Discovery of 6-Aryl-7-alkoxyisoquinoline Inhibitors of IκB Kinase-β (IKK-β)

JA Christopher, P Bamborough, C Alder…

Index: Christopher, John A.; Bamborough, Paul; Alder, Catherine; Campbell, Amanda; Cutler, Geoffrey J.; Down, Kenneth; Hamadi, Ahmed M.; Jolly, Adrian M.; Kerns, Jeffrey K.; Lucas, Fiona S.; Mellor, Geoffrey W.; Miller, David D.; Morse, Mary A.; Pancholi, Kiritkant D.; Rumsey, William; Solanke, Yemisi E.; Williamson, Rick Journal of Medicinal Chemistry, 2009 , vol. 52, # 9 p. 3098 - 3102

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Citation Number: 28

Abstract

The identification and progression of a potent and selective series of isoquinoline inhibitors of IκB kinase-β (IKK-β) are described. Hit-generation chemistry based on IKK-β active-site knowledge yielded a weakly potent but tractable chemotype that was rapidly progressed into a series with robust enzyme and cellular activity and significant selectivity over IKK-α.

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