Synthesis, Insecticidal Activity, Crystal Structure, and Molecular Docking Studies of Nitenpyram Analogues with an ω‑Hydroxyalkyl Ester Arm Anchored on the Tetrahydropyrimidine Ring

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 1H 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 LC50 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.