5,6α-oxido-20-oxo-7-nor-5α-pregnan-3β-yl methanesulfonate | 888500-26-3

• 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: 5,6α-oxido-20-oxo-7-nor-5α-pregnan-3β-yl methanesulfonate
• 英文别名: [(1S,2S,4R,6S,9R,10S,13S,14S,17S)-14-acetyl-9,13-dimethyl-3-oxapentacyclo[8.7.0.02,4.04,9.013,17]heptadecan-6-yl] methanesulfonate
• CAS: 888500-26-3
• 化学式: C₂₁H₃₂O₅S
• 分子量: 396.548
• InChiKey: FTEUOORGSGEZRU-NDNMXYSZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  81.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5,6α-oxido-20-oxo-7-nor-5α-pregnan-3β-yl methanesulfonate 在 potassium nitrite 作用下， 以 二甲基亚砜 为溶剂， 反应 1.5h， 以65%的产率得到3α-hydroxy-5,6α-epoxy-7-nor-5α-pregnan-20-one
  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：

  3β-hydroxy-7-norpregn-5-en-20-one 在 吡啶 、 间氯过氧苯甲酸 作用下， 以 氯仿 为溶剂， 反应 5.0h， 生成 5,6α-oxido-20-oxo-7-nor-5α-pregnan-3β-yl methanesulfonate
  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

文献信息

• 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.