Synthesis and Pharmacological Evaluation of M4 Muscarinic Receptor Positive Allosteric Modulators Derived from VU10004
| Autor: | Patrick M. Sexton, Celine Valant, Arthur Christopoulos, Benvenuto Capuano, Tracey Huynh, Ian Travers Crosby |
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| Rok vydání: | 2015 |
| Předmět: |
Agonist
Muscarinic M4 Receptor Thienopyridines Physiology medicine.drug_class Cognitive Neuroscience Allosteric regulation Cooperativity CHO Cells Receptor targeting Cholinergic Agonists Biochemistry Cricetulus Allosteric Regulation Muscarinic acetylcholine receptor medicine Animals Humans Phosphorylation Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Molecular Structure Receptor Muscarinic M4 Chemistry Cell Biology General Medicine Acetylcholine Biophysics Drug Evaluation Allosteric Site |
| Zdroj: | ACS Chemical Neuroscience. 6:838-844 |
| ISSN: | 1948-7193 |
| DOI: | 10.1021/acschemneuro.5b00035 |
| Popis: | The M4 mAChR is implicated in several CNS disorders and possesses an allosteric binding site for which ligands modulating the affinity and/or efficacy of ACh may be exploited for selective receptor targeting. We report the synthesis of a focused library of putative M4 PAMs derived from VU10004. These compounds investigate the pharmacological effects of target thieno[2,3-b]pyridines assembled from primary cycloalkanamines and cyclic secondary amines providing useful estimates of affinity (KB), cooperativity (αβ), and direct agonist properties (τB). |
| Databáze: | OpenAIRE |
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