Fundamentals of Early Clinical Drug Development: From Synthesis Design to Formulation

An informative look at the intricacies of today's drug development process Once a discovery organization has identified a potential new drug candidate, it is the daunting task of synthetic organic chemists to identify the chemical process suitable for preparation of this compound in a highly regulated environment. Only through a multi-layered chemical process that takes into account such factors as safety, environmental considerations, freedom to operate and cost-effectiveness can researchers begin to refine the drug in terms of quality and yield. This book covers both recent advances in the design and synthesis of new drugs, as well as the myriad other issues facing a new drug candidate as it moves through the development process. Utilizing recent case studies, the authors provide valuable insights into the complexities of the process, from designing new synthetic methodologies and applying new automated techniques for finding optimal reaction conditions to selecting the final drug form and formulation. Both novice and active researchers will appreciate the inclusion of chapters on such diverse topics as: * Cross-coupling methods * Asymmetric synthesis * Automation * Chemical Engineering * Application of radioisotopes * Final form selection * Formulations * Intellectual property A wealth of real-world examples and contributions from leading process scientists, engineers, and related professionals make this book a valuable addition to the scientific literature.Content: Chapter 1 Reflections on Process Research II (pages 1–19): Edward J. J. GrabowskiChapter 2 Development and Scale?Up of a Heterocyclic Cross?Coupling for the Synthesis of 5?[2?(3?Methyl?3H?imidazol?4?yl)?thieno[3,2?b]pyridine?7?yl] amino?2?methyl?1H?indole (pages 21–36): John A. RaganChapter 3 Large?Scale Enantioselective Preparation of 2E,7E, 5S,6R, 5?Hydroxy?6?methyl?8?phenyl?octa?2,7?dienoic Acid, a Key Fragment for the Formal Total Synthesis of the Anti?tumor Agent Cryptophycin 52 (pages 37–51): James Aikins, Tony Y. Zhang, Milton Zmijewski and Barbara BriggsChapter 4 Efforts Toward a Commercially Viable Route and Process to the Synthesis of HIV PI GW640385X (pages 53–72): John C. Roberts, Roman Davis, Thomas C. Lovelace, Daniel E. Patterson, Barry Sickles, Jennifer F. Toczko, Ju Yang, Brian D. Doan and Frank RoschangarChapter 5 Development of an Asymmetric Synthesis of ABT?100 (pages 73–83): Albert W. Kruger, Michael J. Rozema, Bridget D. Rohde, Bhadra Shelat, Lakshmi Bhagavatula, James J. Tien, Weijiang Zhang and Rodger F. HenryChapter 6 Asymmetric Hydrogenation: A New Route to Pregabalin (pages 85–100): Rex Jennings, William S. Kissel, Tung V. Le, Edward Lenoir, Thomas Mulhern and Robert WadeChapter 7 Responsibilities of the Process Chemist: Beyond Synthetic Organic Chemistry (pages 101–112): Stephane CaronChapter 8 Outsourcing—The Challenge of Science, Speed, and Quality (pages 113–128): Simone Andler?Burzlaff, Jason Bertola and Roger E. MartiChapter 9 Automation and the Changing Face of Process Research in the Pharmaceutical Industry (pages 129–161): Edward J. Delaney, Merrill L. Davies, Brent D. Karcher, Victor W. Rosso, A. Erik Rubin and John J. VenitChapter 10 Large?Scale Synthesis: An Engineering Perspective (pages 163–188): Joseph H. ChildersChapter 11 Synthesis and Application of Radioisotopes in Pharmaceutical Research and Development (pages 189–214): Larry E. Weaner and David C. HoerrChapter 12 Selection of the Drug Form in Exploratory Development (pages 215–246): George J. QuallichChapter 13 Strategies to Achieve Particle Size of Active Pharmaceutical Ingredients (pages 247–267): David J. am Ende and Peter R. RoseChapter 14 Challenges in Early Formulation: Turning Drug Substance into Drug Product (pages 269–294): Mark H. Kleinman and Beeah LeeChapter 15 Intellectual Property and Early Development (pages 295–317): Maria I. Shchuka