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2020 , Vol. 40 >Issue 5: 1266 - 1274

DOI: https://doi.org/10.6023/cjoc201908007

研究论文

多取代-5-氨基-3,7-二苯基-7H-噻唑并[3,2-a]嘧啶-6-腈衍生物的合成及生物活性

  • 任璇璇 ,
  • 苑睿 ,
  • 陈雯 ,
  • 周杭 ,
  • 叶菲 ,
  • 师雪荧 ,
  • 胡娟 ,
  • 张鹏 ,
  • 周生亮 ,
  • 宛瑜 ,
  • 吴翚
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  • a 江苏师范大学化学与材料科学学院 江苏徐州 221116;
    b 江苏师范大学江苏省药用植物生物技术重点实验室 江苏徐州 221116;
    c 江苏师范大学生命科学学院 江苏徐州 221116

收稿日期: 2019-08-05

  修回日期: 2019-10-22

  网络出版日期: 2020-02-15

基金资助

江苏省高校优势学科建设工程（三期）、江苏省高校自然科学研究面上项目（No.19KJB430019）、徐州市科技计划项目（No.KC19242）、江苏师范大学博士学位教师科研支持项目（No.17XLR023）和江苏省研究生创新计划（Nos.KYCX18_2111，KYCX18_2116）资助项目.

收起

Synthesis and Biological Evaluation of Polysubstituted 5-Amino-3,7-diphenyl-7H-thiazolo[3,2-a]pyrimidine-6-carbonitriles

  • Ren Xuanxuan ,
  • Yuan Rui ,
  • Chen Wen ,
  • Zhou Hang ,
  • Ye Fei ,
  • Shi Xueying ,
  • Hu Juan ,
  • Zhang Peng ,
  • Zhou Shengliang ,
  • Wan Yu ,
  • Wu Hui
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  • a School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou, Jiangsu 221116;
    b Key Laboratory of Biotechnology for Medicinal Plant of Jiangsu Province, Jiangsu Normal University, Xuzhou, Jiangsu 221116;
    c School of Life Science, Jiangsu Normal University, Xuzhou 221116

Received date: 2019-08-05

  Revised date: 2019-10-22

  Online published: 2020-02-15

Supported by

Project supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions (Third Period), the Natural Science Research Projects in Universities of Jiangsu Provinc(No. 19KJB430019), the Science and Technology Foundation of Xuzhou City (No. KC19242), the Aid Project for Ph.D. Faculties in Jiangsu Normal University (No. 17XLR023) and the Graduate Student Scientific Research Innovation Projects in Jiangsu Province (Nos. KYCX18_2111,KYCX18_2116).

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摘要

以朝格尔碱衍生物（5，12-二甲基-3，10-二苯基-双-1H-吡唑[b，f][4，5]-1，5-二氮杂双环[3.3.1]-2，6-辛二烯，1）为催化剂，以取代的α-溴代苯乙酮、芳香醛、丙二腈和硫脲为原料四组分一锅法合成了一系列噻唑并[3，2-a]嘧啶衍生物.通过1H NMR和化学实验探讨了该反应的机理.体外药理活性实验结果表明，多个产物对人肝癌细胞（HepG2）、人非小细胞肺癌细胞（247）和人非小细胞肺癌细胞（A549）中的一个或多个细胞株具有较高抑制活性，七个产物对耐甲氧西林金黄色葡萄球菌具有抑菌活性.这些结果表明该类化合物在新药开发中具有巨大潜力.

关键词： Tröger碱衍生物; 催化; 噻唑并[3,2-a]嘧啶衍生物; 抗肿瘤; 抑菌

本文引用格式

任璇璇 , 苑睿 , 陈雯 , 周杭 , 叶菲 , 师雪荧 , 胡娟 , 张鹏 , 周生亮 , 宛瑜 , 吴翚 . 多取代-5-氨基-3,7-二苯基-7H-噻唑并[3,2-a]嘧啶-6-腈衍生物的合成及生物活性[J]. 有机化学, 2020 , 40(5) : 1266 -1274 . DOI: 10.6023/cjoc201908007

