Structure-Based Bioisosterism Design, Synthesis, Biological Activity and Toxicity of 1,2,4-Oxadiazole Substituted Benzamides Analogues Containing Pyrazole Rings

Abstract

In order to discover pesticidal lead compounds with high activity and low toxicity, a series of novel benzamides substituted with pyrazole-linked 1,2,4-oxadiazole were designed via bioisosterism. The chemical structures of the target compounds were confirmed via 1H NMR, 13C NMR and HRMS analysis. The preliminary bioassay showed that most compounds exhibited good lethal activities against Mythimna separate, Helicoverpa armigera, Ostrinia nubilalis and Spodoptera frugiperda at 500 mg/L. Particularly in the case of Mythimna separate, compound 14q (70%) exhibited obvious insecticidal activity. In addition, compound 14h demonstrated good fungicidal activity against Pyricularia oryae with an inhibition rate of 77.8%, and compounds 14e, 14k, 14n and 14r also showed certain antifungal activities (55.6–66.7%). The zebrafish toxicity test showed that the LC50 of compound 14h was 14.01 mg/L, which indicated that it may be used as a potential leading compound for further structural optimization.

1,2,4-Oxadiazole as a potential scaffold in agrochemistry: a review

“…The results showed that compound 18 exhibited excellent larvicidal activity (100.0%) against mosquito larvae at 1 mg L −1 , but was less active toward M. separata , Helicoverpa armigera , and Pyrausta nubilalis at 500 mg L −1 . 58 Subsequently, a series of 1,2,4-oxadiazole derivatives were synthesized by incorporating the 3-ethyl-1-methyl-pyrazole-5-yl moiety derived from the insecticide tebufenpyrad. Analog 19 exhibited superior insecticidal activity against M. separata (70.0%) compared to tebufenpyrad (60.0%).…”

“…1,2,4-Oxadiazole-substituted meta-benzamides were reported to exhibit a wide range of insecticidal activities, 58,59 but their fungicidal activities may have been overlooked. Inspired by this, several series of 1,2,4-oxadiazole-based benzamides were prepared by our group in 2021, 74 which aim to obtain diverse outcomes in order to expand the range of potential fungicide candidates.…”