Synthesis and bioevaluation of new vascular-targeting and anti-angiogenic thieno[2,3-d]pyrimidin-4(3H)-ones.,European Journal of Medicinal Chemistry

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Synthesis and bioevaluation of new vascular-targeting and anti-angiogenic thieno[2,3-d]pyrimidin-4(3H)-ones.
European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2020-01-09 , DOI: 10.1016/j.ejmech.2020.112060
Madeleine Gold ₁ , Leonhard Köhler ₁ , Clarissa Lanzloth ₁ , Ion Andronache ₂ , Shrikant Anant ₃ , Prasad Dandawate ₃ , Bernhard Biersack ₁ , Rainer Schobert ₁

Affiliation

A series of forty-six 5,6-annulated 2-arylthieno [2,3-d]pyrimidin-4(3H)-ones were prepared as potentially pleiotropic anticancer drugs with variance in the tubulin-binding trimethoxyphenyl motif at C-2 of a thieno [2,3-d]pyrimidine fragment, enlarged by additional rings of different size and substitution. By assessing their cytotoxicity against various cancer cells, their influence on the polymerization of neat tubulin and the dynamics of microtubule and F-actin cytoskeletons, and their vascular-disrupting and anti-angiogenic activities in vitro and in vivo, structure-activity relations were identified which suggest the 3-iodo-4,5-dimethoxyphenyl substituted thienopyrimidine 2e as a promising anticancer drug candidate for further research. 2020 Elsevier Ltd. All rights reserved.

中文翻译：

新型靶向血管和抗血管生成的噻吩并[2,3-d]嘧啶-4（3H）-的合成及生物评价。

制备了一系列四十六种5,6-环化的2-芳基噻吩并[2,3-d]嘧啶-4（3H）-作为潜在的多效抗癌药物，在C-2的C-2处微管蛋白结合的三甲氧基苯基基序有所不同。噻吩并[2,3-d]嘧啶片段，通过不同大小和取代的附加环扩大。通过评估它们对各种癌细胞的细胞毒性，它们对纯净微管蛋白聚合以及微管和F-肌动蛋白细胞骨架动力学的影响，以及它们在体外和体内的血管破坏和抗血管生成活性，确定了结构-活性关系。这表明3-碘-4,5-二甲氧基苯基取代的噻吩并嘧啶2e作为有希望的抗癌药物有待进一步研究。2020 Elsevier Ltd.保留所有权利。

更新日期：2020-01-10

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