2-(l-取代-1H-[1,2,3]-三氮唑-4-甲硫基)-5-甲基苯并噁唑化合物的合成及其抗肿瘤活性研究
Synthesis and Antitumor Activities of 2-(1-Substitute-1H-[1,2,3]-Triazol-4-Methylthio)-5-Methylbenzoxazole
DOI: 10.12677/JOCR.2017.51002, PDF, HTML, XML, 下载: 1,435  浏览: 2,975  科研立项经费支持
作者: 莫 松, 王 帅, 张 刚, 杓学蓓, 李清寒, 杨学军:西南民族大学化学与环境保护工程学院,四川 成都
关键词: 2-氨基-4-甲基苯酚苯并噁唑123-三氮唑有机合成抗肿瘤活性2-Amino-4-Methylphenol Benzoxazole 123-Triazol Organic Synthesis Antitumor Activity
摘要: 以2-氨基-4-甲基苯酚、二硫化碳和3-溴丙炔为原料,经环化、取代、Click反应合成了8个新的2-(l-取代-1H-[1,2,3]-三氮唑-4-甲硫基)-5-甲基苯并噁唑化合物3(a~h)。其结构均经质谱,氢核磁共振和元素分析所确证。经体外抗肿瘤活性测试表明,在20 uM的浓度下,有4个化合物对CDC25B具有较好的抑制活性,其抑制率高达68.18%,IC50可达13.23 ug/mL。
Abstract: Eight new 2-(1-benzyl-1H-[1,2,3]-triazol-4-methylthio)-5-methylbenzoxazole 3(a~h) were synthe-sized with 2-amino-4-methylphenol, methanedithione and 3-bromoprop-1-yne as starting material, followed by cyclo reaction, substitute reaction and Click reaction. Their structures have been determined by elemental analysis, IR, MS and 1H NMR data. The bioactive assay for the newly pre-pared compounds manifested that four compounds exhibited good inhibitory activity against CDC25B in 20 uM (IC50 value up to 13.23 ug/mL).
文章引用:莫松, 王帅, 张刚, 杓学蓓, 李清寒, 杨学军. 2-(l-取代-1H-[1,2,3]-三氮唑-4-甲硫基)-5-甲基苯并噁唑化合物的合成及其抗肿瘤活性研究[J]. 有机化学研究, 2017, 5(1): 8-14. https://doi.org/10.12677/JOCR.2017.51002

参考文献

[1] Zhang, Y., Bao, J., Deng, X.X., He, W., Fan, J.J., Jiang, F.Q. and Fu, L. (2016) Synthesis, Biological Evaluation and Molecular Docking of 2-Phenyl-benzo[d] Oxazole-7-Carboxamide Derivatives as Potential Staphylococcus aureus Sortase A Inhibitors. Bioor-ganic & Medicinal Chemistry Letters, 26, 4081-4085.
[2] 冯志君, 凌烈锋, 金雅嫔. 2-芳基苯并噁唑的合成和生物活性[J]. 皖南医学院学报, 2012, 31(3): 180-182.
[3] 杨庆益. 2-芳基苯并噁唑类VEGFR-2抑制剂的设计, 合成与抗肿瘤活性[D]: [博士学位论文]. 昆明: 云南大学化学系, 2014.
[4] Shakya, A.K., Kaur, A., Al-Najjar, B.O. and Naik, R.R. (2016) Molecular Modeling, Synthesis, Characterization and Pharmacological Evaluation of benzo[d]-oxazole Derivatives as Non-Steroidal Anti-Inflammatory Agents. Saudi Pharmaceutical Journal, 24, 616-624.
[5] Ryu, C.K., Lee, R.Y., Kim, N.Y., Kim, Y.H. and Song, A.L. (2009) Syn-thesis and Antifungal Activity of Benzo[d]oxazole-4,7-diones. Bioorganic & Medicinal Chemistry Letters, 19, 5924-5926.
[6] 唐莉, 班树荣, 林文翰, 李青山. 天然产物4-O-β-D-葡萄糖-苯并噁唑酮及4-取代苯并噁唑酮衍生物的合成与活性研究[J]. 中国药物化学杂志, 2009, 19(1): 31-35.
