Jeeyeon Kim

Aryl Biphenyl-3-ylmethylpiperazines as 5-HT7 Receptor Antagonists

The 5‐HT7 receptor (5‐HT7R) is a promising therapeutic target for the treatment of depression and neuropathic pain. The 5‐HT7R antagonist SB‐269970 exhibited antidepressant‐like activity, whereas systemic administration of the 5‐HT7R agonist AS‐19 significantly inhibited mechanical hypersensitivity and thermal hyperalgesia. In our efforts to discover selective 5‐HT7R antagonists or agonists, aryl biphenyl‐3‐ylmethylpiperazines were designed, synthesized, and biologically evaluated against the 5‐HT7R. Among the synthesized compounds, 1‐([2′‐methoxy‐(1,1′‐biphenyl)‐3‐yl]methyl)‐4‐(2‐methoxyphenyl)piperazine (28) was the best binder to the 5‐HT7R (pKi=7.83), and its antagonistic property was confirmed by functional assays. The selectivity profile of compound 28 was also recorded for the 5‐HT7R over other serotonin receptor subtypes, such as 5‐HT1R, 5‐HT2R, 5‐HT3R, and 5‐HT6R. In a molecular modeling study, the 2‐methoxyphenyl moiety attached to the piperazine ring of compound 28 was proposed to be essential for the antagonistic function.

Discovery of aryl-biphenyl-2-ylmethylpiperazines as novel scaffolds for 5-HT7 ligands and role of the aromatic substituents in binding to the target receptor

It has been reported that 5-HT(7) receptors are promising targets of depression and neuropathic pain. 5-HT(7) receptor antagonists have exhibited antidepressant-like profiles, while agonists have represented potential therapeutics for pain. In the course of our ongoing efforts to discover novel 5-HT(7) modulators, we designed an arylpiperazine scaffold with a substituted biphenyl-2-ylmethyl group. A series of biphenyl-2-yl-arylpiperazinylmethanes were then prepared, which showed a broad spectrum of binding affinities to the 5-HT(7) receptor depending upon the substituents attached to the biphenyl and aryl functionalities. Among those synthesized compounds, the compounds 1-24 and 1-26 showed the best binding affinities to the 5-HT(7) receptor with K(i) values of 43.0 and 46.0 nM, respectively. Structure-activity relationship study in conjunction with molecular docking study proposed that the 5-HT(7) receptor might have two distinctive hydrophobic binding sites, one specific for aromatic 2-OCH(3) substituents within the arylpiperazine and the other for biphenyl methoxy group.

Linking Findings from Text Analyses to Online Sales Strategies

Much effort has been exerted to analyze online texts and unders tand how empirical results can help improve sales performance. In this research, we aim to extend this stream of research by decomposing online texts based on text sources, namely, companies and consumers. To be specific, we in vestigate how online texts driven by companies differ from those generated by consumers, and the extent to which both types of online texts have different effects on online sales. We obtained sales data from one of the biggest game publ ishers and merged them with online texts provided by companies using news articles and those created by consumers in user communities. The empirical analyses yield the following findings. Word visualization and topic analyses s how that firms and consumers generate different contexts. Specifically, companies spread word to promote their own events whereas consumers produce online words to share winning strategies. Moreover, online sales are influenced by co nsumer-generated community topics whereas firm-driv-en topics in news articles have little to no effect. These find ings suggest that companies should focus more on online texts generated by consumers rather than spreading their own wo rds. Moreover, online sales strategies should take advantage of specific topics that have been proven to increase online sales. In particular, these findings give startup companies and small business owners in variety of industries the advantage when they use the online channel for distribution and as a marketing platform.