CN104530163A - Triazole glycolipid derivatives and application thereof to synergically resist drug-resistant bacteria - Google Patents

Triazole glycolipid derivatives and application thereof to synergically resist drug-resistant bacteria Download PDF

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CN104530163A
CN104530163A CN201410747513.9A CN201410747513A CN104530163A CN 104530163 A CN104530163 A CN 104530163A CN 201410747513 A CN201410747513 A CN 201410747513A CN 104530163 A CN104530163 A CN 104530163A
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triazole
triazole derivatives
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monose
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CN104530163B (en
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贺晓鹏
陈代杰
胡习乐
李丹
程超英
董晓景
邵雷
李忠磊
陈国荣
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East China University of Science and Technology
China State Institute of Pharmaceutical Industry
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East China University of Science and Technology
China State Institute of Pharmaceutical Industry
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/056—Triazole or tetrazole radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives

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Abstract

The invention relates to a kind of triazole glycolipid derivatives and application thereof to synergically resist drug-resistant bacteria. The triazole derivatives containing a monosaccharide group are compounds shown as a formula I, or pharmaceutically acceptable salts. The provided triazole derivatives have synergic bacteriostatic effect for conventional antibiotics, help to substantially reduce usage amount of antibiotics when being combined with the conventional antibiotics for usage, and provide an approach for reasonable safe usage of antibiotics. In the formula I, R1 is an acetyl-protected or non-acetyl-protected monosaccharide group, R2 is a C6-C18 linear or branched alkyl, and n is an integer of 1-4.

Description

The purposes of triazole glycolipid analog derivative and collaborative antimicrobial agent thereof
Technical field
The present invention relates to the purposes of a kind of triazole glycolipid analog derivative and collaborative antimicrobial agent thereof, specifically, relate to a kind of containing the triazole glycolipid analog derivative of monose group and the purposes of collaborative antimicrobial agent thereof.
Background technology
From 19 th century later to 20 beginnings of the century, the cause of disease of disease obtains the great attention of scientists, and many pathogenic bacterias start to be found.Sulfanilamide (SN) has powerful bacteriostatic action, it succeed in developing the life having saved countless people.This is the medicine that the mankind first of finding can resist pathogenic bacteria, has epoch-making meaning.Subsequently, penicillin is called as the contribution of most worthy in modern medicine history, and being described as is the great milestone of in physianthropy history one.Penicillin and Streptomycin sulphate become the pioneer that the mankind enter the microbiotic epoch, and microbiotic not only becomes the most frequently used class medicine of clinical departments doctor, and is the indispensable medicine in family.
But, microbiotic as same the sword of twolip, scientific and reasonable with it, can benefit for the mankind, the incorrect health then wanting harm humans.As excessive in dosage or administration time is long time, microbiotic can cause all untoward reactions, and what have even remains serious.Microbiotic, particularly Broad spectrum antibiotics can cause the flora imbalance in body to cause superinfection.
Summary of the invention
The present inventor, through extensive and deep research, has designed and synthesized the triazole glycolipid analog derivative of a class containing monose group.Find simultaneously, the present invention's synthesis containing monose group triazole glycolipid analog derivative antibioticly antibacterial there is certain synergism to existing, itself and existing Antibiotic combination use, and greatly can reduce antibiotic dosage, for reasonable benefit/risk uses microbiotic to provide a kind of approach.
One object of the present invention is, provides a kind of triazole glycolipid analog derivative containing monose group of novel structure.
Triazole glycolipid analog derivative containing monose group of the present invention is compound shown in formula I, or its pharmaceutically acceptable salt:
In formula I, R 1for have ethanoyl ( referred to as " Ac ") the monose group protecting or do not have ethanoyl to protect; R 2for C 6~ C 18the alkyl of straight or branched.N is the integer of 1 ~ 4;
Wherein said monose group comprises: glucose group (Glc-), semi-lactosi group (Gal-), mannose group (Man-), acetylglucosamine group (GlcNAc-), acetylamino galactosamine group (GlcNAc-), Fucose group (Fuc-) or sialic acids groups (Sia-), and its structure is such as formula shown in II a ~ II g:
In formula II a ~ II g, R 3for H or Ac.
