Kinase array design, back to front: biaryl amides.

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Baldwin I, Bamborough P, Haslam CG, Hunjan SS, Longstaff T, Mooney CJ, Patel S, Quinn J, Somers DO

Kinase array design, back to front: biaryl amides.

Bioorg Med Chem Lett. 2008 Oct 1;18(19):5285-9. doi: 10.1016/j.bmcl.2008.08.051. Epub 2008 Aug 22.

PubMed ID

18789685 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
N-cyclopropyl-2',6-dimethyl-4'-(5-methyl-1,3,4-oxadiazol-2-yl)biphenyl-3-carboxamide	Mitogen-activated protein kinase 14	Ki (nM)	10	N/A	N/A	Details