Ramipril

Abstract

A wealth of published data established the importance of the renin-angiotensin system (RAS) in the maintenance of elevated blood pressure. Pharmacological interference with this system is a long-standing goal in drug research (20). Although in theory prevention of angiotensin I1 (ANG 11) formation can be achieved at any step of the RAS cascade, the only site of therapeutically feasible interaction has been the converting enzyme (CE), which catalyzes the conversion of ANG I to ANG 11. Inhibitors of this enzyme were obtained from snake venom peptides, which also potentiate the action of bradykinin (1 8). Structural analyses of these peptides revealed the importance of proline residues for protection of the enzymes from hydrolysis. The CE inhibitor ramipril contains, therefore, a bicyclic proline derivative. The entire structure provides high selectivity toward CE. Ramipril is a prodrug that is activated enzymatically after absorption. The active moiety is ramiprilat .