Synthesis and Biological Activity of Imidazo[4,5-c]quinoline Derivatives as PI3K/mTOR Inhibitors

doi:10.1007/s40242-017-7074-1

高等学校化学研究 ›› 2017, Vol. 33 ›› Issue (6): 895-902.doi: 10.1007/s40242-017-7074-1

Synthesis and Biological Activity of Imidazo[4,5-c]quinoline Derivatives as PI3K/mTOR Inhibitors

LI Yanjie^1,2, ZHANG Xingmin³, NIU Shengxiu¹, ZHAO Yanping¹, YANG Lijuan¹, SHAO Xiaowei¹, WANG Ensi¹

1. College of Pharmacy, Jilin University, Changchun 130021, P. R. China;
2. College of Pharmacy, Changchun University of Traditional Chinese Medicine, Changchun 130117, P. R. China;
3. Beijing Foreland Pharma Biological Technology Co., Ltd., Beijing 101111, P. R. China

收稿日期:2017-03-01 修回日期:2017-03-29 出版日期:2017-12-01 发布日期:2017-07-21
通讯作者: WANG Ensi,E-mail:wangss@jlu.edu.cn E-mail:wangss@jlu.edu.cn
基金资助:
Supported by the Fund of Jilin University(China) Hi-Tech(Group) Co., Ltd.

Synthesis and Biological Activity of Imidazo[4,5-c]quinoline Derivatives as PI3K/mTOR Inhibitors

LI Yanjie^1,2, ZHANG Xingmin³, NIU Shengxiu¹, ZHAO Yanping¹, YANG Lijuan¹, SHAO Xiaowei¹, WANG Ensi¹

1. College of Pharmacy, Jilin University, Changchun 130021, P. R. China;
2. College of Pharmacy, Changchun University of Traditional Chinese Medicine, Changchun 130117, P. R. China;
3. Beijing Foreland Pharma Biological Technology Co., Ltd., Beijing 101111, P. R. China

Received:2017-03-01 Revised:2017-03-29 Online:2017-12-01 Published:2017-07-21
Contact: WANG Ensi,E-mail:wangss@jlu.edu.cn E-mail:wangss@jlu.edu.cn
Supported by:
Supported by the Fund of Jilin University(China) Hi-Tech(Group) Co., Ltd.

摘要/Abstract

摘要： A series of imidazo[4,5-c]quinoline derivatives(12a-12m) was synthesized with 2-amino-5-bromoben-zoic acid and 4-nitrophenylacetonitrile as starting materials, 6-bromo-4-chloro-3-nitroquinoline as intermediate and Suzuki reaction and closure of the imidazolinone ring with triphosgene as key steps. The structures of the key intermediate and target compounds were confirmed by means of ¹H NMR, ¹³C NMR and HRMS. These compounds show an interesting kinase profile as dual PI3K/mTOR tool compounds.

关键词: Imidazo[4,5-c]quinoline, Suzuki reaction, Dual PI3K/mTOR inhibitor

Abstract: A series of imidazo[4,5-c]quinoline derivatives(12a-12m) was synthesized with 2-amino-5-bromoben-zoic acid and 4-nitrophenylacetonitrile as starting materials, 6-bromo-4-chloro-3-nitroquinoline as intermediate and Suzuki reaction and closure of the imidazolinone ring with triphosgene as key steps. The structures of the key intermediate and target compounds were confirmed by means of ¹H NMR, ¹³C NMR and HRMS. These compounds show an interesting kinase profile as dual PI3K/mTOR tool compounds.

Key words: Imidazo[4,5-c]quinoline, Suzuki reaction, Dual PI3K/mTOR inhibitor

LI Yanjie, ZHANG Xingmin, NIU Shengxiu, ZHAO Yanping, YANG Lijuan, SHAO Xiaowei, WANG Ensi. Synthesis and Biological Activity of Imidazo[4,5-c]quinoline Derivatives as PI3K/mTOR Inhibitors[J]. 高等学校化学研究, 2017, 33(6): 895-902.

