Zou Xia-Juan, Lai Lu-Hua, Jin Gui-Yu, Zhang Zu-Xing
State Key Laboratory for Structural Chemistry Studies of Stable and Unstable Species, Institute of Physical Chemistry, College of Chemistry and Molecular Engineering, Peking University, Beijing, P. R. China, 100871.
J Agric Food Chem. 2002 Jun 19;50(13):3757-60. doi: 10.1021/jf0201677.
A series of novel 5-[1-aryl-1,4-dihydro-6-methylpyridazin-4-one-3-yl] -2-arylamino-1,3,4-oxadiazoles, fungicidally active, were synthesized based on bioisosterism and tested in vivo against wheat leaf rust, Puccinia recondita. These compounds were shown to be fungicidally active, and their activity was influenced by the nature of the substituents. By using the three-dimensional quantitative structure-activity relationships (3D-QSAR) method of comparative molecular field analysis (CoMFA), we have studied the structure and activity relationship of the compounds containing both pyridazinone-substituted 1,3,4-thiadiazoles and pyridazinone-substituted 1,3,4-oxadiazoles. The 3D-QSAR modes gave good correlation between the variations on percent inhibition and the steric-electrostatic properties. The results are consistent with a common mode of action for the pyridazinone-substituted 1,3,4-thiadiazoles and the pyridazinone-substituted 1,3,4-oxadiazoles, which further confirms that the 1,3,4-oxadiazole ring is a bioisosteric analogue of the 1,3,4-thiadiazole ring. These offer important structural insights into designing highly active compounds prior to their synthesis.
基于生物电子等排原理合成了一系列具有杀真菌活性的新型5-[1-芳基-1,4-二氢-6-甲基哒嗪-4-酮-3-基]-2-芳基氨基-1,3,4-恶二唑，并对其进行了小麦叶锈病（隐匿柄锈菌）的体内测试。结果表明这些化合物具有杀真菌活性，且其活性受取代基性质的影响。通过使用比较分子场分析（CoMFA）的三维定量构效关系（3D-QSAR）方法，我们研究了含有哒嗪酮取代的1,3,4-噻二唑和哒嗪酮取代的1,3,4-恶二唑的化合物的结构与活性关系。3D-QSAR模型在抑制率变化与空间静电性质之间给出了良好的相关性。结果与哒嗪酮取代的1,3,4-噻二唑和哒嗪酮取代的1,3,4-恶二唑的共同作用模式一致，这进一步证实了1,3,4-恶二唑环是1,3,4-噻二唑环的生物电子等排类似物。这些为在合成前设计高活性化合物提供了重要的结构见解。
