Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1370904 | Bioorganic & Medicinal Chemistry Letters | 2011 | 5 Pages |
We have increased the potency of imidazo[1,2-b]pyridazine derivatives as IKKβ inhibitors with two strategies. One is to enhance the activity in cell-based assay by adjusting the polarity of molecules to improve permeability. Another is to increase the affinity for IKKβ by the introduction of additional substituents based on the hypothesis derived from an interaction model study. These improved compounds showed inhibitory activity of TNFα production in mice.
Graphical abstractWe have increased the potency of imidazo[1,2-b]pyridazine derivatives as IKKβ inhibitors with two strategies. One is to enhance the activity in cell-based assay by adjusting the polarity of molecules to improve permeability. Another is to increase the affinity for IKKβ by the introduction of additional substituents based on the hypothesis derived from an interaction model study. These improved compounds such as 7c showed inhibitory activity of TNFα production in mice.Figure optionsDownload full-size imageDownload as PowerPoint slide