Synthesis, Nicotinic Acetylcholine Receptor Binding, and Antinociceptive Properties of 2-exo-2-(2‘-Substituted-3‘-phenyl-5‘-pyridinyl)-7-azabicyclo[2.2.1]heptanes. Novel Nicotinic Antagonist

A series of 2‘-substituted-3‘-phenyl epibatidine analogues were synthesized and evaluated for inhibition of binding at nicotine acetylcholine receptors and for antinociceptive properties in mice. The introduction of a bulky phenyl group at the 3‘-position exerted a profound influence on both receptor binding and antinociceptive effects. Substitution of different groups at the 2‘-position distinguished between agonist and antagonist properties. These results demonstrate that structural requirements for receptor activities and recognition are distinctively different.