CN114206899A - 3-羟基-5-孕烷-20-酮衍生物及其用途 - Google Patents
3-羟基-5-孕烷-20-酮衍生物及其用途 Download PDFInfo
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- CN114206899A CN114206899A CN202080054158.0A CN202080054158A CN114206899A CN 114206899 A CN114206899 A CN 114206899A CN 202080054158 A CN202080054158 A CN 202080054158A CN 114206899 A CN114206899 A CN 114206899A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
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Abstract
本发明提供式I所示的3‑羟基‑5‑孕烷‑20酮衍生物或其药学上可接受的盐,及包含所述衍生物或其药学上可接受盐的药物组合物。本发明的衍生物或其药学上可接受的盐或包含上述衍生物或盐的药物组合物可以制备用于治疗中枢神经系统异常引起的疾病的药物。
Description
PCT国内申请,说明书已公开。
Claims (10)
- PCT国内申请,权利要求书已公开。
Applications Claiming Priority (3)
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CN2019107360208 | 2019-08-09 | ||
CN201910736020.8A CN112341511A (zh) | 2019-08-09 | 2019-08-09 | 3-羟基-5-孕烷-20-酮衍生物及其用途 |
PCT/CN2020/107965 WO2021027744A1 (zh) | 2019-08-09 | 2020-08-07 | 3-羟基-5-孕烷-20-酮衍生物及其用途 |
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CN114206899A true CN114206899A (zh) | 2022-03-18 |
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CN201910736020.8A Pending CN112341511A (zh) | 2019-08-09 | 2019-08-09 | 3-羟基-5-孕烷-20-酮衍生物及其用途 |
CN202080054158.0A Pending CN114206899A (zh) | 2019-08-09 | 2020-08-07 | 3-羟基-5-孕烷-20-酮衍生物及其用途 |
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US (1) | US20220289788A1 (zh) |
EP (1) | EP4011898A4 (zh) |
JP (1) | JP2022545047A (zh) |
CN (2) | CN112341511A (zh) |
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CN114907436A (zh) * | 2021-02-08 | 2022-08-16 | 南京诺瑞特医药科技有限公司 | 3-羟基-5-孕烷-20-酮衍生物的晶型及其制备方法和用途 |
IT202100030671A1 (it) | 2021-12-03 | 2023-06-03 | Ind Chimica Srl | PROCESSO PER LA PREPARAZIONE DI (3a,5a)-20-OSSOPREGNAN-3-IL GLICIL-L-VALINATO CLORIDRATO |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2015081170A2 (en) * | 2013-11-26 | 2015-06-04 | Systamedic Inc. | Ganaxolone derivatives for treatment of central nervous systems disorders |
CN108148106A (zh) * | 2016-12-05 | 2018-06-12 | 江苏恩华络康药物研发有限公司 | 一类水溶性别孕烯醇酮衍生物及其用途 |
WO2019108673A1 (en) * | 2017-11-28 | 2019-06-06 | Viewpoint Therapeutics, Inc. | Compounds for treating near vision disorders |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5232917A (en) * | 1987-08-25 | 1993-08-03 | University Of Southern California | Methods, compositions, and compounds for allosteric modulation of the GABA receptor by members of the androstane and pregnane series |
BR9506779A (pt) * | 1994-02-14 | 1997-10-14 | Cocensys Inc | Composto composição farmacéutica método para modular o complexo ionóforo receptor gaba-cloreto em um paciente animal pela ligação ao sitio neuroesteróide no dito complexo método para tratar ou evitar estresse ou ansiedade em um paciente animal método para aliviar ou evitar isônia pms ou pnd em um paciente animal método para tratar ou evitar perturbacões na disposicão de ánimo em um paciente animal e método para induzir anestesia em um paciente animal |
EP2471536A1 (en) * | 2004-09-29 | 2012-07-04 | Harbor BioSciences, Inc. | Steroid analogs and characterization and treatment methods |
US9527881B2 (en) * | 2008-02-26 | 2016-12-27 | Emory University | Steroid analogues for neuroprotection |
US20110118219A1 (en) * | 2008-03-25 | 2011-05-19 | University Of Maryland, Baltimore | Novel prodrugs of c-17-heteroaryl steroidal cyp17 inhibitors/antiandrogens: synthesis, in vitro biological activities, pharmacokinetics and antitumor activity |
CN101585862B (zh) * | 2008-05-20 | 2014-12-17 | 梅克芳股份公司 | 甾族化合物 |
US20110306579A1 (en) * | 2009-01-30 | 2011-12-15 | Emory University | Methods of neuroprotection using neuroprotective steroids and a vitamin d |
CA2786330C (en) * | 2010-01-14 | 2013-11-19 | Umecrine Mood Ab | A pharmaceutical composition comprising 3-beta-hydroxy-5-alpha-pregnan-20-one with improved storage and solubility properties |
WO2011120044A1 (en) * | 2010-03-26 | 2011-09-29 | Duke University | Conjugated neuroactive steroid compositions and methods of use |
US9670247B2 (en) * | 2012-07-02 | 2017-06-06 | The University Of Kansas | Contraceptive agents |
CN103772469A (zh) * | 2014-02-21 | 2014-05-07 | 中国科学院上海有机化学研究所 | 一种含有动物固醇和天然精氨酸结构片段的合成阳离子脂质、合成方法及其应用 |
CN108517001A (zh) * | 2018-05-17 | 2018-09-11 | 江苏恩华络康药物研发有限公司 | 水溶性别孕烯醇酮衍生物及其用途 |
CN109776647B (zh) * | 2019-02-14 | 2021-09-17 | 烟台大学 | 具有抗炎活性的Pyxinol酯化衍生物及其制备方法和应用 |
-
2019
- 2019-08-09 CN CN201910736020.8A patent/CN112341511A/zh active Pending
-
2020
- 2020-08-07 JP JP2022534483A patent/JP2022545047A/ja active Pending
- 2020-08-07 WO PCT/CN2020/107965 patent/WO2021027744A1/zh unknown
- 2020-08-07 CN CN202080054158.0A patent/CN114206899A/zh active Pending
- 2020-08-07 US US17/632,770 patent/US20220289788A1/en active Pending
- 2020-08-07 EP EP20852240.9A patent/EP4011898A4/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2015081170A2 (en) * | 2013-11-26 | 2015-06-04 | Systamedic Inc. | Ganaxolone derivatives for treatment of central nervous systems disorders |
CN108148106A (zh) * | 2016-12-05 | 2018-06-12 | 江苏恩华络康药物研发有限公司 | 一类水溶性别孕烯醇酮衍生物及其用途 |
WO2019108673A1 (en) * | 2017-11-28 | 2019-06-06 | Viewpoint Therapeutics, Inc. | Compounds for treating near vision disorders |
Also Published As
Publication number | Publication date |
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CN112341511A (zh) | 2021-02-09 |
US20220289788A1 (en) | 2022-09-15 |
EP4011898A1 (en) | 2022-06-15 |
JP2022545047A (ja) | 2022-10-24 |
WO2021027744A1 (zh) | 2021-02-18 |
EP4011898A4 (en) | 2023-09-20 |
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