N-(3-(phenylcarbamoyl)arylpyrimidine)-5-carboxamides as potent and selective inhibitors of Lck: structure, synthesis and SAR

Bioorg Med Chem Lett. 2008 Feb 1;18(3):1172-6. doi: 10.1016/j.bmcl.2007.11.123. Epub 2007 Dec 5.

Abstract

N-3-(Phenylcarbamoyl)arylpyrimidine-5-carboxamides are a novel class of selective Lck inhibitors. This series of compounds derives its selectivity from a hydrogen bond with the gatekeeper Thr316 of the enzyme. X-ray co-crystal structural data, structure-activity relationships, and the synthesis of these inhibitors are reported herein.

MeSH terms

  • Amides / chemical synthesis*
  • Amides / chemistry
  • Amides / pharmacology*
  • Combinatorial Chemistry Techniques
  • Crystallography, X-Ray
  • Drug Design
  • Humans
  • Hydrogen Bonding
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / antagonists & inhibitors*
  • Molecular Conformation
  • Molecular Structure
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Structure-Activity Relationship
  • Threonine / chemistry

Substances

  • Amides
  • Pyrimidines
  • Threonine
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)