CN103193752A - Benzo dihydropyran compound and applications to anti-HIV virus - Google Patents
Benzo dihydropyran compound and applications to anti-HIV virus Download PDFInfo
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- CN103193752A CN103193752A CN2013101162723A CN201310116272A CN103193752A CN 103193752 A CN103193752 A CN 103193752A CN 2013101162723 A CN2013101162723 A CN 2013101162723A CN 201310116272 A CN201310116272 A CN 201310116272A CN 103193752 A CN103193752 A CN 103193752A
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Abstract
The invention discloses a benzo dihydropyran compound. The compound has an obvious anti-HIV virus function. The compound or pharmaceutically acceptable salt can antagonize the HIV virus by the Vpu protein of the HIV virus or integrase. The compound is small in toxic and side effects, excellent in treatment effect, thereby necessarily having excellent market prospects.
Description
Technical field
The invention belongs to medical technical field, be specifically related to benzodihydropyrane compounds and the application in anti HIV-1 virus thereof.
Background of invention
Acquired immune deficiency syndrome (AIDS), namely (Acquired Immunodeficiency Syndrome AIDS), is by human immunodeficiency virus (Human Immunodeficiency Virus, the lethality transmissible disease that HIV) causes to acquired immune deficiency syndrome (AIDS).Reviewed the past acquired immune deficiency syndrome (AIDS) popular considerably beyond people's worry and estimation nearly 30 years.There is the aids infection of people more than 7 000 virus in the whole world every day, and to the end of the year 2010, the whole world has 3,400 ten thousand HIV-positives (www.unaids.org).2010,1,800,000 people died from the relative disease that acquired immune deficiency syndrome (AIDS) causes.For many years, positive effort has been made for preventing and treating acquired immune deficiency syndrome (AIDS) by international community, and preventing and controlling make progress to some extent, but acquired immune deficiency syndrome (AIDS) propagation in the world is not effectively controlled yet.Along with the rapid spread of acquired immune deficiency syndrome (AIDS), AIDS preventing and controlling has become the important public health hot spot of society that the whole world is paid close attention to.
The research of anti-AIDS drug is the important topic in drug research field always, there be more than 20 chemicals to be applied to clinical at present, HARRT therapy (two reverse transcriptase inhibitors and the compound preparation that proteinase inhibitor is formed) has been brought into play active effect for prolonging patient in the life-span.But the appearance of the toxicity of medicine, particularly virus drug resistance has been researched and proposed new problem to medicine.Act on the research of the medicine of HIV novel targets (gp41, intergrase, gp24 etc.), be the research emphasis of scientist and drugmaker in the world always.
Summary of the invention
The invention discloses a kind of chroman compounds, this compounds has following general structure (I):
In the logical formula I:
When the R1=phenyl, the 4-hydroxy phenyl, 3, the 4-dihydroxy phenyl, 3-(SO2-X)-the 4-hydroxy phenyl, 3-(SO2-X)-4, the 5-dihydroxy phenyl { wherein, X=OH, ONa, NH2, NHCmH2m+1 (m=1-8), NCnH2n (n=4,5), morpholine, NHCHCOOH, NHCH (CH3) COOH, NHCH (CH2OH) COOH, NHCH (CH2SH) COOH, NHCH (CH2 CH2CH2SCH3) COOH, NHCH (CH2 (CH3)) COOH, NHCH (CH2COOH) COOH, during NHCH (CH2 CH2COOH) COOH}
