Novel retinoid X receptor (RXR) antagonists having a dicarba-closo-dodecaborane as a hydrophobic moiety

We designed and synthesized novel retinoid X receptor (RXR)-selective antagonists bearing a carborane moiety. Compounds 8a–d or 9a–d themselves have no differentiation-inducing activity toward HL-60 cells and no inhibitory activity towards a retinoic acid receptor (RAR) agonist. However, they inhibit the synergistic activity of an RXR agonist, PA024, in the presence of Am80 on the cell differentiation of HL-60. Transactivation assay using RARs and RXRs suggested that the inhibitory activity of 9b resulted from the selective antagonism at the RXR site of RXR–RAR heterodimers.