Optimization Of The Synthesis Process Of R-3117 Intermediate ASM-11 For Anticancer New Drug

Once activated by the enzyme Uridine Cytidine Kinase (UCK2), anticancer new drug RX-3117 inhibits DNA and RNA synthesis resulting in cancer cell death with the potential for a targeted anti-cancer therapy. RX-3117 is researched and developed by the US biotech company Rexahn and investigated anti-cancer therapy that targets treatment with pancreatic cancer. It has been demonstrated that RX-3117 has the ability to treat cancer cells that have become resistant to gemcitabine, which has an important impact on the treatment of pancreatic cancer patients and market prospect and influence.The key intermediate compound ASM-11 is closely related to the quality of anti-cancer new drug API R-3117. In this paper, through the optimization of the synthesis process of the key intermediate ASM-11, four column chromatography operations existing in previous procedures are successfully removed. The continuity, simplicity and economy of operation has been greatly improved. After the optimization, the total yield is improved from previous 1.6% to 24.7%. Significantly, the production-cycle of the 10 kg-batch ASM-11 is reduced to 40 days, which is shorter than previous 82 days. In addition to this, after process optimization, the production of ASM-11 is more economical efficiency with $48 thousand per kilogram, in contrast to previous $200 thousand per kilogram. Through the process optimization, the expected goal was successfully achieved.