Hanessian Natural Products in Medicinal Chemistry

1. Auflage 2013
ISBN: 978-3-527-67656-9
Verlag: Wiley-VCH
Format: EPUB
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.