The
application of agrochemicals is critical to global food safety.
Nowadays, environmentally friendly green agrochemicals are the trend
in field crop protection. The research and development of nematicides
absorbed more attention as a typical representation of agrochemicals.
This review describes the origin of recently commercialized nematicides,
the application of bioisosterism and scaffold hopping in the discovery
and optimization of agrochemicals, especially nematicides, and novel
bioisosteric design strategies for the identification of fluensulfone
analogues. Pesticide repurposing, high-throughput screening, computer-aided
drug design, and incorporation of known pharmacophoric fragments have
been the most successful approach for the discovery of new nematicides.
As outlined, the strategies of bioisosteric replacements and scaffold
hopping have been very successful approaches in the search for new
nematicides for sustainable crop protection. In the exploration of
novel fluensulfone analogues with nematicidal activity, bioisosteric
replacement of sulfone by amide, chain extension by insertion of a
methylene group, and reversal of the amide group have proven to be
successful approaches and yielded new and highly active fluensulfone
analogues. These attempts might result in compounds with an optimal
balance of steric, hydrophobic, electronic, and hydrogen-bonding properties
and contribute to deal with the complex problem during the research
and development of new nematicides. Further ideas are also put forward
to provide new approaches for the molecular design of nematicides.