Abstract
To
develop
the
new
analgesics,
different
approaches
to
modification
of
4‐amino‐5‐phenyl‐3‐(trifluoromethyl)pyrazoles
were
proposed.
A
series
4‐(het)arylimino‐3‐(trifluoromethyl)‐5‐phenylpyrazoles,
existing
as
E
‐isomer,
was
synthesized
by
condensation
4‐aminopyrazoles
with
various
aldehydes.
Methylation
initial
substrates
occurred
at
NH
2
group,
while
alkylation
bromobutyl
successfully
carried
out
only
for
NH‐pyrazole
yield
3‐
and
5‐CF
3
‐isomeric
N‐butyl‐substituted
pyrazoles.
The
addition
phenylisothiocyanate
allowed
us
introduce
a
thiourea
fragment
into
their
structure.
According
computer
calculations,
all
derivatives
aminopyrazoles
have
an
acceptable
ADME
profile.
Using
“hot
plate”
test
in
vivo
,
analgesic
activity
number
compounds
evaluated.
Introducing
phenylmethanimine
allows
obtain
1‐phenyl‐N‐(5‐phenyl‐3‐(trifluoromethyl)pyrazol‐4‐yl)methan‐imine
lead
compound
1.4–2.2
times
more
than
effect
4‐aminopyrazole,
diclofenac
metamizole.
In
addition,
had
low
acute
toxicity.
Non-steroidal
anti-inflammatory
drugs
(NSAIDs)
that
selectively
inhibit
cyclooxygenase-2
(COX-2)
are
indicated
for
managing
pain
across
diverse
conditions
like
osteoarthritis
(OA),
rheumatoid
arthritis
(RA),
and
migraines.
Compared
to
non-selective
NSAIDs,
they
offer
reduced
gastrointestinal
toxicity,
as
evidenced
in
short-term
trials.
However,
concerns
about
cardiovascular
risks
associated
with
traditional
COX-2
inhibitors
have
driven
the
development
of
newer
agents
such
polmacoxib,
which
also
targets
carbonic
anhydrase
(CA)
isoforms.
Originally
approved
South
Korea
2015
CG100649,
polmacoxib
demonstrates
dual
inhibition
CA
enzymes,
suggesting
potential
advantages
efficacy
systemic
safety
over
standard
NSAIDs.
Initial
studies,
primarily
OA
adhesive
capsulitis
among
Asian
population,
indicate
promising
results,
although
comprehensive
clinical
data
various
medical
still
emerging.
Approval
idiopathic
primary
India
highlights
its
emerging
role
an
innovative
therapeutic
option.
The
present
narrative
review
focuses
on
current
knowledge
addressing
gaps
understanding
efficacy.
By
analyzing
from
early
trials
pharmacokinetic
explores
mechanisms
their
implications
practice.
Continuing
research
is
crucial
fully
realize
inflammatory
disorders
guide
future
pharmacotherapy
strategies.
Abstract
To
develop
the
new
analgesics,
different
approaches
to
modification
of
4‐amino‐5‐phenyl‐3‐(trifluoromethyl)pyrazoles
were
proposed.
A
series
4‐(het)arylimino‐3‐(trifluoromethyl)‐5‐phenylpyrazoles,
existing
as
E
‐isomer,
was
synthesized
by
condensation
4‐aminopyrazoles
with
various
aldehydes.
Methylation
initial
substrates
occurred
at
NH
2
group,
while
alkylation
bromobutyl
successfully
carried
out
only
for
NH‐pyrazole
yield
3‐
and
5‐CF
3
‐isomeric
N‐butyl‐substituted
pyrazoles.
The
addition
phenylisothiocyanate
allowed
us
introduce
a
thiourea
fragment
into
their
structure.
According
computer
calculations,
all
derivatives
aminopyrazoles
have
an
acceptable
ADME
profile.
Using
“hot
plate”
test
in
vivo
,
analgesic
activity
number
compounds
evaluated.
Introducing
phenylmethanimine
allows
obtain
1‐phenyl‐N‐(5‐phenyl‐3‐(trifluoromethyl)pyrazol‐4‐yl)methan‐imine
lead
compound
1.4–2.2
times
more
than
effect
4‐aminopyrazole,
diclofenac
metamizole.
In
addition,
had
low
acute
toxicity.
