Page 95 - Medicinal Chemistry Self Assessment

1.25 Sitagliptin
Sitagliptin is an inhibitor of dipeptidyl

A
F
B
C
F
O
NH
2
N
N D
N
F N
CF 3
Sitagliptin

84 1. Conduct a to the questions that follow.
Medicinal Chemistry Self Assessment
2. Sitagliptin is salt form.
2. Sitagliptin is formulated as a phosphate salt. Identify the most basic functional group and modify the

structure to show the phosphate salt form.
F
F
NH 2 O
N
N
N
F N
CF 3
Sitagliptin
Sitagliptin

3. Sitagliptin is marketed as the R-enantiomer. Evaluate the structure of sitagliptin and provide a struc-
3. Sitagliptin is designation.
tural rationale for the R-enantiomer designation.
4. At 38%, the bound (e.g., warfarin).
4. At 38%, the fraction of sitagliptin reversibly bound to plasma proteins is relatively low. By way of
5. Approximately.
reminder, only the unbound fraction of drug is able to exert its biological activity and undergo
metabolism. Describe the relative risk of a plasma protein binding interaction between sitagliptin
6. Assess each of ransformation has occurred.
and another drug that is highly protein bound (e.g., warfarin).

5. Approximately 79% of sitagliptin is excreted unchanged in the urine. Provide a structural rationale
that supports this observation.