2-芳基-2,3-二氢-4H-1,3-苯并噻嗪-4-酮类化合物的设计、合成及抗真菌活性

Design,synthesis and antifungal activity of 2-aryl-2,3-dihydro-4H-1,3-benzothiazin-4-one derivatives

目的设计并合成2-芳基-2,3-二氢-4H-1,3-苯并噻嗪-4-酮类化合物,测定体外抗真菌活性、建立初步构效关系。方法以邻氨基苯甲酸为起始原料,经过重氮化及硫代反应制得二硫代水杨酸,再经过氯代、氨解、缩合等步骤制得目标化合物。采用2倍浓度稀释法,选用8种临床上常见的致病真菌为测试菌株,以氟康唑和伊曲康唑为阳性对照药,测试了目标化合物的体外抗真菌活性。结果与结论设计并合成了24个2-芳基-2,3-二氢-4H-1,3-苯并噻嗪-4-酮类化合物,目标化合物的结构经1H-NMR、MS确证;活性测试结果表明,目标化合物对测试真菌表现出不同程度的体外抑菌活性,所有化合物对红色毛藓菌和根霉菌的活性均好于阳性对照药。

Objective To study the design, synthesis and antifungal activity of 2-aryl-2,3-dihydro-4H-1,3- benzothiazin-4-one derivatives and establish their preliminary SAR. Methods The target compounds were synthesized from anthranilic acid through diazotization, thionation reaction followed by chloronation, ammonolysis and condensation. The antifungal assay against eight isolates of fungi was carded out in vitro by two-fold dilution method, took fluoconazole and itroconazole as the control drugs. Results and Conclusions Twenty-four compounds were synthesized and characterized by 1H-NMR, ES-MS. Preliminary pharmacological results showed that all compounds displayed antifungal activities against the tested fungi in differen.t levels, and exhibited better activity than that of control drugs against T. rubrum and Rhizopus.