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

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

Volume: 9 Issue: 15

Author(s): Fumihiko Akahoshi

Affiliation:

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

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.

Cite this article as:

Akahoshi Fumihiko, Nonpeptidic Chymase Inhibitors: Design and Structure-Activity Relationships of Pyrimidinone Derivatives Based on the Predicted Binding Mode of a Peptidic Inhibitor, Current Pharmaceutical Design 2003; 9 (15) . https://dx.doi.org/10.2174/1381612033454964