Syk inhibitors with high potency in presence of blood

  • Bioorg Med Chem Lett. 2014 May 15;24(10):2278-82. doi: 10.1016/j.bmcl.2014.03.075.
Gebhard Thoma  1 ,  Joachim Blanz  2 ,  Peter Bühlmayer  2 ,  Peter Drückes  2 ,  Matthias Kittelmann  2 ,  Alexander B Smith  2 ,  Maurice van Eis  2 ,  Eric Vangrevelinghe  2 ,  Hans-Günter Zerwes  2 ,  Jianwei John Che  3 ,  Xiaohui He  3 ,  Yunho Jin  3 ,  Christian C Lee  3 ,  Pierre-Yves Michellys  3 ,  Tetsuo Uno  3 ,  Hong Liu  3
Affiliations
  • 1. Novartis Institutes for Biomedical Research, Forum 1 Novartis Campus, 4056 Basel, Switzerland. Electronic address: [email protected].
  • 2. Novartis Institutes for Biomedical Research, Forum 1 Novartis Campus, 4056 Basel, Switzerland.
  • 3. Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
PMID: 24726806 DOI: 10.1016/j.bmcl.2014.03.075
Abstract

We describe two series of Syk inhibitors which potently abrogate Syk kinase function in enzymatic assays, cellular assays and in primary cells in the presence of blood. Introduction of a 7-aminoindole substituent led to derivatives with good kinase selectivity and little or no hERG channel inhibition (3b, 10c).

Keywords
Aldehyde oxidase; BIIB-057; Fostamatinib; Kinase inhibitors; Spleen tyrosine kinase.