Unit of Study Outline: PHAR2821 Drug Discovery and Design B Semester 2, 2016

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Unit of Study Outline
PHAR2821 Drug Discovery and Design B
Semester 2, 2016

Contents
Contact Details ................................................................................................................................. 2
UoS Description................................................................................................................................ 2
UoS Aims/Goals ................................................................................................................................ 2
Learning Outcomes .......................................................................................................................... 3
Alignment of Learning Outcomes, Learning Activities and Assessments ........................................ 4
Learning commitments .................................................................................................................... 6
Learner Preparation ......................................................................................................................... 6
Text and references ......................................................................................................................... 7
Assessment Schedule ....................................................................................................................... 8
Assessment Tasks ............................................................................................................................. 8
Feedback Schedule .......................................................................................................................... 9
Brief description of the content included in each topic .................................................................. 9
Semester Program ........................................................................................................................... 11
Academic honesty ............................................................................................................................ 12
Special Consideration ....................................................................................................................... 12
Attendance and Participation .......................................................................................................... 12
Evaluation ........................................................................................................................................ 12

PHAR2821: Drug Discovery and Design B Page 1

Last modified: Tuesday, 12 July 2016 © 2016 Faculty of Pharmacy • University of Sydney

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Contact Details
Course Coordinator: Prof Paul Groundwater
Contact for: Academic enquiries
Phone: 02 9114 1232
E‐mail: paul.groundwater@sydney.edu.au
Consultation times: Email correspondence is preferred.
Telephone discussion – by appointment only

UoS Description
Drug Discovery and Design B goes beyond the basics to help students develop a deeper
understanding of how drugs work, and how to discover and design new drugs. How drugs are
transformed by metabolism is explored, with a particular focus on the factors which influence
metabolism and pharmacogenetics. A problem‐based learning approach will be used for the
prediction of drug metabolite structures from physical, chemical, biochemical and spectroscopic
data. Elements of statistics, stereochemistry, drug design, drug metabolism, and drug mechanism of
action are integrated to explore the pathway from drug discovery and design to clinical application.

UoS Aims/Goals
How this unit of study relates to Builds upon Drug Discovery and Design A (PHAR2811), and 1st
other studied units year units (PHAR1812, CHEM1611 and CHEM1612)
The key focus or purpose of this The purpose of this unit is to understand and appreciate the
unit need and requirements for the development of new drugs.
Topics of key focus are as follows:
o Structure based drug design
o stereochemistry in relation to biological activity
o general principles relating to the discovery of new
drugs
o methods of drug design
o how drugs are modified by metabolism
o identification and prediction of drug metabolites
o mode of action of drugs in relation to their
pharmaceutical application
This unit also involves the application of skills developed in
Drug Discovery and Design A to a learning task on drug action
focusing on working as a team and searching, critically
evaluating and presenting information accessed from
databases and literature sources.
How this unit of study prepares Development of knowledge and reasoning skills with basic
students for subsequent units chemical and physical properties of medicinal materials and
their targets. This can be applied to the understanding of the
scientific principles of drugs and their targets with respect to
therapeutic actions of relevance to pharmaceutical sciences
and pharmacy (underpinning science for all the integrated



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disease‐based units of study in 3rd year).
How this unit helps students to Development scientific thought processes and rational
develop generic or other skills understanding of drugs and their targets.
Problems solving skills using computation and statistical
evaluation.
Database retrieval skills and critical appraisal skills for
literature information retrieval. Skills for presenting
information in a graphical and long written format.

Learning Outcomes
How this unit contributes to the overall BPharm curriculum outcomes

