Synthesis and immunosuppressant activity of pyrazole carboxamides

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 19, 1998, Pages 2787-2792

  Wang, Alan X ^a   Xie, Qinghua ^a   Lane, Ben ^a   Mollison, Karl W ^a   Hsieh, Gin C ^a   Marsh, Kennan ^a   Sheets, Michael P ^a   Luly, Jay R ^a   Coghlan, Michael J ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

IMMUNOSUPPRESSIVE AGENT; LEFLUNOMIDE; PYRAZOLE DERIVATIVE; TERIFLUNOMIDE;

ANIMAL CELL; ARTICLE; DOSE RESPONSE; DRUG CONFORMATION; DRUG POTENCY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IMMUNOREGULATION; LEUKOCYTE ACTIVATION; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

ANIMALS; BIOLOGICAL AVAILABILITY; HUMANS; IMMUNOSUPPRESSIVE AGENTS; ISOXAZOLES; LYMPHOCYTE ACTIVATION; LYMPHOCYTE CULTURE TEST, MIXED; PYRAZOLES; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; T-LYMPHOCYTES;

ANIMALIA; RODENTIA;

EID: 0032491222     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00501-0     Document Type: Article

References (33)

1. 1. Wahrenberger, A. Crit. Care Nurs. Q. 1995, 17, 27.
2. 2. Treleaven, J. G.; Barrett, A. J. Br. J. Hosp. Med. 1990, 43, 256.
3. 3. Rees, A. J.; Lockwood, C. M. Clinical Aspects of Immunology; Blackwell Scientific: Oxford, 1982; p 507.
4. 4. Schwartsmann, G.; van der Vijgh, W. J.; van Hennik, M. B.; Klein, I.; Vermorken, J. B.; Dodion, P.; ten Bokkel Huinink, W. W.; Joggi, G.; Gall, H.; Crespeigne, N.; et al. Eur. J. Cancer Clin. Oncol. 1989, 25, 1675.
5. 5. Noe, D. A.; Rowinsky, E. K.; Shen, H. S.; Clarke, B. V.; Grochow, L. B.; McGuire, W. B.; Hantel, A.; Adams, D. B.; Abeloff, M. D.; Ettinger, D. S. Cancer Res. 1990, 50, 4595.
6. 6. de Forni, M.; Chabot, G. G.; Armand, J. P.; Fontana, X.; Recondo, G.; Domenge, C.; Carde, P.; Barbu, M.; Gouyette, A. Eur. J. Cancer 1993, 29a, 983.
7. 7. Furst, D. E. Baillieres Clin. Rheumatol. 1995, 9, 711.
8. 8. Mladenovic, V.; Domljan, Z.; Rozman, B.; Jajic, I.; Mihajlovic, D.; Dordevic, J.; Popovic, M.; Dimitrijevic, M.; Zivkovic, M.; Campion, G.; Musikic, P.; Low-Friedrich, I.; Oed, C.; Seifert, H.; Strand, V. Arthritis & Rheumatism 1995, 38, 1595.
9. 9. Bartlett, R. R.; Dimitrijevic, M.; Mattar, T.; Zielinski, T.; Germann, T.; Rude, E.; Thoenes, G. H.; Kuchle, C.; Schorlemmer, H. U.; Bremer, E.; Finnegan, A.; Schleyerbach, R. Agents Actions 1991, 32, 10.
10. 10. A preliminary account of this work has been presented: Wang, A. X.; Xie, Q.; Lane, B.; Mollison, K. W.; Hsieh, G. C.; Marsh, K.; Sheets, M. P.; Luly, J. R.; Coghlan, M. J. Abstracts of papers, 212th National Meeting of the American Chemical Society ACS, Orlando, FL, 1996; Abstract MEDI 187.
11. 11. Doleschall, G.; Seres, P. J. Chem. Soc., Perkin Trans. 1988, 1, 1.