R2=OH，
R3=H or OH,
R4=H or OH,
R5=OH，
R6=SO
2-X { wherein, X=OH, ONa, NH2, NHCmH2m+1 (m=1-8), NCnH2n (n=4,5), morpholine, NHCHCOOH, NHCH (CH3) COOH, NHCH (CH2OH) COOH, NHCH (CH2SH) COOH, NHCH (CH2 CH2 CH2SCH3) COOH, NHCH (CH2 (CH3)) COOH, NHCH (CH2COOH) COOH, NHCH (CH2 CH2COOH) COOH};
When R1=H or OH,
The R2=phenyl, the 4-hydroxy phenyl, 3, the 4-dihydroxy phenyl, 3-(SO2-X)-the 4-hydroxy phenyl, 3,5-two (SO2-X)-4-hydroxy phenyl, 3-(SO2-X)-4, the 5-dihydroxy phenyl { wherein, X=OH, ONa, NH2, NHCmH2m+1 (m=1-8), NCnH2n (n=4,5), morpholine, NHCHCOOH, NHCH (CH3) COOH, NHCH (CH2OH) COOH, NHCH (CH2SH) COOH, NHCH (CH2 CH2CH2SCH3) COOH, NHCH (CH2 (CH3)) COOH, NHCH (CH2COOH) COOH, NHCH (CH2 CH2COOH) COOH}
R3=H or OH,
R4=X{ wherein, X=OH, ONa, NH2, NHCmH2m+1 (m=1-8), NCnH2n (n=4,5), morpholine, NHCHCOOH, NHCH (CH3) COOH, NHCH (CH2OH) COOH, NHCH (CH2SH) COOH, NHCH (CH2 CH2CH2SCH3) COOH, NHCH (CH2 (CH3)) COOH, NHCH (CH2COOH) COOH, NHCH (CH2 CH2COOH) COOH}.
R5=OH，
R6=H。
Particularly preferred compound is:
2-(3,4-dihydroxy phenyl)-3,4-dihydro-2H-1-chromene-3,5, the 7-trihydroxy-abbreviates l-Epicatechol as, and its structural formula is
The invention also discloses a class poly chroman compounds, this compounds has following general structure (II)
In the general formula (II):
R1=R2=H
Or R1=OH, R2=H
Or R1=R2=OH
n=1,2,3,4,5,6,7,8,9
Particularly preferred compound is:
[4,8'-Bi-2H-1-chromene]-3,3', 5,5', 7,7'-hexol, 2,2'-bis (3,4-dihydroxy phenyl)-3,3', 4,4'-tetrahydrochysene-, [2R-[2 α, 3 α, 4 β (2'R*, 3'R*)]], be called for short procyanidin B 2, its structural formula is
The invention also discloses the purposes of medicine in prevention and treatment HIV virus that comprises above-claimed cpd.
Can also add one or more pharmaceutically acceptable carriers in the said medicine, as pharmaceutically acceptable thinner, excipient, weighting agent, tackiness agent, disintegrating agent, absorption enhancer, tensio-active agent, lubricant, flavouring agent and sweeting agent etc.
The medicine that with the The compounds of this invention is the activeconstituents preparation can be tablet, pulvis, capsule, granula or various ways such as oral liquid and injection formulations.The medicine of above-mentioned various formulations all can be by the ordinary method preparation of pharmaceutical field.
Description of drawings
Fig. 1 .SPR detects principle schematic
Fig. 2. l-Epicatechol to HIV-1 intergrase BIAcore in conjunction with figure
Fig. 3. procyanidin B 2 to HIV-1 intergrase BIAcore in conjunction with figure
Fig. 4 .100 μ g/ml l-Epicatechol to HIV-1 reversed transcriptive enzyme p66 subunit BIAcore in conjunction with figure
Fig. 5. procyanidin B 2 to HIV-1 reversed transcriptive enzyme p66 subunit BIAcore in conjunction with figure
Embodiment
Below will adopt specific embodiment to come the present invention is further explained, but should not regard the restriction to initiative spirit of the present invention as.
Embodiment 1
The main agents configuration
Sodium-acetate liquid (10 mmol/L): get 0.8203g CH3COONa(82.03g/mol) fixed molten to 1 L with deionized water.After the packing, transfer PH respectively with acetic acid, from 4.0-8.0 totally 9 kinds of different PH value solution, 0.22 μ m membrane filtration degerming.
