Synthesis and Pharmacological Characterization of exo-2-(2‘-Chloro-5-pyridinyl)-7-(endo and exo)-aminobicyclo[2.2.1]heptanes as Novel Epibatidine Analogues

Procedures were developed for the synthesis of exo-(2‘-chloro-5-pyridinyl)-7-(endo and exo)-amino[2.2.1]heptanes (<BO>3a </BO>and <BO>3b</BO>). The compounds were evaluated for binding to the α4β2 and α7 nicotinic acetylcholine receptors (nAChRs), for pharmacological activity in the mouse tail-flick and hot-plate assays, and for hypothermia and locomotor activity. Compounds <BO>3a</BO> and <BO>3b</BO> possessed α4β2 nAChR binding properties similar to those of (−)-nicotine and were nAChR agonists in all four mouse assays.