Novel Delta Opioid Receptor Agonists with Oxazatricyclodecane Structure
Novel Delta Opioid Receptor Agonists with Oxazatricyclodecane Structure
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DOI：
10.1021/ml400491k
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发表时间：
2014-04-01
影响因子：
4.2
通讯作者：
Nagase, Hiroshi
中科院分区：
文献类型：
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作者：
Fujii, Hideaki;Hayashida, Kohei;Nagase, Hiroshi
我们从新型重排反应产物 2a 中合成了含有氧氮杂三环癸烷结构的化合物 4a,c-f,h,i。所有制备的化合物 4a、c-f、h、i 对 δ 阿片受体 (DOR) 均表现出完全的激动活性。其中，N-甲基衍生物4c具有高选择性，是功能测定中最有效的DOR激动剂。皮下注射 4c 产生剂量依赖性和 NTI（选择性 DOR 拮抗剂）可逆的镇痛作用，在小鼠乙酸扭体试验中没有任何惊厥行为。 N-甲基衍生物 4c 有望成为具有新颖化学型的选择性 DOR 激动剂的有前途的先导化合物。
We synthesized compounds 4a,c-f,h,i containing the oxazatricyclodecane structure from a novel rearrangement reaction product 2a. All the prepared compounds 4a,c-f,h,i exhibited full agonistic activities for the delta opioid receptor (DOR). Among them, the N-methyl derivative 4c was highly selective, and the most effective DOR agonist in functional assays. Subcutaneous administration of 4c produced dose-dependent and NTI (selective DOR antagonist)-reversible antinociception lacking any convulsive behaviors in the mice acetic acid writhing tests. The N-methyl derivative 4c is expected to be a promising lead compound for selective DOR agonists with a novel chemotype.