NHS:N-maloyl Asia (N-hydroxysuccinimide)
EDC: ethyl [3-(dimethylin) propyl group] carbodiimide (1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride), be used for the dextran of activation CM5 chip surface behind NHS and the EDC mixing, GE BIAcore test kit provides.
ETH: diethanolamine hydrochloride, be used for the sealing chip surface not with protein bound position, GE BIAcore test kit provides.
PBS(PH ospH ate Buffer Solution, phosphoric acid buffer): NaCl 8.0g, KCl 0.2g, Na2HPO412H2O 3.58g, KH2PO3 0.24g uses deionized water, and constant volume is to 1 L.121 ℃ of 30min autoclavings.
CCK-8: contain its chemical name of WST-8[: 2-(2-methoxyl group-4-nitrophenyl)-3-(4-nitro)-5-(2,4-disulfonic acid benzene)-2H-tetrazolium list sodium salt in the reagent].It is reduced to the look first a ceremonial jade-ladle, used in libation dyestuff (Formazandye) with high water soluble by the desaturase in the cell under the effect of electron carrier 1-methoxyl group-5-toluphenazine sulphur dimethyl ester (1-Methoxy PMS).The quantity of the first a ceremonial jade-ladle, used in libation thing that generates is directly proportional with the quantity of viable cell, directly carries out cell proliferation and oxicity analysis because utilizing this characteristic.
The high sugar of DMEM(): dry powder is available from Hyclone company, and each small packages adds in the 900 mL deionized waters, adds 3.75g NaHCO3, is settled to 1 L, mixing, filtration sterilization, packing, and 4 ℃ of preservations are standby.
One, cellulotoxic experiment is determined l-Epicatechol and procyanidin B 2 maximal non-toxic dosage
(1) digestion TZM-bl cell, with high sugared DMEM substratum (10% foetal calf serum, 1% glutamine G, 1% mycillin SP) dilution, the inoculation of 96 orifice plates, about 6000 cells in every hole.37 ℃, 5%CO2 overnight incubation.
(2) observe 96 orifice plates, about 50% stratification of cell.
(3) sample preparation: with medicine with high sugared DMEM substratum by 4 times of gradient dilutions, each medicine is established 6 concentration gradients, each concentration is established 3 multiple holes, every hole adds the drug solution after the 100 μ L dilution in 96 holes.37 ℃, 5%CO2 are hatched.
(4) take out 96 orifice plates, mirror lower observation hole inner cell growing state behind the 24h.
(5) take out 96 orifice plates behind the 48h, add CCK8 by 10 μ L/ holes, 37 ℃, 5%CO2 are hatched 30min.
(6) microplate reader detects: the absorbance (OD450/620nm) of measuring each hole
(7) calculate under each concentration l-Epicatechol and procyanidin B 2 to normal TZM-bl cell inhibiting rate according to formula 1, with medicine cytotoxicity (inhibiting rate) is lower than 10% o'clock dosage as maximal non-toxic dosage.The results are shown in Table 1.
Table 1
Table 1 CCK8 method is measured and is become catechin and procyanidin B 2 cytotoxicity
Logarithm with drug level is X-coordinate, being the ordinate zou curve plotting to TZM-bl cell inhibiting rate, utilize the straight-line regression method to calculate regression curve, reckoner catechin and procyanidin B 2 are respectively 96.67 μ g/ml and 42.10 μ g/ml to 50% poisoning concentration (TC50) of TZM-bl cell.
Experimental result shows that l-Epicatechol is lower than 10% to TZM-bl cell inhibiting rate under 12.5 ug/ml dosage, think that this dosage is medicine maximal non-toxic dosage.Procyanidin B 2 is lower than 10% to TZM-bl cell inhibiting rate under 6.25 ug/ml dosage, think that this dosage is medicine maximal non-toxic dosage.
Two, the mensuration of the preparation of HIV-1 pseudovirus and infectivity
1, preparation HIV-1 pseudovirus, rotaring redyeing system sees Table 2.
