Selective Cyclooxygenase Inhibitors: Novel 1,2-Diarylcyclopentenes Are Potent and Orally Active COX-2 Inhibitors

Journal of Medicinal Chemistry

Volumn 37, Issue 23, 1994, Pages 3878-3881

  Reitz, David B ^a   Li, James J ^a   Norton, Monica B ^a   Reinhard, Emily J ^a   Collins, Joe T ^a   Anderson, Gary D ^a   Gregory, Susan A ^a   Koboldt, Carol M ^a   Perkins, William E ^a   Seibert, Karen ^a   Isakson, Peter C ^a  

^a MONSANTO COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (4 FLUOROPHENYL) 2 [(4 METHYLSULFONYL)PHENYL]CYCLOPENTENE; 1 [2 (4 FLUOROPHENYL)CYCLOPENTEN 1 YL] 4 (METHYLSULFONYL)BENZENE; 5 (4 FLUOROPHENYL) 1 [(4 METHYLSULFONYL)PHENYL] 3 TRIFLUOROMETHYLPYRAZOLE; 5 BROMO 2 (4 FLUOROPHENYL) 3 (4 METHYLSULFONYLPHENYL)THIOPHENE; ARACHIDONIC ACID; CORTICOSTEROID; INDOMETACIN; N (2 CYCLOHEXYLOXY 4 NITROPHENYL)METHANESULFONAMIDE; NONSTEROID ANTIINFLAMMATORY AGENT; PROSTAGLANDIN; PROSTAGLANDIN SYNTHASE INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL MODEL; ANIMAL TISSUE; ARTHRITIS; ARTICLE; DOSE RESPONSE; DRUG DISPOSITION; DRUG SELECTIVITY; EDEMA; ENZYME INHIBITION; HUMAN; INFLAMMATION; NONHUMAN; ORAL DRUG ADMINISTRATION; PROSTAGLANDIN SYNTHESIS INHIBITION; RAT; STRUCTURE ACTIVITY RELATION; ULCER;

ADMINISTRATION, ORAL; ANIMAL; ARTHRITIS, EXPERIMENTAL; CYCLOOXYGENASE INHIBITORS; CYCLOPENTANES; MICE; RATS;

EID: 0027944191     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm00049a005     Document Type: Article

References (17)

1. Vane, J. R. Inhibition of Prostaglandin Synthesis as a Mechanism of Action for Aspirin-Like Drugs. Nature [New Biol.] 1971, 231, 232-235.
2. Smith, J. B.; Willis, A. L. Aspirin Selectively Inhibits Prostaglandin Production in Human Platelets. Nature [New Biol.] 1971, 231, 235-237.
3. Allison, M. C.; Howatson, A. G.; Torrance, C. J.; Lee, F. D.; Russell, R. I. Gastrointestinal Damage Associated with the Use of Nonsteroidal Antiinflammatory Drugs. N. Engl. J. Med. 1992, 327, 749-754.
4. 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., Rail, T. W., Nies, A. S., Taylor, P., Eds.; McGraw-Hill: New York, 1993; pp 1442-1452.
5. Hla, T.; Neilson K. Human Cyclooxygenase-2 cDNA. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 7384-7388.
6. 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.
7. Kujubu, D. A.; Fletcher, B. S.; Varnum, B. C.; Lim, R. W.; Herschman, H. R. TIS10, a Phorbol Ester Tumor Promoterinducible mRNA from Swiss 3T3 Cells, Encodes a Novel Prostaglandin Synthase/Cyclooxygenase Homologue. J. Biol. Chem. 1991, 266, 12866-12872.
8. 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.
9. 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.
10. 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. Pharmacol. 1993, 24, 105-110.
11. Futaki, N.; Takahashi, S.; Yokoyama, M.; Arai, L.; Higuchi, S.; Otomo, S. NS-398, A New Antiinflammatory Agent, Selectively Inhibits Prostaglandin G/H Synthase/Cyclooxygenase (COX-2) Activity in vitro. Prostaglandins 1994, 47, 55-59.
12. 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.
13. Isakson, P.; Seibert, K.; Masferrer, J.; Salvemini, D., Lee, L.; Needleman, P. Discovery of a Better Asprin. Presented at the Ninth International Conference on Prostaglandins and Related Compounds, Florence, Italy, June 1994.
14. 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, 513-515.
15. McMurry, J. E. Titanium-induced Dicarbonyl-coupling Reactions. Acc. Chem. Res. 1983, 16, 405-411.
16. Reitz, D. B.; Li, J. U.S. Pat. 5 344 991, 1994.
17. Seibert, K.; Zhang, Y.; Leahy, K. M.; Hauser, S. D.; Masferrer, J. L.; Isakson, P. Procedings of the Third International Conference on Eicosanoids and Other Bioactive Lipids. In Cancer, Inflammation and Radiation Injury; Kluwar Academic Publishers, in press. The in vitro human COX-1 and human COX-2 Assays used are also detailed in the supplementary material.