MPharm Master of Pharmacy Medicinal Chemistry and Drug Design 2 — Questions and Answers
Question 1: Which chemical modification is applied to convert a carboxylic acid to an ester prodrug to improve oral bioavailability?
- N-methylation
- Esterification (Correct answer)
- Hydroxylation
- Glucuronidation
Correct answer: Esterification
Esterification masks the carboxylic acid, increasing lipophilicity and membrane permeability; the ester is then hydrolyzed in vivo to release the active acid.
Question 2: In QSAR studies, which descriptor represents a drug's lipophilicity?
- Molar refractivity
- Log P (Correct answer)
- Topological polar surface area
- Molecular weight
Correct answer: Log P
Log P (partition coefficient between octanol and water) is the standard QSAR descriptor quantifying lipophilicity of a drug molecule.
Question 3: Which type of interaction is primarily responsible for the binding of catecholamine drugs to beta-adrenergic receptors?
- Covalent bonds
- Van der Waals forces only
- Ionic and hydrogen bonding interactions (Correct answer)
- Disulfide bridges
Correct answer: Ionic and hydrogen bonding interactions
Catecholamines interact with beta receptors through ionic interactions between the amine group and aspartate residues plus hydrogen bonds via the catechol hydroxyl groups.
Question 4: What is the significance of chirality in drug design as illustrated by thalidomide?
- One enantiomer is always more water-soluble
- Different enantiomers can have drastically different pharmacological and toxicological effects (Correct answer)
- Chiral drugs are always more potent
- Chirality affects only drug metabolism, not efficacy
Correct answer: Different enantiomers can have drastically different pharmacological and toxicological effects
Thalidomide's R-enantiomer has sedative effects while the S-enantiomer is teratogenic, demonstrating that stereochemistry critically determines drug outcomes.
Question 5: Which property of a drug is described by the term 'metabolic stability'?
- The ability of a drug to resist crystallization
- The rate at which a drug is metabolized by hepatic enzymes (Correct answer)
- The stability of a drug under acidic gastric conditions
- The resistance of a drug to photodegradation
Correct answer: The rate at which a drug is metabolized by hepatic enzymes
Metabolic stability refers to how quickly hepatic enzymes (primarily CYP450s) transform a drug, influencing its half-life and bioavailability.
Question 6: The concept of 'soft drugs' in medicinal chemistry refers to compounds that:
- Have low molecular weight
- Are designed to be metabolized predictably to non-toxic metabolites after exerting their effect (Correct answer)
- Cross the blood-brain barrier easily
- Require refrigeration for stability
Correct answer: Are designed to be metabolized predictably to non-toxic metabolites after exerting their effect
Soft drugs are active therapeutic agents designed to undergo controlled, one-step metabolism to predictably inactive metabolites, minimizing systemic toxicity.
MPharm Master of Pharmacy Medicinal Chemistry and Drug Design 2
Which chemical modification is applied to convert a carboxylic acid to an ester prodrug to improve oral bioavailability?