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Synthesis and biological assessment of racemic benzochromenopyrimidinetriones as promising agents for Alzheimer's disease therapy

AutorDgachi, Youssef; Martin, Hélène; Bonet, Alexandre; Chioua, Mourad ; Iriepa, Isabel; Moraleda, Ignacio; Chabchoub, Fakher; Marco-Contelles, José ; Ismaili, Lhassane
Palabras claveTacrine analogs
Hepatotoxicity
Cholinesterase inhibitors
Cholinesterase enzymes
Antioxidant
Alzheimer’s disease
ADME
Fecha de publicación2017
EditorFuture Science
CitaciónFuture Medicinal Chemistry 9: 715-721 (2017)
ResumenAim: Due to the complex nature of Alzheimer's disease, there is a renewed search for multitarget directed drugs. Results: This paper describes the synthesis and in vitro biological evaluation of six racemic 13-aryl-2,3,4,13-tetrahydro-1H,12H-benzo[6,7]chromeno[2,3-d]pyrido[1,2-a]pyrimidine-7,12,14-triones (1a-6a), and six racemic 15-aryl-8,9,10,11,12,15-hexahydro-14H-benzo[6′,7′]chromeno[2′,3:4,5] pyr-imido [1,2-a]azepine-5,14,16-triones (1b-6b), showing antioxidant and cholinesterase inhibitory capacity. Among these compounds, 13-phenyl-2,3,4,13-tetrahydro-1H,12H-benzo[6,7]chromeno[2,3-d]pyrido[1,2-a]pyrimidine-7,12,14-trione (1a) is a nonhepatotoxic at 300 μmol/l dose concentration, and a selective EeAChE inhibitor showing good antioxidant power. Conclusion: A new family of racemic benzochromenopyrimidinetriones has been investigated for their potential use in the treatment of Alzheimer's disease.
URIhttp://hdl.handle.net/10261/153671
DOI10.4155/fmc-2017-0004
Identificadoresdoi: 10.4155/fmc-2017-0004
issn: 1756-8919
e-issn: 1756-8927
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