Another object of the present invention is, disclose a kind of purposes of the above-mentioned triazole glycolipid analog derivative containing monose group: the triazole glycolipid analog derivative that namely the invention provides containing monose group can be used as the application of antibiotic synergistic agent, in other words, the triazole glycolipid analog derivative that the invention provides containing monose group is preparing the application in microbiotic synergistic agent.
In addition, the present invention also provides the method for compound shown in a kind of preparation formula I, and it comprises the steps:
(1) triazo-compound (R is prepared 1-N 3) step;
(2) by acetylenic halide with corresponding alcohol (R 2oH) intermediate is prepared in reaction step; And
(3) by triazo-compound (R 1-N 3) and intermediate reaction, prepares the step of target compound.
Wherein X is halogen (F, Cl, Br or I), R 1, R 2with the definition of n with described identical above.
Accompanying drawing explanation
Fig. 1 is sterilization-time curve
Embodiment
In the present invention's preferred technical scheme, R 1for glucose group, semi-lactosi group or mannose group that ethanoyl is protected or do not had ethanoyl to protect;
Further optimal technical scheme is:, R 1the glucose group protected for not having ethanoyl, semi-lactosi group or mannose group.
In another preferred technical scheme of the present invention, R 2for C 6~ C 18in there is the alkyl of the straight or branched of even-numbered carbon atom.
In a further preferred technical solution of the present invention, n is 1 or 2.
In the preparation method provided above, triazo-compound (R 1-N 3) can obtain via the classical end group bromination of various acetylize monose and azide substitution, concrete steps see Alvarez S.G. & Alvarez, M.T.Synthesis, 1997,413-414.
Having under NaH existence and room temperature condition, by acetylenic halide with corresponding alcohol (R 2oH) with halohydrocarbon (reaction medium) in react at least 12 hours, successively through steam except reaction medium, extraction, drying, filtration and concentrate etc. step obtain intermediate
By anhydrous CuSO 4under VcNa existence, having rare gas element (not participating in the gas reacted, as nitrogen etc.) existence and room temperature condition, by triazo-compound (R 1-N 3) and intermediate react at least 12 hours; reaction product is successively through washing; extraction, dry, filter, product that concentrated and column chromatography obtains with ethanoyl protection on monose group; again through Deprotection (ethanoyl) reaction (specifically: having under triethylamine existence condition, by monose group with ethanoyl protection product in the water-soluble middle reaction of alcohol) obtain target compound (shown in formula I compound).
Below by embodiment, the invention will be further described, and its object is only better to understand content of the present invention, but not limits the scope of the invention:
Embodiment 1
(1) synthesis of the nitrine glucose (shown in formula A compound) of full ethanoyl protection:
Glucose (3g, 0.017moL) is put into 100mL flask, then under the condition of ice bath, in bottle, slowly adds Ac 2o (11.9mL) and HClO 4(0.072mL) mixed solution, after dripping, removes ice bath, and in room temperature condition reaction, TLC follows the tracks of reaction, disappears (at least needing about 6 hours) to raw material point, stopped reaction.With saturated sodium bicarbonate and the sodium chloride solution washing of ice, then use dichloromethane extraction, then carry out drying (MgSO 4), filter and reduced under vacuum thus obtain crude product (5.85g, 90%).Obtain crude product and directly carry out next step reaction without the need to purifying.
Take the glucose (0.53g of full ethanoyl protection; 0.001moL); add the methylene dichloride of 30mL as solvent; then in system, add the HBr/AcOH solution of 30% of 5mL; react under room temperature; TLC follows the tracks of reaction, disappears (at least needing about 12 hours) to raw material point, stopped reaction.With saturated sodium bicarbonate and the sodium chloride solution washing of ice, then use dichloromethane extraction, then carry out drying (MgSO 4), filter and reduced under vacuum thus obtain crude product (0.35g, 87%).Obtain crude product and add sodium azide (0.28g, 0.004moL) directly to the inside, be react under the condition of 60 DEG C at oil bath temperature, TLC follows the tracks of reaction, disappears (at least needing about 12 hours) to raw material point, stopped reaction.With saturated nacl aqueous solution washing, then use dichloromethane extraction, then carry out drying (MgSO 4), filter and reduced under vacuum thus obtain crude product (0.29g, 93%).Eventually pass through column chromatography (PE/EA=5:1) and obtain pure nitrine glucose (shown in formula A compound).
