Background: Formally belonging to the non-steroidal anti-inflammatory drug class
pyrazolones have long been used in medical practices.
Objective: Our goal is to synthesize N-methylated 1-aryl-3-polyfluoroalkylpyrazolones as fluorinated
analogs of antipyrine, their isomeric O-methylated derivatives resembling celecoxib structure
and evaluate biological activities of obtained compounds.
Methods: In vitro (permeability) and in vivo (anti-inflammatory and analgesic activities, acute toxicity,
hyperalgesia, antipyretic activity, “open field” test) experiments. To suggest the mechanism
of biological activity, molecular docking of the synthesized compounds was carried out into the
tyrosine site of COX-1/2.
Results: We developed the convenient methods for regioselective methylation of 1-aryl-3-
polyfluoroalkylpyrazol-5-ols leading to the synthesis N-methylpyrazolones and O-methylpyrazoles
as antipyrine and celecoxib analogs respectively. For the first time, the biological properties of
new derivatives were investigated in vitro and in vivo.
Conclusion: The trifluoromethyl antipyrine represents a valuable starting point in design of the
lead series for discovery new antipyretic analgesics with anti-inflammatory properties.
Keywords: Polyfluoroalkyl-containing antipyrine , Analgesic and anti-inflammatory activities, Toxicity, Permeability , Molecular docking
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