A closer look at N²,6-substituted 1,3,5-triazine-2,4-diamines: Advances in synthesis and biological activities

N²,6-Substituted 1,3,5-triazine-2,4-diamines (N²-substituted guanamines) attracted significant interest due to their potential in the development of bioactive molecules. With just two points of diversity, this scaffold is proved to be suitable for constructing compounds targeting various enzymes, receptors, transporters, and nucleic acids with an array of therapeutic applications, particularly in cancer, inflammation, and CNS disorders. This review discusses progress in the synthesis of N²,6-substituted 1,3,5-triazine-2,4-diamines and their biological activities ranging from the inhibition of cancer-related enzymes (e.g. DNA topoisomerase IIα, carbonic anhydrases, ubiquitin-conjugating enzyme 2B, lysophosphatidic acid acyltransferase β and various kinases) to the binding to CNS-relevant receptors (e.g. histamine H₄, serotonin 5-HT₆, adenosine A_2a, and α7 nicotinic acetylcholine receptors).