Discovery of GSK143, a highly potent, selective and orally efficacious spleen tyrosine kinase inhibitor
Copyright policy )Discovery of GSK143, a highly potent, selective and orally efficacious spleen tyrosine kinase inhibitor
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.
- Cellzome, GSK, Middlesex, UK.
- GlaxoSmithKline (United Kingdom) United Kingdom
Models, Molecular, Aniline Compounds, Anti-Inflammatory Agents, Intracellular Signaling Peptides and Proteins, Administration, Oral, Protein-Tyrosine Kinases, Crystallography, X-Ray, Rats, Structure-Activity Relationship, Pyrimidines, Drug Discovery, Arthus Reaction, Animals, Humans, Syk Kinase, Protein Kinase Inhibitors
Models, Molecular, Aniline Compounds, Anti-Inflammatory Agents, Intracellular Signaling Peptides and Proteins, Administration, Oral, Protein-Tyrosine Kinases, Crystallography, X-Ray, Rats, Structure-Activity Relationship, Pyrimidines, Drug Discovery, Arthus Reaction, Animals, Humans, Syk Kinase, Protein Kinase Inhibitors
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