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  

Synthesis and Antifungal Activity of 7-Phenyl-6H,7H-1,3,4-thia-diazolo[3,2-a]-thiochromeno[4,3-d]pyrimidine Compounds

作　　者：董金娇 朱昕悦 冯思冉 张超超 刘振明[2] 乔晓强 宋亚丽[1] Dong Jinjiao;Zhu Xinyue;Feng Siran;Zhang Chaochao;Liu Zhenming;Qiao Xiaoqiang;Song Yali(Key Laboratory of Pharmaceutical Quality Control of Hebei Province,College of Pharmaceutical Sciences,Hebei University,Baoding,Hebei 071000;State Key Laboratory of Natural and Biomimetic Drugs,Peking University,Beijing 100191;Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education,Hebei University,Baoding,Hebei 071000)

机构地区：[1]河北大学药学院河北省药物质量分析控制重点实验室,河北保定071000 [2]北京大学天然药物及仿生药物国家重点实验室,北京100191 [3]河北大学药物化学与分子诊断教育部重点实验室,河北保定071000

出　　处：《有机化学》2021年第6期2467-2475,共9页Chinese Journal of Organic Chemistry

基　　金：河北省自然科学基金(No.B2018201269);河北省高等学校科学技术研究(No.ZD2019060);河北省青年拔尖人才、河北大学自然科学多学科交叉研究计划(No.DXK201912);河北大学研究生创新(No.hbu2020ss054)资助项目。

摘　　要：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(^(1)HNMR)、核磁共振碳谱(^(13)C 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4μg·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8μg·mL^(-1).According to the principle of active substructure splicing and bioisosterism,sixteen 7-phenyl-6H,7H-1,3,4-thiadiazolo[3,2-a]-thiochromeno[4,3-d]pyrimidine compounds containing a fused-ring were designed and synthesized.The target compounds were confirmed by ^(1)H NMR,^(13)C 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 5 d was found to be very sensitive(minimum inhibitory concentration(MIC):4μg·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 5 l against Aspergillusnigervan tiegh and Phytophthora infestans was 8μg·mL^(-1).

关 键 词：1 3 4-噻二唑并[3 2-a]-硫色烯并[4 3-d]嘧啶 平板法 抗真菌活性 

分 类 号：TQ450.1[化学工程—农药化工] O626.41[理学—有机化学]