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.

Graphical abstractA 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 full-size imageDownload as PowerPoint slide