Reaction of 3,9 alpha, 17 beta-trihydroxyestra-1,3,5(10)-trien-11-one 17-acetate 3-methyl ether (3) with N3H-BF3 etherate leads mainly to lactam (4) along with the N-azido compound (5) as a minor product. Under similar conditions, 3,17 beta-dihydroxyestra-1,3,5(10)-trien-6-one 17-acetate 3-methyl ether gives lactam (12) and the tetrazole derivative (9). Similar reaction of the diacetate (8) gives only the tetrazole derivative (11). Compounds 4, 6, and 10 prevent implantation in rats at 5-, 10-, and 5-mg/kg doses, respectively. Compounds 4, 6, 9, and 10 show significant estrogenic activity at the respective contraceptive doses.
PIP: Scientists at the Central Drug Research Institute in Lucknow, India, synthesized and evaluated new 6-aza-B-and 11-aza-C-homoestranes to determine the effect of structural changes around C-11 and C-6 in estradiol on its estrogenic and antifertility activities. They used sperm-positive female albino rats (180-220 g) to test the compounds anti-implantation activity and ovariectomized immature rats (25-30 g) to test their estrogenic activity. Adding N3H-BF3 etherate to 3, 9-alpha,17-beta-trihydroxyestra-1,3,5(10)-trien-11-one 17-acetate 3-methyl ether created 11-aza-3,17beta-dihydroxy-C-homoestra-1,3,5(10),8(9)-tetraen-12-one 17-acetate 3-methyl ether and the N-azido compound as a minor product. Adding N3H-BF3 etherate to 3, 17beta-dehyroxyestra-1,3,5(10)-trien-6-one 17-acetate 3-methyl ether created 6-aza-3,17beta-dihydroxy-B-homoestra-1,3,4(10)-trien-7-one 17-acetate 3-methyl ether and the tetrazolo derivative. When N3H-BF3 etherate was added to diacetate, just the tetrazole derivative emerged. 1-aza-3,17beta-dihydroxy-C-homoestra-1,3,5(10),8(9)-tetraen-12-one 17-acetate 3-methyl ether (5 mg-kg dose), 11-aza-3,17beta-dihydroxy-C-homoestra-1,3,5(10),8(9)-tetraen-12-one 3-methyl ether (10 mg/kg dose), and 6-aza-3,17beta-dihydroxy-B-homoestra-1,3,4(10)-trieno[6,7-d]tetrazole 3-methyl ether (5 mg/kg dose) all delivered subcutaneously, prevented implantation in all rats. These compounds and 6-aza-3,17beta-dihydroxy-B-homoestra-1,3,5(10)-trieno[6,7-d] tetrazole 17-acetate 3-methyl ether (10mg/kg dose) showed significant estrogenic activity.