SMALL MOLECULE MEDICINAL CHEMISTRY: STRATEGIES AND TECHNOLOGIES

Stressing strategic and technological solutions to medicinal chemistry challenges, this book presents methods and practices for optimizing the chemical aspects of drug discovery. Chapters discuss benefits, challenges, case studies, and industry perspectives for improving drug discovery programs with respect to quality and costs.

• Focuses on small molecules and their critical role in medicinal chemistry, reviewing chemical and economic advantages, challenges, and trends in the field from industry perspectives
• Discusses novel approaches and key topics, like screening collection enhancement, risk sharing, HTS triage, new lead finding approaches, diversity-oriented synthesis, peptidomimetics, natural products, and high throughput medicinal chemistry approaches
• Explains how to reduce design-make-test cycle times by integrating medicinal chemistry, physical chemistry, and ADME profiling techniques
• Includes descriptive case studies, examples, and applications to illustrate new technologies and provide step-by-step explanations to enable them in a laboratory setting

Author Information
- Werngard Czechtizky is the Head of Medicinal Chemistry of the German Hub of Sanofi, based in Frankfurt, Germany. She has wide experience in lead generation and lead optimization for central nervous system, cardiovascular and diabetes targets, and her teams have been responsible for a number of leads and clinical candidates in these areas over the last years. She was educated at ETH Zürich and Harvard University, USA.

- Peter Hamley is the global head of External Innovation and Sourcing for chemistry, computational chemistry, and screening technologies at Sanofi, based in Frankfurt, Germany. He spent ten years at AstraZeneca in the United Kingdom, and then moved to Sanofi as a medicinal chemistry leader, building their automated chemistry capabilities and natural product technology. He was educated at Imperial College, London, the University of Cambridge and the University of Pennsylvania.

Table of Contents
Part I Exploring Biological Space: Access to New Collections 11
1 Elements for the Development of Strategies for Compound Library Enhancement 13
2 The European Lead Factory 37
3 Access to Compound Collections: New Business Models for Compound Acquisition and Sharing 61

Part II Exploring Biological Space: Access to New Chemistries 77
4 New Advances in Diversity ]Oriented Synthesis 79
5 Solid ]Phase Combinatorial Chemistry 103
6 Recent Advances in Multicomponent Reaction Chemistry: Applications in Small Molecule Drug Discovery 145
7 Computational Techniques to Support Hit Triage 191
8 Fragment ]Based Drug Discovery 221
9 Virtual Screening 251
10 Phenotypic Screening 281

Part IV Technologies for Medicinal Chemistry Optimization 305
11 Advances in the Understanding of Drug Properties in Medicinal Chemistry 307
12 Recent Developments in Automated Solution Phase Library Production 323
13 A DME Profiling: An Introduction for the Medicinal Chemist 353

Part V Medicinal Chemistry beyond Small Molecules 379
14 The Role of Natural Products in Drug Discovery: Examples of Marketed Drugs 381
15 Peptidomimetics of a ]Helical and ß ]Strand Protein Binding Epitopes 431
16 In Vivo Imaging of Drug Action 465
Index 503