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目的设计并合成环吡咯酮类化合物,并评价其与苯二氮受体的结合活性。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,部分化合物具有一定的活性。
Objective To design and synthesize cyclopyrrolone compounds and evaluate their binding activity to benzodiazepine receptor. Methods According to the basic structure of zopiclone, a cyclopyrolidone sedative and hypnotic drug, 17 cyclopirline compounds were designed to alter the side chain of the ester bond. Pyrazinedicarboxylic anhydride and 2-amino-5-chloropyridine were used as starting materials to obtain the target product after 5 steps. The benzodiazepine receptor antagonist tritiated flumazenil ([3H] Ro 15-1788) was used as a tool, and flumazenil was used as a positive control drug. The synthesized compounds were tested for competition with benzodiazepine receptor The activity of the target compound was preliminary evaluated. RESULTS AND CONCLUSIONS Seventeen indirapproxypyrrole compounds were synthesized and their structures were confirmed by MS and 1H-NMR. Active screening experiments show that some compounds have some activity.