title: Discovery of indazoles as inhibitors of Tpl2 kinase.
abstract: Synthesis, modeling and structure-activity relationship of indazoles as inhibitors of Tpl2 kinase are described. From a high throughput screening effort, we identified an indazole hit compound 5 that has a single digit micromolar Tpl2 activity. Through SAR modifications at the C3 and C5 positions of the indazole, we discovered compound 31 with good potency in LANCE assay and cell-based p-Erk assay.
authors: Worldwide Medicinal Chemistry, Pfizer Global Research and Development, 200 CambridgePark Drive, Cambridge, MA 02140, USA.
authors: Yonghan
authors: Y
authors: Hu
authors: Derek
authors: D
authors: Cole
authors: Rajiah Aldrin
authors: RA
authors: Denny
authors: David R
authors: DR
authors: Anderson
authors: Manus
authors: M
authors: Ipek
authors: Yike
authors: Y
authors: Ni
authors: Xiaolun
authors: X
authors: Wang
authors: Suvit
authors: S
authors: Thaisrivongs
authors: Timothy
authors: T
authors: Chamberlain
authors: J Perry
authors: JP
authors: Hall
authors: Julie
authors: J
authors: Liu
authors: Michael
authors: M
authors: Luong
authors: Lih-Ling
authors: LL
authors: Lin
authors: Jean-Baptiste
authors: JB
authors: Telliez
authors: Ariamala
authors: A
authors: Gopalsamy
mesh_terms: D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007191:Indazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D009000:Monocytes / Q000201:enzymology / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007191:Indazoles; D011518:Proto-Oncogene Proteins; D020930:MAP Kinase Kinase Kinases; C069937:MAP3K8 protein, human