KR20190040043A - 결정질 19-노르 c3,3-이치환된 c21-n-피라졸릴 스테로이드 - Google Patents
결정질 19-노르 c3,3-이치환된 c21-n-피라졸릴 스테로이드 Download PDFInfo
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| KR1020237017309A KR20230079470A (ko) | 2016-08-23 | 2017-08-23 | 결정질 19-노르 c3,3-이치환된 c21-n-피라졸릴 스테로이드 |
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| US201662378582P | 2016-08-23 | 2016-08-23 | |
| US62/378,582 | 2016-08-23 | ||
| PCT/US2017/048267 WO2018039378A1 (en) | 2016-08-23 | 2017-08-23 | A crystalline 19-nor c3, 3-disubstituted c21-n-pyrazolyl steroid |
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Families Citing this family (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3572417B1 (en) | 2011-10-14 | 2025-12-17 | Sage Therapeutics, LLC | 3,3 disubstituted 19-nor pregnane compounds, compositions, and uses thereof |
| CA2882708A1 (en) | 2012-08-21 | 2014-02-27 | Sage Therapeutics, Inc. | Methods of treating epilepsy or status epilepticus |
| KR102396328B1 (ko) | 2013-04-17 | 2022-05-10 | 세이지 테라퓨틱스, 인크. | 19-노르 c3,3-이치환된 c21-n-피라졸릴 스테로이드 및 그의 사용 방법 |
| US9725481B2 (en) | 2013-04-17 | 2017-08-08 | Sage Therapeutics, Inc. | 19-nor C3, 3-disubstituted C21-C-bound heteroaryl steroids and methods of use thereof |
| US20160068563A1 (en) | 2013-04-17 | 2016-03-10 | Boyd L. Harrison | 19-nor neuroactive steroids and methods of use thereof |
| EP2986624B1 (en) | 2013-04-17 | 2020-03-25 | Sage Therapeutics, Inc. | 19-nor neuroactive steroids for methods of treatment |
| SI3021852T1 (sl) | 2013-07-19 | 2021-07-30 | Sage Therapeutics, Inc. | Nevroaktivni steroidi, sestavki in uporabe le-teh |
| AU2014308621C1 (en) | 2013-08-23 | 2022-01-06 | Sage Therapeutics, Inc. | Neuroactive steroids, compositions, and uses thereof |
| US10246482B2 (en) | 2014-06-18 | 2019-04-02 | Sage Therapeutics, Inc. | Neuroactive steroids, compositions, and uses thereof |
| JOP20200195A1 (ar) | 2014-09-08 | 2017-06-16 | Sage Therapeutics Inc | سترويدات وتركيبات نشطة عصبياً، واستخداماتها |
| ME03809B (me) | 2014-10-16 | 2021-04-20 | Sage Therapeutics Inc | KOMPOZICIJE I POSTUPCI ZA LEČENJE POREMEĆAJA CNS-a |
| CN117024501A (zh) | 2014-10-16 | 2023-11-10 | 萨奇治疗股份有限公司 | 靶向cns障碍的组合物和方法 |
| WO2016082789A1 (en) | 2014-11-27 | 2016-06-02 | Sage Therapeutics, Inc. | Compositions and methods for treating cns disorders |
| RS61530B1 (sr) | 2015-01-26 | 2021-04-29 | Sage Therapeutics Inc | Kompozicije i postupci za lečenje poremećaja cns |
| EP4155314A1 (en) | 2015-02-20 | 2023-03-29 | Sage Therapeutics, Inc. | Neuroactive steroids, compositions, and uses thereof |
| WO2018013615A1 (en) | 2016-07-11 | 2018-01-18 | Sage Therapeutics, Inc. | C7, c12, and c16 substituted neuroactive steroids and their methods of use |
| MA45599A (fr) | 2016-07-11 | 2019-05-15 | Sage Therapeutics Inc | Stéroïdes neuroactifs substitués en c17, c20 et c21 et leurs procédés d'utilisation |
| EP3504189A1 (en) | 2016-08-23 | 2019-07-03 | Sage Therapeutics, Inc. | A crystalline 19-nor c3, 3-disubstituted c21-n-pyrazolyl steroid |
| WO2019051264A1 (en) * | 2017-09-07 | 2019-03-14 | Sage Therapeutics, Inc. | NEUROACTIVE STEROIDS AND METHODS OF USE |
| CA3075872A1 (en) * | 2017-09-14 | 2019-03-21 | Sage Therapeutics, Inc. | A 19-nor c3,3-disubstituted c21-n-pyrazolyl steroid and methods of use thereof |
