Scaffold Hopping in Medicinal Chemistry

This first systematic treatment of the concept and practice of scaffold hopping shows the tricks of the trade and provides invaluable guidance for the reader?s own projects. The first section serves as an introduction to the topic by describing the concept of scaffolds, their discovery, diversity and representation, and their importance for finding new chemical entities. The following parts contain a general description as well as case studies of the most common tools and methods for scaffold hopping, whether topological, shape–based or structure–based. The final part contains three fully documented real–world examples of successful drug development projects by scaffold hopping that illustrate the benefits of the approach for medicinal chemistry. While most of the case studies are taken from medicinal chemistry, chemical and structural biologists will also benefit greatly from the insights presented here. INDICE: INTRODUCTION TO SCAFFOLD HOPPING Identifying and representing scaffolds Markush structures and chemical patents Diversity of scaffolds from natural products Scaffold diversity in medicinal chemistry space Exploring virtual scaffold spaces TOPOLOGICAL METHODS FOR SCAFFOLD HOPPING CATS vectors Reduced graphs Feature trees (FTrees) Extended connectivity fingerprints (ECFP) Maximum common substructure determination in MedChem Studio SHAPE–BASED METHODS FOR SCAFFOLD HOPPING Radial distribution function codes Rapid overlay of chemical structures (ROCS) FEPOPS ParaFit XED Forcefields and Fieldstere Ultrafast shape recognition (USR) PHARMACOPHORE AND STRUCTURE–BASED METHODS SkelGen Molecular interaction fingerprints ReCore SHOP SCAFFOLD HOPPING CASE STUDIES JAK2 inhibitors mGluR5 inhibitors Phosphatase inhibitors

• ISBN: 978-3-527-33364-6
• Editorial: Wiley VCH
• Encuadernacion: Cartoné
• Páginas: 328
• Fecha Publicación: 04/12/2013
• Nº Volúmenes: 1
• Idioma: Inglés