7-苯基-6H,7H-1,3,4-噻二唑并[3,2-a]-硫色烯并[4,3-d]嘧啶类化合物的合成及抗真菌活性研究
收稿日期: 2021-01-31
修回日期: 2021-02-20
网络出版日期: 2021-03-09
基金资助
河北省自然科学基金(B2018201269); 河北省高等学校科学技术研究(ZD2019060); 河北大学自然科学多学科交叉研究计划(DXK201912); 河北大学研究生创新(hbu2020ss054)
Synthesis and Antifungal Activity of 7-Phenyl-6H,7H-1,3,4-thia- diazolo[3,2-a]-thiochromeno[4,3-d]pyrimidine Compounds
Received date: 2021-01-31
Revised date: 2021-02-20
Online published: 2021-03-09
Supported by
Natural Science Foundation of Hebei Province(B2018201269); Science and Technology Project of Hebei Education Department(ZD2019060); Young Talent of Hebei Province, the Natural Science Interdisciplinary Research Program of Hebei University(DXK201912); Post-Graduate Innovation Fund Project of Hebei University(hbu2020ss054)
利用生物电子等排原理和生物活性基团拼接原理, 设计合成了16个7-苯基-6H,7H-1,3,4-噻二唑并[3,2-a]-硫色烯并[4,3-d]嘧啶类化合物. 目标化合物均经核磁共振氢谱(1H NMR)、核磁共振碳谱(13C NMR)和高分辨质谱仪(HRMS)进行了结构确证. 体外抗真菌活性结果表明, 对于动物病原菌, 化合物对总状毛霉、絮状表皮癣菌、红色毛癣菌和须癣毛癣菌等浅部真菌均有较好的抑制活性, 其中化合物5d对红色毛癣菌的最小抑菌浓度为4 μg•mL –1, 而对新生隐球菌、白念球菌、烟曲霉等深部真菌的抑制活性较差; 化合物对5种植物病原菌均有一定程度的抑制作用, 化合物5l对花生冠腐病菌和马铃薯晚疫病菌的抑菌活性最好, 最小抑菌浓度为8 μg•mL –1.
董金娇 , 朱昕悦 , 冯思冉 , 张超超 , 刘振明 , 乔晓强 , 宋亚丽 . 7-苯基-6H,7H-1,3,4-噻二唑并[3,2-a]-硫色烯并[4,3-d]嘧啶类化合物的合成及抗真菌活性研究[J]. 有机化学, 2021 , 41(6) : 2467 -2475 . DOI: 10.6023/cjoc202101056
According to the principle of active substructure splicing and bioisosterism, sixteen 7-phenyl-6H,7H-1,3,4-thiadia- zolo[3,2-a]-thiochromeno[4,3-d]pyrimidine compounds containing a fused-ring were designed and synthesized. The target compounds were confirmed by1H NMR, 13C NMR and HRMS. The preliminary antifungal activity assay showed that these compounds exhibited a good antifungal activity in vitro on superficial fungi, such as Mucor racemosus,Epidermophyton floccosum,Trichophyton rubrum and Trichophyton mentagrophytes, compound 5d was found to be very sensitive (minimum inhibitory concentration (MIC): 4 μg•mL –1) to Trichophyton rubrum. While on invasive fungi, such as Cryptococcus neoformans, Candida albicans and Aspergillus fumigatus, they exhibited lower activity than that of superficial fungi. They exhibited significant inhibition activity against five plant pathogens. MIC value of compound 5l against Aspergillusnigervan tiegh and Phytophthora infestans was 8 μg•mL –1.
