An orally active chymase inhibitor, BCEAB, suppresses heart chymase activity in the hamster.

摘要

We investigated the effects of a novel chymase inhibitor, BCEAB (4-[1-[[bis-(4-methyl-phenyl)-methyl]-carbamoyl]-3-(2-ethoxy-benzyl)-4-oxo -azetidine-2-yloxy]-benzoic acid). The IC50 value of BCEAB for purified human chymase was 5.4 nM, whereas BCEAB did not inhibit the angiotensin-converting enzyme, elastase and tryptase. In isolated dog arteries, the IC50 value of BCEAB for the angiotensin I-induced contraction in the presence of 1 microM lisinopril was 2.8 microM. In the hamster, the heart chymase activities were significantly suppressed to 42.0% and 26.9% 3 h after oral administration of 100 and 300 mg of BCEAB/kg of body weight, respectively. In conclusion, BCEAB is a useful chymase inhibitor for studying the role of chymase in vivo.