(5'R,6'S,8'R,9'S,10'R,13'S,14'S)-10',13'-dimethyltetradecahydro-2'H-dispiro[[1,3]dioxolane-2,3'-cyclopenta[a]phenanthrene-17',2''-[1,3]dioxolane]-6'-carbonitrile | 953772-21-9

• 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'R,6'S,8'R,9'S,10'R,13'S,14'S)-10',13'-dimethyltetradecahydro-2'H-dispiro[[1,3]dioxolane-2,3'-cyclopenta[a]phenanthrene-17',2''-[1,3]dioxolane]-6'-carbonitrile
• CAS: 953772-21-9
• 化学式: C₂₄H₃₅NO₄
• 分子量: 401.546
• InChiKey: MZAZBFBXFFQSIS-KYMPNAOUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.26
• 重原子数：
  29.0
• 可旋转键数：
  0.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  60.71
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (5'R,6'S,8'R,9'S,10'R,13'S,14'S)-10',13'-dimethyltetradecahydro-2'H-dispiro[[1,3]dioxolane-2,3'-cyclopenta[a]phenanthrene-17',2''-[1,3]dioxolane]-6'-carbonitrile 在 对甲苯磺酸一水合物 作用下， 以 丙酮 为溶剂， 反应 3.0h， 以75%的产率得到6α-cyanoandrostane-3,17-dione
  参考文献：
  名称：

  Novel analogues of Istaroxime, a potent inhibitor of Na+,K+-ATPase: Synthesis, structure–activity relationship and 3D-quantitative structure–activity relationship of derivatives at position 6 on the androstane scaffold

  摘要：

  We report the synthesis and biological properties of novel analogues of Istaroxime acting as positive inotropic compounds through the inhibition of the Na+, K+-ATPase. We explored the chemical space around the position 6 of the steroidal scaffold by changing the functional groups at that position and maintaining a basic oximic chain in position 3. Some compounds showed inhibitory potencies of the Na+, K+-ATPase higher than Istaroxime and many of the compounds tested in vivo were safer than digoxin, the classic digitalis compound currently used for the treatment of congestive heart failure as inotropic agent. The 3D-QSAR analyses using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods have been successfully applied to a set of 63 androstane derivatives as Na+,K+-ATPase inhibitors. The contour plots provide many useful insights into relationships between structural features and inhibitory potency. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.04.095
• 作为产物：
  描述：

  对甲基苯磺酰甲基异腈 、 3,3:17,17-bis(ethylenedioxy)androstan-6-one 在 potassium tert-butylate 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 72.0h， 以31%的产率得到(5'R,6'S,8'R,9'S,10'R,13'S,14'S)-10',13'-dimethyltetradecahydro-2'H-dispiro[[1,3]dioxolane-2,3'-cyclopenta[a]phenanthrene-17',2''-[1,3]dioxolane]-6'-carbonitrile
  参考文献：
  名称：

  Novel analogues of Istaroxime, a potent inhibitor of Na+,K+-ATPase: Synthesis, structure–activity relationship and 3D-quantitative structure–activity relationship of derivatives at position 6 on the androstane scaffold

  摘要：

  We report the synthesis and biological properties of novel analogues of Istaroxime acting as positive inotropic compounds through the inhibition of the Na+, K+-ATPase. We explored the chemical space around the position 6 of the steroidal scaffold by changing the functional groups at that position and maintaining a basic oximic chain in position 3. Some compounds showed inhibitory potencies of the Na+, K+-ATPase higher than Istaroxime and many of the compounds tested in vivo were safer than digoxin, the classic digitalis compound currently used for the treatment of congestive heart failure as inotropic agent. The 3D-QSAR analyses using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods have been successfully applied to a set of 63 androstane derivatives as Na+,K+-ATPase inhibitors. The contour plots provide many useful insights into relationships between structural features and inhibitory potency. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.04.095

文献信息

• Novel analogues of Istaroxime, a potent inhibitor of Na+,K+-ATPase: Synthesis, structure–activity relationship and 3D-quantitative structure–activity relationship of derivatives at position 6 on the androstane scaffold
  作者：Mauro Gobbini、Silvia Armaroli、Leonardo Banfi、Alessandra Benicchio、Giulio Carzana、Patrizia Ferrari、Giuseppe Giacalone、Giuseppe Marazzi、Barbara Moro、Rosella Micheletti

  DOI：10.1016/j.bmc.2010.04.095

  日期：2010.6.15

  We report the synthesis and biological properties of novel analogues of Istaroxime acting as positive inotropic compounds through the inhibition of the Na+, K+-ATPase. We explored the chemical space around the position 6 of the steroidal scaffold by changing the functional groups at that position and maintaining a basic oximic chain in position 3. Some compounds showed inhibitory potencies of the Na+, K+-ATPase higher than Istaroxime and many of the compounds tested in vivo were safer than digoxin, the classic digitalis compound currently used for the treatment of congestive heart failure as inotropic agent. The 3D-QSAR analyses using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods have been successfully applied to a set of 63 androstane derivatives as Na+,K+-ATPase inhibitors. The contour plots provide many useful insights into relationships between structural features and inhibitory potency. (C) 2010 Elsevier Ltd. All rights reserved.