SYNTHESIS AND BIOLOGICAL EVALUATION OF 3-(PROP-2-ENYL)PYRROLIDINE-2,5-DIONE AND 3-(PROP-2-YNYL)PYRROLIDINE-2,5-DIONE DERIVATIVES AS POTENTIAL AROMATASE INHIBITORS

3-(4'-Aminophenyl)pyrrolidine-2,5-dion (WSP3), a known reversible inhi bitor of P450 aromatase, was modified using molecular graphics and our model of reversible inhibitor and substrate binding to resemble 10 be ta-prop-2-ynylestr-4-ene-3, 17-dione (PED), a mechanism-based inactiva tor of the enzyme. The analogues prepared were 3-substituted 3-(prop-2 -enyl) or 3-(prop-2-ynyl) pyrrolidine-2,5-diones and their N-alkyl der ivatives. The reported compounds demonstrated no irreversible (time-de pendent) inhibition of the human placental P450 aromatase enzyme. Howe ver, some reversible activity was seen in several of the 3-(prop-2-yny l) compounds.