RESUMEN
The synthesis of new C-6 1,2,3-triazole adenosine derivatives via microwave assisted 1,3-dipolar cycloaddition as key step is described. The binding on membranes of cells that over express A(1) adenosine receptors (A(1)AR) was also evaluated. Among them, four compounds increased cAMP production, in a dose-dependent manner acting as antagonists of the A(1)AR, while two compounds act as agonists.
Asunto(s)
Adenosina/síntesis química , Agonistas del Receptor Purinérgico P1/síntesis química , Antagonistas de Receptores Purinérgicos P1/síntesis química , Receptores Purinérgicos P1/metabolismo , Triazoles/química , Adenosina/farmacología , Animales , Línea Celular , AMP Cíclico/biosíntesis , Humanos , Estructura Molecular , Agonistas del Receptor Purinérgico P1/farmacología , Antagonistas de Receptores Purinérgicos P1/farmacologíaRESUMEN
The cross talk between different membrane receptors is the source of increasing research. We designed and synthesized a new hetero-bivalent ligand that has antagonist properties on both A(1) adenosine and mu opiate receptors with a K(i) of 0.8+/-0.05 and 0.7+/-0.03 microM, respectively. This hybrid molecule increases cAMP production in cells that over express the mu receptor as well as those over expressing the A(1) adenosine receptor and reverses the antalgic effects of mu and A(1) adenosine receptor agonists in animals.
Asunto(s)
Antagonistas del Receptor de Adenosina A1 , Adenosina/análogos & derivados , Anilidas/farmacología , Diseño de Fármacos , Receptores Opioides mu/antagonistas & inhibidores , Adenosina/síntesis química , Adenosina/química , Adenosina/farmacología , Anilidas/síntesis química , Anilidas/química , Ligandos , Estructura Molecular , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
[reaction: see text] The synthesis of the indole skeleton of new melatoninergic analogues was realized using solid-phase methodology in association with microwave irradiation. This combination speeds up the solid-phase drug discovery process in rigorously established conditions.