(2) synthesis of intermediate (shown in formula B compound):
N-dodecanol (2g, 10.75mmoL) is added in the flask of 100mL, adds DMF and the 10mL CH of 10mL 2cl 2as solvent, then in system, add propargyl bromide (1.9mL, 21.5mmoL), under the condition of ice bath, add NaH (387mg, 16.13mmoL), remove ice bath reaction after 5 minutes and spend the night.TLC follows the tracks of reaction, disappears (at least needing about 12 hours) to raw material point, stopped reaction.Reaction product spins off solvent first under vacuo, then with saturated NaCl, then uses dichloromethane extraction, then carries out drying (MgSO 4), filter and reduced under vacuum thus obtain intermediate (shown in formula B compound) (1.93g, 80%).
(3) synthesis of target compound (shown in formula I A compound):
The intermediate A (400mg, 1.07mmoL) obtained and intermediate B (480mg, 2.14mmoL) are added in the flask of 200mL, adds anhydrous CuSO 4(535.8mg, 2.14mmoL) (catalyzer) and VcNa (849mg, 4.28mmoL); react under the condition of nitrogen protection; TLC follows the tracks of reaction, disappears (at least needing about 12 hours) to raw material point, stopped reaction.With saturated NaCl products therefrom, then use dichloromethane extraction, then carry out drying (MgSO 4), filter and reduced under vacuum thus obtain crude product.Carry out column chromatography (PE/EA=3:1) again and obtain head product (606.8mg, 95%).
The head product (606.8mg, 1.02mmoL) obtained is added in the flask of 100mL, adds solvent methanol 8mL, water 1mL and triethylamine 1mL, react under room temperature condition, TLC follows the tracks of reaction, disappears (at least needing about 10 hours) to raw material point, stopped reaction.White crystal is obtained, target compound (shown in formula I A compound) after being spin-dried for solvent.
1H NMR(400MHz,DMSO)δ8.27(s,1H),5.51(d,J＝9.3Hz,1H),5.37(d,J＝6.0Hz,1H),5.29(d,J＝4.9Hz,1H),5.16(d,J＝5.5Hz,1H),4.63(d,J＝5.5Hz,1H),4.48(s,2H),3.73-3.68(m,2H),3.43(t,J＝6.3Hz,4H),3.38(d,J＝5.0Hz,1H),3.23(dd,J＝8.7,5.6Hz,1H),1.24(s,20H),0.85(t,J＝6.7Hz,3H).
13C NMR(101MHz,DMSO)δ143.9,123.0,87.4,79.9,76.9,71.9,69.7,69.5,63.1,60.7,48.5,31.2,29.1,29.0(3),28.9,28.7,25.6,22.0,13.9。
Embodiment 2
Divided by outside the n-dodecanol in tetradecanol alternative embodiment 1 step (2), other is raw materials used, reagent and step similar to Example 1, compound shown in formula I B can be obtained:
1H NMR(400MHz,DMSO)δ8.32(s,1H),5.57(d,J＝9.3Hz,1H),5.44(d,J＝5.9Hz,1H),5.35(s,1H),5.23(d,J＝5.3Hz,1H),4.70(s,1H),4.54(s,2H),3.86–3.74(m,2H),3.50(d,J＝6.4Hz,4H),3.48(s,1H),3.33–3.25(m,1H),1.30(s,24H),0.91(t,J＝6.7Hz,3H).
13C NMR(101MHz,DMSO)δ143.9,123.0,87.4,79.8,79.2,78.9,78.6,76.9,71.9,69.7,69.5,63.2,60.7,54.8,48.5,31.2,29.1,29.0,28.9,28.7,25.6,22.0,13.9。
Embodiment 3
Divided by outside the n-dodecanol in positive hexadecanol alternative embodiment 1 step (2), other is raw materials used, reagent and step similar to Example 1, compound shown in formula I C can be obtained:
1H NMR(400MHz,DMSO)δ8.33(s,1H),5.57(d,J＝9.3Hz,1H),5.43(d,J＝6.0Hz,1H),5.35(d,J＝4.9Hz,1H),5.22(d,J＝5.5Hz,1H),4.69(s,1H),4.54(s,2H),3.78-3.71(m,2H),3.49(t,J＝6.4Hz,4H),3.45(s,1H),3.28(dd,J＝11.6,6.0Hz,1H),1.30(s,28H),0.91(t,J＝6.7Hz,3H).
