20,20-(ethylenedioxy)-(3R)-spiro[oxirane-2',5β-pregnane] | 185507-66-8

• 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: 20,20-(ethylenedioxy)-(3R)-spiro[oxirane-2',5β-pregnane]
• 英文别名: (3R,5R,8R,9S,10S,13S,14S,17S)-10,13-dimethyl-17-(2-methyl-1,3-dioxolan-2-yl)spiro[1,2,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,2'-oxirane]
• CAS: 185507-66-8
• 化学式: C₂₄H₃₈O₃
• 分子量: 374.564
• InChiKey: BGWBEWADQXHORU-NEKUWPMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  27
• 可旋转键数：
  1
• 环数：
  6.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  31
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  20,20-(ethylenedioxy)-(3R)-spiro[oxirane-2',5β-pregnane] 在 四甲基氯化铵 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以90%的产率得到1-((3R,5R,8R,9S,10S,13S,14S,17S)-3-Chloromethyl-3-hydroxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-ethanone
  参考文献：
  名称：

  Synthesis and in Vitro Activity of 3β-Substituted-3α-hydroxypregnan-20-ones:  Allosteric Modulators of the GABA_A Receptor

  摘要：

  Two naturally occurring metabolites of progesterone, 3 alpha-hydroxy-5 alpha- and 5 beta-pregnan-20-one (1 and 2), are potent allosteric modulators of the GABA(A) receptor. Their therapeutic potential as anxiolytics, anticonvulsants, and sedative/hypnotics is limited by rapid metabolism. To avoid these shortcomings, a series of 3 beta-substituted derivatives of 1 and 2 was prepared. Small lipophilic groups generally maintain potency in both the 5 alpha- and 5 beta-series as determined by inhibition of [S-35]TBPS binding. In the 5 alpha-series, 3 beta-ethyl, -propyl, -trifluoromethyl and -(benzyloxy)methyl, as well as substituents of the form 3 beta-XCH(2), where X is Cl, Br, or I or contains unsaturation, show limited efficacy in inhibiting [S-35]TBPS binding. In the 5 beta-series, the unsubstituted parent 2 is a two-component inhibitor, whereas all of the 3 beta-substituted derivatives of 2 inhibit TBPS via a single class of binding sites. In addition, all of the 3-substituted 5 beta-sterols tested are full inhibitors of [S-35]TBPS binding. Electrophysiological measurements using alpha 1 beta 2 gamma 2L receptors expressed in oocytes show that 3 beta-methyl- and 3 beta-(azidomethyl)-3 alpha-hydroxy-5 alpha-pregnan-20-one (6 and 22, respectively) are potent full efficacy modulators and that 3 alpha-hydroxy-3 beta-(trifluoromethyl)-5 alpha-pregnan-20-one (24) is a low-efficacy modulator, confirming the results obtained from [S-35]TBPS binding. These results indicate that modification of the 3 beta-position in 1 and 2 maintains activity at the neuroactive steroid site on the GABA(A) receptor. In animal studies, compound 6 (CCD 1042) is an orally active anticonvulsant, while the naturally occurring progesterone metabolites I and 2 are inactive when administered orally, suggesting that 3 beta-substitution slows metabolism of the S-hydroxyl, resulting in orally bioavailable steroid modulators of the GABA(A) receptor.

  DOI：

  10.1021/jm960021x
• 作为产物：
  描述：

  20,20-(ethylenedioxy)-5β-pregnan-3-one 在 potassium tert-butylate 、 potassium carbonate 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.5h， 生成 20,20-(ethylenedioxy)-(3R)-spiro[oxirane-2',5β-pregnane]
  参考文献：
  名称：

  Synthesis and in Vitro Activity of 3β-Substituted-3α-hydroxypregnan-20-ones:  Allosteric Modulators of the GABA_A Receptor

  摘要：

  Two naturally occurring metabolites of progesterone, 3 alpha-hydroxy-5 alpha- and 5 beta-pregnan-20-one (1 and 2), are potent allosteric modulators of the GABA(A) receptor. Their therapeutic potential as anxiolytics, anticonvulsants, and sedative/hypnotics is limited by rapid metabolism. To avoid these shortcomings, a series of 3 beta-substituted derivatives of 1 and 2 was prepared. Small lipophilic groups generally maintain potency in both the 5 alpha- and 5 beta-series as determined by inhibition of [S-35]TBPS binding. In the 5 alpha-series, 3 beta-ethyl, -propyl, -trifluoromethyl and -(benzyloxy)methyl, as well as substituents of the form 3 beta-XCH(2), where X is Cl, Br, or I or contains unsaturation, show limited efficacy in inhibiting [S-35]TBPS binding. In the 5 beta-series, the unsubstituted parent 2 is a two-component inhibitor, whereas all of the 3 beta-substituted derivatives of 2 inhibit TBPS via a single class of binding sites. In addition, all of the 3-substituted 5 beta-sterols tested are full inhibitors of [S-35]TBPS binding. Electrophysiological measurements using alpha 1 beta 2 gamma 2L receptors expressed in oocytes show that 3 beta-methyl- and 3 beta-(azidomethyl)-3 alpha-hydroxy-5 alpha-pregnan-20-one (6 and 22, respectively) are potent full efficacy modulators and that 3 alpha-hydroxy-3 beta-(trifluoromethyl)-5 alpha-pregnan-20-one (24) is a low-efficacy modulator, confirming the results obtained from [S-35]TBPS binding. These results indicate that modification of the 3 beta-position in 1 and 2 maintains activity at the neuroactive steroid site on the GABA(A) receptor. In animal studies, compound 6 (CCD 1042) is an orally active anticonvulsant, while the naturally occurring progesterone metabolites I and 2 are inactive when administered orally, suggesting that 3 beta-substitution slows metabolism of the S-hydroxyl, resulting in orally bioavailable steroid modulators of the GABA(A) receptor.

  DOI：

  10.1021/jm960021x