Synthesis and crystal structure of N,N’-disubstituted guanidines

Guanidine and derivatives have piqued the interest of medicinal chemists for decades1, and guanidine-based structures show a range of bioactivities including among others malaria and tuberculosis. In a library screening for activity towards DNA glycosidases (ca. 70 000 compounds), a disubstituted guanidines was identified as a potential inhibitor. Thus, we needed a range of guanidines for structure-activity studies. This work has focused on pyrimidine containing guanidines flanked by benzylic and aliphatic amines. The poster presents synthesis of the cyanamide 3, tuning of the amination using benzylamine as a model compound, and the crystal structures of three new N,N’-disubstituted guanidines.