Design of mechanism-based inactivators of human placental aromatase.
This article reviews the design and study, in our own laboratory and in other laboratories, of new 10 beta-substituted analogs of estr-4-ene-3,17-dione. These compounds, along with a number of known analogs, have been evaluated as reversible or irreversible inhibitors of human placental microsomal aromatase. The only irreversible inhibitors in the group surveyed here are the 10 beta-difluoromethyl, 10 beta-propargyl, and 10 beta-allenyl derivatives of estr-4-ene-3,17-dione. Possible mechanisms for the inactivation processes are discussed. The effects of incorporating the 19-methyl group of adrost-4-ene-3,17-dione into a ring of three, four, five or six carbons are also described.
D047072:Aromatase Inhibitors; D004963:Estrenes / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008861:Microsomes / Q000201:enzymology; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011485:Protein Binding; D013329:Structure-Activity Relationship
D047072:Aromatase Inhibitors; D004963:Estrenes; D010088:Oxidoreductases