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; K. Gadamasetti
Emerging Trends in Process Chemistry; T.F. Braish, F. De Knaep, and K. Gadamasetti
Varenicline: Discovery Synthesis and Process Chemistry Developments; J.W. Coe, H.A. Watson Jr., and R.A. Singer
The SUTENT® Story; R. Vaidyanathan
An Efficient and Scalable Process for the Preparation of a Potent MC4 Receptor Agonist; C. Savarin, J. Chung, J.A. Murry, R.J. Cvetovich, C. McWilliams, D. Hughes, J. Amato, G. Boice, K. Conrad, E. Corley, R. Reamer, and L. DiMichele
Process Research and Development of LY414197, a 5HT2B Antagonist; A. Borghese and A. Merschaert
To Overcome the Hurdles: Coping with the Synthesis of Robalzotan, a Complex Chroman Antidepressant; H. J.Federsel and A. Sveno
Chiral Amine Synthesis—Strategies, Examples, and Limitations; T.C. Nugent
Unnatural Amino Acids; D.J. Ager
The Chemical Development of a Potential Manufacturing Route to the Endothelin Antagonists UK-350,926 and UK-349,862; C.P. Ashcroft, S. Challenger, A.M. Derrick, Y. Hajikarimian, and N.M. Thomson
Cefovecin Sodium: A Single-Dose Long-Acting Antibiotic for Use in Companion Animals; T. Norris
The Lithium–Halogen Exchange Reaction in Process Chemistry; W.F. Bailey and T.L. Rathman
Oxetan-3-one: Chemistry and Synthesis; G. Wuitschik, E.M. Carreira, M. Rogers-Evans, and K. Müller
Well-Defined (NHC)Pd (II) Complexes and Their Use in C–C and C–N Bond-Forming Reactions; O. Navarro and S.P. Nolan
Toward Truly Efficient Organic Reactions in Water; C. Ogawa and S. Kobayashi
The Chemical Development of the Commercial Route to Sildenafil Citrate; P.J. Dunn
Stereoselective Enzymatic Synthesis of Intermediates Used for Antihypertensive, Antiinfective, and Anticancer Compounds; R.L. Hanson
Designing Robust Crystallization Processes for Active Pharmaceutical Ingredients—From Art to Science; D. Wieckhusen
In Situ Mid-Infrared Spectroscopy for Process Development; D.A. Conlon, W. Izzo, J. Christopher McWilliams, R.A. Reamer, F. Xu, and P. Collins
Optimizing an Asymmetric Homologation in a Tandem Asymmetric Homologation–Homoaldol Reaction; J.C. McWilliams and R.A. Reamer
Development of Efficient One-Pot Process in the Synthesis of Sitagliptin: Application of Online-Infrared for Kinetic Studies to Probe the Reaction Mechanism; F. Xu
Mid-Infrared Monitoring Applications during Development of the Vinyl Ether Formation Step in the Preparation of Aprepitant (Emend®); D.A. Conlon, W. Izzo, and P. Collins
Process Analytical Technology in the Manufacture of Bulk Active Pharmaceuticals—Promise, Practice, and Challenges; C.A. Mojica and L. St. Pierre-Berry
PEGylation of Biological Macromolecules; J.J. Buckley, R.F. Finn, J. Mo, L.A. Bass, and S.V. Ho
Microwave Technology in Process Optimization; F. Mavandadi
Process Development Considerations for Therapeutic Monoclonal Antibodies in Mammalian Cell Culture;
S. Casnocha, R. Fedechko, P. Mensah, J. Mott, and S. Nema
Reaction Progress Kinetic Analysis: A Powerful Methodology for Streamlining Pharmaceutical Reaction Steps; N. Zotova, S.P. Mathew, H. Iwamura, and D.G. Blackmond
Trends in Outsourcing; J. Lu and I. Shinkai
Sourcing Pharmaceutical Products in China and India; D. Robins and S. Hannon Index
"The second installment in this progressive series, this volume reviews the latest breakthroughs to advance process chemistry . . . Jointly edited by the founder/ president of Delphian Pharmaceuticals and the director of Chemical R&D at Pfizer, this book brings together contributions by reputed scientists, technologists, engineers, and professors from leading academic institutions and from principal pharmaceutical companies influencing today’s market."
– In Anticancer Research, July/ August 2008, Vol. 28, No. 4A
"This is an excellent book . . . Overall this book is definitely recommended and the editors are to be congratulated on a job well done."
– In Scientific Update, 2008
"This is an excellent book . . . this book is definitely recommended, and the editors are to be congratulated on a job well done."
– W. J. Watson, Scientific Update, in Organic Process Research & Development, October 2008, Vol. 30, No. 20