title: Synthesis and biological evaluation of 1-substituted-3(5)-(6-methylpyridin-2-yl)-4-(quinolin-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-(quinolin-6-yl)pyrazoles 14a-e, 15a-e, 17a-c, and 18a-d have been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The 6-quinolinyl pyrazole analogue 14b inhibited ALK5 phosphorylation with IC(50) value of 0.022 μM and showed 84% inhibition at 0.1 μM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct.
authors: College of Pharmacy, Ewha Womans University, Seoul, Republic of Korea.
authors: Cheng Hua
authors: CH
authors: Jin
authors: Maddeboina
authors: M
authors: Krishnaiah
authors: Domalapally
authors: D
authors: Sreenu
authors: Kota Sudhakar
authors: KS
authors: Rao
authors: Vura Bala
authors: VB
authors: Subrahmanyam
authors: Chul-Yong
authors: CY
authors: Park
authors: Jee-Yeon
authors: JY
authors: Son
authors: Yhun Yhong
authors: YY
authors: Sheen
authors: Dae-Kee
authors: DK
authors: Kim
mesh_terms: D002460:Cell Line; D057075:Enzyme Assays; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
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