A new series of tetrahydropyrido [4,3-d]dihydropyrimidine-2-thiones (3a-3x) were designed and synthesized. Their structures were confirmed by 1 H NMR, IR, MS and elemental analysis, and the conformation of compound 3j was confirmed by X-ray diffraction. Preliminary bioassays indicated that most of the target compounds presented good antiproliferative activities against leukemic K562 cells, ovarian cancer HO-8910 cells and liver cancer SMMC-7721 cells in vitro. Among them the compounds 3i and 3m afford the best activity, the IC 50 of them were 3.22 and 3.65 μg/mL against leukemic K562 cells, respectively, which were lower than the anticancer drug of clinical practice 5-FU (IC 50 ＝8.56 μg/mL). Preliminary mechanism of action studies revealed that compound 3i caused DNA fragmentation and activated caspase-3/7 in leukemic K562 cells.

On the basis of the research of the proposed modes of action between neonicotinoids and insect nicotinic acetylcholine receptor (nAChR), a new series of nitenpyram analogues with an ω-hydroxyalkyl ester arm anchored on the tetrahydropyrimidine ring was designed and synthesized to further enhance the strength of the hydrogen-bonding action they display in binding with the nAChR. The structures of the target compounds were characterized by (1)H NMR, IR, and elemental analysis, and the cis configuration was confirmed by X-ray diffraction. Preliminary bioassays indicated that all of the nitenpyram analogues exhibited good insecticidal activity against Nilaparvata lugens and Myzus persicae at 100 mg/L, whereas analogues 4d and 6a afforded the best in vitro activity that had ≥ 95% mortality at 4 mg/L; the LC(50) values of the analogues 4d and 6a were 0.170 and 0.154 mg/L, respectively. Structure-activity relationship (SAR) studies suggested that their insecticidal potency was also dual-controlled by the flexibility and size of the molecule. In addition, molecular docking simulations revealed that analogues 4d and 6a displayed stronger hydrogen-bonding action in binding with the nAChR, which explained the SARs observed in vitro and implied that the designed nitenpyram analogues are both practical and feasible.

Two series of novel (Z)‐nitenpyram analogs 2a, 2b, 2c, 2d, 2e, 2f, 2g, 2h, 3a, 3b, 3c, 3d were synthesized by introducing various amino acids benzyl ester or amino acids tetrahydrofurfur‐2‐yl ester into nitenpyram and forming a tetrahydropyrimidine ring to fix (Z)‐configuration. The structures of the target compounds were characterized by 1HNMR, MS, IR, and elemental analysis. Preliminary bioassays against Nilaparvata lugens indicated that all the nitenpyram analogs exhibited good insecticidal activity at 100 mg/L, whereas the compounds 3b and 3d afforded the best in vitro inhibitory activities that had ≥ 90% mortality at 20 mg/L.

All synthesized compounds show good insecticidal activity against Nilaparvata lugens.