Abstract
α7 Nicotinic acetylcholine receptors (α7 nAChR) represent promising therapeutic candidates for the treatment of cognitive impairment associated with Alzheimer's disease (AD) and schizophrenia. A medicinal chemistry effort around previously reported compound 1 (SEN15924, WAY-361789) led to the identification of 12 (SEN78702, WYE-308775) a potent and selective full agonist of the α7 nAChR that demonstrated improved plasma stability, brain levels, and efficacy in behavioral cognition models.
MeSH terms
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Animals
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Brain / drug effects*
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CHO Cells
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Calcium / metabolism
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Chemistry, Pharmaceutical
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Cognition / drug effects*
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Cricetinae
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ERG1 Potassium Channel
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Ether-A-Go-Go Potassium Channels / antagonists & inhibitors*
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Humans
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Models, Molecular
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Nicotinic Agonists / chemical synthesis
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Nicotinic Agonists / pharmacology*
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Piperidines / chemical synthesis
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Piperidines / pharmacology*
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Pyrazoles / chemical synthesis
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Pyrazoles / pharmacology*
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Rats
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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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alpha7 Nicotinic Acetylcholine Receptor
Substances
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Chrna7 protein, human
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Chrna7 protein, rat
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ERG1 Potassium Channel
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Ether-A-Go-Go Potassium Channels
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N-(5-(5-fluoropyridin-3-yl)-1H-pyrazol-3-yl)-4-piperidin-1-ylbutyramide
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Nicotinic Agonists
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Piperidines
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Pyrazoles
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Receptors, Nicotinic
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alpha7 Nicotinic Acetylcholine Receptor
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Calcium