Synthesis and biological activity of 17 beta-substituted estradiol.
The dialkylaminoethoxy side chain in triphenylethylene antiestrogens is required for their antiestrogenic activity. Without this side chain the compounds lose their antiestrogenic activity and become essentially estrogenic. Estradiol substituted at the 17 beta-position with dialkylaminoethoxy, dialkylaminoethylamino, or dialkylaminoethylthiol were synthesized and tested for their ability to displace estradiol for its receptor. All of the derivatives tested exhibited low binding affinities to the estrogen receptor, with RBA values ranging between 0 to 1.2 (estradiol = 100). The mouse and rat uterine weight test revealed only low estrogenic activity for this class of compounds. None of the estradiol derivatives synthesized showed antiestrogenic activity.
Qian
X D
XD
Departmnt of Medicinal Chemistry and Pharmacognosy, University of Minnesota, Minneapolis 55455.
Abul-Hajj
Y J
YJ
D000818:Animals; D004958:Estradiol / Q000031:analogs & derivatives*; D045166:Estradiol Congeners / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D007202:Indicators and Reagents; D007700:Kinetics; D051379:Mice; D008968:Molecular Conformation; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011959:Receptors, Estradiol / Q000187:drug effects / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D014599:Uterus / Q000033:anatomy & histology / Q000254:growth & development
D045166:Estradiol Congeners; D007202:Indicators and Reagents; D011959:Receptors, Estradiol; D011960:Receptors, Estrogen; D004958:Estradiol