Page 210 - Medicinal Chemistry Self Assessment

Section 4 Whole Molecule Drug Evaluation

Answers

2.21 Phenobarbital and
Other Barbiturates

Shown below are the structures of butabarbital, secobarbital, and phenobarbital. These drug molecules are used as
2.21 Phenobarbital and Other Barbiturates
sedative-hypnotic agents in the treatment of insomnia and to induce 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
ability to interact with the GABA receptor in the central nervous system (CNS).
Shown below are the structures of buta
A

O
O
2.21 Phenobarbital and Other Barbiturates O O O O

H N NH H N NH H N NH
Shown below are the structures of buta
O O O

Butabarbital Secobarbital Phenobarbital

O O O O O O
1. Conduct a structural previously listed.
1. Conduct a structural analysis of these drug molecules and provide an explanation as to why they can be
H
H
N
NH
Answer: NHNH
N
NH
administered orally for the indications previously listed.
These three drug to their site of action.
Answer O O O

These three drug molecules vary only in the alkyl chains and aromatic rings located at the 5 position of barbi-
Phenobarbital
Secobarbital
Butabarbital

Only site of
turic acid. As shown below, barbituric acid is symmetrical and contains two identical imide functional groups (a
type of β-dicarbonyl). While the pK range for a β-dicarbonyl ranges from 4.5–8.5, imides tend to have values
variation
a
at the upper end of this range. As such, they can be ionized in the small intestine to a limited extent and
1. Conduct a structural previously listed.
participate in hydrogen bonds with water when present in the unionized state. This provides sufficient water
Answer:
solubility for solvation and dissolution. The alkyl chains and aromatic ring provide sufficient lipid solubility to
permit these drug molecules to cross the gastrointestinal mucosal membrane and be orally absorbed. This lipid
These three drug to their site of action.
5
solubility facilitates absorption across the blood–brain barrier to gain access to their site of action.
Imide Imide
1
Only site of 3
variation
Barbituric Acid
5
2. Butabarbital and secobarbital these two administered as their sodium salts.
Imide Imide
Answer: 1 3
Barbituric Acid

199
2. Butabarbital and secobarbital these two administered as their sodium salts.
Answer:
Sodium Butabarbital Sodium Secobarbital Phenobarbital
(Used as Free Acid)

3. Using the information in acting agent (onset of action = 30–60 minutes; duration = 10–16 hours).

Phenobarbital

Sodium Butabarbital Sodium Secobarbital (Used as Free Acid)

3. Using the information in acting agent (onset of action = 30–60 minutes; duration = 10–16 hours).