(8α,9β,10α,13α,14β)-androst-5-ene-3,17-dione, cyclic 3,17-bis(1,2-ethanediyl acetal) | 1355032-33-5

• 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: (8α,9β,10α,13α,14β)-androst-5-ene-3,17-dione, cyclic 3,17-bis(1,2-ethanediyl acetal)
• CAS: 1355032-33-5
• 化学式: C₂₃H₃₄O₄
• 分子量: 374.521
• InChiKey: XQKKPTGNGACJSF-SRHPJPHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  36.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (8α,9β,10α,13α,14β)-androst-5-ene-3,17-dione, cyclic 3,17-bis(1,2-ethanediyl acetal) 在 叔丁基过氧化氢 、 palladium 10% on activated carbon 、 氢气 、 potassium hydride 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 、 异丙醇 、 乙腈 、 mineral oil 为溶剂， 50.0 ℃ 、413.7 kPa 条件下， 反应 74.0h， 生成 (5β,7β,8α,9β,10α,13α,14β)-7-(benzyloxy)androstane-3,17-dione, cyclic 3,17-bis(1,2-ethanediyl acetal)
  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
• 作为产物：
  描述：

  乙二醇 、 dl-Δ⁴-androstene-3,17-dione 在 对甲苯磺酸 作用下， 以 苯 为溶剂， 反应 16.0h， 以83%的产率得到(8α,9β,10α,13α,14β)-androst-5-ene-3,17-dione, cyclic 3,17-bis(1,2-ethanediyl acetal)
  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

• NEUROACTIVE ENANTIOMERIC 15-, 16- AND 17-SUBSTITUTED STEROIDS AS MODULATORS FOR GABA TYPE-A RECEPTORS
  申请人：WASHINGTON UNIVERSITY

  公开号：US20150361125A1

  公开（公告）日：2015-12-17

  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.

  本公开涉及具有额外可选取代基团的碳3、4、6、7、10和13的15、16和17位旋光异构的神经活性取代类固醇及其药学上可接受的盐，例如，用作GABA-A受体调节剂。本公开进一步涉及包含这种化合物的制药组合物。
• 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。
• [EN] NEUROACTIVE ENANTIOMERIC 15-, 16- AND 17-SUBSTITUTED STEROIDS AS MODULATORS FOR GABA TYPE-A RECEPTORS<br/>[FR] STÉROÏDES ÉNANTIOMÈRES NEUROACTIFS SUSBTITUÉS EN POSITION 15, 16 ET 17, UTILISÉS COMME MODULATEURS DE RÉCEPTEURS GABA DE TYPE A
  申请人：UNIV WASHINGTON

  公开号：WO2014127201A1

  公开（公告）日：2014-08-21

  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.
• 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.