Synthesis and pharmacological evaluation of poly(oxyethylene) derivatives of 4-isobutylphenyl-2-propionic acid (ibuprofen)

Abstract

[4-Isobutylphenyl-2-propionic acid (ibuprofen) is a well-known antiinflammatory drug, widely used in therapy.] The synthesis of 3 oligomeric derivatives of ibuprofen, namely, the monoester of tetraethylene glycol (I) and the diesters of poly(oxyethylene) samples having MW of 1000 (.+-. 50) and 2000 (.+-. 150) (II and III), was performed via the imidazolide method. The antiinflammatory activity of I-III, and of equivalent amounts of free drug, was determined in the carrageenan-induced rat paw edema assay at different times after oral administration and was considerably prolonged in the case of the 3 derivatives. The lowest MW derivative (I) had an enhanced initial activity with regard to ibuprofen. These results were confirmed by measuring the plasma levels of ibuprofen in rats at different times after oral administration.