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Structural diversity of selective COX-2 inhibitors

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COX-2 Inhibitors

Part of the book series: Milestones in Drug Therapy MDT ((MDT))

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used agents in the treatment of pain and inflammation, especially rheumatoid arthritis [1]. The first NSAID aspirin was introduced over a century ago, and continues to be a popular over-the-counter medication in the treatment of the symptoms of pain and inflammation. The global production of aspirin is approximately 50,000 tons annually [2]. The pharmacological effects of NSAIDs arise from their inhibition of the prostaglandin synthase or cyclooxygenase (COX) isozymes [3]. COX isozymes catalyze the rate-limiting step in the arachidonic acid cascade involving the conversion of arachidonic acid to prostaglandin H2 (PGH2), the common biosynthetic precursor to prostaglandins and thromboxane (Fig. 1). These bioactive lipids mediate numerous physiological and pathophysiological effects, including pain, fever, inflammation, hemostasis, and regulation of renal function and maintenance of mucosal integrity in the stomach.

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  1. Department of Biochemistry, Vanderbilt Institute of Chemical Biology, Vanderbilt-Ingram Cancer Center, and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee, 37232-0146, USA

    Lawrence J. Marnett

  2. Pharmacokinetics, Dynamics and Metabolism Department, Pfizer Global Research and Development, Groton, CT, 06340, USA

    Amit S. Kalgutkar

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  1. Department of Pulmonary Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, D-88397, Biberach a. d. Riss, Germany

    Michel Pairet

  2. Department Drug Discovery Support, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, D-88397, Biberach a. d. Riss, Germany

    Joanne van Ryn

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Marnett, L.J., Kalgutkar, A.S. (2004). Structural diversity of selective COX-2 inhibitors. In: Pairet, M., van Ryn, J. (eds) COX-2 Inhibitors. Milestones in Drug Therapy MDT. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-7879-1_2

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