Abstract
An expeditious microwave-assisted synthesis of 4BP-TQS, its enantiomeric separation, and their functional evaluation is reported. Electrophysiological characterization in Xenopus oocytes revealed that activity exclusively resided in the (+)-enantiomer 1b (GAT107) and (-)-enantiomer 1a did not affect its activity when coapplied. X-ray crystallography studies revealed the absolute stereochemistry of 1b to be 3aR,4S,9bS. 1b represents the most potent ago-PAM of α7 nAChRs available to date and is considered for further in vivo evaluation.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Allosteric Regulation / drug effects
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Animals
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Binding Sites / drug effects
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Crystallography, X-Ray
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Dose-Response Relationship, Drug
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Microwaves
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Models, Molecular
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Molecular Structure
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Oocytes / chemistry
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Oocytes / drug effects
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Oocytes / metabolism
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Quinolines / chemical synthesis
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Quinolines / chemistry
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Quinolines / pharmacology*
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Stereoisomerism
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Structure-Activity Relationship
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Sulfonamides / chemical synthesis
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Sulfonamides / chemistry
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Sulfonamides / pharmacology*
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Xenopus
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alpha7 Nicotinic Acetylcholine Receptor / agonists*
Substances
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4-(4-bromophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinoline-8-sulfonamide
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Quinolines
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Sulfonamides
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alpha7 Nicotinic Acetylcholine Receptor