Journal of Medicinal Chemistry,
Journal Year:
2021,
Volume and Issue:
64(19), P. 14046 - 14128
Published: Sept. 30, 2021
The
benzene
moiety
is
the
most
prevalent
ring
system
in
marketed
drugs,
underscoring
its
historic
popularity
drug
design
either
as
a
pharmacophore
or
scaffold
that
projects
pharmacophoric
elements.
However,
introspective
analyses
of
medicinal
chemistry
practices
at
beginning
21st
century
highlighted
indiscriminate
deployment
phenyl
rings
an
important
contributor
to
poor
physicochemical
properties
advanced
molecules,
which
limited
their
prospects
being
developed
into
effective
drugs.
This
Perspective
deliberates
on
and
applications
bioisosteric
replacements
for
have
provided
practical
solutions
range
developability
problems
frequently
encountered
lead
optimization
campaigns.
While
effect
compound
contextual
nature,
substitution
can
enhanced
potency,
solubility,
metabolic
stability
while
reducing
lipophilicity,
plasma
protein
binding,
phospholipidosis
potential,
inhibition
cytochrome
P450
enzymes
hERG
channel.
Antibiotics,
Journal Year:
2023,
Volume and Issue:
12(7), P. 1220 - 1220
Published: July 22, 2023
Bacterial
infections
have
attracted
the
attention
of
researchers
in
recent
decades,
especially
due
to
special
problems
they
faced,
such
as
their
increasing
diversity
and
resistance
antibiotic
treatment.
The
emergence
development
SARS-CoV-2
infection
stimulated
even
more
research
find
new
structures
with
antimicrobial
antiviral
properties.
Among
heterocyclic
compounds
remarkable
therapeutic
properties,
benzimidazoles,
triazoles
stand
out,
possessing
antimicrobial,
antiviral,
antitumor,
anti-Alzheimer,
anti-inflammatory,
analgesic,
antidiabetic,
or
anti-ulcer
activities.
In
addition,
literature
last
decade
reports
benzimidazole-triazole
hybrids
improved
biological
properties
compared
simple
mono-heterocyclic
compounds.
This
review
aims
provide
an
update
on
synthesis
methods
these
hybrids,
along
activities,
well
structure-activity
relationship
reported
literature.
It
was
found
that
presence
certain
groups
grafted
onto
benzimidazole
and/or
triazole
nuclei
(-F,
-Cl,
-Br,
-CF3,
-NO2,
-CN,
-CHO,
-OH,
OCH3,
COOCH3),
some
heterocycles
(pyridine,
pyrimidine,
thiazole,
indole,
isoxazole,
thiadiazole,
coumarin)
increases
activity
hybrids.
Also,
oxygen
sulfur
atom
bridge
connecting
rings
generally
mentions
only
benzimidazole-1,2,3-triazole
Both
for
additional
ring
activity,
which
is
agreement
three-dimensional
binding
mode
summarizes
advances
derivatives
potential
agents
covering
articles
published
from
2000
2023.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(13)
Published: Jan. 18, 2024
Abstract
Trifluoromethyl
cationic
carbyne
(CF
3
C
+
:)
possessing
dual
carbene‐carbocation
behavior
emulated
as
trifluoromethyl
metal‐carbynoid
=M)
has
not
been
explored
yet,
and
its
reaction
characteristics
are
unknown.
Herein,
a
novel
α‐diazotrifluoroethyl
sulfonium
salt
was
prepared
used
in
Rh‐catalyzed
three‐component
[2+1+2]
cycloadditions
for
the
first
time
with
commercially
available
N
‐fused
heteroarenes
nitriles,
yielding
series
of
imidazo[1,5‐
]
‐heterocycles
that
interest
medicinal
chemistry,
which
insertion
Rh‐carbynoid
=Rh)
into
C=N
bonds
involved.
This
strategy
demonstrates
synthetic
applications
late‐stage
modification
pharmaceuticals,
construction
CD
‐containing
‐heterocycles,
gram‐scale
experiments,
synthesis
phosphodiesterase
10A
inhibitor
analog.
These
highly
valuable
modifiable
exhibit
good
antitumor
activity
vitro,
thus
demonstrating
their
potential
chemistry.
ACS Chemical Neuroscience,
Journal Year:
2024,
Volume and Issue:
15(9), P. 1828 - 1881
Published: April 22, 2024
Neurodegenerative
diseases
(NDs)
are
one
of
the
prominent
health
challenges
facing
contemporary
society,
and
many
efforts
have
been
made
to
overcome
(or)
control
it.
