RESUMEN
A novel series of cyclohexanamine derivatives was designed and synthesized as potent and selective human neuropeptide Y Y1 receptor antagonists. Modification of high-throughput screening hit compound 1 resulted in the identification of compound 3i, which displays potent Y1 activity and good selectivity towards hERG K(+) channel and serotonin transporter.
Asunto(s)
Ciclohexilaminas/química , Receptores de Neuropéptido Y/antagonistas & inhibidores , Línea Celular , Ciclohexilaminas/síntesis química , Ciclohexilaminas/farmacología , Diseño de Fármacos , Canales de Potasio Éter-A-Go-Go/metabolismo , Humanos , Receptores de Neuropéptido Y/metabolismo , Serotonina/metabolismo , Relación Estructura-ActividadRESUMEN
The synthesis of fullerene-carbohydrate conjugates using a copper-catalyzed [3+2] cycloaddition reaction to facilitate the union of an azido-functionalized sugar and a pentaalkynyl[60]fullerene is straightforward. Thus, fullerenes bearing five oligosaccharides such as Gb3-trisaccharide can be readily accessed. Nanometer-scale molecular architectures presenting as many as 15 sugar moieties in C5-symmetry are readily produced. The cycloaddition reaction proceeds quantitatively under mild conditions without the need to protect the sugar hydroxyl groups.