Synthesis, Analgesic Activity, and Binding Properties of Some Epibatidine Analogs with a Tropine Skeleton

Design, synthesis, and biological activity of 5′-phenyl-1,2,5,6-tetrahydro-3,3′-bipyridine analogues as potential antagonists of nicotinic acetylcholine receptors

“…[24, 25] According to our modeling inspection using the 3D model of the open-channel structures[19] of α3β4, α4β2, and α7 nAChRs, compound 2 (modified from compound 1 with a phenyl ring attached to the pyridine ring) would not fit the binding pocket of the open-channel state of any of the above three receptors. But it might still fit the binding pocket of the closed-channel state.…”

“…A second stage Suzuki coupling of 5a – 5d with pyridine-3-boronic acid under similar conditions proceeded much more cleanly to give 3,3′-bipyridine products 6a – 6d in 71 – 93 % yield. Two-step elaboration of these to target 1-methyl-1,2,5,6-tetrahydro-3,3′-bipyridine derivatives 3a – 3d was achieved by following a literature procedure with close precedence [27]. Thus, treatment of 6a – 6d with excess iodomethane in acetone resulted in selective methylation of the flanking pyridine ring to give 7a – 7d in 72 – 100% yields.…”