5-methyl-3-oxo-5β-estrane-17β-carbonitrile | 181931-08-8

• 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: 5-methyl-3-oxo-5β-estrane-17β-carbonitrile
• 英文别名: (5R,8R,9S,10R,13S,14S,17S)-5,13-dimethyl-3-oxo-1,2,4,6,7,8,9,10,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-17-carbonitrile
• CAS: 181931-08-8
• 化学式: C₂₀H₂₉NO
• 分子量: 299.456
• InChiKey: UMVXABSMFCHTHV-SKAYVDEBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  40.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-methyl-3-oxo-5β-estrane-17β-carbonitrile 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 1.0h， 以46%的产率得到3β-hydroxy-5-methyl-5β-estrane-17β-carbonitrile
  参考文献：
  名称：

  Neurosteroid Analogues. 4. The Effect of Methyl Substitution at the C-5 and C-10 Positions of Neurosteroids on Electrophysiological Activity at GABA_A Receptors

  摘要：

  A series of analogues of the neuroactive steroids 3 alpha-hydroxy-5 alpha-pregnan-20-one and 3 alpha-hydroxy-5 beta-pregnan-20-one were studied to elucidate the mode of binding of 5 alpha- and 5 beta-reduced steroids to steroid binding sites on GABA(A) receptors. Analogues which were either 3 alpha-hydroxy-20-ketosteroids or 3 alpha-hydroxysteroid-17 beta-carbonitriles and which contained various methyl group substitution patterns at C-5 and C-10 were prepared. Evaluations utilized whole-cell patch clamp electrophysiological methods carried out on cultured rat hippocampal neurons, and the results obtained with the rigid 17 beta-carbonitrile analogs were analyzed using molecular modeling methods. The molecular modeling results provide a rationale for the observation that the configuration of the hydroxyl group at C-3 is a greater determinant of anesthetic potency than the configuration of the A,B ring fusion at C-5. The electrophysiological results identify steric restrictions for the space that can be occupied in 5 alpha- and 5 beta-reduced steriod modulators of GABA(A) receptors in the regions of space proximate to the steroid C-5, C-10, and possibly C-4 positions. This information is useful for the development of nonsteroidal analogues that can modulate GABA(A) receptors via interactions at steroid binding sites.

  DOI：

  10.1021/jm960304p
• 作为产物：
  描述：

  3β-hydroxy-5-methyl-5β-estrane-17β-carbonitrile 在 chromium(VI) oxide 、 硫酸 作用下， 以 丙酮 为溶剂， 以95%的产率得到5-methyl-3-oxo-5β-estrane-17β-carbonitrile
  参考文献：
  名称：

  Neurosteroid Analogues. 4. The Effect of Methyl Substitution at the C-5 and C-10 Positions of Neurosteroids on Electrophysiological Activity at GABA_A Receptors

  摘要：

  A series of analogues of the neuroactive steroids 3 alpha-hydroxy-5 alpha-pregnan-20-one and 3 alpha-hydroxy-5 beta-pregnan-20-one were studied to elucidate the mode of binding of 5 alpha- and 5 beta-reduced steroids to steroid binding sites on GABA(A) receptors. Analogues which were either 3 alpha-hydroxy-20-ketosteroids or 3 alpha-hydroxysteroid-17 beta-carbonitriles and which contained various methyl group substitution patterns at C-5 and C-10 were prepared. Evaluations utilized whole-cell patch clamp electrophysiological methods carried out on cultured rat hippocampal neurons, and the results obtained with the rigid 17 beta-carbonitrile analogs were analyzed using molecular modeling methods. The molecular modeling results provide a rationale for the observation that the configuration of the hydroxyl group at C-3 is a greater determinant of anesthetic potency than the configuration of the A,B ring fusion at C-5. The electrophysiological results identify steric restrictions for the space that can be occupied in 5 alpha- and 5 beta-reduced steriod modulators of GABA(A) receptors in the regions of space proximate to the steroid C-5, C-10, and possibly C-4 positions. This information is useful for the development of nonsteroidal analogues that can modulate GABA(A) receptors via interactions at steroid binding sites.

  DOI：

  10.1021/jm960304p

文献信息

• Neurosteroid Analogues. 4. The Effect of Methyl Substitution at the C-5 and C-10 Positions of Neurosteroids on Electrophysiological Activity at GABA_A Receptors
  作者：Mingcheng Han、Charles F. Zorumski、Douglas F. Covey

  DOI：10.1021/jm960304p

  日期：1996.1.1

  A series of analogues of the neuroactive steroids 3 alpha-hydroxy-5 alpha-pregnan-20-one and 3 alpha-hydroxy-5 beta-pregnan-20-one were studied to elucidate the mode of binding of 5 alpha- and 5 beta-reduced steroids to steroid binding sites on GABA(A) receptors. Analogues which were either 3 alpha-hydroxy-20-ketosteroids or 3 alpha-hydroxysteroid-17 beta-carbonitriles and which contained various methyl group substitution patterns at C-5 and C-10 were prepared. Evaluations utilized whole-cell patch clamp electrophysiological methods carried out on cultured rat hippocampal neurons, and the results obtained with the rigid 17 beta-carbonitrile analogs were analyzed using molecular modeling methods. The molecular modeling results provide a rationale for the observation that the configuration of the hydroxyl group at C-3 is a greater determinant of anesthetic potency than the configuration of the A,B ring fusion at C-5. The electrophysiological results identify steric restrictions for the space that can be occupied in 5 alpha- and 5 beta-reduced steriod modulators of GABA(A) receptors in the regions of space proximate to the steroid C-5, C-10, and possibly C-4 positions. This information is useful for the development of nonsteroidal analogues that can modulate GABA(A) receptors via interactions at steroid binding sites.