Synthesis and structure-activity relationships of potent conformationally restricted retinoid X receptor ligands

A series of potent retinoid X receptor (RXR) selective ligands were designed and prepared. The lead compound 6a, showed good binding (Kd; 3–7 nM) and transactivation (EC50; 19–24 nM) to the RXR subfamily of retinoid receptors. More importantly, a small variation on the aromatic ring moiety led to 6b, which had less residual RAR agonist activity with RXR binding and potency of 4–5 nM and 5–13 nM, respectively.