PDE2 inhibition: potential for the treatment of cognitive disorders

Bioorg Med Chem Lett. 2013 Dec 15;23(24):6522-7. doi: 10.1016/j.bmcl.2013.10.014. Epub 2013 Oct 24.

Abstract

Phosphodiesterase inhibition has received much attention in the past 20 years for the potential treatment of CNS disorders. A primary focus of this work is the enhancement of memory and/or cognitive functioning. The role of PDEs in the augmentation of cyclic nucleotide signaling makes these enzymes attractive targets for enhancing the effects of neuronal communication. This review focuses on recent findings with respect to the role of PDE2 inhibition in cognitive functioning. Special attention is paid to recently disclosed, selective tool compounds and the use of these tool compounds to support the role of PDE2 inhibition in cognition. Recently reported SAR and modeling work will be presented along with discussion of the entry of new PDE2 inhibitors into the clinic.

Keywords: Cognition; Drug discovery; Memory; Phosphodiesterase.

Publication types

  • Review

MeSH terms

  • Animals
  • Cognition Disorders / drug therapy
  • Cognition Disorders / metabolism
  • Cognition Disorders / pathology
  • Cyclic Nucleotide Phosphodiesterases, Type 2 / antagonists & inhibitors
  • Cyclic Nucleotide Phosphodiesterases, Type 2 / metabolism*
  • Humans
  • Ligands
  • Permeability / drug effects
  • Phosphodiesterase Inhibitors / chemistry*
  • Phosphodiesterase Inhibitors / pharmacokinetics
  • Phosphodiesterase Inhibitors / therapeutic use
  • Protein Binding
  • Quinolones / chemistry
  • Quinolones / pharmacokinetics
  • Quinolones / therapeutic use
  • Structure-Activity Relationship

Substances

  • Ligands
  • Phosphodiesterase Inhibitors
  • Quinolones
  • Cyclic Nucleotide Phosphodiesterases, Type 2