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

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Schenone S, Brullo C, Bruno O, Bondavalli F, Mosti L, Maga G, Crespan E, Carraro F, Manetti F, Tintori C, Botta M

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

Eur J Med Chem. 2008 Dec;43(12):2665-76. doi: 10.1016/j.ejmech.2008.01.034. Epub 2008 Feb 6.

PubMed ID

18342402 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Imatinib	Tyrosine-protein kinase ABL1	Ki (nM)	13	N/A	N/A	Details