Details

Bioisosteres in Medicinal Chemistry


Bioisosteres in Medicinal Chemistry


Methods and Principles in Medicinal Chemistry, Band 54 1. Aufl.

von: Nathan Brown, Raimund Mannhold, Hugo Kubinyi, Gerd Folkers

135,99 €

Verlag: Wiley-VCH
Format: EPUB
Veröffentl.: 18.06.2012
ISBN/EAN: 9783527654321
Sprache: englisch
Anzahl Seiten: 256

DRM-geschütztes eBook, Sie benötigen z.B. Adobe Digital Editions und eine Adobe ID zum Lesen.

Beschreibungen

Written with the practicing medicinal chemist in mind, this is the first modern handbook to systematically address the topic of bioisosterism.<br> As such, it provides a ready reference on the principles and methods of bioisosteric replacement as a key tool in preclinical drug development.<br> <br> The first part provides an overview of bioisosterism, classical bioisosteres and typical molecular interactions that need to be considered,<br> while the second part describes a number of molecular databases as sources of bioisosteric identification and rationalization. The third part<br> covers the four key methodologies for bioisostere identification and replacement: physicochemical properties, topology, shape, and overlays of<br> protein-ligand crystal structures. In the final part, several real-world examples of bioisosterism in drug discovery projects are discussed.<br> <br> With its detailed descriptions of databases, methods and real-life case studies, this is tailor-made for busy industrial researchers with little time for reading, while remaining easily accessible to novice drug developers due to its systematic structure and introductory section.
PREFACE <br> <br> PART ONE: Principles <br> <br> BIOISOSTERISM IN MEDICINAL CHEMISTRY<br> Introduction<br> Isosterism<br> Bioisosterism <br> Bioisosterism in Lead Optimization<br> Conclusions <br> <br> CLASSICAL BIOISOSTERES <br> Introduction <br> Historical Background <br> Classical Bioisosteres <br> Nonclassical Bioisosteres <br> Summary <br> <br> CONSEQUENCES OF BIOISOSTERIC REPLACEMENT <br> Introduction <br> Bioisosteric Groupings to Improve Permeability<br> Bioisosteric Groupings to Lower Intrinsic Clearance <br> Bioisosteric Groupings to Improve Target Potency<br> Conclusions and Future Perspectives<br> <br> PART TWO: Data <br> <br> BIOSTER: A DATABASE OF BIOISOSTERES AND BIOANALOGUES<br> Introduction <br> Historical Overview and the Development of BIOSTER <br> Description of BIOSTER Database <br> Examples <br> Applications<br> Summary<br> Appendix <br> <br> MINING THE CAMBRIDGE STRUCTURAL DATABASE FOR BIOISOSTERES <br> Introduction <br> The Cambridge Structural Database<br> The Cambridge Structural Database System<br> The Relevance of the CSD to Drug Discovery <br> Assessing Bioisosteres: Conformational Aspects <br> Assessing Bioisosteres: Nonbonded Interactions <br> Finding Bioisosteres in the CSD: Scaffold Hopping and Fragment Linking<br> A Case Study: Bioisosterism of 1H-Tetrazole and Carboxylic Acid Groups <br> Conclusions <br> <br> MINING FOR CONTEXT-SENSITIVE BIOISOSTERIC REPLACEMENTS IN LARGE CHEMICAL DATABASES <br> Introduction <br> Definitions <br> Background <br> Materials and Methods <br> Results and Discussion <br> Conclusions <br> <br> PART THREE: Methods <br> <br> PHYSICOCHEMICAL PROPERTIES <br> Introduction <br> Methods to Identify Bioisosteric Analogues<br> Descriptors to Characterize Properties of Substituents and Spacers <br> Classical Methods for Navigation in the Substituent Space <br> Tools to Identify Bioisosteric Groups Based on Similarity in Their Properties <br> Conclusions <br> <br> MOLECULAR TOPOLOGY <br> Introduction <br> Controlled Fuzziness <br> Graph Theory <br> Data Mining <br> Topological Pharmacophores <br> Reduced Graphs <br> Summary <br> <br> MOLECULAR SHAPE <br> Methods <br> Applications <br> Future Prospects <br> <br> PROTEIN STRUCTURE<br> Introduction <br> Database of Ligand -<br> Protein Complexes <br> Generation of Ideas for Bioisosteres <br> Context-Specific Bioisostere Generation <br> Using Structure to Understand Common Bioisosteric Replacements<br> Conclusions <br> <br> PART FOUR: Applications <br> <br> THE DRUG GURU PROJECT <br> Introduction <br> Implementation of Drug Guru <br> Bioisosteres <br> Application of Drug Guru<br> Quantitative Assessment of Drug Guru Transformations<br> Related Work <br> Summary: The Abbott Experience with the Drug Guru Project<br> <br> BIOISOSTERES OF AN NPY-Y5 ANTAGONIST <br> Introduction <br> Background <br> Potential Bioisostere Approaches <br> Template Molecule Preparation<br> Database Molecule Preparation <br> Alignment and Scoring <br> Results and Monomer Selection <br> Synthesis and Screening <br> Discussion <br> SAR and Developability Optimization <br> Summary and Conclusion <br> <br> PERSPECTIVES FROM MEDICINAL CHEMISTRY <br> Introduction <br> Pragmatic Bioisostere Replacement in Medicinal Chemistry: A Software Maker.s Viewpoint<br> The Role of Quantum Chemistry in Bioisostere Prediction <br> Learn from ''Naturally Drug-Like'' Compounds <br> Bioisosterism at the University of Sheffield <br>
<p>“In all, I believe this book is a musthave handbook on bioisosteres. It is highly valuable both as a text book for graduate students and as a book of reference for the medicinal chemist working in the industry as well as in an academic setting.” (<i>ChemMedChem</i>, 1 July 2013)</p>
<b>Nathan Brown</b> is the Head of the In Silico Medicinal Chemistry group in the Cancer Therapeutics Unit at The Institute of Cancer Research in London (UK). At the ICR, Nathan and his group support our entire drug discovery portfolio together with developing new computational methodologies to enhance our drug design work.<br /> Nathan conducted his doctoral research in Sheffield with Professor Peter Willett focusing on evolutionary algorithms and graph theory. After a two-year Marie Curie fellowship in Amsterdam in collaboration with Professor Johann Gasteiger in Erlangen, he joined the Novartis Institutes for BioMedical Research in Basel for a three-year Presidential fellowship in Basel working with Professors Peter Willett and Karl-Heinz Altmann.<br /> Nathan?s work has led to the pioneering work on mulitobjective de novo design in addition to a variety of discoveries and method development in bioisosteric identification and replacement, scaffold hopping, molecular descriptors and statistical modelling. Nathan continues to pursue his research in all aspects of in silico medicinal chemistry.
Written with the practicing medicinal chemist in mind, this is the first modern handbook to systematically address the topic of bioisosterism.<br> As such, it provides a ready reference on the principles and methods of bioisosteric replacement as a key tool in preclinical drug development.<br> <br> The first part provides an overview of bioisosterism, classical bioisosteres and typical molecular interactions that need to be considered,<br> while the second part describes a number of molecular databases as sources of bioisosteric identification and rationalization. The third part<br> covers the four key methodologies for bioisostere identification and replacement: physicochemical properties, topology, shape, and overlays of<br> protein-ligand crystal structures. In the final part, several real-world examples of bioisosterism in drug discovery projects are discussed.<br> <br> With its detailed descriptions of databases, methods and real-life case studies, this is tailor-made for busy industrial researchers with little time for reading, while remaining easily accessible to novice drug developers due to its systematic structure and introductory section.

Diese Produkte könnten Sie auch interessieren:

Hot-Melt Extrusion
Hot-Melt Extrusion
von: Dennis Douroumis
PDF ebook
126,99 €
Hot-Melt Extrusion
Hot-Melt Extrusion
von: Dennis Douroumis
EPUB ebook
126,99 €
Kunststoffe
Kunststoffe
von: Wilhelm Keim
PDF ebook
99,99 €