title: Structure-activity relationships of N-substituted ligands for the alpha7 nicotinic acetylcholine receptor.
abstract: A series of alpha7 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.
authors: Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA. kathleen.mortell@abbott.com
authors: Kathleen H
authors: KH
authors: Mortell
authors: Michael R
authors: MR
authors: Schrimpf
authors: William H
authors: WH
authors: Bunnelle
authors: David J
authors: DJ
authors: Anderson
authors: Jens Halvard
authors: JH
authors: Gronlien
authors: Kirsten Thorin
authors: KT
authors: Hagene
authors: Murali
authors: M
authors: Gopalakrishnan
mesh_terms: D000818:Animals; D006801:Humans; D008024:Ligands; D018722:Nicotinic Agonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014981:Xenopus; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C549130:2-(6-phenylpyridazin-3-yl)-5-(pyridin-3-ylmethyl)octahydropyrrolo(3,4-c)pyrrole; C579167:Chrna7 protein, human; D008024:Ligands; D018722:Nicotinic Agonists; D011724:Pyridazines; D011758:Pyrroles; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor