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Nonpeptidic Chymase Inhibitors: Design and Structure-Activity Relationships of Pyrimidinone Derivatives Based on the Predicted Binding Mode of a Peptidic Inhibitor

[ Vol. 9 , Issue. 15 ]


Fumihiko Akahoshi   Pages 1191 - 1199 ( 9 )


While the biological reaction of chymase have been often studied for ten years, the pathophysiological role of chymase has not been fully elucidate due to a lack of effective inhibitors featuring potent inhibitory activity, specificity, and metabolic stability. Recently the discovery of a structurally varied range of novel nonpeptidic inhibitors presents new opportunities to explore the role of chymase under both physiological and pathophysiological conditions and to develop therapeutic agents for chymase-induced diseases. In this article the structure and the inhibitory mechanism of nonpeptidic chymase inhibitors are discussed, with special emphasis on design and structure-activity relationships of pyrimidinone derivative where inhibitory activity, protease selectivity, and pharmacokinetic profile are clarified.


nonpeptidic chymase inhibitors, pyrimidinone derivatives, peptidic inhibitor, nonpeptidic inhibitors, pyrimidinone derivative


Research Laboratory II,Research and Development Division, Mitsubishi Pharma Corporation, 1000,Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan.

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