Monocyclic L-nucleosides with type 1 cytokine-inducing activity

Journal of Medicinal Chemistry

Volumn 43, Issue 5, 2000, Pages 1019-1028

  Ramasamy, Kanda S ^a   Tam, Robert C ^a   Bard, Josie ^a   Averett, Devron R ^b,c  

^a Department of Chemistry ^*  (United States)

^b Valeant Pharmaceuticals International   (United States)

^c Averett Consulting   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,2,4 TRIAZOLE DERIVATIVE; GAMMA INTERFERON; INTERLEUKIN 2; NUCLEOSIDE DERIVATIVE; RIBAVIRIN; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ARTICLE; CYTOKINE PRODUCTION; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IMMUNOMODULATION; STRUCTURE ACTIVITY RELATION; T LYMPHOCYTE ACTIVATION;

ADJUVANTS, IMMUNOLOGIC; ANTIVIRAL AGENTS; CYTOKINES; ENZYME-LINKED IMMUNOSORBENT ASSAY; HUMANS; INTERFERON TYPE II; INTERLEUKIN-2; NUCLEOSIDES; RIBAVIRIN; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; T-LYMPHOCYTES; TUMOR NECROSIS FACTOR-ALPHA;

EID: 0034624723     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9905514     Document Type: Article

References (44)

