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ACS Med Chem Lett
2018 Oct 11;911:1144-1148. doi: 10.1021/acsmedchemlett.8b00407.
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B-973, a Novel α7 nAChR Ago-PAM: Racemic and Asymmetric Synthesis, Electrophysiological Studies, and in Vivo Evaluation.
Garai S
,
Raja KS
,
Papke RL
,
Deschamps JR
,
Damaj MI
,
Thakur GA
.
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We report here the total synthesis of B-973 (five steps), a recently identified α7 nAChR ago-PAM, its enantiomeric resolution, and its electrophysiological characterization in Xenopus oocytes to identify (-)-B-973B as the bioactive enantiomer. The asymmetric synthesis of B-973B was accomplished in 99% ee, and X-ray crystallography studies revealed its absolute "S" stereochemistry. B-973B was effective in attenuating pain behavior and decreasing paw edema (formalin test), and its analgesic effects were mediated through α7 nAChR.
Abbott,
The formalin test: scoring properties of the first and second phases of the pain response in rats.
1995, Pubmed
Abbott,
The formalin test: scoring properties of the first and second phases of the pain response in rats.
1995,
Pubmed
Bagdas,
New Insights on Neuronal Nicotinic Acetylcholine Receptors as Targets for Pain and Inflammation: A Focus on α7 nAChRs.
2018,
Pubmed
Bagdas,
The α7 nicotinic receptor dual allosteric agonist and positive allosteric modulator GAT107 reverses nociception in mouse models of inflammatory and neuropathic pain.
2016,
Pubmed
Bertrand,
The wonderland of neuronal nicotinic acetylcholine receptors.
2018,
Pubmed
Davidson,
Intraplantar injection of dextrorphan, ketamine or memantine attenuates formalin-induced behaviors.
1998,
Pubmed
Gill,
Agonist activation of alpha7 nicotinic acetylcholine receptors via an allosteric transmembrane site.
2011,
Pubmed
,
Xenbase
Hone,
Nicotinic acetylcholine receptors in neuropathic and inflammatory pain.
2018,
Pubmed
Horenstein,
Critical Molecular Determinants of α7 Nicotinic Acetylcholine Receptor Allosteric Activation: SEPARATION OF DIRECT ALLOSTERIC ACTIVATION AND POSITIVE ALLOSTERIC MODULATION.
2016,
Pubmed
,
Xenbase
Hudzik,
Preclinical abuse liability assessment of ABT-126, an agonist at the α7 nicotinic acetylcholine receptor (nAChR).
2017,
Pubmed
Manetti,
Designing selective modulators for the nicotinic receptor subtypes: challenges and opportunities.
2018,
Pubmed
Papke,
The activity of GAT107, an allosteric activator and positive modulator of α7 nicotinic acetylcholine receptors (nAChR), is regulated by aromatic amino acids that span the subunit interface.
2014,
Pubmed
,
Xenbase
Papke,
Merging old and new perspectives on nicotinic acetylcholine receptors.
2014,
Pubmed
Perkins,
Initial Cross-Over Test of A Positive Allosteric Modulator of Alpha-7 Nicotinic Receptors to Aid Cessation in Smokers With Or Without Schizophrenia.
2018,
Pubmed
Post-Munson,
B-973, a novel piperazine positive allosteric modulator of the α7 nicotinic acetylcholine receptor.
2017,
Pubmed
Robak,
Synthesis and applications of tert-butanesulfinamide.
2010,
Pubmed
Stokes,
Looking below the surface of nicotinic acetylcholine receptors.
2015,
Pubmed
Thakur,
Expeditious synthesis, enantiomeric resolution, and enantiomer functional characterization of (4-(4-bromophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-8-sulfonamide (4BP-TQS): an allosteric agonist-positive allosteric modulator of α7 nicotinic acetylcholine receptors.
2013,
Pubmed
,
Xenbase
Williams,
Positive allosteric modulators as an approach to nicotinic acetylcholine receptor-targeted therapeutics: advantages and limitations.
2011,
Pubmed
Winterer,
Allosteric alpha-7 nicotinic receptor modulation and P50 sensory gating in schizophrenia: a proof-of-mechanism study.
2013,
Pubmed