PF-04447943

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. 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). 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. It improves deficits in episodic memory induced by scopolamine (Cay-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.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: (Request formulation change), A solid. Solubility: DMF: 25 mg/ml, DMSO: 25 mg/ml, DMSO:PBS (pH 7.2) (1:1): 0.5 mg/ml, Ethanol: 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.