Chinese Journal of Organic Chemistry >
Synthesis and Antitumor Activities Evaluation of 2-Methylthio-4-arylamine Quinazoline Derivatives
Received date: 2018-05-04
Revised date: 2018-06-20
Online published: 2018-07-05
Supported by
Project supported by the National Natural Science Foundation of China (No. 81430085), the Technology Department Project of Henan Province (Nos. 182300410321, 182102310249) and the Students' Platform for Innovation and Entrepreneurship Training Program of Zhengzhou University (No. 2017-cxcy563).
In order to find the efficient and novel antitumor drugs, a series of 2-methylthio-4-arylamine quinazoline derivatives were designed and synthesized. The target compounds were evaluated for antitumor activity in vitro on four human cancer cell lines initially including MGC-803, PC-3, HGC-27 and A549. The results showed that some compounds had good antitumor activities, especially N-(4-fluorophenyl)-2-(methylthio) quinazolin-4-amine (9c) and 2-(methylthio)-N-(p-tolyl)-quina-zolin-4-amine (9m), with IC50 values of 0.18 and 0.68 μmol·L-1, respectively.
Key words： quinazoline derivatives; synthesis; antitumor activity; evaluation
Meng Xiangchuan , Li Na , Li Erdong , Chang Tonghang , Liu Meng , Liu Qingyi , Yuan Wenjuan , Zhang Qingqing , Zhang Yu , Zhou Zhiyu , Song Panpan , Liu Hongmin , Zhang Qiurong . Synthesis and Antitumor Activities Evaluation of 2-Methylthio-4-arylamine Quinazoline Derivatives[J]. Chinese Journal of Organic Chemistry, 2018 , 38(11) : 3063 -3069 . DOI: 10.6023/cjoc201805015
[1] Sangthong, S.; Krusong, K.; Ngamrojanavanich, N.; Vilaivan, T.; Puthong, S.; Chandchawan, S.; Muangsin, N. Bioorg. Med. Chem. Lett. 2011, 21, 4813.
[2] Cao, R. H.; Fan, W. X.; Guo, L.; Ma, Q.; Zhang, G. X.; Li, J. R.; Chen, X. M.; Ren, Z. H.; Qiu, L. Q. Eur. J. Med. Chem. 2013, 60, 135.
[3] Van Horn, K. S.; Burda, W. N.; Fleeman, R.; Shaw, L. N.; Manetsch, R. J. Med. Chem. 2014, 57, 3075.
[4] Liu, F.; Huang, Y. J. Pestic. Biochem. Phys. 2011, 101, 248.
[5] Alafeefy, A. M.; Kadi, A. A.; Al-Deeb, O. A.; El-Tahir, K. E. H.; Al-Jaber, N. A. Eur. J. Med. Chem. 2010, 45, 4947.
[6] Wu, J. W.; Chen, W. T.; Xia, G. X.; Zhang, J.; Shao, J. A.; Tan, B. Q.; Zhang, Z. Z.; Yu, W. W.; Weng, Q. J.; Liu, H. Y.; Hu, M.; Deng, H. L.; Hao, Y.; Shen, J. K.; Yu, Y. P. ACS Med. Chem. Lett. 2013, 4, 974.
[7] Zhang, Y. L.; Chen, L.; Xu, H. J.; Li, X. B.; Zhao, L. J.; Wang, W.; Li, B. L.; Zhang, X. Q. Eur. J. Med. Chem. 2018, 147, 77.
[8] Siegel, R.; Naishadham, D.; Jemal, A. CA Cancer J. Clin. 2013, 67, 11.
[9] Cui, G.; Cui, M.; Li, Y.; Liang, Y.; Li, W.; Guo, H.; Zha, S. Med. Oncol. 2015, 32, 570.
[10] Mathew, M. P.; Tan, E.; Saeui, C. T.; Bovonratwet, P.; Liu, L.; Bhattacharya, R.; Yarema, K. J. Bioorg. Med. Chem. Lett. 2015, 25, 1223.
[11] Smaill, J. B.; Showalter, H. D. H.; Zhou, H.; Bridges, A. J.; McNamara, D. J.; Fry, D. W.; Nelson, J. M.; Sherwood, V.; Vincent, P. W.; Roberts, B. J.; Elliott, W. L.; Denny, W. A. J. Med. Chem. 2001, 44, 429.
[12] Engelman, J. A.; Zejnullahu, F.; Gale, C.-M.; Lifshits, E.; Gonzales, A. J.; Shimamura, T.; Zhao, F.; Vincent, P. W.; Naumov, G. N.; Bradner, J. E.; Althaus, I. W.; Gandhi, L.; Shapiro, G. I.; Nelson, J. M.; Heymach, J. V.; Meyerson, M.; Wong, K. K.; Janne, P. A. Cancer Res. 2007, 67, 11924.
