PF-04447943, inhibitor

PF-04447943

Cat. Num. AAA5755346

• Purity: 98.00%
• Synonyms: PF-04447943; inhibitor

• Purity/Purification: 98.00%
• Form/Format: Solid. Powder

• Solubility: DMSO: 54.6mg/mL (138.07mM); (<1mg/ml refers to the product slightly soluble or insoluble)
• Formula: C20H25N7O2
• SMILES: O=C1C2=C(N(C3CCOCC3)N=C2)N=C([C@@H]4CN(CC5=NC=CC=N5)C[C@H]4C)N1
• CAS Number: 1082744-20-4
• Target & IC50: PDE9A: ic50 12nM
• In Vitro: PF-04447943 concentrations dose-dependently increase in blood, brain, and cerebrospinal fluid (CSF), thirty minutes following oral administration in rats (1-30mg/kg). In mice, PF-04447943 (3, 10, 30mg/kg p.o.) dose-dependently enhances plasma and brain concentrations of PF-04447943 while the brain to plasma ratio ranged from 0.26 to 0.7 although this is not entirely dosed dependent. Based on i.v. and p.o. dosing, pharmacokinetic studies with PF-04447943 in the rat indicate a Tmax of 0.3 h, T1/2 of 4.9 h, Cl of 21.7mL/min/kg, and oral bioavailability of 47%. The brain: plasma exposure ratios 30 minutes after dosing range from 0.13 at the 1mg/kg dose to 0.33 at the 30mg/kg dose. CSF levels are approximately 50% of brain levels. CSF cGMP levels increase in a dose-dependent manner from a basal level of 3pmol/mL to 13.3pmol/mL (3.5-fold) at the 30mg/kg dose. CSF cGMP levels also increase in a dose-dependent manner from a basal level of 3pmol/mL in vehicle-treated animals to 13.3pmol/mL (3.5-fold) at the 30mg/kg dose. CSF cGMP levels are elevated at all doses tested with a maximal effect of 3.5 fold increase above controls at 30mg/kg [2].
• Preparation and Storage: Store at -20 degree C for 3 years powder; -80 degree C for 2 years in solvent

Structure

Related Product Information for PF-04447943, inhibitor

PF-04447943 is an effective inhibitor of human recombinant PDE9A (IC50=12nM). It has >78-fold selectivity, compared to other PDE family members (IC50>1000nM).

Product Categories/Family for PF-04447943, inhibitor

Metabolism; PDE

References

Kleiman RJ, et al. Phosphodiesterase 9A regulates central cGMP and modulates responses to cholinergic and monoaminergic perturbation in vivo. J Pharmacol Exp Ther. 2012 May;341(2):396-409.
Kleiman RJ, et al. Phosphodiesterase 9A regulates central cGMP and modulates responses to cholinergic and monoaminergic perturbation in vivo. J Pharmacol Exp Ther. 2012 May;341(2):396-409.
Hutson, P. H, et al. The selective phosphodiesterase 9 (PDE9) inhibitor PF-04447943 (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) enhances synaptic plasticity and
Hutson, P. H, et al. The selective phosphodiesterase 9 (PDE9) inhibitor PF-04447943 (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) enhances synaptic plasticity and