吗啡作为一类强效的阿片类镇痛药物，其临床应用受限于呼吸抑制、成瘾性、耐受性等相关副作用 , 而开发具备μ/δ受体双重活性的功能分子是解决上述副作用的重要策略。分子模拟对接结果显示，在吗啡的C环修饰带有一定刚性兼疏水性的并环结构，可以有效增强配体分子与δ受体之间的亲和性，发现具备μ/δ受体双重活性的功能性分子。本研究在前期工作的基础上，开发一类吗啡结构的C环并取代四氢嘧啶环以及喹啉环的双重功能分子，并对上述化合物进行活性及副作用等体内外生物评价，以期获得镇痛活性强，低副作用的新型吗啡类衍生物， 为解决吗啡临床应用中存在的副作用问题提供新的思路。

Morphine is the most potent opioid analgesic. But its clinical efficacy is limited due to the μ opioid receptor-induced side effects, such as respiratory depression, addiction, tolerance. The strategy of developing bifunctional ligands with mixed μ/δ affinity was proved to avoid those adverse side effects. The molecular docking results showed that, the annulation of C-ring of morphine scaffold was beneficial for achieving this goal. Based on our previous work, our approach is to develop bifunctional agents such as tetrapyrimidomorphinans and quinolinomorphinans. Further structure optimization and biological evaluation will be carried in order to deliver novel opioid analgesics with mixed μ/δ affinity exhibiting the most optimized analgesic activity free of side effects. And this strategy would address the limit for the developing analgesic drugs.