12. 12. Menozzi, G.; Mosti, L.; Schenone, P. J. Heterocycl. Chem. 1987, 24, 1669.
13. 13. Jackson, A. H.; Shannon, P. V. R.; Wilkins, D. J. J. Chem. Soc., Chem. Commun. 1987, 653.
14. 14. Beckwith, A. L. In The Sythesis of Amides; Zabicky, J. Ed.; J, Wiley & Sons: New York, 1968; pp 75-119.
15. 15. Castro, B.; Dormoy, J. R.; Evin, G.; Selve, C.; Loffet, A. Proc. 14th Eur. Pept. Symp. 1976, 79.
16. 16. Demers, J. P.; Klaubert, D. H. Tetrahedron Lett. 1987, 28, 4933.
17. 17. Guillerm, D.; Linstrumelle, G. Tetrahedron Lett. 1985, 26, 3811.
18. 18. Alternate routes to the 1-alkyl analogs involving N-alkylation of unsubstituted pyrazoles delivered separable mixtures of 3-and 5-methyl regioisomers.
19. 19. Kawai, M.; Lane, B. C.; Hsieh, G. C.; Mollison, K. W.; Carter, G. W.; Luly, J. R. FEBS Lett. 1993, 316, 107.
20. 20. In addition to the increased Cmax and AUC, pyrazole 1af demonstrated a 71% bioavailability in this rat study.
21. 21. Cherwinski, H. M.; McCarley, D.; Schatzman, R.; Devens, B.; Ransom, J. T. J. Pharmacol. Exp. Ther. 1995, 272, 460.
22. 22. Bartlett, R. R.; Dimitrijevic, M.; Mattar, T.; Zielinski, T.; Germann, T.; Rude, E.; Thoenes, G. H.; Kuchle, C. C.; Schorlemmer, H. U.; Bremer, E. Agents Actions 1991, 32, 10.
23. 23. Cao, W. W.; Kao, P. N.; Chao, A. C.; Gardner, P.; Ng, J.; Morris, R. E. J. Heart Lung Transplant. 1995, 14, 1016.
24. 24. Cherwinski, H. M.; Byars, N.; Ballaron, S. J.; Nakano, G. M.; Young, J. M.; Ransom, J. T. Inflamm. Res. 1995, 44, 317.
25. 25. Cherwinski, H. M.; Cohn, R. G.; Cheung, P.; Webster, D. J.; Xu, Y. Z.; Caulfield, J. P.; Young, J. M.; Nakano, G.; Ransom, J. T. J. Pharmacol. Exp. Ther . 1995, 275, 1043.
26. 26. Chong, A. S.; Rezai, K.; Gebel, H. M.; Finnegan, A.; Foster, P.; Xu, X.; Williams, J. W. Transplantation 1996, 61, 140.
27. 27. Davis, J. P.; Cain, G. A.; Pitts, W. J.; Magolda, R. L.; Copeland, R. A. Biochemistry 1996, 35, 1270.
28. 28. Greene, S.; Watanabe, K.; Braatz-Trulson, J.; Lou, L. Biochem. Pharmacol. 1995, 50, 861.
29. 29. Knecht, W.; Bergjohann, U.; Gonski, S.; Kirschbaum, B.; Loffler, M. Eur. J. Biochem. 1996, 240, 292.
30. 30. Xu, X.; Williams, J. W.; Gong, H.; Finnegan, A.; Chong, A. S. Biochem. Pharmacol. 1996, 52, 527.
31. 31. Shvo, Y.; Shanan-Atidi, H. J. Am. Chem. Soc. 1969, 91, 6689.
32. 32. Shvo, Y.; Shanan-Atidi, H. J. Am. Chem. Soc. 1969, 91, 6683.
33. 33. Compound 1a was also studied in several other well defined assays with established MOAs. Studies related to IL-2 synthesis by T cells, IL-2-induced T cell proliferation, B cell proliferation, leukotriene biosynthesis, and modulation of tyrosine kinase activity were undertaken yet compounds such as 1a show little activity in any of these experiments. Determination of the MOA of these pyrazoles remains an area of active interest.