Abstract

Unsymmetrical urea derivatives have been reported to play a significant role in plethora of biological pathways (e.g., neurotransmission, neuromodulation). Notably, urea-based scaffolds are increasingly employed in medicinal chemistry campaigns to engage key protein interactions owing to their tunable physicochemical and structural properties. In this study, we disclose the first examples of unsymmetrical phenethylamine based urea derivatives in aqueous conditions. The reactions involving in-situ generated imidazolide intermediate proceed to completion in the absence of base and under air at room temperature thus allowing access to sensitive functional groups. We also demonstrate a useful product functionalization (i.e., demethylation of 4-methoxyphenethylamine via BBr₃) to access the corresponding tyramine analogues. All urea and phenolic derivatives were characterized with ¹H NMR, ¹³C NMR, FT-IR, and elemental analysis.

Graphic abstract

中文翻译：

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由取代的苯乙胺合成不对称脲的潜在生物活性新型酚衍生物

摘要

据报道，不对称尿素衍生物在过多的生物途径（例如神经传递，神经调节）中起着重要作用。值得注意的是，基于尿素的支架由于其可调节的物理化学和结构特性，越来越多地用于药物化学研究中以参与关键的蛋白质相互作用。在这项研究中，我们公开了在水性条件下基于不对称苯乙胺的脲衍生物的第一个实例。涉及原位生成的咪唑啉中间体的反应在不存在碱的情况下和在室温下于空气中进行至完全，从而允许获得敏感的官能团。我们还证明了有用的产品功能化（即通过BBr ₃使4-甲氧基苯乙胺脱甲基））以访问相应的酪胺类似物。所有脲和酚类衍生物均通过¹ H NMR，¹³ C NMR，FT-IR和元素分析进行​​表征。

图形摘要