Progress in Drug Research is a prestigious book series which provides extensive expert-written reviews on a wide spectrum of highly topical areas in current pharmaceutical and pharmacological research. Founded in 1959 by its current editor, the series has moved from its initial focus on medicinal chemistry to a much wider scope. Today it encompasses all fields concerned with the development of new therapeutic drugs and the elucidation of their mechanisms of action, reflecting the increasingly complex nature of modern drug research. Invited authors present their biological, chemical, biochemical, physiological, immunological, pharmaceutical, toxicological, pharmacological and clinical expertise in carefully written reviews and provide the newcomer and the specialist alike with an up-to-date comprehensive list of prime references. Each volume of Progress in Drug Research contains fully cross-referencing indices which link the books together, forming a virtually encyclopaedic work. The series thus serves as an important, time-saving source of information for researchers concerned with drug research and all those who need to keep abreast of the many recent developments in the quest for new and better medicines.

Jay A. Glasel: Drugs, the human genome, and individual-based medicine.- Vera M. Kolb: Herbal medicine of Wisconsin Indians.- Paul L. Skatrud: The impact of multiple drug resistance (MDR) proteins on chemotherapy and drug discovery.- John W. Ford, Edward B. Stevens, J. Mark Treherne, Jeremy Packer and Mark Bushfield: Potassium channels: Gene family, therapeutic relevance, high-throughput screening technologies and drug discovery.- David T. Wong and Frank P. Bymaster: Dual serotonin and noradrenaline uptake inhibitor class of antidepressants - Potential for greater efficacy of just hype?.- Satya P. Gupta: Advances in QSAR studies of HIV-1 reverse transcriptase inhibitors

This second volume of PDR SPECIAL TOPICS contains five review articles, covering nearly the entire field of fungal diseases in humans as well as therapeutic approaches. The main emphasis of the book lies in antifungal therapy: the most relevant information on the present state of the art of antifungal chemotherapy for dermatomycoses, subcutaneous and invasive mycoses is summarized, and open questions and unsolved problems are presented. The book is ideal for both the practitioner as well as advanced student.

In the treatment of infections caused by rapidly mutating viruses like human immunodeficiency virus (HIV), combination therapy with multiple drugs act ing by different mechanisms offers several advantages over monotherapy. It may provide: synergistic effect, possible reduction of dosages and side-effects, and reduction of the chance of drug resistance. In the past few years, hun dreds of HIV protease inhibitors have been synthesized and tested in order to overcome the limitations of reverse transcriptase inhibitors like zidovudine and others. In this review, emphasis is placed on the development of HIV pro tease inhibitors as antiviral agents against HIY, and structure-activity rela tionship analysis of saquinavir and related compounds. Limitations of some protease inhibitors and ways to overcome the shortcomings are presented. Among these many protease inhibitors five have been marketed during 1995-1999. They are saquinavir, ritonavir, indinavir, nelfinavir and ampre navir. Their different structural features, important physicochemical, phar macokinetic and clinical profiles are presented in a table form for easy com parison. It is hoped that in the future new drugs based on additional mech anisms can be developed for the treatment of AIDS. Contents 4 1 Introduction .................................................................... . HIV protease as a target for chemotherapy ................................... . 2 5 Design of protease inhibitors .................................................. . 3 5 Basis of rational design of HIV protease inhibitors ........................... . 3.1 5 New development of HIV protease inhibitors ................................ . 6 3.2 HIV protease inhibitors on the market ........................................ . 20 4 20 4.1 SAR of saquinavir and related compounds .................................... ."

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