(3α,4β,5α)-3-hydroxy-4-methoxyandrostan-17-one | 1516884-15-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (3α,4β,5α)-3-hydroxy-4-methoxyandrostan-17-one
• 英文别名: (3R,4R,5R,8R,9S,10R,13S,14S)-3-hydroxy-4-methoxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthren-17-one
• CAS: 1516884-15-3
• 化学式: C₂₀H₃₂O₃
• 分子量: 320.472
• InChiKey: QVUDHDZBCMSLHH-YBEMEBNRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.58
• 重原子数：
  23.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  46.53
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (3α,4β,5α)-3-hydroxy-4-methoxyandrostan-17-one 在 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 cerium(III) chloride heptahydrate 、 三乙胺 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 23.0h， 生成 (3α,4β,17β)-4-methoxy-16-(phenylmethylene)-androstane-3,17-diol diacetate
  参考文献：
  名称：

  Neurosteroid Analogues. 18. Structure–Activity Studies of ent-Steroid Potentiators of γ-Aminobutyric Acid Type A Receptors and Comparison of Their Activities with Those of Alphaxalone and Allopregnanolone

  摘要：

  A model of the alignment of neurosteroids and ent-neurosteroids at the same binding site on gamma-aminobutyric acid type A (GABA(A)) receptors was evaluated for its ability to identify the structural features in ent-neurosteroids that enhance their activity as positive allosteric modulators of this receptor. Structural features that were identified included: (1) a ketone group at position C-16, (2) an axial 4 alpha-OMe group, and (3) a C-18 methyl group. Two ent-steroids were identified that were more potent than the anesthetic steroid alphaxalone in their threshold for and duration of loss of the righting reflex in mice. In tadpoles, loss of righting reflex for these two ent-steroids 0 occurs with EC50 values similar to those found for allopregnanolone. The results indicate that ent-steroids have considerable potential to be developed as anesthetic agents and as drugs to treat brain disorders that are ameliorated by positive allosteric modulators of GABA(A) receptor function.

  DOI：

  10.1021/jm401577c
• 作为产物：
  描述：

  雄烯二酮 在 甲酸 、 硫酸 、 双氧水 、 溶剂黄146 、 锌 作用下， 以 二氯甲烷 为溶剂， 反应 7.5h， 生成 (3α,4β,5α)-3-hydroxy-4-methoxyandrostan-17-one
  参考文献：
  名称：

  Neurosteroid Analogues. 18. Structure–Activity Studies of ent-Steroid Potentiators of γ-Aminobutyric Acid Type A Receptors and Comparison of Their Activities with Those of Alphaxalone and Allopregnanolone

  摘要：

  A model of the alignment of neurosteroids and ent-neurosteroids at the same binding site on gamma-aminobutyric acid type A (GABA(A)) receptors was evaluated for its ability to identify the structural features in ent-neurosteroids that enhance their activity as positive allosteric modulators of this receptor. Structural features that were identified included: (1) a ketone group at position C-16, (2) an axial 4 alpha-OMe group, and (3) a C-18 methyl group. Two ent-steroids were identified that were more potent than the anesthetic steroid alphaxalone in their threshold for and duration of loss of the righting reflex in mice. In tadpoles, loss of righting reflex for these two ent-steroids 0 occurs with EC50 values similar to those found for allopregnanolone. The results indicate that ent-steroids have considerable potential to be developed as anesthetic agents and as drugs to treat brain disorders that are ameliorated by positive allosteric modulators of GABA(A) receptor function.

  DOI：

  10.1021/jm401577c

文献信息

• Neuroactive steroids, compositions, and uses thereof
  申请人：Sage Therapeutics, Inc.

  公开号：US11046728B2

  公开（公告）日：2021-06-29

  Described herein are neuroactive steroids of the Formula (I): or a pharmaceutically acceptable salt thereof; wherein R1a and R1b are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use and treatment, e.g., such for inducing sedation and/or anesthesia.

  本文描述的是式 (I) 的神经活性类固醇： 或其药学上可接受的盐；其中 R1a 和 R1b 如本文所定义。在某些实施方案中，此类化合物被设想为 GABA 调节剂。本发明还提供了包含本发明化合物的药物组合物以及使用和治疗方法，例如用于诱导镇静和/或麻醉的方法。
• [EN] NEUROACTIVE STEROIDS, COMPOSITIONS, AND USES THEREOF<br/>[FR] STÉROÏDES NEUROACTIFS, COMPOSITIONS, ET LEURS UTILISATIONS
  申请人：SAGE THERAPEUTICS INC

  公开号：WO2015010054A3

  公开（公告）日：2015-04-09
• NEUROACTIVE STEROIDS, COMPOSITIONS, AND USES THEREOF
  申请人：Sage Therapeutics, Inc.

  公开号：EP3021852B1

  公开（公告）日：2021-01-27
• Neurosteroid Analogues. 18. Structure–Activity Studies of <i>ent</i>-Steroid Potentiators of γ-Aminobutyric Acid Type A Receptors and Comparison of Their Activities with Those of Alphaxalone and Allopregnanolone
  作者：Mingxing Qian、Kathiresan Krishnan、Eva Kudova、Ping Li、Brad D. Manion、Amanda Taylor、George Elias、Gustav Akk、Alex S. Evers、Charles F. Zorumski、Steven Mennerick、Douglas F. Covey

  DOI：10.1021/jm401577c

  日期：2014.1.9

  A model of the alignment of neurosteroids and ent-neurosteroids at the same binding site on gamma-aminobutyric acid type A (GABA(A)) receptors was evaluated for its ability to identify the structural features in ent-neurosteroids that enhance their activity as positive allosteric modulators of this receptor. Structural features that were identified included: (1) a ketone group at position C-16, (2) an axial 4 alpha-OMe group, and (3) a C-18 methyl group. Two ent-steroids were identified that were more potent than the anesthetic steroid alphaxalone in their threshold for and duration of loss of the righting reflex in mice. In tadpoles, loss of righting reflex for these two ent-steroids 0 occurs with EC50 values similar to those found for allopregnanolone. The results indicate that ent-steroids have considerable potential to be developed as anesthetic agents and as drugs to treat brain disorders that are ameliorated by positive allosteric modulators of GABA(A) receptor function.