Fadrozole hydrochloride: a potent, selective, nonsteroidal inhibitor of aromatase for the treatment of estrogen-dependent disease

J Med Chem. 1991 Feb;34(2):725-36. doi: 10.1021/jm00106a038.


A new class of potent, selective, nonsteroidal inhibitors of aromatase have been discovered. The most potent member of this series is fadrozole hydrochloride, CGS 16949 A, 4-(5,6,7,8-tetrahydroimidazo[1,5-alpha]pyridin-5-yl)benzonitrile monohydrochloride, 26a. In addition, the 6,7-dihydropyrrolo[1,2-c]imidazole (21a) and the 6,7,8,9-tetrahydroimidazo[1,5-alpha]azepine (21b) analogues were synthesized and evaluated. CGS 16949 A's ability to selectively inhibit aromatase (IC50 = 4.5 nM) over other cytochrome P-450 enzymes and suppress estrogen production when administered orally make it a suitable candidate to test the potential of an aromatase inhibitor in estrogen-dependent diseases including breast cancer.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / therapeutic use
  • Aromatase Inhibitors*
  • Chemical Phenomena
  • Chemistry
  • Estrogen Antagonists / chemical synthesis*
  • Estrogen Antagonists / therapeutic use
  • Fadrozole
  • Female
  • Humans
  • Imidazoles / therapeutic use*
  • Nitriles / therapeutic use*
  • Rats
  • Structure-Activity Relationship


  • Antineoplastic Agents
  • Aromatase Inhibitors
  • Estrogen Antagonists
  • Imidazoles
  • Nitriles
  • Fadrozole