Abstract
A series of 6-substituted carbamoyl benzimidazoles were designed and synthesised as new nonpeptidic angiotensin II AT(1) receptor antagonists. The preliminary pharmacological evaluation revealed a nanomolar AT(1) receptor binding affinity for all compounds in the series, and a potent antagonistic activity in an isolated rabbit aortic strip functional assay for compounds 6f, 6g, 6h and 6k was also demonstrated. Furthermore, evaluation in spontaneous hypertensive rats and a preliminary toxicity evaluation showed that compound 6g is an orally active AT(1) receptor antagonist with low toxicity.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiotensin II Type 1 Receptor Blockers / chemical synthesis*
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Angiotensin II Type 1 Receptor Blockers / chemistry
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Angiotensin II Type 1 Receptor Blockers / pharmacology
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Animals
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Benzimidazoles / chemical synthesis
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Benzimidazoles / chemistry*
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Benzimidazoles / pharmacology
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Biphenyl Compounds / chemical synthesis
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Biphenyl Compounds / chemistry
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Biphenyl Compounds / pharmacology
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Blood Pressure / drug effects
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Drug Design*
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Models, Molecular
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Protein Binding
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Rabbits
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Rats
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Rats, Inbred SHR
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Receptor, Angiotensin, Type 1 / chemistry*
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Receptor, Angiotensin, Type 1 / metabolism
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Structure-Activity Relationship
Substances
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Angiotensin II Type 1 Receptor Blockers
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Benzimidazoles
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Biphenyl Compounds
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N-(2-Phenyl)propyl-1-(2'-(1H-tetrazol-5-yl)-1,1'-biphenyl-4-yl)methyl-4-methyl-2-n-propyl-1H-benzimidazole-6-carboxamide
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Receptor, Angiotensin, Type 1