N-Alkylated 2-aminotetralins: central dopamine-receptor stimulating activity.
N-Alkylated 2-aminotetralins: central dopamine-receptor stimulating activity.
复制标题
N-烷基化 2-氨基四氢化萘：中枢多巴胺受体刺激活性。
DOI：
10.1021/jm00198a008
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发表时间：
1979
影响因子：
7.3
通讯作者：
D. Sanchez
中科院分区：
文献类型：
--
作者：
U. Hacksell;U. Svensson;J. Nilsson;S. Hjorth;A. Carlsson;H. Wikström;P. Lindenberg;D. Sanchez
为了确定中枢多巴胺受体激动剂2-氨基四氢呋喃的N-取代基的结构要求，合成了一系列N-烷基和N，N-二烷基取代的2-氨基-5-羟基和2-氨基-5-甲氧基四氢吡喃类化合物。对这些化合物进行了生化和行为测试，以确定其多巴胺能活性。从生化数据可以得出结论，氮基上的正丙基是活性最好的。相应的N-乙基取代化合物的活性稍低，而没有N-乙基或N-丙基的化合物几乎没有活性。可以证明这是由于立体而不是亲脂因素造成的。有人认为，一个有效的激动剂的可能要求是它的一个N取代基必须适合受体腔，因为它的大小，可以最大限度地容纳正丙基，但也可以容纳较小的基团，如乙基或甲基。这些活性化合物似乎在突触前和突触后给予类似的相对刺激，对边缘系统和纹状体也有类似的活性。列出的化合物中似乎没有一种具有中枢去甲肾上腺素或5-羟色胺受体刺激活性。
In order to define the structural requirements of N-substituents of 2-aminotetralins as central dopamine receptor agonists, a series of N-alkyl- and N,N-dialkyl-substituted 2-amino-5-hydroxy- and 2-amino-5-methoxytetralins have been synthesized and evaluated. The compounds were tested biochemically and behaviorally for dopaminergic activity. From the biochemical data it is concluded that an n-propyl group on the nitrogen is optimal for activity. The corresponding N-ethyl-substituted compounds are slightly less active, while the absence of N-ethyl or N-propyl groups give almost inactive compounds. It could be demonstrated that this is due to steric and not to lipophilic factors. It is suggested that a possible requirement for a potent agonist is that one of it N substituents must fit into a receptor cavity which, because of its size, can maximally accommodate an n-propyl but also smaller groups like ethyl or methyl. The active compounds appeared to give a similar relative pre- and postsynaptic stimulation and had also similar activities for the limbic system and for striatum. None of the compounds listed seemed to have central noradrenaline- or serotonin-receptor stimulating activity.