title: Synthesis and biological evaluation of 1-substituted-3(5)-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)pyrazoles as transforming growth factor-β type 1 receptor kinase inhibitors.
abstract: A series of 1-substituted-3(5)-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)pyrazoles 14a-d, 15a-d, 17a, 17b, 18a-d, 19a, and 19b has been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The 2-[3-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-pyrazol-1-yl]-N-phenylethanethioamide (18a) inhibited ALK5 phosphorylation with an IC(50) value of 0.013 μM and showed 80% inhibition at 0.1 μM 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: Cheng Hua
authors.initials: CH
authors.lastname: Jin
authors.forename: Domalapally
authors.initials: D
authors.lastname: Sreenu
authors.forename: Maddeboina
authors.initials: M
authors.lastname: Krishnaiah
authors.forename: Vura Bala
authors.initials: VB
authors.lastname: Subrahmanyam
authors.forename: Kota Sudhakar
authors.initials: KS
authors.lastname: Rao
authors.forename: Annaji Venkata
authors.initials: AV
authors.lastname: Nagendra Mohan
authors.forename: Chul-Yong
authors.initials: CY
authors.lastname: Park
authors.forename: Jee-Yeon
authors.initials: JY
authors.lastname: Son
authors.forename: Do-Hyun
authors.initials: DH
authors.lastname: Son
authors.forename: Hyun-Ju
authors.initials: HJ
authors.lastname: Park
authors.forename: Yhun Yhong
authors.initials: YY
authors.lastname: Sheen
authors.forename: Dae-Kee
authors.initials: DK
authors.lastname: Kim
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors*; D021241:Spectrometry, Mass, Electrospray Ionization; D014961:X-Ray Diffraction
chemical_list: D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human