Abstract
Neuronal nicotinic acetylcholine receptors are members of the ligand-gated ion channel receptor superfamily and may play important roles in modulating neurotransmission, cognition, sensory gating, and anxiety. Because of its distribution and abundance in the CNS, the alpha 7 nicotinic receptor is a strong candidate to be involved in some of these functions. In this paper we describe the synthesis and in vitro profile of AR-R17779, (-)-spiro[1-azabicyclo[2.2. 2]octane-3,5'-oxazolidin-2'-one] (4a), a potent full agonist at the rat alpha 7 nicotinic receptor, which is highly selective for the rat alpha 7 nicotinic receptor over the alpha 4 beta 2 subtype. Preliminary SAR of AR-R17779 presented here indicate that there is little scope for modification of this rigid molecule as even minor changes result in significant loss of the alpha 7 nicotinic receptor affinity.
MeSH terms
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Acetylcholine / chemistry*
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Animals
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Bridged-Ring Compounds / chemical synthesis
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Bridged-Ring Compounds / metabolism
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Bridged-Ring Compounds / pharmacology*
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Hippocampus / metabolism
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In Vitro Techniques
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Nicotinic Agonists / chemical synthesis
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Nicotinic Agonists / metabolism
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Nicotinic Agonists / pharmacology*
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Oocytes / metabolism
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Oocytes / physiology
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Prosencephalon / metabolism
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Radioligand Assay
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Rats
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Receptors, Nicotinic / drug effects*
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Receptors, Nicotinic / metabolism
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Spiro Compounds / chemical synthesis
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Spiro Compounds / metabolism
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Spiro Compounds / pharmacology*
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Stereoisomerism
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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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AR-R 17779
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Bridged-Ring Compounds
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Chrna7 protein, rat
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Nicotinic Agonists
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Receptors, Nicotinic
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Spiro Compounds
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alpha7 Nicotinic Acetylcholine Receptor
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nicotinic receptor alpha4beta2
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Acetylcholine