An o-Aminoanilide Analogue of 1α,25-Dihydroxyvitamin D3 Functions as a Strong Vitamin D Receptor Antagonist

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• 作者：Marc Lamblin ; Russell Spingarn ; Tian-Tian Wang ; Melanie C. Burger ; Basel Dabbas ; Nicolas Moitessier ; John H. White ; James L. Gleason
• 刊名：Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：October 28, 2010
• 年：2010
• 卷：53
• 期：20
• 页码：7461-7465
• 全文大小：845K
• 年卷期：v.53,no.20(October 28, 2010)
• ISSN：1520-4804

文摘

Vitamin D receptor (VDR) antagonists have therapeutic potential in treatment of allergic conditions and hypercalcemia driven by granulomatous diseases. We have identified an o-aminoanilide analogue of the hormonal form of vitamin D with a dienyl side chain that functions as a strong VDR antagonist. Modeling studies indicate that antagonism arises from side chain rigidity, when compared to a more flexible saturated analogue, which interferes with H12 folding/alignment.