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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.
During the past fifty years, thousands of natural products have
been isolated from plants, fungi, and bacteria. Apart from intense
searches by pharmaceutical companies for medicinals and the
concentrated effort mounted by the National Cancer Institute, many
of these have not been tested in biological systems. The major
reasons for this appear to be, at least, twofold. First, individual
researchers looking for biologically active natural products will
often isolate only small amounts of material sufficient to
determine a structure and calculate the specific activity for their
particular bioassay systems: insufficient funds preclude
re-isolating the compound unless industrial potential is foreseen.
Second, the difficulty with which original structures were proved
prior to 1972. This required the isolation of relatively large
quantities of a natural product and there followed extensive
degradation, elemental analyses of the parent and its fragments,
then synthesis, piece by piece, of the molecule. All this took time
and energy. No wonder that when the structure was proved the
chemist was enervated. And coupled to this was the fact that many
chemists were not trained to test their materials in biological
systems. In contrast, today a natural product can be isolated, its
mass and molecular formula determined and, if there is some
serendipity, crystals may be obtained for single crystal x-ray
analysis. If conditions are near perfect, it is possible to isolate
and identify a novel compound in a month.
- Up-to-date review on the chemistry and biology of nucleosides
- Modern synthetic methodology
- Comprehensive coverage of antiviral nucleosides
This 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.
During the past fifty years, thousands of natural products have
been isolated from plants, fungi, and bacteria. Apart from intense
searches by pharmaceutical companies for medicinals and the
concentrated effort mounted by the National Cancer Institute, many
of these have not been tested in biological systems. The major
reasons for this appear to be, at least, twofold. First, individual
researchers looking for biologically active natural products will
often isolate only small amounts of material sufficient to
determine a structure and calculate the specific activity for their
particular bioassay systems: insufficient funds preclude
re-isolating the compound unless industrial potential is foreseen.
Second, the difficulty with which original structures were proved
prior to 1972. This required the isolation of relatively large
quantities of a natural product and there followed extensive
degradation, elemental analyses of the parent and its fragments,
then synthesis, piece by piece, of the molecule. All this took time
and energy. No wonder that when the structure was proved the
chemist was enervated. And coupled to this was the fact that many
chemists were not trained to test their materials in biological
systems. In contrast, today a natural product can be isolated, its
mass and molecular formula determined and, if there is some
serendipity, crystals may be obtained for single crystal x-ray
analysis. If conditions are near perfect, it is possible to isolate
and identify a novel compound in a month.
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."
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