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Arch Pharm (Weinheim) ; 352(3): e1800247, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30638282

RESUMEN

Four series of novel compounds based on 4-aminopyridine, glatiramer acetate, pyrone, and coumarin backbones were sufficiently synthesized and identified by spectroscopic methods. CYP enzyme inhibition assays of five predominate human P450 isozymes indicate that all compounds, except for 4-hydrazide pyridine 1c, seem to be less toxic than 4-aminopyridine. Further investigation of the compounds using molecular docking experiments revealed different, the same, or stronger binding modes for most of the synthesized compounds, with both polar and hydrophobic interactions with the 1WDA and 1J95 receptors compared to benzoyl l-arginine amide and 4-aminopyridine, respectively. These results introduce the synthesized compounds as K+ channel blockers that could be considered for in vivo CNS disease studies.


Asunto(s)
4-Aminopiridina/síntesis química , 4-Aminopiridina/farmacología , Cumarinas/síntesis química , Cumarinas/farmacología , Sistema Enzimático del Citocromo P-450/metabolismo , Canales de Potasio/metabolismo , 4-Aminopiridina/análogos & derivados , Enfermedades del Sistema Nervioso Central/tratamiento farmacológico , Enfermedades del Sistema Nervioso Central/enzimología , Cumarinas/química , Descubrimiento de Drogas , Humanos , Simulación del Acoplamiento Molecular , Estructura Molecular , Unión Proteica
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