Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1372684 | Bioorganic & Medicinal Chemistry Letters | 2008 | 5 Pages |
New kinase inhibitors can be found by synthesis of targeted arrays of compounds designed using system-based knowledge as well as through screening focused or diverse compounds. Most array strategies aim to add functionality to a fragment that binds in the purine subpocket of the ATP-site. Here, an alternative pharmacophore-guided array approach is described which set out to discover novel purine subpocket-binding groups. Results are shown for p38α and cFMS kinase, for which multiple distinct series with nanomolar potency were discovered. Some of the compounds showed potency in cell-based assays and good pharmacokinetic properties.
Graphical abstractMost kinase-directed array strategies aim to add functionality to a fragment that binds in the purine subpocket of the ATP-site. Here, an alternative pharmacophore-guided array approach is described which set out to discover novel purine subpocket-binding groups. Results are shown for p38α and cFMS kinase, for which multiple different series with nanomolar potency were discovered.Figure optionsDownload full-size imageDownload as PowerPoint slide