Discovery of triazines as potent, selective and orally active PDE4 inhibitors

Bioorg Med Chem Lett. 2013 Aug 1;23(15):4308-14. doi: 10.1016/j.bmcl.2013.05.099. Epub 2013 Jun 10.

Abstract

Expanding on HTS hit 4 afforded a series of [1,3,5]triazine derivatives as novel PDE4 inhibitors. The SAR development and optimization process with the emphasis on ligand efficiency and physicochemical properties led to the discovery of compound 44 as a potent, selective and orally active PDE4 inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Binding Sites
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / chemistry
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / metabolism*
  • Cyclic Nucleotide Phosphodiesterases, Type 7 / antagonists & inhibitors
  • Cyclic Nucleotide Phosphodiesterases, Type 7 / metabolism
  • Drug Evaluation, Preclinical
  • Half-Life
  • Microsomes, Liver / metabolism
  • Molecular Docking Simulation
  • Phosphodiesterase 4 Inhibitors / chemical synthesis
  • Phosphodiesterase 4 Inhibitors / chemistry*
  • Phosphodiesterase 4 Inhibitors / pharmacokinetics
  • Protein Structure, Tertiary
  • Rats
  • Structure-Activity Relationship
  • Triazines / chemical synthesis
  • Triazines / chemistry*
  • Triazines / pharmacokinetics

Substances

  • Phosphodiesterase 4 Inhibitors
  • Triazines
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Cyclic Nucleotide Phosphodiesterases, Type 7
  • PDE7A protein, human