Literature DB >> 30429960

B-973, a Novel α7 nAChR Ago-PAM: Racemic and Asymmetric Synthesis, Electrophysiological Studies, and in Vivo Evaluation.

Sumanta Garai1, Krishnamohan S Raja1, Roger L Papke2, Jeffrey R Deschamps3, M Imad Damaj4, Ganesh A Thakur1.   

Abstract

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.

Entities:  

Year:  2018        PMID： 30429960      PMCID： PMC6231182          DOI： 10.1021/acsmedchemlett.8b00407

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  19 in total

1.  Critical Molecular Determinants of α7 Nicotinic Acetylcholine Receptor Allosteric Activation: SEPARATION OF DIRECT ALLOSTERIC ACTIVATION AND POSITIVE ALLOSTERIC MODULATION.

Authors:  Nicole A Horenstein; Roger L Papke; Abhijit R Kulkarni; Ganesh U Chaturbhuj; Clare Stokes; Khan Manther; Ganesh A Thakur
Journal:  J Biol Chem       Date:  2016-01-07       Impact factor: 5.157

2.  B-973, a novel piperazine positive allosteric modulator of the α7 nicotinic acetylcholine receptor.

Authors:  Debra J Post-Munson; Rick L Pieschl; Thaddeus F Molski; John D Graef; Adam W Hendricson; Ronald J Knox; Ivar M McDonald; Richard E Olson; John E Macor; Michael R Weed; Linda J Bristow; Laszlo Kiss; Michael K Ahlijanian; James Herrington
Journal:  Eur J Pharmacol       Date:  2017-01-26       Impact factor: 4.432

3.  The α7 nicotinic receptor dual allosteric agonist and positive allosteric modulator GAT107 reverses nociception in mouse models of inflammatory and neuropathic pain.

Authors:  Deniz Bagdas; Jenny L Wilkerson; Abhijit Kulkarni; Wisam Toma; Shakir AlSharari; Zulfiye Gul; Aron H Lichtman; Roger L Papke; Ganesh A Thakur; M Imad Damaj
Journal:  Br J Pharmacol       Date:  2016-07-18       Impact factor: 8.739

Review 4.  Positive allosteric modulators as an approach to nicotinic acetylcholine receptor-targeted therapeutics: advantages and limitations.

Authors:  Dustin K Williams; Jingyi Wang; Roger L Papke
Journal:  Biochem Pharmacol       Date:  2011-05-14       Impact factor: 5.858

5.  Preclinical abuse liability assessment of ABT-126, an agonist at the α7 nicotinic acetylcholine receptor (nAChR).

Authors:  Thomas J Hudzik; Ana M Basso; James J Lynch; William M Bracken; Eric G Mohler; Kathy L Kohlhaas; Hongyu Xu; George Haig; Laura Gault
Journal:  Pharmacol Biochem Behav       Date:  2017-06-01       Impact factor: 3.533

6.  Intraplantar injection of dextrorphan, ketamine or memantine attenuates formalin-induced behaviors.

Authors:  E M Davidson; S M Carlton
Journal:  Brain Res       Date:  1998-02-23       Impact factor: 3.252

7.  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.

Authors:  Ganesh A Thakur; Abhijit R Kulkarni; Jeffrey R Deschamps; Roger L Papke
Journal:  J Med Chem       Date:  2013-10-25       Impact factor: 7.446

8.  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.

Authors:  Roger L Papke; Nicole A Horenstein; Abhijit R Kulkarni; Clare Stokes; Lu W Corrie; Cheol-Young Maeng; Ganesh A Thakur
Journal:  J Biol Chem       Date:  2013-12-20       Impact factor: 5.157

9.  The formalin test: scoring properties of the first and second phases of the pain response in rats.

Authors:  Frances V Abbott; Keith B J Franklin; Frederick R Westbrook
Journal:  Pain       Date:  1995-01       Impact factor: 6.961

Review 10.  New Insights on Neuronal Nicotinic Acetylcholine Receptors as Targets for Pain and Inflammation: A Focus on α7 nAChRs.

Authors:  Deniz Bagdas; Mine S Gurun; Pamela Flood; Roger L Papke; M Imad Damaj
Journal:  Curr Neuropharmacol       Date:  2018       Impact factor: 7.363
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  5 in total

1.  Heteromeric Neuronal Nicotinic Acetylcholine Receptors with Mutant β Subunits Acquire Sensitivity to α7-Selective Positive Allosteric Modulators.

Authors:  Clare Stokes; Sumanta Garai; Abhijit R Kulkarni; Lucas N Cantwell; Colleen M Noviello; Ryan E Hibbs; Nicole A Horenstein; Khalil A Abboud; Ganesh A Thakur; Roger L Papke
Journal:  J Pharmacol Exp Ther       Date:  2019-06-07       Impact factor: 4.030

2.  Allosterically Potentiated α7 Nicotinic Acetylcholine Receptors: Reduced Calcium Permeability and Current-Independent Control of Intracellular Calcium.

Authors:  Douglas R Miller; Habibeh Khoshbouei; Sumanta Garai; Lucas N Cantwell; Clare Stokes; Ganesh Thakur; Roger L Papke
Journal:  Mol Pharmacol       Date:  2020-10-05       Impact factor: 4.436

Review 3.  In Silico Modeling of the α7 Nicotinic Acetylcholine Receptor: New Pharmacological Challenges Associated with Multiple Modes of Signaling.

Authors:  Alican Gulsevin; Roger L Papke; Nicole Horenstein
Journal:  Mini Rev Med Chem       Date:  2020       Impact factor: 3.862

4.  Identification of Koumine as a Translocator Protein 18 kDa Positive Allosteric Modulator for the Treatment of Inflammatory and Neuropathic Pain.

Authors:  Bojun Xiong; Guilin Jin; Ying Xu; Wenbing You; Yufei Luo; Menghan Fang; Bing Chen; Huihui Huang; Jian Yang; Xu Lin; Changxi Yu
Journal:  Front Pharmacol       Date:  2021-06-24       Impact factor: 5.810

Review 5.  Therapeutic Targeting of α7 Nicotinic Acetylcholine Receptors.

Authors:  Roger L Papke; Nicole A Horenstein
Journal:  Pharmacol Rev       Date:  2021-07       Impact factor: 18.923
  5 in total

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