Novel terphenyls as selective cyclooxygenase-2 inhibitors and orally active anti-inflammatory agents

Journal of Medicinal Chemistry

Volumn 39, Issue 9, 1996, Pages 1846-1856

  Li, James J ^a   Norton, Monica B ^a   Reinhard, Emily J ^a   Anderson, Gary D ^a   Gregory, Susan A ^a   Isakson, Peter C ^a   Koboldt, Carol M ^a   Masferrer, Jaime L ^a   Perkins, William E ^a   Seibert, Karen ^a   Zhang, Yan ^a   Zweifel, Ben S ^a   Reitz, David B ^a  

^a MONSANTO COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (4 FLUOROPHENYL) 2 [4 (METHYLSULFONYL)PHENYL]BENZENE; 1,2 DIFLUORO 4 (4 FLUOROPHENYL) 5 [4 (METHYLSULFONYL)PHENYL]BENZENE; 4 [2 (3 CHLORO 4 FLUOROPHENYL) 4,5 DIFLUOROPHENYL]BENZENESULFONAMIDE; 4 [2 (4 FLUOROPHENYL)PHENYL]BENZENESULFONAMIDE; ANTIINFLAMMATORY AGENT; BENZENESULFONAMIDE DERIVATIVE; PROSTAGLANDIN SYNTHASE INHIBITOR; TERPHENYL DERIVATIVE; UNCLASSIFIED DRUG;

ADJUVANT DISEASE; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTHRITIS; ARTICLE; DOSE RESPONSE; DRUG EFFECT; DRUG POTENCY; DRUG SCREENING; DRUG SELECTIVITY; DRUG SYNTHESIS; HYPERALGESIA; NONHUMAN; ORAL DRUG ADMINISTRATION; RAT; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ARTHRITIS, EXPERIMENTAL; CYCLOOXYGENASE 2; CYCLOOXYGENASE 2 INHIBITORS; CYCLOOXYGENASE INHIBITORS; ISOENZYMES; MAGNETIC RESONANCE SPECTROSCOPY; MASS SPECTROMETRY; PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES; RATS; TERPHENYL COMPOUNDS;

EID: 15844425962     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm950878e     Document Type: Article

References (35)

