Page 204 - Medicinal Chemistry Self Assessment

Section 4 Whole Molecule Drug Evaluation

Answers

2.20 Montelukast and Zafirlukast

Shown below are the structures of montelukast and zafirlukast. These drug molecules are administered orally for the
treatment of asthma and allergic rhinitis.

Montelukast

Zafirlukast

1. The structure of montelukast contains one acidic functional group (pK =4.4) and one basic functional
a
group (pK =3.1), whereas the structure of zafirlukast only contains one acidic functional group (pK =4.3).
1. The structure of a solution pH of 8.3.
a
a
Identify these acidic and basic functional groups and predict whether they will be primarily ionized or
Answer:
primarily unionized at a stomach pH=1.9, a urine pH=5.4, a cellular pH=6.1, a plasma pH=7.2, and a solu-
tion pH=8.3.

Carboxylic acid
Acidic (pK = 4.4)
a
Sulfonamide
Acidic (pK = 4.3)
a

Montelukast

Aromatic heterocylic amine
Basic (pK = 3.1)
a

193 Zafirlukast

2. In the previous question, we to calculate the percent of the functional group that would be ionized.
3. The sodium salt an explanation for this difference.