Molecular Mechanism of Target Recognition by Insect Growth Regulators

(1)基于萜类昆虫幼虫激素（JH）模拟物的定量构效关系分析，开发了一类具有JH活性的非萜类化合物- 4-phenoxyphenoxy-和4- benzylphenoxyacetaldoximo -醚。进一步通过改变分子的醛肟部分，我们发现4- phenoxyphenoxypropionaldoximo -ether型化合物具有高活性。该系列化合物的定量结构活性分析表明，分子尺寸或分子形状以及位置特定的电子或疏水性是高JH活性的重要因素。(2)制备了一组拟除虫菊酯类似物，其中醇段和酸段进行了改性。测定了各化合物对美洲蜚蠊的杀虫活性和切除神经制剂的神经生理活性。这些活性的变化主要是由分子组分的空间尺寸和疏水性决定的。它们的杀虫活性与神经活性密切相关。电压箝位研究表明，这些化合物大大增加了钠电流。因此，它们的杀虫作用可能是由于钠离子通道的调节导致了昆虫神经传导系统的损伤。(3)制备了一系列杀虫苯甲酰氨基噻二唑，考察了它们的构效关系。在末端苯的对位上引入一个吸电子取代基，可提高其对蚊子（库蚊）和水稻螟虫（螟）的活性。此外，与结构类似的苯甲酰苯基脲类杀虫剂的结构-活性谱比较表明，两类化合物的疏水性和/或位阻效应对活性的影响是不同的。

(1) Based on the quantitative structure-activity relationship analysis of the terpenoid insect juvenile hormone (JH) mimics, a non-terpenoid class of JH-active compounds, 4-phenoxyphenoxy- and 4-benzylphenoxyacetaldoxime O-ether was developed. Further by alteration of the aldoxime moiety of the molecule, we found 4-phenoxyphenoxypropionaldoxime O-ether type of compounds to be highly active. Quantitative structure-activity analyses of the series of the compounds showed that the molecular dimensions or shape of the molecules are important factors for high JH activity, together with a position specific electronic or hydrophobic property.(2) A set of pyrethroid analogs where the alcohol and acidic moiety were modified was prepared. Insecticidal activity against the American cockroach and neurophysiological activity in excised nerve preparations were determined for each compound. Variations in these activities were shown to be mostly determined by steric dimensions and hydrophobicity of the molecular components. Their insecticidal activity was nicely correlated with the nerve activity. Voltage clamp studies revealed that the compounds greatly increase the sodium current. Thus, their insecticidal effect was concluded to de due to lesion in the nerve conduction system in insects, which was brought about by modulation of the sodium channels.(3) A series of insecticidal benzoylaminothiadiazoles was prepared to examine their structure- activity relationships. The activity against mosquito (Culex pipiens) and rice stem borer (Chilo suppressalis) larvae was found to be risen by introducing an electron-withdrawing substituent into the para position of the terminal benzene. Furthermore, a comparison of the structure-activity profile with that of the structurally analogus insecticides, benzoyl-phenylureas, revealed that the hydrophobic and/or steric effects on activity are different between the two series of compounds.