Select triazole-based small molecules possess potent and selective kappa opioid receptor (KOR) agonism. Here, we designed twenty new analogs to investigate the structure–activity relationship effects for all three functional groups attached to the triazole core. We identified specific groups that are critical for KOR potency and further extended the range of moieties explored. These efforts revealed analogs with potency on par with our lead triazole probe molecule, Triazole 1.1, in addition to analogs possessing a spectrum of less potent KOR agonist activity.

中文翻译：

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三唑类κ阿片受体激动剂的构效关系研究

精选的基于三唑的小分子具有强效和选择性的κ阿片受体 (KOR) 激动作用。在这里，我们设计了 20 种新类似物来研究连接到三唑核的所有三个官能团的构效关系效应。我们确定了对 KOR 效力至关重要的特定组，并进一步扩展了所探索的部分范围。这些努力揭示了具有与我们的先导三唑探针分子 Triazole 1.1 同等效力的类似物，以及具有较弱 KOR 激动剂活性谱的类似物。