Risgaard Rune, Jensen Martin, Jørgensen Morten, Bang-Andersen Benny, Christoffersen Claus T, Jensen Klaus G, Kristensen Jesper L, Püschl Ask
Neuroscience Drug Discovery, H. Lundbeck A/S, 9 Ottiliavej, DK-2500 Valby, Denmark; Department of Drug Design and Pharmacology, The Faculty of Health and Medical Sciences, University of Copenhagen, 2 Universitetsparken, DK-2100 Copenhagen, Denmark.
Neuroscience Drug Discovery, H. Lundbeck A/S, 9 Ottiliavej, DK-2500 Valby, Denmark.
Bioorg Med Chem. 2014 Jan 1;22(1):381-92. doi: 10.1016/j.bmc.2013.11.012. Epub 2013 Nov 15.
The synthesis of a novel series of dopamine receptor agonists are described as well as their in vitro potency and efficacy on dopamine D₁ and D₂ receptors. This series was designed from pergolide and (4aR,10aR)-1-propyl-1,2,3,4,4a,5,10,10a-octahydro-benzo[g]quinolin-6-ol (PHBQ) and resulted in the synthesis of (2R,4aR,10aR)-2-methylsulfanylmethyl-4-propyl-3,4,4a,5,10,10a-hexahydro-2H-naphtho[2,3-b][1,4]oxazin-9-ol (compound 27), which has a D₁ and D₂ receptor profile similar to that of the most recently approved drug for Parkinson's disease, rotigotine.
本文描述了一系列新型多巴胺受体激动剂的合成及其对多巴胺D₁和D₂受体的体外效力和功效。该系列是基于培高利特和(4aR,10aR)-1-丙基-1,2,3,4,4a,5,10,10a-八氢-苯并[g]喹啉-6-醇（PHBQ）设计而成，最终合成了(2R,4aR,10aR)-2-甲硫基甲基-4-丙基-3,4,4a,5,10,10a-六氢-2H-萘并[2,3-b][1,4]恶嗪-9-醇（化合物27），其D₁和D₂受体特征与最近批准用于治疗帕金森病的药物罗替戈汀相似。
