DESIGN OF SPECIFIC INHIBITORS OF ANGIOTENSIN-CONVERTING ENZYME - NEW CLASS OF ORALLY ACTIVE ANTIHYPERTENSIVE AGENTS
DESIGN OF SPECIFIC INHIBITORS OF ANGIOTENSIN-CONVERTING ENZYME - NEW CLASS OF ORALLY ACTIVE ANTIHYPERTENSIVE AGENTS
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DOI：
10.1126/science.191908
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发表时间：
1977-01-01
期刊：
影响因子：
56.9
通讯作者：
CUSHMAN, DW
中科院分区：
文献类型：
--
作者：
ONDETTI, MA;CUSHMAN, DW
血管紧张素转换酶活性位点的一个假设模型，基于已知的化学和动力学性质的酶，导致一类新的有效和特异性抑制剂的设计。这些化合物，羧基烷酰基和巯基烷酰基衍生物脯氨酸，抑制豚鼠回肠条的收缩反应，血管紧张素I和增加其反应缓激肽。当口服给药于大鼠时，这些药物抑制血管紧张素I的升压作用，增强缓激肽的血管降压作用，并降低肾血管性高血压模型中的血压。
A hypothetical model of the active site of angiotensin-converting enzyme, based on known chemical and kinetic properties of the enzyme, led to the design of 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.