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.
L J Browne  1 ,  C Gude ,  H Rodriguez ,  R E Steele ,  A Bhatnager
Affiliations
  • 1. Research Department, CIBA-GEIGY Corporation, Summit, New Jersey 07901.
PMID: 1825337 DOI: 10.1021/jm00106a038
Abstract

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.

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