| MA51046A (fr) | 2017-12-08 | 2021-03-17 | Sage Therapeutics Inc | Dérivés de 21-[4-cyano-pyrazol-1-yl]-19-nor-pregan-3. alpha-ol-20-one deutérés pour le traitement de troubles du snc |
| CA3103421A1 (en) * | 2018-06-12 | 2019-12-19 | Sage Therapeutics, Inc. | A 19-nor c3,3-disubstituted c21 -n-pyrazolyl steroid and methods of use thereof |
| KR20250174100A (ko) | 2018-12-05 | 2025-12-11 | 세이지 테라퓨틱스, 인크. | 신경활성 스테로이드 및 이의 사용 방법 |
| CN111454318A (zh) * | 2019-01-20 | 2020-07-28 | 浙江易众化工有限公司 | 抗抑郁药物sage-217的晶型及其制备方法 |
| CN111770915A (zh) * | 2019-01-31 | 2020-10-13 | 深圳仁泰医药科技有限公司 | γ-氨基丁酸调节剂的晶型X及其制备方法和应用 |
| WO2020242772A1 (en) | 2019-05-28 | 2020-12-03 | Teva Czech Industries S.R.O | Solid state forms of sage-217 and processes for preparation thereof |
| SG11202112391UA (en) | 2019-05-31 | 2021-12-30 | Sage Therapeutics Inc | Neuroactive steroids and compositions thereof |
| CN118027131A (zh) * | 2019-08-07 | 2024-05-14 | 上海翰森生物医药科技有限公司 | 一种甾族类衍生物调节剂的盐及其晶型 |
| US10857163B1 (en) | 2019-09-30 | 2020-12-08 | Athenen Therapeutics, Inc. | Compositions that preferentially potentiate subtypes of GABAA receptors and methods of use thereof |
| EP4125921A1 (en) | 2020-03-25 | 2023-02-08 | Sage Therapeutics, Inc. | Use of agents for treatment of respiratory conditions |
| KR20230041049A (ko) * | 2020-07-20 | 2023-03-23 | 세이지 테라퓨틱스, 인크. | 19-노르 c3,3-이치환된 c21-n-피라졸릴 스테로이드의 제형 및 이의 사용 방법 |
| WO2022072620A1 (en) * | 2020-10-01 | 2022-04-07 | Eliem Therapeutics (UK) Ltd | Methods of treating fibromyalgia with neuroactive steroids |
| KR20230136599A (ko) | 2021-01-28 | 2023-09-26 | 세이지 테라퓨틱스, 인크. | 성 기능장애의 치료를 위한 신경활성 스테로이드의용도 |
| US20240245711A1 (en) * | 2021-03-17 | 2024-07-25 | Sage Therapeutics, Inc. | A 19-nor c3,3-disubstituted c21-n-pyrazolyl steroid for the treatment of major depressive disorder |
| EP4329769A1 (en) | 2021-04-29 | 2024-03-06 | Sage Therapeutics, Inc. | Neuroactive steroid for use in treating major depressive disorder and postpartum depression in a lactating female |
| WO2022232504A1 (en) | 2021-04-29 | 2022-11-03 | Sage Therapeutics, Inc. | 19-nor c3,3-disubstituted c21 -n-pyrazolyl steroid for use in treating major depressive disorder and postpartum depression |
| PE20240780A1 (es) | 2021-07-28 | 2024-04-17 | Sage Therapeutics Inc | Formas cristalinas de un esteroide neuroactivo |
| IL315023A (en) | 2022-02-16 | 2024-10-01 | Sage Therapeutics Inc | Neuroactive steroids for treatment of cns-related disorders |
| WO2023163879A1 (en) | 2022-02-28 | 2023-08-31 | Sage Therapeutics, Inc. | Neuroactive steroids for treatment of gastrointestinal diseases or conditions |
| WO2026055127A2 (en) | 2024-09-04 | 2026-03-12 | Sage Therapeutics, Inc., A Wholly Owned Subsidiary Of Supernus Pharmaceuticals, Inc. | Process for producing a gaba receptor modulator |
Family Cites Families (75)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5120723A (en) | 1987-08-25 | 1992-06-09 | University Of Southern California | Method, compositions, and compounds for modulating brain excitability |
| US7018406B2 (en) | 1999-11-17 | 2006-03-28 | Corevalve Sa | Prosthetic valve for transluminal delivery |
| EP1248869A2 (en) * | 2000-01-07 | 2002-10-16 | Transform Pharmaceuticals, Inc. | High-throughput formation, identification, and analysis of diverse solid-forms |
