Recently reported inhibitors of cyclooxygenase-2

Cyclooxygenase inhibitors exert their effect by preventing the conversion of arachidonic acid (AA) to prostaglandins (PGs), a primary class of mediators of inflammation. Recently, a second isoform of cyclooxygenase, now known as cyclooxygenase-2 (COX-2), has been discovered which is produced in response to inflammatory stimuli. Selective COX-2 inhibitors have been demonstrated to be anti-inflammatory and analgesic without causing the gastrointestinal damage associated with current non-selective cyclooxygenase inhibitors. Mechanistically, selective COX-2 inhibitors decrease inflammation by preventing 'overproduction' of PGs while allowing COX-1 to produce the basal levels of PGs necessary for the health of certain tissues (e.g., the gastrointestinal tract). The realisation that the serious side-effect profile can be markedly reduced has led the pharmaceutical industry to expend much effort to discover novel selective COX-2 inhibitors for the worldwide market (estimated to be about US$5 bn). Many chemical classes of compounds have been developed, some of which are currently in clinical trials. This review will cover the patent literature over the past 15 months.