Synthesis of N-Alkyl-Carbazole Derivatives as 5-HT7R Antagonists

Youngjae Kim, Miyoung Yeom, Soyeon Lee, Jinsung Tae, Hak Joong Kim, Hyewhon Rhim, Jihye Seong, Kyung Il Choi, Sun Joon Min, Hyunah Choo

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Abstract

We designed and synthesized a series of N-alkyl-carbazoles with different alkyl chains and amine moieties, and biological evaluation was performed to discover novel 5-HT7R antagonists. Among 27 synthesized compounds, 20, 21, 23, and 24 showed excellent binding affinities to 5-HT7R (Ki = 65, 64, 55, and 31 nM, respectively), and good selectivity profiles over other serotonin receptors. In functional assays, those compounds showed weak antagonistic activities against 5-HT7R. In particular, the compound 24, 2-(4-(5-(9H-carbazol-9-yl)pentyl)piperazin-1-yl)phenol, could be considered as a potent and selective 5-HT7R ligand with weak antagonistic effect. From the molecular docking study, the aromatic hydroxyl group in 24 was shown to play an important role in binding to 5-HT7R through a hydrogen bonding interaction with Asp142 in the ligand binding pocket of 5-HT7R.

Original languageEnglish
Pages (from-to)1083-1089
Number of pages7
JournalBulletin of the Korean Chemical Society
Volume39
Issue number9
DOIs
Publication statusPublished - 2018 Sep

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All Science Journal Classification (ASJC) codes

  • Chemistry(all)

Cite this

Kim, Y., Yeom, M., Lee, S., Tae, J., Kim, H. J., Rhim, H., Seong, J., Choi, K. I., Min, S. J., & Choo, H. (2018). Synthesis of N-Alkyl-Carbazole Derivatives as 5-HT7R Antagonists. Bulletin of the Korean Chemical Society, 39(9), 1083-1089. https://doi.org/10.1002/bkcs.11555