In
this
research
paper,
we
described
a
practical
one-pot
two-step
three-component
reaction
between
3,4-dihydronaphthalen-1(2H)-one
(1),
aryl(or
heteroaryl)glyoxal
monohydrates
(2a–h),
hydrazine
monohydrate
(NH2NH2•H2O)
for
regioselective
preparation
some
3-aryl(or
heteroaryl)-5,6-dihydrobenzo[h]cinnoline
derivatives
(3a–h).
After
synthesis
characterization
mentioned
cinnolines
(3a–h),
in
silico
multi-targeting
inhibitory
properties
these
heterocyclic
scaffolds
investigated
upon
various
Homo
sapiens-type
enzymes,
including
hMAO-A,
hMAO-B,
hAChE,
hBChE,
hBACE-1,
hBACE-2,
hNQO-1,
hNQO-2,
hnNOS,
hiNOS,
hPARP-1,
hPARP-2,
hLRRK-2(G2019S),
hGSK-3β,
hp38α
MAPK,
hJNK-3,
hOGA,
hNMDA
receptor,
hnSMase-2,
hIDO-1,
hCOMT,
hLIMK-1,
hLIMK-2,
hRIPK-1,
hUCH-L1,
hPARK-7,
hDHODH,
which
confirmed
their
functions
roles
neurodegenerative
(NDs),
based
on
molecular
docking
studies,
obtained
results
were
compared
with
wide
range
approved
drugs
well-known
(with
IC50,
EC50,
etc.)
compounds.
addition,
ADMET
prediction
analysis
was
performed
examine
prospective
drug
synthesized
compounds
The
from
studies
ADMET-related
data
demonstrated
that
series
heteroaryl)-5,6-dihydrobenzo[h]cinnolines
especially
hit
ones,
can
really
be
turned
into
potent
core
new
treatment
and/or
due
having
reactionable
locations,
they
able
further
organic
reactions
(such
as
cross-coupling
reactions),
expansion
(for
example,
using
other
types
monohydrates)
makes
avenue
designing
novel
efficient
purpose.
Journal of Medicinal Chemistry,
Journal Year:
2023,
Volume and Issue:
66(18), P. 13172 - 13188
Published: Sept. 7, 2023
Current
small-molecule
PD-1/PD-L1
inhibitors
are
mainly
based
on
the
arylmethylamine/biphenyl
core
scaffold.
Herein,
we
designed
for
first
time
a
series
of
non-arylmethylamine
analogues
(oxadiazole
thioether
derivatives)
as
inhibitors.
Among
them,
compound
LP23
exhibited
most
potent
PD-L1
inhibitory
activity
with
an
IC50
16.7
nM,
3.2-fold
better
than
lead
BMS-202
(IC50
=
53.6
nM).
The
X-ray
crystal
structure
in
complex
was
solved
at
resolution
2.6
Å,
which
further
confirmed
high
binding
affinity
to
PD-L1.
In
HepG2/Jurkat
T
cell
co-culture
model,
effectively
promoted
HepG2
death
by
restoring
immune
function
cells.
addition,
showed
excellent
vivo
antitumor
efficacy
(TGI
88.6%
30
mg/kg)
and
benign
toxicity
profiles
B16-F10
tumor
model
modulating
summary,
represents
non-arylmethylamine-based
inhibitor
worthy
investigation.
ChemMedChem,
Journal Year:
2023,
Volume and Issue:
18(7)
Published: Jan. 25, 2023
Molecular
hybridization
is
deemed
an
optimistic
approach
in
drug
design
and
the
discovery
of
novel
biologically
active
molecules
as
it
may
advance
their
affinity
potency
while
concurrently
decreasing
associated
resistance
side
effects.
Approximately
20
%
approved
drugs
were
developed
using
this
past
few
years.
Thiazolidinone
one
privileged
pharmacophores
medicinal
chemistry
with
various
biological
activities;
forms
a
functional
unit
several
FDA-approved
drugs.
Consequently,
pharmacophore
has
attracted
attention
many
research
groups
to
further
explore
its
pharmacological
relevance
by
coupling
other
pharmacophoric
moieties.
This
review
presents
concise
account
scholarly
exploits
directed
at
activities
newly
synthesized
thiazolidinone-tagged
molecular
hybrids.
Focused
given
existing
structural
activity
relationship
each
compound
library
toxicity
profile
potent
compounds
including
silico
docking
studies
(where
applicable).
work
would
provide
base
on
which
new
pharmaceuticals
improved
can
be
modelled.
