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4/1/2019 Oxford University Press | Online Resource Centre | Chapter 14

Patrick: An Introduction to Medicinal Chemistry 6e


Chapter 14

Results
You have answered 4 out of 15 questions correctly.
Your percentage score is 26%.
Question 1
Tioconazole is a non-polar antifungal agent which is used topically, whereas fluconazole is a polar drug which is used systemically. Which of the
following statements is correct?

Your answer:
a) The heterocyclic groups in fluconazole contain more nitrogen atoms making the drug less polar.
Correct answer:
d) The alcohol group in fluconazole increases polarity.
Feedback:
Fluconazole is more polar and more water soluble than tioconazole due to the extra nitrogen atoms and the alcohol group.
Option d) is the only correct statement.
Option a) is wrong since the nitrogen atoms make the drug more
polar and not less polar.
Option b) is wrong since increased polarity increases
water solubility. Option c) is wrong since the fluorine substituents have little effect on
water solubility.
Page reference: 249

Question 2
Which of the following strategies will increase the polarity and water solubility of a drug?

Your answer:
a) Removing polar functional groups
Correct answer:
c) Replacing an aromatic ring with a nitrogen containing heterocyclic ring
Feedback:
The extra nitrogen atom increases polarity and water solubility. The other options all increase the hydrophobic character of the drug and will
decrease water solubility.
Page reference: 249-250

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Question 3
Losartin was developed from structure (I) as an antihypertensive agent by replacing a carboxylic acid group with a tetrazole ring. Which of the
following statements is incorrect?

Your answer:
a) The tetrazole ring represents a bio-isostere.
Correct answer:
d) The tetrazole ring is more polar than a carboxylic acid.
Feedback:
The tetrazole ring is ten times less polar than a carboxylic acid. The other statements are accurate.
Page reference: 251

Question 4
Why does chlorpropamide have a longer antibiotic activity than tolbutamide?

Your answer:
b) The methyl group of tolbutamide is susceptible to drug metabolism whereas the chloro substituent of chlorpropamide is not.
Feedback:
The major metabolic reaction carried out on tolbutamide is oxidation of the methyl group to a carboxylic acid. The chloro substituent in
chlorpropamide is resistant to this metabolism.
Page reference: 253

Question 5
Lidocaine is a longer lasting local anaesthetic than procaine. Which of the following statements is false?

Your answer:
c) The amide group in lidocaine is important to its stability.
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Correct answer:
d) The NH group in procaine makes procaine less stable than lidocaine.
2

Feedback:
Option d) is wrong. The amino group plays no role in the stability of the molecule. It is present as an extra binding group for the target
binding site.
The other options are accurate. Procaine has an ester group which is susceptible to hydrolysis. Lidocaine has an amide group which is
more resistant to hydrolysis, and which is also protected by the two methyl groups on the aromatic ring, which act as steric shields.
Page reference: 252

Question 6
Carbachol is more stable than acetylcholine to hydrolysis. Which of the following statements is not true?

Your answer:
a) The blue coloured methyl group of acetylcholine is susceptible to oxidation by cytochrome p450 enzymes.
Feedback:
Acetylcholine is metabolised by esterases which hydrolyse the ester group. It is not metabolised by cytochrome p450 enzymes.
Replacing the acyl methyl group of acetylcholine with an amino group alters the ester functional group to a urethane functional group.
Urethanes are more resistant to hydrolysis, since the nitrogen's lone pair interacts with the neighbouring carbonyl group and makes it less
reactive to nucleophiles such as water.
Page reference: 251-252

Question 7
Some drugs containing an ester group are inactive in vitro, but are active once the drug has been absorbed in vivo. What term is used for such
drugs?

Your answer:
d) prodrugs
Feedback:
These drugs are described as prodrugs. They do not bind to a target binding site in vivo since an important binding group has been masked
by the ester. The ester group is hydrolysed in vivo to reveal the binding group.
There are no such things as postdrugs or predrugs. Metabolites are the structures which are formed after metabolic reactions.
Page reference: 258

Question 8
L791456 is an anti-arthritic drug with a shorter lifetime in the body than L787257. The only difference in the structures is a methyl substituent on
one of the pyridine rings. Why does the presence of a methyl group decrease the lifetime of the drug?

