Structure-activity relationship of estrogens: a study involving cyclofenyl as the model compound.

Bis-(p-acetoxyphenyl)cyclohexylidenemethane [cyclofenyl] has been shown to resemble triarylethylene estrogens quite closely in its receptor binding specificity as well as activity profile. Mono-pyrrolidinoethyl ether of cyclofenyl thus acts as a more potent receptor binder but less potent estrogen than its parent. Like triarylethylene antiestrogens, this derivative of cyclofenyl also acts as an antiuterotrophic agent. This finding would substantiate the proposition that the geminal diaryl residue and not the 1,2-diarylethylene moiety is mainly responsible for the receptor binding and activity profile characteristic of triarylethylenes. This understanding can form a basis for the rationalization of the structure-activity-relationship of estrogens at the molecular level.