| PL215006B1 (pl) | 2002-02-08 | 2013-10-31 | Ono Pharmaceutical Co | Krystaliczna postac pochodnej piperydyny oraz jej zastosowanie |
| US20110152840A1 (en) | 2009-12-23 | 2011-06-23 | Drugtech Corporation | Methods for reducing the occurrence of preterm delivery and other pregnancy-related conditions |
| JP2014521662A (ja) | 2011-07-29 | 2014-08-28 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | ＧＡＢＡＡ受容体のモジュレーターとしての新規な１７β−ヘテロアリール置換ステロイド |
| WO2013043985A1 (en) | 2011-09-23 | 2013-03-28 | The Regents Of The University Of California | Edible oils to enhance delivery of orally administered steroids |
| EP3572417B1 (en) | 2011-10-14 | 2025-12-17 | Sage Therapeutics, LLC | 3,3 disubstituted 19-nor pregnane compounds, compositions, and uses thereof |
| EP2806877B2 (en) | 2012-01-23 | 2025-01-29 | Sage Therapeutics, Inc. | Neuroactive steroid formulations comprising a complex of allopregnanolone and sulfobutyl ether beta-cyclodextrin |
| US20150175651A1 (en) | 2012-06-15 | 2015-06-25 | Sage Therapeutics, Inc. | Neuroactive steroids, compositions, and uses thereof |
| US20140050789A1 (en) | 2012-08-13 | 2014-02-20 | The Regents Of The University Of California | Mitigation of epileptic seizures by combination therapy using benzodiazepines and neurosteroids |
| CA2882708A1 (en) | 2012-08-21 | 2014-02-27 | Sage Therapeutics, Inc. | Methods of treating epilepsy or status epilepticus |
| WO2014058736A1 (en) | 2012-10-08 | 2014-04-17 | Washington University | Neuroactive 19-alkoxy-17(20)-z-vinylcyano-substituted steroids, prodrugs thereof, and methods of treatment using same |
| AU2013352141B2 (en) | 2012-11-30 | 2018-04-05 | The Regents Of The University Of California | Anticonvulsant activity of steroids |
| HUE039057T2 (hu) | 2012-12-18 | 2018-12-28 | Univ Washington | Kezelési eljárásokban alkalmazható neuroaktív 19-alkoxi-17-szubsztituált szteroidok |
| KR102396328B1 (ko) | 2013-04-17 | 2022-05-10 | 세이지 테라퓨틱스, 인크. | 19-노르 c3,3-이치환된 c21-n-피라졸릴 스테로이드 및 그의 사용 방법 |
| US9725481B2 (en) | 2013-04-17 | 2017-08-08 | Sage Therapeutics, Inc. | 19-nor C3, 3-disubstituted C21-C-bound heteroaryl steroids and methods of use thereof |
| EP2986624B1 (en) | 2013-04-17 | 2020-03-25 | Sage Therapeutics, Inc. | 19-nor neuroactive steroids for methods of treatment |
| US20160068563A1 (en) | 2013-04-17 | 2016-03-10 | Boyd L. Harrison | 19-nor neuroactive steroids and methods of use thereof |
| SI3021852T1 (sl) | 2013-07-19 | 2021-07-30 | Sage Therapeutics, Inc. | Nevroaktivni steroidi, sestavki in uporabe le-teh |
| AU2014308621C1 (en) | 2013-08-23 | 2022-01-06 | Sage Therapeutics, Inc. | Neuroactive steroids, compositions, and uses thereof |
| ES2805598T3 (es) | 2014-05-29 | 2021-02-12 | Sage Therapeutics Inc | Esteroides neuroactivos, composiciones y usos de los mismos |
| US10246482B2 (en) | 2014-06-18 | 2019-04-02 | Sage Therapeutics, Inc. | Neuroactive steroids, compositions, and uses thereof |
| JOP20200195A1 (ar) | 2014-09-08 | 2017-06-16 | Sage Therapeutics Inc | سترويدات وتركيبات نشطة عصبياً، واستخداماتها |
| CN117024501A (zh) | 2014-10-16 | 2023-11-10 | 萨奇治疗股份有限公司 | 靶向cns障碍的组合物和方法 |
| ME03809B (me) * | 2014-10-16 | 2021-04-20 | Sage Therapeutics Inc | KOMPOZICIJE I POSTUPCI ZA LEČENJE POREMEĆAJA CNS-a |
