1. Synthesis and evaluation of 4-cycloheptylphenols as selective Estrogen receptor-β agonists (SERBAs).
- Author
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Sampathi Perera KLI, Hanson AM, Lindeman S, Imhoff A, Lu X, Sem DS, and Donaldson WA
- Subjects
- Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Cell Proliferation drug effects, Crystallography, X-Ray, Cycloheptanes chemical synthesis, Cycloheptanes chemistry, Cycloheptanes pharmacokinetics, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Estrogens chemical synthesis, Estrogens chemistry, Humans, MCF-7 Cells, Methanol chemical synthesis, Methanol chemistry, Models, Molecular, Molecular Structure, Phenols chemical synthesis, Phenols chemistry, Structure-Activity Relationship, Antineoplastic Agents pharmacology, Cycloheptanes pharmacology, Estrogen Receptor beta agonists, Estrogens pharmacology, Methanol pharmacokinetics, Phenols pharmacology
- Abstract
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 EC
50 of 30-50 nM in cell-based and direct binding assays., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)- Published
- 2018
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