title: Oxindole derivatives as inhibitors of TAK1 kinase.
abstract: Several series of oxindole analogues were synthesized and screened for inhibitory activity against transforming growth factor-β-activating kinase 1 (TAK1). Modifications around several regions of the lead molecules were made, with a distal hydroxyl group in the D region being critical for activity. The most potent compound 10 shows an IC(50) of 8.9 nM against TAK1 in a biochemical enzyme assay, with compounds 3 and 6 showing low micromolar cellular inhibition.
authors.affiliation: Departments of Chemistry, Myrexis, Inc., Salt Lake City, UT 84108, USA. jeffrey.lockman@myrexis.com
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Lockman
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Reeder
authors.forename: Rosann
authors.initials: R
authors.lastname: Robinson
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Ormonde
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Cimbora
authors.forename: Brandi L
authors.initials: BL
authors.lastname: Williams
authors.forename: J Adam
authors.initials: JA
authors.lastname: Willardsen
mesh_terms: D007211:Indoles / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors*; D000078183:Oxindoles; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D007211:Indoles; D020930:MAP Kinase Kinase Kinases; D000078183:Oxindoles; D047428:Protein Kinase Inhibitors; D000099151:MAP Kinase Kinase Kinase 7; C022960:2-oxindole