The Synthesis Of Non-steroidal Anti-inflammatory Drugs(NSAIDs) Of Oxicam Derivatives

Inflammatory is a very common disease.According to the reports,about one hundred million people in the word are taking orally non-steroidal anti-inflammatory drugs.There are more than 50 percentage people are elderly person,non-steroidal anti-inflammatory drugs in clinical medicine is second to anti-infective drugs.Throughout the development history of non-steroidal anti-inflammatory drugs,since aspirin appeared in 1898,there appeared the bute,indomethacin,ibupropen and other non-steroidal anti-inflammatory drugs.Those drugs are strong acid,easy to caused the side effect,such as indigestion,stomach pain,ulcers,bleeding and perforation,etc.Until the Meloxicam appeared in 1980 s,these side effects of non-steroidal anti-inflammatory drugs have been relieved.Later,the Cox-2 inhibitor Rofecoxib appeared in 1890,however,due to the event of Wan Luo,the safety of these drugs is worth testing.Hence,Oxicam is still palys an important role in the field of anti-inflammatory.Oxicam is a kind of non-steroidal anti-inflammatory drugs and has important implication in clinic medicine.It’s always been a hotspot and difficulty about Oxicam’s synthetic in the fields of medicine and chemistry.There are a lot of methods to synthetic the Oxicam drugs.But most of pathway are need hash reaction conditions,the reagents are not only expensive but also toxicity and unfriendly to environment,besides,the yield is very low.Hence,we carried out a new method to synthetic the Oxicam derivatives.On the one hand,benzo[d]isothiazol-3(2H)-ones were synthetic in a novel method by us,we could use the benzo[d]isothiazol-3(2H)-ones to synthetic Oxicam key chemical intermediate within three steps.On the other hand,after we research the structure – activity relationship of Oxicam,we plans to synthetic 1,3-benzothiazin-4-ones in principle of bioisosteric groups to obtained more Oxicam derivatives.Under the guidance of the above ideas,we developed the novel way to synthetic benzo[d]isothiazol-3(2H)-ones and 1,3-benzothiazin-4-ones.Specifically,we used the potassium bromide as catalyst,oxygen as oxidant,to obtained the benzo[d]isothiazol-3(2H)-ones.What’s more,we used the tripotassium phosphate as base to obtained the 1,3-benzothiazin-4-ones by double 1,4-addition reaction.These two methods are low cost,low toxicity,high yield and environment friendly.It will provide a totally new thought to synthetic the Oxicam derivatives.