Guanidine and 2-aminoimidazoline aromatic derivatives as α2-adrenoceptor antagonists.: 2.: Exploring alkyl linkers for new antidepressants
Guanidine and 2-aminoimidazoline aromatic derivatives as α2-adrenoceptor antagonists.: 2.: Exploring alkyl linkers for new antidepressants
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DOI：
10.1021/jm800026x
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发表时间：
2008-06-12
影响因子：
7.3
通讯作者：
Callado, Luis F.
中科院分区：
文献类型：
--
作者：
Rodriguez, Fernando;Rozas, Isabel;Callado, Luis F.
本文报道了一系列作为潜在的α（2）-肾上腺素受体拮抗剂用于治疗抑郁症的（双）胍和（双）2-氨基咪唑啉衍生物的制备。人脑组织被用来测量他们的亲和力对α（2）-肾上腺素受体在体外。化合物6 b、8b、9 b、10 b、15 b、17 b、18 b、20 b和21 b表现出良好的亲和力（pK（i）> 7），并在人前额叶皮质的体外功能性[（35）S]GTP γ S结合试验中进行了评估，以确定其激动或拮抗活性。在这些化合物中，17 b和20 b显示出拮抗剂的预期行为，并在大鼠中进行体内微透析实验。值得注意的是，这些实验证实了17 b和20 b的拮抗特性，因此这两种化合物都可以被认为是潜在的抗抑郁药。
The preparation of a number of (bis)ouanidine and (bis)2-aminoimidazoline derivatives as potential alpha(2)-adrenoceptor antagonists for the treatment of depression is presented. Human brain tissue was used to measure their affinity toward the alpha(2)-adrenoceptors in vitro. Compounds 6b, 8b, 9b, 10b, 15b, 17b, 18b, 20b, and 21b displayed a good affinity (pK(i) > 7) and were evaluated in in vitro functional [(35)S]GTP gamma S binding assays in human prefrontal cortex to determine their agonistic or antagonistic activity. Among these compounds, 17b and 20b showed the expected behavior for an antagonist and were subject to in vivo microdialysis experiments in rats. Significantly, these experiments confirmed the antagonistic properties of 17b and 20b, and therefore both compounds can be considered as potential antidepressants.