Molecular Diversity in Drug Design

by P.M. Dean

Author	: P.M. Dean
Publisher	: Springer Science & Business Media
Total Pages	: 261
Release	: 2007-05-08
Genre	: Science
ISBN	: 0306468735

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High-throughput screening and combinatorial chemistry are two of the most potent weapons ever to have been used in the discovery of new drugs. At a stroke, it seems to be possible to synthesise more molecules in a month than have previously been made in the whole of the distinguished history of organic chemistry, Furthermore, all the molecules can be screened in the same short period. However, like any weapons of immense power, these techniques must be used with care, to achieve maximum impact. The costs of implementing and running high-throughput screening and combinatorial chemistry are high, as large dedicated facilities must be built and staffed. In addition, the sheer number of chemical leads generated may overwhelm the lead optimisation teams in a hail of friendly fire. Mother nature has not entirely surrendered, as the number of building blocks that could be used to build libraries would require more atoms than there are in the universe. In addition, the progress made by the Human Genome Project has uncovered many proteins with different functions but related binding sites, creating issues of selectivity. Advances in the new field of pharmacogenomics will produce more of these challenges. There is a real need to make hi- throughput screening and combinatorial chemistry into 'smart' weapons, so that their power is not dissipated. That is the challenge for modellers, computational chemists, cheminformaticians and IT experts. In this book, we have broken down this grand challenge into key tasks.

Diversity-Oriented Synthesis

by Andrea Trabocchi

Author	: Andrea Trabocchi
Publisher	: John Wiley & Sons
Total Pages	: 550
Release	: 2013-06-17
Genre	: Science
ISBN	: 1118618149

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Discover an enhanced synthetic approach to developing and screening chemical compound libraries Diversity-oriented synthesis is a new paradigm for developing large collections of structurally diverse small molecules as probes to investigate biological pathways. This book presents the most effective methods in diversity-oriented synthesis for creating small molecule collections. It offers tested and proven strategies for developing diversity-oriented synthetic libraries and screening methods for identifying ligands. Lastly, it explores some promising new applications based on diversity-oriented synthesis that have the potential to dramatically advance studies in drug discovery and chemical biology. Diversity-Oriented Synthesis begins with an introductory chapter that explores the basics, including a discussion of the relationship between diversity-oriented synthesis and classic combinatorial chemistry. Divided into four parts, the book: Offers key chemical methods for the generation of small molecules using diversity-oriented principles, including peptidomimetics and macrocycles Expands on the concept of diversity-oriented synthesis by describing chemical libraries Provides modern approaches to screening diversity-oriented synthetic libraries, including high-throughput and high-content screening, small molecule microarrays, and smart screening assays Presents the applications of diversity-oriented synthetic libraries and small molecules in drug discovery and chemical biology, reporting the results of key studies and forecasting the role of diversity-oriented synthesis in future biomedical research This book has been written and edited by leading international experts in organic synthesis and its applications. Their contributions are based on a thorough review of the current literature as well as their own firsthand experience developing synthetic methods and applications. Clearly written and extensively referenced, Diversity-Oriented Synthesis introduces novices to this highly promising field of research and serves as a springboard for experts to advance their own research studies and develop new applications.

Drug-like Properties: Concepts, Structure Design and Methods

by Li Di

Author	: Li Di
Publisher	: Elsevier
Total Pages	: 549
Release	: 2010-07-26
Genre	: Science
ISBN	: 0080557619

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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

De novo Molecular Design

by Gisbert Schneider

Author	: Gisbert Schneider
Publisher	: Wiley-VCH
Total Pages	: 0
Release	: 2013-12-23
Genre	: Medical
ISBN	: 9783527334612

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Systematically examining current methods and strategies, this ready reference covers a wide range of molecular structures, from organic-chemical drugs to peptides, Proteins and nucleic acids, in line with emerging new drug classes derived from biomacromolecules. A leader in the field and one of the pioneers of this young discipline has assembled here the most prominent experts from across the world to provide first-hand knowledge. While most of their methods and examples come from the area of pharmaceutical discovery and development, the approaches are equally applicable for chemical probes and diagnostics, pesticides, and any other molecule designed to interact with a biological system. Numerous images and screenshots illustrate the many examples and method descriptions. With its broad and balanced coverage, this will be the firststop resource not only for medicinal chemists, biochemists and biotechnologists, but equally for bioinformaticians and molecular designers for many years to come. From the content: * Reaction-driven de novo design * Adaptive methods in molecular design * Design of ligands against multitarget profiles * Free energy methods in ligand design * Fragment-based de novo design * Automated design of focused and target family-oriented compound libraries * Molecular de novo design by nature-inspired computing * 3D QSAR approaches to de novo drug design * Bioisosteres in de novo design * De novo design of peptides, proteins and nucleic acid structures, including RNA aptamers and many more.

