Quantitative structure-activity relationships of nicotine analogues as neuronal nicotinic acetylcholine receptor ligands

Quantitative structure-activity relationships of 34 pyrrolidine-modified nicotine agonists are investigated for their binding affinity toward neuronal nicotinic acetylcholine receptor. The results indicate that a large substituent at the R₁, R₂, and R₃ position is detrimental to the binding affinity. Likewise, a large substituent at the R₂ or R₃ position as well as a hydrogen bond accepting substituent at the R_2β position are not beneficial to the binding.