380424-20-4Relevant articles and documents
Design, synthesis, in vitro and in vivo evaluation of benzylpiperidine-linked 1,3-dimethylbenzimidazolinones as cholinesterase inhibitors against Alzheimer’s disease
Mo, Jun,Chen, Tingkai,Yang, Hongyu,Guo, Yan,Li, Qi,Qiao, Yuting,Lin, Hongzhi,Feng, Feng,Liu, Wenyuan,Chen, Yao,Liu, Zongliang,Sun, Haopeng
, p. 330 - 343 (2019/12/30)
Cholinesterase inhibitor plays an important role in the treatment of patients with Alzheimer’s disease (AD). Herein, we report the medicinal chemistry efforts leading to a new series of 1,3-dimethylbenzimidazolinone derivatives. Among the synthesised compounds, 15b and 15j showed submicromolar IC50 values (15b, eeAChE IC50 = 0.39 ± 0.11 μM; 15j, eqBChE IC50 = 0.16 ± 0.04 μM) towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Kinetic and molecular modelling studies revealed that 15b and 15j act in a competitive manner. 15b and 15j showed neuroprotective effect against H2O2-induced oxidative damage on PC12 cells. This effect was further supported by their antioxidant activity determined in a DPPH assay in vitro. Morris water maze test confirmed the memory amelioration effect of the two compounds in a scopolamine-induced mouse model. Moreover, the hepatotoxicity of 15b and 15j was lower than tacrine. In summary, these data suggest 15b and 15j are promising multifunctional agents against AD.
The design and synthesis of purine inhibitors of CDK2. III
Shum,Peet,Weintraub,Le,Zhao,Barbone,Cashman,Tsay,Dwyer,Loos,Powers,Kropp,Wright,Bitonti,Dumont,Borcherding
, p. 1067 - 1078 (2007/10/03)
Cyclin-dependent kinases (CDKs) belong to a class of enzymes that control the ability of a cell to enter into and proceed through the cell division cycle. Using purine as a scaffold, we have synthesized a number of nanomolar inhibitors of CDK-2/cyclin E. In this report, the synthesis of a series of piperidine-substituted purine analogs will be presented, as well as some of their in vitro and in vivo biological effects.
