5-Heteroatom-substituted pyrazoles as canine COX-2 inhibitors: Part 2. Structure-activity relationship studies of 5-alkylethers and 5-thioethers

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 5, 2006, Pages 1202-1206

  Sakya, Subas M ^a,b   Cheng, Hengmiao ^a   Lundy DeMello, Kristin M ^a   Shavnya, Andrei ^a   Minich, Martha L ^a   Rast, Bryson ^a   Dutra, Jason ^a   Li, Chao ^a   Rafka, Robert J ^a   Koss, David A ^a   Li, Jin ^a   Jaynes, Burton H ^a   Ziegler, Carl B ^a   Mann, Donald W ^a   Petras, Carol F ^a   Seibel, Scott B ^a   Silvia, Annette M ^a   George, David M ^a   Hickman, Anne ^a   Haven, Michelle L ^a   Lynch, Michael P ^a   more..

^a PFIZER INC   (United States)

^b PGRD   (United States)

Author keywords

Aanine; COX 1; COX 2; Heteroatom; Pyrazoles; SAR

Indexed keywords

2 [3 TRIFLUOROMETHYL(THIO)ETHER PYRAZO 1 YL] 5 METHANESULFONYL PYRIDINE; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; CYCLOOXYGENASE 2 INHIBITOR; PYRAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DOG; DOSE RESPONSE; DRUG ABSORPTION; DRUG ELIMINATION; DRUG HALF LIFE; DRUG POTENCY; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ASSAY; ENZYME INHIBITION; NONHUMAN; STRUCTURE ACTIVITY RELATION;

ALKYLATION; ANIMALS; CYCLOOXYGENASE 2; CYCLOOXYGENASE 2 INHIBITORS; DOGS; ETHERS; INHIBITORY CONCENTRATION 50; MOLECULAR STRUCTURE; PYRAZOLES; STRUCTURE-ACTIVITY RELATIONSHIP; SULFHYDRYL COMPOUNDS;

ANIMALIA; CANIS FAMILIARIS;

EID: 31344441756     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.11.110     Document Type: Article

References (29)

1. J.C. Otta, and W.L. Smith J. Lipid Mediators Cell Signalling 12 1995 139
2. J.S. Carter Expert Opin. Ther. Patents 8 1998 21
3. O. Laneuville, D.K. Breuer, D.L. Dewitt, T. Hla, C.D. Funk, and W.L. Smith J. Pharmacol. Exp. Ther. 271 1994 927
4. G.P. O'Neill, J.A. Mancini, S. Kargman, J. Yergey, M.Y. Kwan, J.P. Falgueyret, M. Abramovitz, B.P. Kennedy, M. Ouellet, and W. Cromlish Mol. Pharmacol. 45 1994 245
5. P. Prasit, and D. Riendeau Annu. Rep. Med. Chem. 32 1997 211
6. T.D. Warner, and J.A. Mitchell Proc. Natl. Acad. Sci. U.S.A. 99 2002 13371 and references cited herein
7. D.M. Clive, and J.S. Stoff N. Engl. J. Med. 310 1984 563
8. M.C. Allison, A.G. Howatson, C.J. Torrance, F.D. Lee, and R.I. Russell N. Engl. J. Med. 327 1992 749
9. D.E. Griswold, and J.L. Adams Med. Res. Rev. 16 1996 181
10. B. Cryer, and A. Dubois Prostaglandins Other Lipid Mediat. 56 1998 341
11. T.D. Penning, J.J. Talley, S.R. Bertenshaw, J.S. Carter, P.W. Collins, S. Doctor, M.J. Graneto, L.F. Lee, J.W. Malecha, J.M. Miyashiro, R.S. Rogers, D.J. Rogier, S.S. Yu, G.D. Anderson, E.G. Burton, J.N. Cogburn, S.A. Gregory, C.M. Koboldt, W.E. Perkins, K. Seibert, A.W. Veenhuizen, Y.Y. Zhang, and P.C. Isakson J. Med. Chem. 40 1997 1347
12. F.S. Lehman, and C. Beglinger Curr. Top. Med. Chem. 5 2005 449
13. S.M. Fox, and S.A. Johnston J. Am. Vet. Med. Assoc. 210 1997 1493
14. Proprietary market research, September 1998. Owners of osteoarthritic dogs, sample size: 150. Study no. RI199807. Data on file with Pfizer Animal Health.
15. A.M. Kore Vet. Clin. North Am. Small Anim. Pract. 20 1990 419
16. A.P. Ricketts, K.M. Lundy, and S.B. Seibel Am. J. Vet. Res. 59 1998 1441
17. C. Brideau, C.V. Staden, and C.C. Chan Am. J. Vet. Res. 62 2001 1755
18. J.K. Sessions, L.R. Reynolds, and S.C. Budsberg Am. J. Vet. Res. 66 2005 812
19. Federal Register 2004, 69, 69523.
20. H.K. Streppa, C.J. Jones, and S.C. Budsberg Am. J. Vet. Res. 63 2002 91
21. J. Li, K.M. Lundy DeMello, H. Cheng, S.M. Sakya, B.S. Bronk, R.J. Rafka, B.H. Jaynes, C.B. Ziegler, C. Kilroy, D.W. Mann, E.L. Nimz, M.P. Lynch, M.L. Haven, N.L. Kolosko, M.L. Minich, C. Li, J.K. Dutra, B. Rast, R. Crossan, B.J. Morton, G.W. Kirk, K.M. Callaghan, D.A. Koss, A. Shavnya, L.A. Lund, S.B. Seibel, C.F. Petras, and A. Silvia Bioorg. Med. Chem. Lett. 14 2004 95
22. Cheng, H. M.; Li, J.; Lundy, K. M.; Minich, M. L.; Sakya, S. M. WO 0140126, A1, 2001.
23. S.M. Sakya, K.M.L. Demello, M.L. Minich, B. Rast, A. Shavnya, R.J. Rafka, D.A. Koss, H. Cheng, J. Li, B.H. Jaynes, C.B. Ziegler, D.W. Mann, C.F. Petras, S.B. Seibel, A.M. Silvia, D.M. George, L.A. Lund, S. St. Denis, M.L. Haven, and M.P. Lynch Bioorg. Med. Chem. Lett. 16 2006 288
24. For chemistry details, please see: Cheng, H.; Sakya, S. M.; Dutra, J. K. WO0164669 A1, 2001.
25. L.F. Lee, F.M. Schleppnik, R.W. Schneider, and D.H. Campbell J. Heterocycl. Chem. 27 1990 243
26. S.M. Sakya, and B. Rast Tetrahedron Lett. 44 2003 7629
27. A. Shavnya, S.M. Sakya, M.L. Minich, B. Rast, and B.H. Jaynes Tetrahedron Lett. 46 2005 6887
28. 2).
29. We did not have established canine microsomal stability assays while we were engaged in the COX-2 project. Although we had good rat and human microsomal stability data, it did not correlate well with the canine in vivo studies.