Probing structural requirements of positive allosteric modulators of the M4 muscarinic receptor

Journal of Medicinal Chemistry

Volumn 56, Issue 20, 2013, Pages 8196-8200

  Huynh, Tracey ^a   Valant, Celine ^a   Crosby, Ian T ^a   Sexton, Patrick M ^a   Christopoulos, Arthur ^a   Capuano, Ben ^a  

^a MONASH UNIVERSITY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

3 AMINO N (3 FLUORO 4 METHOXYBENZYL) 4,6 DIMETHYLTHI ENO[2,3B]PYRIDINE 2 CARBOXAMIDE HYDROCHLORIDE; 3 AMINO N (3 METHOXYBENZYL) 4,6 DIMETHYLTHIENO[2,3 B]PYRIDINE 2 CARBOXAMIDE HYDROCHLORIDE; MUSCARINIC RECEPTOR; PROTEIN INHIBITOR; THIENOPYRIDINE DERIVATIVE; UNCLASSIFIED DRUG; VU 0152100; VU 10005;

ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; PROTEIN STRUCTURE;

ACETYLCHOLINE; ALLOSTERIC REGULATION; ALLOSTERIC SITE; ANIMALS; BINDING, COMPETITIVE; CHO CELLS; CRICETINAE; CRICETULUS; HUMANS; KINETICS; MITOGEN-ACTIVATED PROTEIN KINASE 1; MITOGEN-ACTIVATED PROTEIN KINASE 3; MODELS, CHEMICAL; MOLECULAR STRUCTURE; PHOSPHORYLATION; PYRIDINES; RADIOLIGAND ASSAY; RECEPTOR, MUSCARINIC M4; THIOPHENES;

EID: 84886574981     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm401032k     Document Type: Article

References (17)

1. Levey, A. I. Immunological localization of m1-m5 muscarinic acetylcholine receptors in peripheral tissues and brain Life Sci. 1993, 52, 441-448
2. Wess, J. Muscarinic acetylcholine receptors. In Handbook of Contemporary Neuropharmacology; Sibley, D. R.; Hanin, I.; Kuhar, M.; Skolnick, P., Eds.; John Wiley & Sons, Inc.: Hoboken, NJ, 2007; pp 147-192.
3. Shekhar, A.; Potter, W. Z.; Lightfoot, J.; Lienemann, J.; Dube, S.; Mallinckrodt, C.; Bymaster, F. P.; McKinzie, D. L.; Felder, C. C. Selective Muscarinic Receptor Agonist Xanomeline as a Novel Treatment Approach for Schizophrenia Am. J. Psychiatry. 2008, 165, 1033-1039
4. Ellis, J. Allosteric binding sites on muscarinic receptors Drug Dev. Res. 1997, 40, 193-204
5. Melancon, B. J.; Hopkins, C. R.; Wood, M. R.; Emmitte, K. A.; Niswender, C. M.; Christopoulos, A.; Conn, P. J.; Lindsley, C. W. Allosteric Modulation of Seven Transmembrane Spanning Receptors: Theory, Practice, and Opportunities for Central Nervous System Drug Discovery J. Med. Chem. 2011, 55, 1445-1464
6. Holzgrabe, U.; Mohr, K. Allosteric modulators of ligand binding to muscarinic acetylcholine receptors Drug Discovery Today 1998, 3, 214-222
7. 4 receptor as an approach to treating schizophrenia Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 10978-10983
8. 4 Muscarinic Acetylcholine Receptor Allosteric Modulator with Potential Antipsychotic Properties Neuropsychopharmacology 2009, 35, 855-869
9. 4 mAChR modulates hippocampal synaptic transmission Nature Chem. Biol. 2008, 4, 42-50
10. Brady, A. E.; Jones, C. K.; Bridges, T. M.; Kennedy, J. P.; Thompson, A. D.; Heiman, J. U.; Breininger, M. L.; Gentry, P. R.; Yin, H.; Jadhav, S. B.; Shirey, J. K.; Conn, P. J.; Lindsley, C. W. Centrally Active Allosteric Potentiators of the M4Muscarinic Acetylcholine Receptor Reverse Amphetamine-Induced Hyperlocomotor Activity in Rats J. Pharmacol. Exp. Ther. 2008, 327, 941-953
11. Leach, K.; Sexton, P. M.; Christopoulos, A. Allosteric GPCR modulators: taking advantage of permissive receptor pharmacology Trends Pharmacol. Sci. 2007, 28, 382-389
12. Canals, M.; Lane, J. R.; Wen, A.; Scammells, P. J.; Sexton, P. M.; Christopoulos, A. A Monod-Wyman-Changeux Mechanism Can Explain G Protein-Coupled Receptor (GPCR) Allosteric Modulation J. Biol. Chem. 2012, 287, 650-659
13. 1 Receptor: Synthesis and Pharmacological Evaluation of 4-Substituted 2-Amino-3- benzoylthiophenes J. Med. Chem. 2009, 52, 4543-4547
14. 1 Muscarinic Receptor J. Med. Chem. 2013, 56, 5151-5172
15. 4 Muscarinic Acetylcholine Receptor ChemMedChem 2009, 4, 1600-1607
16. Eyduran, F.; Ozyurek, C.; Dilek, N.; Ocak Iskeleli, N.; Sendil, K. 4,6-Dimethyl-2-thioxo-1,2-dihydropyridine-3-carbonitrile Acta Crystallogr., Sect. E: Struct. Rep. Online 2007, 63, o2415-o2417
17. Ferraccioli, R.; Forni, A. Selective Synthesis of Isoquinolin-3-one Derivatives Combining Pd-Catalysed Aromatic Alkylation/Vinylation with Addition Reactions: The Beneficial Effect of Water Eur. J. Org. Chem. 2009, 2009, 3161-3166