Preparation and pharmacological profile of 7-(alpha-azolylbenzyl)-1H-indoles and indolines as new aromatase inhibitors

Bioorg Med Chem Lett. 2003 May 5;13(9):1553-5. doi: 10.1016/s0960-894x(03)00182-3.

Abstract

Aromatase (P450 arom) is a target of pharmacological interest for the treatment of breast cancer. New series of 7-(alpha-azolylbenzyl)-1H-indoles and indolines were synthesized as non-steroidal inhibitors of P450 arom. Selectivity was studied towards P450 17alpha enzyme. The most active compound, 1-ethyl-7-[(imidazol-1-yl)(4-chlorophenyl)methyl]-1H-indole 12c exhibited promising relative potency (rp) of 336 (rp of aminoglutethimide=1) and most of the described azoles were active and selective towards P450 arom.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Aromatase Inhibitors*
  • Azoles / chemical synthesis
  • Azoles / chemistry*
  • Azoles / pharmacology
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • In Vitro Techniques
  • Indoles / chemical synthesis
  • Indoles / chemistry*
  • Indoles / pharmacology
  • Male
  • Microsomes / drug effects
  • Microsomes / enzymology
  • Rats
  • Steroid 17-alpha-Hydroxylase / antagonists & inhibitors
  • Testis / enzymology

Substances

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