Studies On Design And Synthesis Of A New Anti-cancer Drugs Based On C-Met Target

With the development of molecular biology, people had confirmed c-Met receptor tyrosine kinase in the process of various tumor cell migration, invasion and excessive expression played a decisive role. So, more and more researchers have focused on new drugs to c-Met as the target of anti-tumor drugs. For so many c-Met inhibitors, the research of small molecule c-Met kinase inhibitor has been becoming a focus in research of antitumor drugs at home and abroad. Crizotinib is a kind of selective inhibition of c-Met&ALK dual inhibitors, and has been listed on the FDA approved, performed well tolerated in clinical, and it will have a broad market prospect.We had queried about design of new drug related literature at home and abroad, comprehensively employed design based on the structure-based of the Crizotinib, and designed a series of target compounds.In this article,we had chosen the A1and A2as the goal from all the design of target compounds, and designed two synthetic routes that with2-amino pyrazine as raw material through halogenated reaction, Williamson reaction, Sonogashira reaction, Huisgen-Click reaction process of synthesis of target product A1and with3-hydroxy-2-nitro pyridine as raw materials through the Mitsunobu reaction, nitro reduction reaction, halogenated reaction, Sonogashira reaction, Huisgen-Click reaction steps to synthesis target products A2.Finally, we had successfully synthesized the target products A1and A2. Synthetic routes are simple, high feasibility, raw material easy to get, good to excellent yield. The structure of intermediates and target compounds had confirmed by1H NMR,13C NMR,LC-MS.In addition, the target products have been entering the testing phase of biological activity.