1,4-Thienodiazepine-2,5-diones via MCR (I): Synthesis, Virtual Space and p53-Mdm2 Activity
1,4-Thienodiazepine-2,5-diones via MCR (I): Synthesis, Virtual Space and p53-Mdm2 Activity
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DOI：
10.1111/j.1747-0285.2010.00989.x
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发表时间：
2010-08-01
影响因子：
3
通讯作者：
Doemling, Alexander
中科院分区：
文献类型：
--
作者：
Huang, Yijun;Wolf, Siglinde;Doemling, Alexander
以Gewald 2-氨基噻吩为起始原料，通过Ugi-脱保护-环化（UDC）方法合成了1，4-噻吩并二氮杂卓-2，5-二酮。所得的支架是前所未有的，环状的，肽模拟物与四个点的多样性引入容易获得的起始材料。除了18个合成和表征的化合物之外，还生成了虚拟化合物库，并评估了化学空间分布和药物样性质。已经筛选了针对p53-Mdm 2相互作用的活性的1，4-噻吩并二氮杂卓-2，5-二酮的小集中化合物文库。生物活性评价结果表明，部分化合物具有较好的拮抗活性。
1,4-Thienodiazepine-2,5-diones have been synthesized via the Ugi-Deprotection-Cyclization (UDC) approach starting from Gewald 2-aminothiophenes in a convergent and versatile manner. The resulting scaffold is unprecedented, cyclic, and peptidomimetic with four points of diversity introduced from readily available starting materials. In addition to eighteen synthesized and characterized compounds, a virtual compound library was generated and evaluated for chemical space distribution and drug-like properties. A small focused compound library of 1,4-thienodiazepine-2,5-diones has been screened for the activity against p53-Mdm2 interaction. Biological evaluations demonstrated that some compounds exhibited promising antagonistic activity.