title: Synthesis and biochemical evaluation of the novel steroid androsta-4,6,8(9)-triene-3,17-dione.
abstract: According to a proposed aromatisation mechanism by which estrogens are biosynthesized from androgens, the novel steroid androsta-4,6,8(9)-triene-3,17-dione (FCE 24918) should behave as a suicide substrate for aromatase. The synthesis of this triene steroid has been accomplished starting from androsta-4,7-diene-3,17-dione (4) by the acid-catalysed cleavage of the corresponding 7,8 alpha-epoxide, 5, and it was obtained together with androsta-4,6,8(14)-triene-3,17-dione (FCE 24917) as a side product. The time-dependent inactivation of placental aromatase by the two isomers was studied comparatively and showed that the 4,6,8(9)-triene moiety acts as a latent alkylating group.
authors.affiliation: Farmitalia Carlo Erba, Research and Development, Milano, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Panzeri
authors.forename: G
authors.initials: G
authors.lastname: Ornati
authors.forename: E
authors.initials: E
authors.lastname: di Salle
authors.forename: P
authors.initials: P
authors.lastname: Lombardi
mesh_terms: D000733:Androstatrienes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D047072:Aromatase Inhibitors; D005260:Female; D006801:Humans; D008861:Microsomes / Q000201:enzymology; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D013329:Structure-Activity Relationship
chemical_list: D000733:Androstatrienes; D047072:Aromatase Inhibitors; C069517:androsta-4,6,8(9)-triene-3,17-dione