Design and synthesis of novel 4-benzothiazole amino quinazolines Dasatinib derivatives as potential anti-tumor agents

Design and synthesis of novel 4-benzothiazole amino quinazolines Dasatinib derivatives as... 1 Introduction</h5> Chronic myeloid leukemia (CML) is a hematopoietic stem cell cancer that arises following a reciprocal genetic translocation between chromosomes 9 and 22 [1] , resulting in the short Philadelphia (Ph) chromosome carrying the Bcr-Abl (Breakpoint cluster region-Abelson leukemia) oncogene [2–4] . The understanding of the central role played by Bcr-Abl in the pathogenesis of CML gave birth to the so-called “targeted therapy” [5] . In 2001, Imatinib (Gleevec™, Fig. 1 ), a potent Bcr-Abl inhibitor, was approved for the treatment of CML serves as validation of the concept that therapeutic agents targeting cancer-specific pathways can offer significative improvements over traditional chemotherapeutic agents [6] . Imatinib is now considered as a first-line therapy for the majority of CML cases due to its high efficacy and relatively mild side effects [7] .</P>However, the initial enthusiasm generated by the high response rate to this drug has been dampened by the development of resistance, accounting for 16% in newly diagnosed chronic phase CML and more than 50% in more advanced stages [8] . Mutations in the kinase domain of Bcr-Abl are the major mechanism of acquired Imatinib resistance [9–11] . To date, at least 50 different point mutations that encode http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Medicinal Chemistry Elsevier

Design and synthesis of novel 4-benzothiazole amino quinazolines Dasatinib derivatives as potential anti-tumor agents

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Abstract

1 Introduction</h5> Chronic myeloid leukemia (CML) is a hematopoietic stem cell cancer that arises following a reciprocal genetic translocation between chromosomes 9 and 22 [1] , resulting in the short Philadelphia (Ph) chromosome carrying the Bcr-Abl (Breakpoint cluster region-Abelson leukemia) oncogene [2–4] . The understanding of the central role played by Bcr-Abl in the pathogenesis of CML gave birth to the so-called “targeted therapy” [5] . In 2001, Imatinib (Gleevec™, Fig. 1 ), a potent Bcr-Abl inhibitor, was approved for the treatment of CML serves as validation of the concept that therapeutic agents targeting cancer-specific pathways can offer significative improvements over traditional chemotherapeutic agents [6] . Imatinib is now considered as a first-line therapy for the majority of CML cases due to its high efficacy and relatively mild side effects [7] .</P>However, the initial enthusiasm generated by the high response rate to this drug has been dampened by the development of resistance, accounting for 16% in newly diagnosed chronic phase CML and more than 50% in more advanced stages [8] . Mutations in the kinase domain of Bcr-Abl are the major mechanism of acquired Imatinib resistance [9–11] . To date, at least 50 different point mutations that encode

Journal

European Journal of Medicinal ChemistryElsevier

Published: May 1, 2013

References

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  • Design, synthesis, docking and antitumor activity of Quinazolino (3, 4-a) thieno (3, 2-d) pyrimidin-8-one derivatives
    Zheng, Y.G.; Wu, X.Q.; Xue, B.; Li, M.D.; Ji, M.
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