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 language | English |
---|---|
Pages (from-to) | 1083-1089 |
Number of pages | 7 |
Journal | Bulletin of the Korean Chemical Society |
Volume | 39 |
Issue number | 9 |
DOIs | |
Publication status | Published - 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)