Page 82 - Medicinal Chemistry Self Assessment

Section 2 Whole Molecule Drug Evaluation

1.21 Phenobarbital and
Other Barbiturates

Shown below are the structures of butabarbital, secobarbital, and phenobarbital. These drug molecules are used as
1.21 Phenobarbital and Other Barbiturates
sedative-hypnotic agents in the treatment of insomnia and inducing sedation prior to surgical procedures. Phenobar-

bital can be used in the treatment of a number of different seizure disorders. Their sedative properties are due to their
Shown below are the structures of butabarbital, seco
ability to interact with the GABA receptor in the central nervous system (CNS).
A

O O O O O O

H N NH H N NH H N NH

O O O
Butabarbital Secobarbital Phenobarbital

1. Conduct a structural analysis of these drug molecules and provide an explanation as to why they can be
1. Conduct a structural analysis.
administered orally for the indications previously listed.

2. Butabarbital and as to why these two drug molecules need to be administered as their sodium salts.
2. Butabarbital and secobarbital are marketed as their sodium salts and phenobarbital is marketed in its free
acid form (i.e., non-salt form). Draw the sodium salt of either butabarbital or secobarbital and provide an
explanation as to why these two drug molecules need to be administered as their sodium salts.
3. Using the phenobarbital is a long-acting agent (= 30–60 minutes; duration = 10–16 hours).

3. Using the information in questions 1 and 2 and your answers to those questions, provide an explanation
4. Secobarbital contains an ionized or unionized at pH environments of 1.5, 5.9, 6.3, 7.4, and 8.9.
as to why secobarbital is a short-acting agent (onset of action = 10–15 minutes; duration = 3–4 hours),
butabarbital is an intermediate-acting agent (onset of action = 45–60 minutes; duration = 6-8 hours), and
phenobarbital is a long-acting agent (onset of action = 30–60 minutes; duration = 10–16 hours).
5. As stated of the amino acids indicated.

4. Secobarbital contains an ionizable functional group with a pK =7.9. Using the table shown below, identify
6. Shown below. Would you to retain their pharmacological activity? Why or why not?
a
the functional group, provide the normal pK range for the functional group, and identify if the func-
a

tional group would be primarily ionized or unionized at pH environments=1.5, 5.9, 6.3, 7.4, and 8.9.
Acidic or Primarily Ionized or Unionized
Functional Group Basic pK Range 1.5 5.9 6.3 7.4 8.9
a

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Metabolite of Metabolite of Metabolite of
butabarbital secobarbital phenobarbital