PDE2 inhibition by the PI3 kinase inhibitor LY294002 and analogues.
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.
Abbott
Belinda M
BM
Department of Medicine, Monash University, Box Hill Hospital, Box Hill 3128, Australia.
Thompson
Philip E
PE
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000737:chemistry; D001792:Blood Platelets / Q000201:enzymology; D002867:Chromones / Q000494:pharmacology*; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009025:Morpholines / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry*; D013329:Structure-Activity Relationship
D002867:Chromones; D009025:Morpholines; D010726:Phosphodiesterase Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; C517275:PDE2A protein, human