Pharm.D. Doctor of Pharmacy Pharmaceutical Chemistry and Drug Design 2 — Questions and Answers
Question 1: Which property is described by the octanol-water partition coefficient (logP)?
- Aqueous solubility only
- Relative lipophilicity of a compound (Correct answer)
- Ionization constant of a drug
- Molecular weight of the drug
Correct answer: Relative lipophilicity of a compound
LogP measures the relative lipophilicity of a compound by comparing its distribution between octanol (lipid-like) and water phases.
Question 2: Which chemical modification increases water solubility of a poorly soluble drug during pharmaceutical formulation?
- Adding a nonpolar alkyl chain
- Salt formation or adding ionizable groups (Correct answer)
- Cyclization of the molecule
- Esterification with a fatty acid
Correct answer: Salt formation or adding ionizable groups
Salt formation (e.g., converting a weak acid to its sodium salt) or adding ionizable groups significantly increases the aqueous solubility of poorly water-soluble drugs.
Question 3: In the Biopharmaceutics Classification System (BCS), a Class I drug is defined as:
- High solubility, low permeability
- Low solubility, high permeability
- High solubility, high permeability (Correct answer)
- Low solubility, low permeability
Correct answer: High solubility, high permeability
BCS Class I drugs have both high solubility and high permeability, making them the easiest to develop for oral delivery and candidates for biowaiver applications.
Question 4: Which type of drug-receptor interaction is most easily reversed?
- Covalent bond
- Ionic/electrostatic interaction (Correct answer)
- Coordinate covalent bond
- Disulfide bond
Correct answer: Ionic/electrostatic interaction
Ionic (electrostatic) interactions are reversible and weaker than covalent bonds, making them the most easily disrupted type of drug-receptor interaction.
Question 5: Which concept explains why adding a methyl group to a drug can sometimes significantly alter its receptor selectivity?
- The methyl group increases molecular weight beyond Lipinski limits
- Steric effects and the 'methyl magic' phenomenon in medicinal chemistry (Correct answer)
- Methylation always increases toxicity
- The methyl group blocks metabolism at that site
Correct answer: Steric effects and the 'methyl magic' phenomenon in medicinal chemistry
In medicinal chemistry, 'methyl magic' refers to the phenomenon where adding a methyl group creates steric interactions that dramatically alter receptor binding selectivity or potency.
Question 6: Aspirin irreversibly inhibits cyclooxygenase (COX) enzymes through which chemical mechanism?
- Competitive reversible binding at the active site
- Acetylation of a serine residue in the enzyme active site (Correct answer)
- Chelation of a metal cofactor
- Non-competitive allosteric inhibition
Correct answer: Acetylation of a serine residue in the enzyme active site
Aspirin irreversibly acetylates a specific serine (Ser530) residue in the active site of COX-1 and COX-2, permanently blocking arachidonic acid binding.
Pharm.D. Doctor of Pharmacy Pharmaceutical Chemistry and Drug Design 2
Which property is described by the octanol-water partition coefficient (logP)?