Nimesulide Based 1,2,4,5-Tetra Substituted Imidazole Derivative: Synthesis and Characterisation

Nimesulide a preferential ‘‘cyclooxygenase-2 inhibitor’’ is one of the well-known non-steroidal anti-inflammatory drugs that has been utilized to treat pain and other inflammatory diseases. Nimesulide was withdrawn from the market due to its hepatotoxicity which could be due to the presence of nitro group. Imidazoles represent an important class of bioactive molecules that shows a wide range of pharmacological activities besides anti-inflammatory activity. In our strategy to develop safer and potential anti-inflammatory molecules, we have decided to combine some of the structural features of nimesulide and imidazole in a single molecule. We have described the design and synthesis of nimesulide based 1,2,4,5-tetra substituted imidazole of potential biological significance via chemical modifications of a commonly used anti-inflammatory agent nimesulide. This derivative was prepared from nimesulide via a two-step process involving regio selective reduction of nimesulide followed by hetero cyclisation of reduced nimesulide in very 81 % yield. The title compound nimesulide based 1,2,4,5-tetra substituted imidazole was synthesized in very good yield by reaction of benzil, benzaldehyde, ammonium acetate, and N-(4-amino-2-phenoxy phenyl) methane sulphonamide in acetic acid using multi-component strategy and molecular modification. The structure of the synthesized compound was confirmed by IR and H1 NMR spectral analysis.