Novel steroidal 1,4-diketones and pyridazine derivatives as potential antiestrogens.

Abstract

A series of steroidal 1,4-diketone derivatives was synthesized by acid-catalyzed condensation of 2-acetylestradiol-17 beta-acetate with substituted phenylglyoxals. Conversion of the products into the corresponding pyridazine derivatives was achieved by reaction with hydrazine hydrate. The synthesized compounds were evaluated for their uterotrophic, antiuterotrophic, and antifertility activities in mature female albino rats. Among the compounds tested, the phenyl 2, p-bromophenyl 3, and p-methoxyphenyl 5 diketone derivatives displayed uterotrophic activity of 72%, 72%, and 91%, respectively. The gradation of antiestrogenic activity was assessed in vivo by the inhibition of the estrone-stimulated uterine growth. Compounds 2-5 showed moderate antiestrogenic activity of 53-56%. None of the tested compounds elicited antifertility activity as assessed by the post-coital antiimplantation activity test.