Page 90 - Medicinal Chemistry Self Assessment

Section 2 Whole Molecule Drug Evaluation

1.24 Rivastigmine

1.24 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 3 C N O CH 3
N
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
2. Based on their induction.
identified, indicate if it is hydrophilic or hydrophobic in character. Also provide a brief explanation for
your response.
3. Rivastigmine is an e. Glutamic acid, with acetylcholine.
Answer
Labile ester bond
Functional Group Name Hydrophilic or Hydrophobic
A
B
C
D

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. Rivastigmine

3. Rivastigmine is an acetylcholinesterase inhibitor. Inhibition of this enzyme prolongs the half-life of acetyl-
Acetylcholine bound to active site
choline, allowing for higher concentrations of acetylcholine at muscarinic and nicotinic receptors. This
of acetylcholinesterase
action is useful in the treatment of Alzheimer’s disease, myasthenia gravis, and glaucoma. Shown below is

the structure of acetylcholine interacting with the active site of acetylcholinesterase. Glutamic acid, histi-
dine, and serine are involved in the mechanism of ester hydrolysis and can form specific interactions with
A.
Conduct a rivastigmine and indicate how it could interact with acetylcholinestase.
acetylcholine.
B. The serine explanation as to how rivastigmine inhibits acetylcholinesterase.

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Intermediate in the hydrolysis of
acetylcholine Analogous intermediate formed with
rivastigmine