σ受体在神经递质调节方面起着重要作用，可作为神经中枢递质受体，在记忆、学习、运动及姿势平衡方面发挥着作用，其中σ2受体在多种肿瘤细胞中高度表达，可能作为肿瘤增殖状态的生物标志物。目前研究表明，σ2受体结合位点可能是位于内质网的跨膜蛋白97（TMEM97）。随着近红外荧光成像技术的发展，发展靶向σ2受体的荧光分子探针对肿瘤的早期诊断和治疗疗效的评价具有重要的科学意义和临床应用前景。本文以Glennon药效团模型为基础，选择6,7-二甲氧基-1,2,3,4-四氢异喹啉和 5,6-二甲氧基异吲哚为药效团，通过整体设计法设计合成了两个靶向σ2受体的特异性荧光探针。以第一脂溶性基团和碱性氮原子作为药效基团，选择具有萘环骨架的拉电子荧光基团作为第二脂溶性基团，在此基础上，选择氮甲基作为推电子基团，所得化合物推电子能力增强，脂溶性降低，近红外吸收波长更长。其中一化合物经荧光性质测定，最大发射波长为628 nm，斯托克斯位移为144 nm，光学性质较好，有运用于近红外活体成像的潜力。另一化合物分离提纯工作正在进行中，后续检测工作尚待进行。

The σ receptor plays an important role in the regulation of neurotrans-mitters. It acts as a neurotransmitter receptor and contributes to memory, learning, exercise, and posture balance. The σ2 receptor is highly expressed in many tumor cells, and may be a biomarker of tumor prolife-ration status. Current studies suggest that the σ2 receptor binding site may be transmembrane protein 97 (TMEM97) located in the endoplasmic reticulum. With the development of near-infrared fluore-scence imaging technology, developing molecular probes targeting σ2 receptors has important scientific significance and clinical application prospects for the early diagnosis and therapeutic evaluation of tumors.Based on the Glennon pharmacophore model, 6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline and 5,6-dimethoxyisoindole were selected as pharmacophores. Two specific fluorescent probes targeting sigma 2 receptors were designed and synthesized by the overall design method. The first fat-soluble group and the basic nitrogen atom are used as pharmacophores, and the electron-emitting fluorophore having a naphth-alene ring skeleton is selected as the second fat-soluble group. On the basis of this, the nitrogen methyl group is selected as the electron-donating group. In the group, the obtained compound has enhanced electron-promoting ability, reduced fat solubility, and longer near-infrared absorption wavelength. One of the compounds was deter-mined by fluorescence properties, with a maximum emission wavelength of 628 nm and a Stokes shift of 144 nm. It has good optical properties and has potential for near-infrared imaging. The separation and purification of another compound is in progress and subsequent testing is yet to be carried out.