Synthesis and biological evaluation of 4-imidazolylflavans as nonsteroidal aromatase inhibitors

Bioorg Chem. 2004 Dec;32(6):494-503. doi: 10.1016/j.bioorg.2004.06.008.


A series of 4-imidazolylflavans having a variety of substituents on the 2-phenyl ring was synthesized and investigated for their inhibitory effect against aromatase. Structure-activity relationships of these compounds were determined. An additional chlorine atom or a cyano group at the 4' position did not enhance aromatase inhibition as well as a 3'-hydroxyl group. The influence of an additional 4'-hydroxyl group depends on the substitution pattern of A ring. Among these molecules, 4'-hydroxy-4-imidazolyl-7-methoxyflavan is only 2.2-fold less active than the letrozole (as assessed by IC50 values). Letrozole is used as the first-line therapy for metastatic breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aromatase / chemistry
  • Aromatase / drug effects
  • Aromatase Inhibitors* / chemical synthesis
  • Aromatase Inhibitors* / pharmacology
  • Flavonoids* / chemical synthesis
  • Flavonoids* / pharmacology
  • Humans
  • Imidazoles* / chemical synthesis
  • Imidazoles* / pharmacology
  • Microsomes / drug effects
  • Microsomes / enzymology
  • Molecular Conformation
  • Placenta / enzymology
  • Structure-Activity Relationship


  • Aromatase Inhibitors
  • Flavonoids
  • Imidazoles
  • Aromatase