Synthesis and screening of aromatase inhibitory activity of substituted C19 steroidal 17-oxime analogs.

ABSTRACT

The synthesis and aromatase inhibitory activity of androst-4-en-, androst-5-en-, 1ß,2ß-epoxy- and/or androsta-4,6-dien-, 4ß,5ß-epoxyandrostane-, and 4-substituted androst-4-en-17-oxime derivatives are described. Inhibition activity of synthesized compounds was assessed using aromatase enzyme and [1ß-3H]androstenedione as substrate. Most of the compounds displayed similar to or more aromatase inhibitory activity than formestane (74.2%). 4-Chloro-3ß-hydroxy-4-androsten-17-one oxime (14, 93.8%) showed the highest activity, while 4-azido-3ß-hydroxy-4-androsten-17-one oxime (17, 32.8%) showed the lowest inhibitory activity for aromatase.