13C NMR(101MHz,DMSO)δ143.9,123.0,87.4,79.9,78.9,78.6,76.9,71.9,69.7,69.5,63.2,60.7,54.8,48.5,31.2,29.1(2),29.0(3),28.9,28.7,25.6,22.0,13.9。
Embodiment 4
Divided by outside the glucose in semi-lactosi alternative embodiment 1 step (1), other is raw materials used, reagent and step similar to Example 1, compound shown in formula I D can be obtained:
1H NMR(400MHz,DMSO)δ8.20(s,1H),5.47(d,J＝9.2Hz,1H),5.23(d,J＝6.0Hz,1H),5.03(d,J＝5.7Hz,1H),4.71(t,J＝5.7Hz,1H),4.63(d,J＝5.5Hz,1H),4.49(s,2H),4.03(dd,J＝15.3,9.3Hz,1H),3.79–3.65(m,2H),3.59–3.47(m,3H),3.43(t,J＝6.6Hz,2H),1.24(s,20H),0.85(t,J＝6.7Hz,3H).
13C NMR(101MHz,DMSO)δ144.1,122.6,88.0,78.3,73.6,69.6,69.2,68.4,63.2,60.3,54.8,48.5,31.2,29.1,29.0(2),28.9,28.7,25.6,22.0,13.9。
Embodiment 5
Divided by outside the glucose in semi-lactosi alternative embodiment 1 step (1), with outside the n-dodecanol in tetradecanol alternative embodiment 1 step (2), other is raw materials used, reagent and step similar to Example 1, compound shown in formula I E can be obtained:
1H NMR(400MHz,DMSO)δ8.26(s,1H),5.52(d,J＝9.2Hz,1H),5.29(d,J＝6.0Hz,1H),5.09(d,J＝5.6Hz,1H),4.77(t,J＝5.7Hz,1H),4.69(d,J＝5.5Hz,1H),4.55(s,2H),4.15–4.03(m,1H),3.84–3.74(m,2H),3.58-3.49(m,3H),3.49(t,J＝6.5Hz,2H),1.30(s,24H),0.91(t,J＝6.7Hz,3H).
13C NMR(101MHz,DMSO)δ144.1,122.6,88.0,78.3,73.6,69.6,69.2,68.4,63.2,60.3,54.8,48.5,31.2,29.1,29.0(4),28.9,28.7,25.6,22.0,13.9。
Embodiment 6
Divided by outside the glucose in semi-lactosi alternative embodiment 1 step (1), with outside the n-dodecanol in positive hexadecanol alternative embodiment 1 step (2), other is raw materials used, reagent and step similar to Example 1, compound shown in formula I F can be obtained:
1H NMR(400MHz,DMSO)δ8.20(s,1H),5.46(d,J＝9.2Hz,1H),5.23(d,J＝6.0Hz,1H),5.03(d,J＝5.6Hz,1H),4.71(t,J＝5.7Hz,1H),4.63(d,J＝5.5Hz,1H),4.49(s,2H),4.09–3.97(m,1H),3.79–3.65(m,2H),3.57–3.46(m,3H),3.43(t,J＝6.6Hz,2H),1.24(s,28H),0.85(t,J＝6.7Hz,3H).
13C NMR(101MHz,DMSO)δ144.1,122.6,88.0,78.3,73.6,69.7,69.2,68.4,63.2,60.3,54.8,48.5,31.2(2),29.1,29.0(4),28.9(2),28.7,25.6,22.0,13.9。
Embodiment 7
Divided by outside the glucose in seminose alternative embodiment 1 step (1), other is raw materials used, reagent and step similar to Example 1, compound shown in formula I G can be obtained:
1H NMR(400MHz,DMSO)δ8.15(s,1H),5.98(s,1H),5.28(d,J＝5.2Hz,1H),5.02(dd,J＝22.0,5.0Hz,2H),4.62(t,J＝5.9Hz,1H),4.49(s,2H),3.86(s,1H),3.73(dd,J＝11.2,5.1Hz,1H),3.60(d,J＝8.1Hz,1H),3.48(dd,J＝10.3,4.8Hz,3H),3.42(d,J＝6.6Hz,2H),1.24(s,20H),0.85(t,J＝6.7Hz,3H).
