Herein, a series of novel 1-((4-methoxy-3-(piperazin-1-yl)phenyl)sulfonyl)- 1H-indole derivatives were designed and synthesized via hybridization strategy of idalopirdine and SB-271046. The optimal compound C14 (K_i = 0.085 nM), with difluoromethyl on C3 position on indole scaffold, increased the affinity for the 5-HT₆R up to 10-folds than idalopirdine (K_i = 0.83 nM). Additionally, C14 had good pharmacokinetic properties and in vitro metabolic properties. Finally, C14 could efficiently reverse the scopolamine induced emotional memory deficits in novel object recognition assay in rats. Thus, we propose C14 might be considered as a new cognition-enhancing agent and the further studies are now underway in our laboratory.

在此，通过艾达洛定和SB-271046的杂交策略，设计并合成了一系列新型1-((4-甲氧基-3-(哌嗪-1-基)苯基)磺酰基) -1H-吲哚衍生物。最佳化合物C14 (K _i = 0.085 nM)，在吲哚支架上的 C3 位置上具有二氟甲基，与idalopirdine (K _i  = 0.83 nM)相比，对 5-HT ₆ R 的亲和力增加了10 倍。此外，C14具有良好的药代动力学特性和体外代谢特性。最后，C14可以有效地逆转东莨菪碱诱导的大鼠新物体识别试验中的情绪记忆缺陷。因此，我们提出C14可能被认为是一种新的认知增强剂，我们的实验室正在进行进一步的研究。