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Your answer:
d) It increases the rate of N-oxidation and deactivation of the drug.
Correct answer:
c) It is metabolised by oxidative enzymes to an alcohol or carboxylic acid. The resulting polar metabolites are rapidly excreted.
Feedback:
The methyl group is an exposed group which is susceptible to oxidative metabolism by cytochrome P450 enzymes. The resulting
metabolites are more polar than the original drug and are quickly excreted.
The other options are not impossible, but do not occur in this case.
Page reference: 255

Question 9
In Parkinson's disease, there is a lack of the neurotransmitter dopamine in the brain. Adding dopamine itself is not very effective for a variety of
reasons. Which of the following statements is not a valid explanation?

Your answer:
c) Dopamine is metabolised to inactive metabolites.
Correct answer:
b) Dopamine is chemically unstable.
Feedback:
Option b) is wrong. Dopamine is chemically stable.
The other statements are valid explanations as to why dopamine would make a poor drug for the treatment of Parkinson's disease. It cannot
access the brain easily. It shows poor selectivity between different types of receptors and it is rapidly metabolised.
Page reference: 259-260

Question 10
Esters are frequently used as prodrugs. Which of the following statements is false?

Your answer:
c) Esters can be used to mask a polar alcohol, phenol or carboxylic acid group.
Correct answer:
b) Esters are more susceptible to hydrolysis if the alcohol moiety has an electron donating group.
Feedback:
Option b) is wrong. Esters are more susceptible to hydrolysis if the alcohol moiety has an electron- withdrawing group. This stabilises the
alkoxide leaving group and makes it a better leaving group.
Page reference: 258-259

Question 11
Fluphenazine decanoate is an ester prodrug for the antipsychotic drug fluphenazine, and is administered by intramuscular injection. Which of the
following statements is true?

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Your answer:
c) The ester is hydrophilic and rapidly enters the blood supply.
Correct answer:
b) The ester is hydrophobic which means that it is taken up in fat tissue. As a result, it can only enter the blood supply at a slow rate.
Feedback:
Option b) is correct.
Option a) is wrong since an alcohol group is revealed on fluphenazine following hydrolysis.
hydrophobic
Option c) is false since the ester is and is taken up in fat tissue as stated in option b). Option d) is wrong. The statement
implies that the ester spontaneously hydrolyses at slightly alkaline pH, whereas it is the action of esterase enzymes in the blood that results
in rapid hydrolysis.
Page reference: 260-261

Question 12
Structures (I) and (II) are prodrugs of the antibiotic chloramphenicol.

Which of the following statements is true?

Your answer:
a) Structure I is more water soluble than chloramphenicol.
Correct answer:
b) Structure II is more water soluble than chloramphenicol.
Feedback:
Structure I has a hydrophobic ester which lowers water solubility. As a result, it reduces the bitter taste of the drug when it is taken by
mouth. Structure II has a polar ester due to the carboxylic acid, and so it has good water solubility. It can be used to achieve high
concentrations of the drug for injection.
Page reference: 262

Question 13
Which of the following statements is true with respect to phosphate prodrugs?

Your answer:
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b) Phosphate esters are less water soluble than the parent drug.
Correct answer:
a) Phosphate esters are more polar in nature than the parent drug.
Feedback:
Phosphate esters are more polar and more water soluble than the parent drug. As a result, they are less likely to cross cell membranes.
They are susceptible to metabolism. Otherwise they would not be prodrugs!
Page reference: 262-263

Question 14
Candoxatril is an ester prodrug for candoxatrilat which inhibits protease enzymes. Which of the following statements is incorrect?

Your answer:
b) The parent drug can be administered orally, whereas the ester prodrug cannot.
Feedback:
The statement made in option b) is false. The parent drug is too polar to be given orally and has to be administered by injection. The
prodrug is less polar and can be given orally. The other statements are all accurate.
Page reference: 260

Question 15
Some peptides and proteins have been used as drugs. Which of the following statements is untrue?

Your answer:
b) Peptides and proteins generally show poor bioavailability.
Correct answer:
d) Peptide drugs are susceptible to metabolic enzymes but not to digestive enzymes.
Feedback:
Peptides and proteins are susceptible to hydrolysis by digestive enzymes as well as by metabolic enzymes, and so option d) is the false
statement.
The other statements are true. Proteins and polypeptides are large molecules and can induce an immune response. They are poorly
absorbed when taken orally due to their polar nature. The peptide bonds are also prone to hydrolysis by digestive and metabolic enzymes.
Page reference: 266-267

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