PHARMACOPHORIC PATTERN IN VALPROMIDE DERIVATIVES

A conformational and electronic semiempirical quantum-chemical study o f several N-substituted valpromides is presented, followed by a simila rity analysis that takes into account the flexibility of the molecules . Rigid analogs are included in the comparison in order to help identi fy the anticonvulsant active conformations. On the basis of a superpos ition analysis, which includes both active and nonactive structures, a nd uses the global minimum-energy conformation of phenytoin as a templ ate, the pharmacophoric pattern of N-substituted valpromides is define d. It is related to the antiperiplanar orientation of the amide functi on relative to the hydrocarbon chain. (C) 1997 John Wiley & Sone, Inc.