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
  • 1. GlaxoSmithKline R&D, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, UK. [email protected]
PMID: 21903390 DOI: 10.1016/j.bmcl.2011.07.082
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.

Products