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  

Design and synthesis of nitrogen-containing benzoheterocyclic derivatives and their antipsychotic activities

作　　者：彭少平[1] 俞蕾平[2] 李建其[1] 

机构地区：[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201203

出　　处：《药学学报》2009年第9期994-1001,共8页Acta Pharmaceutica Sinica

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,并测定它们体内外的抗精神分裂症活性。化合物结构经1HNMR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0.05mg·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行为,其作用效果与0.1mg·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行深入研究的价值。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 studies showed 20 has potent antipsychotic activities on apomorphine mice model, which is a chance to find a better precursor of D2 partial agonist for further optimization.

关 键 词：抗精神分裂症 部分激动剂 合成 

分 类 号：R916.1[医药卫生—药学]