Page 94 - Medicinal Chemistry Self Assessment

Section 2 Whole Molecule Drug Evaluation

1.25 Sitagliptin

Sitagliptin is an inhibitor of dipeptidyl peptidase IV (DPP-IV), a serine protease that catalyzes the deactivation/degra-
1.25 Sitagliptin
dation of GLP-1. GLP-1 is a 36-amino acid peptide that is responsible for promoting insulin secretion in response to
an increase in blood glucose levels. Currently there are four DPP-IV inhibitors on the market, all of which contain an
Sitagliptin is an inhibitor of dipeptidyl
essential basic amino functional group that represents the penultimate amino-terminal alanine residue found within

GLP-1.
A
F B C
F
NH 2 O D
N
N
N
F N
CF 3
Sitagliptin
Sitagliptin

1. Conduct a structural evaluation of sitagliptin, focusing on the boxed functional groups and use the infor-
mation in the grid to inform your answers to the questions that follow.
1. Conduct a to the questions that follow.
2. Sitagliptin is salt form. Function
Function
Character Amino Acids That Can
Interaction(s) Interact with the Func-
Character Acidic, Basic, Function Possible with tional Group via Ion–
F
Name of Hydrophilic or Neutral ↑ Solubility Biological Target Dipole Interactions at
Functional and/or F Provide pK and/or at Physiological pH=7.4
a NH O
2
Group Hydrophobic When Relevant ↑ Absorption pH=7.4 None Is Acceptable
A N N
B N
F N
C
CF
D Sitagliptin 3

3. Sitagliptin is designation.
4. At 38%, the bound (e.g., warfarin).

5. Approximately.

6. Assess each of ransformation has occurred.
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