Page 228 - Medicinal Chemistry Self Assessment

Section 4 Whole Molecule Drug Evaluation

Answers

2.24 Rivastigmine

2.24 Rivastigmine
Shown below is the structure of rivastigmine. Four of its functional groups have been identified.
Shown below is the structure of rivastigmine. Four of its functional groups have been identified.

CH 3 C CH 3 D
A H C N O CH
3
N 3
O CH 3

B
Rivastigmine

1. Using the table
1. Using the table below, identify the four boxed functional groups. For each of the functional groups you
identified, indicate if it is hydrophilic or hydrophobic in character. Also provide a brief explanation for
2. Based on their induction.
your response.
3. Rivastigmine is an acetylcholinesterase with acetylcholine.
Answer

Functional Group Name Hydrophilic or Hydrophobic
Labile ester bond
A Alkyl chain; alkyl group; aliphatic chain Hydrophobic due to its inability to ionize or form hydrogen bonds; hydrocarbon functional
groups enhance lipid solubility
B Carbamate Hydrophilic due to its ability to act as a hydrogen bond acceptor
C Phenyl ring; aromatic ring; aromatic Hydrophobic due to its inability to ionize or form hydrogen bonds; hydrocarbon functional
hydrocarbon groups enhance lipid solubility
D Tertiary amine Hydrophilic due to its ability to ionize (form an ion–dipole interaction with water) and to
participate in hydrogen bonding (acceptor) in its unionized form

Rivastigmine
2. Based on their electronic properties AND their relative positions in the molecule, identify if functional
groups A and B are electron withdrawing or electron donating. Additionally, identify if this effect is due
to resonance or induction.
Answer Acetylcholine bound to active site
of acetylcholinesterase
• Functional group A is an alkyl (ethyl) group and has a lower electronegativity than the nitrogen atom
of the carbamate; therefore, it acts as an electron donating group through induction. The same is true
for the two methyl groups attached to the tertiary amine.
Conduct a structural analysis of how it could interact with acetylcholinestase.
A.
• Functional group B is a carbamate group that is directly attached to an aromatic ring. Based on its
Answer:al groups to orient themselves in a similar manner within the enzyme binding site.
position, it can donate electrons into the aromatic ring through resonance.

B B
A
A

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Key structural similarities

Similar distances after conformational rotation
(Note: The length of the lines are identical)