Electric‐field mapping of some substituted 3‐pyridinecarboxylic acid cardiotonics and the possible structure–activity relationships

Abstract

AbstractFour esters of 5‐cyano‐1,6‐dihydro‐6‐oxo‐3‐pyridinecarboxylic acid involving substitutions of methyl, isopropyl, tert‐butyl, and phenyl groups at the 2‐position, which exhibit varying degrees of cardiotonic activities, have been studied using the electric‐field and electrostatic potential mapping techniques. The net charge distributions in the molecules were obtained using the MNDO method. Electric‐field mapping has been performed in three‐dimension in order to obtain information about the possible structure–activity relationships of these compounds. The results show a prominent electric‐field region in the methyl‐substituted compound extending from near the oxygen atom O6 to near the methyl group. This fact and orientation of the electric field in this region, in view of the Erhardt model, may be related to the greater cardiotonic activity of the methyl‐substituted molecule in comparison to those of the other molecules of this class. © 1992 John Wiley & Sons, Inc.