A Class of Promising Acaricidal Tetrahydroisoquinoline Derivatives: Synthesis, Biological Evaluation and Structure-Activity Relationships

作者：Yang, Rui; Ruan, Qiao; Zhang, Bing-Yu; Zheng, Zuo-Lue; Miao, Fang; Zhou, Le^*; Geng, Hui-Ling

来源：Molecules, 2014, 19(6): 8051-8066.

DOI：10.3390/molecules19068051

• tetrahydroisoquinoline
• acaricidal activity
• Psoroptes cuniculi
• structure-activity relationship

As part of our continuing research on isoquinoline acaricidal drugs, this paper reports the preparation of a series of the 2-aryl-1-cyano-1,2,3,4-tetrahydroisoquinolines with various substituents on the N-phenyl ring, their in vitro acaricidal activities against Psoroptes cuniculi, a mange mite, and discusses their SAR as well. The structures of all compounds, including 12 new ones, were elucidated by analysis of UV, IR, NMR, ESI-MS, HR-MS spectra and X-ray diffraction experiments. All target compounds showed varying degrees of activity at 0.4 mg/mL. Compound 1 showed the strongest activity, with a 50% lethal concentration value (LC50) of 0.2421 mu g/mL and 50% lethal time value (LT50) of 7.79 h, comparable to the standard drug ivermectin (LC50 = 0.2474 g/mL; LT50 = 20.9 h). The SAR showed that the substitution pattern on the N-aromatic ring exerted a significant effect on the activity. The substituents 2'-F, 3'-F, 2'-Cl, 2'-Br and 2'-CF3 remarkably enhanced the activity. Generally, for the isomers with the same substituents at different positions, the order of the activity was ortho > meta > para. It was concluded that the target compounds represent a class of novel promising candidates or lead compounds for the development of new tetrahydroisoquinoline acaricidal agents.

• 出版日期2014-6
• 单位西北农林科技大学