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.