ent-etiocholanolone | 942499-58-3

• 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: ent-etiocholanolone
• 英文别名: Androstan-17-one,3-hydroxy-, (3a,5b)-；(3S,5S,8S,9R,10R,13R,14R)-3-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthren-17-one
• CAS: 942499-58-3
• 化学式: C₁₉H₃₀O₂
• 分子量: 290.446
• InChiKey: QGXBDMJGAMFCBF-USFNPTTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  0
• 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：

  ent-etiocholanolone 、 乙基三苯基溴化膦 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 以95%的产率得到(3β,5α,8α,9β,10α,13α,14β,17Z)-pregn-17(20)-en-3-ol
  参考文献：
  名称：

  Synthesis, Characterization, and Receptor Interaction Profiles of Enantiomeric Bile Acids

  摘要：

  Bile acids are endogenous steroid detergents with receptor-mediated physiologic actions including activation of the G-protein coupled receptor TGR5 and gene regulation mediated by nuclear receptors. In this study, we report the first synthesis of enantiomeric lithocholic acid (ent-LCA, ent-1) and chenodeoxycholic acid (ent-CDCA, ent-2) via ent-testosterone (3). ent-1 was synthesized in 21 total steps in 4.2% yield, whereas ent-2 was obtained in 23 total steps in 0.8% yield. Critical micelle concentrations of the enantiomeric bile acids were found to be identical to their natural counterparts. Furthermore, enantiomeric bile acids were also tested for their ability to modulate bile acid activated proteins: farnesoid X receptor, vitamin D receptor, pregnane X receptor, and TGR5. Interestingly, ent-1 and ent-2 showed differential interactions with these proteins as compared to their corresponding natural bile acids. These data highlight the potential for using enantioselectivity as away to distinguish between receptor and nonreceptor-mediated functions of natural bile acids.

  DOI：

  10.1021/jm0707931
• 作为产物：
  描述：

  ent-(5β)-androstane-3,17-dione 在 lithium tri-t-butoxyaluminum hydride 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以90%的产率得到ent-etiocholanolone
  参考文献：
  名称：

  Neurosteroid analogues. 12. Potent enhancement of GABA-mediated chloride currents at GABAA receptors by ent-androgens

  摘要：

  Allopregnanolone (1) and pregnanolone (2), steroids containing a 17 beta-acetyl group, are potent enhancers of GABA (gamma-aminobutyric acid) action at GABA(A) receptors. Their effects are enantioselective with the non-naturally occurring enantiomers (ent-1 and ent-2) being less potent. Androsterone (3) and etiocholanolone (4), steroids with a C-17 carbonyl group, are weak enhancers of GABA action at GABA(A) receptors. Unexpectedly, their enantiomers (ent-3 and ent-4) have been found to have enhanced, not diminished, activity at GABA(A) receptors. Furthermore, the C-17 spiro-epoxide analogues (ent-5 and ent-6) of ent-3 and ent-4, respectively, have activities comparable to those of steroids 1 and 2. The results indicate that some ent-steroids are potent modulators of GABA(A) receptors and might have clinical potential as GABAergic drugs of the future. (C) 2007 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2007.02.017

文献信息

• 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。
• [EN] NEUROACTIVE ENANTIOMERIC 15-, 16- AND 17-SUBSTITUTED STEROIDS AS MODULATORS FOR GABA TYPE-A RECEPTORS<br/>[FR] STÉROÏDES ÉNANTIOMÈRES NEUROACTIFS SUSBTITUÉS EN POSITION 15, 16 ET 17, UTILISÉS COMME MODULATEURS DE RÉCEPTEURS GABA DE TYPE A
  申请人：UNIV WASHINGTON

  公开号：WO2014127201A1

  公开（公告）日：2014-08-21

  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.
• Neurosteroid analogues. 12. Potent enhancement of GABA-mediated chloride currents at GABAA receptors by ent-androgens
  作者：Bryson W. Katona、Kathiresan Krishnan、Zu Yun Cai、Brad D. Manion、Ann Benz、Amanda Taylor、Alex S. Evers、Charles F. Zorumski、Steven Mennerick、Douglas F. Covey

  DOI：10.1016/j.ejmech.2007.02.017

  日期：2008.1

  Allopregnanolone (1) and pregnanolone (2), steroids containing a 17 beta-acetyl group, are potent enhancers of GABA (gamma-aminobutyric acid) action at GABA(A) receptors. Their effects are enantioselective with the non-naturally occurring enantiomers (ent-1 and ent-2) being less potent. Androsterone (3) and etiocholanolone (4), steroids with a C-17 carbonyl group, are weak enhancers of GABA action at GABA(A) receptors. Unexpectedly, their enantiomers (ent-3 and ent-4) have been found to have enhanced, not diminished, activity at GABA(A) receptors. Furthermore, the C-17 spiro-epoxide analogues (ent-5 and ent-6) of ent-3 and ent-4, respectively, have activities comparable to those of steroids 1 and 2. The results indicate that some ent-steroids are potent modulators of GABA(A) receptors and might have clinical potential as GABAergic drugs of the future. (C) 2007 Elsevier Masson SAS. All rights reserved.
• Synthesis, Characterization, and Receptor Interaction Profiles of Enantiomeric Bile Acids
  作者：Bryson W. Katona、Carolyn L. Cummins、Andrew D. Ferguson、Tingting Li、Daniel R. Schmidt、David J. Mangelsdorf、Douglas F. Covey

  DOI：10.1021/jm0707931

  日期：2007.11.1

  Bile acids are endogenous steroid detergents with receptor-mediated physiologic actions including activation of the G-protein coupled receptor TGR5 and gene regulation mediated by nuclear receptors. In this study, we report the first synthesis of enantiomeric lithocholic acid (ent-LCA, ent-1) and chenodeoxycholic acid (ent-CDCA, ent-2) via ent-testosterone (3). ent-1 was synthesized in 21 total steps in 4.2% yield, whereas ent-2 was obtained in 23 total steps in 0.8% yield. Critical micelle concentrations of the enantiomeric bile acids were found to be identical to their natural counterparts. Furthermore, enantiomeric bile acids were also tested for their ability to modulate bile acid activated proteins: farnesoid X receptor, vitamin D receptor, pregnane X receptor, and TGR5. Interestingly, ent-1 and ent-2 showed differential interactions with these proteins as compared to their corresponding natural bile acids. These data highlight the potential for using enantioselectivity as away to distinguish between receptor and nonreceptor-mediated functions of natural bile acids.