参考文献

[1] Kang S., Bader A. G., Vogt P. K., Proc. Natl. Acad. Sci., 2005, 102(3), 802
[2] Brown J. B., Cheresh P., Goretsky T., Managlia E., Grimm G. R., Ryu H., Zadeh M., Dirisina R., Barrett T. A., Infection and Immunity, 2011, 79(5), 1863
[3] Cully M., You H., Levine A. J., Mak T. W., Nat. Rev. Cancer, 2006, 6(3), 184
[4] Treins C., Warne P. H., Magnuson M. A., Pende M., Downward J., Oncogene, 2010, 29(7), 1003
[5] Suire S., Coadwell J., Ferguson G. J., Davidson K., Hawkins P., Stephens L., Curr. Biol., 2005, 15(6), 566
[6] Laplante M., Sabatini D. M., Cell, 2012, 149(2), 274
[7] Shapiro G. I., Rodon J., Bedell C., Kwak E. L., Baselga J., Brana I., Pandya S. S., Scheffold C., Laird A. D., Nguyen L. T., Xu Y., Egile C., Edelman G., Clin. Cancer Res., 2014, 20(1), 233
[8] Ma B. B. Y., Lui V. W. Y., Hui E. P., Lau C. P. Y., Ho K., Ng M. H. L., Cheng S. H., Tsao S. W., Chan A. T. C., Invest. New Drugs, 2010, 28(4), 413
[9] Elicabe M. M., Yin D. L., Hadaczek P., Zhai Y. Y., Forsayeth J., Bankiewicz K. S., J. Neurooncol., 2012, 108(1), 53
[10] Raynaud F. I., Eccles S. A., Patel S., Alix S., Box G., Chuckowree I. S., Folkes A. J., Gowan S., Brandon A. D. H., Stefano F. D., Hayes A., Henley A. T., Lensun L., Pergl-Wilson G. H., Robson A., Saghir N., Zhyvoloup P., McDonald E., Sheldrake P., Shuttleworth S., Valenti M., Wan N. C., Clarke P. A., Workman P., Mol. Cancer Ther., 2009, 8(7), 1725
[11] Brunner-Kubath C., Shabbir W., Saferding V., Wagner R., Singer C. F., Valent P., Berger W., Marian B., Zielinski C. C., Grusch M., Grunt T. W., Breast Cancer Res. Treat., 2011, 129(2), 387
[12] Nyfeler B., Chen Y., Li X.Y., Pinzon-Ortiz M., Wang Z., Reddy A., Pradhan E., Das R., Lehar J., Schlegel R., Finan P. M., Cao Z. A., Murphy L. O., Huang A., PLoS One, 2012, 7(11), 488
[13] Baumann P., Mandl-Webber S., Oduncu F., Schmidmaier R., Exp. Cell Res., 2009, 315(3), 485
[14] Stauffer F., Maira S. M., Furet P., Bioorg. Med. Chem. Lett., 2008, 18(3), 1027
[15] Maira S. M., Stauffer F., Brueggen J., Furet P., Schnell C., Fritsch C., Brachmann S., Chene P., Pover A. D., Schoemaker K., Fabbro D., Gabrie D., Simonen M., Murphy L., Finan P., Sellers W., Echeverr? C., Mol. Cancer Ther., 2008, 7(7), 1851
[16] Zhang X. M., Wang E. S., Niu S. X., Guo J., Dai Z. L., Zheng N., Du Z. J., Ji Q., Li Q. Y., Liang T., Imidazole Quinoline Derivatives, Pharmaceutical Compositions and Uses Thereof, CN103833752A, 2012
[17] Zhang X. M., Ji Q., Wang L., Gao C. M., Wang E. S., Du Z. J., Gong L. L., Chen B., Imidazole Derivatives, Pharmaceutical Compositions and Uses Thereof, CN104447740A, 2014
[18] Gerster J. F., Lindstrom K. J., Miller R. L., Tomai M. A., Birmachu W., Bomersine S. N., Gibson S. J., Imbertson L. M., Jacobson J. R., Knafla R. T., Maye P. V., Nikolaides N., Oneyemi F. Y., Parkhurst G. J., Pecore S. E., Reiter M. J., Scribner L. S., Testerman T. L., Thompson N. J., Wagner T. L., Weeks C. E., Andre J. D., Lagain D., Bastard Y., Lupu M., J. Med. Chem., 2005, 48(10), 3481
[19] Bellina F., Carpita A., Rossi R., Synthesis, 2004, 15, 2419
[20] Tawada H., Harcourt M., Kawamura N., Masahiro K., Ishikawa E., Sugiyama Y., Ikeda H., Meguro K., J. Med. Chem., 1994, 37(13), 2079
[21] Zhang W. J., Li Z., Zhou M., Wu F., Hou X. Y., Luo H., Liu H., Han X., Yan G. Y., Ding Z. Y., Li R., Bioorg. Med. Chem. Lett., 2014, 24(3), 799
[22] Suneel M. B., Hulawale Y., Paramasivan S., Hariharan S., Process For the Preparation Of Substituted Imidazo[4,5-c]quinoline Compounds, Intermediates and Polymorphs Thereof, WO145369A1, 2015
[23] Li X., Dong Q., Chen Y., Wang B., Bai D. D., Imidazo Quinoline Derivative and Medicinal Salt Thereof, Perparation Method Thereof and Use in Medicine Thereof, WO053273 A1, 2013
[24] Schiaffo C. E., Shi C., Xiong Z. M., Olin M., Ohlfest J. R., Aldrich C. C., Ferguson D. M., J. Med. Chem., 2014, 57(2), 339
[25] Patel P. R., Sun W., Kim M., Huang X. L., Sanderson P. E., Tanaka T. Q., McKew J. C., Simeonov A., Williamson K. C., Zheng W., Huang W. W., Bioorg. Med. Chem. Lett., 2016, 26(12), 2907
[26] Zegzouti H., Zdanovskaia M., Hsiao K., Goueli S. A., Assay and Drug Development Technologies, 2009, 7(6), 560
[27] Seixas J. D., Luengo-Arratta S. A., Diaz R., Saldivia M., Rojas-Barros D. I., Manzano P., Gonzalez S., Berlanga M., Smith T. K., Navarro M., Pollastri M. P., J. Med. Chem., 2014, 57(11), 4834

