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• W2760649932 abstract "As part of our effort in identifying phosphodiesterase (PDE) 4B-preferring inhibitors for the treatment of central nervous system (CNS) disorders, we sought to identify a positron emission tomography (PET) ligand to enable target occupancy measurement in vivo. Through a systematic and cost-effective PET discovery process, involving expression level (Bmax) and biodistribution determination, a PET-specific structure–activity relationship (SAR) effort, and specific binding assessment using a LC-MS/MS “cold tracer” method, we have identified 8 (PF-06445974) as a promising PET lead. Compound 8 has exquisite potency at PDE4B, good selectivity over PDE4D, excellent brain permeability, and a high level of specific binding in the “cold tracer” study. In subsequent non-human primate (NHP) PET imaging studies, [18F]8 showed rapid brain uptake and high target specificity, indicating that [18F]8 is a promising PDE4B-preferring radioligand for clinical PET imaging." @default.
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• W2760649932 date "2017-10-09" @default.
• W2760649932 modified "2023-10-16" @default.
• W2760649932 title "The Discovery of a Novel Phosphodiesterase (PDE) 4B-Preferring Radioligand for Positron Emission Tomography (PET) Imaging" @default.
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• W2760649932 doi "https://doi.org/10.1021/acs.jmedchem.7b01050" @default.
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