info:eu-repo/semantics/article
Indole-substituted 2,4-diamino-5,8-dihydropyrido[2,3-d]pyrimidines from one-pot process and evaluation of their ability to bind dopamine receptors
Fecha
2018-12Registro en:
Enriz, Ricardo Daniel; Tosso, Rodrigo David; Andujar, Sebastian Antonio; Cabedo, Nuria; Cortés, Diego; et al.; Indole-substituted 2,4-diamino-5,8-dihydropyrido[2,3-d]pyrimidines from one-pot process and evaluation of their ability to bind dopamine receptors; Pergamon-Elsevier Science Ltd; Tetrahedron; 74; 49; 12-2018; 7047-7057
0040-4020
CONICET Digital
CONICET
Autor
Enriz, Ricardo Daniel
Tosso, Rodrigo David
Andujar, Sebastian Antonio
Cabedo, Nuria
Cortés, Diego
Nogueras, Manuel
Cobo, Justo
Vargas Vargas, Didier Farley
Trilleras Vásquez, Jorge Enrique
Resumen
A series of novel 7-indole substituted 2,4-diamino-5,8-dihydropyrido[2,3-d]pyrimidine analogous to the 2,4-diaminopteridine core were synthesized by the three-component one-pot cyclocondensation between 2,4,6-triaminopyrimidine, 3-(2-cyanoacetyl)indole and aromatic aldehydes. The reactions, which exhibited good performance, proceeded in EtOH using indium (III) chloride as catalyst under microwave irradiation, in short reaction times. On the basis of certain structural similarity of these compounds with known ligands of the D2 dopamine receptors (D2DR), the study of these compounds as possible ligands of dopamine D2 and D1 receptors was carried out. Three of them showed moderate affinity to D2-DR since the Ki D1/D2 ratio reached values of 40, 65 and 31 for compounds 4c, 4k and 4j, respectively. Finally, molecular modeling studies revealed stronger molecular interactions of such derivatives with the D2DR than with D1DR, what agrees with the experimental data, and gives an additional support to the observed selectivity to the D2DR.