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

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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

Bibliographical note

Funding Information:
Acknowledgments. We are grateful to the US National Institute of Mental Health (NIMH) Psychoactive Drug Screening Program (contract: HHSN-271-2008-00025-C) for providing binding affinity data. This research is supported by the Original Technology Research Program (NRF-2016M3C7A1904344) funded by the National Research Foundation of Korea (NRF). And this work is additionally funded by the Korea Institute of Science and Technology (KIST) (2E27870 and 2E28412).

Publisher Copyright:
© 2018 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

All Science Journal Classification (ASJC) codes

  • Chemistry(all)

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