CN104530163B - Triazole glycolipid analog derivative and its purposes for cooperateing with antimicrobial agent - Google Patents
Triazole glycolipid analog derivative and its purposes for cooperateing with antimicrobial agent Download PDFInfo
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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
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- C07H19/056—Triazole or tetrazole radicals
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- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
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Abstract
The present invention relates to triazole derivatives of a kind of group containing monose and application thereof, the triazole derivatives of the group containing monose are compound shown in formula I, or its pharmaceutically acceptable salt.The triazole derivatives that the present invention is provided have synergistic effect to the antibacterial of existing antibiotic, and it is used with existing Antibiotic combination, can substantially reduce antibiotic dosage, and a kind of approach is provided using antibiotic for reasonable benefit/risk.In formula I, R1For the monose group for thering is acetyl group to protect or being protected without acetyl group；R2For C6~C18The alkyl of straight or branched；N is 1~4 integer.
Description
Technical field
The present invention relates to the purposes of a kind of triazole glycolipid analog derivative and its collaboration antimicrobial agent, specifically, it is related to
A kind of triazole glycolipid analog derivative of group containing monose and its purposes for cooperateing with antimicrobial agent.
Background technology
From 19 th century laters to early 20th century, the cause of disease of disease obtains the great attention of scientists, and many pathogens open
Beginning is found.Sulfanilamide (SN) has powerful bacteriostasis, and it succeeds in developing the life for having saved countless people.This is that the mankind have found
First can be to the medicine of anti-microbial pathogen, with epoch-making meaning.Then, penicillin is referred to as most having in modern medicine history
The contribution of value, it is a great milestone in physianthropy history to be described as.Penicillin and streptomysin enter as the mankind
The pioneer in antibiotic epoch, antibiotic not only turns into a most frequently used class medicine of clinical departments doctor, and is also family
Indispensable medicine.
However, for example same sword twolip of antibiotic, with it is scientific and reasonable, can be benefited for the mankind, it is incorrect, to endanger
The health of victimization class.As dosage is excessive or during long administration time, antibiotic can cause a variety of adverse reactions, have or even also phase
When serious.Antibiotic, particularly broad-spectrum antibiotic can cause internal flora imbalance to cause suprainfection.
The content of the invention
The present inventor has designed and synthesized the triazole sugar of class group containing monose through extensive and in-depth study
Lipid derivant.Find simultaneously, the triazole glycolipid analog derivative of present invention synthesis group containing monose is to existing antibiotic
Antibacterial to have certain synergistic effect, it is used with existing Antibiotic combination, can substantially reduce antibiotic dosage, is reasonable benefit/risk
A kind of approach is provided using antibiotic.
It is an advantage of the invention to provide a kind of triazole glycolipid class derivative of the novel group containing monose of structure
Thing.
The triazole glycolipid analog derivative of the group of the present invention containing monose, is compound shown in formula I, or it is in pharmacy
Upper acceptable salt：
In formula I, R1For have acetyl group (It is abbreviated as " Ac ") protect or the monose group without acetyl group protection；R2
For C6~C18The alkyl of straight or branched.N is 1~4 integer；
Wherein described monosaccharide groups group includes：Glucose group (Glc-), galactolipin group (Gal-), mannose group
(Man-), acetylglucosamine group (GlcNAc-), acetylamino galactosamine group (GlcNAc-), fucose group
(Fuc-) or sialic acids groups (Sia-), its structure is as shown in the g of a of formula II~II：
In the g of a of formula II~II, R3For H or Ac.
It is another object of the present invention to disclose a kind of use of the triazole glycolipid analog derivative of the above-mentioned group containing monose
On the way：I.e. the present invention provide the group containing monose triazole glycolipid analog derivative can as the synergist of antibiotic application, or
Say, the present invention provides application of the triazole glycolipid analog derivative of the group containing monose in antibiotic synergist is prepared.
In addition, the method that the present invention also provides compound shown in a kind of formula I, it comprises the following steps：
(1) azido compound (R is prepared1-N3) the step of；
(2) by acetylenic halideWith corresponding alcohol (R2OH) reaction prepares intermediateStep
Suddenly；And
(3) by azido compound (R1-N3) and intermediateReaction, the step of preparing object.
Wherein X is halogen (F, Cl, Br or I), R1,R2Definition with n with it is described previously identical.
Brief description of the drawings
Fig. 1 is sterilization-time graph
Embodiment
In a preferred technical scheme of the invention, R1The glucosyl group protected or protected without acetyl group for acetyl group
Group, galactolipin group or mannose group；
Further preferred technical scheme is：, R1For the glucose group, galactolipin group or sweet dew protected without acetyl group
Glycosyl group.
