Synthesis and structure-activity relationship study of novel 3-heteroarylcoumarins based on pyridazine scaffold as selective MAO-B inhibitors

• Tipo: Artigo em Revista Científica Internacional
• Data: 2017

Autores

Costas-Lago, MC (Autor) Outra; Besada, P (Autor) Outra; Rodríguez-Enríquez, F (Autor) Outra; Viña, D (Autor) Outra; Vilar, S (Autor) Outra; Uriarte, E (Autor) Outra; Fernanda Borges (Autor) FCUP; Terán, C (Autor) Outra

Revista

Título: European Journal of Medicinal Chemistry

Vol. 139

Páginas: 1-11

ISSN: 0223-5234

Editora: Elsevier

Indexação

ISI Web of Knowledge - 30 Citações

Scopus - 31 Citações

Outras Informações

ID Authenticus: P-00T-QRT

DOI: 10.1016/j.ejmech.2017.07.045

Abstract (EN): Compounds of hybrid structure pyridazine-coumarin were discovered as potent, selective and reversible inhibitors of monoamine oxidase B (MAO-B). These compounds were synthesized in good yield following a multistep approach based on Knoevenagel reaction and using as key intermediate pyridazinone 16, which was obtained from maleic anhydride and furan. Compounds 9b and 9d are the most active compounds of these series, with IC50 values in the sub-micromolar range, and lack of cytotoxic effects. Theoretical calculation of ADME properties also suggested a good pharmacokinetic profile for both compounds. Docking simulations provided insights into enzyme inhibitor interactions and allowed us to rationalize the observed structure-activity relationships (SARs).

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 11