{[1‐(Arylmethyl)piperidin‐4‐yl]oxy}‐(trifluoromethyl)‐pyridines: Ketanserin Analogues with Insect Growth Regulating Activity
{[1‐(Arylmethyl)piperidin‐4‐yl]oxy}‐(trifluoromethyl)‐pyridines: Ketanserin Analogues with Insect Growth Regulating Activity
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DOI：
10.1002/cbdv.200890172
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发表时间：
2008-09
影响因子：
2.9
通讯作者：
M. Cai;Zhong Li;Qingchun Huang;G. Song
中科院分区：
文献类型：
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作者：
M. Cai;Zhong Li;Qingchun Huang;G. Song
以哺乳动物5‐HT2A受体拮抗剂酮色胺(1)为骨架，设计合成了一系列{[1‐（芳基甲基）哌啶啶‐4‐基]氧}‐（三氟甲基）吡啶衍生物，并对其构-活性关系进行了讨论。生物测定结果表明，大多数标题化合物抑制了昆虫的生长，对粘虫具有中等到良好的生长调节作用。此外，SAR研究表明，当与哺乳动物5‐HT2A受体相互作用的决定特征被保留时，简化的ArCH2基团对昆虫生长抑制活性有很大贡献。研究还发现，CF3基团在吡啶环上的取代位置发挥了关键作用，并且引入了1‐[双（4‐氟苯基）甲基]哌嗪（相当于酮色林的苯甲酰哌啶部分），产生了与上述化合物相似的生物活性，这与酮色林类似物与哺乳动物5‐HT2受体结合的模型一致。
A series of {[1‐(arylmethyl)piperidin‐4‐yl]oxy}‐(trifluoromethyl)‐pyridine derivatives were designed and synthesized on the basis of the ketanserin (1) framework, a prototypic mammalian 5‐HT2A receptor antagonist, and the structure–activity relationship (SAR) was also discussed. The result of the bioassay showed that most of the title compounds inhibited the insect growth and exhibited moderate‐to‐good growth regulating activity against the armyworm Pseudaletia separata Walker. Furthermore, the SAR study revealed that, when the determinant feature, interacting with mammalian 5‐HT2A receptor, was preserved, a simplified ArCH2 group greatly contributed to insect growth inhibitory activities. It was also found that the substituted position of the CF3 group at the pyridine ring played a key role, and that the introduction of 1‐[bis(4‐fluorophenyl)methyl]piperazine, an equivalent of the benzoylpiperidine moiety of ketanserin, resulted in bioactivities similar to those of the title compounds, which were in agreement with the model of ketanserin analogues binding to mammalian 5‐HT2 receptors.