Discovery of GSK143, a highly potent, selective and orally efficacious spleen tyrosine kinase inhibitor.

Article Details

Citation

Copy to clipboard

Liddle J, Atkinson FL, Barker MD, Carter PS, Curtis NR, Davis RP, Douault C, Dickson MC, Elwes D, Garton NS, Gray M, Hayhow TG, Hobbs CI, Jones E, Leach S, Leavens K, Lewis HD, McCleary S, Neu M, Patel VK, Preston AG, Ramirez-Molina C, Shipley TJ, Skone PA, Smithers N, Somers DO, Walker AL, Watson RJ, Weingarten GG

Discovery of GSK143, a highly potent, selective and orally efficacious spleen tyrosine kinase inhibitor.

Bioorg Med Chem Lett. 2011 Oct 15;21(20):6188-94. doi: 10.1016/j.bmcl.2011.07.082. Epub 2011 Aug 12.

PubMed ID

21903390 [ View in PubMed

]

Abstract

The lead optimisation of the diaminopyrimidine carboxamide series of spleen tyrosine kinase inhibitors is described. The medicinal chemistry strategy was focused on optimising the human whole blood activity whilst achieving a sufficient margin over liability kinases and hERG activity. GSK143 is a potent and highly selective SYK inhibitor showing good efficacy in the rat Arthus model.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
2-{[(1R,2S)-2-aminocyclohexyl]amino}-4-[(3-methylphenyl)amino]pyrimidine-5-carboxamide	Tyrosine-protein kinase SYK	IC 50 (nM)	6.31	N/A	N/A	Details