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

Molecules

Rui Yang¹  Qiao Ruan¹  Bing-Yu Zhang¹  Zuo-Lue Zheng¹  Fang Miao²  Le Zhou¹ 

[1] College of Science, Northwest A&F University; Yangling, Shaanxi 712100, China; E-Mails:;College of Life Science, Northwest A&F University; Yangling, Shaanxi 712100, China; E-Mail:

关键词: tetrahydroisoquinoline;    acaricidal activity;    Psoroptes cuniculi;    structure-activity relationship;   

DOI  :  10.3390/molecules19068051

来源: mdpi

【 摘 要 】

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 μg/mL and 50% lethal time value (LT₅₀) of 7.79 h, comparable to the standard drug ivermectin (LC₅₀ = 0.2474 μg/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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.