In presently preferred technical scheme, R2For C6~C18In have even-numbered carbon atom straight or branched
Alkyl.
In a further preferred technical solution of the present invention, n is 1 or 2.
In the preparation method provided above, azido compound (R1-N3) can via various acetylation monose classical end group
Bromination and azide substitution are made, and specific steps are referring to Alvarez S.G.＆Alvarez, M.T.Synthesis, 1997,413-
414。
Under with the presence of NaH and room temperature condition, by acetylenic halideWith corresponding alcohol (R2OH it is) (anti-with halogenated hydrocarbons
Answer medium) in reaction at least 12 hours, successively through be evaporated off reaction medium, extraction, dryings, filter and concentrate etc. step obtain centre
Body
By anhydrous CuSO4With VcNa exist, have inert gas (be not involved in reaction gas, such as nitrogen) exist and
Under room temperature condition, by azido compound (R1-N3) and intermediateReaction at least 12 hours, reaction product is successively
Scrubbed, extraction, dry, filtering, concentration and column chromatography obtain the product protected on monose group with acetyl group, then through remove-insurance
Protecting base (acetyl group) reaction (is specifically：In the case where there is triethylamine existence condition, the product that will be protected on monose group with acetyl group
In the water-soluble middle reaction of alcohol) obtain object (compound shown in formula I).
Below by embodiment, the invention will be further described, and its purpose, which is only that, is best understood from present disclosure,
The protection domain being not intended to limit the present invention：
Embodiment 1
(1) synthesis of the nitrine glucose (compound shown in formula A) of full acetyl group protection：
Glucose (3g, 0.017moL) is put into 100mL flasks, then under conditions of ice bath, slowly added into bottle
Enter Ac2O (11.9mL) and HClO4The mixed liquor of (0.072mL), after dripping, removes ice bath, in room temperature condition reaction, TLC
Tracking reaction, disappears (at least needing about 6 hours) to raw material point, stops reaction.With the saturated sodium bicarbonate and sodium chloride of ice
Solution is washed, then is extracted with dichloromethane, then (MgSO is dried4), filtering and reduced under vacuum be so as to obtaining crude product
(5.85g, 90%).Obtain crude product and directly carry out next step reaction without purifying.
The glucose (0.53g, 0.001moL) of full acetyl group protection is weighed, 30mL dichloromethane is added as solvent,
Then 5mL 30% HBr/AcOH solution is added into system, is reacted at room temperature, TLC tracking reactions disappear to raw material point
(at least needing about 12 hours), stops reaction.Washed with the saturated sodium bicarbonate and sodium chloride solution of ice, then use dichloromethane
Extraction, then (MgSO is dried4), filtering and reduced under vacuum be so as to obtaining crude product (0.35g, 87%).Obtain crude product
Sodium azide (0.28g, 0.004moL) directly is added to the inside, is reacted under conditions of oil bath temperature is 60 DEG C, TLC tracking is anti-
Should, disappeared (at least needing about 12 hours) to raw material point, stop reaction.Washed with saturated nacl aqueous solution, then use dichloromethane
Alkane is extracted, then (MgSO is dried4), filtering and reduced under vacuum be so as to obtaining crude product (0.29g, 93%).Eventually pass through
Column chromatography (PE/EA=5:1) pure nitrine glucose (compound shown in formula A) is obtained.
(2) synthesis of intermediate (compound shown in formula B)：
In the flask that n-dodecanol (2g, 10.75mmoL) is added to 100mL, 10mL DMF and 10mL CH are added2Cl2Make
For solvent, propargyl bromide (1.9mL, 21.5mmoL) is then added into system, added under conditions of ice bath NaH (387mg,
16.13mmoL), ice bath reaction is removed after 5 minutes to stay overnight.TLC tracking reactions, being disappeared to raw material point (at least needs about 12 small
When), stop reaction.Reaction product spins off solvent under vacuo first, then with the NaCl of saturation, then uses dichloromethane
Extraction, then (MgSO is dried4), filtering and reduced under vacuum so as to obtain intermediate (compound shown in formula B) (1.93g,
80%).
(3) synthesis of object (compound shown in the A of formula I)：
Obtained intermediate A (400mg, 1.07mmoL) and intermediate B (480mg, 2.14mmoL) are added to 200mL burning
In bottle, anhydrous CuSO is added4(535.8mg, 2.14mmoL) (catalyst) and VcNa (849mg, 4.28mmoL), in nitrogen protection
Under conditions of react, TLC tracking reaction, to raw material point disappear (at least needing about 12 hours), stop reaction.With the chlorine of saturation
Change sodium washing products therefrom, then extracted with dichloromethane, then (MgSO is dried4), filtering and reduced under vacuum be so as to obtaining
Crude product.Column chromatography (PE/EA=3 is carried out again:1) head product (606.8mg, 95%) is obtained.
