Dömling Alexander, Antuch Walfrido, Beck Barbara, Schauer-Vukasinović Vesna
Department of Pharmaceutical Sciences, University of Pittsburgh, PA 15261, USA.
Bioorg Med Chem Lett. 2008 Jul 15;18(14):4115-7. doi: 10.1016/j.bmcl.2008.05.096. Epub 2008 May 29.
A multi-component reaction strategy was used for the fast and efficient synthesis of amide isosteres of known Bcl-2 inhibitors capable of disrupting protein-protein interactions. Ugi reaction and a subsequent nucleophilic aromatic substitution reaction provide a versatile path to libraries of compounds similar to Abbott's acylsulfonamides. Modeling arguments are used to explain the inferior activity of the amide as opposed to the sulfonamide series.
采用多组分反应策略，快速高效地合成了已知的能够破坏蛋白质 - 蛋白质相互作用的Bcl - 2抑制剂的酰胺生物电子等排体。乌吉反应及随后的亲核芳香取代反应为合成类似于雅培酰基磺酰胺的化合物库提供了一条通用途径。通过模型论证来解释酰胺相对于磺酰胺系列活性较差的原因。
