| Identification | Back Directory | [Name]
Benzonitrile, 4-(8-cyclopropyl-6,7,8,9-tetrahydro-9-oxopyrido[2',3':4,5]pyrrolo[1,2-a]pyrazin-10-yl)-2-fluoro- | [CAS]
2055776-17-3 | [Synonyms]
PF6445974
PF-6445974
PF 6445974
PF-06445974
Benzonitrile, 4-(8-cyclopropyl-6,7,8,9-tetrahydro-9-oxopyrido[2',3':4,5]pyrrolo[1,2-a]pyrazin-10-yl)-2-fluoro- | [Molecular Formula]
C20H15FN4O | [MOL File]
2055776-17-3.mol | [Molecular Weight]
346.36 |
| Chemical Properties | Back Directory | [Boiling point ]
628.5±55.0 °C(Predicted) | [density ]
1.47±0.1 g/cm3(Predicted) | [form ]
Solid | [pka]
5.06±0.20(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
PF-06445974, a promising positron emission tomography (PET) lead, has exquisite potency at PDE4B with an IC50 <1 nM. The IC50 values are 36, 4.7 and 17 nM for PDE4D, PDE4A and PDE4C, respectively. PF-06445974 has good selectivity over PDE4D, excellent brain permeability, and a high level of specific binding in the "cold tracer" study[1]. | [in vivo]
PF-06445974 exhibits high central nervous system (CNS) PET MPO score (4.0). PF-06445974 is a promising radiotracer lead for specific binding assessment. Neuropharmacokinetic study in rats (0.1 mg/kg, IV) confirms high brain permeability with a total brain to plasma ratio of 0.76, corresponding to a free brain to plasma ratio of 0.70[1]. | Animal Model: | Twenty-five drug-naive male 129/B6 PDE4D KO mice (25-35 g)[1] | | Dosage: | 10 μg/kg | | Administration: | Dosed intravenously at 10 μg/kg in a 5 mL/kg dosing volume | | Result: | Showed excellent brain uptake and reached peak concentrations at around 20 minutes.
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| [IC 50]
PDE4B: <1 nM (IC50); PDE4D: 36 nM (IC50); PDE4A: 4.7 nM (IC50); PDE4C: 17 nM (IC50) | [References]
[1] Lei Zhang,?et al. The Discovery of a Novel Phosphodiesterase (PDE) 4B-Preferring Radioligand for Positron Emission Tomography (PET) Imaging. J Med Chem.?2017 Oct 26;60(20):8538-8551. DOI:10.1021/acs.jmedchem.7b01050 |
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