Molecular Mechanism of Target Recognition by Insect Growth Regulators

(1)基于萜类昆虫保幼激素（JH）模拟物的定量构效关系（QSAR）分析，合成了一类具有保幼激素活性的非萜类化合物4-苯氧基苯氧基和4-苄基苯氧基乙醛肟O-醚。进一步通过改变分子的醛肟部分，我们发现4-苯氧基苯氧基丙醛肟O-醚型化合物是高活性的。定量结构活性分析表明，该系列化合物的分子尺寸或形状的分子是高JH活性的重要因素，连同位置特定的电子或疏水性质。(2)制备了一组其中醇和酸性部分被修饰的拟除虫菊酯类似物。测定每种化合物对美洲大蠊的抑制活性和离体神经制备物中的神经生理活性。这些活动的变化被证明主要是由空间尺寸和疏水性的分子组分。它们的杀虫活性与神经活性有很好的相关性。电压钳研究表明，化合物大大增加钠电流。因此，它们的杀虫作用是由于昆虫神经传导系统的损伤，这是由钠通道的调节引起的。(3)合成了一系列具有杀虫活性的苯甲酰氨基噻二唑类化合物，并对其构效关系进行了研究.通过在苯的帕拉引入吸电子取代基，发现其对蚊虫（库蚊）和水稻二化螟（二化螟）幼虫的活性有所提高。此外，与结构类似的杀虫剂苯甲酰基苯基脲的结构-活性谱的比较表明，这两个系列化合物对活性的疏水和/或空间效应不同。

(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.