Introduction to Medicinal Chemistry (DNF) Practice Questions & Answers PDF

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Introduction to Medicinal Chemistry Practice Questions & Answers...

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MEDICINAL CHEMISTRY 1 – PRACTICE QUESTIONS AND ANSWERS Introduction to Medicinal Chemistry – David Fox (L1-2, 7-10) Q1 a) Describe what is meant by the terms hit, lead and candidate within the context of drug discovery. Hit: a compound with confirmed activity (typically 5→0.5 μM) against the target protein. Activity with structurally related compounds may also have been confirmed. Lead: An example from a structural series with activity within 10-fold of the target profile and evidence (within that series) that required selectivity, safety and pharmacokinetics are achievable. Candidate: A single compound from the lead series that meets all minimum requirements for progression towards clinical development.

b) Outline three factors that are key considerations in assessing the quality of a drug molecule, explaining the importance of each factor. Factors could include:  Lipophilicity/polarity/ionisation – solubility, safety, distribution etc.  Potency – impact on dose size  Selectivity – safety and toleration  Size – impact on absorption potential, cost of synthesis  Presence of reactive functional groups/toxicophores – impact on idiosyncratic toxicity c) The table below summarises the lead properties and candidate criteria for a lead optimisation programme. Based on the data provided, highlight which of the candidate criteria requires further optimisation, explaining your reasoning.

Binding affinity at target receptor Selectivity against related targets Predicted pharmacokinetics in human Predicted dose size

Candidate criterion IC50 50-fold

120-fold

Bioavailability >50% Half-life >18 hr

Bioavailability 75% Clearance 5 mL/min/kg Vd = 3 L/kg 20 mg...