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Localization of Plasma Membrane and Intracellular Neuronal Nicotinic Acetylcholine Receptors Using Quantitative Imaging in Mammalian Cells
Published on: December 19, 2025
2-(Arylmethyl)-3-substituted quinuclidines as selective alpha 7 nicotinic receptor ligands
Anatoly Mazurov1, Jozef Klucik, Lan Miao
1Targacept, Inc., Medicinal Chemistry, 200 East First Street, Suite 300, Winston-Salem, NC 27101, USA. anatoly.mazurov@targacept.com <anatoly.mazurov@targacept.com>
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.
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