We report the application of the phosphoramidate ProTide approach, developed by us for antiviral nucleosides, to sugar derivatives with potential chondroprotection against osteoarthritis. In particular, N-acetylglucosamine was converted to a series of 06 arylaminoacyl phosphoramidates with ester and amino acid variation. Compounds were prepared by two routes, with or without sugar protection, and were isolated as phosphate diastereoisomers. The compounds were assayed for cellular toxicity and for inhibition of IL-1 induced glycosaminoglycan (GAG) release (i.e., proteoglycan degradation) from bovine articular cartilage in vitro explant cultures. By comparison to the N-acetyl glucosamine parent, some of the analogues show a significant enhancement in efficacy in the inhibition of inflammatory cytokine-induced proteoglycan degradation.