6-Sulfonylbenzothiazolones as potential scaffolds for the design of 5-HT6 ligands

•A series of potential 5-HT6 ligands was synthesised.•Benzothiazolone was used as scaffold to explore the 5-HT6 receptor.•The affinity for 5-HT6 receptors was determined.•A low cytotoxicity was measured on SY5Y cells.

5-HT6 Receptors are relatively recently discovered receptors that interact with cholinergic, glutamatergic, GABAergic and dopaminergic transmission systems. These receptors have been implicated in the CNS system as therapeutic targets in applications such as psychosis, reduction of body weight or Alzheimer's disease. As part of our efforts to develop 5-HT6 antagonists, we explored the benzothiazolone scaffold substituted in position 3 or 6 respectively with ethylamino chains and an aromatic ring connected through a sulfonyl linker. Final compounds were evaluated in radioligand binding assays for their ability to interact with 5-HT6 receptors. Their potential cytotoxic effects were determined on the human neuroblastoma cell line SY5Y. They showed very low cytotoxicity, and one of them has submicromolar affinity for 5-HT6 receptors.

Graphical abstractA series of potential 5-HT6 ligands were synthesised using benzothiazolinone scaffold. Their affinity for 5-HT6 receptor and their cytotoxic effects were evaluated.Figure optionsDownload full-size imageDownload as PowerPoint slide