Biochemical studies of estr-4-ene-3,6,17-trione and 5 alpha-androstan-17-ones with or without a carbonyl function at C-3 and/or C-6 as aromatase inhibitors.

19-Nor (2) and 5 alpha-reduced (3) derivatives of androst-4-ene-3,6,17-trione (1) as well as 5 alpha-androstan-17-ones 4-6 were tested for their abilities to inhibit aromatase in human placental microsomes. All the steroids except 5 alpha-6-one 4 were fair to good competitive inhibitors of the enzyme, with apparent Ki's ranging from 50 to 820 nM in which 5 alpha-3-one 5 was the most potent among them. The inhibitory activities of the 19-nor and 5 alpha-reduced derivatives (2 and 3) were less potent than that of the parent compound 1.

Synthesis of androst-5-en-7-ones and androsta-3,5-dien-7-ones and their related 7-deoxy analogs as conformational and catalytic probes for the active site of aromatase.

A series of androst-5-en-7-ones and androsta-3,5-dien-7-ones and their 7-deoxy derivatives, respectively, were synthesized and tested for their abilities to inhibit aromatase in human placental microsomes. All the steroids inhibited the enzyme in a competitive manner with Ki's ranging from 0.058 to 45 microM.