Learning Outcomes:
On completion of the module, the student will have a clearer understanding of the principles of the various disciplines that are encompassed by the degree in Medicinal Chemistry and Chemical Biology. Students should have a better understanding of how drug targets are selected/identified, how drug molecules are designed and optimised, and how these drugs interact with receptors. Students will be introduced to medicinal chemistry terminology and gain an excellent appreciation for intermolecular drug binding interactions. They will also be introduced to several natural products of medicinal interest and take a close look at some biological targets.
Indicative Module Content:
1) Brief history of the pharmaceutical industry
2) Timeframe from discovery to market
3) We considered some drug properties
4) Structure of cells
5) Intermolecular interactions – H-bonding; electrostatic; London dispersion forces
6) H-bonding in Nature
7) Structure of amino acids (importance of their side chain)
8) Introduction to drug targets (enzymes)
9) Primary, secondary and tertiary structure of proteins
10) Introduction to how enzymes work
11) Catalytic mechanism of a protease
12) HIV life cycle to highlight potential drug targets
13) Ion channels; GPCRs; nuclear receptors
14) Structure activity relationships (SAR)
15) Binding role of common functional groups
16) Introduction to resonance structures (we look at this for amides, as an example)
17) Importance of testing in vitro and in vivo
SAR: Have a think about all these functional groups discussed and what each functional group change/swap might tell you!
18) Use of SAR in drug optimization
19) Pharmacophore – what is it? Can you recognize one from a panel of similar drugs; Why is it useful to establish the pharmacophore.
20) Terminology: active conformation; lead compound
21) Why necessary to optimize lead compound
22) Drug optimization strategies: variation; extension of structure; chain extension; ring expansion/contraction; ring variation;
simplification; rigidification
23) Drug optimization in-class problems
24) Introduction to pharmacokinetics - ADME
25) Pharmacokinetic parameters: half-life; bioavailability; clearance rate
Phase I (P450s/esterases) and Phase II metabolism (Glucuronidation)
26) A brief look at physiochemical properties of drugs
27) pH variation between various areas of the body
28) Drug ionisation; pKa (carboxylic acids and amines)
29) Lipophilicity and how measured (LogP; LogD)
30) Lipinski’s Rule of 5