| [1] | Guo, D.; Liu, Y.; Li, T.; Wang, N.; Zhai, X.; Hu, C.; Gong, P. Sci. China Chem. 2012, 55,347. |
| [2] | Marini, A. M.; Maresca, A.; Aggarwal, M.; Orlandini, E.; Nencetti, S.; Da Settimo, F.; Salerno, S.; Simorini, F.; La Motta, C.; Taliani, S.; Nuti, E.; Scozzafava, A.; McKenna, R.; Rossello, A.; Supuran, C. T. J. Med. Chem. 2012, 55,9619. |
| [3] | Song, J.; Jones, L. M.; Chavarria, G. E.; Charlton-Sevcik, A. K.; Jantz, A.; Johansen, A.; Bayeh, L.; Soeung, V.; Snyder, L. K.; Lade, S. D., Jr.; Chaplin, D. J.; Trawick, M. L.; Pinney, K. G. Bioorg. Med. Chem. Lett. 2013, 23,2801. |
| [4] | Wei, P.; Liu, J. J.; Ma, J. J.; Yang, G. L. Mod. Appl. Sci. 2010, 4,136. |
| [5] | Liu, Y.; Luo, W.; Sun, L.; Guo, G. Drug Discoveries Ther. 2008, 2,216. |
| [6] | Suresh, L.; Sagar Vijay Kumar, P.; Poornachandra, Y.; Ganesh Kumar, C.; Babu, N. J.; Chandramouli, G. V. P. Bioorg. Med. Chem. 2016, 24,3808. |
| [7] | Suresh, L.; Sagar Vijay Kumar, P.; Poornachandra, Y.; Ganesh Kumar, C.; Chandramouli, G. V. Bioorg. Chem. 2016, 68,159. |
| [8] | Song, Y.-L.; Yang, T.; Dong, Y.-F.; Wu, F.; Yang, G.-L. Chem. Lett. 2014, 43,134. |
| [9] | Song, Y.-L.; Liu, X.-M.; Yang, N.; Yang, G.-L. Asian J. Chem. 2013, 25,1849. |
| [10] | Wang, D.-J.; Hou, Z.; Xu, H.; An, R.; Su, X.; Guo, C. Bioorg. Med. Chem. Lett. 2018, 28,3574. |
| [11] | Ahmad, S.; Abbas, R.; Soheila, N. Bioorg. Med. Chem. Lett. 2005, 15,5553. |
| [12] | Azab, M. E.; Abdel-Wahab, S. S.; Mahmoud, N. F.; Elsayed, G. A. J. Heterocycl. Chem. 2018, 55,2349. |
| [13] | Dake, S. A.; Tekale, S. U.; Sarda, S. R.; Jadhav, W. N.; Bhusare, S. R.; Pawar, R. P. ARKIVOC 2008, 17,241. |
| [14] | Yang, N.; Hao, L.; Lu, Y. Chem. Reagents 2012, 34,1139(in Chinese). |
| [14] | ( 杨娜, 郝琳, 蒋洪, 鲁源, 化学试剂, 2012, 34,1139.) |
| [15] | He, W.-J.; Liu, D.-R.; Gan, X.-H.; Zhang, J.; Liu, Z.-J.; Yi, C.-F.; Song, B.-A. Chin. J. Org. Chem. 2019, 39,2287(in Chinese). |
| [15] | ( 何文静, 刘登日, 甘秀海, 张建, 刘峥军, 易崇粉, 宋宝安, 有机化学, 2019, 39,2287.) |
| [16] | Kukaniev, M. A.; Salimov, T. M.; Murvatulloeva, M. S.; Imatshoey, I. K. Pharm. Chem. J. 2006, 40,421. |
| [17] | Maddila, S.; Gorle, S.; Seshadri, N.; Lavanya, P.; Jonnalagadda, S. B. Arabian J. Chem. 2016, 9,681. |
| [18] | Wang, S.; Yuan, X.-H.; Wang, S.-Q.; Zhao, W.; Chen, X.-B.; Yu, B. Eur. J. Med. Chem. 2021. |
| [19] | Zarenezhad, E.; Farjam, M.; Iraji, A. J. Mol. Struct. 2021, 1230 129833. |
| [20] | Han, X.-Y.; Li, S.-B.; Liang, G.-C.; Song, Y.-L. Acta Pharm. Sin. 2017, 52,113(in Chinese). |
| [20] | ( 韩晓燕, 李生彬, 梁国超, 宋亚丽, 药学学报, 2017, 52,113.) |
| [21] | Liang, G.-C.; Zhou, G.; Zhong, Y.-F.; Han, X.-Y.; Song, Y.-L. Chin. J. Synth. Chem. 2015, 23,1100(in Chinese). |
| [21] | ( 梁国超, 周冠, 钟一凡, 韩晓燕, 宋亚丽, 合成化学, 2015, 23,1100.) |
| [22] | Qi, P.; Jin, Y.-H.; Gou, C.; Fang, L. Chin. J. New Drugs 2004, 13,141(in Chinese). |
| [22] | ( 齐平, 靳颖华, 郭春, 方林, 中国新药杂志, 2004, 13,141.) |
| [23] | Le, C.-G.; Ding, J.-H.; Yang, S.-J. Chem. World 2002, 43,366(in Chinese). |
| [23] | ( 乐长高, 丁健桦, 杨思金, 化学世界, 2002, 43,366.) |
| [24] | Sun, X.-Y.; Feng, J.-J.; Li, S.-B.; Feng, S.-R.; Liu, Z.-M.; Song, Y.-L. Chin. J. Org. Chem. 2019, 39,1037(in Chinese). |
| [24] | ( 孙晓阳, 冯佳佳, 李生彬, 冯思冉, 刘振明, 宋亚丽, 有机化学, 2019, 39,1037.) |
| [25] | Xiao, L.-W.; Li, H.-Z. Chin. J. Org. Chem. 2006, 26,979(in Chinese). |
| [25] | ( 肖立伟, 李慧章, 有机化学, 2006, 26,979.) |
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| 〈 |
|
〉 |
