Applications of Transition Metal Catalysis in Drug Discovery and Development

An Industrial Perspective

Author: Matthew L. Crawley,Barry M. Trost

Publisher: John Wiley & Sons

ISBN: 0470631325

Category: Medical

Page: 376

View: 5270

This book focuses on the drug discovery and development applications of transition metal catalyzed processes, which can efficiently create preclinical and clinical drug candidates as well as marketed drugs. The authors pay particular attention to the challenges of transitioning academically–developed reactions into scalable industrial processes. Additionally, the book lays the groundwork for how continued development of transition metal catalyzed processes can deliver new drug candidates. This work provides a unique perspective on the applications of transition metal catalysis in drug discovery and development – it is a guide, a historical prospective, a practical compendium, and a source of future direction for the field.
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Applications of Transition Metal Catalysis in Drug Discovery and Development

An Industrial Perspective

Author: Matthew L. Crawley,Barry M. Trost

Publisher: John Wiley & Sons

ISBN: 1118309839

Category: Science

Page: 384

View: 4372

This book focuses on the drug discovery and development applications of transition metal catalyzed processes, which can efficiently create preclinical and clinical drug candidates as well as marketed drugs. The authors pay particular attention to the challenges of transitioning academically-developed reactions into scalable industrial processes. Additionally, the book lays the groundwork for how continued development of transition metal catalyzed processes can deliver new drug candidates. This work provides a unique perspective on the applications of transition metal catalysis in drug discovery and development – it is a guide, a historical prospective, a practical compendium, and a source of future direction for the field.
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Transition Metal-Catalyzed Couplings in Process Chemistry

Case Studies From the Pharmaceutical Industry

Author: Javier Magano,Joshua R. Dunetz

Publisher: John Wiley & Sons

ISBN: 3527658920

Category: Science

Page: 401

View: 9200

Transition metal-catalyzed coupling reactions have a rich history that led to the awarding of the 2010 Nobel Prize in Chemistry to Professors Suzuki, Heck, and Negishi for their pioneering contributions to the field. The coming of age of this active area of research is showcased in this book through case studies in which process chemists from the pharmaceutical industry share their personal experiences developing their own transition metal-catalyzed couplings for the large-scale manufacture of active pharmaceutical ingredients. Authors from Pfizer, Merck, Boehringer-Ingelheim, Novartis, Amgen, GSK, AstraZeneca, and other companies describe the evolution of robust coupling processes from inception through early and late development, including commercial routes where applicable. This book covers a wide range of coupling transformations while capturing the lessons learned from each process. Every case study details the optimization of at least one transition metal-catalyzed coupling while elaborating on issues such as design of experiments, scalability and throughput, product purification, process safety, and waste management. The important issue of metal removal and the different technologies available to accomplish this goal are also addressed. Finally, a section covers novel technologies for cross-coupling with high potential for future applications on a large scale, such as microwave and flow chemistry as well as green cross-couplings performed in water. With Forewords by Stephen L. Buchwald, Massachusetts Institute of Technology, Trevor Laird, Editor of Organic Process Research and Development and Neal G. Anderson, Anderson's Process Solutions LLC.
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Synthetic Methods in Drug Discovery

Author: David C Blakemore,Paul M Doyle,Yvette M Fobian

Publisher: Royal Society of Chemistry

ISBN: 178262208X

Category: Science

Page: 455

View: 7776

Synthetic Methods in Drug Discovery Volume 1 focusses on the hugely important area of transition metal mediated methods used in industry. Current methods of importance such as the Suzuki-Miyaura coupling, Buchwald-Hartwig couplings and CH activation are discussed. In addition, exciting emerging areas such as decarboxylative coupling, and the uses of iron and nickel in coupling reactions are also covered. This book provides both academic and industrial perspectives on some key reactions giving the reader an excellent overview of the techniques used in modern synthesis. Reaction types are conveniently framed in the context of their value to industry and the challenges and limitations of methodologies are discussed with relevant illustrative examples. Edited and authored by leading scientists from both academia and industry, this book will be a valuable reference for all chemists involved in drug discovery as well as postgraduate students in medicinal chemistry.
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Palladium-Catalyzed Modification of Nucleosides, Nucleotides and Oligonucleotides

