高等学校化学学报2011，Vol.32Issue(8)：1779-1784,6.
新型多巴胺D3受体抑制剂的发现
Discovery of a Novel Dopamine D3 Receptor Inhibitor
摘要
Abstract
Dopamine D3 receptor regulates the synthesis and release of dopamine in brain. It is implicated in many neurological processes, including motivation, pleasure, cognition, memory, learning, and fine motor control. It is involved in the pathology of psychotic diseases, such as schizophrenia, Parkinson' s disease and drug addiction. It is of great significance to discover novel D3 inhibitors through pharmacophore-based virtual screening for the development of anti-psychotic drugs. In this study, we employed the latest discovered high-resolution crystal structure of human D3 receptor to conduct active-site-analysis, build the receptor-based pharmacophore model and screen the Asinex GOLD Collection database. 7 hits were purchased and tested by pharmacological experiments. A novel inhibitor 04932482 with a high activity against D3 receptor was obtained [Ki = (806. 75 ±34. 58) nmol/L]. The structure analysis was conducted and the ligand-receptor interaction was further investigated by docking to guide the structure modification and optimization of compound 04932482.关键词
多巴胺D3受体/药效团模型/数据库筛选/抑制剂Key words
Dopamine D3 receptor/ Pharmacophore model/ Database screening/ Inhibitor分类
化学化工引用本文复制引用
邓欣贤,沈庆,徐丽丽,熊子君,赵伟利,镇学初,付伟..新型多巴胺D3受体抑制剂的发现[J].高等学校化学学报,2011,32(8):1779-1784,6.基金项目
国家自然科学基金(批准号:20702009)、国家“八六三”计划项目(批准号:2009 AA02Z308)和国家“九七三”计划项目(批准号:2010CB912601)资助. （批准号:20702009）
