Phenyl pyrrolidine analogues as potent nicotinic acetylcholine receptor (nAChR) ligands

The synthesis and SAR of a series of 2-phenyl pyrrolidines as neuronal nAChR ligands are described. Substitution on the aryl ring had a dramatic effect on receptor binding affinity, with Ki values ranging from 46 nM to >10,000 nM. Analogues 8, 9, and 14 were the most potent ligands evaluated, having Ki values of 68 nM, 75 nM, and 46 nM; respectively.