Page 51 - Medicinal Chemistry Self Assessment

40 Medicinal Chemistry Self Assessment

2. Name the phase I metabolic transformation(s) that hydroxyzine undergoes to produce cetirizine.

3. Based on your structural evaluation of both hydroxyzine and cetirizine, name ALL of the phase I
metabolic transformations possible.

4. A metabolic product from a phase II metabolic transformation has been identified. Which phase II
transformations can cetirizine undergo?

5. Review the structure of cetirizine (pK =2.9 and 8.3) and identify all of the acidic and basic functional
a
groups present. Determine the predominant ionization state of each functional group as it travels
through several compartments of the body after oral administration. Complete the table below.
Ionized or Ionized or Ionized or
Name of Acidic or Ionized or Unionized Unionized Unionized at Ionized or
Functional Basic Unionized at at pH=1 at pH=7.4 pH=8 Unionized at
Group (pK ) pH=5 (saliva) (stomach) (plasma) (intestine) pH=6 (urine)
a

6. Provide a structural rationale for why hydroxyzine is classified as a sedating antihistamine and cetiri-
zine is categorized as a non-sedating antihistamine.

Answers can be found in Section 2.11 [this will be linked to section 2.11 title]