Design And Synthesis Of New Pyrazole Keto Compounds With Activity

In this thesis, we have reviewed the recent advances in the studies on the composition, synthesis, structure-activity relationship, structure modification and pharmacology of quinoline carboxylic acid, and studied the method of di-modifying the quinolone analogues with chloride of acids and iniidazole. A series of anti-anerobe and anti-tumour compounds were synthesized. Some quinolone and iniidazole analogues as pro-drug were prepared. Bacterial activities of some compounds synthesized were tested. The result showed that some of them are promising candidates for antibacterial drugs.1) On the basis of reviewing the recent advances in the studies on the composition, synthesis, modification of structure, structure-activity relationship and pharmacology of quinoline carboxylic acid, we chose quinolinic acid analogues as research compounds for overcoming the disadvantage of quinoline carboxylic acid analogues on absorption and Gram-Post activity. A series of quinolone analogues were prepared by the reaction of chloride of acid, chloro-carbonic ester and l-iodoethyl-2-methyl-5-nitro-imidazole with quinoline carboxylic acid analogues, meanwhile the reactive group were introduced to the structure of quinolinic acid for obtaining antibacterial and anti-tumor compounds.2) After studies on the methods of synthesizing 1.7-di-substituted-6-fturo-1.4-dihydro-4-oxo-quinoline-3-carboxylic acid, we designed and synthesized some new quinolone analogues from the 2,4-dichloro-5-fluro-benzoic acid. By reaction of the quinolone analogues synthesized above with chloride of acid, chloro-carbonic ester under the condition of Schotten-Baumann, we synthesized 22 compounds including nineteen new compounds. It is expected that the compounds synthesized would have anti-bacterial as well as anti-tumor activities.3) It's well known that activities of quinoline carboxylic acid analogues to fungus and virus are lower but thioureas are high. Thus, we imagine that by linking of the two kinds of compounds together through organic synthesis, new compounds with bothcharacteristics of them could be produced. As a result, we designed and synthesized a series of new compounds by the reaction between acyl isosulfocyanic ester and 1-alkyl-6-fluro-7-(l-piperazinyl)- l,4-dihydro-4-oxo-quinoline-3-carboxylic acid. Twelve compounds were prepared, and ten of them were new.4) Having studied the synthetic method of novel compounds possessing quinolone and imidazole as active group through the link of epoxy chloropropane, we studied the condition of esterfication between quinoline carboxylic acid and benzyl chloride. Twenty-nine novel compounds were prepared and their structures were confirmed by 'HNMR, IR and elementary analysis .All of the compounds prepared have not been reported yet.5) Bacterial activities of some synthetic compounds in vitro were tested, the activities of three compoundes are higher than norfloxacin. All the ester of quinolinic acid showed lower bacterial activity than norfloxacin.6) It was showed in this thesis that 79 compounds have been prepared, 58 of them are new quinolone analogues.