Answer the following questions about the drug structures shown here (click).

1. List a structural class for each of these drug structures (be as specific as possible). Click here for answers

2. List a therapeutic (not pharmacological) use for each of these drug structures. Click here for answers

3. List those drug structures that are acidic organic compounds (pKa 3-12). Click here for answers

4. List those drug structures that are basic organic compounds (pKa 3-12). Click here for answers

5. List those drug structures that are neutral organic compounds. Click here for answers

6. Describe the structural features of Drug #1 that make it a more useful therapeutic agent than ethanol (C₂H₅OH).

Additional lipophilic hydrocarbon structural features (facilitate distribution to CNS site of action

Tertiary alochol function - greater metabolic stability therefore clinically compatibile biodisposition profile.

7. The duration of therapeutic effects of drug #2 is much shorter than that of drug #4. Provide a plausible explanation for this difference.

Drug #2, a thiobarbiturate derivative, is significantly more lipid soluble than drug #4, a barbiturate derivative. Rapid tissue redistribution will serve to shorten the pharmacological actions of drug #2 to a greater extent than drug #4.

8. Draw the structure of the omega- and omega-1 CYP450 oxidation metabolites of drug #2.

9. Discuss a plausible mechanism for the CNS depressant effects of drug #3. Show the structure of a water-soluble oral dosage form of drug #3.

Since the stucture of drug #3 closely resembles that of valproic acid one can assume that the effects of drug #3 on GABA neurotransmission will be similar to those of valproate, i.e., conservation of the neurotransmitter by inhibiting the catabolic enzyme, GABA-T.

10. Draw the structures of the metabolites of drug #4 resulting from (i) aromatic hydroxylation and (ii) allylic oxidation.

11. Which drug, 5 or 6, will have the longer duration of therapeutic action? Explain why.

Clearance of drug #6 by metabolism will require more extensive biotransformation because of its structural features (note N¹-substituent) thereby providing it with a longer duration of therapeutic action.

12. Drug #5 degrades in acidic solution resulting in the formation of two products. Show these reactions and comment on their pharmaceutical signfiicance.

Benzodiazepines cannot be formulated for parenteral administration in aqueous acid solutions since they degrade via hydrolysis of the 1,4-diazepine ring system. Parenteral formulations must be prepared utilizing nonaqueous solvents.

13. Draw the structure of a prodrug of drug 7 suitable for formulation in an aqeuous, well tolerated parenteral (IV and IM) dosage form.

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