Design, synthesis, and insecticidal activities of novel 5-substituted 4,5-dihydropyrazolo[1,5-a]quinazoline derivatives

Chemical pesticides are the main measures for pest control, but have caused growing resistance of pests and brought a series of environmental problems. Development of high-efficient insecticidal molecules with novel scaffolds is therefore particularly urgent.

Based on a [5 + 1] annulation reaction with 5-amino-1H-phenylpyrazole and dialkyl bromomalonate, 27 novel five-substituted 4,5-dihydropyrazolo[1,5-a]quinazolines were designed following the intermediate derivatization method and synthesized. Bioassay results indicated that most of the test compounds displayed good insecticidal activities against Plutella xylostella, Spodoptera frugiperda, and Solenopsis invicta. In particular, the insecticidal activities of compounds 4a, 4f, and 4m against P. xylostella [median lethal concentration (LC₅₀ ) values ranged from 3.87 to 5.10 mg L^-1 ] were comparable to that of indoxacarb (LC₅₀ = 4.82 mg L^-1 ). In addition, compounds 4a and 9e showed similar high insecticidal activities against Spodoptera frugiperda (mortality rate = 79.63% and 72.12%) at 100 mg L^-1 , comparable to that of fipronil (mortality rate: 68.44%); compound 9a showed possible delayed toxicity against Solenopsis invicta (mortality rate: 95.66%) after 5 days of treatment at 1.0 mg L^-1 .

Due to their high insecticidal activities against P. xylostella, compound 4m, 4a, and 4f could be considered as qualified candidates for novel insecticide. Several other 4,5-dihydropyrazolo[1,5-a]quinazolines with relatively high bioactivity, such as compounds 9a and 9e, are also worth further optimization as potential insecticide or anticide candidates.