We designed the synthesis of a small library of 3-substituted-3,6-diazabicyclo[3.1.1]heptanes whose affinity on neuronal nicotinic receptors (nAChRs) was evaluated. Among the synthesized compounds, the 5-(3,6-diazabicyclo[3.1.1]heptane-3-yl)-N-(2-fluorophenyl)nicotinamide 43 proved to be the most interesting compound with α<sub>4</sub>β<sub>2</sub>Ki value of 10 pM and a very high α<sub>7</sub>/α<sub>4</sub>β<sub>2</sub> selectivity. Furthermore, compounds 35, 39 and 43 elicited a selective partial agonist activity for α<sub>4</sub>β<sub>2</sub> nAChR subtype. Finally, in this paper we also report the conclusions on the 3,6-diazabicyclo[3.1.1]heptanes as ligands for nAChRs, resulting from our consolidated structure activity relationship (SAR) studies on this template.