Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10593252 | Bioorganic & Medicinal Chemistry Letters | 2013 | 4 Pages |
Abstract
We previously showed that fluorination of the carborane-containing selective estrogen receptor modulator (SERM) BE360 altered the agonist/antagonist activity balance and the estrogen receptor (ER) α/β subtype selectivity. Here, we designed and synthesized a series of fluorinated carboranyl phenols as candidate ERβ-selective ligands. Introduction of a fluorine atom onto the carborane cage commonly reduced the binding affinity for ERα, to an extent that depended on the other substituents present. The B-fluorinated m-carboranyl phenol 4a showed fourfold more potent ERβ-binding affinity than the parent non-fluorinated compound 7. 1-Iodo-9-fluoro-m-carboranyl phenol 4f showed high ERβ-binding affinity with an ERβ/ERα selectivity ratio of 8.2. Among the compounds tested, 6 showed the highest ERβ selectivity (10.1-fold) and the highest ER-agonistic activity (EC50: 5.1 Ã 10â10 M) in MCF-7 cell proliferation assay.
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Authors
Kiminori Ohta, Takumi Ogawa, Asako Kaise, Yasuyuki Endo,