Divided into the three main sections of synthesis, analysis and drug development, this handbook covers all stages of the drug development process, including large-scale synthesis and purification of chirally pure pharmaceuticals. The two editors from academia and a major pharmaceutical company have assembled an experienced, international team who provide first-hand practical advice and report previously unpublished data. In the first section, the isolation of chiral drugs from natural sources, their production in enzymatic processes and the resolution of racemic mixtures in preparative chromatography are outlined in separate chapters. For the section on qualitative and quantitative analysis, enantioselective chromatographic methods are presented as well as optical methods and CE-MS, while the final section deals with the pharmacology, pharmacokinetics and metabolic aspects of chiral drugs, devoting whole chapters to stereoselective drug binding and modeling chiral drug-receptor interactions. With its unique industry-relevant aspects, this is a must for medicinal and pharmaceutical chemists.

An integrated view of chiral drugs from concept and synthesisto pharmaceutical properties Chirality greatly influences a drug's biological and pharmacological properties. In an effort to achieve more predictable results from chiral drugs, the Food and Drug Administration now requires that these medicines be as pure as possible, which places great demands on drug synthesis, purification, analysis, and testing. To assist researchers in acquiring the essential knowledge to meet these rigid guidelines, Chiral Drugs focuses on three vital chiral technologies asymmetric synthesis, biocatalytic process, and chiral resolution to offer details on the basic concepts, key developments, and recent trends in chiral drug discovery, along with: The history of chiral drugs development and industrial applications of chiral technologies A section listing twenty-five approved or advanced-trial chiral drugs that lists each drug name, chemical name and properties, a representative synthetic pathway, pharmacological characterizations, and references An interdisciplinary approach combining synthetic organic chemistry, medicinal chemistry, and pharmacology Nearly two-thirds of the drugs on today's market are chiral drugs. Reducing and eliminating their negative characteristics is an ongoing and serious challenge for the pharmaceutical industry. With its well-balanced approach to covering each important aspect of chirality, Chiral Drugs champions important strategies for tipping the medical scale in a positive direction for the production of more effective and safer drugs.

Covering every essential element in the development of chiral products, this reference provides a solid overview of the formulation, biopharmaceutical characteristics, and regulatory issues impacting the production of these pharmaceuticals. It supports researchers as they evaluate the pharmacodynamic, pharmacokinetic, and toxicological characteristics of specific enantiomers and chiral drug compounds and addresses in one convenient reference all the major challenges pertaining to drug chirality that have been neglected in the literature. Chirality in Drug Design and Development collects the latest studies from an interdisciplinary team of experts on chiral drug design.

Chirality in Drug Design and Synthesis is a collection of papers that discusses the property of asymmetry in the structural and synthetic chemistry of natural products, including the significance of chirality in medicinal chemistry. These papers examine the need for the preparation and study of pure enantiomers of chiral drug substances and their mechanism of interaction with enzymes and receptors. These papers also investigate the techniques in studying these interactions, as well as analyze the methods for their synthesis in enantiomerically pure form. One paper discusses the pharmacological and pharmacokinetic analyses made that point to the differences in the activity and disposition of enantiometric pairs. Another paper reviews the implications of the neglect of stereoselectivity at the different levels during the examination process of racemic drugs. Since no general guidelines exists for the development of drugs with chiral centers, one paper suggests a case-by-case approach in evaluating the safety and efficacy of drugs, particularly as regards how isomers differ in their effects. This collection is suitable for the pharmacologist, medicinal chemists, toxicologists, mechanistic chemists and synthetic organic chemists.

