The most common adverse effects of Captopril, skin rash and loss of taste, are the same as caused by mercapto-containing penicillamine. Therefore, a group of researchers aimed at finding potent, selective ACE inhibitors that would not contain a mercapto (SH) function and would have a weaker chelating function. They returned to work with carboxyl compounds and started working with substituted N-carboxymethyl-dipeptides as a general structure (R-CHCOOH-A-A). According to previous research they assumed that cyclic imino acids would result in good potency if substituted on the carboxyl terminus of the dipeptide. Therefore, substituting A with proline gave good results. They also noted that according to the enzymes specificity imino acids in the position next to the carboxyl terminus would not give a potent compound. By substituting R and A groups with hydrophobic and basic residues would give a potent compound. By substituting –NH in the general structure resulted in loss of potency which is consistent to the enzymes need for a –NH in corresponding position on the substrates. The results were 2 active inhibitors: Enalaprilat and Lisinopril. These compounds both have phenylalanine in R position which occupies the S groove in the enzyme. The result was thus these two new, potent tripeptide analogues with zinc-coordinating carboxyl group: Enalaprilat and Lisinopril.