Synthetic Communications,
Год журнала:
2024,
Номер
54(23), С. 2052 - 2063
Опубликована: Окт. 24, 2024
Herein,
we
designed
a
series
of
guanidinobenzoic
acid
ester
derivatives
on
the
basis
approved
AP
drugs,
such
as
nafamostat,
gabexate
and
camostat,
evaluated
their
inhibitory
effects
trypsin
anti-inflammatory
activity.
Among
them,
five
compounds
(6a,
6c–6e,
7j)
showed
excellent
with
IC50
values
0.0756
μM
to
0.1227
μM,
which
are
more
potent
than
nafamostat
gabexate.
Moreover,
6a,
6b
6c
also
significant
potency
against
pro-inflammatory
molecule
NO
1.618
2.276
3.022
respectively.
Consequently,
potential
lead
simultaneously
anti-trypsin
activities
were
identified,
would
profit
further
structural
optimization
for
treatment
AP.
Journal of Enzyme Inhibition and Medicinal Chemistry,
Год журнала:
2022,
Номер
37(1), С. 2304 - 2319
Опубликована: Авг. 23, 2022
Oxadiazole
is
a
five-membered
heterocyclic
compound
containing
two
nitrogen
atoms
and
one
oxygen
atom.
The
1,3,4-oxadiazole
1,2,4-oxadiazole
have
favourable
physical,
chemical,
pharmacokinetic
properties,
which
significantly
increase
their
pharmacological
activity
via
hydrogen
bond
interactions
with
biomacromolecules.
In
recent
years,
oxadiazole
has
been
demonstrated
to
be
the
biologically
active
unit
in
number
of
compounds.
derivatives
exhibit
antibacterial,
anti-inflammatory,
anti-tuberculous,
anti-fungal,
anti-diabetic
anticancer
activities.
this
paper,
we
report
series
compounds
rings
that
published
last
three
years
only
(2020–2022)
as
there
was
no
or
activities
described
any
article
2019,
will
useful
scientists
research
fields
organic
synthesis,
medicinal
chemistry,
pharmacology.
RSC Advances,
Год журнала:
2022,
Номер
12(36), С. 23626 - 23636
Опубликована: Янв. 1, 2022
The
use
of
dual
acetylcholinesterase
(AChE)-monoamine
oxidase
B
(MAO-B)
inhibitors
is
a
new
approach
in
the
treatment
Alzheimer
disease
(AD).
In
this
work,
14
benzothiazoles
(4a-4n)
were
designed
and
synthesized.
biological
activity
studies,
AChE,
butyrylcholinesterase
(BChE),
MAO-A
MAO-B
inhibitory
potentials
all
compounds
evaluated
using
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(6), С. 5406 - 5406
Опубликована: Март 12, 2023
1,2,4-Oxadiazole
is
an
essential
motif
in
drug
discovery
represented
many
experimental,
investigational,
and
marketed
drugs.
This
review
covers
synthetic
methods
that
allow
the
conversion
of
different
types
organic
compounds
into
1,2,4-oxadiazole
at
ambient
temperature
practical
application
latter
approaches
for
preparation
pharmaceutically
important
molecules.
The
discussed
are
divided
three
groups.
first
combines
two-stage
protocols
requiring
preliminary
O-acylamidoximes
followed
by
cyclization
under
action
bases.
advantages
this
route
its
swiftness,
high
efficiency
process,
uncomplicated
work-up.
However,
it
requires
isolation
as
a
separate
step.
second
one-pot
synthesis
1,2,4-oxadiazoles
directly
from
amidoximes
various
carboxyl
derivatives
or
aldehydes
aprotic
bipolar
solvents
(primarily
DMSO)
presence
inorganic
recently
proposed
pathway
proved
to
be
highly
efficient
field
medicinal
chemistry.
third
group
consists
diverse
oxidative
cyclizations,
these
reactions
have
found
modest
design
thus
far.
It
noteworthy
reviewed
obtaining
with
thermosensitive
functions
expand
prospects
using
oxadiazole
core
amide-
ester-like
linker
bioactive
compounds.
Abstract
A
series
of
new
1,2,4-oxadiazole-based
derivatives
were
synthesized
and
evaluated
for
their
anti-AD
potential.
The
results
revealed
that
eleven
compounds
(
1b
,
2a-c
3b
4a-c
5a-c
)
exhibited
excellent
inhibitory
potential
against
AChE,
with
IC
50
values
ranging
from
0.00098
to
0.07920
µM.
Their
potency
was
1.55
125.47
times
higher
than
donepezil
(IC
=
0.12297
µM).
In
contrast,
the
newly
oxadiazole
in
range
16.64
–
70.82
µM
less
selectivity
towards
BuChE
when
compared
rivastigmine
5.88
Moreover,
derivative
2c
463.85
µM)
more
potent
antioxidant
quercetin
491.23
Compounds
536.83
3c
582.44
comparable
activity
quercetin.
Oxadiazole
140.02
4c
117.43
showed
prominent
MAO-B
They
biperiden
237.59
1a
3a
4b
remarkable
MAO-A
potential,
47.25
129.7
1.1
3.03
methylene
blue
143.6
Most
provided
significant
protection
induced
HRBCs
lysis,
revealing
nontoxic
effect
compounds,
thus
making
them
safe
drug
candidates.
unveiled
2b
3b,
4a,
5a
as
multitarget
agents.
high
AChE
can
be
computationally
explained
by
derivatives’
interactions
active
site.
Compound
good
physicochemical
properties.
All
these
data
suggest
could
considered
a
promising
candidate
future
development.
A
novel
series
of
benzothiazole
derivatives
was
synthesized
using
straightforward
and
easily
implementable
procedures,
achieving
a
high
yield.
Among
these
compounds,
amino
acids
containing
the
moiety
were
successfully
produced
through
an
8-step
process,
with
yields
reaching
as
95%.
Notably,
serendipitous
compound
both
benzo[1,4]oxazin-3(4H)-one
moieties
also
same
protocol,
bypassing
purification
at
step
7
proceeding
directly
to
hydrolysis.
This
highlights
unique
role
coupling
reagent
HATU
(hexafluorophosphate
azabenzotriazole
tetramethyluronium)
in
reaction,
it
facilitated
yields,
up
90%.
The
structures
newly
compounds
confirmed
spectral
analysis.
Density
functional
theory
calculations
suggested
that
energy
barriers
can
be
overcome
by
utilizing
from
exothermic
enabling
thermodynamically
favorable
formation
this
structure.
Compounds
6d
6f
demonstrated
significant
inhibitory
activity
against
enzyme
acetylcholinesterase,
IC50
values
32.00
25.33
μg/mL,
respectively.
Molecular
docking
molecular
dynamics
analyses
indicate
hold
potential
for
combating
Alzheimer's
disease,
due
their
interactions
critical
acid
residues
structural
stability.
