Enalaprinate is an angiotesin converting enzyme (ACE) inhibitor. As the ACE enzyme has not been isolated and studied in its native form, this complicated the design process of the drug, resulting in the adoption of a number of approaches.
The first approach was searching for an analogue of the enzyme. If ACE could not be studied directly, it necessitated identifying an enzyme with similar properties, and using that as a reference point. Hence, studies were done on the zinc metalloprotease enzyme carboxypeptidase and its inhibitors.
The second approach would be to compare the activity of the model enzyme and the target enzyme, and determine the key differences between them. For instance, carboxypeptidase catalyzed the hydrolysis of a single amino acid at the C terminus, whereas ACE catalyzed the hydrolysis of dipeptides at the C-terminus. Additionally, there were differences in the binding sites of the enzymes.
Lastly, the third approach would be to modify existing inhibitors of the model enzyme to suit them for inhibition of the target enzyme. This can be done by the process of extension; that is, adding more atoms and functional groups to the inhibitor to ensure its compatibility with the target enzyme. Through this process, potent ACE inhibitors such as enalaprinate have been synthesized.