ANTIPROGESTATIONAL STEROIDS: SYNTHESIS OF 7α-AND 7β-METHYL-A-NOR-5α-ANDROSTANE-2α, 17α-DIETHYNYL-2β, 17β-DIOL

Introducing a methyl group at the 7-position of steroids may increase the biological activity of the alkylated derivative compared to the corresponding parent compound. Considering the various antiprogestational agents such as RMI 12,936 which possesses this structural, feature, we introduced a 7-methyl group into Anordrin, an effective antifertility agent, to yield 7α- and 7β-methyl-A-nor-5α-androstane-2α, 17α-diethynyl-2β, 17β-diol. The synthesis was accomplished by six steps from testosterone as shown in scheme 1 with good yield.Preliminary pharmacological results indicate that Ⅱa exhibited significant inhibition on the decidual reaction in pseudopregnant rats at an oral dose of 2.5 mg/kg. It was shown to be effective in anti-implantation and termination of early pregnancy in female rats, when given orally at a dose of 2.5 mg/kg/d for 4 days and 3.5 mg/kg/d for 4 days respectively. Ⅱb at a dose 10 mg/kg/d for 4 days showed only 30-40% efficacy in termination of early pregnancy.