Creemer Lawrence C, Giampietro Natalie C, Lambert William, Yap Maurice C, deBoer Gerrit J, Adelfinskaya Yelena, Castetter Scott, Wessels Frank J
Dow AgroSciences, Discovery Research, Indianapolis, IN, USA.
Pest Manag Sci. 2017 Apr;73(4):752-760. doi: 10.1002/ps.4358. Epub 2016 Aug 25.
The adrenergic mode of action was investigated for the development of potential new insecticides. Clonidine-related analogs were tested against Myzus persicae (Sulzer) and Bemisia tabaci (Gennadius). Clonidine analogs lack translation owing to a possible vacuole-trapping mechanism. Physical property modulation via a prodrug approach was attempted to overcome this mechanism.
Clonidine showed insecticidal activity against M. persicae and B. tabaci. A prodrug of a known open-chain analog of clonidine was developed. While the prodrug had decreased pK and increased lipophilicity and displayed good activity against M. persicae B. tabaci, the activity did not translate to cotton. Metabolic studies showed that the prodrug was quickly metabolized to the parent compound, and was further metabolized to a known vacuole-trapped oxazoline analog.
Adrenergic active compounds, such as clonidine analogs, show potential as insecticides; however, a designed prodrug approach did not overcome the lack of translation in this case. Studies confirmed that the synthesized prodrug analog metabolized in planta to the proposed vacuole-trapped compound. One possible explanation for the failure of this approach is that the rate of metabolism and vacuole trapping is faster than translaminar flow, and therefore the released pesticide is not biologically available to the target organism. © 2016 Society of Chemical Industry.
研究了肾上腺素能作用模式，以开发潜在的新型杀虫剂。对与可乐定相关的类似物进行了针对桃蚜（Sulzer）和烟粉虱（Gennadius）的测试。由于可能的液泡捕获机制，可乐定类似物缺乏传导性。尝试通过前药方法调节物理性质以克服该机制。
可乐定对桃蚜和烟粉虱表现出杀虫活性。开发了一种已知的可乐定开链类似物的前药。虽然前药的pK值降低，亲脂性增加，并且对桃蚜和烟粉虱表现出良好的活性，但该活性在棉花上并未传导。代谢研究表明，前药迅速代谢为母体化合物，并进一步代谢为一种已知的液泡捕获恶唑啉类似物。
肾上腺素能活性化合物，如可乐定类似物，显示出作为杀虫剂的潜力；然而，在这种情况下，设计的前药方法并未克服缺乏传导性的问题。研究证实，合成的前药类似物在植物体内代谢为所提出的液泡捕获化合物。这种方法失败的一个可能解释是，代谢和液泡捕获的速度比跨层流动快，因此释放的农药对目标生物体没有生物学可用性。©2016化学工业协会。
