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首页> 外文期刊>Bioorganic and Medicinal Chemistry Letters >Structural diversity of nucleoside phosphonic acids as a key factor in the discovery of potent inhibitors of rat T-cell lymphoma thymidine phosphorylase.
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Structural diversity of nucleoside phosphonic acids as a key factor in the discovery of potent inhibitors of rat T-cell lymphoma thymidine phosphorylase.

机译:核苷膦酸的结构多样性是发现大鼠T细胞淋巴瘤胸苷磷酸化酶有效抑制剂的关键因素。

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摘要

Structurally diverse, sugar-modified, thymine-containing nucleoside phosphonic acids were evaluated for their ability to inhibit thymidine phosphorylase (TP, EC 2.4.2.4) purified from spontaneous T-cell lymphomas of an inbred Sprague-Dawley rat strain. From a large set of tested compounds, among them a number of pyrrolidine-based derivatives, 10 nucleotide analogues with IC(50) values below 1 microM were selected. Out of them, four compounds strongly inhibited the enzyme with IC(50) values lying in a range of 11-45 nM. These most potent compounds might be bi-substrate analogues.
机译:评价了结构多样的,糖修饰的,含胸腺嘧啶的核苷膦酸抑制从自交Sprague-Dawley大鼠品系的自发T细胞淋巴瘤中纯化的胸苷磷酸化酶(TP,EC 2.4.2.4)的能力。从一大堆被测化合物中,选择了许多基于吡咯烷的衍生物,选择了IC(50)值低于1 microM的10个核苷酸类似物。其中,四种化合物强烈抑制酶,IC(50)值在11-45 nM之间。这些最有效的化合物可能是双底物类似物。

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