1-Substituted 4-aryl-5-pyridinylimidazoles: A new class of cytokine suppressive drugs with low 5-lipoxygenase and cyclooxygenase inhibitory potency

Journal of Medicinal Chemistry

Volumn 39, Issue 20, 1996, Pages 3929-3937

  Boehm, Jeffrey C ^a   Smietana, Juanita M ^a   Sorenson, Margaret E ^a   Garigipati, Ravi S ^a   Gallagher, Timothy F ^a   Sheldrake, Peter L ^a   Bradbeer, Jeremy ^a   Badger, Alison M ^a   Laydon, Jeffrey T ^a   Lee, John C ^a   Hillegass, Leonard M ^a   Griswold, Donald E ^a   Breton, John J ^a   Chabot Fletcher, Marie C ^a   Adams, Jerry L ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

INTERLEUKIN 1; LIPOXYGENASE INHIBITOR; NONSTEROID ANTIINFLAMMATORY AGENT; PROSTAGLANDIN SYNTHASE; TUMOR NECROSIS FACTOR;

ANTIINFLAMMATORY ACTIVITY; ARACHIDONIC ACID METABOLISM; ARTHRITIS; ARTICLE; BINDING AFFINITY; BONE DENSITY; BONE MINERAL; DRUG POTENCY; ENZYME ACTIVITY; ENZYME BINDING; ENZYME INHIBITION; STRUCTURE ACTIVITY RELATION;

ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ARACHIDONATE 5-LIPOXYGENASE; ARACHIDONIC ACID; ARTHRITIS; BONE DENSITY; CYCLOOXYGENASE INHIBITORS; CYTOKINES; IMIDAZOLES; MICE; MICE, INBRED BALB C; MOLECULAR STRUCTURE; MORPHOLINES; PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES; PROTEIN KINASES; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; TUMOR NECROSIS FACTOR-ALPHA;

EID: 10144243335     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm960415o     Document Type: Article

References (27)