In the flask that obtained head product (606.8mg, 1.02mmoL) is added to 100mL, solvent methanol 8mL, water are added
1mL and triethylamine 1mL, in being reacted under room temperature condition, TLC tracking reactions disappear (at least needing about 10 hours) to raw material point,
Stop reaction.It is spin-dried for after solvent obtaining white crystal, object (compound shown in the A of formula I).
1H NMR (400MHz, DMSO) δ 8.27 (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 the step of tetradecanol alternative embodiment 1 (2), other raw materials used, reagents and step
It is similar to Example 1, compound shown in the B of formula I can be obtained：
1H NMR (400MHz, DMSO) δ 8.32 (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 the positive step (2) of hexadecanol alternative embodiment 1, other raw materials used, reagents and step
It is similar to Example 1, compound shown in the C of formula I can be obtained：
1H NMR (400MHz, DMSO) δ 8.33 (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 the step of galactolipin alternative embodiment 1 (1), other raw materials used, reagents and step and reality
Apply example 1 similar, compound shown in the D of formula I can be obtained：
1H NMR (400MHz, DMSO) δ 8.20 (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 the step of galactolipin alternative embodiment 1 (1), with the step of tetradecanol alternative embodiment 1 (2)
In n-dodecanol outside, other raw materials used, reagents and step are similar to Example 1, can obtain compound shown in the E of formula I：
1H NMR (400MHz, DMSO) δ 8.26 (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 the step of galactolipin alternative embodiment 1 (1), with the positive step of hexadecanol alternative embodiment 1 (2)
In n-dodecanol outside, other raw materials used, reagents and step are similar to Example 1, can obtain compound shown in the F of formula I：
1H NMR (400MHz, DMSO) δ 8.20 (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 the step of mannose alternative embodiment 1 (1), other raw materials used, reagents and step and reality
Apply example 1 similar, compound shown in the G of formula I can be obtained：
1H NMR (400MHz, DMSO) δ 8.15 (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 the step of mannose alternative embodiment 1 (1), with the step of tetradecanol alternative embodiment 1 (2)
In n-dodecanol outside, other raw materials used, reagents and step are similar to Example 1, can obtain compound shown in the H of formula I：
1H NMR (400MHz, DMSO) δ 8.14 (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),
(t, J=6.7Hz, the 3H) of 3.45-3.39 (m, 3H), 1.24 (s, 24H), 0.85
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) antibiotic is directed to the treatment (measure of MIC value) of correlation strain
With reference to M07-A9 standards by antibiotic and new slycolipid compounds doubling dilution in CaMHB culture mediums, Zhi Houjia
Enter freshly prepared bacterium solution, it is 10 to make the final bacterium of every pipe dense7CFU/ml, determines each antibiotic and new slycolipid compounds list respectively
Only MIC (as positive control, the culture of inoculated bacteria is not used as negative control to the CAMHB inoculated tubes using not drug containing).Group
MIC under composite medicine effect equally uses coubling dilution, fixes the end of new slycolipid compounds in CaMHB culture mediums first
Concentration (32mg/L or 16mg/L), then successively by the antibiotic doubling dilution to be measured in composition of medicine in above-mentioned culture medium, it
Freshly prepared bacterium solution is equally added afterwards, and it is 10 to make the final bacterium of every pipe dense7CFU/ml is (with containing single antibiotic or single new sugar
The nutrient solution of compound is positive control, and the culture of inoculated bacteria is not negative control).Nutrient solution is placed in 37 DEG C,
Cultivate after 16h-20h, observe the growing state of bacterium, and the single minimum inhibitory concentration MIC of interpretation medicine and composition of medicine
The MIC of middle antibiotic.
Suppress the least concentration (MIC) that MRSA ATCC43300 growth needs, OXA (oxacillin) is individually
In use, its MIC is 64-128mg/L；When cefotaxime (Ceftazidime) is used alone, its MIC is 256mg/L.But he
When being combined respectively with the compound that provides of the present invention, the MIC of OXA list and cefotaxime will be substantially reduced, specifically such as
Under：
(a) OXA is respectively 32mg/L chemical compounds I A with concentration, chemical compounds I B, chemical compounds I C, chemical compounds I D, changed
The E of compound I, chemical compounds I F and chemical compounds I G, chemical compounds I H, when being used in combination：The MIC of OXA will greatly reduce.
The chemical compounds I A for 32mg/L and OXA combination such as concentration, the MIC of OXA is 2mg/L, in other words,
Chemical compounds I A makes antibacterial (MRSA ATCC43300, similarly hereinafter) 32-64 times of the synergy of OXA.
