SERM-type ligands

From the benzoxathiins reported thus far, 117 exhibits good prospects for further development. The optimized BSC was also tested on other SERM-type ligands, including raloxifene, bazedoxifene and lasofoxifene [151]. Although some increase in ER affinity was observed, no improvement in the rat uterine profile was observed. This result indicates that the optimized side-chain from the benzoxathiins series is not easily transferable to other estrogen ligands. 

Phenantrenes SignalGene reported on phenantrenes as SERM-type ligands for the ERs [180]. Most of the phenantrenes disclosed showed very low affinity for either ER, but dihydrophenantrene analog 143 showed reasonable ERa affinity (K, = 9 nM) and 22-fold ERa selectivity. 

Napthylenes Nafoxidine is one of the earliest discovered SERM-type ER ligands. This ER ligand was discovered by Upjohn in the early 1960s and has been subjected to extensive clinical evaluation. However, the compound turned out to be far too toxic for general clinical use [158]. 

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