Discovery and SAR of novel 4-thiazolyl-2-phenylaminopyrimidines as potent inhibitors of spleen tyrosine kinase (SYK)

Autor:	William Markland, Ernst ter Haar, Darshana Zhaveri, Guy W. Bemis, Thomas Hoock, Martin Connors, Francesco G. Salituro, Shawn D. Britt, Cochran John E, Suganthini Nanthakumar, Edmund Harrington, Jian Wang, Luc J. Farmer, Paul Taslimi
Rok vydání:	2008
Předmět:	Clinical Biochemistry Molecular Conformation Pharmaceutical Science Syk chemical and pharmacologic phenomena Crystallography X-Ray environment and public health Biochemistry Structure-Activity Relationship chemistry.chemical_compound hemic and lymphatic diseases Drug Discovery Animals Combinatorial Chemistry Techniques Syk Kinase Mast Cells Thiazole Protein Kinase Inhibitors Molecular Biology chemistry.chemical_classification Molecular Structure biology Organic Chemistry Intracellular Signaling Peptides and Proteins Degranulation hemic and immune systems Biological activity Protein-Tyrosine Kinases In vitro Rats Thiazoles Pyrimidines Enzyme chemistry Enzyme inhibitor Drug Design Microsomes Liver biology.protein Molecular Medicine biological phenomena cell phenomena and immunity Signal transduction Spleen
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 18:6231-6235
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2008.09.106
Popis:	A series of SYK inhibitors based on the phenylamino pyrimidine thiazole lead 4 were prepared and evaluated for biological activity. Lead optimization provided compounds with nanomolar Ki’s against SYK and potent inhibition in mast cell degranulation assays.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7d2a734cf4205416eba869a8c2e13177 https://doi.org/10.1016/j.bmcl.2008.09.106 Zobrazit plný text záznamu Full Text from ScienceDirect