Design, Synthesis and Antitumor Activity of Novel 6,7-Dimethoxyquinazoline Derivatives Containing Diaryl Urea Moiety

doi:10.1007/s40242-015-5036-z

Chemical Research in Chinese Universities ›› 2015, Vol. 31 ›› Issue (5): 766-773.doi: 10.1007/s40242-015-5036-z

• Articles • Previous Articles Next Articles

Design, Synthesis and Antitumor Activity of Novel 6,7-Dimethoxyquinazoline Derivatives Containing Diaryl Urea Moiety

HOU Yunlei, WU Shasha, MA Longsheng, BAI Jinying, LIU Zijian, ZHAO Yanfang

Key Laboratory of Structure-based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, P. R. China

Received:2015-01-27 Revised:2015-03-16 Online:2015-10-01 Published:2015-04-13
Contact: ZHAO Yanfang, E-mail: yanfangzhao@126.com E-mail:yanfangzhao@126.com
Supported by:
Supported by the Program for Innovative Research Team of the Ministry of Education of the People's Republic of China and Program for Liaoning Innovative Research Team in University, China(No.IRT1073) and the Liaoning Excellent Talents in University of China(No.LJQ2013106).

Abstract

Abstract:

A series of 6,7-dimethoxyquinazoline derivatives connected by diaryl urea scaffolds was designed, synthesized and their in vitro antitumor activities were evaluated. Most of them showed an excellent potency against the four tested cancer cell lines as compared with sorafenib. Particularly, a promising compound 20 was identified, which showed the most potent antitumor activities with IC₅₀ values of 0.08, 0.09, 0.16 and 0.19 μmol/L against H460, HT-29, MKN-45 and MDA-MB-231 cell lines, respectively. The structure-activity relationship(SAR) analysis indicated that compounds with dimethylamino or diethylamino group at the C4 position of 6,7-dimethoxyquinazoline moiety exhibited superior activities than compounds bearing morpholino groups.

Key words: 6,7-Dimethoxyquinazoline derivative, Diaryl urea scaffold, Cytotoxic activity

HOU Yunlei, WU Shasha, MA Longsheng, BAI Jinying, LIU Zijian, ZHAO Yanfang. Design, Synthesis and Antitumor Activity of Novel 6,7-Dimethoxyquinazoline Derivatives Containing Diaryl Urea Moiety[J]. Chemical Research in Chinese Universities, 2015, 31(5): 766-773.

References

[1] WHO Media Centre, www.who.int/mediacentre/factsheets/fs297/en/, Last Accessed:26.03313, 2013
[2] Panda J., Patro V. J., Kumar A., Panda R. K., Sahoo B. M., Pharma Science Monitor, 2012, 3, 2968
[3] Waiker D. K., Karthikeyan C., Poongavanam V., Kongsted J., Lozach O., Meijer L., Trivedi P., Bioorg. Med. Chem., 2014, 22, 1909
[4] Ma A. Q., Yu W. Y., Li F. L., Bleich R. M., Herold J. M., Butler K. V., Norris J. L., Korboukh V., Tripathy A., Janzen W. P., Arrowsmith C. H., Frye S. V., Vedadi M., Brown P. J., Jin J., J. Med. Chem., 2014, 57, 6822
[5] Antonello A., Tarozzi A., Morroni F., Cavalli A., Rosini M., Hrelia P., Bolognesi M. L., Melchiorre C., J. Med. Chem., 2006, 49, 6642
[6] Sarkar S., Mazumdar A., Dash R., Sarkar D., Fisher P. B., Mandal M., Cancer Biol. Ther., 2010, 9, 592
[7] Rowbottom M. W., Faraoni R., Chao Q., Campbell B. T., Lai A. G., Setti E., Ezawa M., Sprankle K. G., Abraham S., Tran L., Struss B., Gibney M., Armstrong R. C., Gunawardane R. N., Nepomuceno R. R., Valenta I., Hua H., Gardner M. F., Cramer M. D., Gitnick D., Insko D. E., Apuy J. L., Jones B. S., Ghose A. K., Herbertz T., Ator M. A., Dorsey B. D., Ruggeri B., Williams M., Bhagwat S., James J., Holladay M. W., J. Med. Chem., 2012, 55, 1082
[8] Srimongkolpithak N., Sundriyal S., Li F. L., Vedadi M., Fuchter M. J., Med. Chem. Comm., 2014, 5, 1821
[9] Jeon Y. T., Yang W., Qiao J. X., Li L., Ruel R., Thibeault C., Hiebert S., Wang T. C., Wang Y. F., Liu Y. J., Clark C. G., Wong H. S., Zhu J. L., Wu D., Sun D., Chen B. C., Mathur A., Chacko S. A., Malley M., Chen X. Q., Shen H., Huang C. S., Schumacher W. A., Bostwick J. S., Stewart A. B., Price L. A., Hua J., Li D. S., Levesque P. C., Seiffert D. A., Rehfuss R., Wexler R. R., Lam P. Y. S., Bioorg. Med. Chem. Lett., 2014, 24, 1294
[10] Kulkarni R. G., Laufer S., Mangannavar C., Garlapati A., Med. Chem., 2013, 9, 213
[11] Nakamura K., Taguchi E., Miura T., Yamamoto A., Takahashi K., Bichat F., Guilbaud N., Hasegawa K., Kubo K., Fujiwara Y., Suzuki R., Shibuya M., Isoe T., Cancer Res., 2006, 66, 9134
[12] Kim H. J., Jung M. H., Kim H., EI-Gamal M. I., Sim T. B., Lee S. H., Hong J. H., Hah J. M., Cho J. H., Choi J. H., Yoo K. H., Oh C. H., Bioorg. Med. Chem. Lett., 2010, 20, 413
[13] Wilhelm S. M., Carter C., Tang L. Y., Wilkie D., McNabola A., Rong H., Chen C., Zhang X. M., Vincent P., McHugh M., Cao Y. C., Shujath J., Gawlak S., Eveleigh D., Rowley B., Liu L., Adnane L., Lynch M., Auclair D., Taylor I., Gedrich R., Voznesensky A., Riedl B., Post L. E., Bollagand G., Trail P. A., Cancer Res., 2004, 64, 7099
[14] Kan R. C., Farrell A. T., Saber H., Tang S., Williams G., Jee J. M., Liang C., Booth B., Chidambaram N., Morse D., Sridhara R., Garvey P., Justice R., Pazdur R., Clin. Cancer Res., 2006, 12, 7271
[15] Keating G. M., Santoro A., Drugs, 2009, 69, 223
[16] Dai Y. J., Hartandi K., Ji Z., Ahmed A. A., Albert D. H., Bauch J. L., Bouska J. J., Bousquet P. F., Cunha G. A., Glaser K. B., Harris C. M., Hickman D., Guo J., Li J. L., Marcotte P. A., Marsh K.C., Moskey M. D., Martin R. L., Olson A. M., Osterling D. J., Pease L. J., Soni N. B., Stewart K. D., Stoll V. S., Tapang P., Reuter D. R., Davidsen S. K., Michaelides M. R., J. Med. Chem., 2007, 50, 1584
[17] Wang X., Horswill J. G., Whalley B. J., Stephens G. J., Mol. Pharmacol., 2011, 79, 758
[18] Qin Y. Z., Lu Y. Y., Wang R. Q., Li W. B., Qu X. J., Biosci. Trends, 2013, 7, 237
[19] Liu Z. J., Wu S. S., Wang Y., Li R. J., Wang J., Wang L. H., Zhao Y. F., G ong P., Eur. J. Med. Chem., 2014, 87, 782

