Synthesis and nicotinic binding of novel phenyl derivatives of UB-165. Identifying factors associated with α7 selectivity

Four racemic phenyl-substituted analogues 3–6 of the potent nicotinic agonist UB-165 1 have been synthesised and evaluated against the α4β2, α3β4, and α7 neuronal nicotinic receptors. The 2′-phenyl derivative 3 shows no activity at these major receptor subtypes, while the 4′-phenyl analogue 4 shows an enhanced level of α7 selectivity as compared to UB-165 and deschloro UB-165 2. These results are discussed within the context of recent pharmacophore models.