文摘
The important role of cyclooxygenase-2 (COX-2) in the pathogenesis of inflammation and side effectlimitations of current COX-2 inhibitor drugs illustrates a need for the design of new compounds based onalternative structural templates. We previously reported a set of substituted 1,5-diarylpyrrole derivatives,along with their inhibitory activity toward COX enzymes. Several compounds proved to be highly selectiveCOX-2 inhibitors and their affinity data were rationalized through docking simulations. In this paper, wedescribe the synthesis of new 1,5-diarylpyrrole derivatives that were assayed for their in vitro inhibitoryeffects toward COX isozymes. Among them, the ethyl-2-methyl-5-[4-(methylsulfonyl)phenyl]-1-[3-fluorophenyl]-1H-pyrrol-3-acetate (1d), which was the most potent and COX-2 selective compound, alsoshowed a very interesting in vivo anti-inflammatory and analgesic activity, laying the foundations fordeveloping new lead compounds that could be effective agents in the armamentarium for the managementof inflammation and pain.