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首页> 外文期刊>Journal of Medicinal Chemistry >Study on Affinity Profile toward Native Human and Bovine Adenosine Receptors of a Series of 1,8-Naphthyridine Derivatives
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Study on Affinity Profile toward Native Human and Bovine Adenosine Receptors of a Series of 1,8-Naphthyridine Derivatives

机译：系列1,8-萘啶衍生物对天然人和牛腺苷受体的亲和力研究

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A new series of 1,8-naphthyridine derivatives (29-44 and 46-52) bearing various substituents in different positions on the heterocyclic nucleus were synthesized in order to analyze the effects produced on the affinity toward the bovine adenosine receptors. These derivatives represent an extension of our previous work on this class of compounds with high affinity toward A_1 adenosine receptors. The results of radioligand binding assays indicate that a large number of the 1,8-naphthyridine derivatives proved to be A_1 selective, with a high affinity toward bovine adenosine receptors in the low nanomolar range, and one (29) in the subnanomolar range. Furthermore, the new series of 1,8-naphthyridine derivatives (29-44 and 46-52), together with the analogous derivatives 1-28 previously studied,19 were tested to evaluate their affinity toward human cortical A_1 receptors and human striatal A_(2A) receptors. The results indicate that all the 1,8-naphthyridine compounds generally possess a higher affinity toward the bovine A_1 receptor compared with the human A_1 receptor. As regards the affinity toward the A_(2A) bovine receptor, only a few compounds possess a moderate affinity, which for some compounds remained approximately the same toward the A2A human receptor. A molecular modeling study of the docking of the 1,8-naphthyridine compounds with both the bovine and the human A_1 adenosine receptors was carried out with the aim of explaining the marked decrease in the affinity toward human A_1 adenosine receptors in comparison with bovine A_1 adenosine receptors. This study indicated that the structural differences, albeit small, of the active sites of the two receptors make differences in the dimensions of the site and this influenced the ability of the title compounds to interact with the two A_1 receptors.
机译：合成了一系列新的1,8-萘啶衍生物（29-44和46-52），它们在杂环核的不同位置带有不同的取代基，以分析其对牛腺苷受体的亲和力。这些衍生物代表了我们先前对这类对A_1腺苷受体具有高亲和力的化合物的研究成果的延伸。放射性配体结合测定的结果表明，大量的1,8-萘啶衍生物被证明具有A_1选择性，对低纳摩尔范围内的牛腺苷受体具有高亲和力，而在亚纳摩尔范围内具有一种（29）。此外，测试了一系列新的1,8-萘啶衍生物（29-44和46-52）以及先前研究的类似衍生物1-2819，以评估它们对人皮质A_1受体和人纹状体A_（ 2A）受体。结果表明，与人A_1受体相比，所有1,8-萘啶化合物通常对牛A_1受体具有更高的亲和力。关于对A_（2A）牛受体的亲和力，只有少数化合物具有中等亲和力，对于某些化合物，其对A2A人受体的亲和力大致相同。进行了分子模型研究，研究1,8-萘啶化合物与牛和人A_1腺苷受体的对接，目的是解释与牛A_1腺苷相比，对人A_1腺苷受体的亲和力显着降低受体。该研究表明，两种受体活性位点的结构差异尽管很小，但在位点尺寸上却有所不同，这影响了标题化合物与两种A_1受体相互作用的能力。

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