Synthesis and biological evaluation of novel < sup > 18 < /sup > F-labeled 2,4-diaminopyrimidine derivatives for detection of ghrelin receptor in the brain

In this study, we newly designed and synthesized diaminopyrimidine derivatives ([18F]BPP-1 and [18F]BPP-2) and evaluated their utility as novel PET probes targeting GHSR. In in vitro competitive binding assays, the binding affinity of BPP-2 for GHSR (Ki = 274 nM) was comparable to that of the diaminopyimidine lead compound Abb8a (Ki = 109 nM). In a biodistribution study using normal mice, [18F]BPP-2 displayed low uptake in the brain and moderate uptake in the pancreas, but high radioactivity accumulation in bone was observed due to its defluorination in vivo. Taken together, although further improvement of the pharmacokinetics is needed, the diaminopyrimidine scaffold has potential for the development of useful GHSR-targeting PET probes.PMID:38253227 | DOI:10.1016/j.bmcl.2024.129625

Source: Bioorganic and Medicinal Chemistry Letters - January 22, 2024 Category: Chemistry Authors: Haruka Saito Hiroyuki Watanabe Masahiro Ono Source Type: research