Acids/Base and Reactions

Enalapril is a prodrug that is converted to Enalaprilat, an active angiotensin-converting enzyme (ACE) inhibitor.  A prodrug is an inactive molecule that undergoes reaction to become an active drug.  Enalapril has handedness or is chiral.  It has 3 chiral centers, so there are 23 = 8 different versions.

Enalapril is hydrolyzed in vivo to the active form Enalaprilat by hydrolysis.  Hydrolysis is a chemical reaction where water (hydro) causes the breaking apart (lysis) of a compound into smaller components.  This hydrolysis alters the molecule’s solubility and acidity (pKa), making Enalaprilat more polar and better suited for binding to ACE.

Action
  • Can you spot the difference between Enalapril and Enalaprilat?
  • Enalapril has one CO2H, while enalaprilat has two CO2H groups.
  • A carboxyl group (-CO2H or  sometimes -COOH) is a functional group consisting of a carbonyl (C=O) and a hydroxyl (-OH) group bonded to the same carbon atom.
  • Note:  The wedges and dashes indicate the chirality.  

 

Take Note
  • A carboxylic acid contains a carboxyl group and can donate a proton (H⁺) in an acid-base reaction.

Additional Reading

Chapter 2 McMurry