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

Autor:	Philip Alan Skone, Donald O. Somers, Marion C. Dickson, Nick Smithers, Ann Louise Walker, Thomas George Christopher Hayhow, Stuart G. Leach, Karen Leavens, Clement Douault, Emma J. Jones, Dorothy Elwes, Robert J. Watson, Margarete Neu, Robert P. Davis, Matthew Gray, Neil Stuart Garton, Clare I. Hobbs, Alex Preston, Michael David Barker, Vipulkumar Kantibhai Patel, Cesar Ramirez-Molina, Paul S. Carter, Scott McCleary, Gordon G. Weingarten, Huw D. Lewis, Francis Louis Atkinson, John Liddle, Tracy Jane Shipley, Neil R. Curtis
Rok vydání:	2011
Předmět:	Models Molecular medicine.drug_class Clinical Biochemistry hERG Anti-Inflammatory Agents Administration Oral Pharmaceutical Science Syk Carboxamide Pharmacology Crystallography X-Ray Biochemistry Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Arthus Reaction medicine Animals Humans Syk Kinase Tyrosine Protein Kinase Inhibitors Molecular Biology Aniline Compounds biology Arthus reaction Drug discovery Kinase Organic Chemistry Intracellular Signaling Peptides and Proteins Protein-Tyrosine Kinases medicine.disease Rats Pyrimidines Diaminopyrimidine chemistry biology.protein Molecular Medicine
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 21:6188-6194
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2011.07.082
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::58fce9afb90ca4e724d4726df2268b6f https://doi.org/10.1016/j.bmcl.2011.07.082 Zobrazit plný text záznamu Full Text from ScienceDirect