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dc.contributor.authorCostas-Lago M.C.
dc.contributor.authorBesada P.
dc.contributor.authorRodríguez-Enríquez F.
dc.contributor.authorViña D.
dc.contributor.authorVilar S.
dc.contributor.authorUriarte E.
dc.contributor.authorBorges F.
dc.contributor.authorTerán C.
dc.date.accessioned2020-09-02T22:15:33Z
dc.date.available2020-09-02T22:15:33Z
dc.date.issued2017
dc.identifier10.1016/j.ejmech.2017.07.045
dc.identifier.citation139, , 1-11
dc.identifier.issn02235234
dc.identifier.urihttps://hdl.handle.net/20.500.12728/4106
dc.descriptionCompounds 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). © 2017 Elsevier Masson SAS
dc.language.isoen
dc.publisherElsevier Masson SAS
dc.subjectADME
dc.subjectCoumarin
dc.subjectMAO-B
dc.subjectMolecular modeling
dc.subjectNeurodegenerative disorders
dc.subjectPyridazine
dc.subject3 (6 bromopyridazin 3 yl) 6 methoxycoumarin
dc.subject3 (6 bromopyridazin 3 yl) 6 methylcoumarin
dc.subject3 (6 bromopyridazin 3 yl) 7 methoxycoumarin
dc.subject3 (6 bromopyridazin 3 yl) 7 methylcoumarin
dc.subject3 (6 bromopyridazin 3 yl) 8 methoxycoumarin
dc.subject3 (6 bromopyridazin 3 yl) 8 methylcoumarin
dc.subject3 (6 chloropyridazin 3 yl) 6 methoxycoumarin
dc.subject3 (6 chloropyridazin 3 yl) 6 methylcoumarin
dc.subject3 (6 chloropyridazin 3 yl) 7 methoxycoumarin
dc.subject3 (6 chloropyridazin 3 yl) 7 methylcoumarin
dc.subject3 (6 chloropyridazin 3 yl) 8 methoxycoumarin
dc.subject3 (6 chloropyridazin 3 yl) 8 methylcoumarin
dc.subject3 (6 methoxypyridazin 3 yl) 6 methylcoumarin
dc.subject3 (6 methoxypyridazin 3 yl) 7 methylcoumarin
dc.subject3 (6 methoxypyridazin 3 yl) 8 methylcoumarin
dc.subject6 methoxy 3 (6 methoxypyridazin 3 yl)coumarin
dc.subject6 methoxy 3 (6 oxo 1,6 dihydropyridazin 3 yl)coumarin
dc.subject7 methoxy 3 (6 methoxypyridazin 3 yl)coumarin
dc.subject7 methoxy 3 (6 oxo 1,6 dihydropyridazin 3 yl)coumarin
dc.subject7 methyl 3 (6 oxo 1,6 dihydropyridazin 3 yl)coumarin
dc.subject8 methoxy 3 (6 methoxypyridazin 3 yl)coumarin
dc.subject8 methoxy 3 (6 oxo 1,6 dihydropyridazin 3 yl)coumarin
dc.subject8 methyl 3 (6 oxo 1,6 dihydropyridazin 3 yl)coumarin
dc.subjectcoumarin derivative
dc.subjectethyl 2 (6 oxo 1,6 dihydropyridazin 3 yl)acetate
dc.subjectfuran
dc.subjectmaleic anhydride
dc.subjectmonoamine oxidase B inhibitor
dc.subjectpyridazine
dc.subjectunclassified drug
dc.subjectamine oxidase (flavin containing)
dc.subjectcoumarin derivative
dc.subjectmonoamine oxidase inhibitor
dc.subjectpyridazine
dc.subjectpyridazine derivative
dc.subjectArticle
dc.subjectcontrolled study
dc.subjectcytotoxicity
dc.subjectdrug potency
dc.subjectdrug selectivity
dc.subjectdrug synthesis
dc.subjecthuman
dc.subjecthuman cell
dc.subjecthybrid
dc.subjectIC50
dc.subjectKnoevenagel condensation
dc.subjectmolecular docking
dc.subjectstructure activity relation
dc.subjecttheoretical model
dc.subjectchemical structure
dc.subjectchemistry
dc.subjectdose response
dc.subjectmetabolism
dc.subjectstructure activity relation
dc.subjectsynthesis
dc.subjectCoumarins
dc.subjectDose-Response Relationship, Drug
dc.subjectHumans
dc.subjectMolecular Docking Simulation
dc.subjectMolecular Structure
dc.subjectMonoamine Oxidase
dc.subjectMonoamine Oxidase Inhibitors
dc.subjectPyridazines
dc.subjectStructure-Activity Relationship
dc.titleSynthesis and structure-activity relationship study of novel 3-heteroarylcoumarins based on pyridazine scaffold as selective MAO-B inhibitors
dc.typeArticle


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