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. © 1994 ESCOM Science Publishers B.V.
Romanelli M.N., Dei S., Scapecchi S., Teodori E., Gualtieri F., Budriesi R., et al. (1994). Semi-rigid analogues of the calcium antagonist verapamil: A molecular modelling study. JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 8(2), 123-134 [10.1007/BF00119863].
Semi-rigid analogues of the calcium antagonist verapamil: A molecular modelling study
Budriesi R.;
1994
Abstract
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. © 1994 ESCOM Science Publishers B.V.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
