A specific chymase inhibitor, 2-(5-formylamino-6-oxo-2-phenyl-1, 6-dihydropyrimidine-1-yl)-N-[{3, 4-dioxo-1-phenyl-7-(2-pyridyloxy)}-2-heptyl] acetamide (NK3201) …

K Tsunemi, S Takai, M Nishimoto, D Jin… - … of Pharmacology and …, 2004 - ASPET
K Tsunemi, S Takai, M Nishimoto, D Jin, M Sakaguchi, M Muramatsu, A Yuda, S Sasaki…
Journal of Pharmacology and Experimental Therapeutics, 2004ASPET
In this study, we investigated the effect of a specific chymase inhibitor, 2-(5-formylamino-6-
oxo-2-phenyl-1, 6-dihydropyrimidine-1-yl)-N-[{3, 4-dioxo-1-phenyl-7-(2-pyridyloxy)}-2-heptyl]
acetamide (NK3201), in the development of abdominal aortic aneurysm in a hamster
experimental model. The abdominal aortic aneurysm was induced by application of elastase
onto the abdominal aorta in hamster. Each hamster was administered NK3201 (30
mg/kg/day po) or placebo beginning 4 days before application of elastase and continuing …
In this study, we investigated the effect of a specific chymase inhibitor, 2-(5-formylamino-6-oxo-2-phenyl-1,6-dihydropyrimidine-1-yl)-N-[{3,4-dioxo-1-phenyl-7-(2-pyridyloxy)}-2-heptyl]acetamide (NK3201), in the development of abdominal aortic aneurysm in a hamster experimental model. The abdominal aortic aneurysm was induced by application of elastase onto the abdominal aorta in hamster. Each hamster was administered NK3201 (30 mg/kg/day p.o.) or placebo beginning 4 days before application of elastase and continuing through the experiments. Sham-operated hamsters received saline application onto the abdominal aorta. Two weeks after application of elastase, the aortic diameter in the placebo-treated group was significantly increased to 1.6-fold compared with the value for the sham-operated group, whereas that in the NK3201-treated group was significantly reduced. The chymase activities in the sham-operated and the placebo-treated groups were 0.35 ± 0.01 and 3.44 ± 0.62 mU/mg protein, respectively, and this difference was significant. NK3201 significantly reduced the chymase activity in the placebo-treated group. Here, we demonstrated for the first time that a chymase inhibitor prevented the development of abdominal aortic aneurysm in a hamster experimental model.
ASPET