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Synthesis of N ‐Alkyl‐Carbazole Derivatives as 5‐HT 7 R Antagonists
Author(s) -
Kim Youngjae,
Yeom Miyoung,
Lee Soyeon,
Tae Jinsung,
Kim Hak Joong,
Rhim Hyewhon,
Seong Jihye,
Choi Kyung Il,
Min SunJoon,
Choo Hyunah
Publication year - 2018
Publication title -
bulletin of the korean chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.237
H-Index - 59
ISSN - 1229-5949
DOI - 10.1002/bkcs.11555
Subject(s) - chemistry , alkyl , hydrogen bond , carbazole , amine gas treating , selectivity , stereochemistry , affinities , ligand (biochemistry) , 5 ht receptor , docking (animal) , serotonin , phenol , receptor , medicinal chemistry , molecule , organic chemistry , biochemistry , medicine , nursing , catalysis
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‐HT 7 R antagonists. Among 27 synthesized compounds, 20 , 21 , 23 , and 24 showed excellent binding affinities to 5‐HT 7 R ( K i = 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‐HT 7 R. In particular, the compound 24 , 2‐(4‐(5‐(9 H ‐carbazol‐9‐yl)pentyl)piperazin‐1‐yl)phenol, could be considered as a potent and selective 5‐HT 7 R 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‐HT 7 R through a hydrogen bonding interaction with Asp142 in the ligand binding pocket of 5‐HT 7 R.