Small-molecule inhibitor: imidapril

Name

Peptidases inhibited: Angiotensin converting enzyme compound peptidase. Also has activity against matrix metallopeptidase 9 (Yamamoto et al., 2007).
Mechanism: In its use as a drug to lower blood pressure imidapril is administered as the prodrug , and this is de-esterified to the active imidaprilat by carboxylesterase 1 in the liver (Geshi et al., 2005). The active metabolite, 6366A inhibited pig kidney and human serum forms of angiotensin-converting enzyme with inhibition constants (K_i) of 0.067 nM and 0.04 nM, respectively (Sugaya et al., 1992).

CID at PubChem: 5464343
Structure
Chemical/biochemical name: (4S)-1-methyl-3-[(2S)-2-[N-((1S)-1-ethoxycarbonyl-3- phenylpropyl)amino]propionyl]-2-oxoimidazolidine-4-carboxylic acid hydrochloride
Formula weight: 405

Inhibitor class: This is a compound in the carboxylate class of reversible metallopeptidase inhibitors. In these, the active site zinc of the enzyme is generally coordinated by a carboxylate of the inhibitor, and this interaction contributes to inhibitory potency. Reviewed by Patchett & Cordes (1985) and Powers & Harper (1986), pp. 268 - 277 (who provide a table of K_i values).