Synthesis and evaluation of analogues of 4-androstene-3,17-dione as aromatase inhibitors.
Twenty-three synthetic analogues of 4-androstene-3,17-dione (androstenedione) have been evaluated as inhibitors of human placental microsomal aromatase enzyme. Among the most potent of these compounds were the 4-hydroxy, 6 alpha-fluoro, 6 beta-fluoro, and 4-fluoroandrostenediones and 4-fluoro-19-nor-4-androstene-3,17-dione. 4-Hydroxy-4-androstene-3,17-dione (4HAD) is an irreversible inhibitor of aromatase in vitro, whereas the four fluoro analogues are reversible inhibitors. 4HAD and 4-fluoro-4-androstene-3,17-dione caused significant regression of the nitrosomethylurea-induced mammary tumor in rats, but the other fluoro derivatives were inactive.
Rowlands
M G
MG
Drug Development Section, CRC Laboratory, Institute of Cancer Research, Sutton, Surrey, UK.
Foster
A B
AB
Mann
J
J
Pietrzak
B
B
Wilkinson
J
J
Coombes
R C
RC
D000735:Androstenedione / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D047072:Aromatase Inhibitors; D055598:Chemical Phenomena; D002621:Chemistry; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D008861:Microsomes / Q000201:enzymology; D010920:Placenta / Q000201:enzymology; D051381:Rats
D047072:Aromatase Inhibitors; D000735:Androstenedione