In this study, we report the synthesis and biological evaluation of a variety of α- and β-hydroxy substituted amino acid derivatives as potential amino acid subunits in inhibitors of GABA uptake transporters (GATs). In order to ensure that the test compounds adopt a binding pose similar to that presumed for related larger GAT inhibitors, lipophilic residues were introduced either at the amino nitrogen atom or at the alcohol function. Several of the synthesized compounds were found to exhibit similar inhibitory activity at the GAT subtypes mGAT2, mGAT3, and mGAT4, respectively, as compared with the reference N-butylnipecotic acid. Hence, these compounds might serve as starting point for future developments of more complex GAT inhibitors.

中文翻译：

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潜在的mGAT1-4抑制剂α-和β-羟基取代的氨基酸衍生物的合成和生物学评估

在这项研究中，我们报告了各种α-和β-羟基取代的氨基酸衍生物作为GABA吸收转运蛋白（GAT）抑制剂的潜在氨基酸亚基的合成和生物学评估。为了确保测试化合物具有与相关的较大的GAT抑制剂所假定的相似的结合姿势，在氨基氮原子或在醇官能团处引入了亲脂性残基。与参考N-丁基己二酸相比，发现几种合成的化合物分别对GAT亚型mGAT2，mGAT3和mGAT4表现出相似的抑制活性。因此，这些化合物可作为更复杂的GAT抑制剂未来开发的起点。