Identification of 2-hydroxymethyl-4-[5-(4-methoxyphenyl)-3-trifluoromethyl-pyrazol-1-yl]-N-propionylbenzenesulfonamide sodium as a potential COX-2 inhibitor for oral and parenteral administration

Synthesis of prodrugs of orally active COX-2 inhibitor 3 involving sulfamoyl (SO2NH2) and hydroxymethyl (CH2OH) groups, and their biological evaluation are described. Of these prodrugs, the N-propionyl sulfonamide sodium 3k was found to be much superior to the parent compound 3 and other marketed COX-2 inhibitors in carrageenan induced rat paw edema model of inflammation due to highly elevated drug levels in systemic circulation. This prodrug has a potential both for oral as well as parenteral administration due to impressive analgesic activity, antipyretic potency, and extraordinary water solubility.

Synthesis and biological evaluation of the prodrugs of a potent COX-2 inhibitor of 1,5-diarylpyrazole class are described. Through this exercise, N-propionyl sulfonamide sodium 3k has been identified as a potential candidate for oral as well as parenteral administration.Figure optionsDownload as PowerPoint slide