PF-06445974

• CAT Number: I034488
• CAS Number: 2055776-17-3
• Molecular Formula: C20H15FN4O
• Molecular Weight: 346.36
• Purity: ≥95%
• Synonyms: 4-(11-cyclopropyl-10-oxo-1,6,11-triazatricyclo[7.4.0.02,7]trideca-2(7),3,5,8-tetraen-8-yl)-2-fluorobenzonitrile
• InChI: InChI=1S/C20H15FN4O/c21-15-10-12(3-4-13(15)11-22)17-18-16(2-1-7-23-18)25-9-8-24(14-5-6-14)20(26)19(17)25/h1-4,7,10,14H,5-6,8-9H2
• InChIKey: YWTCDMZVTLNYLN-UHFFFAOYSA-N
• SMILES: C1CC1N2CCN3C4=C(C(=C3C2=O)C5=CC(=C(C=C5)C#N)F)N=CC=C4

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].
PF-06445974 demonstrates minimal off-target activities in broad-spectrum selectivity panels, with only weak µM activities at PDE10 (IC50=2290 nM), PDE5A (IC50=4640 nM) and GABAA (Ki=3850 nM)[1].
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].

Reference

[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.
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