The Design And Synthesis For New Kind Of Tinib Drugs

At present, the amount of worldwide cancer patients showed a trend of rising, the first member of the total number of cancer patients is patients with lung cancer, and non-small cell lung cancer accounts for eighty-five percent of the total number of patients with lung cancer. The small molecules TKI act on the EGFR has been widely used in the treatment of advanced non-small cell lung cancer, such as Gefitinib, Erlotinib, Icotinib. Because of the drug currently used in the treatment of advanced non-small cell lung cancer most need imports, the full independent intellectual property rights for tinib drugs in our country is very little, resulting in non-small cell lung cancer patients in our country enduring heavy economic burden. In addition, because of drugs with quinazoline ring system structure are poor water-soluble. For the two aspects reason above mentioned, we have designed two series of new compounds of tinib drugs. Through the interaction between ring polyamine and quinazoline ring system, enhancing the activity of drugs and greatly improve the water solubility at the same time. Looking forward to the new drugs will benefit patients with non-small cell lung cancer in our country.The drugs with quinazoline ring system structure through competiing with ATP to combine with EGFR, preventing amino acid kinase phosphorylation itself, thus inhibiting the downstream signal transduction, and the growth of cancer cells. Ring polyamine has special biological activity. It can reduce the levels of ATP in the cell. Through the interaction between ring polyamine and quinazoline ring system to enhance activity of tinib drugs.The series compounds designed base on Gefitinib:on the basis of keeping quinazoline ring system skeleton structure, ring polyamine replace morpholine ring in sixth position of quinazoline ring.The series compounds designed base on Erlotinib and Icotinib:on the basis of keeping quinazoline ring system skeleton structure, chain ether or ring ether on the left side of quinazoline ring is replaced by ring polyamine, and two adjacent carbon atoms of benzene ring in quinazoline ring system directly take part in the building of the ring polyamine.Pharmacological activity tests showed that the series compounds designed base on Gefitinib is superior to Gefitinib in drug activity, and has good water solubility. Although the series compounds designed base on Erlotinib and Icotinib is worse than Erlotinib in drug activity, they also have good drug activity.