Synthesis and biological evaluation of 3-(azolylmethyl)-1H-indoles and 3-(alpha-azolylbenzyl)-1H-indoles as selective aromatase inhibitors

J Enzyme Inhib Med Chem. 2007 Oct;22(5):667-76. doi: 10.1080/14756360701652658.

Abstract

This present study identifies a number of azolyl-substituted indoles as potent inhibitors of aromatase. In the sub-series of 3-(azolylmethyl)-1H-indoles, four imidazole derivatives and their triazole analogues were tested. Imidazole derivatives 11 and 14 in which the benzyl moiety was substituted by 2-chloro and 4-cyano groups, respectively, were the most active, with IC50 values ranging between 0.054 and 0.050 microM. In the other sub-series, eight 3-(alpha-azolylbenzyl)-1H-indoles were prepared and tested. Compound 30, the N-ethyl imidazole derivative, proved to be an aromatase inhibitor, showing an IC50 value of 0.052 microM. All target compounds were further evaluated against 17alpha-hydroxylase/C17,20-lyase to determine their selectivity profile.

MeSH terms

  • Animals
  • Aromatase Inhibitors / chemical synthesis*
  • Aromatase Inhibitors / chemistry
  • Aromatase Inhibitors / pharmacology*
  • Azoles / chemistry*
  • Enzyme Activation / drug effects
  • Female
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Inhibitory Concentration 50
  • Male
  • Microsomes / chemistry
  • Microsomes / drug effects
  • Molecular Structure
  • Placenta / enzymology
  • Rats
  • Steroid 17-alpha-Hydroxylase / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Testis / enzymology

Substances

  • Aromatase Inhibitors
  • Azoles
  • Indoles
  • Steroid 17-alpha-Hydroxylase