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 compound 3 in good yield. When other reagents such as thiosemicarbazide, morpholine, sodium hydroxide or sodium hydride were treated with 2-bromoacetylestrone at room temperature, the furano derivative 3 was also obtained as the sole product. This new type of structural modification provided an estrogen nucleus deprived of the 3-hydroxyl function which was previously thought to be an essential requisite for binding to the estrogen receptor (ER). When evaluated in vitro for binding to the ER and in vivo for uterotrophic and antifertility activities, the furano derivative 3 was capable of inhibiting [3H]E2 binding by 16% while still eliciting high uterotrophic (99%) and postcoital antiimplantation (100%) activities relative to estradiol.
Mohsen
A
A
Department of Pharmaceutical Chemistry, University of Alexandria, Egypt.
Omar
M E
ME
Aboulwafa
O M
OM
Labouta
I M
IM
El-tombary
A A
AA
El-Mallah
A I
AI
D000818:Animals; D003270:Contraceptive Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D010064:Embryo Implantation / Q000187:drug effects*; D004970:Estrone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005663:Furans / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism*; D012756:Sheep; D013329:Structure-Activity Relationship; D014599:Uterus / Q000187:drug effects*
C098806:4',17-dioxo-5'H-estra-1(10),4-dieno(3,2-b)furan; D003270:Contraceptive Agents; D005663:Furans; D011960:Receptors, Estrogen; D004970:Estrone