Design, Synthesis, Biological Evaluation, and Molecular Docking of 2,4-Diaminopyrimidine Derivatives Targeting Focal Adhesion Kinase as Tumor Radiotracers

Abstract

There are two important topics in the field of cancer research: one is targeted molecular therapy and the other is tumor molecular imaging. Focal adhesion kinase (FAK) is considered as an attractive target for oncologic diagnosis and therapy. A series of 2,4-diaminopyrimidine derivatives were labeled with ¹⁸F to study their biological properties and their potential as positron emission tomography tumor imaging agents. They inhibited the activity of FAK with IC₅₀ values in the wide range of 0.6-2164 nM, among which the IC₅₀ of <b>Q6</b> was 3.2 nM. For the biodistribution in S180-bearing mice, the corresponding <b>[</b>^<b>18</b><b>F]Q6</b> was relatively good, with the highest uptake of 3.35 ± 0.32 % ID/g at 30 min postinjection, with a tumor/muscle ratio of 2.08 and a tumor/bone ratio of 2.48. Accordingly, <b>[</b>^<b>18</b><b>F]Q6</b> was considered as a potential PET imaging agent for tumor diagnosis.