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ID: ALA1143532

Journal: Bioorg Med Chem Lett

Title: 2-(Arylmethyl)-3-substituted quinuclidines as selective alpha 7 nicotinic receptor ligands.

Authors: Mazurov A, Klucik J, Miao L, Phillips TY, Seamans A, Schmitt JD, Hauser TA, Johnson RT, Miller C.

Abstract: A series of 2-(arylmethyl)-3-substituted quinuclidines was developed as alpha7 neuronal nicotinic acetylcholine receptor (nAChR) agonists based on a putative pharmacophore model. The series is highly selective for the alpha7 over other nAChRs (e.g., the alpha4beta2 of the CNS, and the muscle and ganglionic subtypes) and is functionally tunable at alpha7. One member of the series, (+)-N-(1-azabicyclo[2.2.2]oct-3-yl)benzo[b]furan-2-carboxamide (+)-8l), has potent agonistic activity for the alpha7 nAChR (EC(50)=33nM, I(max)=1.0), at concentrations below those that result in desensitization.

CiteXplore: 15808471

DOI: 10.1016/j.bmcl.2005.02.045