Pharmaceutical Chemistry and Medicinal Chemistry
Core Concepts
This domain covers drug structure, physicochemical properties, and structure-activity relationships (SAR). Key areas include functional group chemistry, stereochemistry (enantiomers, racemates), drug metabolism (phase I/II), and prodrugs. Candidates must recognize common pharmacophores and understand how lipophilicity (logP), pKa, and hydrogen bonding affect absorption and receptor binding. Medicinal chemistry strategies like bioisosterism and homologation are also tested.
Question Traps
- Prodrug vs. active drug: A prodrug is inactive until metabolized (e.g., enalapril to enalaprilat). Questions may ask which compound is the active form.
- Stereochemistry and activity: Often only one enantiomer is active (e.g., levodopa vs. dopamine). Racemic mixtures may have different potency.
- Phase I vs. Phase II metabolism: Phase I (oxidation, reduction, hydrolysis) often inactivates or activates; Phase II (conjugation) usually increases water solubility for excretion.
Worked Example / Rule of Thumb
Question: Why is levodopa used instead of dopamine for Parkinson’s disease? Levodopa has a carboxyl group that allows transport across the blood-brain barrier via L-amino acid transporter; dopamine is too polar. Rule of thumb: “Like dissolves like” – lipophilic drugs cross membranes better; ionized drugs are excreted more readily.