190711-56-9

Upstream product

• 169590-42-5 4-[5-(4-(methyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulphonamide 
• 122-00-9 para-methylacetophenone 
• 720-94-5 4,4,4-trifluoro-1-(4-methylphenyl)butane-1,3-dione 
• 921617-76-7 4-(5-p-methylphenyl-3-trifluoromethyl-pyrazol-1-yl)-benzenesulfonic acid 
• 190711-64-9 Acetic acid 4-(5-p-tolyl-3-trifluoromethyl-pyrazol-1-yl)-benzenesulfonylmethyl ester 
• 190711-63-8 Acetic acid 4-(5-p-tolyl-3-trifluoromethyl-pyrazol-1-yl)-phenylsulfanylmethyl ester 
• 190711-47-8 1-(4-Methanesulfinyl-phenyl)-5-p-tolyl-3-trifluoromethyl-1H-pyrazole 
• 365530-13-8 4-[5-(4-methylphenyl)-3-trifluoromethyl-1H-pyrazol-1-yl]aniline 

Downstream Products

• 921617-79-0 (R,S)-2-[4-(5-p-methylphenyl-3-trifluoromethyl-pyrazol-1-yl)-benzensulfonylamino-oxy]-propionic acid 
• 169590-42-5 4-[5-(4-(methyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulphonamide 

Relevant academic research and scientific papers

Neuroprotective effect of novel celecoxib derivatives against spinal cord injury via attenuation of COX-2, oxidative stress, apoptosis and inflammation

A novel series of celecoxib derivatives were synthesized and evaluated for cyclooxygenase (COX-1/COX-2) inhibitory activities for benefit in spinal cord injury (SCI). The title compounds were synthesized by conventional methods in good yields and subsequently tested for inhibitory activity against COX-1/COX-2. The most potent COX-2 inhibitor among the tested derivatives was further assayed for protective effect against experimental SCI of Sprague-Dawley rats. The designed compounds showed considerable inhibition of COX-2 as compared to COX-1 revealing compound 7m as most potent inhibitor of COX-2 isoenzyme (IC50 = 0.04 μM). The expression of mitochondrial apoptotic genes (Bcl-2 and Bax) together with COX-2 and iNOS was restored near to normal as evidenced by western blot analysis in SCI rats. Taken altogether, compound 7m was identified as most potent inhibitor of COX-2. It also showed protective action against SCI via attenuation of COX-2, oxidative stress and apoptosis and inflammation in Male Sprague-Dawley rats.

In Cellulo Generation of Fluorescent Probes for Live-Cell Imaging of Cylooxygenase-2

Live-cell imaging with fluorescent probes is an essential tool in chemical biology to visualize the dynamics of biological processes in real-time. Intracellular disease biomarker imaging remains a formidable challenge due to the intrinsic limitations of conventional fluorescent probes and the complex nature of cells. This work reports the in cellulo assembly of a fluorescent probe to image cyclooxygenase-2 (COX-2). We developed celecoxib-azide derivative 14, possessing favorable biophysical properties and excellent COX-2 selectivity profile. In cellulo strain-promoted fluorogenic click chemistry of COX-2-engaged compound 14 with non/weakly-fluorescent compounds 11 and 17 formed fluorescent probes 15 and 18 for the detection of COX-2 in living cells. Competitive binding studies, biophysical, and comprehensive computational analyses were used to describe protein-ligand interactions. The reported new chemical toolbox enables precise visualization and tracking of COX-2 in live cells with superior sensitivity in the visible range.

Preparation method of celecoxib genotoxic impurity

The invention provides a preparation method of a celecoxib genotoxic impurity. The method comprises the following steps: step 1, cyclizing G1 and G2 to generate G3; step 2, carrying out sulfonylationon the G3 to obtain G4; 3, generating G5 by the G4, name

Selective Late-Stage Sulfonyl Chloride Formation from Sulfonamides Enabled by Pyry-BF4

Reported here is a simple and practical functionalization of primary sulfonamides, by means of a pyrylium salt (Pyry-BF4), with nucleophiles. This simple reagent activates the poorly nucleophilic NH2 group in a sulfonamide, enabling the formation of one of the best electrophiles in organic synthesis: a sulfonyl chloride. Because of the variety of primary sulfonamides in pharmaceutical contexts, special attention has been focused on the direct conversion of densely functionalized primary sulfonamides by a late-stage formation of the corresponding sulfonyl chloride. A variety of nucleophiles could be engaged in this transformation, thus permitting the synthesis of complex sulfonamides, sulfonates, sulfides, sulfonyl fluorides, and sulfonic acids. The mild reaction conditions and the high selectivity of Pyry-BF4 towards NH2 groups permit the formation of sulfonyl chlorides in a late-stage fashion, tolerating a preponderance of sensitive functionalities.

