Abstract
Structure-based drug design led to the identification of a novel class of potent, low MW alkylamine renin inhibitors. Oral administration of lead compound 21l, with MW of 508 and IC(50) of 0.47nM, caused a sustained reduction in mean arterial blood pressure in a double transgenic rat model of hypertension.
MeSH terms
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Administration, Oral
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Amino Acid Sequence
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Animals
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Antihypertensive Agents / chemical synthesis
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Antihypertensive Agents / chemistry*
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Antihypertensive Agents / pharmacokinetics
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Blood Pressure
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Computer Simulation
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Crystallography, X-Ray
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Drug Design
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Humans
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Methylamines / chemical synthesis
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Methylamines / chemistry*
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Methylamines / pharmacokinetics
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Rats
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Rats, Transgenic
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Renin / antagonists & inhibitors*
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Renin / metabolism
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Structure-Activity Relationship
Substances
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Antihypertensive Agents
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Methylamines
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Renin