Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: Identification of 4-[5-(4-methylphenyl)- 3(trifluoromethyl)-1h-pyrazol-1-yl]benzenesulfonamide (sc-58635, celecoxib)

Journal of Medicinal Chemistry

Volumn 40, Issue 9, 1997, Pages 1347-1365

  Penning, Thomas D ^a   Talley, John J ^a   Bertenshaw, Stephen R ^a   Carter, Jeffery S ^a   Collins, Paul W ^a   Docter, Stephen ^a   Graneto, Matthew J ^a   Lee, Len F ^a   Malecha, James W ^a   Miyashiro, Julie M ^a   Rogers, Roland S ^b   Rogier, D J ^a   Yu, Stella S ^a   Anderson, Gary D ^a   Burton, Earl G ^a   Cogburn, J Nita ^a   Gregory, Susan A ^a   Koboldt, Carol M ^a   Perkins, William E ^a   Seibert, Karen ^a   Veenhuizen, Amy W ^a   Zhang, Yan Y ^a   Isakson, Peter C ^a   more..

^a PFIZER INC   (United States)

^b Searle Research and Development ^*

Author keywords

[No Author keywords available]

Indexed keywords

4 [5 (4 CHLOROPHENYL) 3 TRIFLUOROMETHYL 1H PYRAZOL 1 YL]BENZENESULFONAMIDE; CELECOXIB; CYCLOOXYGENASE 2 INHIBITOR; PYRAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG HALF LIFE; DRUG POTENCY; DRUG SYNTHESIS; OSTEOARTHRITIS; RHEUMATOID ARTHRITIS; STRUCTURE ACTIVITY RELATION;

ANIMALS; ARTHRITIS, EXPERIMENTAL; ARTHRITIS, RHEUMATOID; CARRAGEENAN; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; CYCLOOXYGENASE 2 INHIBITORS; CYCLOOXYGENASE INHIBITORS; HYPERALGESIA; ISOENZYMES; MAGNETIC RESONANCE SPECTROSCOPY; MALE; MEMBRANE PROTEINS; MOLECULAR STRUCTURE; OSTEOARTHRITIS; PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES; PYRAZOLES; RATS; RATS, INBRED LEW; RATS, SPRAGUE-DAWLEY; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES;

EID: 13444266910     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm960803q     Document Type: Article

References (38)

