Studies On Syntheses And Bioactivities Of N-Substituted Phenylbenzamides

Inflammation is a normal, essential and protective response to any noxious stimulus that may threaten the host and may vary from a localized reaction to a complex response involving the whole organism. The results of pharmacological studies showed that the mechanisms of many diseases were associated with inflammation. Therefore, the NSAIDs with high activity and low toxicity will play an important role in the field of drug research. The discovery of COX-2 led to the concepts that the constitutive COX-1 isoform tends to be homeostatic in function, while COX-2 is induced during inflammation and tends to facilitate the inflammatory response. On this basis, highly selective COX-2 inhibitors, especially diarylheterocyclic compounds, have been developed widely in recent years. Many new chemical entities with high anti-inflammatory activity have been reported abroad and some of them have been launched.Valdecoxib, a selective COX-2 inhibitor, was developed by Pharmacia Corp. and marketed in USA in 2002. In this paper, it was obtained by one synthetic method that was introduced on references and the reaction conditions were changed in order to improve the yield.Benzamide derivatives possess various bioactivities, such as anti-inflammatory and anti-allergic activities. In this paper, TV-substituted phenylbenzamides were designed on the basis of the structure of benzamides and the structure-activity relationship of COX-2 inhibitors withdiarylheterocyclic skeleton, and synthesized by several different synthetic ways. The chemical structures of the target compounds were characterized by means ofIR,1H-NMR and MS.Pharmacological results indicated that among the target compounds synthesized, DL-02, DL-06, DL-08, LYJ-01, LYJ-02, LYJ-04, LYJ-05, LYJ-07, LYJ-09, LYJ-11, LYJ-12 and LYJ-13 exhibited excellent inhibitory effect on xylene-induced ear edema in mice and DL-05, DL-07, LYJ-06 and LYJ-08 exerted the same bioactivity as ibuprofen.