Design and synthesis of carborane-containing estrogen receptor-beta (ERβ)-selective ligands
書誌事項
- 公開日
- 2015-10
- 資源種別
- journal article
- 権利情報
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- https://www.elsevier.com/tdm/userlicense/1.0/
- https://www.elsevier.com/legal/tdmrep-license
- DOI
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- 10.1016/j.bmcl.2015.08.007
- 公開者
- Elsevier BV
この論文をさがす
説明
Candidates for highly selective estrogen receptor-beta (ERβ) ligands (6a-c, 7a-c, 8a and 8b) were designed and synthesized based on carborane-containing ER ligands 1 and 2 as lead compounds. Among them, p-carboranylcyclohexanol derivatives 8a and 8b exhibited high ERβ selectivity in competitive binding assay: for example, 8a showed 56-fold selectivity for ERβ over ERα. Docking studies of 8a and 8b with the ERα and ERβ ligand-binding domains (LBDs) suggested that the p-carborane cage of the ligands is located close to key amino acid residues that influence ER-subtype selectivity, that is, Leu384 in the ERα LBD and Met336 in the ERβ LBD. The p-carborane cage in 8a and 8b appears to play a crucial role in the increased ERβ selectivity.
収録刊行物
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- Bioorganic & Medicinal Chemistry Letters
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Bioorganic & Medicinal Chemistry Letters 25 (19), 4174-4178, 2015-10
Elsevier BV
