PDE2 inhibition by the PI3 kinase inhibitor LY294002 and analogues

Belinda M Abbott; Philip E Thompson

doi:10.1016/j.bmcl.2004.03.043

PDE2 inhibition by the PI3 kinase inhibitor LY294002 and analogues

Bioorg Med Chem Lett. 2004 Jun 7;14(11):2847-51. doi: 10.1016/j.bmcl.2004.03.043.

Authors

Belinda M Abbott¹, Philip E Thompson

Affiliation

¹ Department of Medicine, Monash University, Box Hill Hospital, Box Hill 3128, Australia.

PMID: 15125945
DOI: 10.1016/j.bmcl.2004.03.043

Abstract

Synthetic 2-morpholinochromones, including the known PI3-kinase inhibitor LY294002, have been evaluated in vitro as inhibitors of isolated human platelet phosphodiesterases. Inhibition of the cAMP-phosphodiesterases, PDE2 and PDE3 by LY294002 is reported for the first time. Preliminary screening across a range of 2-morpholinochromones has revealed structural features for optimised PDE2 inhibition.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3',5'-Cyclic-AMP Phosphodiesterases / chemistry
Blood Platelets / enzymology
Chromones / pharmacology*
Cyclic Nucleotide Phosphodiesterases, Type 2
Cyclic Nucleotide Phosphodiesterases, Type 3
Dose-Response Relationship, Drug
Humans
Morpholines / pharmacology*
Phosphodiesterase Inhibitors / chemical synthesis
Phosphodiesterase Inhibitors / pharmacology
Phosphoinositide-3 Kinase Inhibitors
Phosphoric Diester Hydrolases / chemistry*
Structure-Activity Relationship

Substances

Chromones
Morpholines
Phosphodiesterase Inhibitors
Phosphoinositide-3 Kinase Inhibitors
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Phosphoric Diester Hydrolases
3',5'-Cyclic-AMP Phosphodiesterases
Cyclic Nucleotide Phosphodiesterases, Type 2
Cyclic Nucleotide Phosphodiesterases, Type 3
PDE2A protein, human