157671-97-1Relevant academic research and scientific papers
Synthesis and biological evaluation of 2,3-diarylpyrazines and quinoxalines as selective COX-2 inhibitors
Singh, Sunil K.,Saibaba,Ravikumar,Rudrawar, Santosh V.,Daga, Pankaj,Rao, C. Seshagiri,Akhila,Hegde,Rao, Y. Koteswar
, p. 1881 - 1893 (2007/10/03)
Several 2,3-diaryl pyrazines and quinoxalines with 4-sulfamoyl (SO 2NH2)/methylsulfonyl (SO2Me)-phenyl pharmacophores have been synthesized and evaluated for the cyclooxygenase (COX-1/COX-2) inhibitory activity. Smaller groups such as methoxy, methyl and fluoro when substituted at/around position-4 of the adjacent phenyl ring, have great impact on the selective COX-2 inhibitory activity of the series. Many potential compounds were obtained from a brief structure-activity relationship (SAR) study. Two of these, compounds 11 and 25 exhibited excellent in vivo activity in the established animal model of inflammation. Since compound 25 possessed an amenable sulfonamide group, two of its prodrugs 48 and 49 were also synthesized. Both of them have excellent in vivo potential, and represent a new class of COX-2 inhibitor.
Method of treating skin related conditions
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, (2008/06/13)
A class of 3,4-diaryl substituted thiophene, derivatives and analogs thereof, pharmaceutical compositions containing them and methods of using them to treat inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula I: wherein Y is S; wherein X is one or two substituents selected from hydrido, halo, lower alkoxycarbonyl and carboxyl; wherein R2 and R3 are independently aryl or heteroaryl; and wherein R2 and R3 are optionally substituted with one or more radicals selected from sulfamyl, alkylsulfonyl, halo, lower alkoxy and lower alkyl; or a pharmaceutically-acceptable salt thereof.
Antiinflammatory 4,5-diarylimidazoles as selective cyclooxygenase inhibitors
Barta, Thomas E.,Stealey, Michael A.,Collins, Paul W.,Weier, Richard M.
, p. 3443 - 3448 (2007/10/03)
The synthesis and activity of a series of 4,5-diarylimidazole analogs are described. One analog had an IC50 of 80 nM, was 6750-selective against COX-1, and demonstrated in vivo potency in the mouse air pouch model.
Novel terphenyls as selective cyclooxygenase-2 inhibitors and orally active anti-inflammatory agents
Li, James J.,Norton, Monica B.,Reinhard, Emily J.,Anderson, Gary D.,Gregory, Susan A.,Isakson, Peter C.,Koboldt, Carol M.,Masferrer, Jaime L.,Perkins, William E.,Seibert, Karen,Zhang, Yan,Zweifel, Ben S.,Reitz, David B.
, p. 1846 - 1856 (2007/10/03)
A novel series of terphenyl methyl sulfones and sulfonamides have been shown to be highly potent and selective cyclooxygenase-2 (COX-2) inhibitors. The sulfonamide analogs 17 and 21 were found to be much more potent COX-2 inhibitors and orally active anti-inflammatory agents than the corresponding methyl sulfone analogs 16 and 20, respectively, albeit with some decrease in COX-2 selectivity. Structure-activity relationship studies have determined that incorporation of two fluorine atoms in the central phenyl group, as in 20 and 21, is extremely advantageous for both in vitro COX-2 potency and selectivity as well as in vivo activity. Several noticeable examples in the 1,2-diaryl-4,5-difluorobenzenesulfonamide series are 21a-c,k,l,n (COX-2, IC50 = 0.002-0.004 μM), in which all have in vitro COX-1/COX-2 selectivity > 1000. In addition, sulfonamides 21a,b,d,g,j,m,n,q were shown to have greatly enhanced oral activity with more than 90% inhibition of prostaglandin E2 production in the air pouch model of inflammation. Furthermore, sulfonamide 21b was found to be very active in the rat adjuvant-induced arthritis model (ED50 = 0.05 mg/kg) and carrageenan-induced hyperalgesia assay (ED50 = 38.7 mg/kg) with no indication of gastrointestinal toxicity in rats at doses as high as 200 mg/kg.
