Espahbodinia Milad, Ettari Roberta, Wen Wei, Wu Andrew, Shen Yu-Chuan, Niu Li, Grasso Silvana, Zappalà Maria
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Annunziata, 98168 Messina, Italy.
Department of Chemistry, and Center for Neuroscience Research, University at Albany, Albany, NY 12222, United States.
Bioorg Med Chem. 2017 Jul 15;25(14):3631-3637. doi: 10.1016/j.bmc.2017.05.036. Epub 2017 May 19.
In this work, we designed and synthesized novel N-3-bromoisoxazolin-5-yl substituted 2,3-benzodiazepines as noncompetitive AMPAR antagonists, with the aim that this heterocycle could establish favourable interactions with a putative binding pocket of the receptor, like the thiadiazole nucleus of GYKI 47409 does. Within this investigation, we identified some active molecules and, among these 2,3-benzodiazepines, 4c showed a much improved inhibitory potency as compared with unsubstituted 2,3-benzodiazepines.
在本研究中，我们设计并合成了新型的N-3-溴异恶唑啉-5-基取代的2,3-苯并二氮杂卓类化合物作为非竞争性α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）拮抗剂，目的是使该杂环能够与受体的假定结合口袋建立良好的相互作用，就像GYKI 47409的噻二唑核那样。在这项研究中，我们鉴定出了一些活性分子，在这些2,3-苯并二氮杂卓类化合物中，与未取代的2,3-苯并二氮杂卓相比，4c显示出显著提高的抑制效力。
