【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。更多还原

【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 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.更多还原