56190-17-1Relevant articles and documents
Potent, Selective, and Cell Active Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor Developed by Structure-Based Virtual Screening and Hit Optimization
Mao, Ruifeng,Shao, Jingwei,Zhu, Kongkai,Zhang, Yuanyuan,Ding, Hong,Zhang, Chenhua,Shi, Zhe,Jiang, Hualiang,Sun, Dequn,Duan, Wenhu,Luo, Cheng
, p. 6289 - 6304 (2017/08/02)
PRMT5 plays important roles in diverse cellular processes and is upregulated in several human malignancies. Besides, PRMT5 has been validated as an anticancer target in mantle cell lymphoma. In this study, we found a potent and selective PRMT5 inhibitor by performing structure-based virtual screening and hit optimization. The identified compound 17 (IC50 = 0.33 μM) exhibited a broad selectivity against a panel of other methyltransferases. The direct binding of 17 to PRMT5 was validated by surface plasmon resonance experiments, with a Kd of 0.987 μM. Kinetic experiments indicated that 17 was a SAM competitive inhibitor other than the substrate. In addition, 17 showed selective antiproliferative effects against MV4-11 cells, and further studies indicated that the mechanism of cellular antitumor activity was due to the inhibition of PRMT5 mediated SmD3 methylation. 17 may represent a promising lead compound to understand more about PRMT5 and potentially assist the development of treatments for leukemia indications.
SYNTHESIS AND REACTIONS OF 2H-BENZIMIDAZOLE-2-SPIROCYCLOHEXANES : AN APPLICATION OF "UMPOLING"
Iddon, Brian
, p. 673 - 701 (2007/10/02)
The title compounds are available through condensation of an o-phenylenediamine with cyclohexanone followed by oxidation of the resulting product with manganese dioxide.In this article we review their oxidation, reduction, and rearrangement reactions along with their reactions with nitrogen, oxygen, sulphur, and other nucleophiles.As well as the parent compound the reactions of the 5-chloro-, 5,6-dichloro-, 4,6-dibromo-, 5-phenylsulphonyl- and 5-methoxy-derivative are discussed in some detail.Some applications of the methodology developed, particularly to the synthesis of actual or potential benzimidazole anthelminthics, are given also.