Renin inhibitors.

Pharmacological intervention in the renin-angiotensin system (RAS) by inhibition of angiotensin-converting enzyme (ACE) is an effective therapy for the majority of hypertensive patients and a major advance in the treatment of hypertension and congestive heart failure. The success achieved with ACE inhibitors has increased interest in inhibitors of renin. Renin catalyzes the first and rate-limiting step of the RAS and, unlike ACE, has a high specificity for its endogenous protein substrate. A therapeutic agent that inhibits this specific reaction could have advantages over antihypertensive drugs with less specific modes of action. Although inhibitors of renin have been studied for over two decades, only recently has substantial progress been made toward potent, low molecular weight inhibitors likely to become useful therapeutic agents. Recent advances in the development of renin inhibitors, especially progress toward clinically useful inhibitors, is reviewed.