title: Synthesis and evaluation of analogues of 4-androstene-3,17-dione as aromatase inhibitors.
abstract: 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.
authors.affiliation: Drug Development Section, CRC Laboratory, Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: M G
authors.initials: MG
authors.lastname: Rowlands
authors.forename: A B
authors.initials: AB
authors.lastname: Foster
authors.forename: J
authors.initials: J
authors.lastname: Mann
authors.forename: B
authors.initials: B
authors.lastname: Pietrzak
authors.forename: J
authors.initials: J
authors.lastname: Wilkinson
authors.forename: R C
authors.initials: RC
authors.lastname: Coombes
mesh_terms: 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
chemical_list: D047072:Aromatase Inhibitors; D000735:Androstenedione