Isocytosine H2-receptor histamine antagonists. III. The synthesis and biological activity of lupitidine (SK and F 93479) and related compounds

Article abstract of DOI:10.1016/0223-5234(90)90204-G

A series of 2-[2-(5-dimethylaminomethyl-2-furanylmethylthio)ethylamino]-4-pyrimidones is described containing a variety of substituents in the 5-position of the pyrimidone (isocytosine) ring. Good H₂-receptor histamine antagonist activity is retained over a range of basic and neutral, polar and non-polar substituents and the majority of compounds are selective for the H₂-receptor. Modifications have also been made to the furan ring and N,N-dimethylaminomethyl substituent and structure-activity observations are discussed. Compound (16f) 2-[2-(5-dimethylaminomethyl-2-furanylmethylthio)ethylamino]-5-(6-methyl-3- pyridylmethyl)-4-pyrimidone (SK and F 93479, lupitidine), a compound which shows an extended duration of anti-secretory activity in animal models, was selected for clinical investigation.