环吡咯酮类化合物的合成及其与苯二氮卓受体结合 的活性研究

目的 设计并合成环吡咯酮类化合物，并评价其与苯二氮卓受体的结合活性。方法 根据环吡咯酮类镇静催眠药佐匹克隆(zopiclone)的基本活性结构特征，设计了17个改变酯键侧链的环吡咯酮类化合物。以2,3-吡嗪二酸酐、2-氨基-5-氯吡啶为起始原料，经过5步反应得到目标产物。以苯二氮卓受体拮抗剂氚标氟马西尼(3H] Ro 15-1788)为工具药，氟马西尼为阳性对照药，通过测试所合成化合物与苯二氮卓受体竞争性结合活性，对目标化合物进行了初步的活性评价。结果与结论 合成得到了17个未见文献报道的环吡咯酮类化合物，结构均经MS和1H-NMR确证。活性筛选实验表明,部分化合物表现出一定的活性。

Synthesis and benzodiazepine receptor-binding activity research of cyclopyrrolone derivatives

Aim To design and synthesize novel cyclopyrrolone derivatives, and to assay their benzodiazepine receptor-binding activity. Method According to the basic activity structural features of zopiclone, seventeen novel cyclopyrrolone derivatives which changed the zopiclone side chains were designed. The target compounds were synthesized via five steps, with 2,3-pyrazinecarboxylic anhydride and 2-amine-5-chloropyridine performed as starting materials. Taking benzodiazepine receptor antagonist 3H] flumazenil (3H] Ro 15-1788) as a tool, and flumazenil as a positive control drug, by testing receptor-binding capacity of the synthesized compounds for benzodiazepine receptor, the activity of target compounds were then preliminarily assessed. Results and Conclusions seventeen novel cyclopyrrolone derivatives were synthesized, and their structures were confirmed by MS and 1H-NMR. Among them some of derivatives displayed certain activities.