Discovery of oxazole-based PDE4 inhibitors with picomolar potency

Bioorg Med Chem Lett. 2012 Apr 1;22(7):2594-7. doi: 10.1016/j.bmcl.2012.01.115. Epub 2012 Feb 14.

Abstract

Optimization of oxazole-based PDE4 inhibitors has led to the discovery of a series of quinolyl oxazoles, with 4-benzylcarboxamide and 5-α-aminoethyl groups which exhibit picomolar potency against PDE4. Selectivity profiles and in vivo biological activity are also reported.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemical synthesis*
  • Anti-Inflammatory Agents / pharmacology
  • Cyclic N-Oxides / chemistry
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / chemistry*
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / metabolism
  • Drug Discovery
  • Humans
  • Models, Molecular
  • Oxazoles / chemical synthesis*
  • Oxazoles / pharmacology
  • Phosphodiesterase 4 Inhibitors / chemical synthesis*
  • Phosphodiesterase 4 Inhibitors / pharmacology
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Quinolines / pharmacology
  • Rats
  • Structure-Activity Relationship
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors

Substances

  • Anti-Inflammatory Agents
  • Cyclic N-Oxides
  • Oxazoles
  • Phosphodiesterase 4 Inhibitors
  • Quinolines
  • SCH 351591
  • Tumor Necrosis Factor-alpha
  • Cyclic Nucleotide Phosphodiesterases, Type 4