Small Molecule Drug Discovery

by Andrea Trabocchi

Author	: Andrea Trabocchi
Publisher	: Elsevier
Total Pages	: 358
Release	: 2019-11-23
Genre	: Science
ISBN	: 0128183500

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Small Molecule Drug Discovery: Methods, Molecules and Applications presents the methods used to identify bioactive small molecules, synthetic strategies and techniques to produce novel chemical entities and small molecule libraries, chemoinformatics to characterize and enumerate chemical libraries, and screening methods, including biophysical techniques, virtual screening and phenotypic screening. The second part of the book gives an overview of privileged cyclic small molecules and major classes of natural product-derived small molecules, including carbohydrate-derived compounds, peptides and peptidomimetics, and alkaloid-inspired compounds. The last section comprises an exciting collection of selected case studies on drug discovery enabled by small molecules in the fields of cancer research, CNS diseases and infectious diseases. The discovery of novel molecular entities capable of specific interactions represents a significant challenge in early drug discovery. Small molecules are low molecular weight organic compounds that include natural products and metabolites, as well as drugs and other xenobiotics. When the biological target is well defined and understood, the rational design of small molecule ligands is possible. Alternatively, small molecule libraries are being used for unbiased assays for complex diseases where a target is unknown or multiple factors contribute to a disease pathology. - Outlines modern concepts and synthetic strategies underlying the building of small molecules and their chemical libraries useful for drug discovery - Provides modern biophysical methods to screening small molecule libraries, including high-throughput screening, small molecule microarrays, phenotypic screening and chemical genetics - Presents the most advanced chemoinformatics tools to characterize the structural features of small molecule libraries in terms of chemical diversity and complexity, also including the application of virtual screening approaches - Gives an overview of structural features and classification of natural product-derived small molecules, including carbohydrate derivatives, peptides and peptidomimetics, and alkaloid-inspired small molecules

Structure-based Design of Drugs and Other Bioactive Molecules

by Arun K. Ghosh

Author	: Arun K. Ghosh
Publisher	: John Wiley & Sons
Total Pages	: 474
Release	: 2014-08-11
Genre	: Medical
ISBN	: 3527333657

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Drug design is a complex, challenging and innovative research area. Structure-based molecular design has transformed the drug discovery approach in modern medicine. Traditionally, focus has been placed on computational, structural or synthetic methods only in isolation. This one-of-akind guide integrates all three skill sets for a complete picture of contemporary structure-based design. This practical approach provides the tools to develop a high-affinity ligand with drug-like properties for a given drug target for which a high-resolution structure exists. The authors use numerous examples of recently developed drugs to present "best practice" methods in structurebased drug design with both newcomers and practicing researchers in mind. By way of a carefully balanced mix of theoretical background and case studies from medicinal chemistry applications, readers will quickly and efficiently master the basic skills of successful drug design. This book is aimed at new and active medicinal chemists, biochemists, pharmacologists, natural product chemists and those working in drug discovery in the pharmaceutical industry. It is highly recommended as a desk reference to guide students in medicinal and chemical sciences as well as to aid researchers engaged in drug design today.

Molecular Diversity in Drug Design

by P.M. Dean

Author	: P.M. Dean
Publisher	: Springer Science & Business Media
Total Pages	: 261
Release	: 1999-10-31
Genre	: Medical
ISBN	: 0792359801

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This book focuses on the theoretical problems associated with molecular diversity as it is being applied in the pharmaceutical industry. Therefore, this book deals with algorithms that are involved in understanding chemical space and selection of diverse sets of structures. The algorithms also deal with the problem of focused diversity where chemical libraries are being created within a structured physical volume. Diversity is necessarily connected to combinational chemistry, although this book is limited to the application of diversity methods to combinational chemistry and does not deal with synthetic methods. It is this focus on algorithms and strategies for exploiting molecular diversity that makes it different from books on combinational chemistry. The intended readership of the book falls into two categories: those actively engaged in applying molecular diversity in the chemical industry and those in academia who are developing strategies to embrace, understand and accept the many problems thrown up by this new research field of molecular diversity.

Diversity Oriented Synthesis

by Andrea Basso

Author	: Andrea Basso
Publisher	: Frontiers Media SA
Total Pages	: 150
Release	: 2019-03-22
Genre	:
ISBN	: 2889457885

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Has the concept of Diversity Oriented Synthesis remained unchanged over these two decades, or do we observe improvements or deviations from the original guidelines drawn by the pioneers? The aim of this Research Topic is to collect contributions on the state-of-the-art and progress of Diversity Oriented Synthesis, and to foresee its shape in the next decade.

Anticancer Agents from Natural Products

by Gordon M. Cragg

Author	: Gordon M. Cragg
Publisher	: CRC Press
Total Pages	: 610
Release	: 2005-06-13
Genre	: Medical
ISBN	: 1420039652

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Plants, marine organisms, and microorganisms have evolved complex chemical defense and signaling systems that are designed to protect them from predators and provide other biological benefits. These organisms thus produce substances containing novel chemotypes that may have beneficial effects for humans. As collection methods improve and new screen