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 alpha3beta4* functional activity of this series of compounds through modification of the ester. (C) 2004 Elsevier Ltd. All rights reserved.