THEME: BASIC AND PHARMACEUTICAL SCIENCES (BPS)
• Critically examines scientific evidence – both quantitative and qualitative – in order to arrive at
evidence based conclusions
o Apply a framework to summarise and interpret the information published in scientific and
quasi‐scientific publications;
o Interpret and write‐up the results of scientific experiments as conducted in practical classes;
o Prepare and present informative graphical material (figures) for reports and publications.
o Demonstrate an understanding of the limitations of experimental measurements.
• Identifies sources of drugs, the way they are discovered, purified, characterised and analysed,
and their physico‐chemical properties
o Identify the different multi‐disciplinary techniques that are used in the process of drug
design (high throughput synthesis and screening, bioinformatics, molecular biology,
computational modelling of both drugs and targets, standard chemistry)
• Outline fundamental concepts in chemistry necessary for understanding drug delivery, drug
action and therapeutics
o Predict the physicochemical properties of a compound based on its structure
• Demonstrates an understanding of the pharmacological mechanisms of action and the properties
drugs display as biologically active molecules in living systems
o Describe the ways in which drugs can interact with biological macromolecules;
o Explain the principles of ligand‐receptor interaction.
• Applies appropriate numeracy skills to the solution of pharmacy problems
o Apply principles of statistics to the description and analysis of data sets.
o Use the principles of probability in the context of simple pharmaceutical problems
o Describe and apply common statistical tests in the context of pharmaceutical problems
• Demonstrates an ability to deal with the concept of uncertainty – devising alternatives which take
into account qualifying and constraining variables
o Identify the indeterminate nature of a solution due to the quality and/or quantity of
information or data and/or the limitations of the method of calculation used;
o Investigate situations in which parameters might change: A. In computational medicinal
chemistry (including structure based drug design) for calculations required for practical
solution, fundamental and empirical calculations, approximations, indeterminate nature of
some solutions, statistical methods to quantify and evaluate uncertainty; B. In drug design,



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evaluation of the predictive value of models prior to application in de novo design and
virtual screening.
• Applies an understanding of basic and applied sciences to the management and solution of
pharmaceutical and clinical problems – metabolism and degradation of drugs
o Understanding of basic metabolism in relation to drugs and efficacy and safety in relation to
the treatment of disease and/or maintenance of health;
o Problem solving applied to chemical and biological data to identify and predict drug
metabolites.
THEME: PERSONAL AND PROFESSIONAL DEVELOPMENT (PPD)
• Demonstrates appropriate attitudes and values in personal and professional dealings
o Accept and deliver constructive criticism.
• Works effectively and cooperatively as a member of a learning group/team
o Negotiate appropriate group rules for the conduct of group collaborations and assignments;
o Identify individual strengths within a group in order to allocate tasks effectively;
o Adopt different roles within a group collaboration.
• Demonstrates the ability to learn independently and take responsibility for own learning]
o Apply knowledge to problem solving.

Alignment of Learning Outcomes, Learning Activities and Assessments
Learning Outcome Activity type Assessment
Component
Maths / Statistics Lectures / Quiz
 use basic statistics that may be applied to drug discovery and tutorials
design
 apply statistics to the relationship between observations on
two variables
 understand the coefficient of correlation and how it can be
used to provide information about the relationship between
two sets of numbers
 fit a straight line to scatterplots of data using simple linear
regression models
 obtain the line of best fit via the method of least squares
 use of residuals to assess the fit of a simple linear model
 explore transformations that can be applied to data to
achieve an approximate linear relationship
 use Excel to carry out simple regression analyses



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Stereochemistry Lectures Quiz / exam
 explain that most events important for the activity of a drug are
affected by the shape or 3‐dimensional properties of the drug
molecule
 define stereochemistry as 3‐D structure or shape of molecule
(drug) and recognise that the stereochemistry of the receptor
molecule is also important
 define chirality and understand its significance and application
to drugs with respect to stereoisomers, enantiomers &
diastereoisomers
 use R,S convention rules to specify the configuration of
molecules with chiral carbons
 discuss stereospecificity & stereoselectivity of stereoisomers
with respect to transport phenomena, drug ‐ enzyme/receptor
interactions
 explain inversion & racemisation of drugs
 understand the conformation of molecules as shapes of
molecules arising from their flexibility (applies to all
molecules including drug and receptor molecules)
 discuss the relationship between the conformation of drugs and
pharmacological activity
 recognise factors that may influence the conformation of drugs
 understand the significance of the stereochemistry of drugs in
relation to their pharmacological actions
Drug discovery and design Lectures / Workshop /
 recognize the limitations and shortcomings of existing drugs workshops exam
and the ongoing requirement to design new drugs
 recognize where drugs have come from and future sources of
drugs.
 understand where and how to retrieve information about
how drugs bind to receptors and understand the nature of
drug receptor interactions.
 understand the ways and utility of relating drug properties to
drug action in relation to drug design
 understand the process involved in structure based drug
design and gain hands on experience in computational
modelling incl visualising protein and protein complexes, high
throughput virtual screening and optimisation of lead
molecules.
 recognise that most biological events are influenced by the
shape, size, and charge distribution on molecules. Recognise
the 3D properties of drugs and the factors determining their
shape size and other 3D properties.
 understand and know how molecular modelling and QSAR
may be applied to drug design and recognize the advantages
and limitations of this approach.



