T. Brown, R. Blakemore, G. J. Durant
1988
Citations
1
Influential Citations
35
Citations
Quality indicators
Journal
European Journal of Medicinal Chemistry
Abstract
Abstract A series of 2-[2-(5-methyl-4-imidazolylmethylthio)ethylamino]-4-pyrimidones was prepared based on cimetidine 1. The model compound 4 has modest H2-antagonist activity as shown by its ability to antagonise histamine-stimulated tachycardia in guinea pig right atrium in vitro and inhibit histamine-stimulated gastric acid secretion in the lumen-perfused stomach of the anaesthetised rat. Investigation of the effect of substituents in the pyrimidone ring showed that suitable substitution at the 5-position gave compounds with greatly increased activity, whereas substituents at other positions in the ring were not favourable for activity. Some structure—activity and structure—toxicity correlations are discussed. Compound 32 (oxmetidine, SK&F 92994) which has the most favourable combination of properties, was selected for clinical investigation.