Hacksell U, Arvidsson L E, Svensson U, Nilsson J L, Sanchez D, Wikström H, Lindberg P, Hjorth S, Carlsson A
J Med Chem. 1981 Dec;24(12):1475-82. doi: 10.1021/jm00144a021.
Thirty compounds related to the selective dopamine-autoreceptor agonist 3-(3-hydroxyphenyl)-N-n-propylpiperidine have been synthesized and tested for central dopamine-autoreceptor stimulating activity. The 3-(3-hydroxyphenyl)piperidine moiety seems indispensable for high potency and selectivity. Introduction of an additional hydroxyl group into the 4 position of the aromatic ring gives a compound with dopaminergic activity but lacking selectivity for autoreceptors. 3-(3-Hydroxyphenyl)-N-n-propylpyrrolidine, 3-(3-hydroxy)-N-n-propylperhydroazepine, and 3-(3-hydroxyphenyl)quinuclidine were all inactive. The most potent compounds were the N-isopropyl-, N-n-butyl-, N-n-pentyl-, and N-phenethyl-substituted 3-(3-hydroxyphenyl)piperidine derivatives. None of the compounds investigated seemed to have central noradrenaline- or serotonin-receptor stimulating activity.
已合成了30种与选择性多巴胺自受体激动剂3-(3-羟基苯基)-N-正丙基哌啶相关的化合物，并对其进行了中枢多巴胺自受体刺激活性测试。3-(3-羟基苯基)哌啶部分对于高效能和选择性似乎是必不可少的。在芳环的4位引入一个额外的羟基会得到一种具有多巴胺能活性但对自受体缺乏选择性的化合物。3-(3-羟基苯基)-N-正丙基吡咯烷、3-(3-羟基)-N-正丙基全氢氮杂卓和3-(3-羟基苯基)奎宁环均无活性。最有效的化合物是N-异丙基、N-正丁基、N-正戊基和N-苯乙基取代的3-(3-羟基苯基)哌啶衍生物。所研究的化合物似乎均无中枢去甲肾上腺素或5-羟色胺受体刺激活性。
