Page 222 - Medicinal Chemistry Self Assessment

Section 4 Whole Molecule Drug Evaluation

Answers

2.23 Quinapril

2.23 Quinapril

Shown below is the structure of quinapril. It is an angiotensin converting enzyme (ACE) inhibitor that is used in the
Shown below is the structure of quinapril. It is an groups are identified.
treatment of hypertension and heart failure. Five functional groups are identified.

B
H 3 C

O O D
A O
H
N
N
C
CH 3
O
OH
E

1. Using the table below, identify the five boxed functional groups. For each of the functional groups you
1. Using the table below, identify the five explanation for your response.
identified, indicate if it is hydrophilic or hydrophobic in character. Also provide a brief explanation for
your response.
2. Using the h functional ionized or unionized at pH environments of 1.5, 4.8, 6.3, 7.4, and 8.1.
Answer
Functional Group Name Hydrophilic or Hydrophobic
A Phenyl ring; aromatic ring; aromatic Hydrophobic due to its inability to ionize or form hydrogen bonds; hydrocarbon functional
hydrocarbon groups enhance lipid solubility.
B Ethyl ester Contains both hydrophilic and hydrophobic properties. The two oxygen atoms can act as
hydrogen bond acceptors and can contribute to water solubility. The ethyl group can neither
ionize nor form hydrogen bonds and thus contributes to lipid solubility.
C Secondary amine Hydrophilic due to its ability to ionize (form an ion–dipole interaction with water) and to
participate in hydrogen bonding (acceptor and donor) in its unionized form.
Secondary amine
Carboxylic acid
D Amide Hydrophilic due to its ability to form hydrogen bonds as a hydrogen bond acceptor. (Note:

Does not participate as a hydrogen bond donor due to the lack of hydrogen atom.)
E Carboxylic acid Hydrophilic due to its ability to ionize (form an ion–dipole interaction with water) and to

participate in hydrogen bonding (acceptor and donor) in its unionized form.

3. Quinapril is a is administered orally instead of quinaprilat.
2. Using the unmodified structure of quinapril and the following table, identify all of the acidic and basic

functional groups present in the structure, provide the normal pK range for each functional group, and
a
identify if each functional group would be primarily ionized or unionized at pH environments=1.5, 4.8,
6.3, 7.4, and 8.1.

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Quinapril Quinaprilat