(5α)-17-oxo-3,4-secoestrane-2,3-dicarboxylic acid | 93517-78-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (5α)-17-oxo-3,4-secoestrane-2,3-dicarboxylic acid
• 英文别名: 2-[(3aS,5aR,6S,7S,9aR,9bS)-6-(carboxymethyl)-3a-methyl-3-oxo-2,4,5,5a,6,7,8,9,9a,9b-decahydro-1H-cyclopenta[a]naphthalen-7-yl]acetic acid
• CAS: 93517-78-3
• 化学式: C₁₈H₂₆O₅
• 分子量: 322.401
• InChiKey: GZFVGYNDYJGOFD-BBZKFQOASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  91.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (5α)-17-oxo-3,4-secoestrane-2,3-dicarboxylic acid 在 吡啶 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 水 、 sodium methylate 、 乙酰氯 、 lithium chloride 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.08h， 生成 (5α,17β)-17-[[(4-methylphenyl)sulfonyl]oxy]-A-norestran-2-one
  参考文献：
  名称：

  Neurosteroid Analogues. 18. Structure–Activity Studies of ent-Steroid Potentiators of γ-Aminobutyric Acid Type A Receptors and Comparison of Their Activities with Those of Alphaxalone and Allopregnanolone

  摘要：

  A model of the alignment of neurosteroids and ent-neurosteroids at the same binding site on gamma-aminobutyric acid type A (GABA(A)) receptors was evaluated for its ability to identify the structural features in ent-neurosteroids that enhance their activity as positive allosteric modulators of this receptor. Structural features that were identified included: (1) a ketone group at position C-16, (2) an axial 4 alpha-OMe group, and (3) a C-18 methyl group. Two ent-steroids were identified that were more potent than the anesthetic steroid alphaxalone in their threshold for and duration of loss of the righting reflex in mice. In tadpoles, loss of righting reflex for these two ent-steroids 0 occurs with EC50 values similar to those found for allopregnanolone. The results indicate that ent-steroids have considerable potential to be developed as anesthetic agents and as drugs to treat brain disorders that are ameliorated by positive allosteric modulators of GABA(A) receptor function.

  DOI：

  10.1021/jm401577c
• 作为产物：
  描述：

  雌甾-3,17-二酮 在 chromium(VI) oxide 、 硫酸 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 1.0h， 以60%的产率得到(5α)-17-oxo-3,4-secoestrane-2,3-dicarboxylic acid
  参考文献：
  名称：

  Neurosteroid Analogues. 18. Structure–Activity Studies of ent-Steroid Potentiators of γ-Aminobutyric Acid Type A Receptors and Comparison of Their Activities with Those of Alphaxalone and Allopregnanolone

  摘要：

  A model of the alignment of neurosteroids and ent-neurosteroids at the same binding site on gamma-aminobutyric acid type A (GABA(A)) receptors was evaluated for its ability to identify the structural features in ent-neurosteroids that enhance their activity as positive allosteric modulators of this receptor. Structural features that were identified included: (1) a ketone group at position C-16, (2) an axial 4 alpha-OMe group, and (3) a C-18 methyl group. Two ent-steroids were identified that were more potent than the anesthetic steroid alphaxalone in their threshold for and duration of loss of the righting reflex in mice. In tadpoles, loss of righting reflex for these two ent-steroids 0 occurs with EC50 values similar to those found for allopregnanolone. The results indicate that ent-steroids have considerable potential to be developed as anesthetic agents and as drugs to treat brain disorders that are ameliorated by positive allosteric modulators of GABA(A) receptor function.

  DOI：

  10.1021/jm401577c

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. 18. Structure–Activity Studies of <i>ent</i>-Steroid Potentiators of γ-Aminobutyric Acid Type A Receptors and Comparison of Their Activities with Those of Alphaxalone and Allopregnanolone
  作者：Mingxing Qian、Kathiresan Krishnan、Eva Kudova、Ping Li、Brad D. Manion、Amanda Taylor、George Elias、Gustav Akk、Alex S. Evers、Charles F. Zorumski、Steven Mennerick、Douglas F. Covey

  DOI：10.1021/jm401577c

  日期：2014.1.9

  A model of the alignment of neurosteroids and ent-neurosteroids at the same binding site on gamma-aminobutyric acid type A (GABA(A)) receptors was evaluated for its ability to identify the structural features in ent-neurosteroids that enhance their activity as positive allosteric modulators of this receptor. Structural features that were identified included: (1) a ketone group at position C-16, (2) an axial 4 alpha-OMe group, and (3) a C-18 methyl group. Two ent-steroids were identified that were more potent than the anesthetic steroid alphaxalone in their threshold for and duration of loss of the righting reflex in mice. In tadpoles, loss of righting reflex for these two ent-steroids 0 occurs with EC50 values similar to those found for allopregnanolone. The results indicate that ent-steroids have considerable potential to be developed as anesthetic agents and as drugs to treat brain disorders that are ameliorated by positive allosteric modulators of GABA(A) receptor function.