In the late 1980s, it became painfully evident to the pharmaceutical industry that the old paradigm of drug discovery, which involved highly segmented drug - sign and development activities, would not produce an acceptable success rate in the future. Therefore, in the early 1990s a paradigm shift occurred in which drug design and development activities became more highly integrated. This new str- egy required medicinal chemists to design drug candidates with structural f- tures that optimized pharmacological (e. g. , high affinity and specificity for the target receptor), pharmaceutical (e. g. , solubility and chemical stability), bioph- maceutical (e. g. , cell membrane permeability), and metabolic/pharmacokinetic (e. g. , metabolic stability, clearance, and protein binding) properties. Successful implementation of this strategy requires a multidisciplinary team effort, incl- ing scientists from drug design (e. g. , medicinal chemists, cell biologists, en- mologists, pharmacologists) and drug development (e. g. , analytical chemists, pharmaceutical scientists, physiologists, and molecular biologists representing the disciplines of pharmaceutics, biopharmaceutics, and pharmacokinetics/drug metabolism). With this new, highly integrated approach to drug design now widely utilized by the pharmaceutical industry, the editors of this book have provided the sci- tific community with case histories to illustrate the nature of the interdisciplinary interactions necessary to successfully implement this new approach to drug d- covery. In the first chapter, Ralph Hirschmann provides a historical perspective of why this paradigm shift in drug discovery has occurred.

Inhalt
Renin Inhibitors.- The Discovery and Development of Angiotensin II Antagonists.- Development of an Orally Active Tripeptide Arginal Thrombin Inhibitor.- Discovery and Development of an Endothelin a Receptor-Selective Antagonist PD 156707.- Endothelin Receptor Antagonists.- LHRH Antagonists.- LHRH Agonists.- Discovery and Development of Somatostatin Agonists.- Factors Impacting the Delivery of Therapeutic Levels of Pyrone-Based HIV Protease Inhibitors.- The Integration of Medicinal Chemistry, Drug Metabolism, and Pharmaceutical Research and Development in Drug Discovery and Development.- De Novo Design and Discovery of Cyclic HIV Protease Inhibitors Capable of Displacing the Active-Site Structural Water Molecule.- Discovery and Development of the BHAP Nonnucleoside Reverse Transcriptase Inhibitor Delavirdine Mesylate.- Famciclovir.- The Use of Esters as Prodrugs for Oral Delivery of ?-Lactam Antibiotics.- Hematoregulators.- Discovery and Development of GG745, a Potent Inhibitor of Both Isozymes of of 5?-Reductase.- Discovery of a Potent and Selective ?1A Antagonist.- Discovery of Bioavailable Inhibitors of Secretory Phospholipase A2.- The Anxieties of Drug Discovery and Development.- CI-1015.- Orally Active Nonpeptide CCK-A Agonists.- Orally Active Growth Hormone Secretagogues.- Dorzolamide, a 40-Year Wait.- Discovery and Development of Novel Melanogenic Drugs.