Identification of potent pyrimidine inhibitors of phosphodiesterase 7 (PDE7) and their ability to inhibit T cell proliferation

Bioorg Med Chem Lett. 2009 Apr 1;19(7):1935-8. doi: 10.1016/j.bmcl.2009.02.060. Epub 2009 Feb 21.

Abstract

A series of pyrimidine based inhibitors of PDE7 are discussed. The synthesis, structure-activity relationships (SAR) and selectivity against several other PDE family members as well as activity in T cells are presented. These compounds were found to have effects on T cell proliferation, however it is not clear whether the mechanism is related to PDE7 inhibition.

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Cyclic Nucleotide Phosphodiesterases, Type 7 / antagonists & inhibitors*
  • Cyclic Nucleotide Phosphodiesterases, Type 7 / genetics
  • Cyclic Nucleotide Phosphodiesterases, Type 7 / metabolism
  • Gene Knockout Techniques
  • Mice
  • Phosphodiesterase Inhibitors / chemical synthesis
  • Phosphodiesterase Inhibitors / chemistry*
  • Phosphodiesterase Inhibitors / pharmacology
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacology
  • Structure-Activity Relationship
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology

Substances

  • Phosphodiesterase Inhibitors
  • Pyrimidines
  • Cyclic Nucleotide Phosphodiesterases, Type 7