• Up-to-date review on the chemistry and biology of nucleosides • Modern synthetic methodology • Comprehensive coverage of antiviral nucleosidesThis book summarizes the recent advances in nucleosides chemistry and chemotherapy over the past 10-15 years. It covers recently discovered nucleoside antiviral agents, their therapeutic aspects and biochemistry, and also extensive reviews on their chiral synthesis.

Due to the worldwide epidemic of acquired immunodeficiency syndrome (AIDS), the past ten years have witnessed a flurry of activity in the chemotherapy of viral diseases. Unprecedented scientific efforts have been made by scientists and clinicians to combat infections of human immunodeficiency virus (HIY), the causative agent. Looking back over the past ten years, we have made remarkable progress toward the treatment of the viral disease: isolation of HIV only two years after the identification of the disease, plus major strides in the areas of the molecular biology and virology of the retrovirus, etc. More remarkably, the discovery of the chemotherapeutic agent AZT (Retrovir) was made within two years after the isolation and identification of the virus, followed by unprecedented drug development efforts to culminate in the FDA approval of AZT in twenty-three months, which was a record-breaking time for approval of any drug for a major disease. The last six to seven years have particularly been an exciting and productive period for nucleoside chemists. Since the activity of AZI' was established in 1985, nucleoside chemists have had golden opportunities to discover additional anti-HIV nucleosipes, which are hoped to be less toxic and more effective than AZT, and the opportunity continues. As we all are aware, AZT possesses extremely potent anti-HIY activity, and no other nucleoside or non nucleoside has surpassed the potency of AZT in vitro.

The book covers up-to-date information on nucleosides and antiviral chemotherapy contributed by the world experts in the field of nucleoside. This book is the result of a meeting honoring Dr. Jack J. Fox, who was one of the pioneers in nucleoside chemistry and chemotherapy. This book consists of 15 excellent chapters in the area, which include topics from recent synthetic methodologies, nucleoside kinase implicated in chemotherapy and drug design, excellent reviews on antiviral agents, nucleoside metabolism/mode of action in parasites, new compounds under clinical and pre-clinical trials, IMPDH inhibitors to review on nucleoside prodrugs.

Nucleosides, Nucleotides, and Their Biological Applications contains the proceedings of the Fifth International Round Table on Nucleosides, Nucleotides, and Their Biological Applications held at Research Triangle Park, North Carolina on October 20-22, 1982. Contributors focus on the biological applications of nucleosides and nucleotides, along with advances in synthetic chemistry. Topic range from fast-moving biochemical subjects such as the 2',5'-oligoadenylates and their relationship to interferons; adenosine and adenine nucleotide receptors; and nucleosides with selective antiviral action. This volume is organized into 11 chapters and begins with an overview of nucleosides that are used as antiviral agents and their mechanism of action, including idoxuridine, vidarabine, and trifluridine. The discussion then shifts to the chemical and biological properties of nucleosides of purines and ring analogs; 2'-fluoroarabinosyl pyrimidines and purine-like C-nucleosides; and the potential of 2',5'-oligoadenylates as chemotherapeutic agents. The reader is also introduced to receptors for adenosine and adenine nucleotides; the function of pyrrolo[2,3-d]pyrimidine nucleosides in polynucleotides; and unusual nucleoside synthons and oligonucleotide synthesis. A chapter on the synthesis of versatile C-nucleoside precursors and certain C-nucleosides concludes the book. This book will be of value to chemists, biologists, and those with an interest in nucleosides and nucleotides.

Interest in chemical entities capable of blocking or modifying cell metabolism ultimately goes back to the discovery of the structure of DNA in the 1950s. Understanding of the biochemical processes involved in cell metabolism rapidly led to the idea that compounds could be designed which might interfere with these processes, and thus could be used in the treatment of the diseases caused by viral infection. Since then, several classes of drugs have been discovered which depend for their effect on modification of the proper functioning of nucleic acids and, with the introduction of acyclovir for the treatment of Herpes infections, nucleoside analogues have become the cornerstone of antiviral chemotherapy. The success of the early nucleoside agents, the toxicity and metabolic instability of many nucleoside analogues, and the effects of viral pathogens on public health are driving the design, synthesis and evaluation of new nucleoside analogues, with much attention turning to nucleosides containing `non natural' sugar analogues. This book focuses on the development of these agents, and draws together all the available material in an easily consulted form, which at the same time guides the reader into the research literature on the subject. Written primarily for the medicinal chemist, coverage includes both synthetic strategies and outline guidance on the main trends in biological activity. Particular attention is drawn to the comparison of synthetic routes to compounds with their natural analogues. Finally, the important antiviral activities of the compounds are treated, including anti-retrovirus, anti-hepadnavirus and anti-herpes virus properties. Written mainly for medicinal chemists in the pharmaceutical industry and synthetic organic chemists in academe, this book will also be attractive to researchers in institutions focusing on cellular metabolism. Advanced students of organic chemistry will find the clear discussion of the synthetic strategies adopted in the development of these compounds a useful introduction to this exciting and challenging area.

Largely in response to the AIDS epidemic, the amount of research directed toward the discovery of antiviral agents has greatly expanded. This new volume focuses on the potential of nucleotides to exert potent in vivo antiviral effects. It presents the findings of an international group of scientists who are carrying out research at the forefront of the nucleotide drug design. Twelve chapters describe many new concepts and results, much of which has been previously unpublished. This book assembles a valuable collection of information, offering insight into this increasingly important research topic.

Compiles current tested and proven approaches to synthesize novel nucleoside analogues Featuring contributions from leading synthetic chemists from around the world, this book brings together and describes tested and proven approaches for the chemical synthesis of common families of nucleoside analogues. Readers will learn to create new nucleoside analogues with desired therapeutic properties by using a variety of methods to chemically modify natural nucleosides, including: Changes to the heterocyclic base Modification of substituents at the sugar ring Replacement of the furanose ring by a different carbo- or heterocyclic ring Introduction of conformational restrictions Synthesis of enantiomers Preparation of hydrolitically stable C-nucleosides Chemical Synthesis of Nucleoside Analogues covers all the major classes of nucleosides, including pronucleotides, C-nucleosides, carbanucleosides, and PNA monomers which have shown great promise as starting points for the synthesis of nucleoside analogues. The book also includes experimental procedures for key reactions related to the synthesis of nucleoside analogues, providing a valuable tool for the preparation of a number of different compounds. Throughout the book, chemical schemes and figures help readers better understand the chemical structures of nucleoside analogues and the methods used to synthesize them. Extensive references serve as a gateway to the growing body of original research studies and reviews in the field. Synthetically modified nucleosides have proven their value as therapeutic drugs, in particular as antiviral and antitumor agents. However, many of these nucleoside analogues have undesirable side effects. With Chemical Synthesis of Nucleoside Analogues as their guide, researchers have a new tool for synthesizing a new generation of nucleoside analogues that can be used as therapeutic drugs with fewer unwanted side effects.