186534-01-0Relevant articles and documents
Synthesis and evaluation of novel ligustrazine derivatives as multi-targeted inhibitors for the treatment of Alzheimer's disease
Wu, Wenhao,Liang, Xintong,Xie, Guoquan,Chen, Langdi,Liu, Weixiong,Luo, Guolin,Zhang, Peiquan,Yu, Lihong,Zheng, Xuehua,Ji, Hong,Zhang, Chao,Yi, Wei
, (2018)
A series of novel ligustrazine derivatives 8a-r were designed, synthesized, and evaluated as multi-targeted inhibitors for anti-Alzheimer's disease (AD) drug discovery. The results showed that most of them exhibited a potent ability to inhibit both ChEs, with a high selectivity towards AChE. In particular, compounds 8q and 8r had the greatest inhibitory abilities for AChE, with IC50 values of 1.39 and 0.25 nM, respectively, and the highest selectivity towards AChE (for 8q, IC50BuChE/IC50 AChE = 2.91 × 106; for 8r, IC50BuChE/IC50 AChE = 1.32 × 107). Of note, 8q and 8r also presented potent inhibitory activities against Aβ aggregation, with IC50 values of 17.36 μM and 49.14 μM, respectively. Further cellular experiments demonstrated that the potent compounds 8q and 8r had no obvious cytotoxicity in either HepG2 cells or SH-SY5Y cells, even at a high concentration of 500 μM. Besides, a combined Lineweaver-Burk plot and molecular docking study revealed that these compounds might act as mixed-type inhibitors to exhibit such effects via selectively targeting both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChEs. Taken together, these results suggested that further development of these compounds should be of great interest.
Ligustrazine derivatives. Part 6: Design, synthesis and evaluation of novel ligustrazinyl acylguanidine derivatives as potential cardiovascular agents
Li, Zhenyu,Yu, Fang,Zhan, Peng,Shen, Yuemao,Liu, Xinyong,Cui, Lei,Wang, Shouxun
, p. 928 - 933,6 (2020/08/31)
A series of novel Ligustrazinyl acylguanidines was designed, synthesized and evaluated for their protective effect on injured vascular endothelial cell (ECV-304). The preliminary results demonstrated that some compounds possessed more potent activities than that of Ligustrazine in stimulating replication of the injured endothelial cell. Among the active compounds, compounds 8b, 8f and 8l displayed remarkable antioxidative activity with low EC50 values of 0.097, 0.059 and 0.094 mM, respectively. Structure-activity relationships were briefly discussed.
PYRAZOLOPYRIMIDINE COMPOUNDS AND THEIR USE AS PDE10 INHIBITORS
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, (2011/09/30)
The present invention relates to a compound represented by formula [I]: wherein: R1 is hydrogen, halogen, lower alkyl or cyano; Ring A is an optionally substituted heterocyclic group; Ring B is an optionally substituted 3 to 6-membered monocyclic group; and Y is optionally substituted amino, optionally substituted cyclic amino, optionally substituted aliphatic 3 to 6-membered monocyclyloxy, optionally substituted lower alkyl or optionally substituted lower alkyl-O-, or a pharmaceutically acceptable salt thereof, and to their use as PDE10 inhibitor.
