Transcript D9 Drug design

Daniel Brown
D9.1 Discuss the use of a compound library
in drug design.
 Traditionally, a large collection of related compounds
are synthesized individually and evaluated for
biological properties. However this is time consuming
and expensive.
D9.1 Discuss the use of a compound library
in drug design.
 A chemical library or compound library is a collection
of stored chemicals usually used ultimately in highthroughput screening (a method for scientific
experimentation especially used in drug discovery and
relevant to the fields of biology and chemistry)or
industrial manufacture. The chemical library can
consist in simple terms of a series of stored chemicals.
Each chemical has associated information stored in
some kind of database with information such as the
chemical structure, purity, quantity, and
physiochemical characteristics of the compound.
D9.2 Explain the use of combinatorial and
parallel chemistry to synthesize new
drugs.
 Combinatorial chemistry is used to synthesize
a large number of different compounds and
screen them for biological activity, resulting in
a “combinatorial library”. Combinatorial chemistry
involves the rapid synthesis or the computer
simulation of a large number of different but
structurally related molecules or materials.
D9.2 Explain the use of combinatorial and
parallel chemistry to synthesize new
drugs.
 Combinatorial chemistry has probably had its biggest
impact in the pharmaceutical industry. Researchers
attempting to optimize the activity profile of a
compound create a 'library' of many different but
related compounds.
D9.2 Explain the use of combinatorial and
parallel chemistry to synthesize new
drugs.
 Parallel synthesis can produce smaller, more focused
libraries. ‘parallel synthesis’ has certain advantages
over combinatorial chemistry in that all intermediates
and products are generated separately and in sufficient
amounts for full characterization and biological
screening, without the need for long identification
procedures.
D9.3 Describe how computers are used in
drug design.
 Three-dimensional models of drugs can be created
using computer simulation and molecular modeling
software can be used for the virtual development and
evaluation of new drugs.
 Useful in combinatorial chemistry.
D9.4 Discuss how the polarity of a molecule can be
modified to increase its aqueous solubility and how this
facilitates its distribution around the body.
 Acidic (carboxylic acid) and basic (amine) groups have
the ability to form ionic salts.
 For example, soluble aspirin and fluoxetine
hydrochloride (Prozac®).
D9.5 Describe the use of chiral auxiliaries to
form the desired enantiomer.
 A chiral auxiliary is used to convert a non-chiral
molecule into just the desired enantiomer, thus
avoiding the need to separate enantiomers from a
mixture. It works by attaching itself to the non-chiral
molecule to create the stereochemical conditions
necessary to force the reaction to follow a certain path.
Once the new molecule has been formed, the auxiliary
can be taken off (recycled) to leave the desired
enantiomer.
 An example is the synthesis of Taxol, an anti-cancer
drug.
Taxol (Paclitaxel)
D9.5 Describe the use of chiral auxiliaries to
form the desired enantiomer.
 A chiral auxiliary is a chemical compound or unit that
is temporarily incorporated into an organic synthesis
so that it can be carried out asymmetrically with the
selective formation of one of two enantiomers.