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: Marion Donnier-Maréchal, Pascal Carato, Delphine Le Broc, Christophe Furman, Patricia Melnyk
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 92 Pg. 575-82 (Mar 06 2015) ISSN: 1768-3254 [Electronic] France
• PMID: 25602932 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Chemical References

• Benzimidazoles
• Benzothiazoles
• Benzoxazoles
• Heterocyclic Compounds
• Hydrocarbons, Brominated
• Ligands
• Receptors, sigma
• sigma-2 receptor
• benzoxazolone
• benzothiazoline
• benzimidazole

Topics

• Benzimidazoles (chemical synthesis, chemistry, pharmacology)
• Benzothiazoles (chemical synthesis, chemistry, pharmacology)
• Benzoxazoles (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Dose-Response Relationship, Drug
• Heterocyclic Compounds (chemical synthesis, chemistry, pharmacology)
• Humans
• Hydrocarbons, Brominated (chemical synthesis, chemistry, pharmacology)
• Ligands
• Molecular Structure
• Receptors, sigma (antagonists & inhibitors, metabolism)
• Structure-Activity Relationship