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

Abstract

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.