Potential histidine decarboxylase inhibitors. 1. .alpha.- and .beta.-Substituted histidine analogs

Abstract

Histidine analogues with alkyl substitution at C.alpha. and C.beta. were prepared as potential inhibitors of specific histidine decarboxylase. Activity was assessed in vitro using extracts of rat pyloric stomach and a radioisotopic assay of 14CO2 evolved from carboxyl-14C-labeled histidine. .alpha.-Substituted analogues (C2-C4) including 2-hydroxyethyl were less potent than .alpha.-methylhistidine; the .alpha.-n-butyl analogue was completely inactive at 10-3 M. Similarly, .beta.,.beta.-dimethylhistidine and homohistidine failed to exhibit activity at 10-3 M.