Synthesis and biological activity of imidazo[4,5-c]quinoline derivatives as PI3K/mTOR inhibitors

Yanjie Li; Xingmin Zhang; Shengxiu Niu; Yanping Zhao; Lijuan Yang; Xiaowei Shao; Ensi Wang

doi:10.1007/s40242-017-7074-1

Chemical Research in Chinese Universities ›› 2017, Vol. 33 ›› Issue (6) : 895 -902. DOI: 10.1007/s40242-017-7074-1

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Synthesis and biological activity of imidazo[4,5-c]quinoline derivatives as PI3K/mTOR inhibitors

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Abstract

A series of imidazo[4,5-c]quinoline derivatives(12a—12m) was synthesized with 2-amino-5-bromobenzoic 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.

Keywords

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

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Yanjie Li, Xingmin Zhang, Shengxiu Niu, Yanping Zhao, Lijuan Yang, Xiaowei Shao, Ensi Wang. Synthesis and biological activity of imidazo[4,5-c]quinoline derivatives as PI3K/mTOR inhibitors. Chemical Research in Chinese Universities, 2017, 33(6): 895-902 DOI:10.1007/s40242-017-7074-1

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References

Publishing order | Descend order by publishing year | Descend order by cited within

[1]	Kang S., Bader A. G., Vogt P. K. Proc. Natl. Acad. Sci., 2005, 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., Va-lenti 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., Echeverri 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, 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, 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, 2015.

[23]	Li X., Dong Q., Chen Y., Wang B., Bai D. D. Imidazo Quinoline De-rivative and Medicinal Salt Thereof, Perparation Method Thereof and Use in Medicine Thereof, 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.