Abstract

A series of thiazolo[3,2-a]pyrimidine derivatives were synthesized from the reaction of α-bromoacetophenone, aromatic aldehyde, malononitrile and thiourea which was catalyzed by Tröger's base derivative 5,12-dimethyl-3,10-diphenyl- bis-1H-pyrazol[b,f] [4,5]-1,5- diazadicyclo[3.3.1]-2,6-octadiene (1). The reaction mechanism was discussed by the 1H NMR analysis and chemical experiments. The pharmacological activity results of the products indicated that most of products showed high inhibitory on one or more cancer cells in human hepatocarcinoma cell (HepG2), human non-small cell lung cancer cell (247) and human non-small cell lung cancer cell (A549) in vitro. And seven products have antibacterial activity against the methicillin-resistant Staphylococcus aureus. These results showed the great potential of these compounds in drug development.

Key words： Tröger's base derivative; catalysis; thiazolo[3,2-a]pyrimidine derivative; anti-tumor; anti-bacterial

参考文献

[1] Galm, U.; Wendt-Pienkowski, E.; Wang, L.; Huang, S.-X.; Unsin, C.; Tao, M.; Coughlin, J. M.; Shen, B. J. Nat. Prod. 2011, 74, 526.
[2] (a) Pan, B.; Huang, R.; Zheng, L.; Chen, C.; Han, S.; Qu, D.; Zhu, M.; Wei, P. Eur. J. Med. Chem. 2011, 46, 819.
(b) Samvel, N. S.; Domenico, S.; Athina, G.; Viktor, A. K.; Elmira, K. H.; Anush, A. H. Curr. Org. Chem. 2018, 22, 2576.
[3] (a) Zhang, L.; Lin, Y.; Wang, J.; Zhu, X.-L.; Yao, Q.-L.; Yao, Q. Z. Chin. J. Org. Chem. 2015, 35, 497(in Chinese). (张磊, 林娅, 王京, 朱心玲, 姚秋丽, 姚其正, 有机化学, 2015, 35, 497.)
(b) Li, J.; Zhang, S.-T.; Meng, L.-H.; Li, F.; Wu, P.; Deng, S.-N.; Jia, Y. H. Chem. World 2016, 57, 493(in Chinese). (李江, 张诗缇, 孟利红, 李放, 吴鹏, 邓赛男, 贾云宏, 化学世界, 2016, 57. 493.)
(c) Behalo, M. S. J. Heterocycl. Chem. 2018, 55, 1391.
[4] Maddila, S.; Damu, G. L. V.; Oseghe, E. O.; Abafe, O. A.; Rao, C. V.; Lavanya, P. J. Korean Chem. Soc. 2012, 56, 334.
[5] (a) Hu, J.; Wang, Y.; Wei, X.-Y.; Wu, X.-X.; Chen, G.-Z.; Cao, G.-Z.; Shen, X.-Q.; Zhang, X.-H.; Tang, Q.-Q.; Liang, G.; Li, X.-K. Eur. J. Med. Chem. 2013, 64, 292.
(b) Afradi, M.; Foroughifar, N.; Pasdar, H.; Moghanian, H.; Foroughifar, N. Appl. Org. Chem. 2017, 31, 3683.
[6] Mohamed, S. F.; Flefel, E. M.; Amr, A. E.-G. E.; El-Shafy, D. N. A. Eur. J. Med. Chem. 2010, 45, 1494.
[7] (a) El-Messery, S. M.; Hassan, G. S.; Al-Omary, F. A. M.; Ei-Sub-bagh, H. I. Eur. J. Med. Chem. 2012, 54, 615.
(b) Abd Elhameed, A. A.; El-Gohary, N. S.; El-Bendary, E. R.; Shaaban, M. I.; Bayomi, S. M. Bioorg. Chem. 2018, 81, 299.
