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

Bioorg Med Chem Lett. 2010 Sep 1;20(17):5345-8. doi: 10.1016/j.bmcl.2010.02.100. Epub 2010 Mar 3.

Abstract

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].

MeSH terms

  • Animals
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Imidazoles / chemical synthesis*
  • Imidazoles / pharmacology*
  • Inhibitory Concentration 50
  • Male
  • Microsomes / enzymology*
  • Models, Molecular
  • Rats
  • Steroid 17-alpha-Hydroxylase / antagonists & inhibitors*
  • Testis / enzymology*

Substances

  • Enzyme Inhibitors
  • Imidazoles
  • Steroid 17-alpha-Hydroxylase