TITLE:
Synthesis and Evaluation of Glyceride Prodrugs of Naproxen
AUTHORS:
Vivekkumar K. Redasani, Sanjay B. Bari
KEYWORDS:
Naproxen; Glyceride Prodrugs; Anti-Inflammatory; Analgesic; Gastroprotective; Hydrolysis Kinetics
JOURNAL NAME:
Open Journal of Medicinal Chemistry,
Vol.3 No.3,
September
20,
2013
ABSTRACT:
The glyceride ester derivatives 6a and 6b were prepared by reacting 1,2,3-trihydroxy
propane 1,3-dipalmitate/stearate with (S)-naproxen as potential
prodrugs. The synthesis was achieved successfully with the aid of N,N’-dicyclohexyl- carbodiimide.
These prodrugs were evaluated for anti inflammatory, analgesic and gastroprotective
activity. It was found that prodrugs 6a and 6b showed less irritation
to gastric mucosa as indicated by ulcer index. The synthesized glyceride esters were found to possess good pharmacological profile as shown by results of
anti inflammatory and analgesic activity. The aqueous studies were performed in
order to ensure the release of prodrugs. Both prodrugs were found to stable at
acidic pH while undergoes hydrolysis at pH 7.4. These findings suggest that the
glyceride prodrugs 6a and 6b might be used as potential biolabile derivatives.