新型含 1,3,5-三恶嗪三环骨架的三重态药物的合成及其药理学研究。1：含吗啡烷骨架的三重态药物的合成。
Synthesis of novel triplet drugs with 1,3,5-trioxazatriquinane skeletons and their pharmacologies. 1: Synthesis of triplet drugs with morphinan skeletons.
机构信息
School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
出版信息
Bioorg Med Chem Lett. 2011 Jul 1;21(13):4023-6. doi: 10.1016/j.bmcl.2011.04.134. Epub 2011 May 5.
We synthesized symmetrical and nonsymmetrical triplet drugs with 1,3,5-trioxazatriquinane skeletons. The isolation of key intermediates, oxazoline dimers, made it possible to effectively produce nonsymmetrical triplets. Among the synthesized triplets, KNT-93, composed of three identical opioid μ receptor agonists, showed dose-dependent antinociception via the μ receptor. The effect was 56-fold more potent than that of morphine, a representative μ agonist. The profound analgesic effect induced by KNT-93 might result from simultaneous occupation of three μ opioid receptors.
我们合成了具有 1,3,5-三恶嗪烷骨架的对称和非对称三联体药物。关键中间体恶唑啉二聚体的分离使得有效制备非对称三联体成为可能。在所合成的三联体中，由三个相同的阿片类 μ 受体激动剂组成的 KNT-93 通过 μ 受体表现出剂量依赖性的镇痛作用。其效果是代表性 μ 激动剂吗啡的 56 倍。KNT-93 诱导的强烈镇痛作用可能源于同时占据三个 μ 阿片受体。
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