Isocytosine H2-receptor histamine antagonists. IV. The synthesis and biological activity of donetidine (SK and F 93574) and related compounds

Article abstract of DOI:10.1016/0223-5234(93)90091-R

The synthesis and biological activity of some novel 2-amino-4-pyrimidone derivatives is described.Side-chains associated with H₂ antagonist activity are attached through the 2-amino group, whilst a range of 2-hydroxypyridine containing moieties are substituted at the 5-position of the pyrimidone ring.Good H₂-receptor histamine antagonist activity is observed with all the series and the majority of the compounds are selective for the H₂-receptor.High aqueous solubility and iv potency coupled with an extended duration of biological activity in animal models ledto compound 16c, 2-<2-(5-dimethylaminomethyl-2-furanylmethylthio)ethylamino>-5-(2-hydroxypyrid-4-ylmethyl)-4-pyrimidone (donetidine, SK and F 93574) being selected for clinical investigation as a potential parenterally administered therapeutic agent.H₂-receptor antagonists / 2-amino-4-pyrimidones (isocytosines / imidazoles / thiazoles / pyridines / furans / 2-guanidinothiazoles / donetidine (SK and F 93574)