Author: Anant R. Kapdi,Debabrata Maiti,Yogesh S. Sanghvi

Publisher: Elsevier

ISBN: 012811293X

Category: Science

Page: 358

View: 9994

Palladium-Catalyzed Modification of Nucleosides, Nucleotides and Oligonucleotides describes the procedures and protocols related to the modification of nucleosides, nucleotides and oligonucleotides via Pd-mediated cross-coupling processes. The book highlights the growing area of nucleic acid modification and how Pd-mediated coupling reactions can assist this development. Users will find key synthetic protocols for these reactions in this latest volume in the Latest Trends in Palladium Chemistry series. As most of the research in the field of antiviral agents has centered on the use of modified nucleosides that have exhibited promising activity, this book provides an up-to-date reference for both professionals in industry and other interested parties. Provides synthetic routes for useful nucleoside molecules, information otherwise found only through time-consuming literature searches Covers metal-mediated and metal-catalyzed cross coupling processes of nucleosides and related compounds Includes Suzuki-Miyaura, Stille and Sonogashira reactions, as well as C-H bond functionalization Highlights the growing area of nucleic acid modification and how Pd-mediated coupling reactions can assist
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Privileged Structures in Drug Discovery

Medicinal Chemistry and Synthesis

Author: Larry Yet

Publisher: John Wiley & Sons

ISBN: 1118686357

Category: Medical

Page: 560

View: 8448

A comprehensive guide to privileged structures and their application in the discovery of new drugs The use of privileged structures is a viable strategy in the discovery of new medicines at the lead optimization stages of the drug discovery process. Privileged Structures in Drug Discovery offers a comprehensive text that reviews privileged structures from the point of view of medicinal chemistry and contains the synthetic routes to these structures. In this text, the author—a noted expert in the field—includes an historical perspective on the topic, presents a practical compendium to privileged structures, and offers an informed perspective on the future direction for the field. The book describes the up-to-date and state-of-the-art methods of organic synthesis that describe the use of privileged structures that are of most interest. Chapters included information on benzodiazepines, 1,4-dihydropyridines, biaryls, 4-(hetero)arylpiperidines, spiropiperidines, 2-aminopyrimidines, 2-aminothiazoles, 2-(hetero)arylindoles, tetrahydroisoquinolines, 2,2-dimethylbenzopyrans, hydroxamates, and bicyclic pyridines containing ring-junction nitrogen as privileged scaffolds in medicinal chemistry. Numerous, illustrative case studies document the current use of the privileged structures in the discovery of drugs. This important volume: Describes the drug compounds that have successfully made it to the marketplace and the chemistry associated with them Offers the experience from an author who has worked in many therapeutic areas of medicinal chemistry Details many of the recent developments in organic chemistry that prepare target molecules Includes a wealth of medicinal chemistry case studies that clearly illustrate the use of privileged structures Designed for use by industrial medicinal chemists and process chemists, academic organic and medicinal chemists, as well as chemistry students and faculty, Privileged Structures in Drug Discovery offers a current guide to organic synthesis methods to access the privileged structures of interest, and contains medicinal chemistry case studies that document their application.
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Inorganic and Organometallic Transition Metal Complexes with Biological Molecules and Living Cells

Author: Kenneth Kam-Wing Lo

Publisher: Academic Press

ISBN: 012803887X

Category: Science

Page: 406

View: 4664

Inorganic and Organometallic Transition Metal Complexes with Biological Molecules and Living Cells provides a complete overview of this important research area that is perfect for both newcomers and expert researchers in the field. Through concise chapters written and edited by esteemed experts, this book brings together a comprehensive treatment of the area previously only available through scattered, lengthy review articles in the literature. Advanced topics of research are covered, with particular focus on recent advances in the biological applications of transition metal complexes, including inorganic medicine, enzyme inhibitors, antiparasital agents, and biological imaging reagents. Geared toward researchers and students who seek an introductory overview of the field, as well as researchers working in advanced areas Focuses on the interactions of inorganic and organometallic transition metal complexes with biological molecules and live cells Foscuses on the fundamentals and their potential therapeutic and diagnostic applications Covers recent biological applications of transition metal complexes, such as anticancer drugs, enzyme inhibitors, bioconjugation agents, chemical biology tools, and bioimaging reagents
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Modern Methods of Drug Discovery

