3,4-2[1H]-二氢喹啉酮衍生物的设计合成及抗精神分裂症活性研究.pdf

994 药学学报 Acta Pharmaceutica Sinica 2009, 44 (9) : 994 1001 3,4-2 [1H]- 氢喹啉酮衍生物的设计合成及抗精神分裂症活性研究 1 2 1* 彭少平 , 俞蕾平 , 李建其 ( 1. 上海医药工业研究院, 上海 200437; 2. 中国科学院上海药物研究所, 上海 20 1203) 摘要: 以多巴胺D2 受体和5-HT2A 受体为靶点, 设计合成了22 个3, 4-2 [1H]-二氢喹啉酮类化合物, 并测定它 1 们体内外的抗精神分裂症活性。化合物结构经 H NMR 和HR-MS 确证。所合成的多个化合物对 D2 和 5-HT2A 受体具有较高亲和力, 其中化合物20 对两受体的亲和力最高, 符合新型抗精神分裂症药物的受体药理学特征。 腹腔注射 0.05 mg kg− 1 化合物 20 能明显改善阿朴吗啡精神分裂症模型小鼠的刻板 为, 其作用效果与 0.1 mg kg− 1 的阿立哌唑相当 (P 0.05) 。化合物20 具有作为新型抗精神分裂症先导化合物进 深入研究的价值。 关键词: 抗精神分裂症; 部分激动剂; 合成 中图分类号: R916.1 文献标识码:A 文章编号: 0513-4870 (2009) 09-0994-08 Design and synthesis of nitrogen-containing benzoheterocyclic derivatives and their antipsychotic activities 1 2 1* PENG Shao-ping , YU Lei-ping , LI Jian-qi (1.Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China; 2. Shanghai Institute of Materia M edica, Chinese Academy of Sciences , Shanghai 201203, China) Abstract: A series of nitrogen-containing benzoheterocyclic derivatives were synthesized and tested for their antipsychotic activities. Their structures were confirmed by 1H NMR and HR-MS. Preliminary in vitro pharmacological trials showed that most of the target compounds have high affinity with D2 and 5-HT2A receptors. Among the tested compounds, 20 exhibited the highest affinity and D2 partial agonist activity. In vivo studi