Synthesis and Evaluation of 4-Cycloheptylphenols as Selective Estrogen Receptor-β Agonists (SERBAs)
European Journal of Medicinal Chemistry
A short and efficient route to 4-(4-hydroxyphenyl)cycloheptanemethanol was developed, which resulted in the preparation of a mixture of 4 stereoisomers. The stereoisomers were separated by preparative HPLC, and two of the stereoisomers identified by X-ray crystallography. The stereoisomers, as well as a small family of 4-cycloheptylphenol derivatives, were evaluated as estrogen receptor-beta agonists. The lead compound, 4-(4-hydroxyphenyl)cycloheptanemethanol was selective for activating ER relative to seven other nuclear hormone receptors, with 300-fold selectivity for the β over α isoform and with EC50 of 30–50 nM in cell-based and direct binding assays.
Perera, K. L. Iresha Sampathi; Hanson, Alicia M.; Lindeman, Sergey V.; Imhoff, Andrea; Lu, Xingyun; Sem, Daniel S.; and Donaldson, William A., "Synthesis and Evaluation of 4-Cycloheptylphenols as Selective Estrogen Receptor-β Agonists (SERBAs)" (2018). Chemistry Faculty Research and Publications. 987.
ADA Accessible Version
Accepted version. European Journal of Medicinal Chemistry, Vol. 157 (September 5, 2018): 791-804. DOI. © 2018 Elsevier. Used with permission.
Daniel S. Sem was affiliated with Concordia University at the time of publication.