Abstract
A series of (2-aryl-5-methylimidazol-4-ylcarbonyl)guanidines and (2-aryl-5-methyloxazol-4-ylcarbonyl)guanidines were synthesized and evaluated as NHE-1 inhibitors. The structure-activity relationships well matched those of furan derivatives, which were previously investigated. The (2,5-disubstituted)phenyl compounds showed better activities than the other analogues in both imidazole and oxazole compounds. Especially, 2-(2,5-dichlorophenyl)imidazole 52, and 2-(2-methoxy-5-chlorophenyl)imidazole 54 compounds exhibited potent cardioprotective efficacy both in vitro and in vivo as well as high NHE-1 inhibitory activities.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cardiotonic Agents / chemical synthesis
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Cardiotonic Agents / pharmacology
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Cardiotonic Agents / therapeutic use
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Cation Transport Proteins / antagonists & inhibitors*
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Guanidines / chemical synthesis*
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Guanidines / pharmacology*
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Guanidines / therapeutic use
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Humans
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Imidazoles / chemical synthesis*
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Imidazoles / pharmacology*
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Imidazoles / therapeutic use
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Myocardial Infarction / metabolism
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Myocardial Infarction / prevention & control
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Rats
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Sodium-Hydrogen Exchanger 1
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Sodium-Hydrogen Exchangers / antagonists & inhibitors*
Substances
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Cardiotonic Agents
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Cation Transport Proteins
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Guanidines
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Imidazoles
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SLC9A1 protein, human
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Sodium-Hydrogen Exchanger 1
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Sodium-Hydrogen Exchangers