Updated 6 min read
Start from the scaffold
Each major drug class has a core structure — the beta-lactam of penicillins, the catecholamine skeleton of adrenergic drugs, the benzodiazepine ring system. Learn to sketch each scaffold, then mark the few positions where substitution changes activity. Questions almost always target those positions.
Ask what each change does
- Does it change potency?
- Does it change receptor selectivity?
- Does it protect against metabolism or enzymatic breakdown?
- Does it change lipophilicity, and therefore absorption or CNS penetration?
Keep a prodrug list
Prodrugs are a favourite source of questions. List each one with its active form and the reason for the design — better absorption, longer action, site-specific activation or reduced toxicity. Enalapril to enalaprilat and levodopa to dopamine are classic examples.
Metabolism as reactions
Learn phase I reactions (oxidation, reduction, hydrolysis) and phase II conjugations (glucuronidation, sulphation, acetylation, glutathione conjugation) as a short list of reaction types with a drug example for each. Then connect them to pharmacology: slow acetylators and isoniazid, or glutathione depletion in paracetamol toxicity.
Practise little and often
Medicinal chemistry is easy to forget if you leave it for weeks. Short, regular MCQ sets keep scaffolds and SAR rules fresh without long sessions.