title: Octahydropyrrolo[3,4-c]pyrrole: a diamine scaffold for construction of either alpha4beta2 or alpha7-selective nicotinic acetylcholine receptor (nAChR) ligands. Substitutions that switch subtype selectivity.
abstract: A series of 5-(pyridine-3-yl)octahydropyrrolo[3,4-c]pyrroles have been prepared that exhibit high affinity to alpha4beta2 and/or alpha7 nicotinic acetylcholine receptors (nAChRs). Simple substitution patterns have been identified that allow construction of ligands that are highly selective for either nAChR subtype. The effects of substitution on subtype selectivity provide some insight into the differences in the ligand binding domains of the alpha4beta2 and alpha7 receptors, especially in regions removed from the cation binding pocket.
authors: Department R47W, Neuroscience Research, Abbott Laboratories, Abbott Park, Illinois 60064-6117, USA. William.h.bunnelle@abbott.com
authors: William H
authors: WH
authors: Bunnelle
authors: Karin R
authors: KR
authors: Tietje
authors: Jennifer M
authors: JM
authors: Frost
authors: Dan
authors: D
authors: Peters
authors: Jianguo
authors: J
authors: Ji
authors: Tao
authors: T
authors: Li
authors: Marc J C
authors: MJ
authors: Scanio
authors: Lei
authors: L
authors: Shi
authors: David J
authors: DJ
authors: Anderson
authors: Tino
authors: T
authors: Dyhring
authors: Jens H
authors: JH
authors: Grønlien
authors: Hilde
authors: H
authors: Ween
authors: Kirsten
authors: K
authors: Thorin-Hagene
authors: Michael D
authors: MD
authors: Meyer
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D003959:Diamines / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D018722:Nicotinic Agonists / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D011758:Pyrroles / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579167:Chrna7 protein, human; C579165:Chrna7 protein, rat; D003959:Diamines; D008024:Ligands; D018722:Nicotinic Agonists; D011758:Pyrroles; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2