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

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Farmer LJ, Bemis G, Britt SD, Cochran J, Connors M, Harrington EM, Hoock T, Markland W, Nanthakumar S, Taslimi P, Ter Haar E, Wang J, Zhaveri D, Salituro FG

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

Bioorg Med Chem Lett. 2008 Dec 1;18(23):6231-5. doi: 10.1016/j.bmcl.2008.09.106. Epub 2008 Oct 7.

PubMed ID

18938080 [ View in PubMed

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Abstract

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 K(i)'s against SYK and potent inhibition in mast cell degranulation assays.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
2-{2-[(3,5-dimethylphenyl)amino]pyrimidin-4-yl}-N-[(1S)-2-hydroxy-1-methylethyl]-4-methyl-1,3-thiazole-5-carboxamide	Tyrosine-protein kinase SYK	Ki (nM)	9	N/A	N/A	Details
2-{2-[(3,5-dimethylphenyl)amino]pyrimidin-4-yl}-N-[(1S)-2-hydroxy-1-methylethyl]-4-methyl-1,3-thiazole-5-carboxamide	Tyrosine-protein kinase SYK	IC 50 (nM)	70	N/A	N/A	Details