构效关系的可变映射:应用于具有矿物皮质激素活性的17-螺内酯衍生物

Gérard Grassy , Patrick Trape , Jacques Bompart , Bernard Calas , Gilles Auzou
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引用次数: 8

摘要

54种甾体同源物,属于17-旋内酯系列,通过分子和量子力学建模。我们通过描述每种结构及其分子性质的各种参数,研究了这些化合物对细胞质矿物皮质激素受体的亲和力。在经典的初步QSAR研究失败后,证明了亲和力和结构描述符之间的非线性关系,我们构建了一个模型,使我们能够预测新化合物的亲和力。我们的方法是基于简单的图形工具与聚类显著性分析相结合。使用相同的方法,对37种高亲和力化合物的拮抗剂/激动剂特性进行了活性预测的补充研究。揭示了导致选择性活性的主要电子和结构特征。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Variable mapping of structure-activity relationships: Application to 17-spirolactone derivatives with mineralocorticoid activity

Fifty-four steroid homologs, belonging to the series of 17-spirolactones, were modelled by molecular and quantum mechanics. We studied the affinity of these compounds for the cytosolic mineralocorticoid receptor by way of various parameters describing each structure and its molecular properties. After the failure of a classic preliminary QSAR study, demonstrating the nonlinear relationships between affinity and structural descriptors, we constructed a model allowing us to predict the affinity of new compounds. Our method is based on simple graphic tools coupled to a cluster significance analysis. A complementary study of the activity relating the prediction of the antagonist/agonist character of 37 high-affinity compounds was also carried out using the same methodology. The principal electronic and structural characteristics leading to a selective activity were revealed.

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