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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company have assembled an experienced, international team who provide first-hand practical advice and report previously unpublished data.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.
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.
This title was first published in 2001: In the early twentieth century the relevance of chirality to the pharmaceutical industry was established by the fact that one enantiomer of hyoscyamine possessed greater pharmacological activity than the other. Today, most new drugs and those under development consist of a single optically active isomer, and chirality is also becoming an issue for the agrochemical and other industries. Regulatory agencies throughout the world are currently reviewing the importance of chirality with regard to pharmaceutical and agrochemical products. New guidelines from such agencies have been key drivers for the focus on single enantiomer products in these industries. These scientific and regulatory developments have created the need for a guide for workers in the pharmaceutical and chemical industries seeking information on chiral molecules, processes, and commercially available chiral chemicals. Chiral Drugs is a comprehensive listing of over 2500 chiral drugs, classified by therapeutic class, and including structures and physical properties for each entry in the listing. Its companion volume, Chiral Intermediates, presents the same detailed information for over 4700 commercially available chiral chemicals. The 'Chiral Pool' of readily available, relatively inexpensive chiral compounds has been expanding at a rapid rate as more and more products are produced in large quantities at economical prices. New developments in various technologies for isolating, preparing, and purifying chiral materials have greatly increased the opportunities for utilizing optically pure compounds in commercial applications. Novel techniques for classical resolution, new methodologies for developing selective enzymes for biocatalysis, advances in the application of microorganisms for chemical production, and continued progress in the area of asymmetric synthesis have all contributed to the growth of this field. Part One of each book contains four chapters which provide an introduction to topics relevant to the field of chiral chemistry and includes a brief overview of chirality, a short discussion on the current market drivers in the area of chiral chemistry, and a basic presentation of the various sources and methods for obtaining chiral compounds. Part Two presents entries for over 2500 chiral drugs, classified by therapeutic class. For each main entry, the chemical name and a list of trade names and synonyms is provided; the CAS Registry Number, the European Inventory of Existing Commercial Chemical Substances (EINECS) number, and the Merck Index (12th edition) number are given when available. The physical properties, including specific rotation, of each compound are described and indicated applications are presented. The structure of nearly every compound is provided, and the manufacturers and suppliers of the compounds are also given. Indexes, including a master index of names and synonyms and an index of custom manufacturing services for production of chiral compounds, are appended. Chiral Drugs provides an introduction to the types of sources and methods currently in use for obtaining chiral molecules and is an invaluable resource for researchers in the pharmaceutical and biotechnology sectors as well as to those working in the basic biochemical sciences. Chiral Intermediates provides an introduction to the types of sources and methods currently in use for obtaining chiral molecules and is an invaluable resource for information on available chiral molecules. Chiral Intermediates and Chiral Drugs are the most comprehensive and detailed guides to chiral compounds available.
This is a completely revised and updated sequel to 'A Practical Approach to Chiral Separations by Liquid Chromatography' by the same editor. The scope has been extended to further chiral separation techniques like electrophoresis, membrane separations, or biological assays. More emphasis is put on preparative separation techniques. From reviews of the previous edition: 'A team of experts from academic and industrial laboratories throughout the world have compiled their findings and experience to make this book an exceptionally timely and unique contribution to the field' European Journal of Drug Metabolism 'The dense mass of information contained in this book will make it a valuable resource ...' Chemical Engineering Research '... this is a worthwhile addition to the expanding chiral literature and the book should be of value to those working in this field' The Analyst
This book describes the processes that are involved in the development of new drugs. The authors discuss the history, role of natural products and concept of receptor interactions with regard to the initial stages of drug discovery. In a single, highly readable volume, it outlines the basics of pharmacological screening, drug target identification, and genetics involved in early drug discovery. The final chapters introduce readers to stem therapeutics, pharmacokinetics, pharmacovigilance, and toxicological testing. Given its scope, the book will enable research scholars, professionals and young scientists to understand the key fundamentals of drug discovery, including stereochemistry, pharmacokinetics, clinical trials, statistics and toxicology.
While working as a chromatographer in the pharmaceutical industry, it became apparent to the editor that there was a pressing need for a comprehensive reference text for analysts working on the resolution of enantiomers by liquid chromatography (LC). This need arises from the fact that, whereas previously it was very difficult to determine enantiomers by direct means, there is now a wide choice of direct LC methods. At the same time, regulatory authorities have been changing their attitudes towards the administration of pharmaceuticals as racemates, partly because it is now possible to study the individual enantiomers. Clearly this abundance of new information needs to be rationalized. More importantly, the chiral LC systems which are commercially available or readily accessible to the practising chromatographer needed to be reviewed and, to a much greater extent than in existing reviews or books, discussed in terms of their practical application. Accordingly this book is very much orientated towards the practical aspects of these commercially available and readily accessible chiral LC systems. To this end, it is written for practising chromatographers by a team of practising, experienced chromatographers who have spent many years tackling the problems presented by resolving enantiomers by LC. The practical aspects of common chiral LC systems cannot be fully understood if discussed in isolation.
With contributions by numerous experts
This second volume of Chirality in Industry contains new case histories from a wide range of contributors from industry or with strong industrial connections. While it is intended that the new volume will stand on its own, Volumes I and II taken together present an up-to-date and comprehensive picture of the technologies required to produce optically active compounds on a multi-kilogramme to high tonnage scale as well as illustrating the breadth of application of these technologies; the pharmaceuticals, agrochemicals, electronics, food, flavour and fragrance industries are all represented. Chirality in Industry II All new case histories Unique industrial perspective on chiral technology Emphasis on scale-up and process development Comparison of biocatalysis, asymmetric synthesis and classical resolution approaches The chiral infrastructure is now largely in place and there is no reason why large-scale production should not be possible for even moderately priced single enantiomer products. The successful industrial application of chiral chemistry depends on the integration of a range of supporting technologies and there are many examples in this volume of how widely the industrial practitioner must cast the net to achieve practical production methods. As with Volume I, this new volume is of particular interest to those professionally involved in the scale-up processes for single enantiomers. However, students and researchers involved in a more academic pursuit of optical activity will also benefit from some of the facets of large-scale thinking. An economic solution is still most likely to be a simple, elegant solution.