Synthesis of N ‐Alkyl‐Carbazole Derivatives as 5‐HT 7 R Antagonists

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.