Author: Alexander Hillisch,Rolf Hilgenfeld

Publisher: Birkhäuser

ISBN: 3034879970

Category: Medical

Page: 292

View: 6074

Research in the pharmaceutical industry today is in many respects quite different from what it used to be only fifteen years ago. There have been dramatic changes in approaches for identifying new chemical entities with a desired biological activity. While chemical modification of existing leads was the most important approach in the 1970s and 1980s, high-throughput screening and structure-based design are now major players among a multitude of methods used in drug discov ery. Quite often, companies favor one of these relatively new approaches over the other, e.g., screening over rational design, or vice versa, but we believe that an intelligent and concerted use of several or all methods currently available to drug discovery will be more successful in the medium term. What has changed most significantly in the past few years is the time available for identifying new chemical entities. Because of the high costs of drug discovery projects, pressure for maximum success in the shortest possible time is higher than ever. In addition, the multidisciplinary character of the field is much more pronounced today than it used to be. As a consequence, researchers and project managers in the pharmaceutical industry should have a solid knowledge of the more important methods available to drug discovery, because it is the rapidly and intelligently combined use of these which will determine the success or failure of preclinical projects.
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Diversity-Oriented Synthesis

Basics and Applications in Organic Synthesis, Drug Discovery, and Chemical Biology

Author: Andrea Trabocchi

Publisher: John Wiley & Sons

ISBN: 1118618149

Category: Science

Page: 664

View: 6334

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.
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Mass Spectrometry in Drug Discovery

Author: David T. Rossi,Michael Sinz

Publisher: CRC Press

ISBN: 9781420002478

Category: Medical

Page: 432

View: 4967

Mass Spectrometry in Drug Discovery summarizes the theory, instrumentation, techniques, and application of mass spectrometry and atmospheric pressure ionization to screening, evaluating, and improving the performance and quality of drug candidates. It provides time- and cost-efficient approaches for the generation and analysis of effective pharmaceuticals, covers advances in combinatorial chemistry, molecular biology, bioanalysis automation, and computing, and demonstrates the use of mass spectrometry in the assessment of disease states, drug targets, and potential drug agents.
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Green Techniques for Organic Synthesis and Medicinal Chemistry

Author: Wei Zhang,Berkeley Cue

Publisher: John Wiley & Sons

ISBN: 0470711515

Category: Medical

Page: 742

View: 4208

Green chemistry is a new way of looking at organic synthesis and the design of drug molecules, offering important environmental and economic advantages over traditional synthetic processes. Pharmaceutical companies are increasingly turning to the principles of green chemistry in an effort to reduce waste, reduce costs and develop environmentally benign processes. Green Techniques for Organic Synthesis and Medicinal Chemistry presents an overview of the established and emerging techniques in green organic chemistry, highlighting their applications in medicinal chemistry. The book is divided into four parts: Introduction: Introduces the reader to the toxicology of organic chemicals,their environmental impact, and the concept of green chemistry. Green Catalysis: Covers a variety of green catalytic techniques including organocatalysis, supported catalysis, biocatalysis, fluorous catalysis, and catalytic direct C-H bond activation reactions. Green Synthetic Techniques: Presents a series of new techniques, assessing the green chemistry aspects and limitations (i.e. cost, equipment, expertise). Techniques include reactions in alternative solvents, atom economic multicomponent reactions, microwave and ultrasonic reactions, solid-supported synthesis, fluorous and ionic liquid-based recycling techniques, and flow reactors. Green Techniques in Pharmaceutical Industry: Covers applications of green chemistry concepts and special techniques for medicinal chemistry, including synthesis, analysis, separation, formulation, , and drug delivery. Process and business case studies are included to illustrate the applications in the pharmaceutical industry. Green Techniques for Organic Synthesis and Medicinal Chemistry is an essential resource on green chemistry technologies for academic researchers, R&D professionals and students working in organic chemistry and medicinal chemistry.
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Molecularly Imprinted Catalysts

