Abstract: The design, synthesis and angiotensin II(A II) antagonist activities of a series of quinoline derivatives (I~III) with ZD-8731 as lead compound are described. The biphenyl tetrazole moiety of ZD-8731 was replaced by bioisosteric N-phenylprrole carboxylic acid, N-phenylpyrroletetrazole and phenoxyphenylacetic acid to give compounds (I), (II) and (III), respectively. However,these changes proved to be detrimental to activities. In a test for amagonizing A II in vitro usingisolated rabbit aorta rings, all the compounds exeded competitive antagonism. The most potent active angiotensin II receptor antagoniSts of these series wee (Id) (pA2 = 6.8), (IIa) (pA2 = 7.7) and (IIIc) (pA2 = 7.2), respectively, which had the activity 1/40, 1/5 and 1/12 that of ZD-8731 (pA2 = 8.4), respectively. Their structure-activity relationships and conformational comparis0n are discussed.

Key words: Quinoline, Angiotensin II receptor antagonists, Structure-activity relationships