Miao, Shi-Xing; Wan, Lin-Xi; He, Zhen-Xiang; Zhou, Xian-Li; Li, Xiaohuan; Gao, Feng published the artcile< Pd-Catalyzed Direct Diversification of Natural Anti-Alzheimer's Disease Drug: Synthesis and Biological Evaluation of N-Aryl Huperzine A Analogues>, Computed Properties of 401-78-5, the main research area is aryl huperzine preparation anti Alzheimer activity acetylcholinesterase SAR chemoselective; huperzine aryl bromide Buchwald Hartwig coupling palladium catalyst.
The first systematic direct diversification of a complex natural product by metal-catalyzed N-H functionalization was carried out. A new series of N-(hetero)aryl analogs I (Ar = Ph, 2-naphthyl, 4-methylpyridin-2-yl, etc.) of the natural anti-Alzheimer’s disease drug huperzine A (HPA) was prepared via palladium-catalyzed Buchwald-Hartwig cross-coupling reactions of HPA with various aryl bromides ArBr in good yields. Most of the N-aryl-huperzine A (N-aryl-HPA) analogs showed good acetylcholinesterase (AChE) inhibitory activity in in vitro experiments Three arylated huperzine A analogs I (Ar = 4-FC6H4, 4-methoxy-2,6-dimethylphenyl, 5-methoxypyridin-2-yl) exhibited stronger anti-AChE activity than HPA. The 5-methoxy-2-pyridyl analog I (Ar = 5-methoxypyridin-2-yl) displayed the most potent AChE inhibition activity, with an IC50 value of 1.5μM, which was 7.6-fold more active than HPA. Compound I (Ar = 5-methoxypyridin-2-yl) also exhibited better neuroprotective activity for H2O2-induced damage in SH-SY5Y cells than HPA. Structure-activity relationship anal. suggested that the electron d. of the installed aromatic ring or heteroaromatic ring played a significant role in inducing the AChE inhibition activity. Overall, compound I (Ar = 5-methoxypyridin-2-yl) showed the advantages of easy synthesis, high potency and selectivity, and improved neuroprotection, making it a potential huperzine-type lead compound for Alzheimer’s disease drug development.
Journal of Natural Products published new progress about Alzheimer disease. 401-78-5 belongs to class bromides-buliding-blocks, and the molecular formula is C7H4BrF3, Computed Properties of 401-78-5.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary