3-[Substituted]-5-(5-pyridin-2-yl-2H-tetrazol-2-yl)benzonitriles: Identification of highly potent and selective metabotropic glutamate subtype 5 receptor antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 22, 2005, Pages 5061-5064

  Tehrani, Lida R ^a   Smith, Nicholas D ^a   Huang, Dehua ^a   Poon, Steve F ^a   Roppe, Jeffrey R ^a   Seiders, Thomas Jon ^a   Chapman, Deborah F ^a   Chung, Janice ^a   Cramer, Merryl ^a   Cosford, Nicholas D P ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Antagonist; Metabotropic glutamate receptor 5; Occupancy; Tetrazole

Indexed keywords

BENZONITRILE; METABOTROPIC RECEPTOR 5; METABOTROPIC RECEPTOR ANTAGONIST;

ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG PENETRATION; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; HYDROGEN BOND; NONHUMAN; RAT; RECEPTOR OCCUPANCY; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION;

ANIMALS; BRAIN; EXCITATORY AMINO ACID ANTAGONISTS; KINETICS; MICE; MOLECULAR STRUCTURE; NITRILES; PYRIDINES; RATS; RECEPTORS, METABOTROPIC GLUTAMATE; SENSITIVITY AND SPECIFICITY; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY; TETRAZOLES;

EID: 25844475955     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.07.062     Document Type: Article

References (22)

1. Siegel, G. J.; Aganoff, B. W.; Albers, R. W.; Fisher, S. K.; Uhler, M. D. Basic Neurochemistry: Molecular Cellular and Medicinal Aspects, 6th ed.; Lippincott/Williams and Wilkins: Philadelphia/Baltimore, MD, 1998.
2. J.-P. Pin, and F. Acher Curr. Drug Targets: CNS Neurol. Disord. 1 2002 297
3. J. Brodkin, C. Busse, S.J. Sukoff, and M.A. Varney Pharmacol. Biochem. Behav. 73 2002 359
4. W.P.J.M. Spooren, A. Vassout, H.C. Neijt, R. Kuhn, F. Gasparini, S. Roux, R.D. Porsolt, and C. Gentsch J. Pharmacol. Exp. Ther. 295 2000 1267
5. B. Schulz, M. Fendt, F. Gasparini, K. Lingenhöhl, R. Kuhn, and M. Koch Neuropharmacology 41 2001 1
6. A. Klodzinska, E. Tatarczynska, E. Chojnacka-Wojcik, and A. Pilc Pol. J. Pharmacol. 52 2000 463
7. W.P.J.M. Spooren, P. Schoeffter, F. Gasparini, R. Kuhn, and C. Gentsch Eur. J. Pharmacol. 435 2002 161
8. E. Tatarczynska, A. Klodzinska, E. Chojnacka-Wojcik, A. Palucha, F. Gasparini, R. Kuhn, and A. Pilc Br. J. Pharmacol. 132 2001 1423
9. M.A. Varney, and R.W.I. Gereau Curr. Drug Targets: CNS Neurol. Disord. 1 2002 283
10. C. Chiamulera, M.P. Epping-Jordan, A. Zocchi, C. Marcon, C. Cottiny, S. Tacconi, M. Corsi, F. Orzi, and F. Conquet Nat. Neurosci. 4 2001 873
11. K.M. Huber, S.M. Gallagher, S.T. Warren, and M.F. Bear Proc. Natl. Acad. Sci. U.S.A. 99 2002 7746
12. N.D.P. Cosford, L. Tehrani, J. Roppe, E. Schweiger, N.D. Smith, J. Anderson, L. Bristow, J. Brodkin, X. Jiang, I. McDonald, S. Rao, M. Washburn, and M. Varney J. Med. Chem. 46 2003 204
13. J. Roppe, N.D. Smith, D. Huang, L. Tehrani, B. Wang, J. Anderson, J. Brodkin, J. Chung, X. Jiang, C. King, C. King, B. Munoz, M.A. Varney, P. Prasit, and N.D.P. Cosford J. Med. Chem. 46 2004 4645
14. 50 > 10 μM).
15. S. Ito, Y. Tanaka, and K. Kakehi Chem. Lett. 10 1973 1071
16. M.A. Varney, N.D.P. Cosford, C. Jachec, S.P. Rao, A. Sacaan, F.F. Lin, L. Bleicher, E.M. Santori, P.J. Flor, H. Allgier, F. Gasparini, R. Kuhn, S.D. Hess, G. Velicelebi, and E.C. Johnson J. Pharmacol. Exp. Ther. 290 1999 170
17. N.D.P. Cosford, J. Roppe, L. Tehrani, E.J. Schweiger, T.J. Seiders, A. Chaudary, S. Rao, and M.A. Varney Bioorg. Med. Chem. Lett. 13 2003 351
18. D. Huang, S.F. Poon, D.F. Chapman, J. Chung, M. Cramer, T.S. Reger, J.R. Roppe, L. Tehrani, N.D.P. Cosford, and N.D. Smith Bioorg. Med. Chem. Lett. 14 2004 5473
19. J. Anderson, S.P. Rao, B. Rowe, D.R. Giracello, G. Holtz, D.F. Chapman, L. Tehrani, M.J. Bradbury, N.D.P. Cosford, and M.A. Varney J. Pharmacol. Exp. Ther. 303 2002 1044
20. J.J. Anderson, M.J. Bradbury, D.R. Giracello, D.F. Chapman, G. Holtz, J. Roppe, C. King, N.D.P. Cosford, and M.A. Varney Eur. J. Pharmacol. 473 2003 35
21. N.D. Smith, S.F. Poon, D. Huang, M. Green, C. King, L. Tehrani, J.R. Roppe, J. Chung, D.P. Chapman, M. Cramer, and N.D.P. Cosford Bioorg. Med. Chem. Lett. 14 2004 5481
22. S.F. Poon, B.W. Eastman, D.F. Chapamn, J. Chung, M. Cramer, G. Holtz, N.D.P. Cosford, and N.D. Smith Bioorg. Med. Chem. Lett. 14 2004 5477