Abstract: The design, synthesis, and angiotensin II (AII) antagonist activities of several quinazolinone (IV) and quinazoline phenoxyphenylacetic acids (V) are described. Quinazolinone ring was used to replace the quinoline moiety of quinoline phenoxyphenylacetic acids (III) which have been discovered as potent AII antagonists, to give a new series of antagonists (IV), while their quinazoline analogs (V) were obtained as isomers during the synthesis of (IV). However, both series of compounds were not found to increase the potencies. In a test for antagonizing AII in vitro using isolated rabbit aorta rings, all the compounds exerted competitive antagonism. The most potent quinazolinone (IVb) and quinazoline (Vb) had pA2 values of 7.0 and 5.9, respectively.

Key words: Quinazolinone, Quinazolinone, Quinazoline, Quinazoline, Phenoxyphenylacetic acid, Phenoxyphenylacetic acid, Angiotensin II antagonists, Angiotensin II antagonists