Synthesis and Biological Activity of Imidazo[4,5-c]quinoline Derivatives as PI3K/mTOR Inhibitors

Synthesis and Biological Activity of Imidazo[4,5-c]quinoline Derivatives as PI3K/mTOR Inhibitors

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 5

编辑推荐

Metrics

本文评价

[1]	WU Yi, SHANG Guanglei, TANG Qi, ZHANG Baozhen, WANG Ensi. Synthesis and Immunosuppressive Activity of Amino Alcohol Containing Coumarin and Benzothiophene[J]. 高等学校化学研究, 2016, 32(3): 357-365.
[2]	LI Yan-chun, LIN Ying-jie, ZHANG Suo-bo, LI Sheng-hai, DUAN Hai-feng. Aryl-guanidine/Pd-catalyzed Suzuki Cross-coupling Reaction at Room Temperature[J]. 高等学校化学研究, 2012, 28(2): 242-244 .
[3]	LIN Li, LI Sheng-hai* and JIANG Ri-hua*. Microwave-assisted Palladium-micelle-catalyzed Suzuki Cross-coupling Reaction in Water[J]. 高等学校化学研究, 2011, 27(4): 589-591.
[4]	LIU Shi-yong. Colloid of Delaminated Layered Double Hydroxides: a Novel Type of LDH-based Catalyst[J]. 高等学校化学研究, 2010, 26(4): 612-616.
[5]	WU Xiang-mei*, WANG Yan and GUO Sheng-rong. 4-Amino-1,2,4-triazole Resin-supported Palladium Complex as Phosphine-free Catalyst for Suzuki Reaction in Aqueous Phase[J]. 高等学校化学研究, 2010, 26(2): 331-334.