Publication Abstract from PubMed
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 p38alpha 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.
Kinase array design, back to front: biaryl amides.,Baldwin I, Bamborough P, Haslam CG, Hunjan SS, Longstaff T, Mooney CJ, Patel S, Quinn J, Somers DO Bioorg Med Chem Lett. 2008 Oct 1;18(19):5285-9. Epub 2008 Aug 22. PMID:18789685[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
