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
摘要:
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 alpha 7 nAChRs available to date and is considered for further in vivo evaluation.
LIGANDS FOR ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTORS AND METHODS OF TREATING NEUROLOGICAL AND INFLAMMATORY CONDITIONS
申请人:Northeastern University
公开号:EP3180086A1
公开(公告)日:2017-06-21
Ligands for Alpha-7 Nicotinic Acetylcholine Receptors and Methods of Treating Neurological and Inflammatory Conditions
申请人:Northeastern University
公开号:US20170217984A1
公开(公告)日:2017-08-03
Compounds are provided which bind to an allosteric site on the mammalian alpha-7 nicotinic acetylcholine receptor (alpha-7 nAChR) and act as positive allosteric modulators with or without allosteric agonist activity. The compounds are useful in diagnosing, preventing, or treating a variety of disorders involving cognition, learning, memory, neurodegeneration, drug addiction, inflammation, chronic pain, and neuropathic pain. The compounds also can be used to enhance memory and learning in normal individuals.
[EN] LIGANDS FOR ALPHA-7 NICOTINIC ACETYLCHOLINE RECEPTORS AND METHODS OF TREATING NEUROLOGICAL AND INFLAMMATORY CONDITIONS<br/>[FR] LIGANDS POUR LA SOUS-UNITÉ ALPHA-7 DES RÉCEPTEURS NICOTINIQUES DE L'ACÉTYLCHOLINE ET MÉTHODES DE TRAITEMENT DE TROUBLES NEUROLOGIQUES ET INFLAMMATOIRES
申请人:UNIV NORTHEASTERN
公开号:WO2016014847A1
公开(公告)日:2016-01-28
Compounds are provided which bind to an allosteric site on the mammalian alpha-7 nicotinic acetylcholine receptor (alpha-7 nAChR) and act as positive allosteric modulators with or without allosteric agonist activity. The compounds are useful in diagnosing, preventing, or treating a variety of disorders involving cognition, learning, memory, neurodegeneration, drug addiction, inflammation, chronic pain, and neuropathic pain. The compounds also can be used to enhance memory and learning in normal individuals.
Expeditious Synthesis, Enantiomeric Resolution, and Enantiomer Functional Characterization of (4-(4-Bromophenyl)-3a,4,5,9b-tetrahydro-3<i>H</i>-cyclopenta[<i>c</i>]quinoline-8-sulfonamide (4BP-TQS): An Allosteric Agonist-Positive Allosteric Modulator of α7 Nicotinic Acetylcholine Receptors
作者:Ganesh A. Thakur、Abhijit R. Kulkarni、Jeffrey R. Deschamps、Roger L. Papke
DOI:10.1021/jm401267t
日期:2013.11.14
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 alpha 7 nAChRs available to date and is considered for further in vivo evaluation.