Selective COX-2 inhibitors. Part 1: synthesis and biological evaluation of phenylazobenzenesulfonamides.
A series of phenylazobenzenesulfonamide derivatives were designed and synthesized for the evaluation as selective cyclooxygenase-2 (COX-2) inhibitors in a cellular assay using human whole blood (HWB) and an enzymatic assay using purified ovine enzymes. Extensive structure-activity relationships (SAR) were studied within this series, and several of selective COX-2 inhibitors have been identified. Among them, compound 8, 4-(4-amino-2-methylsulfanyl-phenylazo)benzenesulfonamide, showed a potent inhibitory activity to the cyclooxygenase enzymes (IC(50)'s for COX-1: 23.28 microM; COX-2: 2.04 microM), being active but less COX-2 selective than celecoxib.
Tsai
Wei-Jern
WJ
Division of Medicinal Chemistry, National Research Institute of Chinese Medicine, Taipei, Taiwan.
Shiao
Young-Ji
YJ
Lin
Shwu-Jiuan
SJ
Chiou
Wen-Fei
WF
Lin
Lie-Chwen
LC
Yang
Tsang-Hsiung
TH
Teng
Che-Ming
CM
Wu
Tain-Shung
TS
Yang
Li-Ming
LM
D001391:Azo Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001773:Blood Cells / Q000187:drug effects* / Q000201:enzymology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D001391:Azo Compounds; D052246:Cyclooxygenase 2 Inhibitors; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C009850:azobenzene