Abstract
A series of 4'-[(imidazol-1-yl)methyl]biphenylsulfonamides has potent antagonist activity against both angiotensin II AT(1) and endothelin ET(A) receptors. Such dual-acting antagonists could have utility in the treatment of hypertension, heart failure, and other cardiovascular diseases in a broad patient population. Certain compounds in the present series are orally active in a rat model of angiotensin II-mediated hypertension.
MeSH terms
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Angiotensin Receptor Antagonists*
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Animals
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Binding Sites / drug effects
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Biphenyl Compounds / chemical synthesis*
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Biphenyl Compounds / pharmacology*
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Blood Pressure / drug effects
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Caco-2 Cells
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Drug Design
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Endothelin Receptor Antagonists*
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Humans
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Imidazoles / chemical synthesis
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Imidazoles / pharmacology
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Indicators and Reagents
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Male
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Rats
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Rats, Sprague-Dawley
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Receptor, Angiotensin, Type 1
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Receptor, Endothelin A
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Structure-Activity Relationship
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Sulfonamides / chemical synthesis*
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Sulfonamides / pharmacology*
Substances
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Angiotensin Receptor Antagonists
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Biphenyl Compounds
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Endothelin Receptor Antagonists
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Imidazoles
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Indicators and Reagents
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Receptor, Angiotensin, Type 1
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Receptor, Endothelin A
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Sulfonamides