3α-hydroxy-5,6α-epoxy-7-nor-5α-pregnan-20-one | 286862-23-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧烷类
• 英文名称: 3α-hydroxy-5,6α-epoxy-7-nor-5α-pregnan-20-one
• 英文别名: 1-[(1S,2S,4R,6R,9R,10S,13S,14S,17S)-6-hydroxy-9,13-dimethyl-3-oxapentacyclo[8.7.0.02,4.04,9.013,17]heptadecan-14-yl]ethanone
• CAS: 286862-23-5
• 化学式: C₂₀H₃₀O₃
• 分子量: 318.456
• InChiKey: XCJFPPWIIUINAO-GRMBGQMVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3α-hydroxy-5,6α-epoxy-7-nor-5α-pregnan-20-one 在 三氟化硼乙醚 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 20.0h， 以42%的产率得到1-((3S,3aS,8R,9aR,10S,10aS,10bS)-8,10-Dihydroxy-3a,9a-dimethyl-1,2,3,3a,4,5,6,7,8,9,9a,10,10a,10b-tetradecahydro-cyclopenta[a]fluoren-3-yl)-ethanone
  参考文献：
  名称：

  Activity of B-Nor Analogues of Neurosteroids on the GABA_A Receptor in Primary Neuronal Cultures

  摘要：

  A GABA(A) receptor study of several B-nor analogues of allopregnanolone and pregnanolone has been carried out. B-Norallopregnanolone (i.e., 3 alpha-hydroxy-7-nor-5 alpha-pregnan-20-one) was found comparable to allopregnanolone when measured with labeled TBPS. Analogous results were obtained from their effect on neurons in culture: this time, both 3 alpha-hydroxy-7-nor-5 alpha-pregnan-20-ones (5 and 6) were found to stimulate [H-3] flunitrazepam binding and GABA-induced Cl-36(-) influx. These effects were inhibited by GABA(A) receptor antagonists. Other analogues carrying electronegative substituents (epoxides 9 and 10 and ketone 12) in the B ring were inactive. Similarly, B-normal ketones 17, and 18 and 6-azasteroids 20 and 21 were also inactive. B-Nor analogues 5 and 6 did not induce neurotoxicity at relevant concentrations. A computational analysis of active and inactive neurosteroid analogues allowed the proposal of a 3D pharmacophoric hypothesis of their interaction with the GABA(A) receptor.

  DOI：

  10.1021/jm060002f
• 作为产物：
  描述：

  5,6α-epoxy-20-oxo-7-nor-5α-pregnan-3α-yl formate 在 potassium hydrogencarbonate 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以71%的产率得到3α-hydroxy-5,6α-epoxy-7-nor-5α-pregnan-20-one
  参考文献：
  名称：

  Epalons: 6-Substituted Derivatives of 7-Norepiallopregnanolone

  摘要：

  The target compounds (3 alpha-hydroxy-5,6-epoxy-7-nor-5 alpha-pregnan-20-one, 3 alpha-hydroxy-5,6 beta-epoxy-7-nor-5 beta-pregnan-20-one and 3 alpha-hydroxy-7-nor-5 alpha-pregnane-6,20-dione) were prepared from 5,6 beta-dihydroxy-20-oxo-5 alpha-pregnan-3 beta-yl acetate via the corresponding 5,6-seco acid and 3 beta-acetoxy-20-oxo-7-nor-5 beta,6 alpha-pregnane-6,5-carbolactone-actone. Intermediate 3 beta-hydroxy-7-norpregn-5-en-20-one was converted into the corresponding 5 alpha,6 alpha and 5 beta,6 beta epoxides. The latter was isomerized into 3 beta-hydroxy-7-nor-5 alpha-pregnane-6,20-dione. The configuration of the 3 beta-hydroxy group in these compounds was inverted by Mitsunobu reactions. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(00)00263-5

文献信息

• Epalons: 6-Substituted Derivatives of 7-Norepiallopregnanolone
  作者：Alexander Kasal

  DOI：10.1016/s0040-4020(00)00263-5

  日期：2000.5

  The target compounds (3 alpha-hydroxy-5,6-epoxy-7-nor-5 alpha-pregnan-20-one, 3 alpha-hydroxy-5,6 beta-epoxy-7-nor-5 beta-pregnan-20-one and 3 alpha-hydroxy-7-nor-5 alpha-pregnane-6,20-dione) were prepared from 5,6 beta-dihydroxy-20-oxo-5 alpha-pregnan-3 beta-yl acetate via the corresponding 5,6-seco acid and 3 beta-acetoxy-20-oxo-7-nor-5 beta,6 alpha-pregnane-6,5-carbolactone-actone. Intermediate 3 beta-hydroxy-7-norpregn-5-en-20-one was converted into the corresponding 5 alpha,6 alpha and 5 beta,6 beta epoxides. The latter was isomerized into 3 beta-hydroxy-7-nor-5 alpha-pregnane-6,20-dione. The configuration of the 3 beta-hydroxy group in these compounds was inverted by Mitsunobu reactions. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Activity of B-Nor Analogues of Neurosteroids on the GABA_A Receptor in Primary Neuronal Cultures
  作者：Cristina Suñol、Daniel A. García、Jordi Bujons、Zdena Krištofíková、Libor Matyáš、Zoila Babot、Alexander Kasal

  DOI：10.1021/jm060002f

  日期：2006.6.1

  A GABA(A) receptor study of several B-nor analogues of allopregnanolone and pregnanolone has been carried out. B-Norallopregnanolone (i.e., 3 alpha-hydroxy-7-nor-5 alpha-pregnan-20-one) was found comparable to allopregnanolone when measured with labeled TBPS. Analogous results were obtained from their effect on neurons in culture: this time, both 3 alpha-hydroxy-7-nor-5 alpha-pregnan-20-ones (5 and 6) were found to stimulate [H-3] flunitrazepam binding and GABA-induced Cl-36(-) influx. These effects were inhibited by GABA(A) receptor antagonists. Other analogues carrying electronegative substituents (epoxides 9 and 10 and ketone 12) in the B ring were inactive. Similarly, B-normal ketones 17, and 18 and 6-azasteroids 20 and 21 were also inactive. B-Nor analogues 5 and 6 did not induce neurotoxicity at relevant concentrations. A computational analysis of active and inactive neurosteroid analogues allowed the proposal of a 3D pharmacophoric hypothesis of their interaction with the GABA(A) receptor.