title: PDE2 inhibition: potential for the treatment of cognitive disorders.
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.
authors.affiliation: Department of Chemistry, Dart Neuroscience LLC, 7473 Lusk Blvd., San Diego, CA 92121, United States.
authors.forename: Laurent
authors.initials: L
authors.lastname: Gomez
authors.forename: J Guy
authors.initials: JG
authors.lastname: Breitenbucher
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D010539:Permeability / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011485:Protein Binding; D015363:Quinolones / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D010726:Phosphodiesterase Inhibitors; D015363:Quinolones; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2
keywords: Cognition; Drug discovery; Memory; Phosphodiesterase