Synthesis and biological evaluation of 2,3-diarylpyrazines and quinoxalines as selective COX-2 inhibitors
Author(s)
Singh, SK
Saibaba, V
Ravikumar, V
Rudrawar, SV
Daga, P
Rao, CS
Akhila, V
Hegde, P
Rao, YK
Griffith University Author(s)
Year published
2004
Metadata
Show full item recordAbstract
Several 2,3-diaryl pyrazines and quinoxalines with 4-sulfamoyl (SO2NH2)/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 ...
View more >Several 2,3-diaryl pyrazines and quinoxalines with 4-sulfamoyl (SO2NH2)/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.
View less >
View more >Several 2,3-diaryl pyrazines and quinoxalines with 4-sulfamoyl (SO2NH2)/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.
View less >
Journal Title
Bioorganic & Medicinal Chemistry
Volume
12
Issue
8
Subject
Medicinal and biomolecular chemistry
Biologically active molecules
Organic chemistry
Pharmacology and pharmaceutical sciences
Pharmaceutical sciences