Discovery of a potent, selective and orally active canine COX-2 inhibitor, 2-(3-difluoromethyl-5-phenyl-pyrazol-1-yl)-5-methanesulfonyl-pyridine

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 1, 2004, Pages 95-98

  Li, Jin ^a   Lundy DeMello, Kristin M ^a   Cheng, Henry ^a   Sakya, Subas M ^a   Bronk, Brian S ^a   Rafka, Robert J ^a   Jaynes, Burton H ^a   Ziegler, Carl B ^a   Kilroy, Carolyn ^a   Mann, Donald W ^a   Nimz, Eric L ^a   Lynch, Michael P ^a   Haven, Michelle L ^a   Kolosko, Nicole L ^a   Minich, Martha L ^a   Li, Chao ^a   Dutra, Jason K ^a   Rast, Bryson ^a   Crosson, Rhonda M ^a   Morton, Barry J ^a   Kirk, Glen W ^a   Callaghan, Kathleen M ^a   Koss, David A ^a   Shavnya, Andrei ^a   Lund, Lisa A ^a   Seibel, Scott B ^a   Petras, Carol F ^a   Silvia, Annette ^a   more..

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 (3 DIFLUOROMETHYL 5 PHENYLPYRAZOL 1 YL) 5 METHANESULFONYLPYRIDINE; CELECOXIB; CYCLOOXYGENASE 2 INHIBITOR; DERACOXIB; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL LAMENESS; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DOG; DRUG ACTIVITY; DRUG POTENCY; DRUG SELECTIVITY; ENZYME INHIBITION; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; STRUCTURE ACTIVITY RELATION;

CANIS FAMILIARIS;

EID: 0347517818     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2003.10.004     Document Type: Article

References (24)

1. Carter J.S. Exp. Opin. Ther. Pat. 8:1998;21.
2. Laneuville O., Breuer D.K., Dewitt D.L., Hla T., Funk C.D., Smith W.L. J. Pharmacol. Exp. Ther. 271:1994;927.
3. O'Neill G.P., Mancini J.A., Kargman S., Yergey J., Kwan M.Y., Falgueyret J.P., Abramovitz M., Kennedy B.P., Ouellet M., Cromlish W. Mol. Pharmacol. 45:1994;245.
4. Otta J.C., Smith W.L.J. Lipid. Mediat. Cell Signal. 12:1995;139.
5. Prasit P., Riendeau D. Ann. Rep. Med. Chem. 32:1997;211.
6. Warner T.D., Mitchell J.A. Proc. Natl. Acad. Sci. U.S.A. 99:2002;13371, and references cited herein.
7. Clive D.M., Stoff J.S. New Engl. J. Med. 310:1984;563.
8. Allison M.C., Howatson A.G., Torrance C.J., Lee F.D., Russell R.I. New Engl. J. Med. 327:1992;749.
9. Griswold D.E., Adams J.L. Med. Res. Rev. 16:1996;181.
10. Cryer B., Dubois A. Prostag. Oth. Lipid Mediat. 56:1998;341.
11. Penning T.D., Talley J.J., Bertenshaw S.R., Carter J.S., Collins P.W., Doctor S., Graneto M.J., Lee L.F., Malecha J.W., Miyashiro J.M., Rogers R.S., Rogier D.J., Yu S.S., Anderson G.D., Burton E.G., Cogburn J.N., Gregory S.A., Koboldt C.M., Perkins W.E., Seibert K., Veenhuizen A.W., Zhang Y.Y., Isakson P.C. J. Med. Chem. 40:1997;1347.
12. Talley J.J., Brown D.L., Carter J.S., Graneto M.J., Koboldt C.M., Masferrer J.L., Perkins W.E., Rogers R.S., Shaffer A.F., Zhang Y.Y., Zweifel B.S., Seibert K. J. Med. Chem. 43:2000;775.
13. Prasit P., Wang Z., Brideau C., Chan C.-C., Charleson S., Cromlish W., Ethier D., Evans J.F., Ford-Hutchinson A.W., Gauthier J.Y., Gordon R., Guay J., Gresser M., Kargman S., Kennedy B., Leblanc Y., Léger S., Mancini J., O'Neill G.P., Ouellet M., Percival M.D., Perrier H., Riendeau D., Rodger I., Tagari P., Thérien M., Vickers P., Wong E., Xu L.-J., Young R.N., Zamboni R., Boyce S., Rupniak N., Forrest M., Visco D., Patrick D. Bioorg. Med. Chem. Lett. 9:1999;1773.
14. Chauret N., Yergey J.A., Brideau C., Friesen R.W., Mancini J., Riendeau D., Silva J., Styhler A., Trimble L.A., Nicoll-Griffith D.A. Bioorg. Med. Chem. Lett. 11:2001;1059.
15. Fox S.M., Johnston S.A. J. Am. Vet. Med. Assoc. 210:1997;1493.
16. Pfizer Animal Health Data File.
17. Ricketts A.P., Lundy K.M., Seibel S.B. Am. J. Vet. Res. 59:1998;1441.
18. Streppa H.K., Jones C.J., Budsberg S.C. Am. J. Vet. Res. 63:2002;91.
19. Millis D.L., Weigel J.P., Moyers T., Buonomo F.C. Vet. Ther. 3:2002;453.
20. Black W.C., Anderson D.R., Brideau C., Chauret N., Chern R.T., Chen J., Drag M., Fortin R., Hanson P., Haven M., Hickey G.J., McCann M.E., Patrick D., Wang Z.-Y., Young R.N. Drugs Future. 27(Suppl. A):2002;142.
21. Cheng, H. M.; Li, J.; Lundy, K. M.; Minich, M. L.; Sakya, S. M. WO 0140126, A1, 2001.
22. A detailed report in this regard will be published later.
23. 2).
24. Synovitis was induced by injection of media containing pro-inflammatory cytokines generated from a lipopolysaccharide-stimulated culture of canine histiocytes. Knee joints were injected 12 h following the last administration of drug and lameness was scored 3 and 5 h post-injection (15 and 17 h, respectively, post final dose) using a 10 cm visual analogue scale (VAS) scoring system where 0 cm represents no lameness and 10 cm the most severe lameness. Animals were anesthetized during the injection procedure. Capsules of powdered compound were prepared to provide the following doses: 12a at 4.0 mg/kg, carprofen at 4.4 mg/kg (crushed Rimadyl® tablet) or deracoxib at 2.0 mg/kg. Different letters over the error bars indicate statistical differences in the means (p<0.10). The range of lameness scores in dogs that were not treated with a drug prior to knee injection fall between the parallel dashed lines above the bars at each time point.