Synthesis And Activity Of Imatinib Chiral Derivatives

Imatinib mesylate is the first molecularly targeted treatment of chronic myeloid leukemia(Chronic Myeloid Leukemia, CML) tyrosine kinase inhibitor, in the pharmaceutical industry had a tremendous impact. But with used widely in clinical applications, and with the duration, the drug resistance appeared, prompting us to develop a new type of tyrosine kinase inhibitors.In this paper, used 3-acetyl-pyrimidine, 2-methyl-5-nitroaniline as the starting material, via addition reaction, condensation, cyclization, reduction reaction to give an important intermediate N-(5-amino-2-methyl-benzene yl)-4-(3-pyridyl)-2-piperidine-amine,i.e., imatinib amine, Taking the product as basic structure, respectively, different protected groups of amino acids and different dipeptides condensation, thus introducing chirality to imatinib derivatives were designed, and synthesized amino acids imatinib derivative 24, peptides imatinib derivative 7, a total of 31 compounds, and all compounds were detect by IR, 1HNMR, 13 CNMR, HRMS.These compounds were tested of the inhibitory activity by the method of MTT. The data show that YM-4、YM-12、YM-13 、YM-14、YM-16、YM-19、YM-21、YM-23、TN-5 have the same inhibitory activity with imatinib,other compounds also habe some inhibitory activity.