عنوان

Diversity-oriented synthesis : basics and applications in organic synthesis, drug discovery, and chemical biology

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electronic

Title Proper

Diversity-oriented synthesis : basics and applications in organic synthesis, drug discovery, and chemical biology

Specific Material Designation and Extent of Item

xxxiii, 629 pages : illustrations ; 25 cm

Text of Note

"Foreword by Stuart L. Schreiber"--cover

Text of Note

Includes bibliographical references )pages 611-617( and index

Text of Note

edited by Andrea Trabocchi, University of Florence, Sesto Fiorentino, Florence, Italy

Text of Note

Machine generated contents note: Foreword Stuart L. Schreiber Preface List of Contributors Abbreviations 1 The Basics of Diversity-Oriented Synthesis Kieron M. G. O'Connell, Warren R. J. D. Galloway and David R. Spring 1.1 Introduction 1.2 What is Diversity-Oriented Synthesis? 1.3 Small Molecules and Biology 1.4 Comparing DOS, TOS and Combinatorial Chemistry )Focused Library Synthesis( 1.5 Molecular Diversity 1.6 Molecular Diversity and Chemical Space 1.7 Synthetic Strategies for Creating Molecular Diversity 1.8 Reagent-Based Approaches to Diversity Generation 1.9 A Substrate-Based Approach to Skeletal Diversity Generation 1.01 Other Build/Couple/Pair Examples 1.11 Concluding Remarks 1.21 References Part I Chemical Methodology in Diversity-Oriented Synthesis 2 Strategies Applications of Multicomponent Reactions )MCRs( to Diversity-Oriented Synthesis John M. Knapp, Mark J. Kurth, Jared T. Shaw and Ashkaan Younai 2.1 Introduction 2.2 MCR Products for HTS 2.3 MCRs as Starting Points for DOS 2.4 Conclusion 2.5 References 3 Cycloaddition Reactions in Diversity-Oriented Synthesis Giovanni Muncipinto 3.1 Introduction 3.2 ]4+2[ Cycloaddition Reactions 3.3 Diels-Alder Reaction 3.4 Inverse Electron Demand Diels-Alder Reaction 3.5 1,3-dipolar Cycloaddition Reactions 3.6 Miscellaneous Cycloadditions 3.7 Conclusion 3.8 References 4 Phosphine Organocatalysis as the Platform for Diversity-Oriented Synthesis Ohyun Kwon and Zhiming Wang 4.1 Introduction 4.2 DOS using Phosphine Organocatalysis 4.2.1 Phosphine Organocatalysis of Allenes with Imines 4.3 Skeletal Diversity Based on a Phosphine Catalysis/Combinatorial Scaffolding Strategy 4.4 A DOS Library Based on Phosphine Organocatalysis: Biological Screening, Analogue Synthesis, and Structure-Activity Relationship Analysis 4.5 Conclusions 4.6 References 5 Domino Reactions in Library Synthesis Matthew G. LaPorte, John R. Goodell, Sammi Tsegay and Peter Wipf 5.1 Introduction 5.2 Pericyclic Domino Reactions 5.3 Anionic Domino Reactions 5.4 Transition Metal Mediated Domino Reactions 5.5 Radical Domino Reactions 5.6 Conclusions 5.7 References 6 Diversity-Oriented Synthesis of Amino Acid-Derived Scaffolds and Peptidomimetics: A Perspective Andrea Trabocchi 6.1 Introduction 6.2 Definition and Classification of Peptidomimetics 6.3 Early Combinatorial Approaches to Peptidomimetic Scaffolds 6.4 Amino Acid-Derived Scaffolds 6.5 Macrocyclic Peptidomimetic Scaffolds 6.6 Conclusion 6.7 References 7 Solid-phase Synthesis Enabling Chemical Diversity Viktor Krch۸nak and Nad?e da Canka۸rov? 7.1 Introduction 7.2 Skeletal Diversity 7.3 Substrate-Based Strategy )Folding Process( 7.4 Stereochemical Diversity 7.5 Appendages Diversity 7.6 Build/Couple/Pair Strategy 7.7 Scaffold Hopping 7.8 Conclusion 7.9 References 8 Macrocycles as Templates for Diversity Generation in Drug Discovery Eric Marsault 8.1 Introduction 8.2 Challenges Associated with Macrocycles 8.3 Macrocyclic Peptides 8.4 Peptidomimetic Macrocycles 8.5 Diversity-Oriented Strategies Based on Nonpeptidic Natural Products 8.6 Conclusion 8.7 References Part II Chemical Libraries and Diversity-Oriented Synthesis 9 Diversity-Oriented Synthesis of Natural Product-Based Libraries Mark Dow, Francesco Marchetti and Adam Nelson 9.1 Introduction 9.2 Libraries