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

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.
John Liddle 1 Francis L Atkinson Michael D Barker Paul S Carter Neil R Curtis Rob P Davis Clement Douault Marion C Dickson Dorothy Elwes Neil S Garton Matthew Gray Thomas G Hayhow Clare I Hobbs Emma Jones Stuart Leach Karen Leavens Huw D Lewis Scott McCleary Margarete Neu Vipulkumar K Patel Alex G S Preston Cesar Ramirez-Molina Tracy J Shipley Philip A Skone Nick Smithers Donald O Somers Ann L Walker Robert J Watson Gordon G Weingarten
Affiliations

Affiliation

  • 1 GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, UK. john.2.liddle@gsk.com
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.

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