Amide-controlled, one-pot synthesis of tri-substituted purines generates structural diversity and analogues with trypanocidal activity.

Pineda de las Infantas y Villatoro, Maria JUnciti-Broceta, Juan DContreras-Montoya, RafaelGarcia-Salcedo, Jose AGallo Mezo, Miguel AUnciti-Broceta, AsierDiaz-Mochon, Juan J2016-08-302016-08-302015-03-16Pineda de las Infantas y Villatoro MJ, Unciti-Broceta JD, Contreras-Montoya R, Garcia-Salcedo JA, Gallo Mezo MA, Unciti-Broceta A, et al. Amide-controlled, one-pot synthesis of tri-substituted purines generates structural diversity and analogues with trypanocidal activity. Sci Rep. 2015; 5:9139http://hdl.handle.net/10668/2376Journal Article; Research Support, Non-U.S. Gov't;A novel 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 group, 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 μM, being each of those compounds obtained through each of the synthetic pathways.enTécnicas de químicas sintéticaPurinasTripanocidasTrypanosoma brucei bruceiAmidasMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiparasitic Agents::Antiprotozoal Agents::Trypanocidal AgentsMedical Subject Headings::Organisms::Eukaryota::Euglenozoa::Kinetoplastida::Trypanosomatina::Trypanosoma::Trypanosoma brucei bruceiMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::PurinesMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::AmidesMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Organic Chemistry Phenomena::Organic Chemistry Processes::Chemistry Techniques, SyntheticAmide-controlled, one-pot synthesis of tri-substituted purines generates structural diversity and analogues with trypanocidal activity.research article25773920open access10.1038/srep091392045-2322