Fluoro-clomiphene and its synthetic precursors: synthesis and receptor binding.
In an attempt to synthesize compounds with selective estrogen-receptor binding, fluoro- and amino-clomiphene were totally synthesized from benzyl chloride, and their estrogenic/antiestrogenic activity as well as that of some of their chemical intermediates was evaluated. The triazene prepared from the amino-clomiphene was converted into fluoro-clomiphene with 39% yield. In the uterotropic test, both amino- and fluoro-clomiphene exerted mild equipotent estrogenic activity, with minimal saturation doses being 50 and 100 micrograms/rat/day for three days. In the receptor binding test both derivatives demonstrated similar displacement, with an A50% value in the 10(-5) M range, as compared to 10(-6) M for clomiphene and 10(-9) M for diethyl-stilbestrol. This synthesis may be useful for the preparation of 18F-labeled clomiphene for biodistribution studies.
Gazit
A
A
Department of Pharmacology, Hebrew University School of Pharmacy, Jerusalem, Israel.
Livshitz
T
T
Shani
J
J
D000818:Animals; D001667:Binding, Competitive; D002996:Clomiphene / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism
D011960:Receptors, Estrogen; C053254:1-(4-fluorophenyl)-1-(4-(2-N,N-diethylamino)ethoxy)phenyl-2-phenylethylene; D002996:Clomiphene; D004958:Estradiol