| In recent years,antibiotic resistance has become a global problem.Due to the inappropriate use of antibacterial drugs,the drug resistance of bacteria is constantly increasing,seriously threatening human life and health.Gepotidacin is a novel bacterial topoisomerase inhibitor with universal inhibitory effect on drug-resistant bacteria and good clinical adaptability,and has been in phase III clinical practice.After comprehensively analyzing the advantages and disadvantages of the various Gepotidacin synthesis routes reported in the literature,the synthesis route with the most industrialization prospect was selected,and then the synthesis process of the key intermediates 12 was optimized.The cheap,low-toxic reaction conditions reduced the production cost and effectively inhibited the generation of byproducts.In addition,the reaction conditions for the main reaction steps were univariate.The total yield of the optimized process route is increased by 1%,with simple reprocessing,high safety,and has a good industrial application prospect.The latest cancer statistics report of the National Cancer Statistics Center shows that an average of more than 10,000 cancer patients are diagnosed as cancer patients in China every day,and the number of patients is increasing year by year,and cancer has become one of the major diseases that threaten human life.Arenobufagin is a natural active product from the Chinese medicine chansu,which has broad-spectrum antitumor activity,but its toxicity is greater and the treatment window is narrow.In this paper,13 new arenobufagin bisphosphonates derivatives were designed and synthesized,and the antitumor activity in vitro study found that the antitumor activity decreased significantly after 11 substitutions.In vivo antitumor activity and cardiotoxicity studies have shown that the compound ZM350 shows high activity and low cardiotoxicity,which is worthy of further in-depth study. |
PDF Full Text Request