SOME BIOLOGICAL ACTIVITIES OF 17-ETHYNYL AND 17-ALKYL DERIVATIVES OF 17-HYDROXYESTRENONES

Abstract

Some biological activities of 17-ethynyl and 17-alkyl derivatives of 17-hydroxyestrenones were investigated. The most interesting substance in the series with a double bond in the 5(10) position is norethynodrel. Studies have shown that on oral administration norethynodrel produces a progestational response in the estrogen-primed rabbit. This compound has a low but definite inherent estrogenic activity. This estrogenicity prevents the full manifestation of the potential progestational effects of norethynodrel in the rabbit. Norethynodrel causes pituitary gonadotropin inhibition and prevents fertile matings in rats when either the male or the female is treated. However the sterility so induced is temporary as shown both by the rapid recovery in the weights of the gonads and the accessory organs and by the rapid restoration of potency in both females and males after treatment is stopped. Enovid is norethynodrel to which has been added 1.5% of the 3-methyl ether of ethinyl estradiol. This mixture is slightly more estrogenic than norethynodrel but both produce similar progestational responses in the rabbit endometrium. Estrogenicity appears to mask progestational activity in some of the compounds with a double bond in the 5(10) position when they are administered in the uterine lumen. In others of the series as well as in most of those with a double bond in the 4(5) position no estrogenicity was manifest. Many of these compounds produce full progestational effects in the rabbit endometrium and are effective in maintaining pregnancy in the spayed rabbit.