98645-44-4Relevant academic research and scientific papers
The discovery of thienopyridine analogues as potent IκB kinase β inhibitors. Part II
Wu, Jiang-Ping,Fleck, Roman,Brickwood, Janice,Capolino, Alison,Catron, Katrina,Chen, Zhidong,Cywin, Charles,Emeigh, Jonathan,Foerst, Melissa,Ginn, John,Hrapchak, Matt,Hickey, Eugene,Hao, Ming-Hong,Kashem, Mohammed,Li, Jun,Liu, Weimin,Morwick, Tina,Nelson, Richard,Marshall, Daniel,Martin, Leslie,Nemoto, Peter,Potocki, Ian,Liuzzi, Michel,Peet, Gregory W.,Scouten, Erika,Stefany, David,Turner, Michael,Weldon, Steve,Zimmitti, Clare,Spero, Denise,Kelly, Terence A.
scheme or table, p. 5547 - 5551 (2010/04/05)
An SAR study that identified a series of thienopyridine-based potent IκB Kinase β (IKKβ) inhibitors is described. With focuses on the structural optimization at C4 and C6 of structure 1 (Fig. 1), the study reveals that small alkyl and certain aromatic groups are preferred at C4, whereas polar groups with proper orientation at C6 efficiently enhance compound potency. The most potent analogues inhibit IKKβ with IC50s as low as 40 nM, suppress LPS-induced TNF-α production in vitro and in vivo, display good kinase selectivity profiles, and are active in a HeLa cell NF-κB reporter gene assay, demonstrating that they directly interfere with the NF-κB signaling pathway.
