Imidazopyranotacrines As Non-Hepatotoxic, Selective Acetylcholinesterase Inhibitors, And Antioxidant Agents For Alzheimer 1 S Disease Therapy

Herein we describe the synthesis and in vitro biological evaluation of thirteen new, racemic, diversely functionalized imidazo pyranotacrines as non-hepatotoxic, multipotent tacrine analogues. Among these compounds, 1-(5-amino-2-methyl-4-(1-methyl-1H-imidazol-2-yl)-6,7,8,9-tetrahydro-4H-pyrano[2,3-b]quinolin-3-yl)ethan-1-one (4) is non-hepatotoxic (cell viability assay on HepG2 cells), a selective but moderately potent EeAChE inhibitor (IC50 = 38.7 +/- 1.7 mu M), and a very potent antioxidant agent on the basis of the ORAC test (2.31 +/- 0.29 mu mol.Trolox/mu mol compound).