3，4-21H-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

摘要:
以多巴胺D₂受体和5-HT_2A受体为靶点, 设计合成了22个3, 4-21H-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¹H NMR和HR-MS确证。所合成的多个化合物对D₂和5-HT_2A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行为, 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行深入研究的价值。

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-HT_2A 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.