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Bioorg Med Chem Lett. 2006 Jul 15;16(14):3706-12. Epub 2006 May 6.

Discovery and SAR of 2-amino-5-(thioaryl)thiazoles as potent and selective Itk inhibitors.

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  • 1Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA. jagabandhu.das@bms.com

Abstract

A series of structurally novel aminothiazole based small molecule inhibitors of Itk were prepared to elucidate their structure-activity relationships (SARs), selectivity, and cell activity in inhibiting IL-2 secretion in a Jurkat T-cell assay. Compound 3 is identified as a potent and selective Itk inhibitor which inhibits anti-TCR antibody induced IL-2 production in mice in vivo and was previously reported to reduce lung inflammation in a mouse model of ovalbumin induced allergy/asthma.

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