Synthesis, biological evaluation and SAR analysis of novel poly-heterocyclic compounds containing pyridylpyrazole group.

Abstract

In recent years, pyridylpyrazole derivatives, such as pyridylpyrazole-containing anthranilic diamide have attracted much attention by virtue of their useful insecticidal properties and unique action mode. Moreover, some pyridylpyrazole-containing compounds have also been found to possess significant fungicidal activities. With the aim of discovering new bioactive agrochemicals for crop protection, a series of poly-heterocyclic compounds containing pyridylpyrazole and aziridine, or β-lactam, or thiazolinone moieties were synthesized. A series of pyridylpyrazole-containing poly-heterocyclic compounds were obtained, and confirmed through IR, 1 H NMR, 13 C NMR, HRMS and elemental analysis. The crystalline structure of 4-(3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl)-3-chloro-1-mesitylazetidin-2-one (compound 13f) was determined to further illustrate a trans- configuration of the β-lactam motif. In addition, bioassays showed that most of these new compounds exhibited modest insecticidal activity towards Mythimna separate Walker at 200 µg mL-1 . Some of the compounds displayed excellent fungicidal activity towards some plant fungi, including Cercospora arachidicola (13j: EC50 = 14.5 µg mL-1 ), Physalospora piricola (12d and 13d: EC50 = 10.5 and 9.70 µg mL-1 ), Alternaria solani Sorauer (13j: EC50 = 7.29 µg mL-1 ), Puccinia sorghi Schw. (13d: control efficacy 99.0 ± 2.1% at 200 µg mL-1 ) and Erysiphe graminis (14d: control efficacy 95.0 ± 1.4% at 200 µg mL-1 ). Compounds 12b-12e, 13a, 13d, 13f, 13j, 13 k and 14d could be considered potential fungicidal lead compounds to do further structural optimization. The structure-activity relationship analysis in this study brings some new understanding to the biological activities of N-pyridylpyrazole-containing compounds, and provides important information for the research and development of novel agricultural fungicides with poly-heterocyclic structures. © 2017 Society of Chemical Industry.