STUDIES ON NON-STEROIDAL ANTIFERTILITY AGENTS——SYNTHESIS AND ANTIFERTILITY EFFECTS OF 1, 1-DIPHENYL-2-NAPHTHYL ETHYLENES

Seventeen 1, 1-diphenyl-2-naphthylethylenes were synthesized through Grignard reaction followed by acid catalyzed water elimination and tested for their antifertility effects in rats or rabbits. Three of them, compounds 6931, 70082, 70083, completely prevented fertility in female rats at a dose of 10 mg/kg/day by oral adiministration for six days. Compound 6931 was shown to be the most effective which caused complete inhibition of pregnancy in female rabbits at an oral dose of 5 mg/kg/day for three days. Further pharmacological studies revealed that this compound was also highly effective against implantation in female dogs and monkeys and no undesirable side effects has been found at different dosage levels. It was then subjected to clinical trials but the results were not very encouraging.It is interesting to note that the antifertility effects markedly decreased when the olefinic hydrogen in the molecule was replaced by bromine, chlorine or nitro group.