| Abstract: | In an attempt to find a side chain biologically superior to the common acetylene (e.g., 17alpha-ethynyl as in ethisterone, mestranol and ethinyl estradiol) for an orally active protestogen, 17alpha allene derivatives of norethindrone and mestranol were prepared and tested in the rabbit CLAUBERG assay, and in the rat vaginal smear assay. The minimal effective dose for norethindrone in the rabbit test was .05 mg sc for 5 days; .0025 mg for 17alpha-norethindrone-CH=C=CH2; and .005 mg for 17 alpha-norethindrone-C(CH3)=C=CH2. Similar increases in progestational activity were obtained in the antiestrogenicity and ovulation inhibiton tests. When a saturated carbon was inserted, as in 17alpha-norethindrone-CH(CH3)-CH=C=CH2, the beta allenyl derivative was completely inactive. The ED50 for mestranol in the rat vaginal smear assay (estrogenicity) was .003mg; for 17alpha-mestranol-CH=C-CH2 .01 mg; for 17alpha-mestranol-C(CH3)=C=CH2 .015 mg. |
