Selective COX-2 inhibitors. Part 2: synthesis and biological evaluation of 4-benzylideneamino- and 4-phenyliminomethyl-benzenesulfonamides.
Two series of 4-benzylideneamino- and 4-phenyliminomethyl-benzenesulfonamide derivatives were designed and synthesized for the evaluation as selective cyclooxygenase-2 (COX-2) inhibitors in a cellular assay using human whole blood (HWB). Extensive structure-activity relationships (SAR) were studied within these series. Several compounds were found to be novel and selective COX-2 inhibitors. Among them, the most potent and selective was 4-(3-carboxy-4-hydroxy-benzylideneamino)benzenesulfonamide (20, LA2135), (IC(50)'s for COX-1: 85.13 microM; COX-2: 0.74 microM; SI: 114.5), being more active COX-2 selective than celecoxib.
Department of Medicinal Chemistry, College of Pharmacy, Taipei Medical University, 250 Wu-Hsing St., Taipei 110, Taiwan.
Shwu-Jiuan
SJ
Lin
Wei-Jern
WJ
Tsai
Wen-Fei
WF
Chiou
Tsang-Hsiung
TH
Yang
Li-Ming
LM
Yang
D000586:Amination; D001597:Benzylidene Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007097:Imines / Q000737:chemistry*; D008745:Methylation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000096926:Benzenesulfonamides
D001597:Benzylidene Compounds; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D007097:Imines; D013449:Sulfonamides; D000096926:Benzenesulfonamides