title: Synthesis and biological evaluation of 2-pyridyl-substituted pyrazoles and imidazoles as transforming growth factor-beta type 1 receptor kinase inhibitors.
abstract: A series of 2-pyridyl-substituted pyrazoles (16a-d, 17, 18, and 28a-e) and imidazoles (22 and 23) has been synthesized and evaluated for their ALK5 inhibitory activity in cell-based luciferase reporter assays. Among them, 3-(3-(6-methylpyridin-2-yl)-4-(quinolin-6-yl)-1H-pyrazole-1-carbothioamido)benzamide (28c) showed 96% and 93% inhibition at 0.1 microM in luciferase reporter assays using HaCaT cells transiently transfected with p3TP-luc reporter construct and ARE-luc reporter construct, respectively.
authors.affiliation: College of Pharmacy, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-gu, Seoul 120-750, Republic of Korea.
authors.forename: Purushottam M
authors.initials: PM
authors.lastname: Dewang
authors.forename: Dae-Kee
authors.initials: DK
authors.lastname: Kim
mesh_terms: D002460:Cell Line; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors*
chemical_list: D007093:Imidazoles; D011720:Pyrazoles; D018125:Receptors, Transforming Growth Factor beta; D020794:Receptor Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human