PF-04449613

PF-04449613 is a phosphodiesterase 9A (PDE9A) inhibitor (IC50 = 22 nM). It is selective for PDE9A over PDE1C (IC50 = >1,000 nM), as well as over a variety of other PDEs, inhibiting PDE2-8, -10, and -11 activity by less than 30% in a panel of enzymes, ion channels, and transporters at 1 µM but does inhibit the human dopamine transporter (DAT, Ki = 293 nM). PF-04449613 (0.1-100 mg/kg, s.c.) increases cerebrospinal fluid (CSF) levels of cyclic GMP (cGMP) in rats. Subcutaneous administration of PF-04449613 (10 mg/kg) increases the rate of dendritic spine formation and elimination in mouse primary motor cortex pyramidal neurons in vivo. It increases the average running speed of mice in an accelerating rotarod task, indicating improved motor learning, at the same dose.Formal Name: 1,5-dihydro-6-[(1R)-1-(3-phenoxy-1-azetidinyl)ethyl]-1-(tetrahydro-2H-pyran-4-yl)-4H-pyrazolo[3,4-d]pyrimidin-4-one. CAS Number: 1236858-52-8. Molecular Formula: C21H25N5O3. Formula Weight: 395.5. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMSO: 10 mg/ml. SMILES: O=C1N=C([C@@H](C)N2CC(OC3=CC=CC=C3)C2)NC4=C1C=NN4C5CCOCC5. InChi Code: InChI=1S/C21H25N5O3/c1-14(25-12-17(13-25)29-16-5-3-2-4-6-16)19-23-20-18(21(27)24-19)11-22-26(20)15-7-9-28-10-8-15/h2-6,11,14-15,17H,7-10,12-13H2,1H3,(H,23,24,27)/t14-/m1/s1. InChi Key: FHBANDDJQJAZOQ-CQSZACIVSA-N.