Synthesis and CYP24A1 inhibitory activity of N-(2-(1H-imidazol-1-yl)-2-phenylethyl)arylamides

A series of N-(2-(1H-imidazol-1-yl)-2-phenylethyl)arylamides were prepared, using an efficient three-to five-step synthesis, and evaluated for their inhibitory activity against human cytochrome P450C24A1 (CYP24A1) hydroxylase. Inhibition ranged from IC50 0.3-72 mu M compared with the standard ketoconazole IC50 0.52 mu M, with the styryl derivative (11c) displaying enhanced activity (IC50 = 0.3 mu M) compared with the standard, providing a useful preliminary lead for drug development. (C) 2010 Elsevier Ltd. All rights reserved.