aRatio of IC50 values competitive to 17ß-estradiol.

aRatio of IC50 values competitive to 17ß-estradiol.

Figure 26 ERp-selective phytoestrogens.

at C5 on the isoflavone ring system of genistein. Although this additional hydroxyl has no specific interaction with the protein, its presence confers a significant increase in binding selectivity for ERb (20-fold versus fivefold). Indeed, coumestrol (11) and kaempferol (47) also appear to have additional polar functionalities that are more tolerated by ERb than ERa and therefore confer selectivity for ERb. The relative transactivational activity of each compound was also determined at a concentration of 1000nmolL_ 1. Although they were all less potent than E2, some (genistein, zearalenone, and coumestrol) were able to generate a response of the same or greater magnitude than E2. In addition, the rankings of the estrogenic potency of the phytoestrogens differed for the two subtypes.

Schopfer and co-workers have explored the potential of aryl benzothiophenes as lead structures for the generation of selective ERb agonists.104 A series of aryl benzothiophene compounds (Figure 27), was synthesized via a Suzuki

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