混合型多巴胺摄取阻断剂-5-羟色胺释放剂配体：针对转运体的治疗方法的新突破。
Hybrid dopamine uptake blocker-serotonin releaser ligands: a new twist on transporter-focused therapeutics.
作者信息
Blough Bruce E, Landavazo Antonio, Partilla John S, Baumann Michael H, Decker Ann M, Page Kevin M, Rothman Richard B
机构信息
Center for Drug Discovery, Discovery-Science-Technology, RTI International , 3040 Cornwallis Road, Research Triangle Park, North Carolina 27709, United States.
Medicinal Chemistry Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health , Baltimore, Maryland 21224, United States.
出版信息
ACS Med Chem Lett. 2014 Apr 15;5(6):623-7. doi: 10.1021/ml500113s. eCollection 2014 Jun 12.
Abstract
As part of our program to study neurotransmitter releasers, we report herein a class of hybrid dopamine reuptake inhibitors that display serotonin releasing activity. Hybrid compounds are interesting since they increase the design potential of transporter related compounds and hence represent a novel and unexplored strategy for therapeutic drug discovery. A series of N-alkylpropiophenones was synthesized and assessed for uptake inhibition and release activity using rat brain synaptosomes. Substitution on the aromatic ring yielded compounds that maintained hybrid activity, with the two disubstituted analogues (PAL-787 and PAL-820) having the most potent hybrid activity.
摘要
作为我们研究神经递质释放剂项目的一部分，我们在此报告一类具有5-羟色胺释放活性的混合型多巴胺再摄取抑制剂。混合型化合物很有意思，因为它们增加了与转运蛋白相关化合物的设计潜力，因此代表了一种用于治疗药物发现的新颖且未被探索的策略。合成了一系列N-烷基苯丙酮，并使用大鼠脑突触体评估其摄取抑制和释放活性。芳环上的取代产生了保持混合型活性的化合物，其中两个二取代类似物（PAL-787和PAL-820）具有最强的混合型活性。
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