Structure activity studies of ring E analogues of methyllycaconitine. Part 2: Synthesis of antagonists to the α3β4* nicotinic acetylcholine receptors through modifications to the ester

The development of novel agents for the differentiation of neuronal nicotinic acetylcholine receptors (nAChRs) is important for the treatment of a variety of pathological conditions. We have prepared and evaluated a number of simpler analogues of the norditerpeniod alkaloid methyllycaconitine (MLA) in an effort to understand molecular determinants of nAChR•small molecule interactions. We have previously reported the synthesis and evaluation of a series of ring E analogues of MLA. We report here the optimization of the α3β4* functional activity of this series of compounds through modification of the ester. [Copyright &y& Elsevier]