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

Author(s): Fumihiko Akahoshi .

Journal Name: Current Pharmaceutical Design

Volume 9 , Issue 15 , 2003

Abstract:

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.

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

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Article Details

VOLUME: 9
ISSUE: 15
Year: 2003
Page: [1191 - 1199]
Pages: 9
DOI: 10.2174/1381612033454964
Price: $58

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