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].
Owen
Caroline P
CP
School of Science, Faculty of Science and Technology, University of the West of Scotland, Paisley, Scotland, UK.
Shahid
Imran
I
Lee
Wai-Yee
WY
Ahmed
Sabbir
S
D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008297:Male; D008861:Microsomes / Q000201:enzymology*; D008958:Models, Molecular; D051381:Rats; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors*; D013737:Testis / Q000201:enzymology*
D004791:Enzyme Inhibitors; D007093:Imidazoles; D013254:Steroid 17-alpha-Hydroxylase