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Drug metabolism Lectures / Workshop /
 predict possible metabolites from a given drug structure, workshops exam
 recognise those metabolites more likely to be excreted in
urine or faeces,
 classify drug metabolism reactions
 list the enzymes and cofactors involved,
 understand and explain induction of metabolism and its
inhibition,
 develop a strategy to identify drug metabolites using
knowledge of metabolism to predict likely metabolites and
biological, physical and spectroscopic data to determine their
chemical structure
 be able to express a level of confidence in the identity of a
drug metabolite based on the adequacy of the accessible data
 recognise and explain drug metabolic pathways
Drug Action Lectures / Workshop /
 use literature searching databases and reference managing workshop exam
software
 use medline and embase literature searching databases
 be able to keep abreast of current knowledge as applied to
pharmaceutical sciences
 have developed tools to critically appraise the
national/international literature
 have applied the above skills to drugs in a pharmaceutical
science setting

Learning commitments
Credit points 6
Face‐to‐face Total number of lecture hours 33
Learning Total number of tutorial/workshop hours 23
Total number of practical hours 0
Total number of practicum hours 0
Self‐directed Total number of on‐line hours 1
Learning Total number of hours of private study 40
Total number of self‐directed learning hours 21
Total (hours) Commitment 118

Learner Preparation
Pre‐requisites N/A
Co‐requisites PHAR2811 and PCOL2605
Assumed knowledge or skills N/A
Computer access Email and internet access is strongly recommended. Students will
requirements be expected to access materials online (Blackboard).
Preliminary reading required N/A



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Text and references
Essential texts G.L.Patrick (2009) An Introduction to Medicinal Chemistry, 4th Ed,
Chapter 11.4, pages 156‐167. Also, 5th Edition 2013.
Recommended texts Foyes’ (2008) Principles of Medicinal Chemistry 6th Ed, Chapter 10,
Drug Metabolism, pages 253‐326. Also, 7th Edition 2012.

Anderson, Bendell, and Groundwater (2012) Royal Society of
Chemistry Tutorial Chemistry Texts — Organic Spectroscopic Analysis,
RSC, London, ISBN 0 85404‐476‐0 (available from library catalogue)
References Smith & Williams (2006) Introduction to the Principles of Drug Design
and Action, 4th Ed CRC Taylor & Francis Group
Web sites Patrick, An Introduction to Medicinal Chemistry, 4th Ed. Also 5th
Edition 2013. Student on‐line resource
http://global.oup.com/uk/orc/chemistry/patrick5e/
Policies Faculty of Pharmacy Policies
http://sydney.edu.au/pharmacy/current‐students/policies/
University of Sydney (Coursework) Rule 2014
http://sydney.edu.au/policies/showdoc.aspx?recnum=PDOC2014/37
7&RendNum=0
Special Consideration (Special arrangements)
http://sydney.edu.au/current_students/special_consideration/index.
shtml
Student Code of Conduct
5&RendNum=0
Faculty of Pharmacy: Contextualised Graduate Attributes
http://sydney.edu.au/education‐
portfolio/ei/graduateAttributes/facultyGA.cfm?faculty=Pharmacy
Academic Honesty in Coursework Policy 2015
4&RendNum=0
The Bachelor of Pharmacy Third Year Assessment Local Provisions
http://sydney.edu.au/policies/default.aspx?mode=folder&uri=78226
51
University of Sydney Library https://www.library.usyd.edu.au/
Pharmacy subject guide http://libguides.library.usyd.edu.au/content.php?pid=27832
Academic Liaison Librarian Lorraine Evison
(Pharmacy) phone: +61 2 9351 4949
email: lorraine.evison@sydney.edu.au
location: Level 2
address: F03 ‐ Fisher Library



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url: http://sydney.edu.au/library/libraries/medical
Site Services Advisor Erica Demian
phone: +61 2 9351 5315
email: erica.demian@sydney.edu.au
location: SciTech Library
address: G02 ‐ Jane Foss Russell Building
url: http://www.library.usyd.edu.au/

