title: Synthesis and biological evaluation of 1-substituted-3-(6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrazoles as transforming growth factor-β type 1 receptor kinase inhibitors.
abstract: A series of 1-substituted-3-(6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrazoles 14a-ae, 16a, 16b, and 21a-c has been prepared and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(4-methoxyphenyl)-3-(6-methylpyridin-2-yl)-1H-pyrazole-1-carbothioamide (14n) inhibited ALK5 phosphorylation with IC(50) value of 0.57 nM and showed 94% inhibition at 100 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, Republic of Korea.
authors.forename: Cheng Hua
authors.initials: CH
authors.lastname: Jin
authors.forename: Maddeboina
authors.initials: M
authors.lastname: Krishnaiah
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: Annaji Venkata Nagendra
authors.initials: AV
authors.lastname: Mohan
authors.forename: Chul-Yong
authors.initials: CY
authors.lastname: Park
authors.forename: Jee-Yeon
authors.initials: JY
authors.lastname: Son
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; D007313:Insecta / Q000166:cytology; D008156:Luciferases / Q000032:analysis; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; 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* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D018125:Receptors, Transforming Growth Factor beta; D011993:Recombinant Fusion Proteins; D008156:Luciferases; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human