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The Art of Drug Synthesis. Edited by DouglasS. Johnson and JieJack Li

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Angewandte
Books
Chemie
The Art of Drug Synthesis
Edited by Douglas S. Johnson and
Jie Jack Li. John
Wiley & Sons,
Hoboken 2007.
276 pp., hardcover
E 79.90.—ISBN
978-0-471-75215-8
Starting from the identification of a
therapeutic target, a successful drug
candidate passes through many developmental stages before it is approved
for clinical use. During this process the
tasks of medicinal chemists are manifold. At the beginning, the focus is on
the synthesis of a wide variety of individual compounds, in order to identify
and further elaborate a lead structure.
At later stages in the development of the
drug candidate, the challenge of scaleup comes to the fore, eventually leading
to an efficient synthetic pathway for
large-scale production.
The book The Art of Drug Synthesis,
edited by Douglas S. Johnson and Jie
Jack Li, addresses this topic and illustrates it by discussing, as examples, more
than 50 drugs that have been launched
Angew. Chem. Int. Ed. 2008, 47, 5115
in the last 15 years. One such example is
Tamiflu, which received much public
attention with regard to avian influenza.
The editors, who work at Pfizer in the
area of global research and development, have succeeded in recruiting 16
authors who are all engaged in the
industrial drug discovery process.
The book consists of 17 chapters
with a comprehensive index. The first
chapter discusses very briefly the role of
medicinal chemistry in drug discovery.
The second chapter is entitled “Process
Research: How much? How soon?”.
Using selected examples of syntheses,
the chapter introduces the reader to the
considerations involved in the different
scale-up stages that a drug candidate
passes through until its production. The
following 15 chapters are devoted to
individual drug categories, divided into
three major therapeutic areas: 1. cancer
and infectious diseases, 2. cardiovascular
and metabolic diseases, and 3. central
nervous system diseases. The drug categories discussed are: aromatase inhibitors, quinolone antibiotics, triazole antifungals, non-nucleoside HIV reverse
transcriptase inhibitors, neuraminidase
inhibitors, PPAR agonists, angiotensin
AT1 antagonists, ACE inhibitors, dihydropyridine calcium channel blockers,
second-generation HMG-CoA reductase inhibitors, cholesterol absorption
inhibitors, SSNRIs, GABAA receptor
agonists, a2d ligands, and approved
treatments for ADHD.
All these chapters that outline the
synthesis of an individual drug or a
group of related drugs are organized in
the same way. First of all, a “wanted
poster” is given for each drug, including
molecular weight, USAN, trade name,
the name of the pharmaceutical company that developed the drug, and the
year of its launch. There then follows a
short introduction to the therapeutic
area and the mechanism of action. The
main part of the chapter deals with the
synthesis of the drug, introduced by a
“wanted poster”. Starting with the strategy used for the initial synthesis, the
reader gains a very detailed insight into
the optimization and scale-up of individual synthetic steps, as well as entire
synthetic sequences. Additionally, different synthetic pathways are discussed
and compared. This is supported
throughout by clearly presented reaction schemes. However, in some chapters the reader is not always clearly told
which of the synthetic pathways discussed was the starting point for a scaleup and was finally used for production.
Each chapter ends with a comprehensive list of references. The cited literature is very up-to-date throughout, even
including references from 2006. In this
context, a minor point of criticism is that
some authors list literature references
for the chapter as a whole rather than
linking them to specific topics.
In conclusion, the book is very
felicitous and closes a gap in the literature by covering the subject of drug
development in this particular way.
Although it is primarily written for a
readership in the field of medicinal
chemistry, it is also recommended for
students who want to give more attention to this area. Additionally, because
of the high density of information in the
book, it offers an excellent source that
university teachers can use for preparing
lectures in the area of medicinal chemistry.
Norbert Schaschke
Fakult*t f,r Chemie
Universit*t Bielefeld (Germany)
DOI: 10.1002/anie.200785551
3 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5115
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drug, johnson, synthesis, jiejack, art, douglas, edited
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