The pharmaceutical activity of a drug is often limited by its physical and chemical properties. Although occasionaly some drugs are found to hvae new biological activities after their introduction into the market, the derivatization of known drugs allows for potentially greater effects on selectivity and biological actiivity. These deriviatives can also affect biological targets that the original drug did not affect. Celecoxib, a cyclooxygenase-2 inhibitor (COX-2) prescribed under the name Celebrex, is a nonsteroidal ani-inflammatory drug (NSAID) that is used for treating inflammation and acute pain. It has also been recently found to have some anticancer activity. Celecoxib contains a sulfonamide group that is para with respect to the pryazole ring in the core of the molecule. At this time, no derivatives of celecoxib possessing a sulfonamide group in the ortho position have been prepared, though many other strucutral analogues have been reported. The synthesis of these ortho-sulfonamide derivatives begins with the preparation of various substituted diketones via a Claisen condensation with substituted ketones and ethyl trifluoroacetate. Separately, an ortho-sulfonamide phenolhydrazine is prepared from commercially available starting materials as its hydrochloride salt. This substituted phenylhydrazine is then condensed and cyclized with the various diketones to prepare ortho-sulfonamide analogues of celecoxib. By using a variety of substituted ketones in the synthesis, a diverse library of ortho-sulfonamide analogues of celecoxib have been prepared and characterized.

Synthesis of ortho-sulfonamide analogues of the COX-2 inhibitor celecoxib

2019 Spring National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.