(3β,4α,5β,8α,9β,10α,13α,14β,17α)-3,17-dihydroxy-4-methoxyandrostan-16-one diacetate | 1516884-66-4

• 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: (3β,4α,5β,8α,9β,10α,13α,14β,17α)-3,17-dihydroxy-4-methoxyandrostan-16-one diacetate
• 英文别名: [(3S,4S,5S,8S,9R,10S,13R,14R,17S)-17-acetyloxy-4-methoxy-10,13-dimethyl-16-oxo-1,2,3,4,5,6,7,8,9,11,12,14,15,17-tetradecahydrocyclopenta[a]phenanthren-3-yl] acetate
• CAS: 1516884-66-4
• 化学式: C₂₄H₃₆O₆
• 分子量: 420.546
• InChiKey: NKPXUDRNZJCPCK-ZLUURCTGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  78.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3β,4α,5β,8α,9β,10α,13α,14β,17α)-3,17-dihydroxy-4-methoxyandrostan-16-one diacetate 在 samarium diiodide 、 Jones reagent 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.0h， 生成 (3β,4α,5β,8α,9β,10α,13α,14β)-3-hydroxy-4-methoxyandrostan-16-one acetate
  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：

  (3β,4α,5β,8α,9β,10α,13α,14β)-4-methoxy-16-(phenylmethylene)androstane-3,17-diol diacetate 在 臭氧 、 二甲基硫 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 14.0h， 以87%的产率得到(3β,4α,5β,8α,9β,10α,13α,14β,17α)-3,17-dihydroxy-4-methoxyandrostan-16-one 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

文献信息

• Neuroactive enantiomeric 15-, 16- and 17-substituted steroids as modulators for GABA type-A receptors
  申请人：Washington University

  公开号：US10202413B2

  公开（公告）日：2019-02-12

  The present disclosure is generally directed to neuroactive enantiomeric 15-, 16- and 17-substituted steroids with additional optional substituents at carbons 3, 4, 6, 7, 10 and 13, and pharmaceutically acceptable salts thereof, for use as, for example, modulators for GABA type-A receptors. The present disclosure is further directed to pharmaceutical compositions comprising such compounds.

  本公开内容一般涉及在碳3、4、6、7、10和13上具有额外任选取代基的神经活性对映体15、16和17-取代类固醇及其药学上可接受的盐，可用作例如GABA-A型受体的调节剂。本公开进一步涉及包含此类化合物的药物组合物。