[8] Adib, M.; Nosrati, M.; Mahdavi, M.; Zhu, L. G.; Mirzaei, P. Synlett 2007, 2703.
[9] Jia, Y.-H.; Wang, C.-H.; Cai, D. Chemistry 2014, 77, 174.
[10] Wang, D.-L.; Wang, D.; Yan, L.; Pan, G.-Y.; Yang, J.-N. Chin. Chem. Lett. 2016, 27, 953.
[11] Al-Omary, F A M.; Hassan, G S.; El-Messery, S M.; El-Subbagh, H I. Eur. J. Med. Chem. 2012, 47, 65.
[12] Yuan, R.; Wang, Y.-J.; Fang, Y.; Ge, W.-H.; Lin, W.; Li, M.-Q.; Xu, J.-B.; Wan, Y.; Liu Y.; Wu, H. Chem. Eng. J. 2017, 316, 1026.
[13] Paul, A.; Maji, B.; Misra, S. K.; Jain, A. K.; Muniyappa, K.; Bhattacharya, S. J. Med. Chem. 2012, 55, 7460.
[14] Kejik, Z.; Briza, T.; Havlik, M.; Dolensky, B.; Kaplanek, R.; Kralova, J.; Mikula, I.; Martasek, P.; Kral, V. Dyes Pigm. 2016, 134, 212.
[15] (a) Ishiwari, F.; Takeuchi, N.; Sato, T.; Yamazaki, H.; Osuga, R.; Kondo, J. N.; Fukushima, T. ACS Macro Lett. 2017, 6, 775.
(b) Xiao, Y.; Zhang, L.; Xu, L.; Chung, T.-S. J. Membr. Sci. 2017, 521, 65.
(c) Zou, X.; Zhu, G. Adv. Mater. 2018, 30.
[16] (a) Sergeyev, S.; Didier, D.; Boitsov, V.; Teshome, A.; Asselberghs, I.; Clays, K.; Velde, C. M. L. V.; Plaquet, A.; Champagne, B. Chem.-Eur. J. 2010, 16, 8181.
(b) Xi, H.; Liu, Y.; Yuan, C.-X.; Li, Y.-X.; Wang, L.; Tao, X.-T.; Ma, X.-H.; Zhang, C.-F.; Hao, Y. RSC Adv. 2015, 5, 45668.
[17] (a) Elmes, R. B. P.; Erby, M.; Bright, S. A.; Williams, D. C.; Gunnlaugsson, T. Chem. Commun. 2012, 48, 2588.
(b) Wu, Z.; Tang, M.; Tian, T.; Wu, J.; Deng, Y.; Dong, X.; Tan, Z.; Weng, X.; Liu, Z.; Wang, C.; Zhou, X. Talanta 2011, 87, 216.
(c) Calatrava-Pérez, E.; Delente, J. M.; Shanmugaraju, S.; Hawes, C. S.; Williams, C. D.; Gunnlaugsson, T.; Scanlan, E. M. Org. Bio-mol. Chem. 2019, 17, 2116.
[18] Yuan, R.; Li, M.-Q.; Xu, J.-B.; Huang, S.-Y.; Zhou, S.-L.; Zhang, P.; Liu, J.-J.; Wu, H. Tetrahedron 2016, 72, 4081.
[19] (a) Cabrero-Antonino, J. R.; García, T.; Rubio-Marqués, P.; Vidal-Moya, J. A.; Leyva-Pérez, A.; Al-Deyab, S. S.; Al-Resayes, S. I.; Díaz, U.; Corma, A. ACS Catal. 2011, 1, 147.
(b) Pereira, R.; Cvengroš, J. Eur. J. Org. Chem. 2013, 2013, 4233.
(c) Wu, H.; Chen, X.-M.; Wan, Y.; Ye, L.; Xin, H.-M.; Xu, H.-H.; Yue, C.-H.; Pang, L.-L.; Ma, R.; Shi, D.-Q. Tetrahedron Lett. 2009, 50, 1062.
(d) Youssef, A. M. S.; Fouda, A. M.; Faty, R. M. Chem. Cent. J. 2018, 12, 50.
[20] (a) Yuan, R.; Ren, X. X.; Zhang, P.; Chen, W.; Zhou, H.; Wan, Y.; Wu, H. CN 110013483, 2019.
(b) Wan, Y.; Ren, X. X.; Zhang, P.; Yuan, R.; Chen, W.; Zhou, H.; Wu, H. CN 110041348, 2019.
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