1. Vane, J. R. Inhibition of Prostaglandin Synthesis as a Mechanism of Action for Aspirin-like Drugs. Nature (London) New Biol. 1971, 232, 232-235.
2. Smith, J. B.; Willis, A. L. Aspirin Selectively Inhibits Prostaglandin Production in Human Platelets. Nature (London) New Biol. 1971, 231, 235-237.
3. Lombardino, J. G. Nonsteroidal Antiinflammatory Drugs, 1st ed.; John Wiley & Son, Inc.: New York, 1985.
4. Allison, M. C.; Howatson, A. G.; Torrance, C. J.; Lee, F. D.; Russell, R. I. G. Gastrointestinal Damage Associated with the Use of Nonsteroidal Antiinflammatory Drugs. N. Engl. J. Med. 1992, 327, 749-754.
5. Clive, D. M.; Stoff, J. S. Renal Syndromes Associated with Nonsteroidal Antiinflammatory Drugs. N. Engl. J. Med. 1984, 310, 563-572
6. Pirson, Y.; Van Ypersele de Strihou, C. Renal Side Effects of Nonsteroidal Antiinflammatory Drugs: Clinical Relevance. Am. J. Kidney Dis. 1986, 8, 337-344.
7. Hla, T.; Neilson K. Human Cyclooxygenase-2 cDNA. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 7384-7388.
8. Xie, W.; Chipman, J. G.; Robertson, D. L.; Erikson, R. L.; Simmons, D. L. Expression of a Mitogen-response 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. Masferrer, J. L.; Seibert, K.; Zweifel, B.; Needleman, P. Endogenous Glucocorticoids Regulate an Inducible Cyclooxygenase Enzyme. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 3917-3921.
11. For a review, see: Reitz, D. B.; Seibert, K. Selective Cyclooxygenase Inhibitors. Annu. Rep. Med. Chem. 1995, 30, 179-188.
12. For a review, see: Reitz, D. B.; Isakson, P. C. Cyclooxygenase-2 Inhibitors. Curr. Pharm. Des. 1995, 1, 211-220.
13. 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. Antiinflammatory and Safety Profile of Dup 697, a Novel Orally Effective Prostaglandin Synthesis Inhibitor. J. Pharmacol. Exp. Ther. 1990, 254, 180-187.
14. 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 Cyclo-oxygenase. Biochem. J. 1995, 305, 479-484.
15. Futaki, N.; Yoshikawa, K.; Hamasaka, Y.; Arai, I.; Higuchi, S.; Iizuka, H.; Otomo, S. NS-398, a Novel Non-steroidal Antiinflammatory Drug with Potent Analgesic and Antipyretic Effects, Which Causes Minimal Stomach Lesions. Gen. Pharmaccol. 1993, 24, 105-110.
16. 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.
17. Isakson, P.; Seibert, K.; Masferrer, J.; Salvemini, D.; Lee, L.; Needleman, P. Discovery of a Better Aspirin. Presented at 9th International Conference on Prostaglandins and Related Compounds, Florence, Italy, June 1994.
18. Prasit, P.; Black, W. C.; Chan, C.-C.; Ford-Hutchinson, A. W.; Gauthier, J. Y.; Gordon, R.; Quay, D.; Kargman, S.; Lau, C. K.; Li, C.-S.; Mancini, J.; Ouimet, N.; Roy, P.; Tagari, P.: Vickers, P.; Wong, E.; Young, R. N.; Zamboni, R. L-745,337: A Selective Cyclooxygenase-2 Inhibitor. Med. Chem. Res. 1995, 5, 364-374.
19. 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.
20. Reitz, D. B.; Li, J. J.; Norton, M. B.; Reinhard, E. J.; Huang, H.-C.; Penick, M. A.; Collins, J T.; Garland, D. J.; Seibert, K.; Kobold, C. M.; Gregory, S. A.; Veenhuizen, A.; Zhang, Y.; Isakson, P. C. Novel 1,2-Diarylcyclopentenes Are Selective, Potent and Orally Active Cyclooxygenase Inhibitors. Med. Chem. Res. 1995, 5, 351-363.
21. 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-Diarylcyelopentenes as Selective Cyclooxygenase-2 Inhibitors and Orally Active Anti-inflammatory Agents. J. Med. Chem. 1995, 38, 4570-4578.
22. Reitz, D. B.; Huang, H.-C.; Li, J. J.; Garland, D. J.; Manning, R. E.; Anderson, G. D.; Gregory, S. A.; Kobold, C. M.; Perkins, W. E.; Seibert, K; Isakson, P. C. Selective Cyclooxygenase Inhibitors: Novel 4-Spiro 1,2-Diarylcyclopentenes Are Potent and Orally Active COX-2 Inhibitors. Bioorg. Med. Chem. Lett. 1995, 5, 867-872.
23. Huang, H.-C.; Li, J. J.; Garland, D. J.; Chamberlain, 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. Diaryl Spiro[2.4]heptenes as Orally Active, Highly Selective Cyclooxygenase-2 Inhibitors: Synthesis and Structure-Activity Relationships. J. Med. Chem. 1996, 1, 253-266.
24. 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.
25. Pinto, D. J. P.; Copeland, R.; Covington, M.; Orwat, M. J.; Pitts, W.; Jetter, J.; Batt, D. G.; Wang, S.; Giannaras, J.; Andrews, T.; Nurnberg, S.; Wexler, R. R.; Trzaskos, J.; Magolda, R. Selective in vitro Inhibition of Cyclooxygenase 2 (COX 2) by Diarylthiophenes and Terphenyls. Presented at 209th National American Chemical Society Meeting, 1995; MEDI-018.
26. Miyaura, N.; Yanagi, T.; Suzuki, A. The Palladium-catalyzed Cross-coupling Reaction of Phenylboronic Acid with Haloarenes in the Presence of Base. Synth.Commun. 1981, 513-015.
27. Huang, H.-C.; Reinhard, E. J.; Reitz, D. B. A Novel One-Pot Conversion of Methyl Sulfones to Sulfonamides. Tetrahedron Lett. 1994, 35, 7201-7204.
28. Reitz, D. B.; Penick, M. A.; Reinhard, E. J.; Cheng, B. K; Olins, G. M.; Corpus, V. M.; Palomo, M. A.; McGraw, D. E.; McMahon, E. G. 1H-1,2,4-Triazole Angiotensin II Receptor Antagonists: N-Phenylpyridinylmethyl and N-Pyridinylphenylmethyl Analogs of SC-50560. Bioorg. Med. Chem. Lett. 1994, 4, 99-104.
29. Mitchell, T. N. Palladium-Catalyzed Reactions of Organotin Compounds. Synthesis 1992, 803-815.
30. Kajigaeshi, S.; Shinmasu, Y.; Fujisaki, S.; Kakinami, T. Halogenation Using Quaternary Ammonium Polyhalides: Facile Synthesis of Chloro-Substituted Aromatic Ethers by Use of Benzyltrimethylammonium Tetrachloroiodate. Chem. Lett. 1989, 415-418.
31. This one-pot procedure was employed as a time efficient method of preparing small quantity compounds for initial screening, although it gave overall lower yields.
32. 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 Nonulcerogenie. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 3228-3232.
33. 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.
34. 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.
35. See supplementary materials of ref 19.