Product Details of 5451-40-1. Aromatic heterocyclic compounds can also be classified according to the number of heteroatoms contained in the heterocycle: single heteroatom, two heteroatoms, three heteroatoms and four heteroatoms. Compound: 2,6-Dichloropurine, is researched, Molecular C5H2Cl2N4, CAS is 5451-40-1, about Discovery of 3-(((9H-purin-6-yl)amino)methyl)-4,6-dimethylpyridin-2(1H)-one derivatives as novel tubulin polymerization inhibitors for treatment of cancer. Author is Zhang, Qiangsheng; Hu, Xi; Wan, Guoquan; Wang, Jia; Li, Lu; Wu, Xiuli; Liu, Zhihao; Yu, Luoting.
A new series of 3-(((9H-purin-6-yl)amino)methyl)-4,6-dimethylpyridin-2(1H)-one derivatives I [R1 = H, i-Pr, Et2CH, cyclopentyl, tetrahydropyran-2-yl; R2 = H, Cl, 4-F3COC6H4, 3-(morpholin-4-yl)phenyl, 6-(4-methylpiperazin-1-yl)pyridin-3-yl, etc.] was designed, synthesized and demonstrated to act as tubulin polymerization inhibitors. These new derivatives showed significant antitumor activities, among which compound I [R1 = cyclopentyl; R2 = Cl (II)] was found to be the most potent compound, with IC50 values ranging from 44.5 to 135.5 nM against seven colorectal carcinoma (CRC) cell lines. Remarkably, compound II exhibited no activity against other potential targets, such as 420 kinases and EZH2. Besides, compound II inhibited tubulin polymerization, arrested the cell cycle at the G2/M phase and induced apoptosis in CRC cells. Furthermore, compound II suppressed tumor growth in the HCT116 xenograft model without inducing notable major organ-related toxicity, suggesting that this compound could be used as a promising lead compound for the development of new antitumor agents.
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