3-[3-Fluoro-5-(5-pyridin-2-yl-2H-tetrazol-2-yl)phenyl]-4-methylpyridine: A highly potent and orally bioavailable metabotropic glutamate subtype 5 (mGlu5) receptor antagonist

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 22, 2004, Pages 5477-5480

  Poon, Steve F ^a   Eastman, Brian W ^a   Chapman, Deborah F ^a   Chung, Janice ^a   Cramer, Merryl ^a   Holtz, Gregory ^a   Cosford, Nicholas D P ^a   Smith, Nicholas D ^a  

^a GENERAL ATOMICS   (United States)

Author keywords

Antagonist; Metabotropic glutamate; Tetrazole

Indexed keywords

3 [3 FLUORO 5 (5 PYRIDIN 2 YL 2H TETRAZOL 2 YL)PHENYL] 4 METHYLPYRIDINE; 3 FLUORO 5 (5 PYRIDIN 2 YL 2H TETRAZOL 2 YL)BENZONITRILE; BENZONITRILE; METABOTROPIC RECEPTOR 5; METABOTROPIC RECEPTOR ANTAGONIST; PICOLINE DERIVATIVE; TETRAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL TISSUE; ARTICLE; BRAIN; BRAIN CORTEX; BRAIN MEMBRANE; CONTROLLED STUDY; DRUG PENETRATION; DRUG POTENCY; DRUG SYNTHESIS; NONHUMAN; RAT; STRUCTURE ANALYSIS;

ADMINISTRATION, ORAL; ANIMALS; ANTI-ANXIETY AGENTS; BIOLOGICAL AVAILABILITY; MOLECULAR STRUCTURE; NITRILES; PYRIDINES; RATS; RECEPTORS, METABOTROPIC GLUTAMATE; STRUCTURE-ACTIVITY RELATIONSHIP; TETRAZOLES;

EID: 5144224768     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2004.09.011     Document Type: Article

References (21)

1. S. Ozawa, H. Kamiya, and K. Tsuzuki Prog. Neurobiol. (Oxford) 54 1998 581 618
2. J.-P. Pin, and F. Archer Curr. Drug Targets: CNS Neurol. Disord. 1 2002 297 317
3. P.J. Conn, and J.-P. Pin Annu. Rev. Pharmacol. Toxicol. 37 1997 205 237
4. H. Brauener-Osborne, J. Egebjerg, E.O. Nielsen, U. Madsen, and P. Krogsgaard-Larsen J. Med. Chem. 43 2000 2609 2645
5. M.A. Varney, and R.W.I. Gereau Curr. Drug Targets: CNS Neurol. Disord. 1 2002 283 296
6. J. Brodkin, C. Busse, S.J. Sukoff, and M.A. Varney Pharmacol. Biochem. Behav. 73 2002 359 366
7. 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 1275
8. E. Tatarczynska, A. Klodzinska, E. Chojnacka-Wojcik, A. Palucha, F. Gasparini, R. Kuhn, and A. Pilc Br. J. Pharmacol. 132 2001 1423 1430
9. 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 873 874
10. K.M. Huber, S.M. Gallagher, S.T. Warren, and M.F. Bear Proc. Natl. Acad. Sci. U.S.A. 99 2002 7746 7750
11. F. Gasparini, K. Lingenhohl, N. Stoehr, P.J. Flor, M. Heinrich, I. Vranesic, M. Biollaz, H. Allgeier, R. Heckendorn, S. Urwyler, M.A. Varney, E.C. Johnson, S.D. Hess, S.P. Rao, A.I. Sacaan, E.M. Santori, G. Velicelebi, and R. Kuhn Neuropharmacology 38 1999 1493 1503
12. N.D.P. Cosford, L. Tehrani, J. Roppe, E. Schweiger, and N.D. Smith J. Med. Chem. 46 2003 204 206
13. J. Roppe, N.D. Smith, D. Huang, L. Tehrani, B. Wang, J. Anderson, J. Brodkin, J. Chung, X. Jiang, C. King, B. Munoz, M.A. Varney, P. Prasit, and N.D.P. Cosford J. Med. Chem. 47 2004 4645 4648
14. The selectivity of the prototypical tetrazole, 3-(5-pyridin-2-yl-2H- tetrazol-2-yl)benzonitrile, was determined by extensive profiling against a battery of in vitro assays (MDS Pharma Services screen)
15. P.E. Maligres, M.S. Waters, F. Fleitz, and D. Askin Tetrahedron Lett. 40 1999 8193 8195
16. T. Ishiyama, M. Murata, and N. Miyaura J. Org. Chem. 60 1995 7508 7510
17. 3 in methanol, afforded the desired products
18. M.A. Varney, and C.M. Suto Drug Discovery Today: HTS Suppl. 1 2000 20 26
19. N.D.P. Cosford, J. Roppe, L. Tehrani, T.J. Seiders, E.J. Schweiger, S. Chaudary, S. Rao, and M.A. Varney Bioorg. Med. Chem. Lett. 13 2003 351 354
20. L.P. Daggett, A.I. Sacaan, M. Akong, S.P. Rao, and S.D. Hess Neuropharmacology 34 1995 871 886
21. Y. Gong, and W. He Org. Lett. 22 2002 3803 3805