Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex, UK.
Bioorg Med Chem Lett. 2012 May 15;22(10):3560-3. doi: 10.1016/j.bmcl.2012.03.040. Epub 2012 Mar 16.
A series of α7 nicotinic acetylcholine receptor full-agonists with a 1,3,4-oxadiazol-2-amine core has been discovered. Systematic exploration of the structure-activity relationships for both α7 potency and selectivity with respect to interaction with the hERG channel are described. Further profiling led to the identification of compound 22, a potent full agonist showing efficacy in the novel object recognition model of cognition enhancement.
已发现一系列具有 1,3,4-恶二唑-2-胺核心的 α7 烟碱型乙酰胆碱受体全激动剂。本文详细描述了针对 α7 效力和选择性与 hERG 通道相互作用的构效关系的系统研究。进一步的分析导致了化合物 22 的鉴定,这是一种有效的全激动剂,在认知增强的新型物体识别模型中显示出疗效。