Biological evaluation of novel cyclopropyl analogues of stilbene, stilbenediol, and phenanthrene for estrogenic and antiestrogenic activity.

The triphenylethylene-type antiestrogens, such as tamoxifen, are known to be useful in the treatment of estrogen-dependent tumors. However, these compounds display mixed estrogen agonist/antagonist activity which may limit their therapeutic effectiveness. This problem of mixed activity led to the synthesis and identification of a cyclopropyl derivative of cis-stilbene which we have named Analog I. This compound (1,1-dichloro-cis-2,3-diphenylcyclopropane) displayed only antiestrogenic activity in the mouse. The present study was designed to evaluate cyclopropyl derivatives of Analog II for estrogenic and antiestrogenic activity in the rat using the standard 3-d uterotropic assay and the uterine cytoplasmic estrogen receptor assay. Five compounds (B-F) which are cyclopropyl derivatives of stilbene, stilbenediol, and phenanthrene were evaluated in this study. Three of the compounds (B-D) displayed neither estrogenic nor antiestrogenic activity in the rat. The relative estrogenic activities of E and F were 11.3 and 1.5%, respectively, of diethylstilbestrol in the uterotropic assay, and 39 and 6.2%, respectively, of estradiol in the estrogen receptor assay. Neither E nor F was found to display antiestrogenic activity in the rat. The results indicate that the relative estrogenic and receptor binding activities of E and F are similar to those previously observed in the mouse, while B-D appear to be inactive in both species.