13C NMR(101MHz,DMSO)δ143.5,123.4,85.8,80.2,73.1,70.4,69.6,66.1,63.2,61.0,54.8,31.2,29.1,29.0(3),28.9,28.7,25.6,22.0,13.9。
Embodiment 8
Divided by outside the glucose in seminose alternative embodiment 1 step (1), with outside the n-dodecanol in tetradecanol alternative embodiment 1 step (2), other is raw materials used, reagent and step similar to Example 1, compound shown in formula I H can be obtained:
1H NMR(400MHz,DMSO)δ8.14(s,1H),5.98(s,1H),5.25(d,J＝5.2Hz,1H),5.00(dd,J＝20.3,5.4Hz,2H),4.59(t,J＝5.9Hz,1H),4.49(s,2H),3.86(d,J＝3.6Hz,1H),3.73(dd,J＝11.4,5.8Hz,1H),3.61(dd,J＝8.8,5.6Hz,1H),3.49(dd,J＝10.3,5.1Hz,2H),3.45–3.39(m,3H),1.24(s,24H),0.85(t,J＝6.7Hz,3H).
13C NMR(101MHz,DMSO)δ143.5,123.4,85.8,80.2,73.1,70.4,69.6,66.1,63.2,61.0,54.8,31.2,29.1(2),29.0(3),28.9(2),28.7,25.7,22.0,13.9。
Embodiment 9
The pharmaceutical activity of glycolipid
(1) microbiotic is for the treatment (mensuration of MIC value) of dependency bacterial classification
With reference to M07-A9 standard by microbiotic and novel slycolipid compounds doubling dilution in CaMHB substratum, add the bacterium liquid of fresh preparation afterwards, making often to manage final bacterium dense is 10 7cFU/ml, measures each microbiotic and the independent MIC of novel slycolipid compounds (with the CAMHB inoculated tube of not drug containing for positive control, the culture of inoculated bacteria is not as negative control) respectively.MIC under medicinal composition effect adopts coubling dilution equally, first in CaMHB substratum, fix the final concentration (32mg/L or 16mg/L) of novel slycolipid compounds, again successively by the microbiotic doubling dilution to be measured in medicinal composition in above-mentioned substratum, add the bacterium liquid of fresh preparation afterwards equally, making often to manage final bacterium dense is 10 7cFU/ml (with the nutrient solution containing single microbiotic or single novel slycolipid compounds for positive control, the culture of inoculated bacteria is not negative control).All nutrient solution is placed in 37 DEG C, cultivates after 16h-20h, observe the growing state of bacterium, and antibiotic MIC in the independent minimum inhibitory concentration MIC of interpretation medicine and medicinal composition.
Suppress the minimum concentration (MIC) that MRSA ATCC43300 growth needs, when Oxazacillin (oxacillin) is used alone, its MIC is 64-128mg/L; When ceftazime (Ceftazidime) is used alone, its MIC is 256mg/L.But when they are respectively with compound coupling provided by the invention, the MIC of Oxazacillin list and ceftazime will reduce greatly, specific as follows:
(a) Oxazacillin with concentration be respectively chemical compounds I A, the chemical compounds I B of 32mg/L, chemical compounds I C, chemical compounds I D, chemical compounds I E, chemical compounds I F and chemical compounds I G, chemical compounds I H, conbined usage time: the MIC of Oxazacillin will greatly reduce.
As chemical compounds I A and Oxazacillin coupling that concentration is 32mg/L, the MIC of Oxazacillin is 2mg/L, and in other words, chemical compounds I A makes Oxazacillin antibacterial (MRSA ATCC43300, lower same), and synergy 32-64 doubly.
Equally, compd B makes the antibacterial synergy 16-32 of Oxazacillin doubly; Compound C makes the antibacterial synergy 2-4 of Oxazacillin doubly; Compound D makes the antibacterial synergy 2-4 of Oxazacillin doubly; Compd E makes Oxazacillin antibacterial synergy synergy 8-16 doubly; Compound F 17-hydroxy-corticosterone makes the antibacterial synergy 4-8 of Oxazacillin doubly; Compound G makes the antibacterial synergy 16-32 of Oxazacillin doubly; Compound H makes the antibacterial synergy 2-4 of Oxazacillin doubly;
(b) ceftazime with concentration be respectively chemical compounds I A, the chemical compounds I B of 32mg/L, chemical compounds I E and compound G conbined usage time: the MIC of ceftazime will greatly reduce.
