Page 146 - Medicinal Chemistry Self Assessment
P. 146
2.8 Aliskiren 135
Answer
It is important to first determine whether these drugs are basic, acidic, or amphoteric in nature.
Based on a structural evaluation of the entire aliskiren molecule (not just the boxed functional
groups), there is one basic functional group (primary amine) and no acidic functional groups present.
The same evaluation for amlodipine yields identification of two basic functional groups (primary
amine and dihydropyridine ring) and no acidic functional groups. Based on this evaluation, both
drugs are basic and both would be bound to α -acid glycoprotein (plasma protein). It is important to
1
remember that plasma protein binding interactions are likely to happen when a drug is >90% plasma
protein bound. Given the extent to which amlodipine is plasma protein bound, it is highly likely that
a plasma protein binding interaction will occur when aliskiren displaces amlodipine from the glyco-
protein binding site. When this type of interaction occurs, there will be a greater fraction of amlo-
dipine present in its unbound form. This leads to an increase in pharmacological activity resulting in
hypotension (excessively low blood pressure).
Go to Section 1.8 [Link to section 1.8 title]
