Synthesis and biochemical evaluation of a range of potent benzyl imidazole-based compounds as potential inhibitors of the enzyme complex 17α-hydroxylase/17,20-lyase (P45017α)

The cytochrome P-450 enzyme, 17 alpha-hydroxylase/17,20-tyase (P450(17 alpha)), is a potential target in hormone-dependent cancers. Here, we report the synthesis and biochemical evaluation of a range of benzyl imidazole-based compounds which have been targeted against the two components of this enzyme, that is, 17 alpha-hydroxylase (17 alpha-OHase) and 17,20-lyase (lyase). The results from the biochemical testing suggest that the compounds synthesised are good inhibitors, with N-4-iodobenzyl imidazole (5) (IC50 = 10.06 mu M against 17 alpha-OHase and IC50 = 1.58 mu M against lyase) showing equipotent activity against lyase compared to the standard compound, ketoconazole (KTZ) (IC50 = 3.76 +/- 0.01 mu M against 17 alpha-OHase and IC50 = 1.66 +/- 0.15 mu M against lyase). Furthermore, the compounds tested are less potent towards the 17 alpha-OHase component, a desirable property in the development of novel inhibitors of P450(17 alpha). (c) 2006 Elsevier Ltd. All rights reserved.