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Updated: May 29, 2026
06:18
An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Sulfonamides as selective oestrogen receptor β agonists.
Lee R Roberts1, Duncan Armor, Carolyn Barker
1Worldwide Medicinal Chemistry, Pfizer, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK. lee.roberts@pfizer.com
Bioorganic & Medicinal Chemistry Letters
|September 3, 2011
Summary
Researchers discovered novel p-hydroxybenzenesulphonamides that selectively activate the estrogen receptor beta (ERβ). Compound 11 showed promising selectivity and binding, offering a strong foundation for developing new ERβ agonists.
Area of Science:
- Medicinal Chemistry
- Molecular Pharmacology
- Structural Biology
Background:
- Estrogen receptors (ERs) play crucial roles in various physiological processes.
- Selective modulation of ER subtypes, particularly ERβ, is a therapeutic goal.
- Developing selective ERβ agonists requires identification of novel chemical scaffolds.
Purpose of the Study:
- To discover and characterize novel p-hydroxybenzenesulphonamide derivatives as ERβ receptor agonists.
- To assess the selectivity of these compounds against the ERα receptor.
- To investigate the structural basis for selective ERβ binding.
Main Methods:
- Synthesis of a series of p-hydroxybenzenesulphonamide compounds.
- In vitro assays to determine ERβ and ERα receptor binding and activity.
- X-ray crystallography to elucidate the binding conformation of key compounds.
Main Results:
- Several p-hydroxybenzenesulphonamide derivatives demonstrated potent ERβ agonistic activity.
- High selectivity for ERβ over ERα was observed for multiple identified compounds.
- Compound 11 exhibited a favorable binding conformation, detailed by X-ray crystallography.
Conclusions:
- The p-hydroxybenzenesulphonamide scaffold is a promising starting point for developing selective ERβ agonists.
- Compound 11 serves as an excellent lead compound for further optimization.
- Structural insights from compound 11 can guide the design of future selective ERβ modulators.
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