Design, synthesis and biological testing of a novel series of anti-inflammatory drugs

Many of the non-steroidal anti-inflammatory drugs (NSAIDs) currently market ed produce severe gastro-toxic side effects. The benefits of producing NSAI Ds without these side effects are obvious, particularly for patients requir ing long-term therapy. The aim of this investigation was to produce novel N SAIDs, based on paracetamol, that exhibit little or no gastro-toxicity. The work covers design, synthesis and testing of 13 drug candidates. The analg esic and antiinflammatory potencies of the drug candidates were measured us ing the mouse abdominal constriction assay and the carrageenan-induced rat paw oedema assay, respectively. The stomachs of the rats were examined post -mortem, to assess the gastro-toxicity of the drugs. Of the 13 compounds de scribed herein, 11 were shown to possess analgesic activity at 2-10 times t he potency of aspirin, while 8 demonstrated anti-inflammatory activity at 3 -10 times the potency of aspirin. Significantly, all of the compounds showe d very low gastro-toxicity when compared with aspirin. The results of this study indicate that it is possible to develop novel, potent NSAIDs based on the structure of paracetamol. These compounds have the advantage of demons trating much lower gastro-toxicity than NSAIDs currently available. Drugs o f this type may, in future, provide effective treatments for inflammatory d isorders.