The past fifteen years have seen a revolution in the field of stereochemistry, with breakthrough analytical techniques in enantiomeric separation profoundly affecting drug development and use. This practical reference written by leading researchers focuses on the important roles chirality and stereoisomerism play in drug development efforts--presenting for the first time a comprehensive overview of this rapidly evolving area of pharmacological research. The book explores analytical, pharmacological, and regulatory topics in dealing with the theory and practice of stereochemistry in the pharmaceutical industry today. This exciting, broad-appeal treatment extends from the analytical viewpoint in enantiomeric separation to the regulatory issues involved in the "racemate-versus-enantiomer" debate. The authors include numerous examples and case studies, and integrate material from a wide range of studies, publications, and workshops. The introductory chapters outline the pharmacological effects of stereochemistry, cover stereochemistry in drug metabolism, and discuss problems inherent in the duality of enantiomers--chemically identical yet spatially different molecules. Contributions on the specific aspects of chirality and drug activity explore the toxicological effects of stereoselectivity, illustrate how an understanding of the stereochemical composition of certain drugs can help avoid problems, and offer tips on new clinical applications for existing drugs. A full chapter is devoted to research opportunities in the development of new chirally pure drugs. Other practical research topics range from the preparation of chirally pure compounds to the analytical determination of stereochemical composition, to applications of circular dichroism (CD) spectroscopy. Regulatory issues concerning the development and approval of stereoisomeric drugs are discussed in the final chapters. This section offers an international perspective as well as a historical review of the ongoing debate surrounding regulatory guidelines. Impact of Stereochemistry on Drug Development and Use is an essential reference for medicinal and analytical chemists, pharmacologists, drug metabolism and pharmacokinetic scientists, and personnel of regulatory agencies. It is also a useful text for graduate students in stereochemistry, and for anyone who wants to keep up with the swift pace of change in this dynamic field. Impact of Stereochemistry on Drug Development and Use is an essential reference for medicinal and analytical chemists, pharmacologists, drug metabolism and pharmacokinetic scientists, and personnel of regulatory agencies. It is also a useful text for graduate students in stereochemistry, and for anyone who wants to keep up with the swift pace of change in this dynamic field. IMPACT OF STEREOCHEMISTRY ON DRUG DEVELOPMENT AND USE Twenty-three expert contributions on the "stereochemical revolution" of the last fifteen years--covering analytical, pharmacological, and regulatory topics--show that "drug development can no longer occur without consideration of drug stereochemistry." "We have...come full circle and stand alongside Pasteur in amazement of nature's duality, symmetry and dissymmetry, and its chemical and pharmacological consequences."--from the Preface

Axially Chiral Compounds Explore this comprehensive and current volume summarizing the characteristics, synthesis, and applications of axial chirality Appearing widely in natural products, biologically active molecules, asymmetric chemistry, and material science, axially chiral motifs constitute the core backbones of the majority of chiral ligands and organocatalysts in asymmetric catalysis. In a new work of particular relevance to synthetic chemists, Axially Chiral Compounds: Asymmetric Synthesis and Applications delivers a clearly structured and authoritative volume covering the classification, characteristics, synthesis, and applications of axial chirality. A must read for every synthetic chemist practicing today, the book follows the development history, research status, and applications of axial chirality. An introductory chapter familiarizes the reader with foundational material before the distinguished authors describe the different classes and the synthesis of axial chiral compounds used in asymmetric synthesis. The book concludes with a focus on the applications of chiral ligands, chiral catalysts, and materials. Readers will also benefit from the inclusion of: A thorough introduction to asymmetric synthesis, including biaryls atropisomers, heterobiaryls atropisomers, and non-biaryls atropisomers Explorations of chiral allene, spiro skeletons, and natural products Practical discussions of asymmetric transformation, chiral ligands, and chiral catalysts An examination of miscellaneous applications of axially chiral compounds Perfect for organic chemists, chemists working with or on organometallics, catalytic chemists, and materials scientists, Axially Chiral Compounds: Asymmetric Synthesis and Applications will also earn a place in the libraries of natural products chemists who seek a one-stop reference for compounds exhibiting axial chirality.

Highlighting 15 selected chiral structures, which represent candidate or marketed drugs, and their chemical syntheses, the authors acquaint the reader with the fascinating achievements of synthetic and medicinal chemistry. The book starts with an introduction treating the discovery and development of a new drug entity. Each of the 15 subsequent chapters presents one of the target structures and begins with a description of its biological profile as well as any known molecular mechanisms of action, underlining the importance of its structural and stereochemical features. This section is followed by detailed discussions of synthetic approaches to the chiral target structure, highlighting creative ideas, the scaling-up of laboratory methods and their replacement by efficient modern technologies for large-scale production. Nearly 60 synthetic reactions, most of them stereoselective, catalytic or biocatalytic, as well as chiral separating methodologies are included in the book. Vitomir Sunjic and Michael J. Parnham provide an invaluable source of information for scientists in academia and the pharmaceutical industry who are actively engaged in the interdisciplinary development of new drugs, as well as for advanced students in chemistry and related fields.