Synthesis and evaluation of hexahydrochrysene and tetrahydrobenzofluorene ligands for the estrogen receptor

To prepare novel estrogen receptor (ER) ligands, we have developed a facile approach to substituted hexahydrochrysene and tetrahydrobenzo[ a]fluorene systems. Substituents, including basic side chains, were added to these systems, and their binding affinity to ERα and ERβ, and in some cases their transcriptional activity were evaluated. Derivatives in two bis-phenolic tetracyclic systems have been prepared and evaluated as estrogen receptor ligands and transcriptional activators.