7-Substituted 2-phenyl-benzofurans as ERβ selective ligands

• Published in: Bioorganic & medicinal chemistry letters Vol. 14; no. 19; pp. 4925 - 4929
• Main Authors: Collini, Michael D., Kaufman, David H., Manas, Eric S., Harris, Heather A., Henderson, Ruth A., Xu, Zhang B., Unwalla, Rayomand J., Miller, Chris P.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 04.10.2004; Elsevier
• Subjects: Benzofurans - chemical synthesis; Benzofurans - metabolism; Biological and medical sciences; Cell Line, Tumor; Estrogen Receptor beta - agonists; Estrogen Receptor beta - chemistry; Estrogen Receptor beta - metabolism; Humans; Insulin-Like Growth Factor Binding Protein 4 - genetics; Ligands; Medical sciences; Miscellaneous; Pharmacology. Drug treatments; RNA, Messenger - analysis; Structure-Activity Relationship; Estrogen receptor β; Lipophilic compound; Affinity; Selectivity; Benzofuran derivatives; Chemical synthesis; Biological activity
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2004.07.029

Substituted benzofuran 21 is a potent and selective ER ligand. A series of 2-(4-hydroxy-phenyl)-benzofuran-5-ols with relatively lipophilic groups in the 7-position of the benzofuran was prepared and the affinity and selectivity for ERβ was measured. Many of the analogues were found to be potent and selective ERβ ligands. Additional modifications at the benzofuran 4-position as well as at the 3′-position of the 2-phenyl group were found to further increase selectivity. Such modifications led to compounds with <10 nM potency and >100-fold selectivity for ERβ.