Synthesis and insecticidal evaluation of novel N-pyridylpyrazolecarboxamides containing cyano substituent in the ortho-position

• Published in: Bioorganic & medicinal chemistry letters Vol. 23; no. 1; pp. 42 - 46
• Main Authors: Mao, Mingzhen, Li, Yuxin, Liu, Qiaoxia, Zhou, Yunyun, Zhang, Xiulan, Xiong, Lixia, Li, Yongqiang, Li, Zhengming
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.01.2013; Elsevier
• Subjects: Amides - chemical synthesis; Amides - chemistry; Amides - pharmacology; Animals; calcium; Calcium - metabolism; Calcium channel; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Cyano; endoplasmic reticulum; image analysis; Insecticidal activity; insecticidal properties; insecticides; Insecticides - chemical synthesis; Insecticides - chemistry; insects; Larva - drug effects; Life Sciences & Biomedicine; Moths - drug effects; Moths - growth & development; Mythimna separata; N-Pyridylpyrazolecarboxamides; neurons; Pharmacology & Pharmacy; Physical Sciences; Plutella xylostella; Pyrazoles - chemistry; Pyridines - chemistry; Ryanodine Receptor Calcium Release Channel - chemistry; Ryanodine Receptor Calcium Release Channel - metabolism; Science & Technology; N-Pyridylpyrazolecarboxamides; Insecticidal activity; Cyano; Calcium channel; DESIGN
• ISSN: 0960-894X; 1464-3405; 1464-3405
• DOI: 10.1016/j.bmcl.2012.11.045

The calcium imaging technique experiments demonstrated that compounds 6 deliver calcium from endoplasmic reticulum to cytoplasm, which proved that the title compounds 6 were the possible activators of insect RyR. In an attempt to search for potent insecticides targeting the ryanodine receptor (RyR), a series of novel N-pyridylpyrazolecarboxamides containing cyano substituent in the ortho-position were designed and synthesized. Their insecticidal activities of target compounds against oriental armyworm (Mythimna separata) and diamondback moth (Plutella xylostella) indicated that most of the compounds showed moderate to high activities at the tested concentrations. In particular, compound 6l and 6o showed 86% larvicidal activities against Plutella xylostella at the concentration of 0.1mg/L, while the activity of compound 6h against Mythimna separate was 80% at 1mg/L. The calcium imaging technique was applied to investigate the effects of some title compounds on the intracellular calcium ion concentration ([Ca2+]i), experimental results demonstrated that compound 6h stimulates a transient elevation in [Ca2+]i in the absence of external calcium after the central neurons dye loading with fluo-3 AM. However, when the central neurons were dyed with fluo-5N and incubated with 2-APB, [Ca2+]i decreased transiently by treated of compound 6h. All of the calcium imaging technique experiments demonstrated that these novel compounds deliver calcium from endoplasmic reticulum to cytoplasm, which proved that the title compounds were the possible activators of insect RyR.