Synthesis and biochemical evaluation of a range of sulfonated derivatives of 4-hydroxybenzyl imidazole as highly potent inhibitors of rat testicular 17alpha-hydroxylase/17,20-lyase (P-450(17alpha))

Sabbir Ahmed; Imran Shahid; Sachin Dhanani; Caroline P Owen

doi:10.1016/j.bmcl.2009.06.070

Synthesis and biochemical evaluation of a range of sulfonated derivatives of 4-hydroxybenzyl imidazole as highly potent inhibitors of rat testicular 17alpha-hydroxylase/17,20-lyase (P-450(17alpha))

Bioorg Med Chem Lett. 2009 Aug 15;19(16):4698-701. doi: 10.1016/j.bmcl.2009.06.070. Epub 2009 Jun 21.

Authors

Sabbir Ahmed¹, Imran Shahid, Sachin Dhanani, Caroline P Owen

Affiliation

¹ School of Science, University of the West of Scotland, Paisley, PA1 2BE Scotland, UK. sabbir.ahmed@uws.ac.uk

PMID: 19608417
DOI: 10.1016/j.bmcl.2009.06.070

Abstract

We report the synthesis and biochemical evaluation of a range of 4-sulfonated derivatives of 4-hydroxybenzyl imidazole which has been targetted against the two components of 17alpha-hydroxylase/17,20-lyase (P-450(17alpha)), namely, 17alpha-hydroxylase (17alpha-OHase) and 17,20-lyase (lyase). The results from the biochemical testing suggest that the compounds synthesised are highly potent inhibitors possessing excellent selectivity towards the lyase component.

MeSH terms

Animals
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
Imidazoles / chemical synthesis*
Imidazoles / chemistry
Imidazoles / pharmacology
Ketoconazole / pharmacology
Male
Rats
Steroid 17-alpha-Hydroxylase / antagonists & inhibitors*
Steroid 17-alpha-Hydroxylase / metabolism
Sulfones / chemistry
Testis / enzymology*

Substances

Enzyme Inhibitors
Imidazoles
Sulfones
Steroid 17-alpha-Hydroxylase
Ketoconazole