Amide-controlled, one-pot synthesis of tri-substituted purines generates structural diversity and analogues with trypanocidal activity Pineda de las Infantas y Villatoro, María J. Unciti-Broceta, Juan Diego Contreras-Montoya, Rafael García-Salcedo, José Antonio Gallo Mezo, Miguel Ángel Unciti-Broceta, Asier Díaz Mochón, Juan José Reaction mechanisms Parasite biology Purines Trypanosoma brucei Trypanocidal activity Anovel one-pot synthesis of tri-substituted purines and the discovery of purine analogues with trypanocidal activity are reported. The reaction is initiated by a metal-free oxidative coupling of primary alkoxides and diaminopyrimidines with Schiff base formation and subsequent annulation in the presence of large N,N-dimethylamides (e.g.N,N-dimethylpropanamide or larger). This synthetic route is in competition with a reaction previously-reported by our group1, allowing the generation of a combinatorial library of tri-substituted purines by the simple modification of the amide and the alkoxide employed. Among the variety of structures generated, two purine analogues displayed trypanocidal activity against the protozoan parasite Trypanosoma brucei with IC50 , 5 mM, being each of those compounds obtained through each of the synthetic pathways. 2015-04-10T07:14:51Z 2015-04-10T07:14:51Z 2015 info:eu-repo/semantics/article Pineda de las Infantas y Villatoro, M.J.; et al. Amide-controlled, one-pot synthesis of tri-substituted purines generates structural diversity and analogues with trypanocidal activity. Scientific Reports, 5: 9139 (2015). [http://hdl.handle.net/10481/35509] 2045-2322 http://hdl.handle.net/10481/35509 10.1038/srep09139 eng http://creativecommons.org/licenses/by-nc-nd/3.0/ info:eu-repo/semantics/openAccess Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License Nature Publishing Group