A PDE9A inhibitor
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PF-04447943

Item No. 24299

Product Insert (PDF)Safety Data Sheet (SDS) (PDF)
Technical Information
Formal Name
1,5-dihydro-6-[(3S,4S)-4-methyl-1-(2-pyrimidinylmethyl)-3-pyrrolidinyl]-1-(tetrahydro-2H-pyran-4-yl)-4H-pyrazolo[3,4-d]pyrimidin-4-one
CAS Number
1082744-20-4
Molecular Formula
C20H25N7O2
Formula Weight
395.5
Purity
≥98%
Formulation
A solid
Solubility(Learn about Variance in Solubility)
DMF: 25 mg/mlDMSO: 25 mg/mlDMSO:PBS (pH 7.2) (1:1): 0.5 mg/mlEthanol: 12.5 mg/ml
SMILES
O=C1N=C([C@H]2[C@H](C)CN(CC3=NC=CC=N3)C2)NC4=C1C=NN4C5CCOCC5
InChi Code
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
Shipping & Storage Information
Storage
-20°C
Shipping
Room temperature in continental US; may vary elsewhere
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    1 mg

    $40

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    5 mg

    $105

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    10 mg

    $190

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    25 mg

    $423

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    Product Description

    PF-04447943 is a brain-permeable phosphodiesterase (PDE) inhibitor that is selective for PDE9A (IC50 = 12 nM) over other PDEs (IC50s = >940 nM) in enzymatic assays of second messenger hydrolysis.1 It is over 1,000-fold more selective for PDE9A over 79 non-PDE targets, with the exception of the melatonin MT3/ML2 receptor (Ki = 3,800 nM). PF-04447943 also inhibits rat and rhesus monkey PDE9A (Kis = 18.1 and 4.5 nM, respectively).2 It increases neurite outgrowth and the density of synapsin puncta in primary rat hippocampal neurons when used at a concentration of 0.03 μM. PF-04447943 increases the cGMP level in the striatum and frontal cortex of mice and in the cerebrospinal fluid (CSF) of rats when administered at 10 and 1 mg/kg, respectively.1 It improves deficits in episodic memory induced by scopolamine (Item No. 14108) in rats and increases the time spent exploring the novel object in the novel object recognition (NOR) test when administered at a dose of 1 mg/kg. PF-04447943 (3.2 mg/kg) also improves spatial memory in the Morris water maze (MWM) and decreases the distance traveled to the hidden platform.

    WARNING This product is not for human or veterinary use.

    References & Product Citations
    Product Description References

    1. Kleiman, R.J., Chapin, D.S., Christoffersen, C., et al. Phosphodiesterase 9A regulates central cGMP and modulates responses to cholinergic and monoaminergic perturbation in vivo. J. Pharmacol. Exp. Ther. 341(2), 396-409 (2012).

    2. Hutson, P.H., Finger, E.N., Magliaro, B.C., 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 cognitive function in rodents. Neuropharmacology 61(4), 665-676 (2011).