1,4-噻吩并二氮杂*-2,5-二酮通过 MCR（I）合成：虚拟空间与 p53-Mdm2 活性。
1,4-Thienodiazepine-2,5-diones via MCR (I): synthesis, virtual space and p53-Mdm2 activity.
机构信息
Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15261, USA.
出版信息
Chem Biol Drug Des. 2010 Aug;76(2):116-29. doi: 10.1111/j.1747-0285.2010.00989.x. Epub 2010 May 18.
Abstract
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.
摘要
1,4-噻二氮杂环庚二酮通过 Ugi 脱保护-环化（UDC）方法从 Gewald 2-氨基噻吩出发，以收敛和通用的方式合成。所得支架是前所未有的、环状的、具有肽模拟性的，从易得的起始原料引入了四个多样性点。除了十八个合成和表征的化合物外，还生成了一个虚拟化合物库，并对其进行了化学空间分布和类药性评价。一小部分 1,4-噻二氮杂环庚二酮的聚焦化合物库被筛选用于抑制 p53-Mdm2 相互作用的活性。生物学评价表明，一些化合物表现出有希望的拮抗活性。
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