1. Lombardino, G. Nonsteroidal Antiinflammatory Drugs; Wiley Interscience, John Wiley & Sons: New York, 1985.
2. Clive, D. M.; Stoff, J. S. Renal Syndromes Associated with Nonsteroidal Antiinflammatory Drugs. N. Engl. J. Med. 1984, 310, 563-572.
3. Pirson, Y.; Van Ypersele de Strihou, C. Renal Side Effects of Nonsteroidal Anti-Inflammatory Drugs: Clinical Relevance. Am. J. Kidney Dis. 1986, 8, 337-344.
4. Allison, M. C.; Howatson, A. G.; Torrance, C. J.; Lee, F. D.; Russell, R. I. G. Gastrointestinal Damage Associated with the Use of Non-Steroidal Antiinflammatory Drugs. N. Engl. J. Med. 1992, 327, 749-754.
5. Haynes, R. C., Jr. Adrenocorticotropic Hormones; Adrenocortical Steroids and Their Synthetic Analogs; Inhibition of the Synthesis and Actions of Adrenocortical Hormones. In The Pharmacological Basis of Therapeutics, 8th ed.; Gilman, A. G., Rall, T. W., Nies, A. S., Taylor, P., Eds.; McGraw-Hill: New York, 1993; pp 1442-1452.
6. Vane, J. R. Inhibition of Prostaglandin Synthesis as a Mechanism of Action for Aspirin-Like Drugs. Nature [New Biol.] 1971, 231, 232-235.
7. Smith, J. B.; Willis, A. L. Aspirin Selectively Inhibits Prostaglandin Production in Human Platelets. Nature [New Biol.] 1971, 231, 235-237.
8. Xie, W.; Chipman, J. G.; Robertson, D. L.; Erikson, R. L.; Simmons, D. L. Expression of a Mitogen-responsive Gene Encoding Prostaglandin Synthase is Regulated by mRNA Splicing. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 2692-2696.
9. Kujubu, D. A.; Fletcher, B. S.; Varnum, B. C.; Lim, R. W.; Herschman, H. R. TIS10, a Phorbol Ester Tumor Promoter-inducible mRNA from Swiss 3T3 Cells, Encodes a Novel Prostaglandin Synthase/Cyclooxygenase Homologue. J. Biol. Chem. 1991, 266, 12866-12872.
10. Hla, T.; Neilson, K. Human Cyclooxygenase-2 cDNA. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 7384-7388.
11. Masferrer, J. L.; Zweifel, B. S.; Manning, P. T.; Hauser, S. D.; Leahy, K. M.; Smith, W. G.; Isakson, P. C.; Seibert, K. Selective Inhibition of Inducible Cyclooxygenase-2 In Vivo is Antiinflammatory and Nonulcerogenic. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 3228-3232.
12. Reitz, D. B.; Isakson, P. C. Cyclooxygenase-2 Inhibitors. Curr. Pharm. Des. 1995, 1, 211-220.
13. Reitz, D. B.; Seibert, K. Selective Cyclooxygenase Inhibitors. Annu. Rep. Med. Chem. 1995, 30, 179-188.
14. Futaki, N.; Takahashi, S.; Yokoyama, M.; Arai, I.; Higuchi, S.; Otomo, S. NS 398, a New Anti-inflammatory Agent, Selectively Inhibits Prostaglandin G/H Synthase/Cyclooxygenase (COX-2) Activity In Vitro. Prostaglandins 1994, 47, 55-59.
15. Li, C. S.; Black, W. C.; Chan, C. C.; Ford-Hutchinson, A. W.; Gauthier, J.-Y.; Gordon, R.; Guay, D.; Kargman, S.; Lau, C. K.; Mancini, J.; Ouimet, N.; Roy, P.; Vickers, P.; Wong, E.; Young, R. N.; Zamboni, R.; Prasit, P. Cyclooxygenase-2 Inhibitors: Synthesis and Pharmacological Activities of 5-Methanesulfonamido-1-indanone Derivatives. J. Med. Chem. 1995, 38, 4897-4905.
