Chinese Journal of Organic Chemistry >
Design, Synthesis, and Biological Evaluation of Novel 2-Amino-4-phenylthiazole Derivatives as c-Met Inhibitors
Received date: 2018-03-25
Revised date: 2018-06-06
Online published: 2018-06-15
Supported by
Project supported by the National Natural Science Foundation for Young Scientists of China (No. 21601075), the Natural Science Foundation of Liaoning Province (No. 2015020249) and the General Research Projects of Liaoning Provincial Department of Education (No. JQL201715410).
Two series of novel 2-amino-4-phenylthiazole derivatives were designed and synthesized based on the structural features of crizotinib. The cell proliferation inhibition efficacy was estimated against A549, HT29, Hela and Karpas299 cell lines. The results revealed that some target compounds exhibited strong or moderate proliferation inhibition efficacy against tumor cells. N-(3-(2-Aminothiazol-4-yl)phenyl)-3-chlorobenzamide (3d) displayed significant activity against HT29 cancer cell with IC50 value of 4.42 μmol/L, and influence of this compound on the expression of related proteins in the MET signaling pathway in HT29 cells was investigated by Western blot. In addition, the preliminary structure-activity relationship (SAR) of the derivatives was rationalized by docking studies.
Zhang Zhihua , Chen Yu , Wu Hongmei , Cui Bo , Xiong Wulin , Lin Tenghui , Lin Rongnan , Yu Guo . Design, Synthesis, and Biological Evaluation of Novel 2-Amino-4-phenylthiazole Derivatives as c-Met Inhibitors[J]. Chinese Journal of Organic Chemistry, 2018 , 38(10) : 2648 -2656 . DOI: 10.6023/cjoc201803041
[1] Gimenezxavier, P.; Pros, E.; Bonastre, E.; Moran, S.; Aza, A.; Graña, O.; Gómezlópez, G.; Derdak, S.; Dabad, M.; Estevecodina, A. Mol. Cancer Ther. 2017, 16, 1366.
[2] Miekus, K. Oncol. Rep. 2017, 37, 647.
[3] BachleitnerHofmann, T.; Sun, M. Y.; Chen, C.; Tang, L.; Song, L.; Zeng, Z.; Shah, M.; Christensen, J. G.; Rosen, N.; Solit, D. B. Mol. Cancer Ther. 2008, 7, 3499.
[4] Turke, A. B.; Zejnullahu, K.; Wu, Y.-L.; Song, Y.; Dias-Santagata, D.; Lifshits, E.; Toschi, L.; Rogers, A.; Mok, T.; Sequist, L.; Lindeman, N. I.; Murphy, C.; Akhavanfard, S.; Yeap, B. Y.; Xiao, Y.; Capelletti, M.; Iafrate, A. J.; Lee, C.; Christensen, J. G.; Engelman, J. A.; Jänne, P. A. Cancer Cell 2010, 17, 77.
[5] Tang, Z.; Du, R.; Jiang, S.; Wu, C.; Barkauskas, D. S.; Richey, J.; Molter, J.; Lam, M.; Flask, C.; Gerson, S. Br. J. Cancer 2008, 99, 911.
[6] Cui, J. J.; Tran-Dubé, M.; Shen, H.; Nambu, M.; Kung, P. P.; Pairish, M.; Jia, L.; Meng, J.; Funk, L.; Botrous, I. J. Med. Chem. 2011, 54, 6342.
[7] Wang, X.; Defrances, M. C.; Dai, Y.; Pediaditakis, P.; Johnson, C.; Bell, A.; Michalopoulos, G. K.; Zarnegar, R. Mol. Cell 2002, 9, 411.
[8] Liu, Y.; Gray, N. S. Nat. Chem. Biol. 2006, 2, 358.
[9] Rosoux, A.; Duplaquet, F.; Ocak, S. Case Rep. Oncol. 2017, 10, 447.
[10] Mavridis, L.; Hudson, B. D.; Ritchie, D. W. J. Chem. Inf. Model. 2007, 47, 1787.
[11] Ballester, P. J.; Richards, W. G. J. Comput. Chem. 2007, 28, 1711.
[12] Forlani, L.; Tocke, A. L.; Del, V. E.; Lakhdar, S.; Goumont, R.; Terrier, F. J. Org. Chem. 2006, 71, 5527.
[13] Tseng, C. K. Magn. Reson. Chem. 2010, 25, 105.
[14] forlani, L.; Maria, P. D.; Fini, A. J. Chem. Soc., Perkin Trans. 2 1980, 163.
[15] Wang, Y. Z.; Wu, A. X. Chin. J. Org. Chem. 2008, 28, 997(in Chinese). (王宇宙, 吴安心, 有机化学, 2008, 28, 997.)
[16] Zhang, Z. H, Chen, Y.; Chai, B. S.; Yang, X, M.; Cai, X. Y.; Cui, B.; You, S. Chin. J. Org. Chem. 2017, 37, 2377(in Chinese). (张志华, 陈羽, 柴宝山, 杨小漫, 蔡晓瑜, 崔博, 游松, 有机化学, 2017, 37, 2377.)
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