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  • 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.
    Author: Bunnelle WH, Tietje KR, Frost JM, Peters D, Ji J, Li T, Scanio MJ, Shi L, Anderson DJ, Dyhring T, Grønlien JH, Ween H, Thorin-Hagene K, Meyer MD.
    Journal: J Med Chem; 2009 Jul 23; 52(14):4126-41. PubMed ID: 19552432.
    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.
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