| WO2016082789A1 (en) | 2014-11-27 | 2016-06-02 | Sage Therapeutics, Inc. | Compositions and methods for treating cns disorders |
| RS61530B1 (sr) | 2015-01-26 | 2021-04-29 | Sage Therapeutics Inc | Kompozicije i postupci za lečenje poremećaja cns |
| EP4155314A1 (en) | 2015-02-20 | 2023-03-29 | Sage Therapeutics, Inc. | Neuroactive steroids, compositions, and uses thereof |
| EP3280420B1 (en) | 2015-04-10 | 2024-03-27 | Sage Therapeutics, Inc. | Compositions and methods for treating cns disorders |
| AR105044A1 (es) | 2015-06-18 | 2017-08-30 | Sage Therapeutics Inc | Soluciones de esteroides neuroactivos y sus métodos de uso, recipiente |
| UY36741A (es) | 2015-06-21 | 2016-12-30 | Prevacus Inc | Compuesto de esteroide c-20, sus composiciones y usos para tratar la lesión cerebral traumática (tbi), que incluye las conmociones cerebrales |
| CA2998134A1 (en) | 2015-09-08 | 2017-03-16 | Viewpoint Therapeutics, Inc. | Compounds and formulations for treating ophthalmic diseases |
| AU2016338672A1 (en) | 2015-10-16 | 2018-04-12 | Marinus Pharmaceuticals, Inc. | Injectable neurosteroid formulations containing nanoparticles |
| MA43284A (fr) | 2015-11-20 | 2018-09-26 | Sage Therapeutics Inc | Composés et leurs méthodes d'utilisation |
| KR20240157128A (ko) | 2016-03-08 | 2024-10-31 | 세이지 테라퓨틱스, 인크. | 신경활성 스테로이드, 조성물, 및 그의 용도 |
| US10226550B2 (en) | 2016-03-11 | 2019-03-12 | Brigham Young University | Cationic steroidal antimicrobial compositions for the treatment of dermal tissue |
| WO2018013615A1 (en) | 2016-07-11 | 2018-01-18 | Sage Therapeutics, Inc. | C7, c12, and c16 substituted neuroactive steroids and their methods of use |
| MA45599A (fr) | 2016-07-11 | 2019-05-15 | Sage Therapeutics Inc | Stéroïdes neuroactifs substitués en c17, c20 et c21 et leurs procédés d'utilisation |
| EP3504189A1 (en) | 2016-08-23 | 2019-07-03 | Sage Therapeutics, Inc. | A crystalline 19-nor c3, 3-disubstituted c21-n-pyrazolyl steroid |
| CN108727453A (zh) | 2017-04-20 | 2018-11-02 | 华东理工大学 | 新型pd-1抑制剂及其应用 |
| WO2019018119A1 (en) | 2017-07-18 | 2019-01-24 | Pairnomix, Llc | METHODS FOR TREATING EPILEPSY AND DISORDERS ASSOCIATED WITH KCNTI |
| US11285139B2 (en) | 2017-08-31 | 2022-03-29 | Takeda Pharmaceutical Company Limited | Treatment of CNS conditions |
| WO2019051264A1 (en) | 2017-09-07 | 2019-03-14 | Sage Therapeutics, Inc. | NEUROACTIVE STEROIDS AND METHODS OF USE |
| US20200276209A1 (en) | 2017-09-11 | 2020-09-03 | Sage Therapeutics, Inc. | Methods of treating epilepsy or status epilepticus |
| CA3075872A1 (en) | 2017-09-14 | 2019-03-21 | Sage Therapeutics, Inc. | A 19-nor c3,3-disubstituted c21-n-pyrazolyl steroid and methods of use thereof |
| MY204493A (en) | 2017-11-10 | 2024-08-30 | Marinus Pharmaceuticals Inc | Ganaxolone for use in treating genetic epileptic disorders |
| MA51046A (fr) | 2017-12-08 | 2021-03-17 | Sage Therapeutics Inc | Dérivés de 21-[4-cyano-pyrazol-1-yl]-19-nor-pregan-3. alpha-ol-20-one deutérés pour le traitement de troubles du snc |
| BR112020012761A2 (pt) | 2017-12-22 | 2021-02-17 | Sage Therapeutics, Inc. | composições e métodos para o tratamento de distúrbios do snc |
| MX2020006599A (es) | 2017-12-22 | 2020-11-06 | Sage Therapeutics Inc | Composiciones y metodos para el tratamiento de trastornos en el sistema nervioso central. |
