Synthesis of 2-(aminomethyl)aziridines and their microwave-assisted ring opening to 1,2,3-triaminopropanes as novel antimalarial pharmacophores

A variety of 2-(aminomethyl)aziridines was prepared and converted into the corresponding 1,2,3-triaminopropanes through a novel, microwave-assisted and regioselective ring opening by diethylamine in acetonitrile. Antiplasmodial assays revealed antimalarial activity for 2-[(1,2,4-triazol-1-yl)methyl]aziridines and 2-(N,N-diethylaminomethyl)aziridines, as well as for the corresponding 1-(diethylamino)propanes obtained through ring opening, pointing to the relevance of both the 2-(aminomethyl)aziridine and the 1,2,3-triaminopropane unit as novel antimalarial pharmacophores.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights► Straightforward conversion of 2-(aminomethyl)aziridines into 1,2,3-triaminopropanes. ► Microwave-assisted regioselective ring opening using Et2NH·HCl/Et2NH in acetonitrile. ► 2-(Aminomethyl)aziridines and 1,2,3-triaminopropanes are novel antimalarial pharmacophores. ► Biological relevance of a 1,2,4-triazole group and a N,N-diethylamino moiety.