Page 84 - Medicinal Chemistry Self Assessment

Section 2 Whole Molecule Drug Evaluation

1.22 Pravastatin and Fluvastatin

1.22 Pravastatin and Fluvastatin

Shown below are the structures of pravastatin and fluvastatin. These drug molecules are used in the treatment of
Shown below are the structures of groups have been boxed.
various types of hyperlipidemia/dyslipidemias. A total of six functional groups have been boxed.

F
C

B
D

A

E

Pravastatin
Fluvastatin

1. Using the table below, identify the six boxed functional groups. For each of the functional groups you
1. Using the table below, or hydrophobic in explanation for your response.
identify, indicate if it is hydrophilic or hydrophobic in character. Also provide a brief explanation for your
2. The log P drug a structural explanation for the difference in these log P values.
response.
3. The normal pK a range for normal range.
Answer
4. Pravastatin, and as to how pravastatin and fluvastain inhibit HMG CoA reductase.
Hydrophilic or Hydrophobic
Functional Group Name
A
B
C HMG CoA
D Reductase
E
F

HMG CoA Mevalonic Acid
2. The log P values of pravastatin and fluvastatin are 1.44 and 3.62, respectively. Conduct a structural analysis

of these drug molecules and provide a structural explanation for the difference in these log P values.
5. Shown below are the postulate a reason why this structural change results in a loss in activity.

3. The normal pK range for carboxylic acids is 2.5 to 5. The pK values for the carboxylic acids present within
a
a
the structures of pravastatin and fluvastatin are 4.21 and 4.56. Conduct a structural analysis and provide a
reason why these pK values are at the high end of the normal range.
a

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Fluvastatin Conformationally
Restricted Analog
of Fluvastatin