Neuronal nicotinic acetylcholine receptor binding affinities of boron-containing nicotine analogues

A series of boron-containing nicotine (NIC) analogues 7–9 was synthesized and evaluated for binding to α4β2 and α7 nicotinic receptors. Compound ACME-B inhibited [3H]methyllycaconitine binding to rat brain membranes with a similar potency compared to NIC (Ki=2.4 and 0.77 μM, respectively), but was markedly less potent in inhibiting [3H]NIC binding when compared to NIC (Ki=0.60 μM and 1.0 nM, respectively). Thus, tethering a two-carbon bridge between the 2-pyridyl and 3′-pyrrolidino carbons of NIC or 7 affords analogues that bind to the α7 receptor in a manner similar to NIC, but with a dramatic loss of affinity for the α4β2 receptor.