The estrogen receptors, responsible for the effects of this hormone, are known to be able to recognize nonsteroidogenic molecules, and this has led to the development of molecules with therapeutic potential. The phenomenon of nonsteroidal ligands of the estrogen receptors is also thought to play a major role in food and environmental sciences, with the winepolyphenol resveratrol and the insecticide DDT thought to act as estrogenic substances. It is therefore evident that it is of great interest to develop specific nonsteroidal substances that interfere with the estrogen receptors in a receptor-specific and/or tissue-specific manner and that display agonistic, antagonistic, or partial agonistic properties. Indeed, a number of strategies have been or could be employed to generate new structures, namely the screening of existing chemical libraries, the screening of natural compound libraries, novel modifications of known compounds with estrogenic potential, or the de novo generation of chemical libraries using rapid synthetic methods. Click chemistry is an increasingly common method for rapid synthesis of novel biologically active compounds. This term, coined by Barry K. Sharpless, now refers to reactions yielding the product in high yield without the need for further purification, without generating offensive byproducts, and operating in a benign solvent, usually water. In this way, it is possible to generate a plethora of new compounds reliably and thereby accelerate the process of drug discovery. Briefly, the paradigmatic “click” reaction is the [3+2] cycloaddition between an azide and an alkyne in the presence of copper (I) salts which generate the 1,4 disubstituted 1H-1,2,3-triazole ring in excellent yield. Three distinct observations have drawn our attention to the possibility of applying click chemistry to the synthesis of ER ligands: 1) reports that a pyrazole core can be used to build compounds that are ER ligands, 2) the successful bioisosteric replacement of pyrazole with a triazole in fibronil, an insecticide acting as a GABA receptor antagonist, and 3) our report that several resveratrol analogues synthesized by click chemistry retain estrogen-like activity. We have therefore used the archetypical [3+2] azide-alkyne cycloaddition to link two phenol rings, bearing the hydroxyl moieties in different positions, with a distance comparable to estradiol or diethylstilbestrol. Azides (1–3, Figure 1) were obtained by reacting commercially available amine phenols, via diazonium salt, with sodium azide. The desired ethynyl phenols (4–6, Figure 1) were ob-