New Nitrogen Azole Derivatives Synthesis And Activity Of Study

In recent years,with the development of biotechnology,radiotherapy,chemotherapy,intervention and other methods and means have been widely used in the treatment of cancer,AIDS and organ transplant patients,which is forcing immunosuppressants,broadspectrum antibiotics,corticosteroids and other drugs have been widely used in clinical practice.There is a multiple upward trend in deep fungal infection which threats to human health seriously because these technologies have been widely used and the deep fungal infection has been the third most serious infectious disease now.Therefore,the deep researches of antifungal drugs are more and more urgent and attracted.Dithio amino acid esters(DTCs)have a variety of biological activities and its advantages such as low toxicity and easy synthesis have become hot in the medicinal chemistry research area.My research has designed and synthesized 1-(1H-1,2,4-trazol-1-yl)-2-(2,4-difluorophenyl)-3-substituted-2-propanol compound which has used DTC to synthesize different lengths substituted benzyl side chains.It is based on the basic pharmacophore groups: tertiary alcohol structure,basic triazole ring and 2,4-difluorophenyl group remained and the research of azole antifungals mechanism and azole antifungals structure-activity relationship.The structure of the target compound have been proved by 1H-NMRand ESI-MS.My research has done the in vitro test for synthesis of the target compounds referring to the standard antifungal susceptibility test methods proposed by National Clinical Laboratory Standards Committee(NCCLS).8 kinds of fungi are selected: Candida albicans ATCC14053,Read aureus nearly smooth,Cryptococcus neoformans ATCC32609;Trichophytonrubrum,plaster-like spores,Aspergillusfumigatus,Candida glabrata and SCZ20352.The positive controls are fluconazole,ketoconazole,itraconazole,voriconazoleVfend,terbinafine phenol and amphotericin B.Preliminary results of In vitro experiments have showed most of the compound have antibacterial activity to the six kinds of fungus except Aspergillusfumigatus and Microsporum.The compounds 1c-d,1r-s,2a-s have showed good antibacterial activity whose are better than the control drugs ittraconazole,terbinafine,fluconazole and amphotericin B.In addition,the activity of the compounds with the isopropylamine on the nitrogen atom of the side chain is more than which with the allylamine.It has the value for the further study.