Assessment Schedule
Assessment * Test Individua Assessme Lengt Weig How to Due Date
Name Type l / Group nt h ht submit
Condition
s
Maths / Short I MCQ 45 10% 18th Aug
Statistics Quiz Answer mins
Stereochemistry MCQ I Workshop 3 h 10% Weeks 3,4
Quiz plus MCQ
Structure‐Based NA G 10% Turnitin Weeks
Drug Design * 5,6
Drug NA I Problem‐ 3h 10% Weeks
Metabolism solving in 9,10,11
workshop
Drug Action Oral G Presentatio 10% Turnitin Weeks 11,12
n
Final * MCQ I MCQ, SAQ 2h 50%
Examination and
Short
Answer

*This denotes an individual assessment component must be passed satisfy the requirements of the
Unit of Study.

To achieve a pass, a minimum mark of 50% must be obtained for both the unseen written final
examination paper (relative weighting 50%) and the total for the in‐semester assessment
components.
In addition, the final marks for the Unit‐of‐Study must be 50% or greater.

Assessment Tasks
Maths / Statistics Quiz (10 %)
Stereochemistry Workshop and Quiz (10 %)
DD3 Structure‐Based Drug Design assessment (10 %)
DA3 Drug Metabolism (10 %)
DA4 Drug Action (10 %)



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Examination (50 %)

The information in this section provides a brief overview of each assessment task. For more detailed
information, go to the Assessment Outlines page of your Blackboard website.

Feedback Schedule
Task / Component Type of Feedback Timeframe
Maths/Statistics Quiz Mark August / September
Stereochemistry Workshop and Quiz Mark August / September
Structure‐Based Drug Design Dialogue with tutor and September
Workshop group assessment mark
Drug Metabolism Workshop Dialogue with tutor and October
group assessment mark
Drug Action Workshop Dialogue with tutor and October
group assessment mark
Q & A Session Dialogue with coordinator October
Examination Review Session Formative feedback related December
to exam performance

Brief description of the content included in each topic
Topic 1: Maths / Statistics
These lectures will focus on the relationship between observations on two variables. The coefficient
of correlation will be introduced as a statistic that can be used to provide information about the
nature of the association between the two sets of numbers.

Simple linear regression models are used to fit a straight line to scatterplots of data. The line of best
fit will be obtained via the method of least squares. The lectures will illustrate how to use residuals
to assess the fit of a simple linear model. Transformations that can be applied to data to achieve an
approximate linear relationship will also be explored.

Students will be shown how to use Excel to carry out simple regression analyses.

Topic 2: Stereochemistry
Exploration of the significance of the 3‐dimensional structure of drugs and their receptors in relation
to their pharmacological and physiological activity. Definition of stereoisomers and their
classification as enantiomers and diastereoisomers. Physical and chemical properties of
stereoisomers. Examples of specific types of diastereoisomers, including anomers, epimers and
geometric isomers. Definition of configuration and conformation in terms of describing the shape
and flexibility of drugs and their receptors. Factors determining the shape of drug molecules and
examples indicating the importance of stereochemistry for medicinal actions.



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Topic 3: Drug Design and Discovery
An overview of drug design and discovery. Selection of targets for drug action and identification of
'lead' drugs. Sources of new drugs. Optimisation and development of 'lead' drugs. Quantitative
structure‐activity relationships.

Introduction to the use of computer graphics for molecular modelling and drug design.
Determination of the shape and other three‐dimensional properties of drugs by computer
calculations. Examples of the use of molecular modelling to relate the three‐dimensional properties
of drug molecules to biological action.

Topic 4: Drug Metabolism
Lectures on the metabolism of drugs as foreign compounds will focus on the range of reactions that
occur during the biotransformation of foreign compounds in the body. Examples will be drawn,
wherever practicable, from current drugs.

Methods of obtaining information about metabolism require experimentation with the drug itself.
Studies may be done in the living animal (in vivo) or in the test tube (in vitro), and there are two
questions that are asked. What are the products formed from the drug, and how much of each is
produced?
The question of how much metabolite is produced (the quantitative aspect) is answered by
techniques such as chromatography. The metabolic reactions considered will include functional
group changes such as these produced by oxidation, dealkylation, epoxidation, hydrolyses, and
reductions. These are phase 1 reactions, and they will be contrasted with phase 2 reactions in which
the metabolic product is generally much more water soluble, and therefore more readily excreted.
Urinary, biliary and faecal excretion of drugs will be mentioned. Also the effects of other chemical
substances on drug metabolism will be discussed since metabolism may be modulated by the
presence of other substances. Enzymes and biochemical mechanisms will be presented to explain
and facilitate understanding of key metabolic processes.

