Functionalization of 1,3,5‐Triazines: A Modular Entry to Cyanine‐Conjugated Imaging Probes

Multifunctional platforms are essential tools in biomedical research, particularly to develop dual imaging probes that combine, for example, fluorescence imaging (FLI) and positron emission tomography (PET). We report the design of a modular trisubstituted 1,3,5‐triazine scaffold synthesized from 2,4,6‐trichloro‐1,3,5‐triazine via sequential nucleophilic aromatic substitutions with amino‐functionalized spacers. Orthogonal protecting groups enabled selective conjugation with a cyanine dye (Cy) and a DOTA chelator for FLI and PET, respectively. The third arm was functionalized with DUPA, a prostate‐specific membrane antigen (PSMA)‐targeting pseudopeptide, via CuAAC chemistry. Despite unsuccessful attempts with Cy7 derivative (IR780), dual labeling with Cy5 and DOTA was achieved efficiently. Compound 19 exhibited optical properties comparable to commercial Cy5. These results highlight the versatility of this synthetic strategy and the potential of 19 as a dual‐modality imaging agent.