Acta Pharmaceutica Sinica B,
Год журнала:
2019,
Номер
10(8), С. 1492 - 1510
Опубликована: Дек. 27, 2019
Simultaneous
inhibition
of
MDM2
and
CDK4
may
be
an
effective
treatment
against
glioblastoma.
A
collection
chiral
spirocyclic
tetrahydronaphthalene
(THN)-oxindole
hybrids
for
this
purpose
have
been
developed.
Appropriate
stereochemistry
in
THN-fused
spirooxindole
compounds
is
key
to
their
inhibitory
activity:
selectivity
differed
by
over
40-fold
between
the
least
most
potent
stereoisomers
time-resolved
FRET
KINOMEscan®
vitro
assays.
Studies
glioblastoma
cell
lines
showed
that
active
compound
ent-4g
induced
apoptosis
cycle
arrest
interfering
with
-P53
interaction
activation.
Cells
treated
up-regulation
proteins
involved
P53
pathways.
The
good
anti-tumor
efficacy
xenografts
mice.
These
results
suggested
rational
design,
asymmetric
synthesis
biological
evaluation
novel
fused
spirooxindoles
could
generate
promising
MDM2-CDK4
dual
inhibitors
therapy.
Future Medicinal Chemistry,
Год журнала:
2025,
Номер
unknown, С. 1 - 19
Опубликована: Март 19, 2025
TB
drug
discovery
needs
scientists'
attention
since
resistance
in
TB,
including
extensively
drug-resistant
(XDR-TB)
and
multidrug-resistant
(MDR-TB),
is
a
major
healthcare
concern.
Since
millions
of
fatalities
from
tuberculosis
are
recorded
each
year,
there
an
urgent
need
to
discover
new
anti-tubercular
medications
that
will
either
eradicate
or
control
the
disease.
Spiro
compounds
have
garnered
lot
medicinal
chemistry
these
days
because
various
biological
activities
mainly
their
adaptability
structural
resemblance
significant
pharmacophores.
This
article
overviews
synthesis
activity
spirocyclic
as
agents.
Both
synthesized
naturally
occurring
spiro
chemicals
exhibit
antitubercular
properties.
The
promising
potential
shown
by
some
has
attracted
scientists
explore
them
further
develop
molecules
with
improved
pharmacodynamic
pharmacokinetic
properties
mechanisms
action
enhanced
safety
efficacy
tuberculosis.
current
review
covers
exploration
year
2004
2024
for
combat
Tuberculosis.
gives
comprehensive
advancements
this
scaffold
which
would
help
logical
design
powerful,
less
toxic,
more
effective
anti-TB
molecules.
The Journal of Organic Chemistry,
Год журнала:
2019,
Номер
84(6), С. 3214 - 3222
Опубликована: Фев. 19, 2019
A
chiral
guanidine-catalyzed
asymmetric
[4
+
1]
cyclization
of
benzofuran-derived
azadienes
with
3-chlorooxindoles
has
been
established,
which
constructed
spirooxindole
frameworks
in
situ
generation
a
five-membered
ring
high
diastereoselectivities
(up
to
>95:5
dr)
and
good
enantioselectivities
94:6
er).
This
reaction
represents
the
first
catalytic
azadienes,
will
enrich
research
field
cyclizations
such
reactants.
In
addition,
this
provides
useful
strategy
for
enantioselective
construction
ring-based
scaffolds.
Organic Letters,
Год журнала:
2019,
Номер
21(4), С. 1058 - 1062
Опубликована: Фев. 5, 2019
The
hydride
transfer
involved
redox-neutral
cascade
cyclization
has
been
developed
to
construct
the
spirocyclic
bisoxindoles
featuring
a
[3,4]-fused
oxindole
moiety
from
rationally
designed
C4-amine-substituted
isatins,
affording
diverse
tricyclic
oxindoles
with
three
consecutive
chiral
centers
in
good
yields
and
excellent
diastereoselectivities
(>20:1).
Acta Pharmaceutica Sinica B,
Год журнала:
2019,
Номер
10(8), С. 1492 - 1510
Опубликована: Дек. 27, 2019
Simultaneous
inhibition
of
MDM2
and
CDK4
may
be
an
effective
treatment
against
glioblastoma.
A
collection
chiral
spirocyclic
tetrahydronaphthalene
(THN)-oxindole
hybrids
for
this
purpose
have
been
developed.
Appropriate
stereochemistry
in
THN-fused
spirooxindole
compounds
is
key
to
their
inhibitory
activity:
selectivity
differed
by
over
40-fold
between
the
least
most
potent
stereoisomers
time-resolved
FRET
KINOMEscan®
vitro
assays.
Studies
glioblastoma
cell
lines
showed
that
active
compound
ent-4g
induced
apoptosis
cycle
arrest
interfering
with
-P53
interaction
activation.
Cells
treated
up-regulation
proteins
involved
P53
pathways.
The
good
anti-tumor
efficacy
xenografts
mice.
These
results
suggested
rational
design,
asymmetric
synthesis
biological
evaluation
novel
fused
spirooxindoles
could
generate
promising
MDM2-CDK4
dual
inhibitors
therapy.