The preparation cotransfection system of table 2 HIV-1 pseudovirus
| Plasmid | Quality (μ g) |
| PNL4-3 Δ Env-GFP skeleton plasmid | 0.5 |
| HIV-1 B hypotype coating plasmid | 1 |
Adopt FuGENE HD transfection reagent respectively with in plasmid pNL4-3 Δ Env-GFP skeleton plasmid, HIV-1 B hypotype coating plasmid 293 FT, the HeLa cell, method is as follows.
(1) the day before yesterday is inoculated 5 * 105 ~ 1 * 106/ porocyte in transfection in six orifice plates.
(2) next day, cell density reached 60 % stratification.
(3) get 100 μ L Opti-MEM substratum respectively and add in 2 EP pipes, respectively add 0.5 μ g pNL4-3 Δ Env-GFP skeleton plasmid, 1 μ g HIV-1 B hypotype coating plasmid again.
(4) 6 μ L FuGENE HD are joined in the Opti-MEM plasmid mixed system, wink is left standstill 30 min from the back room temperature.
(5) above-mentioned mixture is added in the corresponding hole.
Collect cell culture fluid after (6) 48 hours, collect centrifugal back and supernatant liquor is preserved in packing.
2, measure the infectivity of HIV-1 pseudovirus in TZM-bl
(1) 96 porocyte culture plate inoculation TZMbl cell, 6000 ~ 8000cells/ hole, 37 ℃, 5%CO2 are cultivated 24h, about 50% stratification of cell.
(2) preparation contains the DMEM of 20 μ g/mL DEAE.
(3) virus dilution: with the DMEM substratum virus dilution stock solution that contains 20 μ g/mL DEAE, every hole inoculum size is 100 μ L.
(4) culture supernatant is abandoned in suction gently, adds above-mentioned virus dilution liquid 100 μ L rapidly.Set up cell control group (not adding virus) simultaneously.4 multiple holes are done in every papova triplicate experiment, each dosage.
(5) 37 ℃, cultivate 40-48 h in the 5%CO2 incubator.
(6) preparation stationary liquid and staining fluid:
The stationary liquid preparation (is faced and is used new system, totally 25 mL.）：
37% formaldehyde, 675 μ L
25% glutaraldehyde, 200 μ L
PBS?24.1?mL
The staining fluid preparation (is faced and is used new system, totally 12 mL.）：
0.2M yellow prussiate of potash 240 μ L
0.2 the M Tripotassium iron hexacyanide 240 μ L
2.0M?MgCl2?12?μL
40mg/mL?X-gal?120?μL
PBS?11.4?mL
The X-gal stock solution: preparation 40mg/mL is dissolved in DMSO.-20 ℃ of dark places, storage.
(7) fixing: every hole adds stationary liquid 100 μ L, and room temperature is fixed 5 min, PBS washing 2 times.
(8) dyeing: every hole adds staining fluid 100 μ L, hatches 50 min for 37 ℃, PBS washing 2 times.
(9) every hole adds 100 μ L PBS, adopts ImagePro Plus software autoscan under the Olympus inverted fluorescence microscope and counts the locus coeruleus number.Select for use the suitable virus concentration of locus coeruleus number to be used for subsequent experimental.
3, MAGI-test measures l-Epicatechol and procyanidin B 2 anti-HIV-1 activity
(1) 96 porocyte culture plate inoculation TZMbl cell, 6000 ~ 8000cells/ hole, 37 ℃, 5%CO2 are cultivated 24h, about 50% stratification of cell.
(2) sample preparation: soup is diluted to suitable concn with high sugared DMEM.
(3) viral dilution: the DMEM(for preparing 20 μ g/mL DEAE gets 100 μ L 2mg/mL DEAE and adds in the 9.9 mLDMEM substratum); Take out virus in the liquid nitrogen container, with the DMEM dilution that contains 20 μ g/mL DEAE (1 mL virus solution adds 21.6 mL and contains in the DMEM substratum of 20 μ g/mL DEAE mixing).
