title: Synthesis and biological evaluation of 2-benzylamino-4(5)-(6-methylpyridin-2-yl)-5(4)-([1,2,4]triazolo[1,5-a]-pyridin-6-yl)thiazoles as transforming growth factor-β type 1 receptor kinase inhibitors.
abstract: A series of 2-benzylamino-4(5)-(6-methylpyridin-2-yl)-5(4)-([1,2,4]triazolo[1,5-a]pyridin-6-yl)thiazoles 12a-ab, 13a, 13b, and 18a-d has been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The N-(3-fluorobenzyl)-4-(6-methylpyridin-2-yl)-5-([1,2,4]triazolo[1,5-a]pyridin-6-yl)thiazol-2-amine (12b) inhibited ALK5 phosphorylation with an IC(50) value of 7.01 nM and showed 61% inhibition at 30 nM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct.
authors.affiliation: College of Pharmacy, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-gu, Seoul 120-750, South Korea.
authors.forename: Maddeboina
authors.initials: M
authors.lastname: Krishnaiah
authors.forename: Cheng Hua
authors.initials: CH
authors.lastname: Jin
authors.forename: Domalapally
authors.initials: D
authors.lastname: Sreenu
authors.forename: Vura Bala
authors.initials: VB
authors.lastname: Subrahmanyam
authors.forename: Kota Sudhakar
authors.initials: KS
authors.lastname: Rao
authors.forename: Do-Hyun
authors.initials: DH
authors.lastname: Son
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Park
authors.forename: Seung Won
authors.initials: SW
authors.lastname: Kim
authors.forename: Yhun Yhong
authors.initials: YY
authors.lastname: Sheen
authors.forename: Dae-Kee
authors.initials: DK
authors.lastname: Kim
mesh_terms: D002461:Cell Line, Transformed; D057075:Enzyme Assays; D017930:Genes, Reporter; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology; D008156:Luciferases; D062105:Molecular Docking Simulation; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D014162:Transfection
chemical_list: D047428:Protein Kinase Inhibitors; D018125:Receptors, Transforming Growth Factor beta; D013844:Thiazoles; D008156:Luciferases; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human