Development
Enalapril was developed by research worker at Merck & Co. as part of their efforts to develop novel treatments for hypertension by modulating the renin-angiotensin-aldosterone (RAS) system.

A profits of Squibb inside getting a number one inhibitor, captopril, provided a major impetus for Merck's science lab to have the competing product. Captopril wwhen non forswearing its problems, all a same, as it was believed (& shown to become confessedly) that the sulfhydryl-moeity of captoril wwhen responsible for such adverse results as metal taste.

Enalaprilat
Enalaprilat, a 1st dicarboxylate-containing Angiotensin-converting enzyme inhibitor, was developed partially to overcome these limitations of capoten. the sulfhydryl-moeity was replaced by the carboxylate-moeity, however extra modifications were mandatory within its structure-depending project to achieve a similar potency to capoten.

Enalaprilat itself, but, was non forgoing its problems. A effect of the structural modifications was that it proved to exist as own unfavorable ionisation characteristics to allow sufficient potency for unwritten administration (within tablets). So enalaprilat was exclusively suitable for intravenous administration. This was overcome per investigator at Merck per esterification of enalaprilat with fermentation alcohol to make enalapril. As a prodrug, enalapril is metabolised within vivo to the active form enalaprilat by various esterases.

A prototype for others
Virtually all importantly, maybe, a QSAR-based modifications inside structure serendipitously led to an improved understanding of the structure of ACE which aided in the development of subsequent carboxylate-containing ACE inhibitors.