Design, synthesis, and biological activity of novel spiro‐pyrazolo[1,5‐a]quinazolines derivatives as potential insecticides

BACKGROUND Arylpyrazole insecticides display broad‐spectrum insecticidal activity against insect pests. However, the high toxicity toward honeybees associated with fipronil prohibits its agronomic utility. To explore reducing the toxicity of aryl pyrazole analogs to bees, a series of new spiro‐pyrazolo[1,5‐a]quinazoline derivatives were designed and synthesized. RESULTS Bioassay results showed that these compounds exhibited good insecticidal activity. In particular, the insecticidal activity of compound 5f against Plutella xylostella larvae (median lethal contentration, LC50 = 1.43 mg L−1) was equivalent to that of fipronil. Moreover, some compounds also showed good insecticidal activity against Solenopsis invicta. Importantly, the bee toxicity study confirmed that compound 5f had much lower acute oral toxicity, with a median lethal dose (LD50) = 1.15 μg bee−1 that was three to four orders of magnitude greater than that of fipronil (0.0012 μg bee−1). Electrophysiological studies were conducted using honeybee γ‐aminobutyric acid receptor heterologously expressed in Xenopus oocytes to explain the reduced bee toxicity of compound 5f. The inhibitory effect of compound 5f (16.29 μmol L−1) was determined to be approximately 700‐fold lower than that of fipronil (0.023 μmol L−1). CONCLUSION These spiro‐pyrazolo[1,5‐a]quinazoline derivatives could be potential candidates and lead structures for the discovery of novel insecticides with low bee toxicity. © 2022 Society of Chemical Industry. To explore reducing the bee toxicity of aryl pyrazole analogs, a series of new spiro‐pyrazolo[1,5‐a]quinazolines derivatives were designed and synthesized based on a scaffold hopping strategy. These valuable derivatives could be used as potential candidates and lead structures for the discovery of novel insecticides.