Chemical compounds I A makes the antibacterial synergy of ceftazime 64 times, and chemical compounds I B makes the antibacterial synergy of ceftazime 32 times, and chemical compounds I E makes the antibacterial synergy of ceftazime 32 times, and chemical compounds I G makes the antibacterial synergy of ceftazime 32 times.
C () microbiotic and chemical compounds I A combined needle are to correlative clinical bacterial classification
During with the conbined usage of Oxazacillin for 12 strain clinical bacterium, the MRSA of the clinical separation of 12 strain respectively: R15, R16, R36, R49, R50, R53, R302, R304, R306, R308, R313, R314 (China State Institute of Pharmaceutical Industry provides).What chemical compounds I A had a synergism to it has 10 strains.Respectively: R15, R16, R36, R49, R50, R53, R302, R306, R308, R314.
(2) time-kill curve
Fresh for the ATCC43300 being in exponential phase of growth strain cultured solution is diluted to 10 7cFU/ml obtains the initial bacterium liquid for inoculating, the medicine (mixture of 2mg/L Oxacillin, 32mg/L chemical compounds I A and 2mg/LOxacillin and 32mg/L chemical compounds I A) of different concns is added in initial bacterium liquid, simultaneously do blank group with what do not add any medicine, respectively at 0,1h, 2h, 4h, 6h, 8h, 12h, 24h quantitative sampling.By bacterium liquid 10 times of dilutions successively of taking out, the diluent 20 μ l getting acceptable diluent multiple respectively coats on counting culture medium flat plate, and each extension rate coating 2-3 parallel plate, cultivation 24 ~ 28h is inverted in 36 DEG C ± 1 DEG C constant incubator, carry out enumeration, represent with colony-forming unit (Colony-Forming Units, CFU).The logarithm of each culture tube enumeration and incubation time are mapped at rectangular coordinates, obtains time-kill curve (see Fig. 1), evaluate the fungicidal effectiveness of medicinal composition.

Claims (7)

1. containing the triazole derivatives of monose group, it is characterized in that, described triazole derivatives is compound shown in formula I, or its pharmaceutically acceptable salt:
In formula I, R 1for the monose group having ethanoyl to protect or do not have ethanoyl to protect; R 2for C 6~ C 18the alkyl of straight or branched; N is the integer of 1 ~ 4.
2. triazole derivatives as claimed in claim 1, it is characterized in that, wherein said monose group is: glucose group, semi-lactosi group, mannose group, acetylglucosamine group, acetylamino galactosamine group, Fucose group or sialic acids groups.
3. triazole derivatives as claimed in claim 2, it is characterized in that, monose group wherein used is: the glucose group not having ethanoyl to protect, semi-lactosi group or mannose group.
4. triazole derivatives as claimed in claim 1, is characterized in that, wherein R 2for C 6~ C 18in there is the alkyl of the straight or branched of even-numbered carbon atom.
5. triazole derivatives as claimed in claim 1, it is characterized in that, wherein n is 1 or 2.
6. if the triazole derivatives in Claims 1 to 5 as described in any one is as the application of antibiotic synergistic agent, in other words, as the triazole derivatives in Claims 1 to 5 as described in any one is preparing the application in microbiotic synergistic agent.
7. apply as claimed in claim 6, it is characterized in that, wherein said microbiotic is Oxazacillin (oxacillin) or ceftazime (Ceftazidime).
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CN111205344A (en) * 2020-01-14 2020-05-29 华东理工大学 Pure organic phosphorescent small-molecule material for methanol solvent recognition and preparation method thereof

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107857782A (en) * 2017-12-13 2018-03-30 北京农学院 A kind of glucofuranose base triazole compound and preparation method thereof and bactericide
CN107857782B (en) * 2017-12-13 2019-10-01 北京农学院 A kind of glucofuranose base triazole compound and preparation method thereof and fungicide
CN111205344A (en) * 2020-01-14 2020-05-29 华东理工大学 Pure organic phosphorescent small-molecule material for methanol solvent recognition and preparation method thereof
CN111205344B (en) * 2020-01-14 2023-03-14 华东理工大学 Pure organic phosphorescent small-molecule material for methanol solvent recognition and preparation method thereof

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