2. Academic Validation
  3. Structure-based optimization of pyrazolo[3,4-d]pyrimidines as Abl inhibitors and antiproliferative agents toward human leukemia cell lines

Structure-based optimization of pyrazolo[3,4-d]pyrimidines as Abl inhibitors and antiproliferative agents toward human leukemia cell lines

  • J Med Chem. 2008 Mar 13;51(5):1252-9. doi: 10.1021/jm701240c.
Fabrizio Manetti 1,  Chiara Brullo,  Matteo Magnani,  Francesca Mosci,  Beatrice Chelli,  Emmanuele Crespan,  Silvia Schenone,  Antonella Naldini,  Olga Bruno,  Maria Letizia Trincavelli,  Giovanni Maga,  Fabio Carraro,  Claudia Martini,  Francesco Bondavalli,  Maurizio Botta
Affiliations

Affiliation

  • 1 Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Via Alcide de Gasperi 2, I-53100, Siena, Italy.
PMID: 18257513 DOI: 10.1021/jm701240c
Abstract

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.

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