(3β,5α,8α,9β,10α,13α,14β,17α)-3-hydroxypregnan-20-one | 210692-32-3

• 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: (3β,5α,8α,9β,10α,13α,14β,17α)-3-hydroxypregnan-20-one
• 英文别名: ent-pregnanolone；ent-(3α,5β)-3-hydroxypregnan-20-one；ent-3α-hydroxy-5β-pregnan-20-one；1-[(3S,5S,8S,9R,10R,13R,14R,17R)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanone
• CAS: 210692-32-3
• 化学式: C₂₁H₃₄O₂
• 分子量: 318.5
• InChiKey: AURFZBICLPNKBZ-ZGLJFNAKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3β,5α,8α,9β,10α,13α,14β,17α)-3-hydroxypregnan-20-one 在 吡啶 、 三甲基氨基磺酸 、 氨 作用下， 反应 432.0h， 以89%的产率得到(3β,5α,8α,9β,10α,13α,14β,17α)-3-(sulfooxy)pregnan-20-one ammonium salt
  参考文献：
  名称：

  Neurosteroid Analogues. 6. The Synthesis and GABA_A Receptor Pharmacology of Enantiomers of Dehydroepiandrosterone Sulfate, Pregnenolone Sulfate, and (3α,5β)-3-Hydroxypregnan-20-one Sulfate

  摘要：

  The unnatural enantiomers of dehydroepiandrosterone sulfate (1), pregnenolone sulfate (2), and (3 alpha,5 beta)-3-hydroxypregnan-20-one sulfate (3), compounds 4-6, respectively, were prepared by total steroid synthesis. The enantioselectivity of the compounds as negative modulators of the GABA(A) receptors present in cultured rat hippocampal neurons was examined using electrophysiological methods. Enantioselectivity was found for the inhibitory actions of the dehydroepiandrosterone enantiomers, The IC(50)s for compounds 1 and 4 were 11 +/- 1 and 80 +/- 14 mu M, respectively. Little, if any, enantioselectivity was found for the other two pairs of steroid sulfate inhibitors. The IC(50)s for compounds 2 and 5 were 82 +/- 12 and 76 +/- 27 mu M, respectively. The IC(50)s for compounds 3 and 6 were 39 +/- 7 and 46 +/- 2 mu M, respectively. The results suggest that the sites of action for the androstane and pregnane series of steroid sulfate blockers of GABA-mediated current are different. The observed enantioselectivity for the actions of dehydroepiandrosterone sulfate indicates that its inhibitory actions are mediated via a chiral recognition site and provides new evidence in support of the earlier hypothesis that there is a binding site for this compound on GABA(A) receptors. Conversely, the failure to observe enantioselectivity for the actions of pregnenolone sulfate and steroid sulfate 3 indicates that a chiral recognition site far these steroids does not exist on GABA(A) receptors and suggests that the effects of these compounds on this receptor's function may arise indirectly as a consequence of steroid-induced membrane perturbation.

  DOI：

  10.1021/jm980148h
• 作为产物：
  描述：

  dl-Δ⁴-androstene-3,17-dione 在 4-二甲氨基吡啶 、 sodium hydroxide 、 硼烷四氢呋喃络合物 、 dimsylsodium 、 potassium tert-butylate 、 四丁基氟化铵 、 双氧水 、 sodium acetate 、 lithium tri-t-butoxyaluminum hydride 、 三乙胺 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 二氯甲烷 、 叔丁醇 为溶剂， 反应 67.0h， 生成 (3β,5α,8α,9β,10α,13α,14β,17α)-3-hydroxypregnan-20-one
  参考文献：
  名称：

  Neurosteroid Analogues. 6. The Synthesis and GABA_A Receptor Pharmacology of Enantiomers of Dehydroepiandrosterone Sulfate, Pregnenolone Sulfate, and (3α,5β)-3-Hydroxypregnan-20-one Sulfate

