Synthesis and histamine H2-antagonist activity of 4-quinazolinone derivatives.

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Abstract
With the aim of developing new antiulcer agents, a series of 4-quinazolinone derivatives was synthesized and tested for histamine H2-antagonist activity and gastric antisecretory activity. Thus, 2-alkylamino- (8a-d, 10a-s), 2-alkylthio- (15), 2-alkyl-4-quinazolinones (18a-k) were prepared by the condensation of alkylamines with 2-chloro- or 2-methylthio-4-quinazolinones, the condensation of alkyl bromides with 2-mercapto-4-quinazolinones, and the condensation of alkylcarboxylic acids with anthranilamides, respectively. Several of the 4-quinazolinone derivatives thus synthesized showed potent H2-antagonist activity, and one of them, 2-[3-[3-(1-piperidinylmethyl)phenoxy]propylamino]4-(3H)-quinazolinone (8d) showed the most potent antisecretory activity. The structure-activity relationships are discussed.