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 T-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.