Inhibition of Tpl2 kinase and TNF-alpha production with 1,7-naphthyridine-3-carbonitriles: synthesis and structure-activity relationships

Bioorg Med Chem Lett. 2005 Dec 1;15(23):5288-92. doi: 10.1016/j.bmcl.2005.08.029. Epub 2005 Sep 13.

Abstract

The synthesis and structure-activity studies of a series of 6-substituted-4-anilino-[1,7]-naphthyridine-3-carbonitriles as inhibitors of Tpl2 kinase are described. The early exploratory work described here may lead to the discovery of compounds with significant therapeutic potential for treating rheumatoid arthritis and other inflammatory diseases.

MeSH terms

  • Arthritis, Rheumatoid / drug therapy
  • Humans
  • MAP Kinase Kinase Kinases / antagonists & inhibitors*
  • Naphthyridines / chemical synthesis
  • Naphthyridines / chemistry*
  • Naphthyridines / pharmacology
  • Nitriles / chemical synthesis
  • Nitriles / chemistry*
  • Nitriles / pharmacology*
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology*
  • Proto-Oncogene Proteins / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Tumor Necrosis Factor-alpha / biosynthesis*

Substances

  • Naphthyridines
  • Nitriles
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Tumor Necrosis Factor-alpha
  • MAP Kinase Kinase Kinases
  • MAP3K8 protein, human