2-[(2E)-2-[[(3S,5R,8R,9S,10S,13R,14S,17S)-3,14-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]methylidene]hydrazinyl]-1,4-dihydroimidazol-5-one

• 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: 2-[(2E)-2-[[(3S,5R,8R,9S,10S,13R,14S,17S)-3,14-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]methylidene]hydrazinyl]-1,4-dihydroimidazol-5-one
• 化学式: C₂₃H₃₆N₄O₃
• 分子量: 416.564
• InChiKey: LMKFRTJLDCIUTG-HFMFQCIOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  106
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3β,14β-dihydroxy-5β-androstane-17β-carboxaldehyde 在 盐酸 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 24.0h， 生成 2-[(2E)-2-[[(3S,5R,8R,9S,10S,13R,14S,17S)-3,14-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]methylidene]hydrazinyl]-1,4-dihydroimidazol-5-one
  参考文献：
  名称：

  Synthesis and Quantitative Structure−Activity Relationships of 17β-(Hydrazonomethyl)-5β-androstane-3β,14β-diol Derivatives That Bind to Na⁺,K⁺-ATPase Receptor

  摘要：

  A series of 17 beta-(hydrazonomethyl)-5 beta-androstane-3 beta,14 beta-diol derivatives was synthesized and evaluated in the displacement of [H-3]ouabain binding from Na+,K+-ATPase. The data were explored with multiple linear regression and partial least-squares to find possible quantitatives structure-activity relationships. Good correlations were found between binding to the receptor and van der Waals volumes or molar refractivities of the 17 beta-hydrazonomethyl substituents and pK(a) values of the compounds. Equivalent results were obtained using the proton affinity (calculated using MOPAC) of the hydrazone residues instead of experimental pK(a). As basicity or related electronic factors of the substituents explain a significant portion of the observed changes in the activity, an ion-pair interaction between a carboxylate residue of the enzyme and the protonated 17 beta-hydrazonomethyl group, as postulated by Thomas, plays an important role in the interaction of the ligand to the Na+,K+-ATPase receptor.

  DOI：

  10.1021/jm950806n

文献信息

• Hydrazono-5.beta., 14.beta.-androstane derivatives active on the
  申请人：SIGMA-TAU Industrie Farmaceutiche Riunite S.p.A.

  公开号：US05538960A1

  公开（公告）日：1996-07-23

  The present invention relates to new 17-hydrazonomethyl- and 17-hydrazono-14.beta.-hydroxy-5.beta.-androstane derivatives active on the cardiovascular system, to a process for their preparation and to pharmaceutical compositions containing same for the treatment of cardiovascular disorders, such as heart failure and hypertension.

  本发明涉及对心血管系统活性的新17-酰肼甲基和17-酰肼基-14-β-羟基-5-β-雄烷衍生物，以及它们的制备方法和含有相同物质的用于治疗心血管疾病，如心力衰竭和高血压的药物组合物。
• New hydrazono-5-beta-androstane derivatives active on the cardiovascular system, processes for their preparation and pharmaceutical compositions containing same
  申请人：Sigma-Tau Industrie Farmaceutiche Riunite S.p.A.

  公开号：EP0583606A2

  公开（公告）日：1994-02-23

  17-Hydrazonomethyl- and 17-hydrazone-14β-hydroxy-5β-androstane derivatives of general formula (I): wherein the symbols A, --- and Y have the meaning as indicated in the specification. Processes for producing these derivatives, pharmaceutical compositions containing them as well as their use are also disclosed.

  通式（I）的 17-肼甲基-和 17-腙-14β-羟基-5β-雄甾烷衍生物： 其中符号 A、---和 Y 的含义如说明书所示。此外，还公开了这些衍生物的生产工艺、含有这些衍生物的药物组合物及其用途。
• US5538960A
  申请人：——

  公开号：US5538960A

  公开（公告）日：1996-07-23
• Synthesis and Quantitative Structure−Activity Relationships of 17β-(Hydrazonomethyl)-5β-androstane-3β,14β-diol Derivatives That Bind to Na⁺,K⁺-ATPase Receptor
  作者：Luisa Quadri、Alberto Cerri、Patrizia Ferrari、Elena Folpini、Massimo Mabilia、Piero Melloni

  DOI：10.1021/jm950806n

  日期：1996.1.1

  A series of 17 beta-(hydrazonomethyl)-5 beta-androstane-3 beta,14 beta-diol derivatives was synthesized and evaluated in the displacement of [H-3]ouabain binding from Na+,K+-ATPase. The data were explored with multiple linear regression and partial least-squares to find possible quantitatives structure-activity relationships. Good correlations were found between binding to the receptor and van der Waals volumes or molar refractivities of the 17 beta-hydrazonomethyl substituents and pK(a) values of the compounds. Equivalent results were obtained using the proton affinity (calculated using MOPAC) of the hydrazone residues instead of experimental pK(a). As basicity or related electronic factors of the substituents explain a significant portion of the observed changes in the activity, an ion-pair interaction between a carboxylate residue of the enzyme and the protonated 17 beta-hydrazonomethyl group, as postulated by Thomas, plays an important role in the interaction of the ligand to the Na+,K+-ATPase receptor.