Synthesis and evaluation of the male antifertility properties of a series of N-unsubstituted sulfamates

This paper describes the synthesis and evaluation of a series of 6 aliphatic and 1 carbocyclic N-unsubstituted sulfamates as potential male antifertility agents. The compounds were prepared by treating a glycol with sulfamoyl chloride in the presence of sodium hydride and 12-dimethoxyethane or by the cleavage of a tert-butylsulfamate by trifluoroacetic acid. The sulfamates and methanesulfonic acid ester were orally administered in propylene glycol to male Sprague-Dawley rats for 14 consecutive days prior to mating with proestrus females which were sacrificed 14 days after the mating and examined for status of pregnancy. The males were autopsied for examination of the testes epididymis and accessory sex organs. Of all the sulfamates tested 3 compounds (12-ethaneydiyl sulfamate or compound 1 13-propanediyl sulfamate or compound 2 and 14-butanediyl sulfamate or compound 3) exhibited "functional sterility" with the most potency being exhibited by compounds 1 and 3. There was a decrease in the number of pregnant females and/or implantation coupled with increased embryonic and fetal resorption. Sulfamates probably act by altering the normal function of spermatids and epididymal spermatozoa.