Chapter 19. Selective Cyclooxygenase Inhibitors

Publisher Summary Cyclooxygenase (COX) catalyzes the rate-limiting initial step in the biosynthesis of prostaglandins (PGs) from arachidonic acid. Like aspirin, the nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the COX enzyme, accounting for the anti-inflammatory and analgesic activity observed with these drugs in vivo . The significant advances made in the recent years in the discovery of selective cyclooxygenase inhibitors have been impressive. The current availability of human recombinant COX-1 and COX-2 assays used in determining enzyme selectivity has facilitated the discovery and development of selective COX-2 inhibitors as therapeutic agents for the treatment of inflammation. With the recent discovery of an inducible cyclooxygenase (COX-2), which appears associated with inflammation, the pharmaceutical industry now possesses a novel target for designing the therapeutic agents that could provide suitable anti-inflammatory and analgesic activity with greatly reduced gastrointestinal (GI) or renal toxicity. The identification of a second COX-2 enzyme that is induced in inflammatory cells and tissues made it possible to hypothesize that selective inhibition of COX-2 would yield anti-inflammatory activity without inhibiting vital COX-l-mediated PG formation in the gut or kidney. This chapter describes only cyclooxygenase inhibitors whose selectivity is documented by supporting COX-1 and COX-2 enzyme data.