(4) application of sample: take out 96 porocyte culture plates, discard substratum gently, add 100 μ L/ hole testing samples (each concentration testing sample is established 4 multiple holes) fast, add 100 μ L viral dilution liquid then.Set up virus control group (only adding DMEM substratum and viral dilution liquid, 100 μ L/ holes) and cell control group (only adding DMEM and the DMEM substratum that contains 20 μ g/mL DEAE, 100 μ L/ holes) simultaneously.37 ℃, 5%CO2 cultivates 48h.
(5) fixing dyeing
A. dosing:
The stationary liquid preparation (is faced and is used new system, totally 25 mL.）：
37% formaldehyde, 675 μ L
25% glutaraldehyde, 200 μ L
PBS?24.1?mL
The staining fluid preparation (is faced and is used new system, totally 12 mL.）：
0.2M yellow prussiate of potash 240 μ L
0.2 the M Tripotassium iron hexacyanide 240 μ L
2.0M?MgCl2?12?μL
40mg/mL?X-gal?120?μL
PBS?11.4?mL
The X-gal stock solution: preparation 40mg/mL is dissolved in DMSO.-20 ℃ of dark places, storage.
B. inhale gently and remove substratum in the hole, add 200 μ L stationary liquids gently to every hole, room temperature is accurately hatched 5min.
D. 50min, is accurately hatched in 100 μ L staining fluid/holes by 37 ℃.
F. microscopic counting locus coeruleus.
(6) calculate medicine to the inhibiting rate of virus according to formula 2.Experimental result sees Table 3.
Table 3 MAGI-test measures medicine HIV (human immunodeficiency virus)-resistant activity result
Being X-coordinate with the drug level, is the ordinate zou curve plotting with the inhibiting rate to virus, utilizes the straight-line regression method to calculate regression curve, 50% inhibition virus concentration (IC50) of reckoner catechin and procyanidin B 2.
Table 3 result shows that l-Epicatechol has the obvious suppression effect to the HIV-1 pseudovirus in the TZM-bl cell, and its IC50 is 5.0407 μ g/ml.Procyanidin B 2 has the obvious suppression effect to the HIV-1 pseudovirus in the TZM-bl cell, its IC50 is 1.0355 μ g/ml.
Embodiment 2
Target point protein is coupled the BIAcore chip
The core of BIAcore technology is surface plasma resonance technology (Surface Plasmon Resonance, SPR), the variation of the liquid refractivity that is directly proportional with institute binding biomolecules quality by monitoring sensing chip surface comes the interaction between the real-time follow-up biomolecules.When sample to be measured (Chinese medicine, natural drug, compound) flows through chip surface by microjet dish card, detector can detect in real time to have or not between target protein and the testing sample and interact and bonding strength, it can represent (concentration that the response value of 1 RU is equivalent to the chip surface binding substance has changed 1 pg/mm2) with RU in conjunction with situation, and principle is shown in Fig. 1.
At first target spot is coupled on the BIAcore chip in vain.
(1) target protein and chip surface are coupled in advance: prepare the about 80 μ L/ of pre-coupled protein pipe, with different PH values
Sodium-acetate (10 mmol/L) dilution makes its final concentration reach about 20-50 μ g/ μ L, and 0.22 μ m filter filters.
By adjusting protein concentration and pH value, make albumen and chips incorporate value be higher than 2000 RU(response unites,
RU), to guarantee to have when formally being coupled albumen and the chips incorporate of capacity.
(2) target protein formally is coupled with chip surface: 1. activation: NHS 100 μ L are mixed with EDC 100 μ L
Sample on centrifugal (need as far as possible remove bubble) back, the dextran of activation CM5 chip surface.2. coupled protein:
Prepare the target protein of the best PH value of 400 μ L and concentration, centrifugal back goes up sample 200 μ L and chip is coupled.3. seal
Close: sample is gone up in the centrifugal back of 1.0 mol/L pH, 8.5 confining liquids (diethanolamine hydrochloride), 200 μ L, with the sealing chip
The surface not with protein bound position.
