302912-43-2Relevant articles and documents
Design and discovery of quinazoline- and thiourea-containing sorafenib analogs as EGFR and VEGFR-2 dual TK inhibitors
Sun, Shaofeng,Zhang, Jingwen,Wang, Ningning,Kong, Xiangkai,Fu, Fenghua,Wang, Hongbo,Yao, Jianwen
, (2018/01/03)
Both EGFR and VEGFR-2 play a critical role in tumor growth, angiogenesis and metastasis, and targeting EGFR and VEGFR-2 simultaneously represents a promising approach to cancer treatment. In this work, a series of novel quinazoline- and thiourea-containing sorafenib analogs (10a–v) were designed and synthesized as EGFR and VEGFR-2 dual TK inhibitors. Their in vitro enzymatic inhibitory activities against EGFR and VEGFR-2, and antiproliferative activities against HCT-116, MCF-7 and B16 cell lines were evaluated and described. Most of the compounds showed potent activities against both cell lines and TK kinases. Compounds 10b and 10q which exhibited the most potent inhibitory activities against EGFR (IC50 = 0.02 μM and 0.01 μM, respectively), VEGFR-2 (IC50 = 0.05 μM and 0.08 μM, respectively), and good antiproliferative activities, also displayed competitive anti-tumor activities than sorafenib in vivo by B16 melanoma xenograft model test.
Design and discovery of thioether and nicotinamide containing sorafenib analogues as multikinase inhibitors targeting B-Raf, B-RafV600E and VEGFR-2
Sun, Shaofeng,He, Zuopeng,Huang, Mindong,Wang, Ningning,He, Zongzhong,Kong, Xiangkai,Yao, Jianwen
, p. 2381 - 2391 (2018/04/11)
New sorafenib derivatives containing thioether and nicotinamide moiety were designed and synthesized as B-Raf, B-RafV600E and VEGFR-2 multikinase inhibitors. Their in vitro enzymatic inhibitory activities against B-Raf, B-RafV600E and VEGFR-2 and their antiproliferative activities against HCT-116 and B16BL6 cell lines were evaluated and described. Most of the compounds showed potent activities against both cell lines and specific kinases. Compounds a1, b1 and c4, which exhibited the most potent inhibitory activities against B-Raf with IC50 of 21 nM, 27 nM and 17 nM, B-RafV600E with IC50 of 29 nM, 28 nM and 16 nM, VEGFR-2 with IC50 of 84 nM, 46 nM and 63 nM, respectively, and good antiproliferative activities, also demonstrated competitive antiangiogenic activities to sorafenib in in vitro HUVEC tube formation assay.
A block containing nicotinamide diphenyl thiourea compound and its salt preparation method and use of
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Paragraph 0085; 0086; 0092, (2017/08/02)
The invention relates to a diphenyl thiourea compound containing niacinamide building blocks and salt of the diphenyl thiourea compound. The chemical structure of the diphenyl thiourea compound is as shown in the description. The diphenyl thiourea compound and the salt, pharmaceutically acceptable, of the diphenyl thiourea compound have inhibiting effects on various tumour cell strains and can serve as effective components for preparing tumour treatment medicine.
The structure of the amine-containing thiourea compound and its preparation method and application
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Paragraph 0076; 0077; 0078; 0079; 0085, (2017/08/08)
A disclosed thiourea compounds containing an arylamine structure comprises compounds of a general formula I and pharmaceutically acceptable salts. In the general formula I shown in the specification, R1 is selected from H, C1-C8 alkyl, halogens, -CF3, -OCF3, -NO2, -CN, R2O-, -SO2NH2, -NHSO2R3, -NR4R5, -CONR6R7, -COOR8, R9CO- and disubstituted and trisubstituted combinations thereof, R2, R3, R4, R5, R6, R7, R8 and R9 are respectively H or C1-C8 alkyl, L is selected from -NHR10, -NHOR11, -NR12R13, pyrrolidin-1-yl, 4-piperidyl and (4-methyl-1-piperazinyl)methylene, and R10, R11, R12 and R13 are respectively H, C1-C8 alkyl, cycloalkyl or aryl. The compounds have inhibiting effect on multiple tumor cell strains.
Synthesis and biological evaluation of terminal functionalized thiourea-containing dipeptides as antitumor agents
Huang, Ri-Zhen,Zhang, Bin,Huang, Xiao-Chao,Liang, Gui-Bin,Qin, Jian-Mei,Pan, Ying-Ming,Liao, Zhi-Xin,Wang, Heng-Shan
, p. 8866 - 8878 (2017/02/10)
A series of antitumor agents based on terminal functionalized dipeptide derivatives containing the thiourea moiety were synthesized and evaluated for antiproliferative activity using a panel of cancer cell lines, and the effects and mechanism of apoptosis induction were determined. These compounds exhibited significant selectivity to different cancer cell lines with IC50 values at micromolar concentrations. In particular, compound I-11 appeared to be the most potent compound, with an IC50 = 4.85 ± 1.44 μM against the NCI-H460 cell line, at least partly, by the induction of apoptosis. Mechanistically, compound I-11 induced the activation of caspase-12 and CHOP, which triggered apoptotic signalling via the ROS-dependent endoplasmic reticulum pathway and arrested the cell cycle at the S phase. Thus, we concluded that dipeptide derivatives containing the thiourea moiety terminally functionalized by electron-withdrawing substituents may be potential antitumor agents for further investigation.
Design, synthesis and biological evaluation of thiourea and nicotinamide-containing sorafenib analogs as antitumor agents
Kong, Xiangkai,Yao, Zeyu,He, Zuopeng,Xu, Wenfang,Yao, Jianwen
, p. 867 - 870 (2015/05/27)
A series of thiourea and nicotinamide-containing sorafenib analogs (7a-n) were designed and synthesized and their antiproliferative activities were tested against HCT116, MDA-MB-231, PC-3 and HepG2 cell lines. Most of the compounds showed potent activities against the four cell lines, compound 7h showed better activities than sorafenib against all four cell lines, and compounds 7a and 7e showed better activities against HCT116 and MDA-MB-231 cell lines. The anti-angiogenic activities of 7e and 7h were also better than that of sorafenib in both in vitro HUVEC tube formation assay and ex vivo rat thoracic aorta ring assay.
