Small Molecule Medicinal Chemistry (eBook)

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.

"This book describes a large variety of methodologies that are employed in drug discovery and early development. The subjects covered range from the design and administration of chemical libraries, access to new chemical scaffolds and chemical diversity, to characterization of target binding and ADME profiling methods. While the book focuses on traditional small-molecule medicinal chemistry, an outlook to non-traditional targets such as protein-protein interactions and imaging applications is also provided. Most of the authors have a background in the pharmaceutical industry. The book therefore allows an insight into laboratories that are less prone to publish their experiences than their academic counterparts, and the trends and observations which accumulate over the years. In addition, particularly the academic reader is presented with sometimes refreshingly independent views on certain popular topics in medicinal chemistry and chemical biology that have reached "nuisance" status in recent years. For example, the discussion on "hit triage" contains a wide range of literature reference points beyond the currently over-debated assay-interference compounds that will allow the interested reader to obtain a well-balanced view. For an academic who is heavily involved in teaching duties, the book offers numerous highly useful overviews, such as the development chart of combinatorial chemistry methods. Although the heydays of combi-chem have long passed, the concept has remained an important addition to the toolbox of medicinal

chemistry, also in academic laboratories. Fittingly, one of the following chapters provides a review of multicomponent

reactions. This chapter is filled with numerous highly appreciated figures that collect and demonstrate the broad chemical diversity which is accessible via traditional and recently developed multicomponent reactions, a real treasure chest that will certainly be useful in teaching and research. There are some weaker parts in the book. This is, for example, the natural

products chapter, which starts with a reference to a "famous", highly biased publication that "proves" the importance of

natural products by classifying, for example, purely synthetic ATP-competitive kinase inhibitors as somehow natural-product- derived. This is followed by a long table that is mostly, and not surprisingly, composed of antibiotics and steroids of semisynthetic origin. Next, however, appear some interesting examples of such semi-synthetic strategies, which will be highly instructive for students and practitioners of medicinal chemistry. And these latter examples clearly demonstrate that it is actually not necessary to make natural products appear more important by creating just the right definition for terms such as "natural-product-derived". Somewhat annoying is the use of an insert for color figures, requiring frequent "lookups", particularly since the captions are not provided along with the color figures. However, this technical aspect is really minor, and may have been necessary to keep the price of the book at a reasonable level--about £130, which could also be in the range of interested students. For the reviewer, selected fragments of the book will certainly be integrated into the teaching curriculum, and the book will be recommended for students at all levels. "
(Prof. Christian Klein Heidelberg University - ChemMedChem, July 2017)