Design and synthesis of selective, high-affinity inhibitors of human cytochrome P450 2J2

The active site topology, substrate specificity, and biological roles of the human cytochrome P450 CYP2J2, which is mainly expressed in the cardiovascular system, are poorly known even though recent data suggest that it could be a novel biomarker and potential target for therapy of human cancer. This paper reports a first series of high-affinity, selective CYP2J2 inhibitors that are related to terfenadine, with Ki values as low as 160 nM, that should be useful tools to determine the biological roles of CYP2J2.

Graphical abstractA series of terfenadine analogs were synthetized and evaluated as human CYP2J2 inhibitors. Some of these compounds are high-affinity, selective inhibitors of this enzyme (R = Pr, Ki = 160 nM).Figure optionsDownload full-size imageDownload as PowerPoint slide