STUDIES ON NONPEPTIDE ANGIOTENSIN-II RECEPTOR ANTAGONISTS - III - SYNTHESIS AND BIOLOGICAL EVALUATION OF 5-ALKYLIDENE-3,5-DIHYDRO-4H-IMIDAZOL-4-ONE DERIVATIVES

5-Alkylidene-3,5-dihydro-4H-imidazol-4-one derivatives mere synthesize d and evaluated for activity as angiotensin II receptor antagonists. S ubstitutions at C-2 and C-5, respectively, with a propyl group and a 1 -methylethylidene group resulted in the optimal compound, ihydro-5-(1- methylethylidene)-2-propyl-3-[[2'-(1H- razol-5-yl)biphenyl-4-yl]methyl ]-4H-imidazol-4-one (2b), with a pA(2) value of 8.85 in rabbit aorta. When administered orally to rats, 2b showed a greater inhibitory effec t on angiotensin II-induced presser response than DuP 753. Compound 2b also showed a good antihypertensive effect when administered orally t o conscious sodium-depleted spontaneously hypertensive rats, with a du ration of action of 24 h, These data suggest that 2b maybe a useful ag ent for the treatment of angiotensin II-dependent diseases such as hyp ertension.