6-Aryl-3-pyrrolidinylpyridines as mGlu5 receptor negative allosteric modulators

Bioorganic and Medicinal Chemistry Letters

Volumn 21, Issue 16, 2011, Pages 4891-4899

  Weiss, Jesse M ^a   Jimenez, Hermogenes N ^a   Li, Guiying ^a   April, Myriam ^a   Uberti, Michelle A ^a   Bacolod, Maria D ^a   Brodbeck, Robb M ^a   Doller, Darío ^a  

^a LUNDBECK RESEARCH USA   (United States)

Author keywords

CNS drug discovery; GPCR; Metabotropic glutamate receptors; mGlu5 NAM; mGluR

Indexed keywords

6 ARYL 3 PYRROLIDINYLPYRIDINE DERIVATIVE; ALKYNE DERIVATIVE; METABOTROPIC RECEPTOR; OXADIAZOLE DERIVATIVE; PYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; BINDING AFFINITY; CALCIUM MOBILIZATION; DRUG BINDING SITE; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG PENETRATION; DRUG POTENCY; DRUG RECEPTOR BINDING; HUMAN; HUMAN CELL; IN VITRO STUDY; MOUSE; NONHUMAN; PHYSICAL CHEMISTRY; SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION;

ANIMALS; DOSE-RESPONSE RELATIONSHIP, DRUG; HEK293 CELLS; HUMANS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PYRIDINES; PYRROLIDINES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, METABOTROPIC GLUTAMATE; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

RODENTIA;

EID: 79960899999     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2011.06.014     Document Type: Article

References (30)

1. Stahl, S. M. Stahl's Essential Psychopharmacology, 3rd ed.; Cambridge University press: 2008; Watkins, J. C. Biochem. Soc. Trans. 2000, 28, 297.
2. S.M. Foord, T.I. Bonner, R.R. Neubig, E.M. Rosser, J.P. Pin, A.P. Davenport, M. Spedding, and A.J. Harmar Pharmacol. Rev. 57 2005 279
3. G Protein-Coupled Receptors in Drug Discovery K.H. Lundstrom, and M.L. Chiu Taylor & Francis 2006 CRC Press
4. D.P. Behan, and D.T. Chalmers Nat. Rev. Drug Discov. 1 2002 599
5. D.D. Schoepp, and P.J. Conn Trends Pharmacol. Sci. 14 1993 13
6. D.D. Schoepp Neurochem. Int. 24 1994 439
7. F. Bordi, and A. Ugolini Prog. Neurobiol. 59 1999 55
8. S. Topiol, M. Sabio, and M. Uberti Neuropharmacology 60 2011 93
9. P.J. Conn, A. Christopoulos, and C.W. Lindsley Nat. Rev. Drug Discovery 8 2009 41
10. A. Ritzen, J.M. Mathiesen, and C. Thomsen Basic Clin. Pharmacol. Toxicol. 97 2005 202
11. J.N. Kew Pharmacol. Ther. 104 2004 233
12. R.H.P. Porter, G. Jaeschke, W. Spooren, T.M. Ballard, B. Büttelmann, S. Kolczewski, J.-U. Peters, E. Prinssen, J. Wichmann, E. Vieira, A. Mühlemann, S. Gatti, V. Mutel1, and P. Malherbe J. Pharmacol. Exp. Ther. 315 2005 711
13. A. Dekundy, A. Gravius, M. Hechenberger, M. Pietraszek, J. Nagel, C. Tober, M. van der Elst, F. Mela, C.G. Parsons, and W. Danysz J. Neural. Transm. 2010 10.1007/s00702-010-0526-0 Published online on December 16, 2010
14. K.L. Phan, D.A. Fitzgerald, B.M. Cortese, N. Seraji-Bozorgzad, M.E. Tancer, and G.J. Moore Neuroreport 16 2005 183
15. S.J. Mathew, R.B. Price, and D.S. Charney Am. J. Med. Genet. C Semin. Med. Genet. 148C 2008 89
16. N. Breysse, C. Baunez, W. Spooren, F. Gasparini, and M. Amalric J. Neurosci. 22 2002 5569
17. J.C. Marin, and P.J. Goadsby Expert Opin. Investig. Drugs 19 2010 555
18. F. Zerbib, C. Keywood, and G. Strabach Neurogastroenterol. Motil. 22 2010 859
19. Jacquemont, S.; Curie, A.; des Portes, V.; Berry-Kravis, E.; Hagerman, R. J.; Ramos, F.; Cornish, K.; He, Y.; Paulding, C.; Torrioli, M. G.; Neri, G.; Chen, F.; Hadjikhani, N.; Martinet, D.; Meyer, J.; Beckmann, J. S.; Delange, K.; Brun, A.; Bussy, G.; Gasparini, F.; Hilse, T.; Floesser, A.; Branson, J.; Bilbe, G.; Johns, D.; Gomez-Mancilla, B. American Society of Human Genetics 60th Annual Meeting. Nov 2-6, 2010; Washington DC, US, 2010.
20. D. Berg, J. Godau, C. Trenkwalder, A. Eggert, I. Csoti, A. Storch, F. Gasparini, S. Hariry, M. Vandermeulebroecke, D. Johns, and B. Gomez-Mancilla Mov. Disord. 25 Suppl. 2 2010 S290
21. Development of ADX10059 Ended for Long-term Use. http://www.addexpharma. com/press-releases/press-release-details/article/development-of-adx10059-ended- for-long-term-use/ accessed on October 15, 2010.
22. G. Wágner, C. Wéber, O. Nyéki, K. Nógrádi, A. Bielik, L. Molnár, A. Bobok, A. Horváth, B. Kiss, S. Kolok, J. Nagy, D. Kurkó, K. Gál, I. Greiner, Z. Szombathelyi, G.M. Keser, and G. Domány Bioorg. Med. Chem. Lett. 20 2010 3737
23. J.P. Lamb, D.W. Engers, C.M. Niswender, A.L. Rodriguez, D.F. Venable, P.J. Conn, and C.W. Lindsley Bioorg. Med. Chem. Lett. 21 2011 2711
24. A. Graven Sams, G.K. Mikkelsen, R.M. Brodbeck, X. Pu, and A. Ritzén Bioorg. Med. Chem. Lett. 2011 10.1016/j.bmcl.2011.03.103
25. Geometry optimizations were conducted using ChemBio3D Ultra 12.0, interfaced to GAMESS, using the HF method, basis set 6-31G, wave function R-closed shell and Pople exponent, which is distributed by CambridgeSoft of 100 Cambridge Park Drive, Cambridge, MA 02140.
26. Jimenez, H. N.; Li, G.; Doller, D.; Grenon, M.; White, A. D.; Guo, M.; Ma, G. WO 2010011570.
27. H. Stetter, M. Schreckenberg, and K. Wiemann Ber. 109 1976 541
28. C.L. Shaffer Annu. Rep. Med. Chem. 43 2010 55 and references cited therein
29. S.S. Hecht, C.B. Chen, and B. Hoffmann J. Med. Chem. 23 1980 1175
30. 2. The dialysis block was placed on an orbital shake. After 2.5 h incubation, buffer and serum samples (or brain homogenate samples) were collected and transferred into a 96-well matrix plate with tube inserts. Internal standards were added and the samples were vortexed and mixed, and analyzed by LC-MS/MS.