4,5-Diaryl-2,2-Dimethyl-3(2Η)Furanone Derivatives as COX-2 Inhibitors-Next Generation Anti-Arthritis Candidate-

Inflammation is an outcome or an end effect of disruption of complex immunological balance. A variety of approaches to control immunological unbalance have been tried, and some of them are in practice in the clinic. Since inflammatory disorders are reflection of very complex immunological responses, it should be difficult to have such disorders under complete control. Thus, most of the drugs, being marketed and under development, possess some degrees of undesired side offsets originating from disruption of immunological balance. Steroids are excellent drugs suppressing inflammation in short term, however, long-term use of steroids would incur a serious side effect of "rebound". Another example is TNF-${\alpha}$-neutralizing agents, such as enbrel and infliximab. TNF-${\alpha}$ has been known to play a key role in the exacerbation of inflammation, and knock-out of TNF-${\alpha}$ is regarded essential to control of chronic inflammation. The TNF-${\alpha}$-neutralizing drugs in the market are regarded very efficient in the management of rheumatoid arthritis. Upon long term use, however, those drugs cause sepsis to a certain proportion of patients. It is ironical that a high plasma level of TNF-${\alpha}$ is known to be responsible for sepsis, and that the drugs scavenging TNF-${\alpha}$ cause sepsis. The above two examples illustrate well the difficulty of discovering an anti-inflammatory drug without unwanted immunological side effects. An anti-inflammatory drug would make a case in the market, as long as the drug has huge therapeutic benefits compared to its expected but unwanted immunological side effects, where cyclooxygenase-2 inhibitors are positioning. In this presentation, will be discussed general aspects of cyclooxygenase-2 inhibition in conjunction with 3(2Η)furanone derivatives, a novel class of COX-2 inhibitors.