Synthesis and biological evaluation of a novel sigma-1 receptor antagonist based on 3,4-dihydro-2(1H)-quinolinone scaffold as a potential analgesic.
Yu Lan, Yin Chen, Xiangqing Xu, Yinli Qiu, Shicheng Liu, Xin Liu, Bi-Feng Liu, Guisen Zhang
文献索引:Eur. J. Med. Chem. 79 , 216-30, (2014)
全文:HTML全文
摘要
The synthesis and sigma-1 receptor (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 (Ki1=1.22nM) 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.
相关化合物
相关文献:
2015-01-15
[J. Ethnopharmacol. 159 , 93-101, (2014)]
2014-11-01
[J. Am. Soc. Mass Spectrom. 25(11) , 1897-907, (2014)]
2014-07-01
[Autophagy 10(7) , 1241-55, (2014)]
2015-01-01
[Arch. Toxicol. 89(1) , 107-19, (2015)]
2014-12-01
[Biochim. Biophys. Acta 1842(12 Pt A) , 2345-56, (2014)]