Structure-activity relations between alkyl nucleophilic chemicals causing duodenal ulcer and adrenocortical necrosis.
Structure-activity relationships were qualitatively and quantitatively examined for 56 chemicals (e.g., derivatives of propionitrile, acrylonitrile and cysteamine) which caused duodenal ulcer and/or adrenocortical necrosis in rats. For the first time the duodenal ulcerogenic property of numerous chemicals has been studied in a rational and predictive manner. Ulcerogenic activity was most intense in the carbonitriles attached to two or three carbon backbones and diminished by shortening, lengthening, branching, unsaturating, halogenating or hydroxylating the carbon chains. Different modes of action are implied. Adrenocorticolytic potency was associated with unsaturation of the carbon chain and substitution of the nitrile by thiol or amine radicals. An action of these chemicals on the central nervous system has been suggested.
D000302:Adrenal Cortex / Q000187:drug effects* / Q000473:pathology; D000588:Amines / Q000633:toxicity; D000818:Animals; D004381:Duodenal Ulcer / Q000139:chemically induced*; D004583:Electrons; D005260:Female; D009336:Necrosis / Q000139:chemically induced; D009570:Nitriles / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000633:toxicity
D000588:Amines; D009570:Nitriles; D013438:Sulfhydryl Compounds