Design, Synthesis and Antitumor Activity of Novel 6,7-Dimethoxyquinazoline Derivatives Containing Diaryl Urea Moiety

Knowledge

Cited

Abstract

Cite this article

share this article

References

Related Articles 7

Recommended Articles

Metrics

Comments

[1]	WU Qian, JIN Yongri, YAO Hua, LIU Ying, LI Peng, LI Xuwen. Two New Baccharane Glycosides from Seeds of Impatientis balsamina L. with in vitro Growth Inhibitory Activity in Human Cancer A375 Cells [J]. Chemical Research in Chinese Universities, 2017, 33(5): 753-757.
[2]	GUO Jinhua, TAN Bei, YE Qingmei, LIANG Guangping, YI Min, JIANG Renwang. Synthesis and Cytotoxic Activities of Spin-labeled Derivatives of Cinobufagin [J]. Chemical Research in Chinese Universities, 2017, 33(4): 581-586.
[3]	HU Hao, JIANG Mingyan, XIE Lijun, HU Gang, ZHANG Cuirong, ZHANG Lixia, ZHOU Shunguang, ZHANG Meihui, GONG Ping. Design, Synthesis and Pharmacological Evaluation of Novel 4-Phenoxyquinoline Derivatives as Potential Antitumor Agents [J]. Chemical Research in Chinese Universities, 2015, 31(5): 746-755.
[4]	SU Ran, LÜ Lei, ZHENG Songzhi, JIN Yinghua, AN Shengji. Synthesis and Characterization of Novel Azo-containing or Azoxy-containing Schiff Bases and Their Antiproliferative and Cytotoxic Activities [J]. Chemical Research in Chinese Universities, 2015, 31(1): 60-64.
[5]	SONG Kaizhen, MA Junjie, WANG Xiao, GONG Ping, ZHAO Yanfang. Synthesis and Antitumor Activities of Novel 4-Morpholinothieno[3,2-d]pyrimidine Derivatives [J]. Chemical Research in Chinese Universities, 2014, 30(1): 75-81.
[6]	LIAO Xiao-jian, TANG Li-dan, LIANG Yuan-wei, GENG Hua-wei and XU Shi-hai*. Isolation and Identification of Two New Polyhydroxylated Sterols from Soft Coral Sinularia sp. [J]. Chemical Research in Chinese Universities, 2011, 27(2): 217-220.
[7]	ZHANG Xing, WU Jiao, HAN Zhuang, MEI Wen-li* and DAI Hao-fu*. Antioxidant and Cytotoxic Phenolic Compounds of Areca Nut(Areca catechu) [J]. Chemical Research in Chinese Universities, 2010, 26(1): 161-164.