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

  • Bioorg Med Chem Lett. 2006 Jul 15;16(14):3706-12. doi: 10.1016/j.bmcl.2006.04.060.
Jagabandhu Das  1 ,  Joseph A Furch ,  Chunjian Liu ,  Robert V Moquin ,  James Lin ,  Steven H Spergel ,  Kim W McIntyre ,  David J Shuster ,  Kathleen D O'Day ,  Becky Penhallow ,  Chen-Yi Hung ,  Arthur M Doweyko ,  Amrita Kamath ,  Hongjian Zhang ,  Punit Marathe ,  Steven B Kanner ,  Tai-An Lin ,  John H Dodd ,  Joel C Barrish ,  John Wityak
Affiliations
  • 1. Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA. [email protected]
PMID: 16682193 DOI: 10.1016/j.bmcl.2006.04.060
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.