选择性SSRI/5-HT1A/5-HT7三靶点抗抑郁剂具有起效快、副作用低、改善认知功能等优点，为目前发现高效、低毒抗抑郁活性分子的新途径。本课题前期发现一类二芳基哌嗪类化合物可选择性作用于SSRI/5-HT1A/5-HT7三靶点，体内显示较好的抗抑郁活性，药代特性较理想，安全性较高并具有潜在的认知改善作用，具有进一步研究价值。.本课题进一步设计合成系列新化合物，通过初步成药性试验，探讨在SSRI/5-HT1A双靶点作用基础上，增加5-HT7受体拮抗作用对抗抑郁起效快慢、认知功能改善以及性功能的影响；在完善化合物构效关系的基础上，构建SSRI/5-HT1A/5-HT7三靶点作用药效团模型，为发现高效、低毒且能改善认知功能的新型抗抑郁活性分子提供指导和借鉴。

The antidepressants with SSRI/5-HT1A /5-HT7 selectively have the advantage of rapid-onset of action, low side effects and cognitive function improvement, which provided a new strategy for developing and research on efficient and low toxicity antidepressant currently. The previous studies have found a class of diaralkyl piperazine derivatives with SSRI/5-HT1A/5-HT7 activity selectively. Those compounds displayed great efficacy of antidepressant in vivo, good pharmacokinetic profiles, low side effects, and potential cognitive function improvement. .Based on the previous study, a series of new compounds with good druggabilities will be designed and synthesized. Further researches will be focused on the function and affinity of 5-HT7 receptor antagonist, aiming at increasing the rapid-onset of action and improving cognitive function, reducing the side effects such as sexual dysfunction. On the basis of structure-function relationship study, a rational three targets pharmacophore model of SSRI/5-HT1A/5-HT7 will be established. The results provide guidance for the discovery of a new class of diaralkyl piperazine derivatives with high efficiency, low toxicity and cognitive function improvement as antidepressants.