Captopril was the first ACE inhibitor patented in 1975 from a viper venom. Although it helped saving many patients from hypertensive conditions, it had some adverse effects such as persistent dry cough. With the aim of reducing such effects, brought mainly by the thiol (-SH) group, the pro-drug enalapril and its derivative lisinopril were derived, which contain a carboxylic group (-COOH) and improved the oral drug activity and its tolerability.
Plot the drug development tree of ACE inhibitors highlighting the key steps in their development: