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

摘要

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, 12Hbenzo[ 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-2,3,4,13tetrahydro- 1H, 12H-benzo[ 6,7] chromeno[2,3-d] pyrido[1,2-a] pyrimidine-7,12,14-trione (1a) is a nonhepatotoxic at 300 mu mol/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.