  摘要：

  The unnatural enantiomers of dehydroepiandrosterone sulfate (1), pregnenolone sulfate (2), and (3 alpha,5 beta)-3-hydroxypregnan-20-one sulfate (3), compounds 4-6, respectively, were prepared by total steroid synthesis. The enantioselectivity of the compounds as negative modulators of the GABA(A) receptors present in cultured rat hippocampal neurons was examined using electrophysiological methods. Enantioselectivity was found for the inhibitory actions of the dehydroepiandrosterone enantiomers, The IC(50)s for compounds 1 and 4 were 11 +/- 1 and 80 +/- 14 mu M, respectively. Little, if any, enantioselectivity was found for the other two pairs of steroid sulfate inhibitors. The IC(50)s for compounds 2 and 5 were 82 +/- 12 and 76 +/- 27 mu M, respectively. The IC(50)s for compounds 3 and 6 were 39 +/- 7 and 46 +/- 2 mu M, respectively. The results suggest that the sites of action for the androstane and pregnane series of steroid sulfate blockers of GABA-mediated current are different. The observed enantioselectivity for the actions of dehydroepiandrosterone sulfate indicates that its inhibitory actions are mediated via a chiral recognition site and provides new evidence in support of the earlier hypothesis that there is a binding site for this compound on GABA(A) receptors. Conversely, the failure to observe enantioselectivity for the actions of pregnenolone sulfate and steroid sulfate 3 indicates that a chiral recognition site far these steroids does not exist on GABA(A) receptors and suggests that the effects of these compounds on this receptor's function may arise indirectly as a consequence of steroid-induced membrane perturbation.

  DOI：

  10.1021/jm980148h

文献信息

• Total Synthesis of <i>ent</i>-Pregnanolone Sulfate and Its Biological Investigation at the NMDA Receptor
  作者：Vojtech Kapras、Vojtech Vyklicky、Milos Budesinsky、Ivana Cisarova、Ladislav Vyklicky、Hana Chodounska、Ullrich Jahn

  DOI：10.1021/acs.orglett.7b03838

  日期：2018.2.16

  A unique asymmetric total synthesis of the unnatural enantiomer of pregnanolone, as well as a study of its biological activity at the NMDA receptor, is reported. The asymmetry is introduced by a highly atom-economic organocatalytic Robinson annulation. A new method for the construction of the cyclopentane D-ring consisting of CuI-catalyzed conjugate addition and oxygenation followed by thermal cyclization

  据报道，孕烯醇酮的非天然对映体的独特的不对称全合成以及对NMDA受体的生物活性的研究。不对称性是通过高度原子经济的有机催化Robinson环空法引入的。开发了一种新的环戊烷D-环的构建方法，该方法由Cu I催化的共轭物加成和氧合，然后利用持久自由基效应进行热环化。ent-孕烷醇硫酸盐是令人惊讶的仅2.6倍比天然神经类固醇活性较低。
• 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。
• Neurosteroid Analogues. 6. The Synthesis and GABA_A Receptor Pharmacology of Enantiomers of Dehydroepiandrosterone Sulfate, Pregnenolone Sulfate, and (3α,5β)-3-Hydroxypregnan-20-one Sulfate
  作者：Kent R. Nilsson、Charles F. Zorumski、Douglas F. Covey

  DOI：10.1021/jm980148h

  日期：1998.7.1

  The unnatural enantiomers of dehydroepiandrosterone sulfate (1), pregnenolone sulfate (2), and (3 alpha,5 beta)-3-hydroxypregnan-20-one sulfate (3), compounds 4-6, respectively, were prepared by total steroid synthesis. The enantioselectivity of the compounds as negative modulators of the GABA(A) receptors present in cultured rat hippocampal neurons was examined using electrophysiological methods. Enantioselectivity was found for the inhibitory actions of the dehydroepiandrosterone enantiomers, The IC(50)s for compounds 1 and 4 were 11 +/- 1 and 80 +/- 14 mu M, respectively. Little, if any, enantioselectivity was found for the other two pairs of steroid sulfate inhibitors. The IC(50)s for compounds 2 and 5 were 82 +/- 12 and 76 +/- 27 mu M, respectively. The IC(50)s for compounds 3 and 6 were 39 +/- 7 and 46 +/- 2 mu M, respectively. The results suggest that the sites of action for the androstane and pregnane series of steroid sulfate blockers of GABA-mediated current are different. The observed enantioselectivity for the actions of dehydroepiandrosterone sulfate indicates that its inhibitory actions are mediated via a chiral recognition site and provides new evidence in support of the earlier hypothesis that there is a binding site for this compound on GABA(A) receptors. Conversely, the failure to observe enantioselectivity for the actions of pregnenolone sulfate and steroid sulfate 3 indicates that a chiral recognition site far these steroids does not exist on GABA(A) receptors and suggests that the effects of these compounds on this receptor's function may arise indirectly as a consequence of steroid-induced membrane perturbation.

表征谱图