Structure-activity relationships of N-substituted ligands for the alpha 7 nicotinic acetylcholine receptor

A series of alpha 7 neuronal nicotinic acetylcholine receptor ligands were designed based on a structural combination of a potent, but non-selective ligand, epibatidine, with a selective lead structure, 2. Three series of compounds in which aryl moieties were attached via a linker to different positions on the core structure were studied. A potent and functionally efficacious analog, (3aR,6aS)-2-(6-phenylpyridazin-3-yl)-5-(pyridin-3-ylmethyl) octahydropyrrolo[3,4-c]pyrrole (3a), was identified. (C) 2009 Elsevier Ltd. All rights reserved.