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 |
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Authors: | Ricardo D Enriz Rodrigo D Tosso Sebastián A Andújar Nuria Cabedo Diego Cortés Manuel Nogueras Justo Cobo Didier F Vargas Jorge Trilleras |
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Institution: | 1. IMIBIO-SL, CONICET, Facultad de Química Bioquímica y Farmacia, UNSL, San Luis, 5700, Argentina;2. Departamento de Farmacología, Laboratorio de Farmacoquímica, Facultad de Farmacia, Universidad de Valencia, Valencia, 46100, Spain;3. Departamento de Química Inorgánica y Orgánica, Universidad de Jaén, 23071, Jaén, Spain;4. Grupo de Investigación en Compuestos Heterocíclicos, Programa de Química, Facultad de Ciencias Básicas, Universidad del Atlántico, Puerto Colombia, 81007, Atlántico, Colombia |
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Abstract: | A series of novel 7-indole substituted 2,4-diamino-5,8-dihydropyrido2,3-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. |
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Keywords: | Pyridopyrimidine Three-component synthesis Bind dopamine D1 and D2 receptors Molecular modeling |
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