The Search for Anti-Inflammatory Drugs

Perspectives on Anti-Inflammatory Drugs Inflammation is a very complicated process of interrelated events and cas­ cades that does not allow for an easily defined, focused attack for drug discovery. It is evident from years of research and development that certain classes of compounds (e.g., NSAIDs, steroids, and so on) have had a meas­ ure of success in alleviating pain and even dampening cellularlhormonal mechanisms involved in the process. Clear, mechanism-related therapies (e.g., for arthritis) and targeted drugs (e.g., for transplantation) have not been available in the past and, in reality, research in inflammation has re­ lied on more phenomenological approaches for resolving symptoms or on blatant cytoreductive approaches in cases like organ transplantation. In the last decade, approaches that have revealed novel cellular pathways in which intervention is possible for lymphocyte regulation (for example, cyclosporine and FK506) and small molecular weight mediators (e.g., leu­ kotriene inhibitors) are now either standard therapy or will be in a short time. These latter approaches have been the result of research from the 1970s up to the present.

Inhalt
1 The Discovery of Drugs to Treat Arthritis: A Historical View.- 2 The History of the Discovery and Development of Cyclosporine (Sandimmune®).- 3 Discovery and Development of FK506 (Tacrolimus), A Potent Immunosuppressant of Microbial Origin.- 4 Discovery of Sulindac, a Reversible Prodrug, as a Second-Generation Indomethacin.- 5 The Discovery of Zileuton (Leutrol®).- 6 Discovery of Accolate(TM) (ICI 204,219), a Peptide Leukotriene Antagonist for Asthma.- 7 Discovery of ZD2138, a Potent, Selective, Well-Tolerated, Nonredox Inhibitor of the Enzyme 5-Lipoxygenase.- 8 Development of MK 0591: An Orally Active Leukotriene Biosynthesis Inhibitor with a Novel Mechanism of Action.- 9 Discovery of BIRM 270: A New Class of Leukotriene Biosynthesis Inhibitors.- 10 Discovery and Development of the Immunomodulatory Azaspiranes.- Keyword Index.

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