Molecular design . Concepts and applications

This book focuses on how different concepts and molecular modeling strategies could be exploited to design the molecular architecture of ligands for specific targets, as new drug candidates. The authors have large experience in drug discovery, occupying head positions in European pharmaceutical industries, which was crucial to their particular form to address the main design-related medicinal chemistry topics along the five chapters of the book. The foreword written by Hugo Kubinyi describes the importance of integrated and multidisciplinary work for the successful of rational drug design process. So, Schneider and Baringhaus used an easy and clear language to show the main advantages and disadvantages of several different approaches and technologies applied in molecular design of new chemical entities, highlighting the pitfalls and risks of the complex task of discovery a new drug. The first chapter presents the principal structural elements related to the molecules and what features should be persecuted to avoid or minimize the probability of unsuccessful during the clinical trials due to inadequate ADMET properties. In addition to the description of druglikeness properties, an important discussion about the importance of getting informations about the shape and the bioactive conformation of the bioligands is included. The second one introduces the phenomena related to receptor-ligand interactions pointing the more frequent types of bonds involved in the binding and how the enthalpic and entropic contributions could benefit the formation of stable complexes. At this point, the classical QSAR methods are introduced, demonstrating their evolution for the tridimensional (3D) approaches to access, indirectly, the structure of Carlos Alberto Manssour Fraga Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil cmfraga@pharma.ufrj.br