The Design Of New Type Of Benzoic Acid Derivatives As Neuraminidase Inhibitors,Synthesis And Activity Evaluation And The Synthesis Of Chiral Side Chain Of Moxifloxacin

This paper employs benzoic acid derivatives neuraminidase inhibitors and the chiral side chain of quinolone antibacterial moxifloxacin as the research object,and proceeding the structure design,synthesis and activity study.The first part:the design,synthesis and activity evaluation of benzoic acid derivatives neuraminidase inhibitorsWe according to the benzoic acid derivatives neuraminidase?NA?inhibitors structure-activity relationship reported in the literature,designing the new inhibitor structure;Respectively employ 3-methyl-4-nitro benzoic acid and amino-3-4-methyl iodine benzoic acid as raw material,through coupling,acylation,hydrolysis reaction obtaining benzoic acid derivatives influenza neuraminidase inhibitors I-IV and VI-IX,structured by ¹HNMR,¹³CNMR and MS analysis,and the inhibition rate of targetcompoundsonneuraminidasedeterminedbychemical fluorescence,the test choosed the influenza virus strains two subtypes of influenza A virus strains H3N2?California/04?,H1N1?California/99?and B?Shanghai/02?.Results showed that compounds I to IV possessed excellent neuraminidase inhibitory effect,which has asymmetric branch side chain?II and IV?had better inhibitory activity,has the branch of annular II possessd the best activity of H3N2,H1N1 and B,half inhibitory concentration were 0.13,0.27,0.14 umol/L;Among VI to IX,the greater side chain at C3 position of benzene ring,the lower the activity of compounds,compound IX has the stronges tactivity,the half inhibitory concentration of H3N2 and H1N1,B were 1.0,2.1,1.6 umol/L;In X-XII,hydroxyl groups on the benzene ring side chain?carbon possessed better activity than on?carbon,compounds containing single hydroxyl on the?carbon of benzene ring side chains assist the strongest activity of two kinds of type A influenza virus,half inhibitory concentration were 0.15 and0.2 umol/L.The coverage on influenza virus of 11 compounds in this study is wide,and has excellent neuraminidase inhibition efficiency,possess certain medicine outlook,providing new ideas to laterdrugs designed on benzoicacid derivatives against influenza virus.The second part:the synthesis of moxifloxacin chiral side chainMoxifloxacin as the fourth class generation quinolone antibacterial drugs,possessing wide antimicrobial spectrum,strong sterilization ability,low light toxicity,widely used in clinic.Because of the synthesis of chiral side chain of moxifloxacin is complex,leading its expensive price,which increased the economic burden of patients.We through the literature research,using cheaper and easy to get L-asparagine as the starting material,taking advantage of the basis that the raw material has a chiral center to induce the synthesis the another chiral center at side chain;This avoids chiral resolution in the synthesis process,which can greatly reduce the cost of the synthesis of chiral side chain moxifloxacin,possessing broad application prospects.