Non-steroidal anti-inflammatory agents. Part 23. Synthesis and Pharmacological Activity of Enaminones which inhibit both bovine cyclooxygenase and 5-lipoxygenase

The synthesis and stereochemical characteristics of pyrrolidino-, isoquinolino- and indolo-enaminones 2–11 are reported. The inhibition of cyclooxygenase was determined in a bovine thrombocyte intact cell assay and that of 5-lipoxygenase using intact bovine polymorphonuclear leucocytes. Except compound 2c′ which is a well-balanced dual inhibitor of both enzymes, all other enaminone derivatives are weak inhibitors of both cyclooxygenase and 5-lipoxygenase. Structure-activity relationships of the enaminones in relation to known anti-inflammatory drugs are discussed.