Design and discovery of 6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (PF-04447943), a selective brain penetrant PDE9A inhibitor for the treatment of cognitive disorders.

Verhoest, Patrick R

Design and discovery of 6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (PF-04447943), a selective brain penetrant PDE9A inhibitor for the treatment of cognitive disorders. [electronic resource] - Journal of medicinal chemistry Nov 2012 - 9045-54 p. digital

Publication Type: Journal Article

1520-4804

10.1021/jm3007799 doi


3',5'-Cyclic-AMP Phosphodiesterases--antagonists & inhibitors
Amyloid beta-Protein Precursor--genetics
Animals
Brain--metabolism
Catalytic Domain
Cognition Disorders--drug therapy
Crystallography, X-Ray
Cyclic GMP--metabolism
Dogs
Drug Design
Hippocampus--drug effects
Humans
Long-Term Potentiation--drug effects
Maze Learning--drug effects
Mice
Mice, Transgenic
Microsomes, Liver--metabolism
Models, Molecular
Protein Conformation
Pyrazoles--chemical synthesis
Pyrimidinones--chemical synthesis
Rats
Stereoisomerism
Structure-Activity Relationship
Synapses--drug effects