Synthesis and biological evaluation of pyridine-modified analogues of 3-(2-Aminoethoxy)pyridine as novel nicotinic receptor ligands

Analogues of the potent nicotinic receptor agonist 3-(2-aminoethoxy)pyridine substituted at the 5′ and 6′-positions of the pyridine ring were synthesized and tested in vitro for nicotinic receptor binding activity (displacement of [3H](−)cytisine from whole rat brain synaptic membranes). The substituted analogues exhibited Ki values ranging from 0.076 to 319 nM compared to a Ki value of 26 nM for compound 1. Among the compounds tested, 5′-vinyl-6′-chloro substituted 1 was the most potent.