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

• Type: Article in International Scientific Journal
• Date: 2017

Authors

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

Journal

Title: European Journal of Medicinal Chemistry

Vol. 139

Pages: 1-11

ISSN: 0223-5234

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 30 Citations

Scopus - 31 Citations

Other information

Authenticus ID: 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).

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11