Novel Insecticidal Pyridylhydrazono Derivatives Identified via Scaffold Hopping and Conformation Regulation Strategies
Chemistry & Biodiversity,
Год журнала:
2024,
Номер
21(12)
Опубликована: Авг. 26, 2024
Abstract
Insect
transient
receptor
potential
vanilloid
(TRPV)
channels
are
critical
targets
for
insecticides.
In
this
study,
various
scaffold‐hopping
strategies
were
employed
in
the
rational
design
of
pyridylhydrazono
derivatives
as
insect
TRPV
modulators.
Insecticidal
bioassay
demonstrated
that
initial
target
compounds
exhibited
lower
insecticidal
activity
compared
to
pymetrozine,
with
optimal
compound
B3
exhibiting
a
mortality
rate
53.3
%
against
Aphis
craccivora
at
400
mg
L
−1
.
Conformation
analysis
indicated
high
energy
barrier
required
transition
from
lowest‐energy
conformation
active
may
be
key
factor
contributing
reduced
activities
compounds.
Further
structural
optimizations
aimed
reducing
through
binding
mode‐based
regulation
led
identification
4‐(3′‐pyridylhydrazono)pyrazol‐5‐one
C1
and
C2
These
barriers
improved
activity,
moderate
66.3
75.7
A.
,
respectively.
findings
provide
valuable
insights
future
research
on
discovery
modulators
have
significant
implications
development
more
effective
agricultural
Язык: Английский
Design, Synthesis, and Insecticidal Activity of 3‐(6‐Methyltriazinone)‐3,4‐dihydrobenzo[b][1,5]diazin‐2(1H)‐ones: Conformationally Restricted Pymetrozine Analogues
ChemistrySelect,
Год журнала:
2024,
Номер
9(42)
Опубликована: Ноя. 1, 2024
Abstract
A
series
of
novel
3‐(6‐methyltriazinone)‐3,4‐dihydrobenzo[
b
][1,5]diazin‐2(1
H
)‐one
derivatives
was
designed
and
synthesized
as
conformationally
restricted
analogues
insecticide
pymetrozine.
Conformational
physicochemical
properties
analyses
indicated
the
rationality
in
reducing
energy
barrier
between
lowest‐energy
predicted
bioactive
conformations,
well
pesticide‐likeness.
Insecticidal
bioassays
showed
that
optimal
compound
VI‐6b
exhibited
a
mortality
rate
67.7%
against
Aphis
craccivora
at
400
mg
L
−1
.
The
molecular
docking
study
within
Nilaparvata
lugens
TRPV
channel
elucidated
binding
mode,
wherein
forms
hydrogen
bonds
with
Arg646
Glu727,
while
engaging
π‐π
interactions
Phe688.
However,
revealed
low
lipophilicity
poor
aqueous
solubility
limited
insecticidal
efficacy
these
compounds.
This
provides
valuable
insights
for
future
design
insecticides
targeting
channel.
Язык: Английский
Novel Insecticidal Benzo[4,5]imidazo[1,2‐b]pyrazole Derivatives Identified through Ring‐Closure Scaffold Hopping on Fipronil
Chemistry & Biodiversity,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 27, 2024
Abstract
A
series
of
innovative
benzo[4,5]imidazo[1,2‐
b
]pyrazole
scaffold
containing
compounds
were
rationally
designed
through
a
ring‐closure
hopping
strategy
and
synthetized
with
an
intermediate
derivatization
approach.
Physicochemical
properties
analysis
indicated
the
potential
pesticide‐likeness
target
compounds.
The
optimal
compound
A14
showed
relatively
good
insecticidal
activity
against
P.
xylostella
,
LC
50
value
37.58
mg/L,
demonstrated
lower
acute
fish
toxicity
compared
to
fipronil.
Docking
binding
mode
that
bound
GABAR
H‐bond
between
amide
group
residue
6’Thr.
differences
in
modes
fipronil
may
be
key
factor
for
reduced
activities.
elucidated
SAR
profile
lay
foundation
further
structural
optimization
derivatives.
Язык: Английский