Equally, compound B makes 16-32 times of OXA antibacterial synergy；Compound C makes 2-4 times of OXA antibacterial synergy；
Compound D makes 2-4 times of OXA antibacterial synergy；Compound E makes antibacterial 8-16 times of the synergy synergy of OXA；Compound F makes
4-8 times of OXA antibacterial synergy；Compound G makes 16-32 times of OXA antibacterial synergy；Compound H makes OXA antibacterial
2-4 times of synergy；
(b) cefotaxime joins with concentration for 32mg/L chemical compounds I A, chemical compounds I B, chemical compounds I E and compound G respectively
When conjunction is used：The MIC of cefotaxime will greatly reduce.
Chemical compounds I A makes 64 times of the antibacterial synergy of cefotaxime, and chemical compounds I B makes 32 times of the antibacterial synergy of cefotaxime, chemical compounds I
E makes 32 times of the antibacterial synergy of cefotaxime, and chemical compounds I G make 32 times of the antibacterial synergy of cefotaxime.
(c) antibiotic and chemical compounds I A combined needles are to correlative clinical strain
With OXA when being used in combination for 12 plants of clinical bacterium, 12 plants of MRSA being clinically separated are respectively：R15、
R16, R36, R49, R50, R53, R302, R304, R306, R308, R313, R314 (China State Institute of Pharmaceutical Industry's offer).
What chemical compounds I A had synergistic effect to it has 10 plants.It is respectively：R15、R16、R36、R49、R50、R53、R302、R306、
R308、R314。
(2) time-kill curve
The fresh strain cultured solutions of ATCC43300 in exponential phase of growth are diluted to 107CFU/ml obtains being used to be inoculated with
Initial bacterium solution, into initial bacterium solution add various concentrations medicine (2mg/L Oxacillin, 32mg/L chemical compounds I A and
2mg/LOxacillin and 32mg/L chemical compounds Is A mixture), while the blank control group of doing to be not added with any medicine, respectively
In 0,1h, 2h, 4h, 6h, 8h, 12h, 24h quantitative sampling.By the bacterium solution of taking-up successively 10 times of dilutions, acceptable diluent times is taken respectively
Several μ l of dilution 20 are coated on counting culture medium flat plate, and each extension rate is coated with 2-3 parallel-plate, at 36 DEG C ± 1
24~28h of culture is inverted in DEG C constant incubator, colony counting is carried out, with CFU (Colony-Forming
Units, CFU) represent.The logarithm of each culture tube colony counting and incubation time are mapped in rectangular co-ordinate, m- sterilization when obtaining
Curve (see Fig. 1), evaluates the fungicidal effectiveness of composition of medicine.
Claims (3)
1. the triazole derivatives of a kind of group containing monose, it is characterised in that described triazole derivatives are chemical combination shown in Formulas I
Thing, or its pharmaceutically acceptable salt：
In Formulas I, R1For the glucose group, galactolipin group or mannose group protected without acetyl group；R2For C12~C16Directly
Alkyl group；N is 1 or 2；
But do not include following compounds：
2. application of the triazole derivatives as claimed in claim 1 in the synergist of OXA or cefotaxime is prepared.
3. a kind of triazole derivatives for the group containing monose that structure is shown below are preparing OXA or cefotaxime
Application in synergist：
Wherein, R1For the glucose group, galactolipin group or mannose group protected without acetyl group.
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| WO2005113569A1 (en) * | 2004-05-21 | 2005-12-01 | Forskapatent I Syd Ab | Novel 3-triazolyl-galactoside inhibitors of galectins |
| WO2005118625A1 (en) * | 2004-06-04 | 2005-12-15 | Chiralix B.V. | Triazole-linked glycoamino acids and glycopeptides |
| CN101475615A (en) * | 2008-12-05 | 2009-07-08 | 华东理工大学 | Amino acid glucide compound and its use |
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2014
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| WO2005113569A1 (en) * | 2004-05-21 | 2005-12-01 | Forskapatent I Syd Ab | Novel 3-triazolyl-galactoside inhibitors of galectins |
| WO2005118625A1 (en) * | 2004-06-04 | 2005-12-15 | Chiralix B.V. | Triazole-linked glycoamino acids and glycopeptides |
| CN101475615A (en) * | 2008-12-05 | 2009-07-08 | 华东理工大学 | Amino acid glucide compound and its use |
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| Structure Activity Relationships of N -linked and Diglycosylated Glucosamine-Based Antitumor Glycerolipids;Makanjuola Ogunsina，等;《Molecules》;20131210;第18卷;第15290页化合物5 * |
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