Design,Synthesis And Anti-tumor Activity Of Mono- And Di-aryloxypyrimidine Derivatives

In our country,cancer prevention and control has become the focus of health strategies,and it has entered a new era of overflight.With the continuous advancement of modern medicine,more and more heterocyclic compounds are used as anti-tumor agents.Among them,pyrimidine compounds have lots of advantages,such as high efficiency,low toxicity,and unique mode of action.It’s a hot spot in the research of heterocyclic compounds and a hot field in the research of new drug molecular design,synthesis and biological activity.It’s demonstrated that molecules containing pyrimidine rings,including monocyclic and fused analogs,have rich pHarmacological effects,including anti-tumor effects,anti-bacterial and fungal effects,anti-HIV effects,and anti-inflammatory effects.Therefore,we modified the structure of 4,6-dichloropyrimidine by introducing aryloxy group(s)at the 4-position or 4,6-position of the pyrimidine ring,and adding active cinnamic acids,glycyrrhetinic acid,benzothiazole,benzoxazole and other substances are combined with intermediates to synthesize pyrimidine derivatives,and the anti-tumor activity of the target compound is tested by the MTT method.The research work of this article mainly includes four parts:The first part mainly includes the structure,pHysicochemical properties of pyrimidine and the research progress in related fields,and confirms the basis of this article,research purpose and significance.The second part mainly introduces the design and synthetic route of three types of 42 pyrimidine derivatives,including 4-aryloxy-6-chloropyrimidine derivatives,4-aryloxy-6-chloropyrimidine cinnamate analogs,4,6-bisaryloxypyrimidine derivatives,and the target compounds were characterized by 1H NMR,13C NMR,HRMS.In the third part,the anti-tumor activity of the target compound against human lung cancer cells A549 and H1299 and human liver cancer cells HepG-2 and SMMC-7221 was studied.The results showed that 18 compounds had anti-cancer activity between 2-19 μM,and 8 of them were below 8 μM,showing good anti-cancer activity.And except for 51c and 63g,the other compounds are non-toxic to normal lung 2B cells and normal liver L-O2 cells.The fourth part discusses the related synthetic routes and cytotoxicity experiment results,and preliminary analysis summarizes the structure-activity relationship of the target compound.