Structure-activity relationships for ulcerogenic and adrenocorticolytic effects of alkyl nitriles, amines, and thiols

Abstract

In rats, a single administration of acrylonitrile (vinyl cyanide) produces a rapidly occurring bilateral adrenal apoplexy. Structure-activity studies have shown that a close derivative, propionitrile (ethyl cyanide), causes duodenal ulcer without markedly affecting the adrenal glands. Prolonging the two-carbon chain of propionitrile by a methyl group (n-butyronitrile) enhances, replacing the methyl by bromide or nitrile decreases, while substitution by an amino group abolistes the ulcerogenic potency and variably affects the adrenocorticolytic action. On assaying a large number of nonnitrile compounds as well for ulcerogenic effect, such as thiols and amines, this effect was found to be related to a two-carbon structure bearing electronegative radicals on one or both ends of the chain.