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按文献报道采用立体选择性合成方法,合成了新抗真菌药物——Oxiconazole(奥昔康唑,4a),并对其合成中间体N-(2,4-二氯苯甲酰甲基)咪唑(2)的制备方法进行了改进。为通过结构改造获得抗真菌活性更强的化合物,我们合成了7个咪唑肟醚类衍生物(4b-g,7),其中6个系首次报道。合成产物经元素分析证明结构。体外抑菌试验表明化合物4a-g和7对多数菌株的抗菌活性强于克霉唑,且化合物4c具有抗曲霉菌活性,而Oxiconazole等其它眯唑肟醚类化合物则无此作用。化合物4a的结构经UV、IR、~1H-NMR、MS确证,并首次提供了其粉末X射线衍射图及数据。此化合物已用于临床试验,其对股癣的2周治愈率达94.10％,明显高于益康唑(84.24％,P<0.01)。
The novel antifungal drug Oxiconazole (oxiconazole, 4a) was synthesized by stereoselective synthesis reported in the literature and its synthetic intermediate N- (2,4-dichlorophenacyl) imidazole (2) The preparation method was improved. To obtain compounds with stronger anti-fungal activity through structural transformation, we synthesized 7 derivatives of imidazole oxime ethers (4b-g, 7), of which 6 were reported for the first time. The product was confirmed by elemental analysis. In vitro antibacterial tests showed that the compounds 4a-g and 7 had stronger antibacterial activity than most clotrimazole, and compound 4c had anti-Aspergillus activity, while others such as Oxiconazole did not. The structure of compound 4a was confirmed by UV, IR, ~ 1H-NMR and MS, and the powder X-ray diffraction pattern and data were provided for the first time. The compound has been used in clinical trials. The cure rate of tinea corporis was 94.10% in two weeks, which was significantly higher than that of econazole (84.24%, P <0.01).