(3α,5α,7β,17β)-spiro[7-(benzyloxy)androstane-17,2'-oxiran]-3-ol | 1355032-08-4

• 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: (3α,5α,7β,17β)-spiro[7-(benzyloxy)androstane-17,2'-oxiran]-3-ol
• 英文别名: (3R,5R,7S,8R,9S,10S,13S,14S,17S)-10,13-dimethyl-7-phenylmethoxyspiro[1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthrene-17,2'-oxirane]-3-ol
• CAS: 1355032-08-4
• 化学式: C₂₇H₃₈O₃
• 分子量: 410.597
• InChiKey: CDBFPAYYTGGOCC-HPBYYPRXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3β-hydroxy-17,17-ethylenedioxo-5-androstene 在 盐酸 、 叔丁基过氧化氢 、 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 、 palladium 10% on activated carbon 、 potassium tert-butylate 、 氢气 、 sodium acetate 、 potassium hydride 、 potassium tri-sec-butyl-borohydride 、 N,N-二异丙基乙胺 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 、 mineral oil 为溶剂， -78.0~50.0 ℃ 、344.75 kPa 条件下， 反应 117.0h， 生成 (3α,5α,7β,17β)-spiro[7-(benzyloxy)androstane-17,2'-oxiran]-3-ol
  参考文献：
  名称：

  Neurosteroid Analogues. 17. Inverted Binding Orientations of Androsterone Enantiomers at the Steroid Potentiation Site on γ-Aminobutyric Acid Type A Receptors

  摘要：

  The enantiomer pair androsterone and ent-androsterone are positive allosteric modulators of gamma-aminobutyric acid (GABA) type A receptors. Each enantiomer was shown to bind at the same receptor site. Binding orientations of the enantiomers at this site were deduced using enantiomer pairs containing OBn substituents at either C-7 or C-11. 11 beta-OBn-substituted steroids and 7 alpha-OBn-substituted ent-steroids potently displace [S-35]-tert-butylbicyclophosphorothionate, augment GABA currents, and anesthetize tadpoles. In contrast, 7 beta-OBn-substituted steroids and 11 alpha-OBn-substituted ent-steroids have diminished actions. The results suggest that the binding orientations of the active analogues are inverted relative to each other with the 7 alpha- and 11 beta-substituents similarly located on the edges of the molecules not in contact with the receptor surface. Analogue potentiation of the GABA current was abrogated by an alpha(1) subunit Q241L mutation, indicating that the active analogues act at the same sites in alpha(1)beta(2)gamma(2L) receptors previously associated with positive neurosteroid modulation.

  DOI：

  10.1021/jm2014925

文献信息

• Neurosteroid Analogues. 17. Inverted Binding Orientations of Androsterone Enantiomers at the Steroid Potentiation Site on γ-Aminobutyric Acid Type A Receptors
  作者：Kathiresan Krishnan、Brad D. Manion、Amanda Taylor、John Bracamontes、Joseph H. Steinbach、David E. Reichert、Alex S. Evers、Charles F. Zorumski、Steven Mennerick、Douglas F. Covey

  DOI：10.1021/jm2014925

  日期：2012.2.9

  The enantiomer pair androsterone and ent-androsterone are positive allosteric modulators of gamma-aminobutyric acid (GABA) type A receptors. Each enantiomer was shown to bind at the same receptor site. Binding orientations of the enantiomers at this site were deduced using enantiomer pairs containing OBn substituents at either C-7 or C-11. 11 beta-OBn-substituted steroids and 7 alpha-OBn-substituted ent-steroids potently displace [S-35]-tert-butylbicyclophosphorothionate, augment GABA currents, and anesthetize tadpoles. In contrast, 7 beta-OBn-substituted steroids and 11 alpha-OBn-substituted ent-steroids have diminished actions. The results suggest that the binding orientations of the active analogues are inverted relative to each other with the 7 alpha- and 11 beta-substituents similarly located on the edges of the molecules not in contact with the receptor surface. Analogue potentiation of the GABA current was abrogated by an alpha(1) subunit Q241L mutation, indicating that the active analogues act at the same sites in alpha(1)beta(2)gamma(2L) receptors previously associated with positive neurosteroid modulation.