Synthesis and bioactivity of substituted indan-1-ylideneaminoguanidine derivatives

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.

A series of substituted indan-1-ylidene aminoguanidine derivatives were synthesized and evaluated for their NHE1 inhibitory effects. Compound 5m proved to be sixty-nine times more potent than cariporide in a rat platelet swelling assay. Furthermore, when tested in vivo, compound 5m also demonstrated superior cardioprotective effects against SD rat myocardial ischemic–reperfusion injury over those of cariporide.Figure optionsDownload as PowerPoint slide