16. Gans, K. R.; Galbraith, W.; Roman, R. J.; Haber, S. B.; Kerr, J. S.; Schmidt, W. K.; Smith, C.; Hewes, W. E.; Ackerman, N. R. Anti-inflammatory and Safety Profile of DuP 697, a Novel Orally Effective Prostaglandin Synthesis Inhibitor. J. Pharmacol. Exp. Ther. 1990, 254, 180-187.
17. (a) Reitz, D. B.; Li, J. J.; Norton, M. B.; Reinhard, E. J.; Collins, J. T.; Anderson, G. D.; Gregory, S. A.; Koboldt, C. M.; Perkins, W. E.; Seibert, K.; Isakson, P. C. Selective Cyclooxygenase Inhibitors: Novel 1,2-Diarylcyclopentenes are Potent and Orally Active COX-2 Inhibitors. J. Med. Chem. 1994, 37, 3878-3881.
18. (b) Reitz, D. B.; Li, J. J.; Norton, M. B.; Reinhard, E. J.; Huang, H. C.; Penick, M. A.; Collins, J. T.; Garland, D. J. Novel 1,2-Diarylcyclopentenes are Selective, Potent, and Orally Active Cyclooxygenase Inhibitors. Med. Chem. Res. 1995, 5, 531-563.
19. (c) Li, J. J.; Anderson, G. D.; Burton, E. G.; Cogburn, J. N.; Collins, J. T.; Garland, D. J.; Gregory, S. A.; Huang, H.-C.; Isakson, P. C.; Koboldt, C. M.; Logusch, E. W.; Norton, M. B.; Perkins, W. E.; Reinhard, E. J.; Seibert, K.; Veenhuizen, A. W.; Zhang, Y.; Reitz, D. B. 1,2-Diarylcyclopentenes as Selective Cyclooxygenase-2 Inhibitors and Orally Active Anti-inflammatory Agents. J. Med. Chem. 1995, 38, 4570-4578.
20. Seibert, K.; Zhang, Y.; Leahy, K.; Hauser, S.; Masferrer, J.; Perkins, W.; Lee, L.; Isakson, P. Pharmacological and Biochemical Demonstration of the Role of Cyclooxygenase-2 in Inflammation and Pain. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 12013-12017.
21. Recently a number of reports on this class of inhibitors have appeared; see: (a) Reitz, D. B.; Huang, H. C.; Li, J. J.; Garland, D. J.; Manning, R. E.; Anderson, G. D.; Gregory, S. A.; Koboldt, C. M.; Perkins, W. E.; Seibert, K.; Isakson, P. C. Selective Cyclooxygenase Inhibitor: Novel 4-Spiro 1,2-Diarylcyclopentenes are Potent and Orally Active COX-2 Inhibitors. Bioorg. Med. Chem. Lett. 1995, 5, 867-872.
22. (b) Pinto, D. J.; Pitts, W. J.; Copeland, R. A.; Covington, M. B.; Trzaskos, J.; Magolda, R. Selective Inhibition of Cyclooxygenase-2: Diaryl Heterocycles vs Classical NSAIDs. Med. Chem. Res. 1995, 5, 394-398.
23. (c) Wilkerson, W. W.; Copeland, R. A.; Covington, M. B.; Grubb, M. F.; Hewes, W. E.; Kerr, J. S.; Trzaskos, J. M. Cyclooxygenase-2 Inhibitory 2-Substituted 4,5-Diarylpyrroles. Med. Chem. Res. 1995, 5, 399-408.
24. (d) Wilkerson, W. W.; Copeland, R. A.; Covington, M.; Trzaskos, J. M. Antiinflammatory 4,5-Diarylpyrroles. 2. Activity as a Function of Cyclooxygenase-2 Inhibition. J. Med. Chem. 1995, 38, 3895-3901.
25. (e) Huang, H. C.; Li, J. J.; Garland, D. J.; Chamberlin, T. S.; Reinhard, E. J.; Manning, R. E.; Seibert, K.; Koboldt, C. M.; Gregory, S. A.; Anderson, G. D.; Veenhuizen, A. W.; Zhang, Y.; Perkins, W. E.; Burton, E. G.; Cogburn, J. N.; Isakson, P. C.; Reitz, D. B. Diarylspiro[2.4]heptenes as Orally Active, Highly Selective Cyclooxygenase-2 Inhibitors: Synthesis and Structure-Activity Relationships. J. Med. Chem. 1996, 39, 253-266.