New celecoxib derivatives as anti-inflammatory agents

A series of 1,5-diarylpyrazoles with a substituted benzenesulfonamide moiety was synthesized and evaluated for cyclooxygenase (COX-1/COX-2) inhibitory activities. Some compounds, for example, (±)-2-[4-(5-p-tolyl-3- trifluoromethyl-pyrazole-1-yl)-benzenesulfonylaminooxy]-propionic acid 16 and its disodium salt 21, had a higher in vivo anti-inflammatory activity compared to celecoxib, despite having no in vitro COX-1 or COX-2 inhibitory activity. Their gastrointestinal side effect profile is essentially more favorable than that of celecoxib.

NEW 1 , 2 -DIARYL PYRAZOLES USEFUL AS ANALGETIC AND ANTI-INFLAMMATORY AGENTS

The present invention relates to new compounds of formula (I), (I) wherein the meaning of R1 is hydrogen atom, C1-C5 acyl group, benzoyl group or R2- COOR3 group, Y is hydrogen atom or alkali ion, R2 is C1-C4 straight or branched alkylidene group and R3 is hydrogen atom, C1-C4 alkyl group or alkali ion, and/or stereoisomers and/or diastereomers and/or pharmaceutically acceptable salts and/or hydrates and/or solvates thereof, which are suitable for the treatment of pain of acute and chronic inflammation origin as well as postoperative pain and dysmenorrhea. The invention also relates to the process of the synthesis of compounds of formula (I) as well as the pharmaceutical composition containing the same and the use for treatment of pain, inflammation and disorders associated with inflammation.

Design and synthesis of novel celecoxib analogues as selective cyclooxygenase-2 (COX-2) inhibitors: Replacement of the sulfonamide pharmacophore by a sulfonylazide bioisostere

A group of celecoxib analogues in which the para-SO2NH 2 substituent on the N1-phenyl ring was replaced by a para-sulfonylazido (SO2N3) 4, or a meta-SO 2N3 8, substituent were designed for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. In vitro COX-1 and COX-2 inhibition studies showed that 4-[5-(4-methylphenyl)-3-trifluoromethyl-1H- pyrazol-1-yl]benzenesulfonyl azide (4) with a para-SO2N3 substituent was a selective COX-1 inhibitor. In contrast, 3-[5-(4-methylphenyl)- 3-trifluoromethylpyrazol-1-yl]benzenesulfonyl azide (8a) having a meta-SO 2N3 substituent (COX-1 IC50 >100 μM; COX-2 IC50=5.16 μM; COX-2 selectivity index >19.3) is a selective COX-2 inhibitor. A molecular modeling (docking) study showed that the SO2N3 group of 8a inserts deep inside the secondary pocket of the COX-2 binding site. The SO2N3 moiety of 8a can undergo a dual H-bonding interaction via one of its SO2 oxygen-atoms, and an electrostatic (ion-ion) interaction via the terminal azido (N3) nitrogen-atom, to the guanidino NH2 of Arg 513 in the secondary pocket of COX-2. These observations indicate that an appropriately positioned SO2N3 moiety is a novel alternative bioisostere to the traditional SO2NH2 and SO2Me pharmacophores present in selective COX-2 inhibitors, that are only capable of H-bonding interactions with the COX-2 isozyme, for use in drug design.

Remarkably Mild and Simple Preparations of Sulfinates, Sulfonyl Chlorides and Sulfonamides from Thioanisoles

New and high yielding procedures to convert thioanisoles into versatile sulfonyl chloride derivatives were developed by strategically taking advantage of the Pummerer reaction.