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

6533b7d3fe1ef96bd1260094

RESEARCH PRODUCT

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

Didier F. Vargas Manuel Nogueras Sebastian A. Andujar Diego Cortes Rodrigo D. Tosso Jorge Trilleras Nuria Cabedo Justo Cobo Ricardo D. Enriz

subject

Indole test PYRIDOPYRIMIDINE 010405 organic chemistry Chemistry Stereochemistry Organic Chemistry Ciencias Químicas THREE-COMPONENT SYNTHESIS 010402 general chemistry BIND DOPAMINE 01 natural sciences Biochemistry 0104 chemical sciences Química Orgánica D1 AND D2 RECEPTORS Dopamine receptor Drug Discovery MOLECULAR MODELING CIENCIAS NATURALES Y EXACTAS

description

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. Fil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina Fil: Tosso, Rodrigo David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina Fil: Andujar, Sebastian Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina Fil: Cabedo, Nuria. Universidad de Valencia; España Fil: Cortés, Diego. Universidad de Valencia; España Fil: Nogueras, Manuel. Universidad de Jaén; España Fil: Cobo, Justo. Universidad de Jaén; España Fil: Vargas Vargas, Didier Farley. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad del Atlántico; Colombia Fil: Trilleras Vásquez, Jorge Enrique. Universidad del Atlántico; Colombia

year	journal	country	edition	language
2018-12-01	Tetrahedron

https://doi.org/10.1016/j.tet.2018.10.038