Quantitative Drug Design: A Critical Introduction

This eighth book is a positively delightful addition to the Medicinal Research Series. It is intended as a self-study guide for workers unfamiliar with various methods of quantitative drug design, but with a reasonable background in biochemistry and mathematics. It is basically a "how to do it" book, and Martin informs us her "6enthusiasm for writing this book arose from my experiences as a referee of manuscripts ... as well as from the unreliability of predictions of drug potency which I have made." With singleness of purpose-that of improving the quality of drug research-she has created a truly inspirational introductory text which is much more than merely an introduction. Martin's emphasis is on the newer methods (specifically the Hansch extrathermo-dynamic and de novo, or Free-Wilson, approaches) which have helped drug design develop over the past 20 years from inspired guesswork to a rational, quantitative (if still semi-empirical) discipline, involving extensive computer calculations. With this emphasis, her stress on the standards of quality work, and her straightforward presentation, this work is certain to achieve its purpose of improving the character of research in this field, if it is widely read. Martin presents a broad, understandable review of non-covalent interactions, so critical to drug activity. This is followed by definitions and calculations of physical properties, including partition coefficients, constants and parameters for quantitating non-covalent effects, and a brief discussion of Huckel molecular orbital calculations. Next comes a section on the requirements for good biological tests and relative potency calculations: "How one converts biological data into a measure of potency." The equations relating relative potency to physical properties are presented; Martin explores both empirical and theoretical relationships. The author then launches into a substantial review of statistical techniques: linear, multiple, and non-linear regression , analysis of variance, and even some more esoteric methods, such as discrimi-nant analysis. She follows this with a discussion of philosophical and practical approaches to the design/testing decision-making process. The book closes with some detailed examples of applications and an entirely too short section on other approaches, especially the very promising subject of suicide enzyme inhibitors. Martin makes no attempt to be all-encompassing, covering only those subjects not discussed in other such texts. This can be misleading to the novice; for instance, the chapter on non-covalent bonds is not included to imply their greater importance over covalent interactions, but rather because understanding by the student may be lacking. However, …