Topic 5: NMR / IR / MS
Questions of the qualitative nature of metabolites (what are they?) are answered using
spectroscopic and spectrometric methods of analysis. The use of the powerful tools, nuclear
magnetic resonance (NMR) and mass spectrometry (MS), will be illustrated as they provide
information essential for the understanding of structural changes and the determination of drug
action.

Topic 6: Drug Design to Clinical Application
A number of lectures to tie all the elements presented for drug discovery and design together
showing the direction towards clinical application.



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Semester Program
PLEASE REFER TO YOUR BLACKBOARD WEBSITE FOR THE MOST UP‐TO‐DATE VERSION OF YOUR
TIMETABLE
Wk Beginning Lecture Topic Tutorial Topic

1 25 Jul
26 Jul Introduction / Stereochemistry (PWG)
28 Jul Maths (JO)
29 Jul Maths (JO)
2 1 Aug Maths tutorials
2 Aug Stereochemistry (PWG)
4 Aug Maths (JO)
5 Aug Stereochemistry (PWG)
3 8 Aug Maths tutorials / Drug design 1
9 Aug Maths (JO)
11 Aug Drug Design 1 (DEH)
4 15 Aug Drug design 1 / Drug design 2
19 Aug Drug Discovery 1 (TB)
5 22 Aug Drug design 2 / Drug design 3
26 Aug Drug Metabolism 1 (PWG)
6 29 Aug Drug design 3 / Drug action 1
30 Aug Drug Metabolism 2 (PWG)
1 Sep Drug Metabolism 3 (PWG)
7 5 Sep Drug action 1 / Drug action 2
8 Sep NMR/ IR/MS 1 (NW)
8 12 Sep Drug action 2
15 Sep Metabolism worked examples 1 (PWG)
16 Sep Worked example drop in session (PWG)
9 19 Sep Drug action 3
20 Sep Metabolism worked examples 1 (JRH)
22 Sep Metabolism worked examples 1 (NW)
23 Sep Worked example drop in session (JRH)
MID 26 Sep
SEM
10 3 Oct Drug action 3
4 Oct Worked example drop in session (NW)
6 Oct No lecture
7 Oct No lecture



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11 Oct Drug Design to Clinical Application 1 (JRH)
18 Oct Drug Design to Clinical Application 1 (PWG)
20 Oct Drug Design to Clinical Application 1 (PWG)

Academic honesty
The University takes a serious attitude towards academic honesty.
You are strongly advised to read the Academic Honesty in Coursework Policy available at
http://sydney.edu.au/policies/showdoc.aspx?recnum=PDOC2012/254&RendNum=0.
The University uses text matching software to assist in identifying potential plagiarism.
If you are uncertain about what is acceptable, please seek advice from the course coordinator.

Special Consideration
If you have a serious illness, injury or circumstances arise that affect your ability to complete or
submit an assessment, you may have grounds to apply for special consideration. For more
information see: http://sydney.edu.au/study/academic‐support/learning‐support/staying‐on‐
track.html.

Attendance and Participation
In accordance with the faculty local provisions on Attendance, students are expected to attend at
least 85% of the compulsory sessions in any Unit of Study. You must attend practical and workshop
classes and the attendance rule must be met even with medical certification

Students are advised that it is a requirement of the BPharm/MPharm degree that they participate
appropriately, in all classroom and examination tasks, including role plays and group work involving
all genders. The Faculty is unable to exempt students from these tasks.

For further information please see the Coursework Policy and Coursework Rule and related
documents on the University website.

Evaluation
The following changes were made to this unit of study based on the feedback provided by students
who participated in the S1, 2015 USS survey:
1. Re‐designed the Drug Design Workshop and Assessment to include Structure‐Based Drug
Design (and removed the QSAR Workshop)
2. Provided greater support (and examples of problem‐solving methodologies) for the Drug
Metabolism Workshops
3. Provided greater help with spectroscopic interpretation
4. Revised the weighting of the assessment to 5% final examination, 50% in semester
assessment



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