3-Amino-pyrazolo[3,4-d]pyrimidines as p38α kinase inhibitors: design and development to a highly selective lead

Bioorg Med Chem Lett. 2011 Jun 1;21(11):3452-6. doi: 10.1016/j.bmcl.2011.03.098. Epub 2011 Apr 1.

Abstract

Learnings from previous Roche p38-selective inhibitors were applied to a new fragment hit, which was optimized to a potent, exquisitely selective preclinical lead with a good pharmacokinetic profile.

MeSH terms

  • Animals
  • Crystallography, X-Ray
  • Drug Design*
  • Enzyme Activation / drug effects*
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Inhibitory Concentration 50
  • Mitogen-Activated Protein Kinase 14 / antagonists & inhibitors*
  • Models, Molecular
  • Molecular Structure
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Rats

Substances

  • Enzyme Inhibitors
  • Pyrazoles
  • Pyrimidines
  • Mitogen-Activated Protein Kinase 14