| This thesis includes two sections:1. Design and synthesis of novel EGFR/HER2 inhibitor pyrrolo[3,2-d] pyrimidine derivatives.Receptor tyrosine kinases are important antitumor target. Studies have shown that high expression of deposit EGFR/HER2 expression or abnormal phenomenon in many solid tumors, therefore,EGFR and HER2 and can serve as ideal targets of anticancer drugs.With the development of depth understanding of the pathogenesis and molecular biology, genomics, and other related disciplines, single target TKI has been difficult over blocking tumorigenesis, acting on multi-target inhibitors may achieve more good effect.The first part of this paper introduces the EGFR and HER2 firstly, and their use in cancer development,and reviewed the targeting EGFR and HER2 tyrosine kinase inhibitors.In order to find new,efficient dual inhibitor of EGFR and HER2, on the basis of EGFR tyrosine kinase inhibitors with the structure-activity relationships, we summarized pharmacophore model.According to the characteristic of each pharmacophore structure, we have designed and synthesized two types of pyrrolo [3,2-d] pyrimidine compounds, and the pharmacological activity of these compounds was preliminary determined.2. Synthesis technics of s-oxiracetam.Oxiracetam is a piracetam analog, available in 1987, which promotes the synthesis of phosphorylcholine and phosphorylethanolamine, increases the ratio of brain cells in the ATP/ADP, so that increased synthesis of proteins and nucleic acids in the brain, thereby enhancing excitatory nerve conduction, improve age-related memory impairment.Clinical for the treatment of moderate vascular dementia, senile dementia, and other disorders caused by injury; also canbe against brain damage caused by physical factors, chemical factors.Since the solubility of chiral substance in the solvent is much larger than the racemate, the key of oxiracetam synthesis process is the crystalline purification after the reaction, the racemic oxiracetam process method can not be applied directly in the synthesis of s-oxiracetam. In the second part of this paper, we summarize the current synthesis technics of oxiracetam route, we select the one step reaction by s-4-chloro-3-hydroxybutyricethylester and glycinamide hydrochloride,and the reaction was further optimized, so that route is simple, easy to operate, environmental friendly, less costs, and suitable for industrial production. |
