School of Pharmacy and Pharmaceutical Science, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK.
Eur J Med Chem. 2012 Oct;56:246-53. doi: 10.1016/j.ejmech.2012.08.022. Epub 2012 Aug 24.
The tetrahydroazepinone pharmacophore is a component of many interesting compounds, including several marine natural products, with anti-cancer properties. The synthesis and biological evaluation of a novel series of pyrroloazepinone and indoloazepinone oximes is reported. These compounds showed promising growth inhibition activity against four human cancer cell lines but did not significantly inhibit the cell cycle regulator cyclin dependent kinase 2. The most active compounds in this series displayed improved anti-proliferative activity over the related synthetic indoloazepine kenpaullone. The structure activity relationships exhibited by the azepinone pharmacophore suggests several novel lead compounds for anti-cancer drug discovery.
四氢氮杂卓药效团是许多有趣化合物的组成部分，包括几种具有抗癌特性的海洋天然产物。本文报道了一系列新型吡咯并氮杂卓和吲哚并氮杂卓肟的合成和生物评价。这些化合物对四种人癌细胞系表现出有希望的生长抑制活性，但对细胞周期调节剂细胞周期蛋白依赖性激酶 2 没有明显的抑制作用。该系列中最活跃的化合物显示出比相关的合成吲哚氮杂卓 kenpaullone 更好的抗增殖活性。氮杂卓药效团的构效关系表明，有几个新型的先导化合物可用于抗癌药物的发现。
