Synthesis and CYP24A1 inhibitory activity of N-(2-(1H-imidazol-1-yl)-2-phenylethyl)arylamides

Bioorg Med Chem. 2010 Jul 15;18(14):4939-46. doi: 10.1016/j.bmc.2010.06.011. Epub 2010 Jun 9.

Abstract

A series of N-(2-(1H-imidazol-1-yl)-2-phenylethyl)arylamides were prepared, using an efficient three- to five-step synthesis, and evaluated for their inhibitory activity against human cytochrome P450C24A1 (CYP24A1) hydroxylase. Inhibition ranged from IC50 0.3-72 microM compared with the standard ketoconazole IC50 0.52 microM, with the styryl derivative (11c) displaying enhanced activity (IC50=0.3 microM) compared with the standard, providing a useful preliminary lead for drug development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry
  • Amides / pharmacology*
  • Benzofurans / chemical synthesis
  • Benzofurans / chemistry
  • Benzofurans / pharmacology
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Models, Molecular
  • Protein Binding
  • Steroid Hydroxylases / antagonists & inhibitors*
  • Steroid Hydroxylases / chemistry
  • Steroid Hydroxylases / metabolism*
  • Vitamin D3 24-Hydroxylase

Substances

  • Amides
  • Benzofurans
  • Enzyme Inhibitors
  • Imidazoles
  • Steroid Hydroxylases
  • CYP24A1 protein, human
  • Vitamin D3 24-Hydroxylase