Structure-Based Optimization of Pyrazolo[3,4-d]pyrimidines as Abl Inhibitors and Antiproliferative Agents toward Human Leukemia Cell Lines
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- 作者：Fabrizio Manetti ; Chiara Brullo ; Matteo Magnani ; Francesca Mosci ; Beatrice Chelli ; Emmanuele Crespan ; Silvia Schenone ; Antonella Naldini ; Olga Bruno ; Maria Letizia Trincavelli ; Giovanni Maga ; Fabio Ca
- 刊名：Journal of Medicinal Chemistry
- 出版年：2008
- 出版时间：March 13, 2008
- 年：2008
- 卷：51
- 期：5
- 页码：1252 - 1259
- 全文大小：1294K
- 年卷期：v.51,no.5(March 13, 2008)
- ISSN：1520-4804
文摘
Results from molecular docking calculations and Grid mapping laid the foundations for a structure-based optimization approach to improve the biological properties of pyrazolo-pyrimidine derivatives in terms of inhibition of Abl enzymatic activity and antiproliferative properties toward human leukemia cells. Insertion of halogen substituents with various substitution patterns, suggested by simulations, led to a significant improvement of leukemia cell growth inhibition and to an increase up to 1 order of magnitude of the affinity toward Abl.