CN107513085A - A kind of compound and its preparation method and application - Google Patents
A kind of compound and its preparation method and application Download PDFInfo
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- CN107513085A CN107513085A CN201610431943.9A CN201610431943A CN107513085A CN 107513085 A CN107513085 A CN 107513085A CN 201610431943 A CN201610431943 A CN 201610431943A CN 107513085 A CN107513085 A CN 107513085A
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- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
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- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
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- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
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Abstract
The invention provides a kind of compound with structure shown in formula (I), and hand-foot-and-mouth disease and/or respiratory syncytial virus infection medicine are treated available for preparing.
Description
Technical field
The present invention relates to pharmaceutical technology field, more particularly to a kind of compound and its preparation method and application.
Background technology
Hand-foot-and-mouth disease is the infectious disease as caused by enterovirus, triggers the enterovirus of hand-foot-and-mouth disease and has kind more than 20, wherein
It is most commonly seen with coxsackie virus A 16-type (Cox A16) and enterovirns type 71 (EV71).The disease was occurred in less than 5 years old
There is exanthema vesiculosum or aphtha in the position such as children, performance stomatalgia, apocleisis, low-heat, hand, foot, oral cavity, and most infants one week or so are certainly
More, a small number of infants can cause the complication such as myocarditis, pulmonary edema, aseptic meningoencephalitis.Indivedual children with serious disease disease development are fast,
Cause death.Lack effective medicine at present and carry out symptomatic treatment.
Respiratory Syncytial Virus(RSV) (respiratory syncytial virus, RSV) category paramyxovirus section pneumonia category,
Morris in 1956 isolates first plant of RSV from the one only nasopharyngeal secretions of the experimental animal chimpanzee of cold symptoms.
Nineteen fifty-seven Chanock is successively separated to from the throat swab of the 2 wheezing symptoms infants that suffer from an inflammation of the lungs and have respectively in Baltimore cities.
Gained the name because it can form special syncytium formation in tissue cultures.Respiratory Syncytial Virus(RSV) is infant's respiratory tract sense
Serious bronchiolitis and pneumonia often occurs after contaminating month young infant rsv infection of most common pathogen, particularly 2~6.It is logical
Chang Dong, spring throttling row.The infant for needing hospitalization because of rsv infection every year in different parts of the world is 1 ‰~5 ‰, is lived
Institute's patient's case fatality rate is 1 ‰~3 ‰.
The content of the invention
In view of this, the technical problem to be solved in the present invention is to provide a kind of compound and its preparation method and application,
The compound of preparation can be used for preparing treatment hand-foot-and-mouth disease and respiratory syncytial virus infection medicine.
The invention provides compound shown in a kind of formula (I)：
Present invention also offers the preparation method of compound shown in a kind of formula (I), including：
A Reduning injection) is subjected to pillar layer separation, successively using water, 25%~35% ethanol, 90%~100%
Ethanol gradient elution, collect 90%~100% ethanol eluate；
B 90%~100% ethanol eluate) is subjected to pillar layer separation, uses chloroform-methanol mixed solvent to wash
De- agent, it is 9 to collect chloroform-methanol ratio:1 component；
C) by step B) component collected carries out pillar layer separation, and use Methanol+Water to be carried out for eluant, eluent terraced
Degree elution, it is 1 to collect methanol-water ratio:1 component；
D) by step C) collect component separated through semi-preparative liquid chromatography, obtain compound shown in formula (I)；
Preferably, the semi-preparative liquid chromatography is specially：Using ratio as 25:75 acetonitrile-water is mobile phase, detects ripple
A length of 254nm and 220nm, flow velocity 4mL/min, it is 21.4min to prepare the retention time in liquid phase half.
Preferably, the step A) in pillar layer separation be macroporous absorbent resin.
Preferably, the step B) in pillar layer separation be silica gel column chromatography separation.
Preferably, the step C) in pillar layer separation be ODS pillar layer separations.
