Progress in Drug Research

by Ernst Jucker

Overview

Due tothedevelopmentofdrugresistanceandotherlimitationsinthe treat ment of AIDS patients with reverse transcriptase (RT) inhibitors like zidovu dineandothers, itbecamenecessarytoexploreantiviralagentsactingontar getsotherthan RT. Inthepastfewyears, hundredsofHIVproteaseinhibitoLs have been synthesized and tested. Among these protease inhibitors, saquinavir, ritonavir, indinavir and nelfinavir have been marketed during 1995-1997. In this review, emphasis is placed on the development of HIV protease inhibitors as antiviral agents against HIV, structure-activity rela tionship (SAR) analysis ofsaquinavirand relatedcompounds, comparisonof four marketed HIV protease inhibitors, and future prospect in developing new anti-HIV drugs. 2 Introduction HIV protease inhibitors 3 HIV protease as a target for chemotherapy HIV protease was first suggested as a potential target for AIDS therapy by Kramer et a1. in 1986 [5]. HIV protease is a proteolytic enzyme responsible for cleaving large numbers of amino acid sequences. This enzyme regulates conversionoftheselargeaminoacid sequencesintobiologicallyactive struc tural and functional protein products. Specifically, HIV protease is responsi the enzymatic processing of the gagand gag-pol genes of HIV, which ble for encode for functional core proteins and viral enzymes (reverse transcriptase, ribonuclease H, integrase, and HIV protease). The polyproteins encoded by the gagand gag-pol genes undergo post-translational processing by HIV pro tease to form functional protein products as the viral particles budding out from infected cells. Therefore, inhibition of HIV protease by a protease inhibitor results in the release ofimmature, noninfectious viral particles [4]."

Product Details

ISBN-13:	9783034897983
Publisher:	Birkhäuser Basel
Publication date:	11/12/2011
Series:	Progress in Drug Research , #51
Edition description:	Softcover reprint of the original 1st ed. 1998
Pages:	326
Product dimensions:	6.69(w) x 9.61(h) x 0.03(d)

About the Author

Jucker, Ernst, PhD

Table of Contents

Development of HIV protease inhibitors: A survey.- Insulin resistance, impaired glucose tolerance and non-insulin-dependent diabetes, pathologic mechanisms and treatment: Current status and therapeutic possibilities.- Peptide drug delivery into the central nervous system.- Abnormalities of protein kinases in neurodegenerative diseases.- Biomimicry as a basis for drug discovery.- Serotonin in migraine: Theories, animal models and emerging therapies.- The application of high-throughput screening to novel lead discovery.- Index Vol. 51.- Index of titles, Vol. 1–51.- Author and paper index, Vol. 1–51.

Editorial Reviews

4 Stars! from Doody

Volume 45 of Progress in Research (PDR 45) contains eight reviews and various indexes which facilitate its use and establish the connection with the previous PDR volumes. The chapters in this volume deal with neuropeptides, calmodulin, benzodiazepine receptor binding sites, and other topics. PDR has been in existence for 36 years. The series is published twice yearly, at which time the chemical, pharmacological, and clinical aspects of pharmaceutical research are discussed. With this new volume, the author's intention is to disseminate drug research information and to provide the reader with a valuable resource tool. Although the numerous volumes of PDR do meet many of the objectives of the author, textbooks become outdated quickly; journal articles are often preferred. The PDR series is an encyclopedic information source focused on a variety of research topics. The reviews are useful to nonspecialists and specialists (primarily pharmaceutical scientists and pharmacologists). Readers can conveniently obtain an overview of a particular field of drug research. In addition, active researchers will appreciate the reviews' comprehensive bibliographies as well as the new research ideas. The book is well illustrated. All figures, tables, and drawings are easily understood. The illustrations greatly add to the understanding of the research topics. The references after each chapter appear to be current and highly pertinent to the subject matter discussed. This book represents the various chemical, pharmacological, and clinical aspects of pharmaceutical research. The series will help the researcher to secure significant research data quickly and thoroughly aswell as to acquire fresh ideas. It is most valuable to the researcher as a library reference, although bookstores may also want to purchase this reference.

