Monocyclic L-nucleosides with type 1 cytokine-inducing activity

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 i n 1-beta-ribofuranosyl-1,2,4-triazole-3-carboxamidine hydrochloride(10), wh ich induced cytokine levels comparable to 5 for two of the three type 1 cyt okines examined. Modification of the carbohydrate moiety of 5 provided comp ounds of reduced activity. Significantly, ICN 17261 offers interesting immu nomodulatory potential for the treatment of diseases where type 1 cytokines play an important role.