26. (f) Gauthier, J. Y.; Leblanc, Y.; Black, W. C.; Chan, C. C.; Cromlish, W. A.; Gordon, R.; Kennedey, B. P.; Lau, C. K.; Zhaoyin, S. L.; Ethier, D.; Quay, J.; Mancini, J.; Riendeau, D.; Tagari, P.; Vickers, P.; Wong, E.; Xu, L.; Prasit, P. Synthesis and Biological Evaluation of 2,3-Diarylthiophenes as Selective COX-2 Inhibitors. Part II: Replacing the Heterocycle. Bioorg. Med. Chem. Lett. 1996, 6, 87-92.
27. (g) Bertenshaw, S. R.; Talley, J. J.; Rogier, D. J.; Graneto, M. J.; Rogers, R. S.; Kramer, S. W.; Penning, T. D.; Koboldt, C. M.; Veenhuizen, A. W.; Zhang, Y.; Perkins, W. E. 3,4-Diarylthiophenes are Selective COX-2 Inhibitors. Bioorg. Med. Chem. Lett. 1995, 5, 2919-2922.
28. (h) Leblanc, Y.; Gauthier, J. Y.; Ethier, D.; Guay, J.; Mancini, J.; Riendeau, D.; Tagari, P.; Vickers, P.; Wong, E.; Prasit, P. Synthesis and Biological Evaluation of 2,3-Diarylthiophenes as Selective COX-2 and COX-1 Inhibitors. Bioorg. Med. Chem. Lett. 1995, 5, 2123-2138.
29. (i) Huang, H. C.; Chamberlain, T. S.; Seibert, K.; Koboldt, C. M.; Isakson, P. C.; Reitz, D. B. Diaryl Indenes and Benzofurans: Novel Classes of Potent and Selective Cyclooxygenase-2 Inhibitors. Bioorg. Med. Chem. Lett. 1995, 5, 2377-2380.
30. (j) Li, J. J.; Norton, M. B.; Reinhard, E. J.; Anderson, G. D.; Gregory, S. A.; Isakson, P. C.; Koboldt, C. M.; Masferrer, J. L.; Perkins, W. E.; Seibert, K.; Zhang, Y.; Zweifel, B. S.; Reitz, D. B. Novel Terphenyls as Selective Cyclooxygenase-2 Inhibitors and Orally Active Antiinflammatory Agents. J. Med. Chem. 1996, 39, 1846-1856.
31. Copeland, R. A.; Williams, J. M.; Giannaras, J.; Nurnbero, S.; Covington, M.; Pinto, D.; Pick, S.; Trzaskos, J. M. Mechanism of Selective Inhibition of the Inducible Isoform of Prostaglandin G/H Synthase. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 11202-11206.
32. Copeland, R. A.; Williams, J. M.; Rider, N. L.; VanDyk, D. E.; Giannaras, J.; Nurburg, S.; Covington, M.; Pinto, D.; Magolda, R. L.; Trzaskos, J. M. Selective Time Dependent Inhibition of Cyclooxygenase-2. Med. Chem. Res. 1995, 5, 384-393.
33. Ouellet, M.; Percival, M. D. Effect of Inhibitor Time-dependency on Selectivity Towards Cyclooxygenase Isoforms. Biochem. J. 1995, 306, 247-251.
34. Gierse, J. K.; Hauser, S. D.; Creely, D. P.; Koboldt, C.; Rangwala, S. H.; Isakson, P. C.; Seibert, K. Expression and Selective Inhibition of the Constitutive and Inducible Forms of Human Cyclooxygenase. Biochem. J. 1995, 305, 479-484.
35. Winter, C. A.; Risley, E. A.; Nuss, G. W. Carrageenan-Induced Edema in Hind Paw of the Rat as an Assay for Antiinflammatory Drugs. Proc. Soc. Exp. Biol. Med. 1962, 111, 544-547.
36. Jaffee, B. D.; Kerr, J. S.; Jones, E. A.; Giannaras, J. V.; McGowan, M.; Ackerman, N. R. The Effect of Immunomodulating Drugs on Adjuvant-induced Arthritis in Lewis Rats. Agents Actions 1989, 27, 344-346.
37. Hargreaves, K.; Dubner, R.; Brown, F.; Flores, C.; Joris, J. A. New and Sensitive Method for Measuring Thermal Nociception in Cutaneous Hyperalgesia. Pain 1988, 32, 77-88.
38. Hubbard, R. C.; Mehlisch, D. L.; Jasper, D. R.; Nugent, M. J.; Yu, S.; Isakson, P. C. SC-58635, a Highly Selective Inhibitor of COX-2, is an Effective Analgesic in an Acute Post-surgical Pain Model. J. Invest. Med. 1996, 44, 293A.