Position 6 of the morphinan skeleton plays a key role in the μ-opioid receptor (MOR) activity in vitro and in vivo. We describe the consequence of the 6-carbonyl group deletion in N-methylmorphinan-6-ones 1–4 on ligand–MOR interaction, signaling, and antinociception. While 6-desoxo compounds 1a, 2a, and 4a show similar profiles to their 6-keto counterparts, the 6-desoxo-14-benzyloxy substituted 3a displays significantly increased MOR binding and agonist potency and a distinct binding mode compared with its analogue 3.

中文翻译：

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6-Desoxo- N-甲基吗啡喃作为有效的μ阿片受体激动剂的合成，药理学和分子对接研究

吗啡喃骨架的6位在体外和体内的μ阿片受体（MOR）活性中起着关键作用。我们描述了在6 -羰基缺失的结果Ñ -methylmorphinan -6-酮1 - 4上的配体- MOR相互作用，信号，和抗伤害感受作用。虽然6-desoxo化合物1a，2a和4a与它们的6-keto对应物具有相似的分布，但6-desoxo-14-苄氧基取代的3a与其类似物3相比，其MOR结合力和激动剂效能显着提高，结合方式也不同。