Convulsant and anticonvulsant barbiturates. 1. Molecular conformations from classical potential-energy calculations.

Conformational energy calculations are reported for a series of convulsant and anticonvulsant barbiturates derived from 5-ethyl-5-(1'-methylbutyl)barbituric acid (pentobarbital) by minor structural changes to the butyl side chain. A number of low-energy conformations are identified for each barbiturate. In each case substantial barriers to rotation exist between the alternative conformations, and the magnitudes of these barriers suggest that the barbiturates may be conformationally restricted even at physiological temperatures. Fully extended conformations, with both side chains perpendicular to the plane of the barbiturate ring, are favored. In the 1'-methyl derivatives, conformations with the 1'-methyl group located directly above the barbiturate ring are equally low in energy.