Design and Synthesis of 1,4-Diazepines as Selective Cox-II Inhibitors

The NSAIDs have known to cause serious problems such as gastric ulceration, bleeding and renal disorders on long term medication. These severe side effects are partially due to their nonselectivity towards to COX-2 enzyme. Hence, newer, selective COX-2 enzyme inhibitors have been developed to overcome the toxicity problems. Recently, Rofecoxib and Celecoxib were withdrawn due to cardiac toxicity.1,2-disubstituted five-membered heterocyclic compounds have shown selectivity towards COX-2 inhibition. But, the toxicity reports of drugs like Rofecoxib and Celecoxib in this category prompted us to synthesize 1,2-diaryl diazepines (E) and their derivatives as, survey of literature indicated the diazepine heterocyclic system to have anti-inflammatory activity.