MChem Master of Chemistry Master of Chemistry: Pharmaceutical Chemistry 3 — Questions and Answers
Question 1: Which mechanism underlies the anticoagulant action of warfarin at the molecular level?
- Direct thrombin inhibition
- Inhibition of vitamin K epoxide reductase (Correct answer)
- Activation of antithrombin III
- Blockade of fibrinogen receptor GPIIb/IIIa
Correct answer: Inhibition of vitamin K epoxide reductase
Warfarin inhibits vitamin K epoxide reductase, preventing regeneration of reduced vitamin K required for γ-carboxylation of clotting factors II, VII, IX, and X.
Question 2: In QSAR studies, the Hammett sigma constant (σ) characterizes which molecular property of substituents?
- Steric bulk
- Electronic effects on aromatic systems (Correct answer)
- Lipophilicity contribution
- Hydrogen bonding capacity
Correct answer: Electronic effects on aromatic systems
The Hammett σ constant quantifies the electron-donating or electron-withdrawing electronic effect of substituents on aromatic ring systems.
Question 3: Which salt form strategy is most effective for improving the dissolution rate of a BCS Class II drug?
- Lyophilization
- Conversion to a hydrochloride or sodium salt (Correct answer)
- Increasing particle size
- Lowering storage temperature
Correct answer: Conversion to a hydrochloride or sodium salt
Forming ionizable salts (e.g., HCl or Na salts) dramatically increases the dissolution rate of poorly soluble BCS Class II drugs by improving wettability and solubility.
Question 4: The Hansch analysis in medicinal chemistry uses the partition coefficient (π) to quantify which parameter?
- Molecular flexibility
- Substituent lipophilicity (Correct answer)
- Molar refractivity
- pKa contribution
Correct answer: Substituent lipophilicity
The Hansch π parameter measures the relative lipophilicity contribution of a substituent compared to hydrogen (π = logP_substituted − logP_unsubstituted).
Question 5: Which crystal form consideration is critical during pharmaceutical development due to its impact on bioavailability?
- Crystal color
- Polymorphism (Correct answer)
- Crystal transparency
- Crystal habit symmetry
Correct answer: Polymorphism
Polymorphism (existence of multiple crystal forms of the same molecule) critically affects solubility, dissolution rate, and consequently oral bioavailability.
Question 6: Which type of drug-receptor interaction is typically irreversible and results in prolonged pharmacological effect?
- Ionic interaction
- Van der Waals interaction
- Covalent bond formation (Correct answer)
- Hydrogen bonding
Correct answer: Covalent bond formation
Covalent bond formation between drug and receptor creates irreversible binding, extending pharmacological effect beyond the drug's plasma half-life.
Question 7: In high-throughput screening (HTS), what does a Z' factor value > 0.5 indicate about an assay?
- The assay has too many false positives
- The assay is suitable for screening (excellent quality) (Correct answer)
- The assay requires reformatting
- The compound library is too diverse
Correct answer: The assay is suitable for screening (excellent quality)
A Z' factor > 0.5 indicates an excellent assay with sufficient separation between positive and negative controls for reliable HTS campaigns.
MChem Master of Chemistry Master of Chemistry: Pharmaceutical Chemistry 3
Which mechanism underlies the anticoagulant action of warfarin at the molecular level?