Omega-carboxypyridyl substituted ureas as Raf kinase inhibitors: SAR of the amide substituent

Bioorg Med Chem Lett. 2004 Feb 9;14(3):783-6. doi: 10.1016/j.bmcl.2003.11.041.

Abstract

Bis-aryl ureas have been disclosed previously as a potent class of Raf kinase inhibitors. Modifications in the amide portion led to an improvement in aqueous solubility, an important characteristic for an oral drug. Based on this finding, we hypothesize that this portion of the molecule is directed towards the solvent in Raf-1.

Publication types

  • Comparative Study

MeSH terms

  • Amides / chemical synthesis
  • Amides / pharmacology
  • Baculoviridae / genetics
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • MAP Kinase Kinase Kinase 1*
  • MAP Kinase Kinase Kinases / antagonists & inhibitors
  • Molecular Structure
  • Proto-Oncogene Proteins c-raf / antagonists & inhibitors*
  • Pyridines / chemistry
  • Pyridines / pharmacology
  • Recombinant Proteins / antagonists & inhibitors
  • Solubility
  • Structure-Activity Relationship
  • Urea / analogs & derivatives*
  • Urea / chemical synthesis
  • Urea / pharmacology*

Substances

  • Amides
  • Enzyme Inhibitors
  • Pyridines
  • Recombinant Proteins
  • Urea
  • Proto-Oncogene Proteins c-raf
  • MAP Kinase Kinase Kinase 1
  • MAP Kinase Kinase Kinases
  • MAP3K1 protein, human