Page 59 - Medicinal Chemistry Self Assessment

48 Medicinal Chemistry Self Assessment
Fenofibrate

2. Fenofibrate is administered as a prodrug and undergoes hydrolysis to the active drug. Draw the
active drug. Provide a brief rationale for the value of administering fenofibrate as a prodrug.
1. Conduct a complete structural follow:
2. Fenofibrate is of administering fenofibrate as a prodrug.
3. The calculated log P for fenofibrate is 5.24, whereas the calculated log P for gemfibrozil is 3.9.
1.14 and 2.14 (drug name – remove bold)
Provide a structural rationale for the difference in this pharmacokinetic property.

3. The calculated in this pharmacokinetic property.

Fenofibrate Gemfibrozil

Fenofibrate
Gemfibrozil

Letter “C” – add bold
4. From an elimination perspective, 60% of a fenofibrate dose is found in the urine and 25% is found
1.14 and 2.14 (drug name – remove bold)

in the feces. The active form of fenofibrate undergoes both phase I and phase II metabolic trans-

formations. The phase II conjugate is eliminated in the urine. Oxidative metabolism does not occur.

Evaluate each of the metabolic products and determine if it is the conjugate that is eliminated in the
4. From an elimination perspective, 60% of a ve phase I transformation (that does NOT occur).
urine (that does occur), the product of a non-oxidative phase I transformation (that does occur), or
the product of an oxidative phase I transformation (that does NOT occur).

O O
H O O
C OH
H 3 C CH Fenofibrate Gemfibrozil
3
Cl

2.14 – remove bold from label
A Letter “C” – add bold B

B F
A C D

E
C C
Fenofibrate

2.14 – remove bold from label
Name of Metabolic Transformation Type of Product
2.14 – remove bold from label
A
B B F
O O CH O O
C 3 Ester
A O O C CH D 3 Hydrolysis O OH

H 3 C CH 3 H 3 C CH 3
Cl Cl
E
Inactive Active
Fenofibrate

2.14 – remove bold from label

O O CH 3 O O
Ester
O Hydrolysis O
O CH 3 OH
H 3 C CH 3 H 3 C CH 3
Cl Cl

Inactive Active