Nigeria And Its Derivatives Synthesis Of Anti-leukemia Drug Imatinib

The pathogenesis of chronic myelogenous leukemia (CML) and present treatment for CML were briefly reviewed in this dissertation. Anti-cancer protein-tyrosine kinase inhibitor Imatinib was chiefly introduced, including its action mechanism、clinical curative effects and its side effects. The research progress of inhibitors against Bcr-Abl protein tyrosine kinase was also reviewed.The synthetic routes and process improvement of Imatinib were investigated, and some procedures were improved. o-Toluidine and 3-acetylpyridine were selected as the starting materials, then the final product was obtained in nine steps including nitration、guanidinium reaction、reduction and acylation, et al. Imatinib has been synthesized in the total yield 10.8%. Compared with the reported methods, the operation was simpler, intermediates can be obtained without column chromatography. This method is more suitable for preparing Imatinib on a large scale.Based on the strategy of avoiding intellectual property rights and computer aided drug design, we designed and synthesized 14 new compounds whose structures were confirmed by ~1H-NMR、MS and IR. The activity assay shows that the activity of HT-008 is quite close to Imatinib.