Xu, Ana; He, Feng; Zhang, Xiangna; Li, Xiaoyang; Ran, Yingying; Wei, Chao; James Chou, C.; Zhang, Rui; Wu, Jingde published the artcile< Tacrine-hydroxamate derivatives as multitarget-directed ligands for the treatment of Alzheimer's disease: Design, synthesis, and biological evaluation>, Recommanded Product: Ethyl 2-chloropyrimidine-5-carboxylate, the main research area is tacrine hydroxamate derivative preparation anti Alzheimer; structure activity tacrine hydroxamate cholinesterase inhibitor; Alzheimer’s disease; Antioxidant; Cholinesterase inhibitor; Metal chelator; Multitarget-directed ligands.
In order to develop multitarget-directed ligands as potential treatments for Alzheimer’s disease, twenty-eight new tacrine-hydroxamate derivatives were designed, synthesized, and biol. evaluated. As expected, most of the compounds exhibited inhibitory activities against cholinesterases (ChEs) and histone deacetylase (HDACs). Among the tested compounds, I showed not only potent and selective inhibition on AChE at sub-nanomolar potency (AChEIC50 = 0.12 nM, BChEIC50 = 361.52 nM) but also potent inhibition on HDAC (IC50 = 0.23 nM). Moreover, I exhibited inhibitory activity on Aβ1-42 self-aggregation as well as disaggregation activity on pre-formed Aβ fibrils. Furthermore, I exhibited antioxidant activity and metal chelating properties. Further mechanistic studies demonstrated that I is a pan-inhibitor of HDACs and a mixed-type inhibitor for AChE. It was shown that I is a BBB penetrant by online prediction. Taken together, the results indicate that I can serve as a lead compound to develop promising candidate analogs as AD therapeutics.
Bioorganic Chemistry published new progress about Alzheimer disease. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Recommanded Product: Ethyl 2-chloropyrimidine-5-carboxylate.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia