title: Synthesis and biological evaluation of benzenesulfonamide-substituted 4-(6-alkylpyridin-2-yl)-5-(quinoxalin-6-yl)imidazoles as transforming growth factor-beta type 1 receptor kinase inhibitors.
abstract: A series of benzenesulfonamide-substituted 4-(6-alkylpyridin-2-yl)-5-(quinoxalin-6-yl)imidazoles have been synthesized and evaluated for their ALK5 inhibitory activity in cell-based luciferase reporter assays. Among them, 4-[5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-ylmethyl]benzenesulfonamide and 4-[5-(6-ethylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-ylmethyl]benzenesulfonamide showed more than 90% inhibition at 0.5 microM in a luciferase reporter assay using HaCaT cells transiently transfected with p3TP-luc reporter construct, but inhibited p38alpha MAP kinase activity only 11 and 8% at a concentration of 10 microM, respectively.
authors.affiliation: College of Pharmacy, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-gu, Seoul 120-750, South Korea. dkkim@ewha.ac.kr
authors.forename: Dae-Kee
authors.initials: DK
authors.lastname: Kim
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Jung
authors.forename: Ho Soon
authors.initials: HS
authors.lastname: Lee
authors.forename: Purushottam M
authors.initials: PM
authors.lastname: Dewang
mesh_terms: D002460:Cell Line; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013449:Sulfonamides; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D000096926:Benzenesulfonamides
chemical_list: D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta; D013449:Sulfonamides; D048051:p38 Mitogen-Activated Protein Kinases; D000096926:Benzenesulfonamides; C000625841:TGFBR1 protein, human