Abstract
In our efforts to discover more potent and lasting NHE1 inhibitors, we designed and synthesized a series of substituted indan-1-ylidene aminoguanidine derivatives (5). NHE1 inhibitory activity of twenty-one compounds 5 was evaluated in a rat platelet swelling assay. It is found that most of the tested compounds possess NHE1 inhibitory effects. 2-(5-methoxybenzimidazol-2-ylthio)-5-chloro-2,3-dihydroinden-1-ylidene aminoguanidine hydrobromide (5m) proved to be sixty-nine times more potent than cariporide. Furthermore, when tested in vivo, compound 5m also displayed superior cardioprotective effects against SD rat myocardial ischemic-reperfusion injury over those of cariporide.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blood Platelets / metabolism
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Cardiotonic Agents / chemical synthesis
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Cardiotonic Agents / chemistry*
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Cardiotonic Agents / pharmacology
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Cardiotonic Agents / therapeutic use*
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Female
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Guanidines / chemical synthesis
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Guanidines / chemistry*
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Guanidines / pharmacology
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Guanidines / therapeutic use*
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Indans / chemical synthesis
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Indans / chemistry*
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Indans / pharmacology
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Indans / therapeutic use*
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Male
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Myocardial Infarction / drug therapy
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Myocardial Infarction / pathology
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Myocardium / pathology
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Rats
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Rats, Sprague-Dawley
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Reperfusion Injury / drug therapy
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Sodium-Hydrogen Exchanger 1
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Sodium-Hydrogen Exchangers / antagonists & inhibitors*
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Sodium-Hydrogen Exchangers / metabolism
Substances
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Cardiotonic Agents
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Guanidines
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Indans
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Slc9a1 protein, rat
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Sodium-Hydrogen Exchanger 1
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Sodium-Hydrogen Exchangers
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pimagedine