Liu Danyang, Wikström Håkan V, Dijkstra Durk, de Vries Jan B, Venhuis Bastiaan J
Department of Medicinal Chemistry, University Centre for Pharmacy, University of Groningen, Antonius Deusinglaan 1, NL-9713 AV Groningen, The Netherlands.
J Med Chem. 2006 Feb 23;49(4):1494-8. doi: 10.1021/jm051111h.
Enone prodrugs of dopaminergic catecholamines represent a new type of prodrug in the research area of dopamine agonists. Here, we demonstrate the first benzo[g]quinoline-derived enone that induces potent dopamine agonist effects similar to aminotetralin-derived enones. Significant effects of (-)-4 were observed in microdialysis studies after administration of 1 nmol kg(-1) sc and 3 nmol kg(-1) po. With a potency comparable to that of the most potent apomorphines, (-)-4 could potentially compete with L-DOPA and apomorphine in the treatment of Parkinson's disease.
多巴胺能儿茶酚胺的烯酮前药是多巴胺激动剂研究领域中的一种新型前药。在此，我们展示了首个苯并[g]喹啉衍生的烯酮，其能诱导出与氨基四氢萘衍生的烯酮相似的强效多巴胺激动剂效应。皮下注射1 nmol kg(-1)和口服3 nmol kg(-1)的(-)-4后，在微透析研究中观察到了显著效果。(-)-4的效力与最有效的阿扑吗啡相当，在帕金森病治疗中可能与左旋多巴和阿扑吗啡形成竞争。