| TW201930269A (zh) | 2018-01-12 | 2019-08-01 | 美商賽吉醫療公司 | 用於治療cns病症之組合物及方法 |
| CA3103421A1 (en) | 2018-06-12 | 2019-12-19 | Sage Therapeutics, Inc. | A 19-nor c3,3-disubstituted c21 -n-pyrazolyl steroid and methods of use thereof |
| EP4321519B1 (en) | 2018-10-12 | 2026-04-08 | Sage Therapeutics, LLC | Neuroactive steroids substituted in position 10 with a cyclic group for use in the treatment of cns disorders |
| ES3039267T3 (en) | 2018-10-19 | 2025-10-20 | Sage Therapeutics Inc | 9(11)-unsaturated neuroactive steroids and their methods of use |
| KR20250174100A (ko) | 2018-12-05 | 2025-12-11 | 세이지 테라퓨틱스, 인크. | 신경활성 스테로이드 및 이의 사용 방법 |
| WO2020132504A1 (en) | 2018-12-21 | 2020-06-25 | Sage Therapeutics, Inc. | 3.alpha.-hydroxy-17.beta.-amide neuroactive steroids and compositions thereof |
| TW202523658A (zh) | 2019-05-24 | 2025-06-16 | 美商賽吉醫療公司 | 化合物、組合物及使用方法 |
| SG11202112391UA (en) | 2019-05-31 | 2021-12-30 | Sage Therapeutics Inc | Neuroactive steroids and compositions thereof |
| CN114729000A (zh) | 2019-06-27 | 2022-07-08 | 萨奇治疗股份有限公司 | 用于治疗cns病症的化合物 |
| JP7754725B2 (ja) | 2019-06-27 | 2025-10-15 | セージ セラピューティクス， インコーポレイテッド | Ｃｎｓ障害を治療するための組成物及び方法 |
| CA3143509A1 (en) | 2019-06-27 | 2020-12-30 | Sage Therapeutics, Inc. | Compositions and methods for treating cns disorders |
| KR20220112803A (ko) | 2019-12-05 | 2022-08-11 | 세이지 테라퓨틱스, 인크. | 19-nor c3,3-이치환된 c21-n-피라졸릴 스테로이드 및 그의 사용 방법 |
| WO2021188778A2 (en) | 2020-03-18 | 2021-09-23 | Sage Therapeutics, Inc. | Neuroactive steroids and their methods of use |
| EP4125921A1 (en) | 2020-03-25 | 2023-02-08 | Sage Therapeutics, Inc. | Use of agents for treatment of respiratory conditions |
| US20230250129A1 (en) | 2020-06-24 | 2023-08-10 | Sage Therapeutics, Inc. | Neuroactive steroids and compositions thereof |
| KR20230041049A (ko) | 2020-07-20 | 2023-03-23 | 세이지 테라퓨틱스, 인크. | 19-노르 c3,3-이치환된 c21-n-피라졸릴 스테로이드의 제형 및 이의 사용 방법 |
| WO2022115381A1 (en) | 2020-11-25 | 2022-06-02 | Sage Therapeutics, Onc. | Compositions and methods for treating cns disorders cross reference to related application |
| KR20230136599A (ko) | 2021-01-28 | 2023-09-26 | 세이지 테라퓨틱스, 인크. | 성 기능장애의 치료를 위한 신경활성 스테로이드의용도 |
| WO2022177718A1 (en) | 2021-02-18 | 2022-08-25 | Sage Therapeutics, Inc. | Use of neuroactive steroid for treatment of sexual dysfunction |
| US20240245711A1 (en) | 2021-03-17 | 2024-07-25 | Sage Therapeutics, Inc. | A 19-nor c3,3-disubstituted c21-n-pyrazolyl steroid for the treatment of major depressive disorder |
| JP2024513581A (ja) | 2021-04-12 | 2024-03-26 | セージ セラピューティクス， インコーポレイテッド | 本態性振戦の治療 |
| WO2022232504A1 (en) | 2021-04-29 | 2022-11-03 | Sage Therapeutics, Inc. | 19-nor c3,3-disubstituted c21 -n-pyrazolyl steroid for use in treating major depressive disorder and postpartum depression |
| EP4329769A1 (en) | 2021-04-29 | 2024-03-06 | Sage Therapeutics, Inc. | Neuroactive steroid for use in treating major depressive disorder and postpartum depression in a lactating female |
| IL315023A (en) | 2022-02-16 | 2024-10-01 | Sage Therapeutics Inc | Neuroactive steroids for treatment of cns-related disorders |
| WO2023163879A1 (en) | 2022-02-28 | 2023-08-31 | Sage Therapeutics, Inc. | Neuroactive steroids for treatment of gastrointestinal diseases or conditions |
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