[7] 李嘉宾, 江振洲, 王涛, 刘明明, 夏俊, 吴斌, 夏霖. 新型α-1受体拮抗剂先导化合物的寻找(I): 5-氯-2-(4-(芳氧烷基)哌嗪-1-基)苯并噁唑类化合物的设计, 合成及生物活性研究[J]. 化学学报, 2008(24): 2725-2729.
[8] Gadakh, A.V., Pandit, C., Rindhe, S.S. and Karale, B.K. (2010) Synthesis and Antimicrobial Activity of Novel Fluorine Containing 4-(substituted-2-hydroxybenzoyl)-1H-pyrazoles and Pyrazolyl Benzo[d]oxazoles. Bioorganic & Medicinal Chemistry Letters, 20, 5572-5576.
[9] Fan, W.Q. and Katritzky, A.R. (1996) 1,2,3-Triazoles. In: Katritzky, A.R., Rees, C.W. and Scriven, E.F., Eds., Comprehensive Heterocyclic Chemistry II, Vol. 4, Elsevier Science, Oxford, 1-2.
[10] 刘进兵, 张春霞, 李秀玲, 林崇懒, 宋化灿. 1-(2-(4-取代)苯氧乙基)-1H-1,2,3-三氮唑衍生物的合成及其抗菌活性研究[J]. 中山大学学报自然科学版, 2008, 47(2): 65-68.
[11] 文逸宁, 袁伟媛, 吴勇巍, 陈雪, 相玉红, 张卓勇, 刘宁宁. 1,2,3-三氮唑类化合物的合成及抗病毒活性[J]. 中国药物化学杂志, 2016, 26(1): 18-23.
[12] Li, Q.H., Ding, Y. and Huang, N.W. (2014) Synthesis and Biological Activities of Dithiocarbamates Containing 1,2,3-triazoles Group. Chinese Chemical Letters, 25, 1469-1472.
[13] Bakunov, S.A., Bakunova, S.M., Wenzler, T., Ghebru, M., Werbovetz, K.A., Reto Brun, R. and Tidwell, R.R. (2010) Synthesis and Antiprotozoal Activity of Cationic 1,4-Diphenyl-1H-1,2,3-triazoles. Journal of Medicinal Chemistry, 53, 254-272.
https://doi.org/10.1021/jm901178d
[14] 李清寒, 李子成, 陈淑华, 蒋宁. 三氮唑核苷及衍生物的设计合成与生物活性研究[J]. 有机化学, 2004, 24(11): 1432-1435.
[15] Zhu, L.L., Xu, X.Q., Shi, J.W., Chen, B.L. and Chen, Z.L. (2016) N2-Selective Iodofunctionalization of Olefins with NH-1,2,3-Triazoles to Provide N2-Alkyl-Substituted1,2,3-triazoles. Journal Organic Chemistry, 81, 3568-3575.
https://doi.org/10.1021/acs.joc.6b00185
[16] 李清寒, 张刚, 丁勇, 陈峰, 张震, 莫松. 新型三氮唑Schiff碱衍生物的合成及抗肿瘤活性研究[J]. 西南民族大学学报(自然科学版), 2014, 40(6): 826- 832.
[17] Ding, Y., Zhang, Z., Zhang, G., Mo, S., Li, Q.H. and Zhao, Z.G. (2016) Green Synthesis and Evaluation of the Antitumor Activity of a Novel Series of 3-[4-bi-(4- fluoro-phenyl)methylpiperazinyl]-4-amino-5-thione-1,2,4-triazole Schiff Bases. Research on Chemical Intermediates, 42, 3105-3116.
https://doi.org/10.1007/s11164-015-2200-5
[18] Baig, R.B.N. and Varma, R.S. (2012) A Highly Active Magnetically Recover-able Nano Ferrite-Glutathione-Copper (Nano-FGT-Cu) Catalyst for Huisgen 1,3-dipolar Cycloadditions. Green Chemistry, 14, 625-632.
https://doi.org/10.1039/c2gc16301b
[19] Angell, Y.L. and Burgess, K. (2007) Peptidomimetics via Copper-Catalyzed Az-ide-Alkyne Cycloadditions. Chemical Society Reviews, 36, 1674-1689.
https://doi.org/10.1039/b701444a