A series of novel 1-(1-benzoylpiperidin-4-yl) methanamine derivatives were synthesized and evaluated for the serotonin reuptake inhibitory abilities and binding affinities to the 5-HT_1A receptor. The metabolic stabilities of these compounds were measured in vitro using human or mouse liver microsomes and the antidepressant activities were explored In vivo using the forced swimming test (FST) and tail suspension test (TST) in mice. The results indicated that the compound 12a exhibited strongest serotonin reuptake inhibition (IC₅₀ = 8.2 nM) and marked 5-HT_1A receptor affinity (Ki = 0.069 nM), which were significantly superior to lead compounds Ⅰ and Ⅱ. Meanwhile, compound 12a showed good metabolic stability in vitro and exhibited potential antidepressant-like effects in the FST and TST in mice.

合成了一系列新型 1-(1-benzoylpiperidin-4-yl) 甲胺衍生物，并评估了 5-羟色胺再摄取抑制能力和与 5-HT _1A受体的结合亲和力。使用人或小鼠肝微粒体在体外测量这些化合物的代谢稳定性，并在小鼠体内使用强迫游泳试验 (FST) 和悬尾试验 (TST)探索抗抑郁活性。结果表明，化合物12a表现出最强的5-羟色胺再摄取抑制（IC ₅₀  = 8.2 nM）和显着的5-HT _1A受体亲和力（Ki = 0.069 nM），显着优于先导化合物Ⅰ和Ⅱ．同时，化合物12a在体外表现出良好的代谢稳定性，并在小鼠的FST和TST中表现出潜在的抗抑郁样作用。