The Anticancer Drug Imatinib Structure Modification And Its Derivative Synthesis

Imatinib is based on understanding the mechanism of action of cancer cells and rational design and development of molecular targeted therapy drugs.It is mainly used for the treatment of chronic myeloid leukemia.At present,it is the first-line drugs treatment of chronic myeloid leukemia.Because of high specificity,low side effects and take effect rapidly,imatinib has deeply attract researchers’ widespread concern.Its achievements are huge.Unfortunately,with the widespread use of imatinib in clinical,the corresponding drug resistance and some adverse reactions are inevitable,but the research and development of novel tyrosine kinase inhibitors is still a hot area.In this study,we choose imatinib as a lead compound,keeping the key intermediate of imatinib,Immaamine,then using drug activity splicing method,a class of formamid imatinib derivatives that containing 1,3,4-oxadiazole structure was prepared by splicing 1,3,4-oxadiazole ring onto Imamamine and other class of acetamide imatinib derivatives containing both sulfur atom and 1,3,4-oxadiazole structure;In addition,nitrogen-containing heterocycles and thiourea imatinib derivatives were prepared separately.We have been synthesized four series of compounds,the total of 37 imatinib derivatives that had not been reported in the literature.All target compounds have been fully characterized by ¹H NMR,¹³C NMR and MS.