Synthesis and biochemical evaluation of a range of (4 substituted phenyl)sulfonate derivatives of 4 hydroxybenzyl imidazole based compounds as potent inhibitors of 17alpha hydroxylase/17,20 lyase (P45017alpha) derived from rat testicular microsomes.
We report the synthesis, biochemical evaluation and rationalisation of the inhibitory activity of a range of (4 substituted phenyl)sulfonate derivatives of 4 hydroxybenzyl imidazole against the two components of 17alpha hydroxylase/17,20 lyase (P450(17alpha) namely, 17alpha hydroxylase (17alpha OHase) and 17,20 lyase (lyase) The results show the compounds to be highly potent inhibitors with limited selectivity towards the lyase component [e.g. toluene 4 sulfonic acid 4 imidazol 1 ylmethyl phenyl ester (4) possessed an IC(50) value of 40 nM against 17alpha OHase and 30 nM against lyase]
Bioorganic medicinal chemistry letters