Reviews Medicinal chemistry
Innovative methods in drug design
T
he discovery of new medicines relies on, indeed often starts with, the ability to make new chemical or biological entities with a defined pharmacological profile. New synthetic technologies that make previously uncharted areas of chemical space accessible, or help to produce known chemical entities more efficiently, are therefore of great value for drug discovery. This title, which is the latest addition to the successful RSC Drug discovery series, gives an overview of such technologies that have emerged over the past 15–20 years and have had, or are expected to have, a considerable impact on the way new drugs are being discovered today and in the future. The scientific material presented in the book is
organised in five chapters. All have been written by experts in the respective field, often with substantial first-hand drug discovery experience in the pharmaceutical industry. There is, therefore, often a welcome focus on practical applications, with many examples from recent drug discovery efforts.
Given the different authors, the style and
structure of the individual chapters varies necessarily. Thus, the chapter on high-throughput chemistry – including combinatorial chemistry – takes a historical perspective, tracing the evolution of high-throughput chemistry from its
New synthetic technologies in medicinal chemistry
Editor Elizabeth Farrant Publisher RSC Publishing Year 2011 Pages 164 Price £99.99 ISBN 978-1-84973-305-2
beginnings in peptide chemistry in the early 1990s to current approaches and the high-throughput synthesis of small molecules. The power of high-throughput approaches is illustrated with specific examples from recent drug discovery, both in lead identification, for example, follicle stimulating hormone receptor agonists, and SAR development, for example, NPY-5 receptor antagonists and cholesterol ester transfer protein inhibitors. The chapter on high-throughput reaction
screening illustrates the power of these methods not only for the generation of large libraries of compounds, but also for the optimisation of individual compound syntheses. The chosen examples place a particular emphasis on metal- catalysed reactions as well as biotransformations. The success of high-throughput reaction screening has often been intricately linked to the availability of new synthetic methodologies, such as flow chemistry and microwave chemistry, which are discussed in detail later in the book. The impact microwave chemistry has had on synthetic and medicinal chemistry over the past 15 years or so is illustrated with selected examples of transformations that are central to medicinal chemistry today, including metal- catalysed reactions, transfer hydrogenations, and the synthesis of heterocycles. The dedicated chapter provides an excellent
demonstration of the range of chemistries that can now be performed under microwave conditions, and of the advantages this offers over conventional heating, such as shorter reaction times and milder conditions.
Flow chemistry is only just beginning to grow, at least in terms of its industrial application. Perhaps for this reason, its coverage is more technical, providing an introduction to basic flow theory and a comprehensive overview of relevant experimental parameters. The book concludes with the chapter:
‘Emerging synthetic technologies’. This title is a little misleading because the chapter focuses on
48 Chemistry&Industry • November 2012
concepts such as dynamic combinatorial chemistry (DCC), which have been around for a while – indeed, DCC is also briefly covered in the chapter on high-throughput chemistry. It can be argued that DCC has so far had less of an impact on medicinal chemistry than originally hoped for, and certainly less so than technological advances such as microwave chemistry, and that the best of this technique is yet to come. Although arguably beyond the ‘chemistry’
remit of this book, it would have been interesting and useful if this final chapter had also touched upon relevant emerging techniques in adjacent fields, such as synthetic biology. While at present it may mean different things to different people, there is little doubt that synthetic biology will very likely have a considerable impact on the way medicinal chemistry is done in the future. Overall, this book represents
a valuable resource for medicinal chemists in both industry and academia. It provides concise introductions to technologies that have become cornerstones of modern medicinal chemistry and includes many practical examples. The book has been carefully edited and contains numerous reaction schemes and illustrations, as well as a comprehensive subject index. If it remains the ambition of the pharmaceutical industry to make more and better drugs, faster, the past decade will have been a little disappointing. There may be many reasons for this relative lack of success in bringing new drugs to market. As this book reminds us, a lack of new and innovative techniques to identify new drug candidates is not one of them.
Gerd Wagner is a senior lecturer in medicinal chemistry at King’s College London, UK.
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