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    InvivoChem Cat #: V4471
    CAS #: 1082744-20-4 Purity ≥98%

    Description: PF-04447943 is a novel and potent inhibitor of human recombinant PDE9A with IC50 of 12 nM and with >78-fold selectivity over other PDE family members (IC50>1000 nM). PF-04447943 was found to have high affinity (Ki of 2.8, 4.5 and 18 nM) for human, rhesus and rat recombinant PDE9 respectively and high selectivity for PDE9 versus PDEs1-8 and 10-11. PF-04447943 significantly increased neurite outgrowth and synapse formation (as indicated by increased synapsin 1 expression) in cultured hippocampal neurons at low (30-100 nM) but not high (300-1000 nM) concentrations. PF-04447943 significantly facilitated hippocampal slice LTP evoked by a weak tetanic stimulus at a concentration of 100 nM but failed to affect response to the weak tetanus at either 30 or 300 nM, or the LTP produced by a theta burst stimulus. Systemic administration of PF-04447943 (1-30 mg/kg p.o.) dose-dependently increased cGMP in the cerebrospinal fluid 30 min after administration indicating target engagement in the CNS of rats. PF-04447943 (1-3 mg/kg p.o.) significantly improved cognitive performance in three rodent cognition assays (mouse Y maze spatial recognition memory model of natural forgetting, mouse social recognition memory model of natural forgetting and rat novel object recognition with a scopolamine deficit). When administered at a dose of 3 mg/kg p.o., which improved performance in novel object recognition, PF-04447943 significantly increased phosphorylated but not total GluR1 expression in rat hippocampal membranes. Collectively these data indicate that PF-04447943 is a potent, selective brain penetrant PDE9 inhibitor that increased indicators of hippocampal synaptic plasticity and improved cognitive function in a variety of cognition models in both rats and mice. Results with PF-04447943 are consistent with previously published findings using a structurally diverse PDE9 inhibitor, BAY73-6199, and further support the suggestion that PDE9 inhibition may represent a novel approach to the palliative remediation of cognitive dysfunction.

    References: J Pharmacol Exp Ther. 2012 May;341(2):396-409. 2011 Sep;61(4):665-76.

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    Name: PF-04447943
    CAS#: 1082744-20-4
    Chemical Formula: C20H25N7O2
    Exact Mass: 395.207
    Molecular Weight: 395.467
    Elemental Analysis: C, 60.74; H, 6.37; N, 24.79; O, 8.09
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Technical InformationSynonym: PF-04447943; PF 04447943; PF04447943; PF-4447943; PF 4447943; PF4447943.
    IUPAC/Chemical Name: 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
    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
    SMILES Code: O=C1C2=C(N(C3CCOCC3)N=C2)N=C([[email protected]@H]4CN(CC5=NC=CC=N5)C[[email protected]]4C)N1

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