The research that l-Epicatechol, procyanidin B 2 are combined with target protein
(1) sample is prepared: prepare 1 * PBS, 0.2 μ M filter filters; Drug dilution is arrived lower concentration about 100
μ g/mL arranges several concentration gradients, and sample is gone up in centrifugal back, is used for SPR and analyzes.
(2) SPR analyzes: a SPR circulation comprises the injection (in conjunction with the phase) of sample to be checked, the damping fluid core of flowing through
Sheet surface (dissociating the phase), 5 mmol/L or 10 mmol/LNaOH wash-outs are combined with the chip surface target protein
Sample (regeneration period).The response value in each period (RU) all can detect in real time.The SPR testing process is at 25 ℃
Carry out in the environment, the lasting flow of damping fluid is 10 μ L/min.
Table 4 l-Epicatechol and procyanidin B 2 are combined situation to HIV-1 Vpu protein B IAcore
| Medicine | Concentration (μ g/ml) | Vpu(hangs protein content 3998) |
| L- | 100 | 260.7 RU |
| Procyanidin B 2 | 100 | -4.9 RU |
Table 4 result shows, l-Epicatechol has to a certain degree specificity combination to HIV-1 Vpu albumen under 100 μ g/ml concentration.And procyanidin B 2 does not have the specificity combination to HIV-1 Vpu under 100 μ g/ml concentration.
Table 5 l-Epicatechol and procyanidin B 2 are combined situation to HIV-1 integrase protein BIAcore
| Medicine | Concentration (μ g/ml) | Intergrase (hanging protein content 10167.2) |
| L- | 50 | 85 RU |
| Procyanidin B 2 | 50 | 959.5 RU |
Table 5 result shows that l-Epicatechol has faint specificity combination to the HIV-1 integrase protein under 50 μ g/ml concentration.And procyanidin B 2 has significant specificity combination to the HIV-1 intergrase under 50 μ g/ml concentration.
Table 6 l-Epicatechol and procyanidin B 2 are combined situation to HIV-1 reversed transcriptive enzyme p66 protein B IAcore
Table 6 result shows that l-Epicatechol HIV-1 reversed transcriptive enzyme p66 albumen is had faint specificity combination, and binding ability has dose-dependence under 25 μ g/ml concentration.And procyanidin B 2 has atomic weak combination to HIV-1 reversed transcriptive enzyme p66 albumen under 25 μ g/ml concentration, thinks that it does not have the specificity combination.
Though, above with general explanation and embodiment detailed explanation having been done in this case, on basis of the present invention, can make some modifications or improvements it, this will be apparent to those skilled in the art.Therefore, the modification of doing without departing from theon the basis of the spirit of the present invention or improvement all belong to the scope of protection of present invention.
Claims (5)
1. chroman compounds or its pharmacy acceptable salt application in the medicine of preparation treatment or prevention HIV infection.
