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Arch Pharm (Weinheim) ; 352(3): e1800247, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30638282

RESUMO

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.


Assuntos
4-Aminopiridina/síntese química , 4-Aminopiridina/farmacologia , Cumarínicos/síntese química , Cumarínicos/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Canais de Potássio/metabolismo , 4-Aminopiridina/análogos & derivados , Doenças do Sistema Nervoso Central/tratamento farmacológico , Doenças do Sistema Nervoso Central/enzimologia , Cumarínicos/química , Descoberta de Drogas , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Ligação Proteica
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