Present invention also offers compound shown in a kind of formula (I) in the medicine for preparing anti-EV71 viruses and/or RSV viruses
Application,
Present invention also offers compound shown in a kind of formula (I) to prepare preventing and treating hand-foot-and-mouth disease and/or respiratory tract infection
Application in medicine,
Present invention also offers a kind of medicine, including compound shown in formula (I),
Present invention also offers said medicine answering in the product of preventing and treating hand-foot-and-mouth disease and/or respiratory tract infection is prepared
With.
Compared with prior art, the invention provides a kind of compound with structure shown in formula (I), controlled available for preparation
Treat hand-foot-and-mouth disease and/or respiratory syncytial virus infection medicine.
Brief description of the drawings
Fig. 1 is the HR-ESI-Q-TOF-MS of compound；
Fig. 2 is compound1H-NMR is composed；
Fig. 3 is compound13C-NMR composes to be composed with DEPT-135；
Fig. 4 is compound1H-NMR is composed and break oxygen loganic acid and (1S, 7R, 8R.10S)；-7,8,11-
Trihydroxy-1-hydroperoxy-4-guaien-3-one's1The comparison of H-NMR spectrums；
Fig. 5 is that the HMBC of compound is composed；
Fig. 6 is the H of compound1-H1COSY is composed；
Fig. 7 is that the ROSEY of compound is composed；
Fig. 8 is the hsqc spectrum of compound.
Embodiment
The invention provides compound shown in a kind of formula (I)：
It is the noval chemical compound that sequiterpene and iridoid glycoside are polymerized, and in structure above, the group of omission is mended
Charge and whole be：
Present invention also offers the preparation method of compound shown in a kind of formula (I), including：
A Reduning injection) is subjected to pillar layer separation, successively using water, 25%~35% ethanol, 90%~100%
Ethanol gradient elution, collect 90%~100% ethanol eluate；
B 90%~100% ethanol eluate) is subjected to pillar layer separation, uses chloroform-methanol mixed solvent to wash
De- agent, it is 9 to collect chloroform-methanol ratio:1 component；
C) by step B) component collected carries out pillar layer separation, and use Methanol+Water to be carried out for eluant, eluent terraced
Degree elution, it is 1 to collect methanol-water ratio:1 component；
D) by step C) collect component separated through semi-preparative liquid chromatography, obtain compound shown in formula (I)；
For the present invention using Reduning injection as raw material, the Reduning injection (Chinese medicines quasi-word Z20050217) is Jiangsu
The kind new medicine of former Chinese medicine two of Kang Yuan medicine companies limited company independent research, its prescription are sweet wormwood, honeysuckle, cape jasmine, and auxiliary material is
Polyoxyethylene sorbitan monoleate.Reduning injection is caught a cold caused by affection of exogenous wind-heat, coughed, generating heat, the clinic of upper respiratory tract infection
It is widely used in treatment, it acts on rapid, significant effect.
Reduning injection is carried out pillar layer separation by the present invention first, and present invention preferably employs large pore resin absorption column color
Spectrum separation, more preferably using HP-20 large pore resin absorption column chromatographic isolations.
Specifically, collect respectively wash respectively using water, 25%~35% ethanol, 90%~100% ethanol gradient elution successively
De- liquid.25%~35% ethanol, 90%~100% ethanol are ethanol water.
In some embodiments of the invention, 25%~35% ethanol can be that 25%~30% ethanol is water-soluble
Liquid, 25% ethanol water, 30% ethanol water, or 35% ethanol water；90%~100% ethanol can be
90%~95% ethanol water, 90% ethanol water, 95% ethanol water or 100% ethanol.
Then 90%~100% ethanol eluate obtained above is concentrated into no alcohol taste, carries out pillar layer separation, this hair
It is bright preferably to be separated using silica gel column chromatography.
Specifically, using chloroform-methanol mixed solvent as eluant, eluent, it is 9 to collect chloroform-methanol ratio:1 component；Institute
Chloroform-methanol in the mixed solvent is stated, the ratio of the two can be adjusted voluntarily as needed, and the present invention is to this and is not particularly limited.
