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 (3a and 3b). The compounds were evaluated for binding to the alpha 4 beta 2 and alpha 7 nicotinic acetylcholine receptors (nAChRs), for pharmacological activity in the mouse tail-flick and hot-plate assays, and for hypothermia and locomotor activity. Compounds 3a and 3b possessed alpha 4 beta 2 nAChR binding properties similar to those of (-)-nicotine and were nAChR agonists in all four mouse assays