新型2-杂环芳基苯并二氢吡喃-4-酮衍生物的三维定量构效关系研究

为开发新型环境友好杀菌剂，选择了黄烷酮类植物抗毒素为先导，利用生物等排取代原理对其结构进行修饰，设计合成了23个未见文献报道的2-杂环芳基苯并二氢吡喃-4-酮类化合物，并系统测定了所有化合物对水稻稻瘟病抑制活性的IC~5~0值。在此基础上，采用CoMFA方法对它们进行了三维定量结构活性关系研究，系统考查了网格结构、探针以及场类型对CoMFA结果的影响。研究结果表明，苯并二氢吡喃-4-酮苯环5,6,7位上应该引入一些体积较小且具有强供电子能力的取代基有利于提高化合物的杀菌活性。CoMFA分析对7位氧原子和19位氧原子的电性要求与前文采用Hansch-Fujita方法的分析结果是相一致的。

Three dimentional quantitative structure-activity relationships of novel 2-heteroaryl-4-chromanone derivatives

In order to develop novel fungicides, the structure of flavanane phytoalexins was modified in view of bioisosterism and 23 novel title compounds, 2-heteroaryl-4-chromanones, were designed and synthesized, whose structures were confirmed by 1 H NMR, MS and elemental analyses. The fungicidal IC50 in vitro against rice blast disease of the title compounds were measured and the quantitative relationship between the structures and fungicidal activities was established using the comparative molecular field analysis (CoMFA) approach. The results of 3D-QSAR analysis suggested that the introduction of small steric bulk but strong electron-releasing group onto the 5, 6, 7-position of the benzene ring would be favorable to the activity of the compound. The CoMFA analyses about the electronic property requirement of 7-O and 19-O were consistent with those derived from the Hansch-Fujita approach.