Thiophene inhibitors of PDE4: crystal structures show a second binding mode at the catalytic domain of PDE4D2

Bioorg Med Chem Lett. 2011 Dec 1;21(23):7089-93. doi: 10.1016/j.bmcl.2011.09.109. Epub 2011 Oct 5.


PDE4 inhibitors have been identified as therapeutic targets for a variety of conditions, particularly inflammatory diseases. We have serendipitously identified a novel class of phosphodiesterase 4 (PDE4) inhibitor during a study to discover antagonists of the parathyroid hormone receptor. X-ray crystallographic studies of PDE4D2 complexed to four potent inhibitors reveal the atomic details of how they inhibit the enzyme and a notable contrast to another recently reported thiophene-based inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Catalytic Domain
  • Crystallography, X-Ray
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / chemistry*
  • Models, Molecular*
  • Phosphodiesterase 4 Inhibitors / chemical synthesis
  • Phosphodiesterase 4 Inhibitors / chemistry*
  • Protein Binding
  • Thiophenes / chemical synthesis*
  • Thiophenes / chemistry
  • Thiophenes / pharmacology


  • Phosphodiesterase 4 Inhibitors
  • Thiophenes
  • Cyclic Nucleotide Phosphodiesterases, Type 4