烯丙胺和苄胺类抗真菌药物比较分子力场分析(CoMFA)的研究  

COMPARATIVE MOLECULAR FIELD ANALYSIS(CoMFA) OF ALLYLAMINE AND BENZYLAMINE ANTIMYCOTICS

作　　者：季海涛[1] 张万年[1] 周有骏[1] 吕加国[1] 朱驹[1] 李科[1] 陈卫平[1] 刘宁[1] 

机构地区：[1]第二军医大学药学院

出　　处：《药学学报》1998年第3期188-193,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金

摘　　要：本实验采用“活性类似物法”搜寻到烯丙胺和苄胺类抗真菌化合物的药效构象。其与药物萘替芬、特比萘芬的晶体构象相同。以此构象构建各化合物，采用ｒｍｓｆｉｔ规则叠合各分子，进行ＣｏＭＦＡ研究，得到预测能力很强的抗６种常见致病真菌的３ＤＱＳＡＲ模型。并用８个本实验室设计合成的新化合物和５个文献报道的化合物对模型预测能力进行验证。最后结合２ＤＱＳＡＲ方程首次提出了烯丙胺、苄胺类抗真菌化合物与受体蛋白相互作用模式图。“Active analog approach” has been employed to search the pharmacophoric conformation of the allylamine and benzylamine antimycotics. A local mimimum energy conformation, which is very similar to the crystallgraphically determined coordinate of naftifine or terbinafine, has been applied to build all compounds. Comparative molecular field analysis (CoMFA) has been used to examine the correlations between the activities against 6 common human pathogenic fungi and the physicochemical properties of 62 allylamine and benzylamine compounds which had been aligned by rms fit rule. The predictive abilities of the resulting 3DQSAR models have been tested by 8 new synthetic compounds and 5 reported compounds. Finally, we propose an interaction pattern between allylamine, benzylamine antimycotics and the active site of pseudoreceptor based on the results of 2DQSAR and 3DQSAR.

关 键 词：烯丙胺类 抗真菌化合物 苄胺类 比较分子力场 

分 类 号：R978.5[医药卫生—药品]