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Synthesis and biological evaluation of a novel sigma-1 receptor antagonist based on 3,4-dihydro-2(1H)-quinolinone scaffold as a potential analgesic.
- Source :
-
European Journal of Medicinal Chemistry . May2014, Vol. 79, p216-230. 15p. - Publication Year :
- 2014
-
Abstract
- Abstract: The synthesis and sigma-1 receptor (σ 1R) antagonist activity of a new series of 3,4-dihydro-2(1H)-quinolinone derivatives are reported. The new compounds were evaluated in vitro in sigma-1 and sigma-2 receptor-binding assays in guinea pig brain membranes. The structure–activity relationship led us to the promising derivative 7-(3-(piperidin-1-yl)propoxy)-1-(4-fluorobenzyl)-3,4-dihydro-2(1H)-quinolinone (35). The compounds with highest affinity and greatest selectivity were further profiled, and compound 35 had a high binding constant for sigma-1 receptor (K i σ 1 = 1.22 nM) and high sigma-1/2 selectivity (1066-fold). Thus, compound 35, which proved to be an antagonist of sigma-1 receptor, emerged as the most interesting candidate. In addition, compound 35 exerted dose-dependent anti-nociceptive effects in the formalin test. These characteristics suggested that the potent and selective compound 35 could be a potent candidate for pain treatment. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 02235234
- Volume :
- 79
- Database :
- Academic Search Index
- Journal :
- European Journal of Medicinal Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 95825227
- Full Text :
- https://doi.org/10.1016/j.ejmech.2014.04.019