Jan E. Markind

This volume contains seven review articles on various unrelated areas of research potentially leading to new therapeutic drugs. Also included are various indexes of the contents of the 54 volumes of the series. The purpose of the series is to disseminate information about actual trends and crucial points in drug research. The seven chapters include an eclectic collection of contributions dealing with gastrointestinal absorptions, appetite suppression, neuropeptides, regulation of NMDA receptors by ethanol, diabetic drugs, and developmental biology. Each of the chapters is well written by experts in the respective areas, and the contributions are directed towards other biomedical researchers in each of those areas. Because there is no theme to the volume, any given researcher is likely to be interested, at most, in a single contribution. Most of the areas are rather narrow, such as the effect of one drug (ethanol) on one receptor subfamily (the NMDA receptors of the glutamate receptor family). On the other hand, one chapter is very broad and contributors attempt to cover all of the neuropeptides in 20 pages. Thus, several important families of peptides, such as the opioid peptides are just superficially covered in a single page. A nice feature of the book is that pictures of most of the contributors are included at the start of the various chapters. This book will be of interest to a subset of researchers whose area of interest happens to correspond to one of the seven chapters. They will find their chapter of interest to be useful, although probably not as current as an article from a recent review journal.

David B. Bylund

The series presents, in volumes published twice yearly, larger survey articles on topical fields of pharmaceutical research in which the chemical as well as the pharmacological and clinical aspects are discussed. Volume 44 contains six reviews that deal with problems of drug discovery during "the golden age of drug research," with histamine H1-receptor agonists, with antifungal therapy, with antifolates in cancer therapy, with menses-regulating agents, and with developments in anticonvulsants. The reviews are extensively referenced and the volume concludes with a subject index to the volume and cumulative indexes of titles and of authors/papers. Annotation c. Book News, Inc., Portland, OR (booknews.com)

Booknews

Reviewer: Thomas L. Pazdernik, PhD (University of Kansas Medical Center)
Description: This volume in the Progress in Drug Research series contains seven well written and timely reviews on: the polyamine oxidase inactivator by MDL 72527 by N. Seiler, B. Duranton and F. Raul; pleiotropic mechanisms of ribavirin antiviral activities by Z. Hong and C.E. Cameron; protein phosphorylation networks in motor neuron death by J.H. Hu and C. Krieger; the functioning neuronal transporters for dopamine: kinetic mechanisms and effects of amphetamines, cocaine and methylphenidate by J.O. Schenk; central nervous system effects of thyrotropin-releasing hormone and its analogues: opportunities and perspectives for drug discovery and development by L. Prokai; a new category of psychotropic drugs: neuroactive lipids as exemplified by ethyl eicosapentaenoate (E-E) by D. Horrobin; and current status of the estrogen receptors by S. Ray, R. Rastogi and A. Kumar.
Purpose: The purpose of this series is dissemination of information on trends and developments, discussion of crucial points and creation of new prospects on future drug design. The seven reviews in this volume uphold the high standards and reputation of this very valuable series that was initiated in 1958. This is a valuable resource for any individual who works in drug research or drug discovery.
Audience: This series is targeted towards scientists working in the field of drug discovery; however, the reviews should be of interest to both the practitioner and experimentalist who have an interest in the given topic.
Features: The first review describes the properties, applications and therapeutic potentials of polyamine oxidase inactivators. The second review describes the mechanism of action of ribavirin and proposes new strategies for development of nucleoside analogs in the treatment of hepatitis C infections. The third review discusses the role of protein phosphorylation networks in motor neuron death in amyotrophic lateral sclerosis (ALS). The fourth review expands the information on the role of dopamine transporters with respect to the pharmacology of amphetamines, cocaine and methylphenidate. The fifth review, first gives an overview of the extrahypothalaminc and receptor distribution, and of the neurophysiological, neuropharmacological and neurochemical effects of thyrotropin-releasing hormone (TRH), and then discusses the potential for developing TRH analogs to treat maladies affecting the brain and spinal cord. The sixth review discusses ethyl eicosapentaenoate as a novel neuroactive lipid with potential for treating depression, unresponsive schizophrenia and in tardive dyskinesia. The last review deals with estrogen-dependent disorders. The author describes the problems associated with the development of tissue selective estrogen receptor modulators for the treatment of estrogen-dependent disorders.
Assessment: This high quality series is targeted towards scientists with an interest in drug discovery, but these seven reviews are written with such clarity that anyone with an interest in the topic would find this a worthwhile read. Each chapter has a biographical sketch of the author(s), a summary of the review at the beginning, an outline of contents, and some chapters have a glossary of the terms and abbreviations that are extremely valuable for the non-expert. I highly recommend these reviews.

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