[13] Li, D.; Ambrogio, L.; Shimamura, T.; Kubo, S.; Takahashi, M.; Chirieac, L. R.; Padera, R. F.; Shapiro, G. I.; Baum, A.; Himmelsbach, F.; Rettig, W. J.; Meyerson, M.; Solca, F.; Greulich, H.; Wong, K. K. Oncogene 2008, 27, 4702.
[14] Al-Rashood, S. T.; Aboldahab, I. A.; Nagi, M. N.; Abouzeid, L. A.; Abdel-Aziz, A. A. M.; Abdel-Hamide, S. G.; Youssef, K. M.; Al-Obaid, A. M.; El-Subbagh, H. I. Bioorg. Med. Chem. 2006, 14, 8608.
[15] Shao, K. P.; Zhang, X. Y.; Chen, P. J.; Xue, D. Q.; He, P.; Ma, L. Y.; Zheng, J. X.; Zhang, Q. R.; Liu, H. M. Bioorg. Med. Chem. Lett. 2014, 24, 3877.
[16] Wang, C.; Cao, Q.; Yang, H.; Song, P.; Xue, D.; Cui, F.; Gu, Y.; Zhang, X.; Tian, Y.; Zhang, Q.; Liu, H. Chin. J. Org. Chem. 2016, 36, 1626(in Chinese). (王超杰, 曹钦坡, 杨慧, 宋攀攀, 薛登启, 崔飞, 顾一飞, 张孝松, 田亚楠, 张秋荣, 刘宏民, 有机化学, 2016, 36, 1626.)
[17] Li, N.; Xin, J. C.; Ma, Q. S.; Li, E. D.; Meng, Y. Q.; Bao, C. N.; Yang, P.; Song, P. P.; Cui, F.; Cheng, P. J.; Gu, Y. F.; Zhao, P. R.; Ke, Y.; Liu, H. M.; Zhang, Q. R. Chin. J. Org. Chem. 2018, 38, 665(in Chinese). (栗娜, 辛景超, 马启胜, 李二冬, 孟娅琪, 包崇男, 杨鹏, 宋攀攀, 崔飞, 陈鹏举, 顾一飞, 赵培荣, 可钰, 刘宏民, 张秋荣, 有机化学, 2018, 38, 665.)
[18] Xin, J. C.; Li, N.; Ma, Q. S.; Li, E. D.; Meng, X. C.; Ke, Y.; Liu, H. M.; Zhang, Q. R. Chin. J. Org. Chem. 2018, 32, 451(in Chinese). (辛景超, 栗娜, 马启胜, 李二冬, 孟祥川, 可钰, 刘宏民, 张秋荣, 有机化学, 2018, 32, 451.)
[19] Abdullaev, N. P.; Kayumov, K.; Shakhidoyatov, K. M. Uzb. Khim. Zh. 1997, 2, 29.
[20] Kikelj, D. In Science of Synthesis, Product Class 13:Quinazolines, Vol. 16, Eds.:Yamamoto, Y.; Bellus, D.; Jacobsen, E. N.; Ley, S. V.; Noyori, R.; Regitz, M.; Reider, P. J.; Schaumann, E.; Shinkai, I.; Thimas, E. J.; Trost, B. M., Thieme, Stuttgart, 2004, p. 573.
[21] Song, P. P.; Cui, F.; Li, N.; Xin, J. C.; Ma, Q. S.; Meng, X. C.; Wang, C. J.; Cao, Q. P.; Gu, Y. F.; Ke, Y.; Zhang, Q. R.; Liu, H. M. Chin. J. Chem. 2017, 35, 1633(in Chinese). (宋攀攀, 崔飞, 栗娜, 辛景超, 马启胜, 孟祥川, 王超杰, 曹钦坡, 顾一飞, 可钰, 刘宏民, 张秋荣, 有机化学, 2017, 35, 1633.)
[22] Shao, K. P.; Zhang, X. Yao.; Chen, P. J.; Xue, D. Q.; He, P.; Ma, L. Y.; Zheng, J. X.; Zhang, Q. R.; Liu, H. M. Bioorg. Med. Chem. Lett. 2014, 24, 3877.
[23] Chen, P. J.; Yang, A.; Gu, Y. F.; Zhang, X. S.; Shao, K. P.; Xue, D. Q.; He, P.; Jiang, T. F.; Zhang, Q. R.; Liu, H. M. Bioorg. Med. Chem. Lett. 2014, 24, 2741.
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