Synthesis, radiolabeling, and evaluation of a potent β-site APP cleaving enzyme (BACE1) inhibitor for PET imaging of BACE1 in vivo.

A fluoropropyl side chain was introduced to the phenyl of the 3,4-dihydroquinazoline scaffold to generate the novel BACE1 PET ligand. Although the in-vitro evaluations of this ligand indicated it possess favorable properties, its poor brain uptake hindered the in-vivo imaging of BACE1. Further investigation would be required to optimize the scaffold for the development of a blood-brain-barrier-permeable BACE1-targeted PET ligand. [Display omitted] The β -site APP-cleaving enzyme 1 (BACE1) plays important roles in the proteolytic processing of amyloid precursor protein, and can be regarded as an important target for the diagnosis and treatment of AD. This study aimed to report the synthesis and evaluation of an 18F-labeled 2-amino-3,4-dihydroquinazoline analog as a potential BACE1 radioligand. A fluoropropyl side chain was introduced to the phenyl of this 3,4-dihydroquinazoline scaffold to generate the radioligand. Our preliminary data indicated that although the 2-amino-3,4-dihydroquinazoline scaffold possessed favorable in-vitro properties as a PET ligand, its poor brain uptake hindered the in-vivo imaging of BACE1. Further investigation would be required to optimize the scaffold for the development of a blood-brain-barrier-permeable BACE1-targeted PET ligand. [ABSTRACT FROM AUTHOR]