| abstract |
The internally cyclized congeners of hydroxy-substituted nucleotide analogues have been found to exhibit substantially lower toxicity in vivo than their uncyclized analogues, while retaining essentially the same antiviral activity. This was unexpected because the prior art would have suggested that the cyclic analogues offered no significant advantages in respect to toxicity in vivo. This finding permits the administration of much greater doses of the cyclic congeners than otherwise would have been possible and/or allows the clinician to omit toxicity ameliorating interventions. Novel compounds are provided for use in the method of this invention. Novel methods for the preparation of these compounds also are provided. |