Novel, potent and selective anilinoquinazoline and anilinopyrimidine inhibitors of p38 MAP kinase

Bioorg Med Chem Lett. 2004 Nov 1;14(21):5389-94. doi: 10.1016/j.bmcl.2004.08.007.

Abstract

SAR studies led to the identification of 4-(3-benzoylamino-6-methyl-anilino)quinazolines as potent and selective inhibitors of p38 MAP kinase. Further optimisation led to the identification of a series of 4-(3-benzoylamino-6-methyl-anilino)pyrimidines as potent inhibitors of the p38 MAP kinase signalling pathway in vitro and in vivo.

MeSH terms

  • Adenosine Triphosphate / chemistry
  • Administration, Oral
  • Aniline Compounds / chemical synthesis*
  • Aniline Compounds / pharmacokinetics
  • Aniline Compounds / pharmacology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Antirheumatic Agents / chemical synthesis
  • Antirheumatic Agents / pharmacokinetics
  • Antirheumatic Agents / pharmacology
  • Binding Sites
  • Biological Availability
  • Crystallography, X-Ray
  • Humans
  • In Vitro Techniques
  • Models, Molecular
  • Protein Binding
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / pharmacokinetics
  • Pyrimidines / pharmacology
  • Quinazolines / chemical synthesis*
  • Quinazolines / pharmacokinetics
  • Quinazolines / pharmacology
  • Rats
  • Signal Transduction
  • Structure-Activity Relationship
  • Time Factors
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / physiology

Substances

  • Aniline Compounds
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antirheumatic Agents
  • Pyrimidines
  • Quinazolines
  • Adenosine Triphosphate
  • p38 Mitogen-Activated Protein Kinases