Synthesis, Biological Evaluation of SPF-32629A-Based 2- and 4-Pyridone Analogs as Chymase Inhibitors

摘要

Chymase (EC 3.4.21.39) is a chymotrypsin-like serine protease present in the secretory granules of mast cells, located mainly in the heart, blood vessels, and skin of in many mammalian species. Its physiological substrate is angiotensin I, which upon cleavage by chymase yields angiotensin II in steps of the renin-angiotensin system. In addition it is known to promote mast cell degranulation and plays a role in airway secretions and in atopic or allergic inflammation of the skin. Therefore chymase is regarded as a potential therapeutic target for cardiovascular diseases as well as allergic/inflammatory diseases.