Parkinson's disease (PD) is the second most common neurodegenerative disorder. Early diagnosis is the key to treatment but is still a great challenge in the clinic now. The discovery of alpha-synuclein (α-syn) aggregates ligands has become an attractive strategy to meet the early diagnosis of PD. Herein, we designed and synthesized a series of styrylaniline derivatives as novel α-syn aggregates ligands. Several compounds displayed good potency to α-syn aggregates with K_d values less than 0.1 μM. The docking study revealed that the hydrogen bonds and cation-pi interaction between ligands and α-syn aggregates would be crucial for the activity. The representative compound 7–16 not only detected α-syn aggregates in both SH-SY5Y cells and brain tissues prepared from two kinds of α-syn preformed-fibrils-injected mice models but also showed good blood-brain barrier penetration characteristics in vivo with a brain/plasma ratio over 1.0, which demonstrates its potential as a lead compound for further development of in vivo imaging agents.

帕金森病 (PD) 是第二常见的神经退行性疾病。早期诊断是治疗的关键，但在临床上仍然是一个很大的挑战。α-突触核蛋白 (α-syn) 聚集体配体的发现已成为满足 PD 早期诊断的有吸引力的策略。在此，我们设计并合成了一系列苯乙烯基苯胺衍生物作为新型 α-syn 聚集体配体。几种化合物对 α-syn 聚集体表现出良好的效力，K _d值小于 0.1 μM。对接研究表明，配体和 α-syn 聚集体之间的氢键和阳离子-π 相互作用对活性至关重要。代表化合物7-16不仅在 SH-SY5Y 细胞和由注射了两种 α-syn 预制原纤维的小鼠模型制备的脑组织中检测到 α-syn 聚集体，而且在体内表现出良好的血脑屏障穿透特性，脑/血浆比超过1.0，这证明了其作为进一步开发体内显像剂的先导化合物的潜力。