Probing Structural Requirements of Positive Allosteric Modulators of the M4 Muscarinic Receptor
| Autor: | Tracey Huynh, Patrick M. Sexton, Celine Valant, Arthur Christopoulos, Benvenuto Capuano, Ian Travers Crosby |
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| Rok vydání: | 2013 |
| Předmět: |
Agonist
Pyridines medicine.drug_class Allosteric regulation Cooperativity CHO Cells Thiophenes Binding Competitive Radioligand Assay Cricetulus Allosteric Regulation Cricetinae Drug Discovery Muscarinic acetylcholine receptor medicine Animals Humans Phosphorylation Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Molecular Structure Receptor Muscarinic M4 biology Chemistry Chinese hamster ovary cell biology.organism_classification Acetylcholine Kinetics Models Chemical Biochemistry Molecular Medicine Allosteric Site |
| Zdroj: | Journal of Medicinal Chemistry. 56:8196-8200 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm401032k |
| 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 VU0152100 and VU10005. These compounds investigate the pharmacological effects of previously identified methoxy and fluoro substituents, providing useful estimates of affinity (KB), cooperativity (αβ), and direct agonist properties (τB). |
| Databáze: | OpenAIRE |
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