Rofecoxib Analogues Possessing a Nitric Oxide Donor Sulfohydroxamic Acid (SO2NHOH) Cyclooxygenase-2 Pharmacophore: Synthesis, Molecular Modeling, and Biological Evaluation as Anti-inflammatory Agents



original image

Expertly tailored! The development of safe anti-inflammatory (AI) agents that are highly selective COX-2 inhibitors has been challenging, as indicated by the clinical withdrawal of rofecoxib, valdecoxib, and lumiracoxib. We report novel rofecoxib analogues with a sulfohydroxamic acid nitric oxide (NO) donor COX-2 pharmacophore that exhibit potent AI activity. The release of NO is expected to circumvent the contraindicated cardiovascular effects of rofecoxib.