As pharmaceutical companies strive to develop safer medicines at a lower cost, they must keep pace with the rapid growth of technology and research methodologies. Defying the misconception of process chemistry as mere scale-up work, Process Chemistry in the Pharmaceutical Industry, Vol. 2: Challenges in an Ever Changing Climate explores novel applications of synthetic, physical, and analytical chemistry in drug discovery and development. It offers an accurate depiction of the most up-to-date process research and development methods applied to synthesis, clinical trials, and commercializing drug candidates.
The second installment in this progressive series, this volumereviews the latest breakthroughs to advance process chemistry, including asymmetric synthesis, crystallization, morphology, enzymatic intervention, green chemistry, macromolecules (monoclonal antibodies, biological molecules, polymers), enantioselectivity, organometallic chemistry, process analytical tools, chemical engineering controls, regulatory compliance, and outsourcing/globalization. It explores new approaches to synthetic processes, examines the latest safety methods and experiment design, and suggests realistic solutions to problems encountered in manufacturing and process development. Significant topics include atom economy, ease of synthesis, instrumentation, automization, quality control, cost considerations, green practices, and future trends.
Jointly edited by the founder/president of Delphian Pharmaceuticals and the director of Chemical R&D at Pfizer, this book brings together contributions byreputed scientists, technologists, engineers, and professors from leading academic institutions, such as the Imperial College, UK, the University of Tokyo, ETH, Switzerland, the International University at Bermen, Germany, and the University of Connecticut, USA, and from principal pharmaceutical companies that include Merck, Bristol Myers Squibb, Pfizer, Novartis, Eli Lilly, Astrazeneca and DSM.
Table of Contents
Process Chemistry in the Pharmaceutical Industry: Challenges in an Ever Changing Climate—An Overview. Emerging Trends in Process Chemistry. Varenicline: Discovery Synthesis and Process Chemistry Developments. The SUTENT® Story. An Efficient and Scalable Process for the Preparation of a Potent MC4 Receptor Agonist. Process Research and Development of LY414197, a 5HT2B Antagonist. To Overcome the Hurdles: Coping with the Synthesis of Robalzotan, a Complex Chroman Antidepressant. Chiral Amine Synthesis—Strategies, Examples, and Limitations. The Chemical Development of a Potential Manufacturing Route to the Endothelin Antagonists UK-350,926 and UK-349,862. Cefovecin Sodium: A Single-Dose Long-Acting Antibiotic for Use in Companion Animals. The Lithium–Halogen Exchange Reaction in Process Chemistry. Oxetan-3-one: Chemistry and Synthesis. Well-Defined (NHC)Pd (II) Complexes and Their Use in C–C and C–N Bond-Forming Reactions. Toward Truly Efficient Organic Reactions in Water. The Chemical Development of the Commercial Route to Sildenafil Citrate. Stereoselective Enzymatic Synthesis of Intermediates Used for Antihypertensive, Antiinfective, and Anticancer Compounds. Designing Robust Crystallization Processes for Active Pharmaceutical Ingredients—From Art to Science. In Situ Mid-Infrared Spectroscopy for Process Development. Optimizing an Asymmetric Homologation in a Tandem Asymmetric Homologation–Homoaldol Reaction. Development of Efficient One-Pot Process in the Synthesis of Sitagliptin: Application of Online-Infrared for Kinetic Studies to Probe the Reaction Mechanism. Mid-Infrared Monitoring Applications during Development of the Vinyl Ether Formation Step in the Preparation of Aprepitant (Emend®). Process Analytical Technology in the Manufacture of Bulk Active Pharmaceuticals—Promise, Practice, and Challenges. PEGylation of Biological Macromolecules. Microwave Technology in Process Optimization. Process Development Considerations for Therapeutic Monoclonal Antibodies in Mammalian Cell Culture. Reaction Progress Kinetic Analysis: A Powerful Methodology for Streamlining Pharmaceutical Reaction Steps. Trends in Outsourcing. Sourcing Pharmaceutical Products in China and India. Index.
Kumar Gadamasetti, Tamim Braish