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EXAMINATION PAPER: ACADEMIC SESSION 2022/2023

Campus Medway
Faculty Engineering & Science
Level 7
Exam Session April 2023
MODULE CODE CHEM1110
MODULE TITLE DRUG DISCOVERY AND MEDICINAL CHEMISTRY
Exam Duration 2 hours

Instructions to Candidates

Answer TWO out of THREE questions

All questions carry equal marks

Students will be required to achieve an overall grade of 50% to achieve a pass.

Page 1 of 6
Session: April 2023
Module Title: Drug Discovery and Medicinal Chemistry
Module Code: CHEM1110
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Answer TWO questions

Q1. Answer ALL parts of this question

a)
Amoxicillin (below) is a b-lactam antibiotic, typically used to treat chest infections,
dental abscesses and ear infections.

NH2
H
N
S
HO O
N
O
OH
O

i) Label/circle all of the acidic/basic sites, clearly indicating which is which.

[4 marks]

ii) Label/circle all hydrogen bond donors (HBD) and hydrogen bond acceptors (HBA),
clearly labelling which is which
[8 marks]

iii) Label all sites which could potentially interact with a target, and clearly indicate the
type of interaction that would be involved (eg, hydrogen bonding, ionic interactions
etc…)
[10 marks]

iv) Label four possible sites of primary metabolism, clearly indicating the type of
reaction/transformation at each site.
[8 marks]

Q1 continued overleaf
Page 2 of 6
Session: April 2023
Module Title: Drug Discovery and Medicinal Chemistry
Module Code: CHEM1110
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Q1 continued
b)
i) The main types of chemistry used in the pharmaceutical industry are medicinal
chemistry and process chemistry. When scaling up chemistry, the choice of synthetic
route is very important. Describe 5 considerations when choosing the synthetic route,
giving rationale behind you answer.
[10 marks]

ii) A library of compounds related to amoxicillin was prepared by mix and split
combinatorial synthesis. With the aid of a diagram, explain what is meant by the mix
and split method.
[10 marks]
[Total 50 marks]

Page 3 of 6
Session: April 2023
Module Title: Drug Discovery and Medicinal Chemistry
Module Code: CHEM1110
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Q2. Answer ALL parts of this question

a)
The anti-cancer drug docetaxel has the molecular structure below.

Docetaxel

i) what is the molecular formula of docetaxel?

[6 marks]

ii) how many chiral centres does this drug possess?

[6 marks]

iii) what is the fraction of sp3 hybridised carbon atoms, Fsp3, in this drug?
[6 marks]

iv) how is the molecular shape of docetaxel influenced by Fsp3?

[6 marks]

v) how many diastereomers and enantiomers are possible for docetaxel: give your
calculation and logic?
[6 marks]

Q2 continued overleaf

Page 4 of 6
Session: April 2023
Module Title: Drug Discovery and Medicinal Chemistry
Module Code: CHEM1110
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Q2 continued
b)
Mutations in human DNA may give rise to amino acid changes in the corresponding
translated protein structure.

i) give an example of a conservative change in amino acid type with an explanation of

your choice of amino acids and a molecular structure for the original and the changed
amino acid.
[6 marks]

ii) give an example of a non-conservative change in amino acids with an explanation

of your choice of amino acids and a molecular structure for the original and the
changed amino acid.
[6 marks]

iii) give an example of a non-conservative change in an amino acid in a protein leading

to a human disease, with a concise explanation of how the amino acid change in the
particular protein leads to disease formation.
[8 marks]
[Total 50 marks]

Page 5 of 6
Session: April 2023
Module Title: Drug Discovery and Medicinal Chemistry
Module Code: CHEM1110
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Q3. Answer ALL parts of this question

a)
Describe Pharma industry approaches to the treatment of cerebral ischemic brain
damage following a stroke.

Your answer should describe known and tried drug targets based on:

i) Understanding of the mechanisms of cerebral ischemic damage and neuronal cell

death.
[10 marks]

ii) New science that has evolved following the Covid-19 infection pandemic with
increased cardiovascular and stroke risk.
[5 marks]

iii) Approaches to restoring blood flow and stroke prevention.

[10 marks]

b)
The excitatory neurotransmitter, glutamate has been implicated in major depressive
disorder.

i) Discuss how the glutamatergic system is involved in depression, and how this
emerging theory is different from the monoamine theory of depression
[18 marks]

ii) Explain how the dissociative anaesthetic, Ketamine can be used as a treatment for
major depressive disorder.
[7marks]
[Total 50 marks]
END OF PAPER

Page 6 of 6
Session: April 2023
Module Title: Drug Discovery and Medicinal Chemistry
Module Code: CHEM1110