Comprehensive Accounts of Pharmaceutical Research and Development
From Discovery to Late-Stage Process Development Volume 2
Woehler's landmark synthesis of urea from ammonium cyanate (the first synthesis of an 'organic' molecule from an 'inorganic' source) which heralded the birth of modern organic chemistry. Les mer
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Woehler's landmark synthesis of urea from ammonium cyanate (the first synthesis of an 'organic' molecule from an 'inorganic' source) which heralded the birth of modern organic chemistry. Drug discovery has evolved from relying on luck, accident and serendipity to a complex endeavor that is at the
interface of several disciplines (e.g. pharmacology, biology, chemistry), and is built on the understanding of mechanisms and causes of diseases.
This book is produced to celebrate the evolution of drug discovery and development. It will prove useful to synthetic organic chemists in both pharmaceutical industry and in academia, and can serve as a teaching tool to students who want to learn and understand the processes and challenges of drug discovery and development with real examples from top pharmaceutical companies. The chapters contain citations of a large number of valuable selected references to the primary literature. The book
highlights the tireless efforts of discovery and process chemists, and their roles in the advancement of drug discovery and development.
The chapters presented in this book are written by a selected group of outstanding, very accomplished medicinal and process chemists with noted experiences and diverse backgrounds, representing some of the top pharmaceutical companies. The chapters highlight examples of emerging concepts, new developments and challenges arising in the discovery of new drug candidates and the development of new practical synthetic chemistry processes to produce these drug candidates on large scale. The discovery
of each drug or drug candidate is presented by the discovery chemist(s) and the process chemist(s) who developed the drug. These writing teams describe the drug's development to give the reader a complete story of drug discovery and development.
1. Synthesis of a Potent NAE Inhibitor: Pevonedistat
2. Process Development and GMP Production of a Potent NEDD8-Activating Enzyme (NAE) Inhibitor: Pevonedistat
3. The Discovery and Synthesis of the CGRP Receptor Antagonist MK-3207
4. Design and Enabling Development of Hydroxyethylamine-Derived BACE1 Inhibitor
5. Identification and Optimization of a Series of Non-Steroidal Trifluoromethylcarbinol Glucocorticoid Receptor Agonists
6. Development of an Asymmetric Route for Large-Scale Synthesis of a Glucocorticoid Agonist
7. The Medicinal Chemistry and Commercial Manufacturing Behind the Discovery and Development of the Hedgehog Inhibitor Vismodegib
8. Discovery and Process Development of Class I PI3K and Class I PI3K/mTOR Inhibitors GDC-0941 and GDC-0980
9. The Development and Manufacture of Azacitidine, Decitabine, and Cladribine: Stereoselective Ribonucleoside Drug Synthesis Using the Vorbruggen Glycosylation
then moved to the Process Chemistry Group at Johnson & Johnson PRD (1987-2008) as a Senior Scientist and rose through the ranks to Senior Research Fellow. He joined Therachem Research Medilab in 2009 where he holds the title of Executive VP and Chief Scientific Officer.
Jaan A. Pesti received his BS degree from Long Island University, Brooklyn, NY in 1976 and his Ph.D. in organic chemistry from Columbia University in 1981. Following postdoctoral research in synthetic organic chemistry at University of California, Berkeley from 1981-1983, he joined the staff of Dupont's Medical Products Division in Wilmington, DE and Deepwater, NJ. He later transitioned to Dupont Merck Pharmaceuticals, Dupont Pharmaceuticals, and joined Bristol-Myers Squibb Pharmaceuticals in
2001. He retired from BMS in 2013 after 30 years of service, but has worked for NAL Pharma, Gelest Inc., and EnginZyme AB since that date.
Rajappa Vaidyanathan obtained his Bachelor's degree from Loyola College, Madras, and his Master's from the Indian Institute of Technology, Madras. He completed his Ph.D. in 1998 from the University of California, Irvine. After a post-doctoral appointment at Eli Lilly and Company, he joined the Chemical Process R&D group of Pharmacia Corporation, Kalamazoo, MI, and subsequently Pfizer in Groton, CT. He is currently Group Director and Head of Chemical, Synthetic and Analytical Development at
Bristol-Myers Squibb in Bangalore, India.