- Discovery of novel 2-substituted-4-phenoxypyridine derivatives as potential antitumor agents
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A series of 2-substituted-4-phenoxypyridine derivatives were designed, synthesized, and evaluated for their antiproliferative activity against 4 cancer cell lines (A549, HT-29, H460, and U87MG) in vitro. Most compounds showed moderate to excellent potency. Nine tyrosine kinases (c-Met, Flt-3, ALK, VEGFR-2, VEGFR-3, PDGFR-α PDGFR-β c-Kit, and EGFR) were used to evaluate the inhibitory activities with the most promising analogue 39, which showed the Flt-3/c-Met IC50 values of 2.18/2.61 nM. Structure-activity relationship studies indicated that n-Pr served as R1 group showed a higher preference, and stronger mono-EWGs on the phenyl ring (such as R2 = 4-F) was benefited to the potency.
- Duan, Yongli,Xu, Shan,Xiong, Hehua,Wang, Linxiao,Zhao, Bingbing,Wang, Ping,Wang, Caolin,Peng, Yiqing,Cai, Shifan,Luo, Rong,Zheng, Pengwu,Tang, Qidong
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p. 254 - 259
(2018/01/10)
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- Thiourea and thioether derivatives of sorafenib: Synthesis, crystal structure, and antiproliferative activity
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A series of novel sorafenib derivatives containing diaryl thiourea and thioether, 9a-u, was designed and synthesized, and their antiproliferative activities against HCT116 and MDA-MB-231 cell lines were also evaluated and described. Most compounds exhibited potent antiproliferative activity against HCT116 cells with IC50 = 1.8-80.4 μM. Compounds 9p, 9r, and 9s demonstrated competitive antiproliferative activities to sorafenib, against all two cancer cell lines. The structures of all the newly synthesized compounds were determined by 1H NMR, 13C NMR, and HRMS, and compound 9n was characterized by single-crystal X-ray diffraction. Primary structure-activity relationships (SAR) have also been established.
- Yao, Jianwen,Chen, Jing,He, Zuopeng,Sun, Wei,Fang, Hao,Xu, Wenfang
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p. 3959 - 3968
(2013/07/26)
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- Design, synthesis and biological activities of sorafenib derivatives as antitumor agents
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A series of novel sorafenib derivatives, 9a-w, was designed and synthesized in high yields using various substituted anilines, and their antiproliferative activities against HCT116, PC-3 and MDA-MB-231 cell lines were also evaluated and described. All compounds exhibited potent antiproliferative activity against HCT116 and PC-3 cells with IC50 = 2.8-52.0 and 2.2-45.6 μM; compounds 9p and 9q demonstrated competitive antiproliferative activities to sorafenib against all three cancer cell lines, the cytotoxicity of compound 9r is more potent than that of sorafenib. Compounds (9g, 9p, 9q and 9r) were chosen for further evaluation of the anti-angiogenesis activity, and showed the inhibition of sprout formation from aortic ring ex vivo. The structures of all the newly synthesized compounds were determined by 1H NMR, 13C NMR and HRMS.
- Yao, Jianwen,He, Zuopeng,Chen, Jing,Sun, Wei,Fang, Hao,Xu, Wenfang
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p. 6549 - 6553,5
(2012/12/12)
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- OMEGA-CARBOXYARYL SUBSTITUTED DIPHENYL UREAS AS RAF KINASE INHIBITORS
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This invention relates to the use of a group of aryl ureas in treating raf mediated diseases, and pharmaceutical compositions for use in such therapy.
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Page/Page column 23
(2010/01/31)
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