (en) | 1979-12-26 | 1983-07-05 | Syva Company | Test strip kits in immunoassays and compositions therein |
| IL72729A (en) | 1983-09-26 | 1988-02-29 | Lilly Co Eli | Trans(+_)octahydropyrazole-ring alkylated pyrazoloquinolines,their preparation and pharmaceutical compositions containing them |
| JP3160941B2 (ja) | 1991-06-17 | 2001-04-25 | 東レ株式会社 | カルバゾール誘導体および免疫抑制剤 |
| FR2697252B1 (fr) | 1992-10-28 | 1994-12-09 | Fournier Ind & Sante | Dérivés de 1,2,3,5,6,7,8,8a-octahydro-5,5,8a-triméthyl-(8abeta)-6-isoquinolineamine, leur procédé de préparation et leur utilisation en thérapeutique. |
| CA2168853A1 (en) | 1993-08-06 | 1995-02-16 | Giulio Dondio | Hydroisoquinoline derivatives |
| CA2683097A1 (en) | 1998-03-10 | 1999-09-16 | Research Triangle Institute | Novel opiate compounds, methods of making and methods of use |
| GB9911053D0 (en) | 1999-05-12 | 1999-07-14 | Pharmacia & Upjohn Spa | 4,5,6,7-tetrahydroindazole derivatives process for their preparation and their use as antitumour agents |
| EP1629845A3 (en) * | 2000-11-02 | 2006-03-22 | Akzo Nobel N.V. | Use of cortisol-sequestering agents for the treatment of hypercortisolaemia related disorders |
| US7238778B2 (en) | 2001-07-17 | 2007-07-03 | Smithkline Beecham Corporation | Crystallized glucocorticoid receptor ligand binding domain polypeptide and screening methods employing same |
| WO2003009853A1 (en) * | 2001-07-23 | 2003-02-06 | Corcept Therapeutics, Inc. | Methods for preventing antipsychotic-induced weight gain |
| US6679935B2 (en) * | 2001-08-14 | 2004-01-20 | Apex Advanced Technologies, Llc | Lubricant system for use in powdered metals |
| CA2473886C (en) | 2002-01-22 | 2012-08-21 | The Regents Of The University Of California | Non-steroidal ligands for the glucocorticoid receptor, compositions and uses thereof |
| TW200503994A (en) | 2003-01-24 | 2005-02-01 | Novartis Ag | Organic compounds |
| BRPI0414066A (pt) | 2003-09-03 | 2006-10-24 | Wyeth Corp | 42-éster de rapamicina amorfo com ácido 3-hidróxi-2-( hidroximetil )-2-metilproipiÈnico e composições farmacêuticas que o contenha |
| EP1761497B1 (en) | 2004-01-09 | 2008-09-03 | Corcept Therapeutics, Inc. | Azadecalin glucocorticoid receptor modulators |
| US7790745B2 (en) | 2005-10-21 | 2010-09-07 | Bristol-Myers Squibb Company | Tetrahydroisoquinoline LXR Modulators |
| EP2209780B1 (en) * | 2007-11-01 | 2014-01-01 | Bristol-Myers Squibb Company | Nonsteroidal compounds useful as modulators of glucocorticoid receptor ap-1 and/or nf- kappa b activity and use thereof |
| EP2247597A1 (en) * | 2008-02-07 | 2010-11-10 | Bristol-Myers Squibb Company | Fused heteroaryl modulators of glucocorticoid receptor, ap-1, and/or nf-kb activity and use thereof |
| EP2429529B1 (en) | 2009-05-12 | 2015-01-14 | Corcept Therapeutics, Inc. | Solid forms and process for preparing |
| US8710035B2 (en) * | 2010-03-24 | 2014-04-29 | The University Of Chicago | Methods and compositions related to glucocorticoid receptor antagonists and breast cancer |
| US8829024B2 (en) | 2011-01-07 | 2014-09-09 | Corcept Therapeutics, Inc. | Combination steroid and glucocorticoid receptor antagonist therapy |
| US20130225633A1 (en) | 2012-02-27 | 2013-08-29 | Corcept Therapeutics, Inc. | Phenyl heterocycloalkyl glucocorticoid receptor modulators |
| PL3590517T3 (pl) * | 2012-05-25 | 2021-09-20 | Corcept Therapeutics Incorporated | Modulatory receptorów glukokortykoidowych typu azadekaliny skondensowanej z heteroaryloketonem |
| US8859774B2 (en) | 2012-05-25 | 2014-10-14 | Corcept Therapeutics, Inc. | Heteroaryl-ketone fused azadecalin glucocorticoid receptor modulators |
| BR112016011826B1 (pt) * | 2013-11-25 | 2022-09-27 | Corcept Therapeutics, Inc | Composto, composição farmacêutica e uso do referido composto |
| US9943505B2 (en) * | 2016-09-09 | 2018-04-17 | Corcept Therapeutics, Inc. | Glucocorticoid receptor modulators to treat pancreatic cancer |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0375210A1 (en) * | 1988-12-08 | 1990-06-27 | Lilly Industries Limited | Pyrazoloisoquinoline derivatives, process for their preparation and pharmaceutical compositions containing them |
| WO2005087769A1 (en) * | 2004-03-09 | 2005-09-22 | Corcept Therapeutics, Inc. | Fused ring azadecalin glucocorticoid receptor modulators |
| RU2381217C2 (ru) * | 2005-04-05 | 2010-02-10 | Ф.Хоффман-Ля Рош Аг | Пиразолы |
| US20120220565A1 (en) * | 2010-08-27 | 2012-08-30 | Corcept Therapeutics, Inc. | Pyridyl-amine fused azadecalin modulators |
Non-Patent Citations (1)
| Title |
|---|
| RU 2381217 C2. * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12433882B2 (en) | 2022-10-28 | 2025-10-07 | Corcept Therapeutics Incorporated | Treatments for amyotrophic lateral sclerosis using dazucorilant |
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