This book examines drug degradation pathways with an emphasis on the underlying chemical mechanisms.

Standard medicinal chemistry courses and texts are organized by classes of drugs with an emphasis on descriptions of their biological and pharmacological effects. This book represents a new approach based on physical organic chemical principles and reaction mechanisms that allow the reader to extrapolate to many related classes of drug molecules. The Second Edition reflects the significant changes in the drug industry over the past decade, and includes chapter problems and other elements that make the book more useful for course instruction. - New edition includes new chapter problems and exercises to help students learn, plus extensive references and illustrations - Clearly presents an organic chemist's perspective of how drugs are designed and function, incorporating the extensive changes in the drug industry over the past ten years - Well-respected author has published over 200 articles, earned 21 patents, and invented a drug that is under consideration for commercialization

The vast majority of drugs are organic molecular entities. A clear understanding of the organic chemistry of drug degradation is essential to maintaining the stability, efficacy, and safety of a drug product throughout its shelf-life. During analytical method development, stability testing, and pharmaceutical manufacturing troubleshooting activities, one of the frequently occurring and usually challenging events would be the identification of drug degradants and understanding of drug degradation mechanisms and pathways. This book is written by a veteran of the pharmaceutical industry who has first-hand experience in drug design and development, drug degradation mechanism studies, analytical development, and manufacturing process troubleshooting and improvement. The author discusses various degradation pathways with an emphasis on the mechanisms of the underlying organic chemistry, which should aid greatly in the efforts of degradant identification, formulation development, analytical development, and manufacturing process improvement. Organic reactions that are significant in drug degradation will first be reviewed and then illustrated by examples of drug degradation reported in the literature. The author brings the book to a close with a final chapter dedicated to the strategy for rapid elucidation of drug degradants with regard to the current regulatory requirements and guidelines. One chapter that should be given special attention is Chapter 3, Oxidative Degradation. Oxidative degradation is one of the most common degradation pathways but perhaps the most complex one. This chapter employs more than sixty drug degradation case studies with in-depth discussion in regard to their unique degradation pathways. With the increasing regulatory requirements on the quality and safety of pharmaceutical products, in particular with regard to drug impurities and degradants, the book will be an invaluable resource for pharmaceutical and analytical scientists who engage in formulation development, analytical development, stability studies, degradant identification, and support of manufacturing process improvement. In addition, it will also be helpful to scientists engaged in drug discovery and development as well as in drug metabolism studies.

Of the thousands of novel compounds that a drug discovery project team invents and that bind to the therapeutic target, typically only a fraction of these have sufficient ADME/Tox properties to become a drug product. Understanding ADME/Tox is critical for all drug researchers, owing to its increasing importance in advancing high quality candidates to clinical studies and the processes of drug discovery. If the properties are weak, the candidate will have a high risk of failure or be less desirable as a drug product. This book is a tool and resource for scientists engaged in, or preparing for, the selection and optimization process. The authors describe how properties affect in vivo pharmacological activity and impact in vitro assays. Individual drug-like properties are discussed from a practical point of view, such as solubility, permeability and metabolic stability, with regard to fundamental understanding, applications of property data in drug discovery and examples of structural modifications that have achieved improved property performance. The authors also review various methods for the screening (high throughput), diagnosis (medium throughput) and in-depth (low throughput) analysis of drug properties. - Serves as an essential working handbook aimed at scientists and students in medicinal chemistry - Provides practical, step-by-step guidance on property fundamentals, effects, structure-property relationships, and structure modification strategies - Discusses improvements in pharmacokinetics from a practical chemist's standpoint

Targeting protein degradation using small molecules is one of the most exciting small-molecule therapeutic strategies in decades and a rapidly growing area of research. In particular, the development of proteolysis targeting chimera (PROTACs) as potential drugs capable of recruiting target proteins to the cellular quality control machinery for elimination has opened new avenues to address traditionally ‘difficult to target’ proteins. This book provides a comprehensive overview from the leading academic and industrial experts on recent developments, scope and limitations in this dynamically growing research area; an ideal reference work for researchers in drug discovery and chemical biology as well as advanced students.

This book aims to guide and inspire drug researchers as they enter the 21st century. Stereochemistry is an essential dimension in pharmacology and should be understood as such by all drug researchers whatever their background. When used as probes or medicines, stereoisomeric drugs offer invaluable insights or innovative therapeutic strategies. The book spans the subject from the molecular to the clinical. The first section on chemical aspects contains chapters on chemical synthesis, analysis, natural products, chiral stability (racemezation) and physical properties. The second section is on experimental pharmacology, with chapters on drug-receptor interactions, chiral recognition, ion channels, and molecular toxicology. The third section focuses on drug disposition, with chapters on absorption, distribution, protein binding, metabolism and elimination. The final section is dedicated to regulatory and clinical aspects.

Drug Stability for Pharmaceutical Scientists is a clear and easy-to-follow guide on drug degradation in pharmaceutical formulation. This book features valuable content on both aqueous and solid drug solutions, the stability of proteins and peptides, acid-base catalyzed and solvent catalyzed reactions, how drug formulation can influence drug stability, the influence of external factors on reaction rates and much more. Full of examples of real-life formulation problems and step-by-step calculations, this book is the ideal resource for graduate students, as well as scientists in the pharmaceutical and related industries. - Illustrates important theoretical concepts with numerous examples, figures, calculations, learning problems and questions for self-study and retention of material - Provides answers and explanations to test your knowledge - Enables you to better understand key concepts such as rate and order of reaction, reaction equilibrium, complex reaction mechanisms and more - Includes an in-depth discussion of both aqueous and solid drug solutions and contains the latest international regulatory requirements on drug stability