title: Amide-controlled, one-pot synthesis of tri-substituted purines generates structural diversity and analogues with trypanocidal activity.
abstract: 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.
authors.affiliation: Departamento de Química Farmacéutica y Orgánica. University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Pineda de las Infantas y Villatoro
authors.affiliation: Pfizer - Universidad de Granada - Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), Parque Tecnológico de Ciencias de la Salud (PTS), Avenida de la Ilustración 114, 18016 Granada, Spain.
authors.forename: Juan D
authors.initials: JD
authors.lastname: Unciti-Broceta
authors.affiliation: Pfizer - Universidad de Granada - Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), Parque Tecnológico de Ciencias de la Salud (PTS), Avenida de la Ilustración 114, 18016 Granada, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Contreras-Montoya
authors.affiliation: 1] Pfizer - Universidad de Granada - Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), Parque Tecnológico de Ciencias de la Salud (PTS), Avenida de la Ilustración 114, 18016 Granada, Spain [2] Unidad de Enfermedades Infecciosas y Microbiología, Complejo Hospitalario de Granada, Instituto de Investigación Biosanitaria de Granada, Dr. Azpitarte, 4, 18012 Granada, Spain.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Garcia-Salcedo
authors.affiliation: Departamento de Química Farmacéutica y Orgánica. University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Gallo Mezo
authors.affiliation: Edinburgh Cancer Research UK Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, UK.
authors.forename: Asier
authors.initials: A
authors.lastname: Unciti-Broceta
authors.affiliation: 1] Departamento de Química Farmacéutica y Orgánica. University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain [2] Pfizer - Universidad de Granada - Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), Parque Tecnológico de Ciencias de la Salud (PTS), Avenida de la Ilustración 114, 18016 Granada, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Diaz-Mochon
mesh_terms: D000577:Amides / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic; D011687:Purines / Q000737:chemistry*; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000187:drug effects
chemical_list: D000577:Amides; D011687:Purines; D014344:Trypanocidal Agents; C030985:purine