1.
Synthesis and evaluation of 4-cycloheptylphenols as selective Estrogen receptor-ß agonists (SERBAs).
Eur J Med Chem
; 157: 791-804, 2018 Sep 05.
Artigo
em Inglês
| MEDLINE
| ID: mdl-30144697
RESUMO
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 ß over α isoform and with EC50 of 30-50â¯nM in cell-based and direct binding assays.