title: 6-Sulfonylbenzothiazolones as potential scaffolds for the design of 5-HT6 ligands.
abstract: 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.
authors: Université de Lille, F-59000 Lille, France; UDSL, EA 4481, UFR Pharmacie, F-59000 Lille, France; Inserm UMR-S1172, Jean-Pierre Aubert Research Center, F-59000 Lille, France. Electronic address: paul-emmanuel.larchanche@univ-lille2.fr.
authors: Paul-Emmanuel
authors: PE
authors: Larchanche
authors: Université de Lille, F-59000 Lille, France; UDSL, Laboratoire de RMN, UFR Pharmacie, F-59000 Lille, France. Electronic address: vincent.ultre@univ-lille2.fr.
authors: Vincent
authors: V
authors: Ultré
authors: Université de Lille, F-59000 Lille, France; UDSL, EA 4483, UFR Pharmacie, F-59000 Lille, France. Electronic address: delphine.lebroc@univ-lille2.fr.
authors: Delphine
authors: D
authors: Le Broc
authors: CERMN, EA 4258, UFR des Sciences Pharmaceutiques, UNICAEN, F-14032 Caen, France. Electronic address: celine.ballandone@unicaen.fr.
authors: Céline
authors: C
authors: Ballandone
authors: Université de Lille, F-59000 Lille, France; UDSL, EA 4483, UFR Pharmacie, F-59000 Lille, France. Electronic address: christophe.furman@univ-lille2.fr.
authors: Christophe
authors: C
authors: Furman
authors: CERMN, EA 4258, UFR des Sciences Pharmaceutiques, UNICAEN, F-14032 Caen, France. Electronic address: patrick.dallemagne@unicaen.fr.
authors: Patrick
authors: P
authors: Dallemagne
authors: Université de Lille, F-59000 Lille, France; UDSL, EA 4481, UFR Pharmacie, F-59000 Lille, France; Inserm UMR-S1172, Jean-Pierre Aubert Research Center, F-59000 Lille, France. Electronic address: patricia.melnyk@univ-lille2.fr.
authors: Patricia
authors: P
authors: Melnyk
authors: Université de Lille, F-59000 Lille, France; UDSL, EA 4481, UFR Pharmacie, F-59000 Lille, France. Electronic address: pascal.carato@univ-poitiers.fr.
authors: Pascal
authors: P
authors: Carato
mesh_terms: D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D052160:Benzothiazoles; D008024:Ligands; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C097216:serotonin 6 receptor
keywords: 5-HT(6) ligand; Benzothiazolone