Journal of Chemical Information and Modeling,
Год журнала:
2023,
Номер
63(24), С. 7768 - 7777
Опубликована: Дек. 12, 2023
Peptides
have
attracted
much
attention
recently
owing
to
their
well-balanced
properties
as
drugs
against
protein–protein
interaction
(PPI)
surfaces.
Molecular
simulation-based
predictions
of
binding
sites
and
amino
acid
residues
with
high
affinity
PPI
surfaces
are
expected
accelerate
the
design
peptide
drugs.
Mixed-solvent
molecular
dynamics
(MSMD),
which
adds
probe
molecules
or
fragments
functional
groups
solutes
hydration
model,
detects
hotspots
cryptic
induced
by
small
molecules.
The
detection
results
vary
depending
on
type
molecule;
thus,
they
provide
important
information
for
drug
design.
For
rational
using
MSMD,
we
proposed
MSMD
residue
probes,
named
probe-based
(AAp-MSMD),
detect
identify
favorable
types
protein
bind.
We
assessed
our
method
in
terms
hotspot
at
level
free
energy
prediction
probes
site
complex
structure
that
formed
PPI.
In
detection,
max-spatial
probability
distribution
map
(max-PMAP)
obtained
from
AAp-MSMD
detected
site,
each
can
bind
favorably.
ΔGFE
roughly
estimated
experimental
affinities
structure–activity
relationship.
AAp-MSMD,
provides
a
target
protein.
European Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
275, С. 116556 - 116556
Опубликована: Июнь 5, 2024
Azepanes
or
azepines
are
structural
motifs
of
many
drugs,
drug
candidates
and
evaluated
lead
compounds.
Even
though
compounds
having
N-heterocyclic
7-membered
rings
often
found
in
nature
(e.g.
alkaloids),
the
natural
this
group
rather
rare
as
approved
therapeutics.
Thus,
recently
studied
azepane
azepine-congeners
predominantly
consist
semi-synthetically
synthetically-obtained
scaffolds.
In
review
a
comparison
drugs
investigated
leads
was
proposed
taking
into
regard
their
aspects
(stereochemistry),
biological
activities,
pharmacokinetic
properties
confirmed
molecular
targets.
The
N-heterocycles
reveal
wide
range
not
only
against
CNS
diseases,
but
also
e.g.
antibacterial,
anticancer,
antiviral,
antiparasitic
allergy
agents.
As
most
potential
structures,
belonging
to
N-heterocycles,
synthetic
scaffolds,
report
reveals
different
efficient
metal-free
cascade
approaches
useful
synthesize
both
simple
azepine-containing
congeners
those
oligocyclic
structures.
Stereochemistry
azepane/azepine
fused
systems,
view
data
binding
with
targets,
is
discussed.
Apart
from
we
compare
advances
SAR
studies
(mainly
2018
2023),
whereas
related
part
concerning
various
domino
strategies
focused
on
last
ten
years.
Medicinal Research Reviews,
Год журнала:
2023,
Номер
43(6), С. 2352 - 2391
Опубликована: Май 21, 2023
Abstract
The
U.S.
Food
and
Drug
Administration
has
approved
a
total
of
37
new
drugs
in
2022,
which
are
composed
20
chemical
entities
17
biologics.
In
particular,
entities,
including
small
molecule
drugs,
1
radiotherapy,
2
diagnostic
agents,
provide
privileged
scaffolds,
breakthrough
clinical
benefits,
mechanism
action
for
the
discovery
more
potent
candidates.
structure‐based
drug
development
with
clear
targets
fragment‐based
scaffolds
have
always
been
important
modules
field
discovery,
could
easily
bypass
patent
protection
bring
about
improved
biological
activity.
Therefore,
we
summarized
relevant
valuable
information
application,
action,
synthesis
newly
2022.
We
hope
this
timely
comprehensive
review
creative
elegant
inspiration
on
synthetic
methodologies
novel
extended
indications.
ACS Catalysis,
Год журнала:
2024,
Номер
14(14), С. 11087 - 11100
Опубликована: Июль 9, 2024
Fluoroalkyl
fragments
have
played
a
critical
role
in
the
design
of
pharmaceutical
and
agrochemical
molecules
recent
years
due
to
enhanced
biological
properties
fluorinated
compared
their
non-fluorinated
analogues.
Despite
potential
advantages
conferred
by
incorporating
difluoromethyl
group
organic
compounds,
industrial
adoption
difluoromethylation
methods
lags
behind
fluorination
trifluoromethylation.
This
is
part
challenges
applying
common
sources
towards
applications.
We
report
here
nickel-catalyzed
cross-electrophile
coupling
(hetero)aryl
bromides
with
2-pyridyl
sulfone,
sustainably
sourced,
crystalline
reagent.
The
scope
this
reaction
demonstrated
24
examples
(67
±
16%
average
yield)
including
diverse
array
heteroaryl
precursors
difluoromethyl-containing
preclinical
pharmaceuticals.
can
be
applied
small-scale
parallel
synthesis
benchtop
scale-up
under
mild
conditions.
As
sulfone
reagents
are
uncommon
electrophiles
coupling,
mechanism
process
was
investigated.
Studies
confirmed
formation
•CF2H
instead
difluorocarbene.
A
series
modified
sulfones
revealed
that
reactivity
does
not
correlate
exclusively
reduction
coordination
cations
or
nickel
pyridyl
essential
reactivity,
setting
out
parameters
for
matching
coupling.
Journal of Nephrology,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 25, 2025
Abstract
Background
Chronic
kidney
disease-associated
pruritus
(CKD-aP)
is
a
debilitating
symptom
that
can
significantly
impact
patients’
daily
activities
and
quality
of
life.
This
systematic
review
aimed
to
assimilate
the
latest
evidence
on
relationship
between
CKD-associated
pruritis
patient-centred
outcomes.
Methods
A
comprehensive
search
was
conducted
identify
relevant
studies
in
PubMed,
Medline
Embase
via
OVID,
CINAHL,
Web
Science
from
2000
June
2024.
Quality
appraisal
subsequent
data
extraction
were
performed
using
Joanna
Briggs
Institute
(JBI)
tools
modified
form
derived
JBI.
Results
The
included
29
with
total
147,174
CKD
patients,
including
those
haemodialysis
(HD)
peritoneal
dialysis
(PD).
most
frequently
reported
outcomes
life
(
n
=
21),
sleep
17),
anxiety/depression
11)
mortality
7).
There
paucity
patients
pre-dialysis
stages,
undergoing
PD,
following
conservative
(non-dialytic)
pathway.
contingent
severity
pruritus.
an
association
increased
medication
usage,
decreased
compliance
HD
treatments
higher
rates
hospitalisation
experiencing
severe
Conclusion
Our
underscores
pernicious
patient
emphasises
importance
effective
management
improve
Additional
investigations
are
warranted
among
pathways,
achieve
more
understanding
these
groups.
Graphical
abstract