Principles, Syntheses, and Applications

Author: Songjun Li,Shunsheng Cao,Sergey A. Piletsky,Anthony P.F. Turner

Publisher: Elsevier

ISBN: 012801444X

Category: Technology & Engineering

Page: 310

View: 5475

Molecularly Imprinted Catalysts: Principle, Synthesis, and Applications is the first book of its kind to provide an in-depth overview of molecularly imprinted catalysts and selective catalysis, including technical details, principles of selective catalysis, preparation processes, the catalytically active polymers themselves, and important progress made in this field. It serves as an important reference for scientists, students, and researchers who are working in the areas of molecular imprinting, catalysis, molecular recognition, materials science, biotechnology, and nanotechnology. Comprising a diverse group of experts from prestigious universities and industries across the world, the contributors to this book provide access to the latest knowledge and eye-catching achievements in the field, and an understanding of what progress has been made and to what extent it is being advanced in industry. The first book in the field on molecularly imprinted catalysts (MIPs) Provides a systematic background to selective catalysis, especially the basic concepts and key principles of the different MIP-based catalysts Features state-of-the art presentation of preparation methods and applications of MIPs Written by scientists from prestigious universities and industries across the world, and edited by veteran researchers in molecular imprinting and selective catalysis
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Spectral Methods in Transition Metal Complexes

Author: K. Sridharan

Publisher: Elsevier

ISBN: 0128096543

Category: Science

Page: 202

View: 3110

Spectral Methods in Transition Metal Complexes provides a conceptual understanding on how to interpret the optical UV-vis, vibrational EPR, and NMR spectroscopy of transition metal complexes. Metal complexes have broad applications across chemistry in the areas of drug discovery, such as anticancer drugs, sensors, special materials for specific requirements, and catalysis, so a thorough knowledge in preparation and characterization of metal complexes, while niche, is critical. Accessible to both the seasoned researcher and the graduate student alike, this book provides readers with a single source of content that addresses spectral methods in transition metal complexes. Provides readers with a single reference on metal complexes and coordination compounds Contains more than 100 figures, tables, and illustrations to aid in the retention of key concepts Authored by a scientist with nearly 40 years of experience in research and instruction
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Organic Synthesis Using Transition Metals

Author: Roderick Bates

Publisher: John Wiley & Sons

ISBN: 1118313666

Category: Science

Page: 464

View: 5674

Transition metals open up new opportunities for synthesis, because their means of bonding and their reaction mechanisms differ from those of the elements of the s and p blocks. In the last two decades the subject has mushroomed - established reactions are seeing both technical improvements and increasing numbers of applications, and new reactions are being developed. The practicality of the subject is demonstrated by the large number of publications coming from the process development laboratories of pharmaceutical companies, and its importance is underlined by the fact that three Nobel prizes have been awarded for discoveries in this field in the 21st Century already. Organic Synthesis Using Transition Metals, 2nd Edition considers the ways in which transition metals, as catalysts and reagents, can be used in organic synthesis, both for pharmaceutical compounds and for natural products. It concentrates on the bond-forming reactions that set transition metal chemistry apart from "classical" organic chemistry. Each chapter is extensively referenced and provides a convenient point of entry to the research literature. Topics covered include: introduction to transition metals in organic synthesis coupling reactions C-H activation carbonylative coupling reactions alkene and alkyne insertion reactions electrophilic alkene and alkyne complexes reactions of alkyne complexes carbene complexes h3- or p-allyl -allyl complexes diene, dienyl and arene complexes cycloaddition and cycloisomerisation reactions For this second edition the text has been extensively revised and expanded to reflect the significant improvements and advances in the field since the first edition, as well as the large number of new transition metal-catalysed processes that have come to prominence in the last 10 years – for example the extraordinary progress in coupling reactions using “designer” ligands, catalysis using gold complexes, new opportunities arising from metathesis chemistry, and C-H activation – without neglecting the well established chemistry of metals such as palladium. Organic Synthesis Using Transition Metals, 2nd Edition will find a place on the bookshelves of advanced undergraduates and postgraduates working in organic synthesis, catalysis, medicinal chemistry and drug discovery. It is also useful for practising researchers who want to refresh and enhance their knowledge of the field.
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Green Synthetic Approaches for Biologically Relevant Heterocycles

Author: Goutam Brahmachari

Publisher: Elsevier

ISBN: 0128005904

Category: Science

Page: 632

View: 5096

Green Synthetic Approaches for Biologically Relevant Heterocycles reviews this significant group of organic compounds within the context of sustainable methods and processes. Each clearly structured chapter features in-depth coverage of various green protocols for the synthesis of a wide variety of bioactive heterocycles classified on the basis of ring-size and/or presence of heteratoms(s). Techniques covered include microwave heating, ultrasound, ionic liquids, solid phase, solvent-free, heterogeneous catalysis, and aqueous media, along with multi-component reaction strategies. This book also integrates advances in green chemistry research into industrial applications and process developments. Green Synthetic Approaches for Biologically Relevant Heterocycles is an essential resource on green chemistry technologies for academic researchers, R&D professionals, and students working in medicinal, organic, natural product, and agricultural chemistry. Includes global coverage of a wide variety of green synthetic techniques Features cutting-edge research in the field of bioactive heterocyclic compounds Focuses extensively on applications, with numerous examples of biologically relevant heterocycles
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Drug-Like Properties

