Romanelli M N, Dei S, Scapecchi S, Teodori E, Gualtieri F, Budriesi R, Mannhold R
Dipartimento di Scienze Farmaceutiche, Università di Firenze, Italy.
J Comput Aided Mol Des. 1994 Apr;8(2):123-34. doi: 10.1007/BF00119863.
In this work the rigid-analogue approach has been used to obtain information on the active conformation(s) of the calcium antagonist verapamil. A series of semi-rigid analogues of verapamil were synthesized and their biological activities evaluated on guinea-pig heart and aorta. These molecules were analysed by means of molecular modelling techniques. On the basis of the pharmacological profile and conformational analysis of these compounds, two different models for negative inotropic and negative chronotropic activity are proposed. The two actions seem to be due to conformations of the molecules which differ in the orientation of their phenylethylamino groups.
在这项研究中，采用刚性类似物方法来获取钙拮抗剂维拉帕米活性构象的信息。合成了一系列维拉帕米的半刚性类似物，并在豚鼠心脏和主动脉上评估了它们的生物活性。借助分子建模技术对这些分子进行了分析。基于这些化合物的药理学特征和构象分析，提出了两种不同的负性肌力和负性变时活性模型。这两种作用似乎是由于分子构象不同，其苯乙胺基的取向也不同。
