Design And Antitumor Activity Of Pyrido Pyrimidine Compounds

In the past few decades,people have discovered several key signaling pathways related to tumors.The occurrence of tumor depends on the signal pathway which infiniting cell proliferation,invasion,metastasis,etc.PI3K/Akt/mTOR signaling pathway is one of the most important signaling pathways in the development of cancer drugs.Pyrido pyrimidine compounds are highly bioactive in medicine and pesticide.It has important research value and commercial value in oncology drugs.In order to obtain stronger mTOR inhibitors,the data and structure-activity relationships of pyridine pyrimidine compounds entering clinical research are reviewed in this paper.The pyridine pyrimidine structure was designed and synthesized as the parent nucleus.A series of new compounds which Long chain urea ends are saturated fat chains or fat heterocyclic structures that have not been reported in the literature.During the synthesis process,the existing routes were optimized,and the unreported route was designed and optimized.On this basis,a raw material is easy to get,and the method is simple and the yield is high.The first step is to obtain2-amino-5-brominated nicotinic acid through the participation of 2-nicotinic acid and bromine in the electrophilic substitution.The second step is to produce 6-brominated pyridine pyrimidine-2,4-glycol through the urea ring.The third step is to synthesize highly functionalized pyrido pyrimidine derivatives by means of POCl3/DIEA reagent.Finally,the Suzuki reaction is coupled to a saturated fatty chain or a fatty(hetero)ring boric acid ester.The structure is confirmed by MS and ~1H NMR.It screen for initial tumor activity.