4-hydroxy-2-methyl-N-(2-thiazole)-2H-1,2-benzothiazine-3-carboxamide-1, 1-dioxide (EX15) and its Cu(II) complex as new oxicam selective cyclooxygenase-2 inhibitors

Abstract

4-Hydroxy-2-methyl-N-(2-thiazole)-2H-1,2-benzothiazine-3-carboxamide-1, 1-dioxide (EX15) as nonsteroidal antiinflammatory drug (NSAIDs) of oxicam family has been synthesized bearing high selectivity for cyclooxygenase-2 (COX-2) inhibition and high ability to chelate with Cu(II) ions. The EX15- Cu(II) complex, and [Cu(EX15)(OAc)(H 2O) 2], were synthesized and characterized by using elemental analysis, spectral (UV-Vis, IR), conductance, thermal and magnetic studies. Two equations were predicted using quantitative structure activity relationship (QSAR) and regression analysis for the COX-2 and COX-1 selectivity (microsomal assay) with a regression correlation (R) close to unity. Two techniques were used to investigate the validity of these equations; macrophage cell line (in vitro) selectivity and collagenadjuvant arthritis model in rats (in vivo) which showed a significant antioxidant, analgesic and antirheumatic effect for 4-hydroxy-2-methyl-N-(2-thiazole)-2H-1,2-benzothiazine- 3-carboxamide-1,1- dioxide and its Cu(II) complex, [Cu(EX15)(OAc)(H 2O) 2].