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.
Copyright 2009 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Humans
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Ligands*
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Nicotinic Agonists / chemical synthesis
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Nicotinic Agonists / chemistry*
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Nicotinic Agonists / pharmacology
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Oocytes / metabolism
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Pyridazines / chemical synthesis
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Pyridazines / chemistry*
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Pyridazines / pharmacology
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Pyrroles / chemical synthesis
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Pyrroles / chemistry*
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Pyrroles / pharmacology
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Receptors, Nicotinic / chemistry*
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Receptors, Nicotinic / metabolism
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Structure-Activity Relationship
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Xenopus
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alpha7 Nicotinic Acetylcholine Receptor
Substances
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2-(6-phenylpyridazin-3-yl)-5-(pyridin-3-ylmethyl)octahydropyrrolo(3,4-c)pyrrole
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Chrna7 protein, human
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Ligands
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Nicotinic Agonists
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Pyridazines
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Pyrroles
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Receptors, Nicotinic
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alpha7 Nicotinic Acetylcholine Receptor