1. Monocyclic L-nucleosides with type 1 cytokine-inducing activity.
- Author
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Ramasamy KS, Tam RC, Bard J, and Averett DR
- Subjects
- Adjuvants, Immunologic chemistry, Adjuvants, Immunologic pharmacology, Antiviral Agents chemistry, Antiviral Agents pharmacology, Enzyme-Linked Immunosorbent Assay, Humans, In Vitro Techniques, Interferon-gamma metabolism, Interleukin-2 metabolism, Nucleosides chemistry, Nucleosides pharmacology, Ribavirin chemistry, Ribavirin pharmacology, Stereoisomerism, Structure-Activity Relationship, T-Lymphocytes drug effects, T-Lymphocytes metabolism, Tumor Necrosis Factor-alpha metabolism, Adjuvants, Immunologic chemical synthesis, Cytokines metabolism, Nucleosides chemical synthesis, Ribavirin chemical synthesis
- Abstract
A series of 1,2,4-triazole L-nucleosides were synthesized and evaluated for their ability to stimulate type 1 cytokine production by activated human T cells in direct comparison to the known active agent ribavirin. Among the compounds prepared, 1-beta-L-ribofuranosyl-1,2,4-triazole-3-carboxamide (5, ICN 17261) was found to be the most uniformly potent compound. Conversion of the 3-carboxamide group of 5 to a carboxamidine functionality resulted in 1-beta-L-ribofuranosyl-1,2,4-triazole-3-carboxamidine hydrochloride (10), which induced cytokine levels comparable to 5 for two of the three type 1 cytokines examined. Modification of the carbohydrate moiety of 5 provided compounds of reduced activity. Significantly, ICN 17261 offers interesting immunomodulatory potential for the treatment of diseases where type 1 cytokines play an important role.
- Published
- 2000
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