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Accounts in Drug Discovery describes recent case studies in medicinal chemistry with a particular emphasis on how the inevitable problems that arise during any project can be surmounted or overcome. The Editors cover a wide range of therapeutic areas and medicinal chemistry strategies, including lead optimization starting from high throughput screening "hits" as well as rational, structure-based design. The chapters include "follow-ons" and "next generation" compounds that aim to improve upon first generation agents. This volume surveys the range of challenges commonly faced by medicinal chemistry researchers, including the optimization of metabolism and pharmacokinetics, toxicology, pharmaceutics and pharmacology, including proof of concept in the clinic for novel biological targets. The case studies include medicinal chemistry stories on recently approved and marketed drugs, but also chronicle "near-misses", i.e., exemplary compounds that may have proceeded well into the clinic but for various reasons did not result in a successful registration. As the vast majority of projects fail prior to registration, much can be learned from such narratives. By sharing a wide range of drug discovery experiences and information across the community of medicinal chemists in both industry and academia, we believe that these accounts will provide insights into the art of medicinal chemistry as it is currently practiced and will help to serve the needs of active medicinal chemists.
Joel C. Barrish was awarded his Ph.D. in Organic Chemistry from Columbia University; spent 25 years as a medicinal chemist in Drug Discovery Research; co-inventor of the anti-cancer agent SPRYCEL and is currently Vice President in Discovery Chemistry responsible for multiple programs across therapeutic areas. Percy H. Carter was awarded his Ph.D. in Organic Chemistry from Harvard University; 10 years as a medicinal chemist in Drug Discovery Research and is currently Group Director in Discovery Chemistry responsible for multiple programs Inflammation Research. Peter T. W. Cheng was awarded Ph.D. in Organic Chemistry from the University of Toronto; approximately 20 yrs as a medicinal chemist in Drug Discovery Research and is currently a Research Fellow in Metabolic Diseases Chemistry. Robert Zahler gained his Ph.D. in Organic Chemistry from the California Institute of Technology; approximately 30 yrs experience as a medicinal chemist in Drug Discovery Research and is the inventor of the anti-infective agent Entecavir.
Front Matter; Foreword; Preface; Contents; Chapter 1. The Discovery of the Dipeptidyl Peptidase-4 (DPP4) Inhibitor OnglyzaOE: From Concept to Market; Chapter 2. The Discovery of Vorapaxar (SCH 530348), a Thrombin Receptor (Protease Activated Receptor-1) Antagonist with Potent Antiplatelet Effects; Chapter 3. The Discovery of Piragliatin, a Glucokinase Activator; Chapter 4. The Discovery of OSI-906, a Small-molecule Inhibitor of the Insulin-like Growth Factor-1 and Insulin Receptors; Chapter 5. The Genesis of the Antibody Conjugate Gemtuzumab Ozogamicin (Mylotarg") for Acute Myeloid Leukemia; Chapter 6. Novel Androgen Receptor Antagonists for the Treatment of Prostate Cancer; Chapter 7. The Discovery of UK-390957: the Challenge of Targeting a Short Half-life, Rapid Tmax SSRI; Chapter 8. The Discovery of the Long-acting PDE5 Inhibitor PF-489791 for the Treatment of Pulmonary Hypertension; Chapter 9. From HTS to Market: the Discovery and Development of Maraviroc, a CCR5 Antagonist for the Treatment of HIV; Chapter 10. The Discovery of GS-9131, an Amidate Prodrug of a Novel Nucleoside Phosphonate HIV Reverse Transcriptase Inhibitor; Chapter 11. 2'-F-2'-C-Methyl Nucleosides and Nucleotides for the Treatment of Hepatitis C Virus: from Discovery to the Clinic; Chapter 12. A Case History on the Challenges of Central Nervous System and Dual Pharmacology Drug Discovery; Chapter 13. The Discovery of TRPV1 Antagonists: Turning up the Heat; Chapter 14. Uncoupling Neuroprotection from Immunosuppression: the Discovery of ILS-920; Chapter 15. Identification of a7 Nicotinic Acetylcholine Receptor Agonists for their Assessment in Improving Cognition in Schizophrenia; Subject Index
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- ID: 9781849731263
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