Page 216 - Medicinal Chemistry Self Assessment

Section 4 Whole Molecule Drug Evaluation

Answers

2.22 Pravastatin and Fluvastatin

2.22 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 pravastatin. A total of six functional 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, drophilic or hydrophobic in character. for your response.
2. The log P values of s and provide a structural explanation for the difference in these log P values.
1. Using the table below, identify the six boxed functional groups. For each of the functional groups you
identify, indicate if it is hydrophilic or hydrophobic in character. Also provide a brief explanation for your
Answer
response.
The log P value is a functional groups than the structure of fluvastatin, it has a lower log P value.
Answer

Functional Group Name Hydrophilic or Hydrophobic
3',5'-Dihydroxy-
heptanoic acid
A Alkyl group; alkyl chain; aliphatic chain Hydrophobic due to its inability to ionize or form hydrogen bonds; hydrocarbon functional
Ester groups enhance lipid solubility
B Ester Hydrophilic due to its ability to act as a hydrogen bond acceptor
C Secondary hydroxyl (secondary alcohol) Hydrophilic due to its ability to form hydrogen bonds as either a donor or an acceptor
Isobutyl chain
D Halogen; fluorine Effects can vary; fluorine can act as a hydrogen bond acceptor; however, studies have
shown that the substitution of a hydrogen atom with a fluorine atom tends to slightly
enhance lipid solubility
E Aromatic ring system; heterocyclic Hydrophobic due to its inability to ionize or form hydrogen bonds; the lone pair of
aromatic ring; indole electrons present on the nitrogen atom are involved in the aromaticity of the ring system
and therefore are not available to form hydrogen bonds; the remaining hydrocarbons
comprising the ring system enhance lipid solubility Isopropyl chain
Secondary p-Fluoro-
F Carboxylic acid Hydrophilic due to its ability to ionize (form an ion–dipole interaction with water) and to
phenyl ring
Hydroxyl participate in hydrogen bonding (acceptor and donor) in its unionized form Indole ring
Pravastatin Decalin ring
Fluvastatin

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