1. (a) Aulitzky, W. E.; Huber, C.; Peschel, C. Cytokine therapy of neoplastic and inflammatory disease. Int. Arch. Allergy Immunol. 1993, 101, 221-226.
2. (b) Kroemer, G.; Hirsch, F.; Gonzalez-Garcia, A.; Martinez, C. Differential involvement of Th1 and Th2 cytokines in autoimmune diseases. Autoimmunity 1996, 24, 25-33.
3. Simon, A. K.; Seipelt, E.; Sieper, J. Divergent T-cell cytokine patterns in inflammatory arthritis. Proc. Natl. Acad. Sci. U.S.A. 1994, 30, 8562-8566.
4. Mosmann, T. R.; Coffman, R. L. Th1 and Th2 Cells: Different Patterns of Lymphokine Secretion Lead to Different Functional Properties. Annu. Rev. Immunol. 1989, 7, 145-173.
5. Dubey, C.; Bellon, B.; Druet, P. Th1 and Th2 Dependent Cytokines in Experimental Autoimmunity and Immune Reactions Induce by Chemicals. Eur. Cytokine Network 1991, 2, 147-152.
6. Beraud, E.; Lorberboun-Galski, H.; Chan, C. C.; FitzGerald, D.; Pastan, I.; Nussenblatt, R. B. Immunospecific suppression of encephalitogenic-activated T lymphocytes by chimeric cytotoxin IL-2-PE40. Cell Immunol. 1991, 133, 379-389.
7. Hahn, H. J.; Gerdes, J.; Lucke, S.; Liepe, L.; Kauert, C.; Volk, H. D.; Wacker, H. H.; Brocke, S.; Stein, H.; Diamantstein, T. Phenotypical characterization of the cells invading pancreatic islets of diabetic BB/OK rats: Effect of interleukin 2 receptor-targeted immunotherapy. Eur. J. Immunol. 1988, 18, 2037-2042.
8. Kapsenberg, M. L.; Wierenga, E. A.; Bos, J. D.; Jansen, H. M. Functional subsets of allergen-reactive human CD4+ T cells. Immunol. Today 1991, 12, 392-395.
9. (a) Walker, C.; Bode, E.; Boer, L.; Hansel, T. T.; Blaser, K.; Virchow, J. C., Jr. Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage. Am. Rev. Respir. Dis. 1992, 146, 109-115.
10. (b) van der Heijden, F. L.; Wierenga, E. A.; Bos, J. D.; Kapsenberg, M. L. High frequency of IL-4-producing CD4+ allergen-specific T lymphocytes in atopic dermatitis lesional skin. J. Invest. Dermatol. 1991, 97, 389-394.
11. Finkelman, F. D.; Pearce, E. J.; Urban, J. F., Jr.; Sher, A. Regulation and biological function of helminth-induced cytokine responses. Immunol. Today 1991, 12, A62-66.
12. Caceres-Dittmar. G.; Tapia, F. J.; Sanchez, M. A.; Yamamura, M.; Uyemura, K.; Modlin, R. L.; Bloom, B. R.; Convit, J. Determination of the cytokine profile in American cutaneous leishmaniasis using the polymerase chain reaction. Clin. Exp. Immunol. 1993, 91, 500-505.
13. Del Prete, G.; Tiri, A.; Maggi, E.; De Carli, M.; Macchia, D.; Parronchi, P.; Rossi, M. E.; Pietrogrande, M. C.; Ricci, M.; Romagnani, S. Defective in vitro production of gamma-interferon and tumor necrosis factor-alpha by circulating T cells from patents with the hyper-immunoglobulin E syndrome. J. Clin. Invest. 1989, 84, 1830-1835.
14. Schandene, L.; Ferster, A.; Mascart-Lemone, F.; Crusiaux, A.; Gerard, C.; Marchant, A.; Lybin, M.; Velu, T.; Sariban, E.; Goldman, M. T helper type 2-like cells and therapeutic effects of interferon-gamma in combined immunodeficiency with hypereosinophilia (Omenn's syndrome). Eur. J. Immunol. 1993, 23, 56-60.
15. + cell response against human immunodeficiency virus: Implications for long-term survival. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 11135-11139.
16. Hall, C. B.; McBride, J. T.; Walsh, E. E.; Bell, D. M.; Gala, C. L.; Hildreth, S.; Ten Eyck, L. G.; W. J. Hall. Aerosolized ribavirin treatment of infants with respiratory syncytial viral infection. N. Engl. J Med. 1983, 308, 1443-1447.
17. Reichard, O.; Norkrans, G.; Fryden, A.; Braconier, J.-H.; Sonnerborg, A.; Weiland, O. Randomized, double blind, placebo controlled trial of interferon alpha 2B with and without ribavirin for chronic hepatitis C. Lancet 1998, 351, 83-87.
18. Hultgren, C.; Milich, D. R.; Weiland, O.; Sällberg, M. The antiviral compound ribavirin modulates the T helper (Th)1/Th2 subset balance in hepatitis B and C virus-specific immune responses. J. Gen. Virol. 1998, 79, 2381-2391.
19. Ning, Q.; Brown, D.; Parodo, J.; Cattral, M.; Fung, L.; Gorczynski, R.; Cole, E., Fung, L.; Ding, J. W.; Liu, M. F.; Rotstein, O.; Phillips, M. J.; Levy, G. Ribavirin inhibits viral-induced macrophage production of tumor necrosis factor, interleukin-1, procoagulant activity fg12 prothrombinase and preserves Th1 cytokine production but inhibits Th2 cytokine response. J. Immunol. 1998, 160, 3487-3493.
20. Martin, M. J.; Navas, S.; Quiroga, J. A.; Pardo, M.; Carreno, V. Effects of the ribavirin-interferon alpha combination on cultured peripheral blood mononuclear cells from chronic hepatitis C patients. Cytokine 1998, 79, 2381-2391.
21. Tam, R. C.; Pai, B.; Bard, J.; Lim, C.; Averett, D. R.; Phan, U. T.; Milovanovic, T. Ribavirin polarizes human T cell responses towards a Type 1 cytokine profile. J. Hepatol. 1999, 30, 376-382.
22. Tam, R. C.; Lim, C.; Bard, J.; Pai, B. Contact hypersensitivity responses following ribavirin treatment in vivo are influenced by Type 1 cytokine polarization, regulation of IL-10 expression and costimulatory signaling. J Immunol. 1999, 163, 3709-3717.
