Studies On Synthesis And Biological Activity Of Triazole Nucleoside Derivatives, Piperazine Substituted Ribose, And Isopropanol Derivatives

Studies on Antiviral, anti-arrhythmia and anti-hypertension drugs are a hot field in modem medicinal chemistry. Nucleosides were studied because which accounted for more than half of the antiviral agents by now; except "-pril" kind, isopropanol derivatives occupied a majority of anti-arrhythmia and anti-hypertension drugs, so further studies on these fields may develop better drugs, these -receptor inhibiting drugs can be suitable for different sufferers with lower side-function, long or super-short effect. Based on nucleic acid as the target, 27 compounds of two series of triazole nucleoside derivatives and piperidinyl substituted ribofuranoses were designed and synthesized and have not been reported in literature; 26 compounds of 5 series of isopropanol derivatives were also designed and synthesized. Two kinds were added up to 53 compounds, among them 44 compounds have not been reported in literatures. Their chemical structures were confirmed by the means of 'HNMR, MS, elemental analysis or IR.The synthetic methods of isopropylidene of nucleosides and ribose have been researched, and a mixture of triethyl orthoformate and acetone was chosen, which has the same function as 2,2-diethoxyacetone, and the yield has been raised, which is a convenient and high yield method to protect ortho-diol.In the process of synthesis of unsaturated nucleosides, an effective method was developed, a mixture of a-acetoxy-isobutyryl chloride and LiBr was acted as a substitute of a-acetoxy-isobutyryl bromide, and the synthesis of the latter was difficult or low yield. The nucleosides reacted with the mixtureto give a unique product and high yield.The synthetic methods of 1 - or/and 5-positions substituted on ribose with piperazino- or N-substituted piperazino have been investigated, and suitable conditions were chosen. Work-on of the reacted mixture were easily simplified with N-substituted piperazine reacted with protected furanosylribose.Antitumor and antiviral activity of some of these compounds (7~10, 15~18, and 24) of triazole nucleoside derivatives in A-549 cells, BEL-7402 cells, and Flu-A cells revealed that only compound 9 (1-(5-iodo-5-deoxy-β-D-ribofuranosyl)-1,2,4-triazole- 3-carboxamide) provided a weak level of protection against viral infection, IC25=0.4 umol/ml, no cytotoxicity was evidenced at that concentration.These preliminary results showed that researches on antiviral agents still need a very long route, and bioactivity of target compounds can't be forecasted simply from SAR or QSAR.Biological activities of other two kinds of target compounds are still being carried out.