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. Epub 2014 Apr 3.

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.

MeSH terms

  • Humans
  • Indoles / blood
  • Indoles / chemistry
  • Indoles / pharmacology
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors*
  • Intracellular Signaling Peptides and Proteins / blood*
  • Protein Kinase Inhibitors / blood*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / blood*
  • Syk Kinase

Substances

  • Indoles
  • Intracellular Signaling Peptides and Proteins
  • Protein Kinase Inhibitors
  • Protein-Tyrosine Kinases
  • SYK protein, human
  • Syk Kinase