Pharmacophoric pattern in valpromide derivatives

Abstract

A conformational and electronic semiempirical quantum-chemical study of several N-substituted valpromides is presented, followed by a similarity analysis that takes into account the flexibility of the molecules. Rigid analogs are included in the comparison in order to help identify the anticonvulsant active conformations. On the basis of a superposition analysis, which includes both active and nonactive structures, and uses the global minimum-energy conformation of phenytoin as a template, the pharmacophoric pattern of N-substituted valpromides is defined. It is related to the antiperiplanar orientation of the amide function relative to the hydrocarbon chain. © 1997 John Wiley & Sons, Inc. Int J Quant Chem 65: 1107–1114, 1997