Matrix metalloproteinase-12 (MMP-12, macrophage elastase) is a member of the MMP family that is responsible for the degradation of extracellular matrix, and is associated with the inflammatory process of chronic obstructive pulmonary disease (COPD). COPD, characterized by progressive and irreversible airflow obstruction, is recently a major cause of mortality and morbidity worldwide. Herein, to develop radioiodinated probes for the early diagnosis of COPD, we designed and synthesized novel MMP-12-targeted dibenzofuran compounds (1–3) with a variety of linker structures (carbamate, amide, and sulfonamide). In competitive enzyme activity assays, it was revealed that the linker structures significantly affected the inhibitory activity against and selectivity for MMP-12. Compound 1, with carbamate linker, demonstrated potent MMP-12 inhibitory activity (IC₅₀ = 8.5 nM) compared to compound 2, with amide linker, and compound 3, with sulfonamide linker. Using bromo-substituted carbamate 13 as a radioiodination precursor, [¹²⁵I]1 was successfully prepared to high radiochemical purity (over 98%) and good specific radioactivity (4.1 GBq/μmol). These results suggest that radioiodinated compound 1 is potent as a novel MMP-12-targeted probe.

基质金属蛋白酶-12（MMP-12，巨噬细胞弹性蛋白酶）是MMP家族的成员，负责细胞外基质的降解，并与慢性阻塞性肺疾病（COPD）的炎症过程有关。慢性阻塞性肺病的特征是进行性和不可逆的气流阻塞，最近已成为世界范围内死亡率和发病率的主要原因。这里，开发用于COPD的早期诊断放射性碘标记的探针，我们设计并合成了新的MMP-12靶向二苯并呋喃的化合物（1 - 3）与各种接头结构（氨基甲酸酯，酰胺，和磺胺）的。在竞争性酶活性测定中，揭示了接头结构显着影响了对MMP-12的抑制活性和选择性。化合物与具有酰胺连接体的 化合物2和具有磺酰胺连接体的化合物3相比，具有氨基甲酸酯连接体的图1显示出有效的MMP-12抑制活性（IC ₅₀ = 8.5 nM）。使用溴取代的氨基甲酸酯13作为放射性碘化的前体，成功制备了[ ¹²⁵ I] 1以达到高放射化学纯度（超过98％）和良好的比放射性（4.1 GBq /μmol）。这些结果表明，放射性碘标记的化合物1作为新型MMP-12靶向探针是有效的。