title: A class of promising acaricidal tetrahydroisoquinoline derivatives: synthesis, biological evaluation and structure-activity relationships.
abstract: 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.
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China. yrer01018@126.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China. qiaoruanchem@gmail.com.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Ruan
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China. bingyuzhang607@gmail.com.
authors.forename: Bing-Yu
authors.initials: BY
authors.lastname: Zhang
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China. zhengzuolue@gmail.com.
authors.forename: Zuo-Lue
authors.initials: ZL
authors.lastname: Zheng
authors.affiliation: College of Life Science, Northwest A&F University, Yangling, Shaanxi 712100, China. miaofangmf@163.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Miao
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China. zhoulechem@nwsuaf.edu.cn.
authors.forename: Le
authors.initials: L
authors.lastname: Zhou
authors.affiliation: College of Science, Northwest A&F University, Yangling, Shaanxi 712100, China. genghuiling5@163.com.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Geng
mesh_terms: D056810:Acaricides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D009682:Magnetic Resonance Spectroscopy; D040042:Psoroptidae / Q000187:drug effects*; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D056810:Acaricides; D044005:Tetrahydroisoquinolines