23. Wilson, J. E.; Martin, J. L.; Borroto-Esoda, K.; Hopkins, S.; Painter, G.; Liotta, D. C.; Furman, P. A. The 5-triphosphates of the (-) and (+) enantiomers of cis-5-fluoro-1-[2-hydroxymethyl)-1,3-oxathiolane-5-yl cytosine equally inhibit human immunodeficiency virus type 1 reverse transcriptase. Antimicrob. Agents Chemother. 1993, 37, 1720-1722.
24. Skalski, V.; Chang, C. N.; Dutschman, G.; Cheng, Y. C. The biochemical basis for the differential anti-human immunodeficiency virus activity of two cis enantiomers of 2',3'-dideoxy-3'-thiacytidine. J. Biol. Chem. 1993, 268, 23234-23238.
25. (a) Zhu, Y. L.; Dutschman, D. E.; Liu, S. H.; Bridges, E. G.; Cheng, Y. C. Anti-hepatitis B virus and metabolism of 2',3'-dideoxy-2',3'-dihydro-beta-L(-)-5-fluorocytidine. J. Biol. Chem. 1993, 268, 23234-23238.
26. (b) Furman, P. A.; Davis, M.; Liotta, D. C.; Paff, M.; Frick, L.; Nelson, D.; Dornsife, R.; Wurster, J. A.; Wilson, L. J.; Fyfe, J.; Tuttle, J.; Condreay, L.; Averett, D. R.; Schinazi, R.; Painter, G. The Anti-Hepatitis B Virus Activity, Cytotoxicity, and Anabolic Profile of the (-) and (+) Enantiomers of Cis-5-fluoro-1-{2-(hydroxymethyl)-1,3-oxythiolane-5-yl}cytosine. Antimicrob. Agents Chemother. 1992, 36, 2686-2692.
27. (c) Paff, M. T.; Averett, D. R.; Prus, K. L.; Nelson, D. J. Intracellular Metabolism of (-) and (+) Cis-5-fluoro-1-{2-(hydroxymethyl)-1,3-oxathiolane-5-yl}cytosine in HepG2(2.2.15/P5A) Cells. Antimicrob. Agents Chemother. 1994, 38, 1230-1238.
28. (d) Van Draanen, N. A.; Tisdale, M.; Parry, M.; Jansen, R.; Dornsife, R.; Tuttle, J. V.; Averett, D. R.; Koszalka, G. W. The Influence of Stereochemistry on the Antiviral Activities and Resistance Profiles of Dideoxycytidine Nucleosides. Antimicrob. Agents Chemother. 1994, 38, 868-871.
29. (e) Pelicano, H.; Pierra, C.; Ericksson, S.; Gosselin, G.; Imbach, J. L.; Maury, G. J. Med. Chem. 1997, 40, 3969-7393.
30. (f) Miller, W. H.; Daluge, S. M.; Garvey, E. P.; Hopkins, S.; Reardon, J. E.; Boyd, F. L.; Miller, R. L. J. Biol. Chem. 1992, 267, 21220-21224.
31. Guthrie, R. D.; Smith, S. C. An Improved Preparation of 1,2,3,5-Tetra-O-acetyl-β-D-ribofuranose. Chem. Ind. 1968, 547-548.
32. Chipen, G. I.; Grinshtein, V. Ya. Chem. Heterocycl. Compd. (USSR) 1965, 1, 420.
33. Witkowski, J. T.; Robins, R. K.; Sidwell, R. W.; Simon, L. N. Design, Synthesis, and Broad Spectrum Antiviral Activity of 1-β-D-ribofuranosyl-1,2,4-triaole-3-carboxamide and Related Nucleosides. J. Med. Chem. 1972, 15, 1150-1154.
34. Markiewicz, W. T. Tetraisopropyldisiloxane-1,3-diyl, a group for simultaneous protection of 3'- and 5'-hydroxy functions of nucleosides. J. Chem. Res. (S) 1979, 24-25.
35. (a) Barton, D. H. R.; McCombie, S. W. A New Method for the Deoxygenation of Secondary Alcohols. J. Chem. Soc., Perkin Trans. 1 1975, 1574-1585.
36. (b) Barton, D. H. R.; Subramanian, R. Reactions of Relevance to the Chemistry of Aminoglycoside Antibiotics. Part 7. Conversion of Thiocarbonates into Deoxysugars. J. Chem. Soc., Perkin Trans. 1 1977, 1718-1723.
37. Gosselin, G.; Bergogne, M.-C.; Imbach, J.-L. Synthesis and Antiviral Evaluation of β-L-Xylo-furanosyl Nucleosides of the Five Naturally Occurring Nucleic Acid Bases. J. Heterocycl. Chem. 1993, 30, 1229-1233.
38. Gosselin, G.; Mathé, C.; Bergogne, M.-C.; Aubertin, A.-M.; Kirn, A.; Sommadossi, J.-P.; Schinazi, R.; Imbach, J.-L. 2'- And/Or 3'-Deoxy-β-L-Pentofuranosyl Nucleoside Derivatives: Stereospecific Synthesis and Antiviral Activities. Nucleosides Nucleotides 1995, 14, 611-617.
39. Ma, T.; Pai, S. B.; Zhu, Y. L.; Lin, J. S.; Shanmuganathan, K.; Du, J.; Wang, C.; Kim, H.; Newton, M. G.; Cheng, Y. C.; Chu, C. K. Structure-Activity Relationships of 1-(2-Deoxy-2-fluoro-β-L-arabinofuranosyl)pyrimidine Nucleosides as Anti-Hepatitis B Virus Agents. J. Med. Chem. 1996, 39, 2835-2843.
40. (a) Misra, S.; Jain, S.; Avasthi, K.; Bhakuni, D. S. Studies on Nucleosides: Part XXVIII. Synthesis of 4-Amino (or Hydroxy)-6-methylthio-1-(3'-Deoxy-β-D-ribofuranosyl)-1-H-Pyrazolo[3,4-d] pyrimidines. Nucleosides Nucleotides 1990, 9, 837-846.
41. (b) Nair, V.; Sinhababu, A. K. Selective Transformations of Sugar Tosylhydrazones to Deoxy and Unsaturated Sugars. J. Org. Chem. 1978, 43, 5013-5017.
42. Vorbrüggen, H. Adventures in Silicon-Organic Chemistry. Acc. Chem. Res. 1995, 28, 509-520.
43. Witkowski, J. T.; Fuertes, M.; Cook, P. D.; Robins, R. K. Nucleosides of 1,2,4-Triazole-3-carboxamide: Synthesis of Certain Pentofuranosyl, Deoxypentofuranosyl and Pentopyranosyl 1,2,4-Triazoles. J. Carbohydr. Nucleosides Nucleotides 1975, 2, 1-36.
44. Tam, R. C.; Ramasamy, K. S.; Bard, J.; Pai, B.; Lim, C.; Averett, D. R. The ribavirin analogue ICN 17261 demonstrates reduced toxicity and antiviral effects with retention of both immunomodulatory activity and reduction of hepatitis-induced serum alanine aminotransferase levels. Antimicrob. Agents Chemother. 1999, submitted for publication.