4',17-DIOXO-5'H-ESTRA-1(10),4-DIENO[3,2-B]FURAN - SYNTHESIS, BINDING-AFFINITY TO THE ESTROGEN-RECEPTOR, UTEROTROPHIC AND ANTIIMPLANTATION ACTIVITIES

4',17-Dioxo-5'H-estra-1(10),4-dieno[3,2-b]furan (3) has been prepared by several routes starting from 2-bromoacetylestrone (2). Performance of the reaction with thiourea at elevated temperature provided compoun d 3 in good yield. When other reagents such as thiosemicarbazide, morp holine, sodium hydroxide or sodium hydride were treated with 2-bromoac etylestrome at room temperature, the furano derivative 3 was also obta ined as the sole product. This new type of structural modification pro vided an estrogen nucleus deprived of the 3-hydroxyl function which wa s previously thought to be an essential requisite for binding to the e strogen receptor (ER). When evaluated in vitro for binding to the ER a nd in vivo for uterotrophic and antifertility activities, the furano d erivative 3 was capable of inhibiting[H-3]E(2) binding by 16% while st ill eliciting high uterotrophic (99%) and postcoital antiimplantation (100%) activities relative to estradiol.