Page 38 - Medicinal Chemistry Self Assessment
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Section 2 Whole Molecule Drug Evaluation
1.8 Aliskiren
Aliskiren is an orally active agent used in the treatment of hypertension. This non-peptide drug acts as an inhibitor
of renin, the enzyme that converts angiotensinogen (its endogenous substrate) to angiotensin I. Biologically inactive,
angiotensin I is rapidly converted to angiotensin II by angiotensin converting enzyme. Angiotensin II is a potent
agonist when bound to its receptor and produces significant vasoconstriction, as well as an increase in blood pressure.
In the presence of aliskiren, angiotensinogen is not converted to angiotensin I so less angiotensin II is produced to
activate the angiotensin II receptor. Consequently, less vasoconstriction occurs, and a drop in blood pressure results.
Medicinal Chemistry Self-Assessment Book: Batch Two
Chapters 1.8 and 2.8
1. Conduct a structural evaluation of aliskiren, focusing on the boxed functional groups, and use the infor-
Chapter 1.8/2.8 (remove bold from drug name x2)
mation in the grid to inform your answers to the questions that follow.
E
D F
A
B
Aliskiren
C
Function
Character Function Amino Acids That
Acidic, Basic, Interaction(s) Can Interact with the
Character or Neutral Function Possible with Functional Group via
Name of Hydrophilic Provide ↑ Solubility Biological Target Ion–Dipole Interactions
Functional and/or pK When and/or at Physiological at pH=7.4
a
Group Hydrophobic Relevant ↑ Absorption pH=7.4 None Is Acceptable
A Aliskiren
B
C
D
E
F
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