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

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

来源：Bioorganic & Medicinal Chemistry Letters, 2011, 21(20): 6188-6194.

DOI：10.1016/j.bmcl.2011.07.082

• Spleen
• Tyrosine
• Kinase
• Inhibitor
• Herg
• SYK

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.

• 出版日期2011-10-15