Abstract：
In order to speculate the three-dimensional structure of the potential binding pocket of the chitin synthase inhibitor, a series of 2,4-diphenyloxazoline derivatives with different lengths of alkyl chains and heteroatoms were designed and synthesized by a homologous strategy. The bioassay results indicate that both the length of the alkyl chains and the type of substituents can affect the acaricidal activity against mite eggs. Compounds containing chloropropyl, alkoxyalkyl, and para-substituted phenoxyalkyl or phenylthioalkyl groups exhibit good activity, while those containing steric hindrance substituents or carbonyl substituents on the benzene ring exhibit reduced activity. Three-dimensional quantitative structure-activity relationship (3D-QSAR) study showed that there may be a narrow hydrophobic region deep in the pocket, and the steric effect plays a more important role than the electrostatic effect. The current work will provide assistance for future molecular design and target binding research.
摘要：
为了推测几丁质合酶抑制剂的潜在结合口袋的三维结构，通过同源策略设计并合成了一系列具有不同长度的烷基链和杂原子的2,4-二苯基恶唑啉衍生物。生物测定结果表明，烷基链的长度和取代基的类型都会影响对螨卵的杀螨活性。含氯丙基的化合物，烷氧基烷基，和对位取代的苯氧基烷基或苯基硫代烷基表现出良好的活性，而在苯环上含有位阻取代基或羰基取代基的化合物则表现出降低的活性。三维定量构效关系(3D-QSAR)研究表明,口袋深处可能存在一个狭窄的疏水区,空间效应比静电效应起更重要的作用。目前的工作将为未来的分子设计和靶标结合研究提供帮助。
