Endogenous estrogens, such as 17β-estradiol (1, Scheme 1), have long been recognized as the primary hormones involved in the development and maintenance of the female sex organs, mammary glands and other sexual characteristics. More recently, their involvement in the growth and/or function of a number of other tissues, such as the skeleton, the cardiovascular system and the central nervous system has been recognized. These natural steroids are all derived from a common structural platform represented by the 18-carbon estrogen ring system (1, Scheme 1). Critical structural features within this framework include: (i) a phenol at the C-3 position of the aromatic A-ring, (ii) a relatively flat and rigid hydrocarbon core and (iii) a ketone or alcohol function at the C-17 position. Of these features, a detailed pharmacophore model postulates the important contribution of the two hydroxy groups of 17β-estradiol (1) to receptor binding, with the C-3 hydroxy acting as the major contributor to the binding free energyAnstead et al. 1997). This model is supported by recent X-ray crystallographic data showing 17β-estradiol bound to the ligand-binding domain of the estrogen receptor (ER) (Brzozowski et al. 1997).