摘要
目的 设计、合成三唑类抗真菌新化合物并进行活性筛选。方法 分别以咪康唑和伊曲康唑为先导化合物 ,根据相关构效关系进行设计并合成 ;采用纸片琼脂扩散法和 96孔微量稀释法测定各新化合物的体外抑菌活性。结果 合成了 12个 1 三唑基 2 氟代苯基 3 取代氨基 2 丙醇类新化合物 (M )和 13个 2 取代苯基 5 三唑甲基 5 氟代苯基 N 取代恶唑烷类新化合物 (A) ,用MS ,1 HNMR确证结构。大多数目标化合物对白色念珠菌有一定抑制活性 ,其中A10 ,A12 ,A13的活性强于对照品氟康唑和伊曲康唑 ,且对酵母菌亦显示一定抑制作用。结论 化合物A10 ,A12 ,A13值得进一步研究。
Aim Design, synthesis and activity study of novel antifungal triazoles. Methods The structures of two lead-compounds miconazole and itrconazole were modified on the basis of SAR studied by our group and reported in the literature and their antifungal activities in vitro were tested by standard program. Results Twelve 1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-substituted amino-2-propanol compounds and thirteen 2-substituted phenyl-5-(1H-1,2,4-triazole-1-methyl) 5-(2,4-difluorophenyl)-N-substituted oxazolidine compounds were synthesized and confirmed by 1HNMR and MS. In vitro inhibitory tests showed that most of them have more or less inhibitory effects on C.albicans and some inhibit S.cerevisiae also. Especially the effects of A10, A12 and A13 on C.albicans were more potent than (or equal to) that of fluconazole or itraconazole. Conclusion Compounds A10, A12 and A13 are worthy to be intensively studied.
出处
《药学学报》
CAS
CSCD
北大核心
2004年第11期904-909,共6页
Acta Pharmaceutica Sinica
关键词
三唑
氟代苯基
取代丙醇
取代恶唑烷
抗真菌
合成
活性
triazole
difluorophenyl
substituted propanol
substituted oxazolidine
antifungi
synthesis
activity