Concepts, Structure Design and Methods from ADME to Toxicity Optimization

Author: Li Di,Edward H Kerns

Publisher: Academic Press

ISBN: 0128013222

Category: Science

Page: 580

View: 9580

Of the thousands of novel compounds that a drug discovery project team invents and that bind to the therapeutic target, only a fraction have sufficient ADME (absorption, distribution, metabolism, elimination) properties, and acceptable toxicology properties, to become a drug product that will successfully complete human Phase I clinical trials. Drug-Like Properties: Concepts, Structure Design and Methods from ADME to Toxicity Optimization, Second Edition, provides scientists and students the background and tools to understand, discover, and develop optimal clinical candidates. This valuable resource explores physiochemical properties, including solubility and permeability, before exploring how compounds are absorbed, distributed, and metabolized safely and stably. Review chapters provide context and underscore the importance of key concepts such as pharmacokinetics, toxicity, the blood-brain barrier, diagnosing drug limitations, prodrugs, and formulation. Building on those foundations, this thoroughly updated revision covers a wide variety of current methods for the screening (high throughput), diagnosis (medium throughput) and in-depth (low throughput) analysis of drug properties for process and product improvement. From conducting key assays for interpretation and structural analysis, the reader learns to implement modification methods and improve each ADME property. Through valuable case studies, structure-property relationship descriptions, and structure modification strategies, Drug-Like Properties, Second Edition, offers tools and methods for ADME/Tox scientists through all aspects of drug research, discovery, design, development, and optimization. Provides a comprehensive and valuable working handbook for scientists and students in medicinal chemistry Includes expanded coverage of pharmacokinetics fundamentals and effects Contains updates throughout, including the authors’ recent work in the importance of solubility in drug development; new and currently used property methods, with a reduction of seldom-used methods; and exploration of computational modeling methods
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Catalytic Cascade Reactions

Author: Peng-Fei Xu,Wei Wang

Publisher: John Wiley & Sons

ISBN: 1118016025

Category: Science

Page: 440

View: 7686

Demonstrates the advantages of catalytic cascade reactions for synthesizing natural products and pharmaceuticals Riding the wave of green chemistry, catalytic cascade reactions have become one of the most active research areas in organic synthesis. During a cascade reaction, just one reaction solvent, one workup procedure, and one purification step are needed, thus significantly increasing synthetic efficiency. Featuring contributions from an international team of pioneers in the field, Catalytic Cascade Reactions demonstrates the versatility and application of these reactions for synthesizing valuable compounds. The book examines both organocatalysis and transition-metal catalysis reactions, bringing readers up to date with the latest discoveries and activities in all major areas of catalytic cascade reaction research. Catalytic Cascade Reactions begins with three chapters dedicated to organocatalytic cascade reactions, exploring amines, Brønsted acids, and the application of organocatalytic cascade reactions in natural product synthesis and drug discovery. Next, the book covers: Gold-catalyzed cascade reactions Cascade reactions catalyzed by ruthenium, iron, iridium, rhodium, and copper Palladium-catalyzed cascade reactions of alkenes, alkynes, and allenes Application of transition-metal catalyzed cascade reactions in natural product synthesis and drug discovery Engineering mono- and multifunctional nanocatalysts for cascade reactions Multiple-catalyst-promoted cascade reactions All chapters are thoroughly referenced, providing quick access to important original research findings and reviews so that readers can explore individual topics in greater depth. Drawing together and analyzing published findings scattered across the literature, this book provides a single source that encapsulates our current understanding of catalytic cascade processes. Moreover, it sets the stage for the development of new catalytic cascade reactions and their applications.
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Transition Metals in the Synthesis of Complex Organic Molecules

Author: Louis S. Hegedus

Publisher: University Science Books

ISBN: 9781891389047

Category: Science

Page: 337

View: 9332

This second edition offers easy access to the field of organotransition metal chemistry. The book covers the basics of transition metal chemistry, giving a practical introduction to organotransition reaction mechanisms.
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