Synthesis and characterization of a novel F-labeled 2,5-diarylnicotinamide derivative targeting orexin 2 receptor

• Published in: MedChemComm Vol. 1; no. 12; pp. 2126 - 213
• Main Authors: Watanabe, Hiroyuki, Matsushita, Naoki, Shimizu, Yoichi, Iikuni, Shimpei, Nakamoto, Yuji, Togashi, Kaori, Ono, Masahiro
• Format: Journal Article
• Published: 12.12.2019
• ISSN: 2040-2503; 2040-2511
• DOI: 10.1039/c9md00397e

Orexin 2 receptor (OX 2 R) is thought to play an important role in the arousal-promoting function, but its distribution and function in the pathophysiology of orexin-mediated disorders remains to be fully elucidated. In the present study, we synthesized and characterized a novel 18 F-labeled 2,5-diarylnicotinamide (DAN) derivative as a potential positron emission tomography (PET) probe for in vivo imaging of OX 2 R. In in vitro binding experiments, [ 18 F]DAN-1 selectively bound to OX 2 R. In a biodistribution study using normal mice, [ 18 F]DAN-1 displayed moderate brain uptake (2.10% ID per g at 10 min post-injection). In addition, the radioactivity in the mouse brain at 30 min post-injection was significantly decreased by co-injection with nonradioactive DAN-1, but high nonspecific binding was observed. These results suggested that further structural modifications of [ 18 F]DAN-1 are needed to use it for imaging OX 2 R in the brain. A novel 18 F labeled probe ([ 18 F]DAN-1) selectively bound to orexin 2 receptor (OX 2 R) and displayed moderate uptake into the mouse brain.