Hanessian Natural Products in Medicinal Chemistry

1. Auflage 2013
ISBN: 978-3-527-67655-2
Verlag: Wiley-VCH
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, Band 60, 652 Seiten, E-Book

Reihe: Methods and Principles in Medicinal Chemistry

The inspiration provided by biologically active natural products to conceive of hybrids, congeners, analogs and unnatural variants is discussed by experts in the field in 16 highly informative chapters.   Using well-documented studies over the past decade, this timely monograph demonstrates the current importance and future potential of natural products as starting points for the development of new drugs with improved properties over their progenitors.   The examples are chosen so as to represent a wide range of natural products with therapeutic relevance among others, as anticancer agents, antimicrobials, antifungals, antisense nucleosides, antidiabetics, and analgesics.   From the content: * Part I: Natural Products as Sources of Potential Drugs and Systematic Compound Collections * Part II: From Marketed Drugs to Designed Analogs and Clinical Candidates * Part III: Natural Products as an Incentive for Enabling Technologies * Part IV: Natural Products as Pharmacological Tools * Part V: Nature: The Provider, the Enticer, and the Healer

Autoren/Hrsg.

Hanessian, Stephen

Weitere Mitwirkende

Mannhold, Raimund

Kubinyi, Hugo

Folkers, Gerd

Inhaltsverzeichnis

Preface   PART ONE: Natural Products as Sources of Potential Drugs and Systematic Compound Collections   NATURAL PRODUCTS AS DRUGS AND LEADS: AN INTRODUCTION AND PERSPECTIVE AS OF THE END OF 2012 Introduction The Sponge-Derived Nucleoside Link to Drugs Initial Recognition of Microbial Secondary Metabolites as Antibacterial Drugs Beta-Lactams of All Classes Tetracycline Derivatives Glycopeptide Antibacterials Lipopeptide Antibacterials Macrolide Antibiotics Pleuromutilin Derivatives Privileged Structures The Origin of the Benzodiazepines Benzopyrans: A Source of Unusual Antibacterial and Other Agents Multiple Enzymatic Inhibitors from Relatively Simple Natural Product Secondary Metabolites A Variation on BIOS: The "Inside-Out" Approach Other Privileged Structures Privileged Structures and Inhibitors of Protein-Protein Interactions Underprivileged Scaffolds So Where Should One Look in the Twenty-First Century for Novel Structures from Natural Sources? Conclusions   NATURAL PRODUCT-DERIVED AND NATURAL PRODUCT-INSPIRED COMPOUND COLLECTIONS Introduction Modern Approaches to Produce Natural Product Libraries Prefractionated Natural Product Libraries Libraries of Pure Natural Products Semisynthetic Libraries of Natural Product-Derived Compounds Synthetic LIbraries of Natural Product-Inspired Compounds Compound Collections with Carbocyclic Core Structures Compound Cllections iwth Oxa-Heterocyclic Scaffolds Compound Collections with Aza-Heterocyclic Scaffolds Macrocyclic Compound Collections Outlook   PART TWO: From Marketed Drugs to Designed Analogs and Clinical Candidates   CHEMISTRY AND BIOLOGY OF EPOTHILONES Introduction: Discovery and Biological Activity Synthesis of Natural Epothilones Synthesis and Biological Activity of Nonnatural Epothilones Conformational Studies and Pharmacophore Modeling Conclusions   TAXOL, TAXOIDS, AND RELATED TAXANES Introduction and Historical Background Mechanism of Action and Drug Resistance Structure-Activity Relationships (SAR) of Taxol Structural and Chemical Biology of Taxol New-Generation Taxoids from 10-DAB Taxoids in Clinical Development New Applications of Taxanes Conclusions and Perspectives   CAMPTOTHECIN AND ANALOGS Introduction Biology Activity Camptothecin in Clinical Use and Under Clinical Trials Chemistry Structure-Activity Relationship Xenograft Studies Prodrug/Targeting Developments of Modern Chromatographic Methods Applied to CPT Conclusions and Perspectives   A SHORT HISTORY OF THE DISCOVERY AND DEVELOPMENT OF NALTREXONE AND OTHER MORPHINE DERIVATIVES Introduction History and Development Pharmacology Structure-Activity Relationship of Morphine and its Analogs Conclusions and Outlook   LINCOSAMIDE ANTIBACTERIALS Introduction Mechanism of Action Antibacterial Spectrum Resistance Pseudomembraneous Colitis Next-Generation Lincosamides Conclusions   PLATENSIMYCIN AND PLATENCIN Introduction and Historical Background Discovery and Bioactivities of Platensimycin and Platencin Total and Formal Syntheses of Platensimycin Total and Formal Syntheses of Platencin Analogs of Platensimycin and Platencin Conclusions and Perspective   FROM NATURAL PRODUCT TO NEW DIABETES THERAPY: PHLORIZIN AND THE DISCOVERY OF SGLT2 INHIBITOR CLINICAL CANDIDATES Introduction Phlorizin: A Drug Lead from Apple Trees Phlorizin: Mechanism of Action Phlorizin, SGLTs, and Diabetes Phlorizin Analogs: O-Glucosides Phlorizin Analogs: C-Glucosides C-Glucosides: Aglycone Modifications C-Glucosides: Sugar Modifications Conclusions   AERUGINOSINS AS THROMBIN INHIBITORS Introduction Targeting the Blood Coagulation Cascade Structure of Thrombin The Aeruginosin Family Mimicking Nature Conclusions   PART THREE: Natural Products as an Incentive for Enabling Technologies   MACROLIDES AND ANTIFUNGALS VIA BIOTRANSFORMATION Introduction to Polyketides and Their Activity Mechanism of Polyketide Biosynthesis Conclusions   UNNATURAL NUCLEOSIDE ANALOGS FOR ANTISENSE THERAPY Nature Uses Nucleid Acid Polymers for Storage, Transfer, Synthesis, and Regulation

Über Autor(innen)

Stephen Hanessian holds the Isis Pharmaceuticals Research Chair at the University of Montreal and is also on the faculty of the Departments of Chemistry, Pharmaceutical Sciences and Pharmacology at the University of California, Irvine. He has received numerous awards and distinctions, the latest being the 2012 Ernest Guenther Award in the Chemistry of Natural Products from the American Chemical Society, the IUPAC-Richter Prize in Medicinal Chemistry, and the Montreal InVivo Prize for innovation. Professor Hanessian has over 500 journal publications to his name, which span a wide cross-section of areas related to organic, bioorganic, and medicinal chemistry. His latest book "Design and Strategy in Organic Synthesis - From the Chiron Approach to Catalysis" (Wiley-VCH) has received wide acclaim.