Fadrozole hydrochloride: a potent, selective, nonsteroidal inhibitor of aromatase for the treatment of estrogen-dependent disease.
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.
Browne
L J
LJ
Research Department, CIBA-GEIGY Corporation, Summit, New Jersey 07901.
Gude
C
C
Rodriguez
H
H
Steele
R E
RE
Bhatnager
A
A
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D047072:Aromatase Inhibitors; D055598:Chemical Phenomena; D002621:Chemistry; D004965:Estrogen Antagonists / Q000138:chemical synthesis* / Q000627:therapeutic use; D017316:Fadrozole; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D009570:Nitriles / Q000627:therapeutic use*; D051381:Rats; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004965:Estrogen Antagonists; D007093:Imidazoles; D009570:Nitriles; D017316:Fadrozole