Medicines and Drugs Practice #6—Drug Design
1.
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paroxetine
a. Using an asterisk (*), identify the chiral carbon atom(s), if any, in each of the above structures.
b. Explain, with an example, the importance of chirality in drug action.
c.
Describe the use of chiral auxiliaries to synthesize the desired enantiomer of a drug.
chiral auxiliaries are themselves chiral;
attach to the non-chiral molecule (to enable the desired enantiomer to be formed);
after the desired enantiomer is formed the chiral auxiliary is removed/recycled;
d. Paroxetine is usually prescribed in the form of its hydrochloride salt.
i.
Explain why it is used in this form.
ii.
State the structural feature of a molecule of paroxetine that enables it to form a salt.
e. Ibuprofen is virtually insoluble in water. Explain how ibuprofen can be made more water soluble, and write an
equation for the reaction.
f.
Prozac®, fluoxetine hydrochloride, a depressant, is water-soluble and is made by reacting fluoxetine with
hydrochloric acid. Use Table 20 in the Data Booklet to deduce the structure of fluoxetine.
2. Combinatorial chemistry in being increasingly used to produce compounds that may have physiological activity.
a. Explain what is meant by combinatorial chemistry and how it is used to increase the efficiency of drug synthesis.
techniques, such as split and mix, used to produce random combinations;
chemical building blocks joined to each other in many combinations / OWTTE (‘Or Words To That Effect’)
produces large variety of molecules/combinatorial libraries/collection of compounds / OWTTE;
these molecules may be screened for physiological activity/drug action;
b. State one advantage of solid-phase chemistry during combinatorial synthesis.
purification of the product is relatively easy / product can be isolated by
washing and filtration;
c.
How are mix-split synthesis (combinatorial chemistry) and parallel synthesis different?
in parallel synthesis, each combination of functional groups is produced in a separate container. In
mix-split synthesis, each container contains multiple compounds (differing combinations of
functional groups).
d. How are both techniques advantageous compared to previous methods of drug synthesis?
both techniques allow the rapid production of multiple molecules for testing.
e. Describe how computers are used in drug design.
models interaction between drug and active site; [accept computers used in molecular modelling/3D
modelling / OWTTE;]
combinatorial library/database used to search for molecules/groups with
required/specific properties;
f.
Describe how computers can be used to predict how changes to the structure of a drug might affect its activity.
can model (three-dimensional) shape/3D pharmacophore of drug molecule; [Allow molecular
modelling.]
can model interaction/activity of the drug with target molecule / OWTTE;
can predict how changes affect interaction with target molecule / OWTTE;