pharmaceutical organic chemistry
DESCRIPTION
Combinatorial chemistryTRANSCRIPT
PHARMACEUTICAL ORGANIC CHEMISTRY RESEARCH
Combinatorial Chemistry
INTRODUCTION :
*Combinatorial chemistry is one of the important new
methods developed by academics and researchers in
the pharmaceutical, chemical, and biotechnology
industries to reduce the time and costs associated with
producing effective, marketable, and competitive new
drugs.
*Simply, scientists use combinatorial chemistry to
create large populations of molecules, or libraries ,
that can be screened efficiently .
* By producing larger, more diverse compound
libraries, companies increase the probability that they
will find novel compounds of significant therapeutic
and commercial value.
*The field represents: a convergence of chemistry and
biology, made possible by fundamental advances in
miniaturization, robotics, and receptor development.
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* And not surprisingly, it has also captured the
attention of every major player in the pharmaceutical,
biotechnology, and agrochemical arena.
*Technique invented in the late 1980s and early 1990s
to enable tasks to be applied to many molecules
simultaneously
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DEFINITION :
*Combinatorial chemistry is a technique by which large
numbers of structurally distinct molecules may be
synthesized in a time and submitted for pharmacological
assay.
*The key of combinatorial chemistry is that a large range
of analogues is synthesized using the same reaction
conditions, the same reaction vessels.
*In this way, the chemist can synthesize many hundreds
or thousands of compounds in one time instead of
preparing only a few by simple methods .
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In the past
*chemists have traditionally made one compound at a
time.
* For example compound A would have been reacted with
compound B to give product AB, which would have been
isolated after reaction work up and purification through
crystallization, distillation, or chromatography.
In contrast to this approach
*combinatorial chemistry offers the potential to make
every combination of compound A1 to An with compound
B1 to Bn.
The range of combinatorial techniques is highly diverse,
and these products could be made individually in a
parallel or in mixtures, using either solution or solid phase
techniques. Whatever the technique used the common
denominator is that productivity has been amplified
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beyond the levels that have been routine for the last
hundred years.
TOOLS:
- Solid-phase synthesis
– Resins
– Reagents (Monomers)
– Linkers
– Screening methods
METHODS :
1-Use of solid supports for peptide synthesis led to wider
applications
2-Products from one reaction are divided and reacted
with other reagents in succession
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Benefits to material science :
1-Combinatorial approaches now being applied to solid-
state and materials applications
2-Also to search for new catalysts
Application of Combinatorial Chemistry :
*Applications of combinatorial chemistry are very wide.
* For example in pharmaceutical companies for drug
designs. For illustrate this, one a practical example:
Transition-state analog HIV protease inhibitors.
-Extensive efforts toward the rational design of aspartyl
protease inhibitors such as renin and HIV have led to
the discovery of several transition-states analog
mimics.
-These templates can serve as the central unit around
which molecular diversity can be generated by
application of appropriate chemistries.
- Recently, solid phase synthesis of hydroxyethylamine
and 1,2-diol transition-state pharmacophore units and
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their utility for synthesis of HIV protease inhibitors have
been reported by two different groups.
-The first instance, bi functional linker are used by
Wang to serve the dual purpose of protecting the
hydroxyl group of these BBs and providing point for
attachment on solid support.
-Thus, one linker possesses a vinyl ether group at one
end and a free carboxylate group at the other.
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-The vinyl ether moiety is reacted with diamino alcohol
BB 1 under acid-catalysed conditions to form an acetal
protecting group and the carboxylic acid group is used
for ester-type linkage to the solid support.
-The other linker possesses a methyl ketone and
carboxylic groups at the two ends, with the ketone
group forming a ketal with diol 3.
-Resulting intermediates 2 and 4 are now well suited
for a bi-directional solid phase synthesis strategy for
preparing C2 symmetric HIV protease inhibitors.
- The two terminal amino groups of 2 and 4 are
deprotected and reacted with a variety of carboxylic
acid, sulfonyl chlorides, isocyanates, and
chloroformates to extend the core unit in both
directions and generate a wide variety of aspartyl
protease inhibitors.
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ADVANTAGES AND DISADVANTAGES :
1-ADVANTAGES:
1-save time
2-fast
3-produce unexpected new compounds
4-used in many biological & chemical applications
5-save money
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2-DISADVANTAGES:
1-Can't used with Many compounds had undesirable
properties like
– Size
– Solubility
– Inappropriate functional groups
2-Early libraries often based on a single skeleton (basic
structure)
3-Limited number of skeletons accessible
4-Individual library members were structurally similar
5-Compounds tended to be achiral or racemic
6-Initial emphasis on creating mixtures of very large
numbers of compounds now out of favor
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REFRENCES :
1-http://www.combichemistry.com/
combichem_applications.html
2-http://en.wikipedia.org/wiki/
Combinatorial_chemistry
3-http://www.wiziq.com/tutorial/2967-Combinatorial-
Chemistry-and-Library-Design
4-http://www.netsci.org/Science/Combichem/
feature02.html
5-http://www.chem.msu.su/rus/books/patrick/part1.pdf
MADE BY SECTION(2) :
1- Jehan Essam Mahmoud (112) .
2-Aya Ahmed Saber Yosif (86).
3-Eman Mohammed Mostafa Sherra (83).
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4-Eman Ahmed Alaa Elshamy .
5-Aya Samir .
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