NOVEL STEROIDAL 1,4-DIKETONES AND PYRIDAZINE DERIVATIVES AS POTENTIALANTIESTROGENS

A series of steroidal 1,4-diketone derivatives was synthesized by acid -catalyzed condensation of 2-acetylestradiol-17 beta-acetate with subs tituted phenylglyoxals. Conversion of the products into the correspond ing pyridazine derivatives was achieved by reaction with hydrazine hyd rate. The synthesized compounds were evaluated for their uterotrophic, antiuterotrophic, and antifertility activities in mature female albin o rats. Among the compounds tested, the phenyl 2, p-bromophenyl 3, and p-methoxyphenyl 5 diketone derivatives displayed uterotrophic activit y of 72%, 72%, and 91%, respectively. The gradation of antiestrogenic activity was assessed in vivo by the inhibition of the estrone-stimula ted uterine growth. Compounds 2-5 Showed moderate antiestrogenic activ ity of 53-56%. None of the tested compounds elicited antifertility act ivity as assessed by the post-coital antiimplantation activity test.