Novel Carbohydrate Conjugates as Potential Prodrugs of Acyclovir

Abstract

Fifteen novel carbohydrate conjugates of desciclovir {2-[(2-amino-9 H-purin-9-yl]-methoxy]ethanol} were synthesized and evaluated as potential double prodrugs for acyclovir. The compounds were prepared by an acid-catalyzed reaction between reducing sugars and the 2-amino group of desciclovir. Spectral data indicated that the carbohydrate moieties in the products were predominately in the pyranose form. The suitability of each analogue as a double prodrug of acyclovir was evaluated by the urinary recovery of acyclovir from rats after oral dosing. The results showed that these highly water-soluble conjugates were poor prodrugs. Similar results were obtained with the glucose conjugate of acyclovir itself. A comparison of intraperitoneal vs. oral administration for six of the conjugates suggested that the unsuitability of these conjugates as prodrugs results from poor gastrointestinal absorption as well as inefficient metabolic removal of the carbohydrate moieties.