1. A solution to the problem of the adverse effects of NSAIDs may be selective inhibition of PGHS-2 (see refs 2 and 3). In this report we suggest yet another approach.
2. Mitchell, J. A.; Akarasereenont, P.; Thiemermann, C.; Flower, R. J.; Vane, J. R. Selectivity of Nonsteroidal Antiinflammatory Drugs as Inhibitors of Constitutive and Inducible Cyclooxygenase. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 11693-11697.
3. Griswold, D. E.; Adams, J. L. Constitutive Cyclooxygenase (COX-1) and Inducible Cyclogenase(COX-2); Rationale for Selective Inhibition and Progress to Date. Med. Res. Rev. 1996, 16, 181-206.
4. Lee, J. C.; Laydon, J. L.; McDonnel, P. C.; Gallagher, T. F.; Kumar, S.; Green, D.; McNulty, D.; Blumenthal, M. J.; Heyes, J. R.; Landvatter, S. W.; Strickler, J. F.; McLaughlin, M. M.; Siemens, I. R.; Fisher, S. M.; Livi, G. P.; White, J. R.; Adams, J. L.; Young, P. R. A Protein Kinase Involved In The Regulation Of Inflammatory Cytokine Biosynthesis. Nature (London) 1994, 372 (6508), 739-736.
5. Han, J.; Lee, J.-D.; Bibbs, L.; Ulevitch, R. J. A MAP Kinase Targeted by Endotoxin and Hyperosmoarity in Mammalian Cells. Science 1994, 265, 808-811.
6. Lantos, I.; Bender, P. E.; Razgaitis, K. A.; Button, B. M.; DiMartino, M. J.; Griswold, D. E.; Waltz, D. T. Antiinflammatory Activity of 5,6-Diaryl-2,3-dihydroimidazo[2,1-b]thiazoles. Isomeric 4-Pyridyl and 4-Substituted Phenyl Derivatives. J. Med. Chem. 1984, 27, 72-75.
7. Lee, J. C.; Badger, A. M.; Griswold, D. E.; Dunnington, D.; Truneh, A.; White, J. R.; Young, P. R.; Bender, P. E. Bicyclic Imidazoles as a Novel Class of Cytokine Biosynthesis Inhibitors. Ann. N.Y. Acad. Sci. 1993, 696, 149-170.
8. Gallagher, T. M.; Fier-Thompson, S. M.; Garigpati, R. S.; Sorenson, M. E.; Smietana, J. M.; Lee, D.; Lee, J. C.; Laydon, J. T.; Griswold, D. E.; Chabot-Fletcher, M. C.; Breton, J. L.; Adams, J. L. 2,4,5-Triarylimidazole Inhibitors of IL-1 Biosynthesis. Bioorg. Med. Chem. Lett. 1995, 5, 1171-1176.
9. Badger, A. M.; Bradbeer, J. N.; Votta, B.; Lee, J. C.; Adams, J. L.; Griswold, D. E. Pharmacological Profile of SB 203580, a Selective Inhibitor of CSBP/p38 Kinase, in Animal Models of Arthritis, Bone Resorption, Endotoxin Shock and Immune Function. J. Pharmacol. Exp. Ther., in press.
10. van Leusen, A. M.; Wildeman, J.; Oldenziel, O. H. Base-Induced Cycloaddition of Sulfonylmethyl Isocyanides to C,N Double Bonds. Synthesis of 1,5-Disubstituted and 1,4,5-Trisubstituted Imidazoles from Aldimines and Imidoyl Chlorides. J. Org. Chem. 1977, 42, 1153-1159.
11. Shih, N.-Y. Novel Synthesis of N-Unsubstituted Imidazoles Using Trimethylsilylimines. Tetrahedron Lett. 1993, 34, 595-598.
12. Joseph Sisko, Smithkline Beecham Department of Chemical Development, personal communication.
13. (a) Yamanaka, H.; Abe, H.; Sakamoto, T.; Hiranuma, H.; Kamata, A. Studies of Pyrimidine Deritivatives. II. Reaction of Some Dimethyl and Trimethyl-heteroaromatics with Ethyl Nitrite. Chem. Pharm. Bull. 1977, 25, 1821-1826.
14. (b) The reported procedure was slightly modified with commercially available butyl nitrite substituted for the less convenient ethyl nitrite reported as the reagent for the synthesis of the intermediate oximes.
15. Nobuhiko, H.; Kashiwaba, H.; Hosoda, A.; Sekine, Y.; Isowa, Y.; Yamura, T.; Sekine, A. New N-Aminomethylpyridyl oxy-2-fufuryl thioacetamide Derivatives and Antagonists of Histamine H2. Receptors Useful as Antiulcer Agents and New Intermediates. Eur. Pat. 0 282077, March 11, 1988.
16. Katritsky, A. E. Physical Methods in Heterocyclic Chemistry; Academic Press: New York, 1963; Vol. 1.
17. Gallagher, T. F.; Seibel, G. L.; Kassis, S.; Laydon, J. L.; Blumenthal, M. J.; Lee, J. C.; Lee, D.; Boehm, J. C.; Fier-Thompson, S. T.; Abt, J. A.; Soreson, M. E.; Smietana, J. M.; Hall, R. A.; Garigipati, R. A.; Bender, P. A.; Erhard, K. A.; Krog, A. J.; Hofmann, G. A.; Sheldrake, P. L.; Adams, J. L. Regulation of Stress-Induced Cytokine Production by Pyridinylimidazoles: Inhibition of CSBP Kinase. Bioorg. Med. Chem., in press.
18. Griswold, D. E.; Hillegass, L. M.; Breton, J. J.; Esser, K. M.; Adams, J. L. Differentiation in vivo of Classical Non-Steroidal Antiinflammatory Drugs from Cytokine Supprressive Antiinflammatory Drugs and Other Pharmacological Classes using Mouse Tumour Necrosis Factor Alpha Production. Drugs Exp. Clin. Res. 1993, XIX, 243-248.
19. Marshall, P. J.; Griswold, D. W.; Breton, J.; Webb, E. F.; Hillegass, L. M.; Sarau, H. M.; Newton, J.; Lee, J. C.; Bender, P. E.; Hanna, N. Pharmacology of the Pyrroloimidazole, SK&F 105809 - I. Biochem. Pharmacol. 1991, 42, 313-324.
20. Shen, T. Y. Indomethacin, Sulindac and Their Analogs. Anti-Inflammatory and Anti-Rheumatic Drugs; Rainsford, K. D., Ed.; CRC Press, Inc.: Boca Raton, FL, 1985; Vol. 1, pp 149-159.
21. Newton, J. F.; Yodis, L. P.; Keohand, D.; Eckardt, R.; Dewey, R.; Dent, J.; Mico, B. Pharmacokinetics and Metabolism of SK&F 86002 in Male and Female Sprague-Dawley Rats. Drug Metab. Dispos. 1989, 17, 174-179.
22. Preventing metabolic oxidation by steric hinderence is exemplified by 16,16-dimethylprostaglandin F2α (see ref 22).
23. Granstrom, E.; Hansson, G. Effect of Chemical Modifications on the Metabolic Transformations of Prostaglandins. Adv. Prostaglandin Thromboxane Res. 1976, 1, 215-219.
24. Albrightson, C. R.; Dytko, G.; Griswold, D. E. CSBP/P38 Kinase May be Involved in the Signal Transduction Pathway for PGE2 Production. Abstract submitted to the National Kidney Foundation 46th Annual Meeting, Oct 31-Nov 3, 1996.
25. Breton, J.; Keller, P.; Chabot-Fletcher, M.; Hillegass, L.; DeWoIf, W., Jr.; Griswold, D. Use of a Continuous Assay of Oxygen Consumption to Evaluate the Pharmacology of 5-Lipoxygenase Inhibitors. Prostaglandins, Leukotrienes Essent. Fatty Acids 1993, 49, 929-937.
26. 4 Synthetase Activities. Mol. Pharmacol. 1986, 30, 510-519.
27. DeWitt, D. L.; El-Harith, E. A.; Kraemer, S. A.; Andres, M. J.; Yao, E. F.; Armstrong, R. L.; Smith, W. L. The Aspirin and Heme-Binding Sites of Ovine and Murine Prostaglandin Endoperoxide Synthases. J. Biol. Chem. 1990, 265, 5192-5198.