Fundamentals of Early Clinical Drug Development: From Synthesis Design to Formulation
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
* Chemical Engineering
* Application of radioisotopes
* Final form selection
* 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.
1. Reflections on Process Research II (Edward J. J. Grabowski).
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 (John A. Ragan).
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 (James Aikins, Tony Y. Zhang, Milton Zmijewski, and Barbara Briggs).
4. Efforts Toward a Commercially Viable Route and Process to the Synthesis of HIV PI GW640385X (John C. Roberts, Roman Davis, Brian D. Doan, Thomas C. Lovelace, Daniel E. Patterson, Frank Roschangar, Barry Sickles, Jennifer F. Toczko, and Ju Yang).
5. Development of an Asymmetric Synthesis of ABT-100 (Albert W. Kruger, Michael J. Rozema, Bridget D. Rohde, Bhadra Shelat, Lakshmi Bhagavatula, James J. Tien, Weijiang Zhang, and Rodger F. Henry)
6. Asymmetric Hydrogenation: A New Route to Pregabalin (Rex Jennings, William S. Kissel, Tung V. Le, Edward Lenoir, Thomas Mulhern, and Robert Wade).
7. Responsibilities of the Process Chemist: Beyond Synthetic Organic Chemistry (Stéphane Caron).
8. Outsourcing—The Challenge of Science, Speed, and Quality (Simone Andler-Burzlaff, Jason Bertola, and Roger E. Marti).
9. Automation and the Changing Face of Process Research in the Pharmaceutical Industry (Edward J. Delaney, Merrill L. Davies, Brent D. Karcher, Victor W. Rosso, A. Erik Rubin, and John J. Venit)
10. Large-Scale Synthesis: An Engineering Perspective (Joseph H. Childers, Jr.)
11. Synthesis and Application of Radioisotopes in Pharmaceutical Research and Development (Larry E. Weaner and David C. Hoerr).
12. Selection of the Drug Form in Exploratory Development (George J. Quallich).
13. Strategies to Achieve Particle Size of Active Pharmaceutical Ingredients (David J. am Ende and Peter R. Rose).
14. Challenges in Early Formulation: Turning Drug Substance into Drug Product (Mark H. Kleinman and Beeah Lee).
15. Intellectual Property and Early Development (Maria I. Shchuka).
STÉPHANE CARON is a Director in Chemical Research and Development at Pfizer Global R&D.
‘…this is an excellent book…It is highly recommended to all scientists involved in developing new processes for APIs.’ (Organic Process Research and Development Journal, July 2007)