Isocytosine H2-receptor histamine antagonists II. Synthesis and evaluation of biological activity at histamine H1- and H2-receptors of 5-(heterocyclyl)methylisocytosines

Article abstract of DOI:10.1016/0223-5234(89)90166-9

A series of 2-<2-(5-methyl-4-imidazolylmethylthio)ethylamino>-4-pyrimidones was synthesized based on oxmetidine 2, in which the methylenedioxyphenyl group of 2 was replaced by a heterocyclic ring.Good H₂-receptor antagonist activity was retained over a range of basic and neutral heterocyclic substituents.Replacement of the 5-methyl-4-imidazolyl ring in selected compounds with 2-thiazolyl and, particularly, 3-bromo-2-pyridyl rings gave a series of compounds which have both H₁- and H₂-receptor histamine antagonist activities.Some structure-activity and structure-toxicity correlations are discussed.Compound 6d, 2-<2-(5-methyl-4-imidazolylmethylthio)ethylamino>-5-(6-methylpyrid-3-yl)-4-pyrimidone, has the most favourable combination of properties for H₂-antagonism and has been evaluated further as an anti-secretory agent.