The Search for Anti-Inflammatory Drugs : Case Histories From Concept to Clinic

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. Front Matter....Pages i-x The Discovery of Drugs to Treat Arthritis: A Historical View....Pages 1-26 The History of the Discovery and Development of Cyclosporine (Sandimmune®)....Pages 27-63 Discovery and Development of FK506 (Tacrolimus), A Potent Immunosuppressant of Microbial Origin....Pages 65-104 Discovery of Sulindac, a Reversible Prodrug, as a Second-Generation Indomethacin....Pages 105-128 The Discovery of Zileuton (Leutrol®)....Pages 129-160 Discovery of Accolate TM (ICI 204,219), a Peptide Leukotriene Antagonist for Asthma....Pages 161-189 Discovery of ZD2138, a Potent, Selective, Well-Tolerated, Nonredox Inhibitor of the Enzyme 5-Lipoxygenase....Pages 191-231 Development of MK 0591: An Orally Active Leukotriene Biosynthesis Inhibitor with a Novel Mechanism of Action....Pages 233-251 Discovery of BIRM 270: A New Class of Leukotriene Biosynthesis Inhibitors....Pages 253-274 Discovery and Development of the Immunomodulatory Azaspiranes....Pages 275-301 Back Matter....Pages 303-304 This book will be a valuable asset for a medical or university library, as well as for researchers and clinicians. It will make an enticing reading for non-specialists interested in the history behind modern pharmacology, and can be used as a textbook in graduate courses.

The book contains black-and-white illustrations.

This work provides a background on how some of the current anti-inflammatory drugs were discovered and some of the problems and highlights that took place in the research and development process. It aims to cover the true nature of the discovery/development process for anti-inflammatory drugs.