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. 1977 Apr 22;196(4288):441-4.
doi: 10.1126/science.191908.

Design of specific inhibitors of angiotensin-converting enzyme: new class of orally active antihypertensive agents

M A Ondetti, B Rubin, D W Cushman

Design of specific inhibitors of angiotensin-converting enzyme: new class of orally active antihypertensive agents

M A Ondetti et al. Science. .

Abstract

A hypothetical model of the active site of angiotensin-converting enzyme, based on known chemical and kinetic properties of the enzyme, has enabled us to design a new class of potent and specific inhibitors. These compounds, carboxyalkanoyl and mercaptoalkanoyl derivatives of proline, inhibit the contractile response of guinea pig ileal strip to angiotensin I and augment its response to bradykinin. When administered orally to rats, these agents inhibit the pressor effect of angiotensin I, augment the vasodepressor effect of bradykinin, and lower blood pressure in a model of renovascular hypertension.

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