PF-04447943

InvivoChem Cat #:V4471CAS #: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.; Neuropharmacology. 2011 Sep; 61(4):665-76.

-20C for 3 years in powder form

Synonym: 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 Key: IWXUVYOOUMLUTQ-CZUORRHYSA-N
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([CH]4CN(CC5=NC=CC=N5)C[CH]4C)N1