Bioisosteres in Medicinal Chemistry

PREFACE
 
PART ONE: Principles
 
BIOISOSTERISM IN MEDICINAL CHEMISTRY
Introduction
Isosterism
Bioisosterism
Bioisosterism in Lead Optimization
Conclusions
 
CLASSICAL BIOISOSTERES
Introduction
Historical Background
Classical Bioisosteres
Nonclassical Bioisosteres
Summary
 
CONSEQUENCES OF BIOISOSTERIC REPLACEMENT
Introduction
Bioisosteric Groupings to Improve Permeability
Bioisosteric Groupings to Lower Intrinsic Clearance
Bioisosteric Groupings to Improve Target Potency
Conclusions and Future Perspectives
 
PART TWO: Data
 
BIOSTER: A DATABASE OF BIOISOSTERES AND BIOANALOGUES
Introduction
Historical Overview and the Development of BIOSTER
Description of BIOSTER Database
Examples
Applications
Summary
Appendix
 
MINING THE CAMBRIDGE STRUCTURAL DATABASE FOR BIOISOSTERES
Introduction
The Cambridge Structural Database
The Cambridge Structural Database System
The Relevance of the CSD to Drug Discovery
Assessing Bioisosteres: Conformational Aspects
Assessing Bioisosteres: Nonbonded Interactions
Finding Bioisosteres in the CSD: Scaffold Hopping and Fragment Linking
A Case Study: Bioisosterism of 1H-Tetrazole and Carboxylic Acid Groups
Conclusions
 
MINING FOR CONTEXT-SENSITIVE BIOISOSTERIC REPLACEMENTS IN LARGE CHEMICAL DATABASES
Introduction
Definitions
Background
Materials and Methods
Results and Discussion
Conclusions
 
PART THREE: Methods
 
PHYSICOCHEMICAL PROPERTIES
Introduction
Methods to Identify Bioisosteric Analogues
Descriptors to Characterize Properties of Substituents and Spacers
Classical Methods for Navigation in the Substituent Space
Tools to Identify Bioisosteric Groups Based on Similarity in Their Properties
Conclusions
 
MOLECULAR TOPOLOGY
Introduction
Controlled Fuzziness
Graph Theory
Data Mining
Topological Pharmacophores
Reduced Graphs
Summary
 
MOLECULAR SHAPE
Methods

Nathan Brown is the Head of the In Silico Medicinal Chemistry group in the Cancer Research UK Cancer Therapeutics Unit at the Institute of Cancer Research in London (UK). At the ICR, Dr. Brown and his group support the entire drug discovery portfolio together with developing new computational methodologies to enhance the drug design work. Nathan Brown conducted his doctoral research in Sheffield with Professor Peter Willett focusing on evolutionary algorithms and graph theory applied to challenges in chemoinformatics.
 
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.
 
His work has led to the pioneering work on mulitobjective design in addition to a variety of discoveries and method development in bioisosteric identification and replacement, scaffold hopping, molecular descriptors and statistical modeling. Nathan continues to pursue his research in all aspects of medicinal chemistry.

"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." ( ChemMedChem , 1 July 2013)

"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." ( ChemMedChem , 1 July 2013)