title: Synthesis and pharmacological evaluation of benzannulated derivatives as potent and selective sigma-1 protein ligands.
abstract: The σ1 proteins are considered to be a new class of target structures for several central nervous system disorders, including depression, anxiety, psychosis, and Parkinson's and Alzheimer's diseases. Recently, the involvement of these receptors in neuropathic pain and cancer has also been observed. So far, only a few ligands are in clinical trials. In a continuation of our previous studies on the development of σ1 ligands, a new series of benzannulated heterocycles was designed and synthesised. In vitro competition binding assays showed that many of them possessed high σ1 receptor affinity (Ki = 0.6-10.3 nM), and good σ2/σ1 subtype selectivity, without cytotoxic effects on SY5Y cells (human neuroblastoma cell line).
authors.affiliation: Univ Lille Nord de France, F-59000 Lille, France; UDSL, EA 4481, UFR Pharmacie, F-59000 Lille, France. Electronic address: marion.donnier-marechal@univ-lille2.fr.
authors.forename: Marion
authors.initials: M
authors.lastname: Donnier-Maréchal
authors.affiliation: Univ Lille Nord de France, F-59000 Lille, France; UDSL, EA 4481, UFR Pharmacie, F-59000 Lille, France. Electronic address: pascal.carato@univ-lille2.fr.
authors.forename: Pascal
authors.initials: P
authors.lastname: Carato
authors.affiliation: Univ Lille Nord de France, F-59000 Lille, France; UDSL, EA 4483, UFR Pharmacie, F-59000 Lille, France. Electronic address: delphine.lebroc@univ-lille2.fr.
authors.forename: Delphine
authors.initials: D
authors.lastname: Le Broc
authors.affiliation: Univ Lille Nord de France, F-59000 Lille, France; UDSL, EA 4483, UFR Pharmacie, F-59000 Lille, France. Electronic address: christophe.furman@univ-lille2.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Furman
authors.affiliation: Univ Lille Nord de France, F-59000 Lille, France; UDSL, EA 4481, UFR Pharmacie, F-59000 Lille, France. Electronic address: patricia.melnyk@univ-lille2.fr.
authors.forename: Patricia
authors.initials: P
authors.lastname: Melnyk
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001583:Benzoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D015394:Molecular Structure; D017480:Receptors, sigma / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles; D052160:Benzothiazoles; D001583:Benzoxazoles; D006571:Heterocyclic Compounds; D006842:Hydrocarbons, Brominated; D008024:Ligands; D017480:Receptors, sigma; C106107:sigma-2 receptor; C017057:benzoxazolone; C058836:benzothiazoline; C031000:benzimidazole
keywords: Alzheimer; Benzazolinone; Benzimidazole; Benzimidazolone; Sigma 1