Scaffold hopping from pyridones to imidazo[1,2-a]pyridines. New positive allosteric modulators of metabotropic glutamate 2 receptor - PubMed

Affiliations

• PMID: 19932615
• DOI: 10.1016/j.bmcl.2009.11.008

Scaffold hopping from pyridones to imidazo[1,2-a]pyridines. New positive allosteric modulators of metabotropic glutamate 2 receptor

Gary Tresadern et al. Bioorg Med Chem Lett. 2010.

Abstract

Imidazo[1,2-a]pyridines were identified via their shape and electrostatic similarity as novel positive allosteric modulators of the metabotropic glutamate 2 receptor. The subsequent synthesis and SAR are described. Potent, selective and metabolically stable compounds were found representing a promising avenue for current further studies.

Similar articles

• New positive allosteric modulators of the metabotropic glutamate receptor 2 (mGluR2): identification and synthesis of N-propyl-8-chloro-6-substituted isoquinolones.

  Trabanco AA, Duvey G, Cid JM, Macdonald GJ, Cluzeau P, Nhem V, Furnari R, Behaj N, Poulain G, Finn T, Lavreysen H, Poli S, Raux A, Thollon Y, Poirier N, D'Addona D, Andrés JI, Lutjens R, Le Poul E, Imogai H, Rocher JP. Trabanco AA, et al. Bioorg Med Chem Lett. 2011 Feb 1;21(3):971-6. doi: 10.1016/j.bmcl.2010.12.048. Epub 2010 Dec 21. Bioorg Med Chem Lett. 2011. PMID: 21232953

• Discovery of 5-aryl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones as positive allosteric modulators of metabotropic glutamate subtype-2 (mGlu2) receptors with efficacy in a preclinical model of psychosis.

  Layton ME, Reif AJ, Hartingh TJ, Rodzinak K, Dudkin V, Wang C, Arrington K, Kelly MJ 3rd, Garbaccio RM, O'Brien JA, Magliaro BC, Uslaner JM, Huszar SL, Fillgrove KL, Tang C, Kuo Y, Jacobson MA. Layton ME, et al. Bioorg Med Chem Lett. 2016 Feb 15;26(4):1260-4. doi: 10.1016/j.bmcl.2016.01.021. Epub 2016 Jan 11. Bioorg Med Chem Lett. 2016. PMID: 26810316

• SAR study of a subtype selective allosteric potentiator of metabotropic glutamate 2 receptor, N-(4-phenoxyphenyl)-N-(3-pyridinylmethyl)ethanesulfonamide.

  Barda DA, Wang ZQ, Britton TC, Henry SS, Jagdmann GE, Coleman DS, Johnson MP, Andis SL, Schoepp DD. Barda DA, et al. Bioorg Med Chem Lett. 2004 Jun 21;14(12):3099-102. doi: 10.1016/j.bmcl.2004.04.017. Bioorg Med Chem Lett. 2004. PMID: 15149652

• Allosteric modulators of metabotropic glutamate receptors: lessons learnt from mGlu1, mGlu2 and mGlu5 potentiators and antagonists.

  Johnson MP, Nisenbaum ES, Large TH, Emkey R, Baez M, Kingston AE. Johnson MP, et al. Biochem Soc Trans. 2004 Nov;32(Pt 5):881-7. doi: 10.1042/BST0320881. Biochem Soc Trans. 2004. PMID: 15494040 Review.

• Recent progress in the development of allosteric modulators of mGluR5.

  Rodriguez AL, Williams R. Rodriguez AL, et al. Curr Opin Drug Discov Devel. 2007 Nov;10(6):715-22. Curr Opin Drug Discov Devel. 2007. PMID: 17987523 Review.

Cited by

• Identification of Allosteric Modulators of Metabotropic Glutamate 7 Receptor Using Proteochemometric Modeling.

  Tresadern G, Trabanco AA, Pérez-Benito L, Overington JP, van Vlijmen HWT, van Westen GJP. Tresadern G, et al. J Chem Inf Model. 2017 Dec 26;57(12):2976-2985. doi: 10.1021/acs.jcim.7b00338. Epub 2017 Dec 12. J Chem Inf Model. 2017. PMID: 29172488 Free PMC article.

• Is there a path forward for mGlu(2) positive allosteric modulators for the treatment of schizophrenia?

  Hopkins CR. Hopkins CR. ACS Chem Neurosci. 2013 Feb 20;4(2):211-3. doi: 10.1021/cn400023y. ACS Chem Neurosci. 2013. PMID: 23421671 Free PMC article.

• Discovery of 1,5-disubstituted pyridones: a new class of positive allosteric modulators of the metabotropic glutamate 2 receptor.

  Cid JM, Duvey G, Cluzeau P, Nhem V, Macary K, Raux A, Poirier N, Muller J, Boléa C, Finn T, Poli S, Epping-Jordan M, Chamelot E, Derouet F, Girard F, Macdonald GJ, Vega JA, de Lucas AI, Matesanz E, Lavreysen H, Linares ML, Oehlrich D, Oyarzábal J, Tresadern G, Trabanco AA, Andrés JI, Le Poul E, Imogai H, Lutjens R, Rocher JP. Cid JM, et al. ACS Chem Neurosci. 2010 Dec 15;1(12):788-95. doi: 10.1021/cn1000638. Epub 2010 Aug 23. ACS Chem Neurosci. 2010. PMID: 22778815 Free PMC article.

• Molecular Scaffold Hopping via Holistic Molecular Representation.

  Grisoni F, Schneider G. Grisoni F, et al. Methods Mol Biol. 2021;2266:11-35. doi: 10.1007/978-1-0716-1209-5_2. Methods Mol Biol. 2021. PMID: 33759119

• Design and synthesis of systemically active metabotropic glutamate subtype-2 and -3 (mGlu2/3) receptor positive allosteric modulators (PAMs): pharmacological characterization and assessment in a rat model of cocaine dependence.

  Dhanya RP, Sheffler DJ, Dahl R, Davis M, Lee PS, Yang L, Nickols HH, Cho HP, Smith LH, D'Souza MS, Conn PJ, Der-Avakian A, Markou A, Cosford ND. Dhanya RP, et al. J Med Chem. 2014 May 22;57(10):4154-72. doi: 10.1021/jm5000563. Epub 2014 May 9. J Med Chem. 2014. PMID: 24735492 Free PMC article.

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database

• Chemical Information

  • BindingDB

• Miscellaneous

  • NCI CPTAC Assay Portal