2. application as claimed in claim is characterized in that, described chroman compounds is shown in general structure (I) or general structure (II);
General structure (I):
In the logical formula I:
When the R1=phenyl, the 4-hydroxy phenyl, 3, the 4-dihydroxy phenyl, 3-(SO2-X)-the 4-hydroxy phenyl, 3-(SO2-X)-4, the 5-dihydroxy phenyl { wherein, X=OH, ONa, NH2, NHCmH2m+1 (m=1-8), NCnH2n (n=4,5), morpholine, NHCHCOOH, NHCH (CH3) COOH, NHCH (CH2OH) COOH, NHCH (CH2SH) COOH, NHCH (CH2 CH2CH2SCH3) COOH, NHCH (CH2 (CH3)) COOH, NHCH (CH2COOH) COOH, during NHCH (CH2 CH2COOH) COOH}
R2=OH，
R3=H or OH,
R4=H or OH,
R5=OH，
R6=SO
2-X { wherein, X=OH, ONa, NH2, NHCmH2m+1 (m=1-8), NCnH2n (n=4,5), morpholine, NHCHCOOH, NHCH (CH3) COOH, NHCH (CH2OH) COOH, NHCH (CH2SH) COOH, NHCH (CH2 CH2 CH2SCH3) COOH, NHCH (CH2 (CH3)) COOH, NHCH (CH2COOH) COOH, NHCH (CH2 CH2COOH) COOH};
When R1=H or OH,
The R2=phenyl, the 4-hydroxy phenyl, 3, the 4-dihydroxy phenyl, 3-(SO2-X)-the 4-hydroxy phenyl, 3,5-two (SO2-X)-4-hydroxy phenyl, 3-(SO2-X)-4, the 5-dihydroxy phenyl { wherein, X=OH, ONa, NH2, NHCmH2m+1 (m=1-8), NCnH2n (n=4,5), morpholine, NHCHCOOH, NHCH (CH3) COOH, NHCH (CH2OH) COOH, NHCH (CH2SH) COOH, NHCH (CH2 CH2CH2SCH3) COOH, NHCH (CH2 (CH3)) COOH, NHCH (CH2COOH) COOH, NHCH (CH2 CH2COOH) COOH}
R3=H or OH,
R4=X{ wherein, X=OH, ONa, NH2, NHCmH2m+1 (m=1-8), NCnH2n (n=4,5), morpholine, NHCHCOOH, NHCH (CH3) COOH, NHCH (CH2OH) COOH, NHCH (CH2SH) COOH, NHCH (CH2 CH2CH2SCH3) COOH, NHCH (CH2 (CH3)) COOH, NHCH (CH2COOH) COOH, NHCH (CH2 CH2COOH) COOH};
R5=OH，
R6=H；
General structure (II)
In the general formula (II):
R1=R2=H
Or R1=OH, R2=H
Or R1=R2=OH
n=1,2,3,4,5,6,7,8,9。
3. application as claimed in claim 1 or 2 is characterized in that, described chroman compounds is: 2-(3,4-dihydroxy phenyl)-3, and 4-dihydro-2H-1-chromene-3,5, the 7-trihydroxy-, structural formula is
Perhaps [4,8'-Bi-2H-1-chromene]-3,3', 5,5', 7,7'-hexol, 2,2'-bis (3,4-dihydroxy phenyl)-3,3', 4,4'-tetrahydrochysene-, [2R-[2 α, 3 α, 4 β (2'R*, 3'R*)]], its structural formula is
。
4. application as claimed in claim 2 is characterized in that, the compound of described formula (I) comes antagonism HIV virus by specificity in conjunction with HIV virus Vpu albumen; The compound of described formula (II) comes antagonism HIV virus by specificity in conjunction with HIV viral integrase enzyme.
5. let alone a described application as claim 1-5, it is characterized in that, described HIV infect to as if the human or animal.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023241799A1 (en) * | 2022-06-15 | 2023-12-21 | Université Libre de Bruxelles | Flavanols for use in the treatment of retroviral infections |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040260076A1 (en) * | 2002-10-11 | 2004-12-23 | Castillo Gerardo M. | Isolation, purification and synthesis of procyanidin B2 and uses thereof |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040260076A1 (en) * | 2002-10-11 | 2004-12-23 | Castillo Gerardo M. | Isolation, purification and synthesis of procyanidin B2 and uses thereof |
Non-Patent Citations (1)
| Title |
|---|
| 张旋等: "《我国中药来源的抗HIV 天然化合物研究进展》", 《药学学报》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023241799A1 (en) * | 2022-06-15 | 2023-12-21 | Université Libre de Bruxelles | Flavanols for use in the treatment of retroviral infections |
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Application publication date: 20130710 |