A Textbook of Drug Design and Development [antikvár]

PREFACE Studies of operational and regulatory cell mechanisms are in a state of rapid progress. The introduction of advanced biochemical, biophysical and physicochemical techniques in basic biological research has accelerated the disclosure of the complex mechanisms underlying cell function. Genetic technologies have revolutionized enzyme and receptor research and have made detailed mapping of receptor subtypes possible. Comparative studies of normal and diseased cells in vivo and in vitro have shed light on the nature of the biochemical and physiological malfunctions characterizing a number of diseases. These studies have disclosed potential targets for therapeutic attack in the relevant diseases. Namral toxins and analogues of endogenous ligands have been used for the exploration of such sites and their susceptibility to pharmacological manipulation. Lack of specificity does, however, frequently limit the utility of such compounds. Using synthetic and enzymatic techniques it has been possible to convert non-specific toxins or ligands into compounds with highly specific actions on the cellular mechanisms under study. Such specific experimental tools represent the initial steps in the development of therapeutic agents. Rational and systematic approaches along these lines have provided therapeutically useful dmgs and are likely to lead to the development of novel classes of dmgs against diseases, which, so far, have escaped effective treatment. In the present textbook all important aspects of modem dmg design and development will be described and exemplified. The first edition of this textbook, published in 1991, was co-edited by Professor Hans Bundgaard, who played an important role in the publication of the book and contributed a major chapter on design and appUcation of prodrugs. From the early seventies and until his tragic and far too early death in 1992, Hans Bundgaard made an impressive series of original discoveries in this field of pharmaceutical sciences. In light of the rapid, in some fields almost explosive, developments in industrial and academic dmg research, we initiated the planning of the second edition of this textbook in 1994. The objective was to incorporate the major new developments in the field and to produce a new edition with even further emphasis on the educational level of the text. New topics in this second edition of the textbook include combinatorial approaches to lead discovery, computational pharmacophore mapping, recombinant receptors, design and development of peptidomimetics, ligands labelled with short-lived isotopes for imaging purposes, and examples of biostracture-based drag design. Povl Krogsgaard-Larsen Tommy Liljefors UlfMadsen