5.38337

PDE9 Inhibitor, PF-04447943

• Synonym(s): PDE9 Inhibitor, PF-04447943, 6-((3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one, PF04447943, PF 04447943, Phosphodiesterase 9A Inhibitor, PF-04447943
• Empirical Formula (Hill Notation): C₂₀H₂₅N₇O₂
• CAS Number: 1082744-20-4
• Molecular Weight: 395.46
• MDL number: MFCD22665724
• UNSPSC Code: 12352200
• NACRES: NA.77

Properties

• Assay: ≥97% (HPLC)
• Quality Level: 100
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: off-white
• solubility: DMSO: 50 mg/mL
• storage temp.: −20°C
• InChI: 1S/C20H25N7O2/c1-13-10-26(12-17-21-5-2-6-22-17)11-16(13)18-24-19-15(20(28)25-18)9-23-27(19)14-3-7-29-8-4-14/h2,5-6,9,13-14,16H,3-4,7-8,10-12H2,1H3,(H,24,25,28)/t13-,16-/m1/s1
• InChI key: IWXUVYOOUMLUTQ-CZUORRHYSA-N

Description

General description

A cell-permeable, blood-brain barrier permeant, pyrazolo[3,4 d]pyrimidinone compound that acts as a highly potent, selective, and active site-targeting inhibitor of phosphodiesterase 9A (PDE9A; K_i = 2.8 nM, 4.5 nM, and 18 nM for human, rhesus monkey, and rat recombinant PDE9A, respectively). Exhibits high selectivity over other phosphodiesterases (K_i = 8.6, 99, 50, 29, 14.9, 5.3, 75, 50, 51.2, and 80 µM for PDE1, PDE2A3, PDE3A, PDE4A, PDE5A, PDE6C, PDE7A2, PDE8A, PDE10, PDE11, respectively). Does not affect the activity of 60 other enzymes and receptors. Shown to diminish ANP-stimulated cGMP levels in human embryonic kidney cells expressing rhesus PDE9A2 (IC₅₀ = 375 nM). Shown to improve performance in novel object recognition in rats (~ 3 mg/kg, p.o.). Exhibits desirable pharmacokinetic properties with t_1/2 = 4.9 h, T_max = 0.3 h in rat.

A cell-permeable, blood-brain barrier permeant, pyrazolo[3,4 d]pyrimidinone compound that acts as a highly potent, selective, and active site-targeting inhibitor of phosphodiesterase 9A (PDE9A; K_i = 2.8 nM, 4.5 nM, and 18 nM for human, rhesus monkey, and rat recombinant PDE9A, respectively). Exhibits high selectivity over other phosphodiesterases (K_i = 8.6, 99, 50, 29, 14.9, 5.3, 75, 50, 51.2, and 80 µM for PDE1, PDE2A3, PDE3A, PDE4A, PDE5A, PDE6C, PDE7A2, PDE8A, PDE10, PDE11, respectively). Does not affect the activity of 60 other enzymes and receptors. Shown to diminish ANP-stimulated cGMP levels in human embryonic kidney cells expressing rhesus PDE9A2 (IC₅₀ = 375 nM). Shown to improve performance in novel object recognition in rats (~ 3 mg/kg, p.o.). Exhibits desirable pharmacokinetic properties with t_1/2 = 4.9 h, T_max = 0.3 h in rat.

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
PDE9

Reversible: yes

Target IC₅₀: 2.8 nM, 4.5 nM and 18 nM for human, rhesus and rat PDE9A inhibition respectively

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Other Notes

Lee, D., et al. 2015. Nature.519, 472

Verhoest, P. R., et al. 2012. J. Med. Chem.55, 9045.

Hutson, P.H., et al. 2011. Neuropharmacology.61, 665.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Safety Information

• Storage Class Code: 13 - Non Combustible Solids
• WGK: WGK 3
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable