Synthesis of 6- or 4-functionalized indoles via a reductive cyclization approach and evaluation as aromatase inhibitors

Bioorg Med Chem Lett. 2008 Aug 15;18(16):4713-5. doi: 10.1016/j.bmcl.2008.06.094. Epub 2008 Jul 3.

Abstract

Two new series of benzonitrile derivatives on position 6 or 4 of indole ring were successfully synthesized via a Leimgruber-Batcho reaction. All the compounds were evaluated in vitro on the inhibition of aromatase (CYP19) and 17alpha-hydroxylase-C17,20-lyase (CYP17). The racemate, 4-[(1H-imidazol-1-yl)(1H-indol-4-yl)methyl]benzonitrile 9, showed high level of inhibitory activity towards CYP19 (IC(50)=11.5 nM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aromatase / chemical synthesis
  • Aromatase / chemistry*
  • Aromatase / metabolism
  • Aromatase Inhibitors / chemical synthesis*
  • Aromatase Inhibitors / pharmacology
  • Breast Neoplasms / drug therapy
  • Estradiol / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Hormones / metabolism
  • Humans
  • Indoles / chemistry*
  • Inhibitory Concentration 50
  • Models, Chemical
  • Molecular Structure
  • Nitriles / chemistry
  • Receptors, Estrogen / metabolism
  • Steroid 17-alpha-Hydroxylase / antagonists & inhibitors*
  • Steroid 17-alpha-Hydroxylase / chemistry

Substances

  • Aromatase Inhibitors
  • Hormones
  • Indoles
  • Nitriles
  • Receptors, Estrogen
  • Estradiol
  • benzonitrile
  • Aromatase
  • Steroid 17-alpha-Hydroxylase