NOVEL CARBOHYDRATE CONJUGATES AS POTENTIAL PRODRUGS OF ACYCLOVIR

Fifteen novel carbohydrate conjugates of desciclovir (2-[(2-amino-9H-p urin-9-yl]-methoxy]ethanol) were synthesized and evaluated as potentia l double prodrugs for acyclovir. The compounds were prepared by an aci d-catalyzed reaction between reducing sugars and the P-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 th e urinary recovery of acyclovir from rats after oral dosing. The resul ts showed that these highly water-soluble conjugates were poor prodrug s. Similar results were obtained with the glucose conjugate of acyclov ir itself. A comparison of intraperitoneal vs. oral administration for six of the conjugates suggested that the unsuitability of these conju gates as prodrugs results from poor gastrointestinal absorption as wel l as inefficient metabolic removal of the carbohydrate moieties.