Synthesis, biological evaluation and docking studies of 4-amino substituted 1H-pyrazolo[3,4-d]pyrimidines

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• 作者：Silvia Schenone ; Chiara Brullo ; Olga Bruno ; Francesco Bondavalli ; Luisa Mosti ; Giovanni Maga ; Emmanuele Crespan ; Fabio Carraro ; Fabrizio Manetti ; Cristina Tintori ; Maurizio Botta
• 关键词：Abl ; Src ; Pyrazolo-pyrimidines ; Chronic myeloid leukemia ; Docking
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：December 2008
• 年：2008
• 卷：43
• 期：12
• 页码：2665-2676
• 全文大小：384 K

文摘

The synthesis of new 4-amino substituted pyrazolo[3,4-d]pyrimidines along with their activity in cell-free enzymatic assays on Src and Abl tyrosine kinases is reported. Some compounds emerged as good dual inhibitors of the two enzymes, showed antiproliferative effects on two Bcr–Abl positive leukemia cell lines K-562 and KU-812, and induced apoptosis, as demonstrated by the PARP assay. Docking studies have been also performed to analyze the binding mode of compounds under study and to identify the structural determinants of their interaction with both Src and Abl.