Synthesis and Biological Evaluation of Polyfluoroalkylated Antipyrines and their Isomeric O-Methylpyrazoles

Abstract

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. Conclusion: The trifluoromethyl antipyrine represents a valuable starting point in design of the lead series for discovery new antipyretic analgesics with anti-inflammatory properties.

Au@ZnO Core–Shell: Scalable Photocatalytic Trifluoromethylation Using CF3CO2Na as an Inexpensive Reagent under Visible Light Irradiation

“…Another potential benefit of our method is its potential use for biologically active molecules. To demonstrate this, some active molecules such as an anti-inflammatory drug, 45 a flavorant, and a DNA base analogue were chosen to obtain their CF 3 analogues. High regioselectivity was observed, and in all cases, the trifluoromethylation occurred at a single position.…”

5‐Alkoxy‐1‐aryl‐3‐polyfluoroalkylpyrazoles with Antinociceptive Activity: Partial Agonists of TRPV1 Ion Channels

“…We studied the analgesic effect of pyrazoles 2 – 5 in the hot plate test on SD rats in vivo ( ip ). Based on our previous data on the analgesic activity of O‐methyl pyrazole derivatives [33] and the assessment of acute toxicity, a dose of 15 mg/kg was chosen for screening the antinociceptive effect of the compounds. Diclofenac, metamizole, and Celebrex were used as reference drugs.…”

“…[25] We are also actively carrying out research on the development of analgesics based on fluorine-containing pyrazoles. [26][27][28][29][30][31][32] Recently, we have synthesized polyfluoroalkylcontaining MeN-and MeO-derivatives of pyrazol-5-ols as analogues of antipyrine and celecoxib, [33] which revealed the pronounced analgesic activity in the hot plate test. Among the obtained derivatives, 5-methoxy-3-(trifluoromethyl)-1phenylpyrazole was distinguished by a combination of high analgesic activity in the in vivo hot plate test with low acute toxicity, which is a very important point for the development of new analgesics.…”

Polyfluoroalkylated antipyrines in Pd-catalyzed transformations

“… 37 CF 3 -antipyrine (1-methyl-2-phenyl-5-trifluoromethyl-1,2-dihydro-3 H -pyrazolon-3-one) was found to show an anti-inflammatory and analgesic activity at the level of diclofenac and metamizole or significantly higher, and its antipyretic effect was higher than that of paracetamol. 38 Therefore, the promising challenge is the development of methods for functionalization of polyfluoroalkyl-antipyrines.…”