(D)-Glucosamine and other nutritional supplements have emerged as a safe and alternative therapy for osteoarthritis (OA), a chronic and degenerative articular joint disease. To improve the oral bioavailability of (D)-glucosamine we used the phosphoramidate ProTide approach, developed by us for antiviral nucleosides. In particular, N-acetylglucosamine was converted to a series of 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 release (i.e., proteoglycan degradation) from bovine and human articular cartilage in vitro explant cultures.

Novel phosphate prodrugs of N-acetyl-(D)-glucosamine for the treatment of osteoarthritis

243rd National Meeting (2012)

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