Inspired by Natural Product Scaffolds 9.3 Folding Pathways in the Synthesis of Natural Product-Like Libraries 9.4 Branching Pathways in the Synthesis of Natural Product-Like Libraries 9.5 Oligomer-Based Approaches to Natural Product-Like Libraries 9.6 Summary 9.7 References 01 Chemoinformatic Characterization of the Chemical Space and Molecular Diversity of Compound Libraries Jose Luis Medina-Franco 01.1 Introduction 01.2 Concept of Chemical Space 01.3 General Aspects of Chemoinformatic Methods to Analyze the Chemical Space 01.4 Chemoinformatic-Based Analysis of Libraries Using Different Representations 01.5 Recent Trends in Computational Approaches to Characterize Compound Libraries 01.6 Concluding Remarks 01.7 References 11 DNA-Encoded Chemical Libraries Luca Mannocci 11.1 Introduction 11.2 DNA-Encoded Chemical Libraries )DECL( 11.3 Selection and Decoding 11.4 Drug Discovery by DNA-Encoded Chemical Libraries 11.5 DNA-Encoded Chemical Libraries: Prospects and Outlook 11.6 Conclusion 11.7 References PART III Screening Methods and Lead Identification 21 Experimental Approaches for Rapid Profiling and Characterization of Specific Biological Effects of Diversity-Oriented Synthesis Compounds Eduard A. Sergienko and Susanne Heynen-Genel 21.1 Introduction 21.2 Basic Principles of HTS 21.3 Common Assay Methods and Techniques 21.4 Future Perspectives 21.5 References 31 Small-Molecule Microarrays Hongyan Sun 31.1 Introduction 31.2 Chemical Library Design and Synthesis 31.3 Fabrication of SMMs 31.4 Applications of SMM 31.5 Summary and Outlook 31.6 References 41 Yeast as a Model in High-Throughput Screening of Small Molecule Libraries Duccio Cavalieri, Carlotta De Filippo and Irene Stefanini 41.1 Introduction 41.2 Chemical Genetics and S. cerevisiae 41.3 Chemical Genomics and S. cerevisiae 41.4 Conclusions: the Route of Drug Discovery with the Budding Yeast 41.5 References 51 Virtual Screening Methods Jurgen Bajorath 51.1 Introduction 51.2 Basic Virtual Screening Concepts 51.3 Molecular Similarity in Virtual Screening 51.4 Spectrum of Virtual Screening Approaches 51.5 Docking 51.6 Similarity Searching 51.7 Compound Classification 51.8 Machine Learning 51.9 Conclusions 51.01 References 61 Structure-Activity Relationship Data Analysis: Activity Landscapes and Activity Cliffs Jurgen Bajorath 61.1 Introduction 61.2 Numerical SAR Analysis Functions 61.3 Principles and Intrinsic Limitations of Activity Landscape Design 61.4 Activity Landscape Representations 61.5 Defining and Identifying Activity Cliffs 61.6 Activity Cliff Survey 61.7 Activity Cliffs and SAR Information 61.8 Concluding Remarks 61.9 References PART IV Applications in Chemical Biology and Drug Discovery 71 Diversity-Oriented Synthesis and Drug Development: Facilitating the Discovery of Novel Probes and Therapeutics Jeremy R. Duvall, Eamon Comer and Sivaraman Dandapani 71.1 Introduction 71.2 Case Study 1 - Inhibition of Cytokine-Induced ]symbol for square[-Cell Apoptosis 71.3 Case Study 2 - Identification of Anti-Malarials 71.4 Case Study 3 - Targeting Protein-Protein and Protein-DNA Interactions 71.5 Conclusion 71.6 References 81 DOS-Derived Small-Molecule Probes in Chemical Biology Nicholas Hill, Lingyan Du and Qiu Wang 81.1 Introduction 81.2 DOS-Derived Small-Molecule Probes 81.3 Developing Small-Molecule Probes of Complex Biological Pathways 81.4 Expanding the Collection of Important Biological Probes 81.5 Developing Probes for Therapeutically Desirable Phenotypes 81.6 Natural Product-Inspired Small-Molecule Probes Developed from DOS and Biology-Oriented Synthesis 81.7 Summary and Outlook 81.8 References Index

Entry Element

Synthesis ، Organic compounds

Entry Element

، Drug development

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، Biosynthesis

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، SCIENCE / Chemistry / Organic

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TI

AU Trabocchi, Andrea