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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
Author(s) -
Omar A. Mohsen M. E.,
Aboulwafa Omaima M.,
Labouta Ibrahim M.,
Eltombary Alaa A. A.,
ElMallah Ahmed I.
Publication year - 1996
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19963290202
Subject(s) - chemistry , morpholine , thiourea , sodium hydride , furan , estrogen receptor , yield (engineering) , derivative (finance) , stereochemistry , in vivo , estrogen , medicinal chemistry , organic chemistry , medicine , materials science , microbiology and biotechnology , cancer , breast cancer , economics , financial economics , metallurgy , biology
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[ 3 H]E 2 binding by 16% while still eliciting high uterotrophic (99%) and postcoital antimplantation (100%) activities relative to estradiol.