Hugo Kubinyi
Список книг автора Hugo KubinyiHandbook of Molecular Descriptors
Quantitative studies on structure-activity and structure-property relationships are powerful tools in directed drug research. In recent years, various strategies have been developed to characterize and classify structural patterns by means of molecular descriptors. It has become possible not only to assess diversities or similarities of structure databases, but molecular descriptors also facilitate the identification of potential bioactive molecules from the rapidly increasing number of compound libraries. They even allow for a controlled de-novo design of new lead structures. This is the most comprehensive collection of molecular descriptors and presents a detailed review from the origins of this research field up to present day. This practically oriented reference book gives a thorough overview of the different molecular descriptors representations and their corresponding molecular descriptors. All descriptors are listed with their definition, symbols and labels, formulas, some numerical examples, data and molecular graphs, while numerous figures and tables aid comprehension of the definitions. Cross-references throughout, a list of acronyms and notations allow easy access to the information needed to solve a specific research problem. Examples of descriptor calculations along with tables of descriptor values for a set of selected reference compounds and an up-to-date reference list add to the practical value of the book, making it an invaluable guide for all those dealing with bioactive molecules as well as for researchers.
Structure-based Ligand Design
Most drugs bind to a clearly defined macromolecular target that is complementary in terms of structure and chemistry. This observation is the basic paradigm of structure-based ligand design. Although this method first emerged in the 1980s, it has already become a powerful tool for pharmaceutical research. Much has been learned, however, since the first attempts to discover drugs on the basis of available biochemical and structural data. Nowadays, structure-based ligand design is an established method for creating drugs with new structural features, for modifying binding activities and pharmacokinetic properties, and for elucidating binding modes and structure-activity relationships. This volume presents the underlying principles of the approach and highlights real-life applications such as the discovery of HIV-protease inhibitors. It shows that structure-based ligand design has many advantages over other more traditional approaches to designing new drugs, providing it is employed properly and with a thorough knowledge of the pitfalls to avoid. The straightforward presentation and extensive list of references to the original literature as well as numerous color figures illustrating structural relationships make this volume an indispensable tool for every scientist working in the area of drug discovery.
Pharmacophores and Pharmacophore Searches
This handbook is the first to address the practical aspects of this novel method. It provides a complete overview of the field and progresses from general considerations to real life scenarios in drug discovery research. Starting with an introductory historical overview, the authors move on to discuss ligand-based approaches, including 3D pharmacophores and 4D QSAR, as well as the concept and application of pseudoreceptors. The next section on structure-based approaches includes pharmcophores from ligand-protein complexes, FLIP and 3D protein-ligand binding interactions. The whole is rounded off with a complete section devoted to applications and examples, including modeling of ADME properties. With its critical evaluation of pharmacophore-based strategies, this book represents a valuable aid for project leaders and decision-makers in the pharmaceutical industry, as well as pharmacologists, and medicinal and chemists.
Chirality in Drug Research
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.
Chemoinformatics in Drug Discovery
This handbook provides the first-ever inside view of today's integrated approach to rational drug design. Chemoinformatics experts from large pharmaceutical companies, as well as from chemoinformatics service providers and from academia demonstrate what can be achieved today by harnessing the power of computational methods for the drug discovery process. With the user rather than the developer of chemoinformatics software in mind, this book describes the successful application of computational tools to real-life problems and presents solution strategies to commonly encountered problems. It shows how almost every step of the drug discovery pipeline can be optimized and accelerated by using chemoinformatics tools – from the management of compound databases to targeted combinatorial synthesis, virtual screening and efficient hit-to-lead transition. An invaluable resource for drug developers and medicinal chemists in academia and industry.
Evolutionary Algorithms in Molecular Design
When trying to find new methods and problem-solving strategies for their research, scientists often turn to nature for inspiration. An excellent example of this is the application of Darwin's Theory of Evolution, particularly the notion of the 'survival of the fittest', in computer programs designed to search for optimal solutions to many kinds of problems. These 'evolutionary algorithms' start from a population of possible solutions to a given problem and, by applying evolutionary principles, evolve successive generations with improved characteristics until an optimal, or near-optimal, solution is obtained. This book highlights the versatility of evolutionary algorithms in areas of relevance to molecular design with a particular focus on drug design. The authors, all of whom are experts in their field, discuss the application of these computational methods to a wide range of research problems including conformational analysis, chemometrics and quantitative structure-activity relationships, de novo molecular design, chemical structure handling, combinatorial library design, and the study of protein folding. In addition, the use of evolutionary algorithms in the determination of structures by X-ray crystallography and NMR spectroscopy is also covered. These state-of-the-art reviews, together with a discussion of new techniques and future developments in the field, make this book a truly valuable and highly up-to-date resource for anyone engaged in the application or development of computer-assisted methods in scientific research.
Virtual Screening for Bioactive Molecules
Recent progress in high-throughput screening, combinatorial chemistry and molecular biology has radically changed the approach to drug discovery in the pharmaceutical industry. New challenges in synthesis result in new analytical methods. At present, typically 100,000 to one million molecules have to be tested within a short period and, therefore, highly effective screening methods are necessary for today's researchers – preparing and characterizing one compound after another belongs to the past. Intelligent, computer-based search agents are needed and «virtual screening» provides solutions to many problems. Such screening comprises innovative computational techniques designed to turn raw data into valuable chemical information and to assist in extracting the relevant molecular features. This handbook is unique in bringing together the various efforts in the field of virtual screening to provide the necessary methodological framework for more effective research. Leading experts give a thorough introduction to the state of the art along with a critical assessment of both successful applications and drawbacks. The information collated here will be indispensable for experienced scientists, as well as novices, working in medicinal chemistry and related disciplines.
Mass Spectrometry in Medicinal Chemistry
This first overview of mass spectrometry-based pharmaceutical analysis is the key to improved high-throughput drug screening, rational drug design and analysis of multiple ligand-target interactions. The ready reference opens with a general introduction to the use of mass spectrometry in pharmaceutical screening, followed by a detailed description of recently developed analytical systems for use in the pharmaceutical laboratory. Applications range from simple binding assays to complex screens of biological activity and systems containing multiple targets or ligands – all highly relevant techniques in the early stages in drug discovery, from target characterization to hit and lead finding.
Protein Crystallography in Drug Discovery
The rational, structure-based approach has become standard in present-day drug design. As a consequence, the availability of high-resolution structures of target proteins is more often than not the basis for an entire drug development program. Protein structures suited for rational drug design are almost exclusively derived from crystallographic studies, and drug developers are relying heavily on the power of this method. Here, researchers from leading pharmaceutical companies present valuable first-hand information, much of it published for the first time. They discuss strategies to derive high-resolution structures for such important target protein classes as kinases or proteases, as well as selected examples of successful protein crystallographic studies. A special section on recent methodological developments, such as for high-throughput crystallography and microcrystallization, is also included. A valuable companion for crystallographers involved in protein structure determination as well as drug developers pursuing the structure-based approach for use in their daily work.
Molecular Biology in Medicinal Chemistry
This readily comprehensible book explains the identification of molecular targets via cellular assays, reporter genes or transgenic models, as well as surveying recent advances in the synthesis, separation and analysis of drugs. A special section is devoted to molecular genetics methods. With its examination of these novel methods and generous practical advice, this is essential reading for all pharmaceutical chemists, molecular biologists and medical researchers using molecular methods to study drugs and their action.