Xanthoxyline (
1
), a small natural methyl
ketone, was
previously reported as a plant growth inhibitor. In this research,
related methyl ketones bearing electron-donating and electron-withdrawing
groups, together with heteroaromatics, were investigated against seed
germination and seedling growth of Chinese amaranth (
Amaranthus tricolor L.
) and barnyard grass [
Echinochloa crus-galli (L.) Beauv
]. The structure–activity
relationships (SARs) of methyl ketone herbicides were clarified, and
which types and positions of substituents were crucially important
for activity were also clarified. Indole derivatives, namely, 3-acetylindole
(
43
) and 3-acetyl-7-azaindole (
44
) were
found to be the most active methyl ketones that highly suppressed
plant growth at low concentrations. The molecular docking on the 4-hydroxyphenylpyruvate
dioxygenase (HPPD) enzyme indicated that carbonyl, aromatic, and azaindole
were key interactions of HPPD inhibitors. This finding would be useful
for the development of small ketone herbicides.