Then the component of above-mentioned collection is subjected to pillar layer separation, present invention preferably employs ODS pillar layer separations.
Specifically, using Methanol+Water to carry out gradient elution for eluant, eluent, it is 1 to collect methanol-water ratio:1
Component；In the Methanol+Water, the ratio of the two can be adjusted voluntarily as needed, and it is special that the present invention has no to this
Limit.
Then the component by above-mentioned collection separates through semi-preparative liquid chromatography, you can obtains compound shown in formula (I).
In the present invention, the semi-preparative liquid chromatography actual conditions is preferably：Using ratio as 25:75 acetonitrile-water is stream
Dynamic phase, Detection wavelength are 254nm and 220nm, flow velocity 4mL/min, and it is 21.4min to prepare the retention time in liquid phase half.
The present invention by physicochemical property and Modern spectroscopy learns to do section, as UV, IR, MS,1H-NMR、13C-NMR and 2D-NMR,
Structural Identification is carried out to isolated compound, as a result referring to Fig. 1~Fig. 8, it was demonstrated that it is newization of structure shown in formula I
Compound.
Present invention also offers compound shown in a kind of formula (I) in the medicine for preparing anti-EV71 viruses and/or RSV viruses
Application.
By the embodiment of the present invention, the compound that inventor provides is to hand-foot-mouth disease EV 71 virus and respiratory syncystial
Viral RSV has certain inhibitory action.
Present invention also offers compound shown in above-mentioned formula (I) to prepare preventing and treating hand-foot-and-mouth disease and/or respiratory tract infection
Application in medicine.
Present invention also offers a kind of medicine, including compound shown in formula (I).
In the medicine, only using compound of formula I as active component, or also answered including other active components with compound of formula I
Match somebody with somebody.The of the invention pair of compound compounded with compound of formula I is simultaneously not particularly limited, and can be compounded with compound of formula I, be played medicine association
Same or synergistic effect compound.
Currently preferred, the medicine includes above-mentioned compound of formula I and one or more are pharmaceutically acceptable auxiliary
Material.
The present invention is to the content of compound shown in Formulas I and is not particularly limited, therapeutically effective amount.
The present invention is to the formulation of said medicine and is not particularly limited, the formulation that can be well known in the art, such as oral formulations
Or ejection preparation, the oral formulations be preferably tablet, capsule, pill, granule, decoction, paste, distillate medicinal water, oral solutions,
Pill or syrup, the ejection preparation are preferably parenteral solution or powder-injection.
Present invention also offers a kind of said medicine in the product of preventing and treating hand-foot-and-mouth disease and/or respiratory tract infection is prepared
Using.
The hand-foot-and-mouth disease is disease caused by EV71, in addition to myocarditis, pulmonary edema, aseptic meningoencephalitis etc. are concurrently
Disease.
The respiratory tract infection is breathing problem caused by RSV viruses, including pneumonia, bronchiolitis, upper breathing
Road infection etc..
Invention has obtained compound shown in formula (I) by carrying out extraction research to Reduning injection, and by above-mentioned
Compound carries out cell experiment, it is found that it there is obvious suppression to make hand-foot-mouth disease EV 71 virus and Respiratory Syncytial Virus(RSV) RSV
With, and then there is potential application preparing prevention, treatment hand-foot-and-mouth disease and/or respiratory tract infection drug field.Experiment shows, this
The compound that invention provides is used to suppress EV71 viruses, EC50Value is up to 15.6 μm of ol；For suppressing RSV viruses, EC50It is worth reachable
12.6μmol。
In order to further illustrate the present invention, with reference to embodiment to compound provided by the invention and preparation method thereof and
Using being described in detail.
Embodiment 1
(1) take Reduning injection finished product, through HP-20 macroporous adsorbent resin chromatography post separations, successively with water, 25%~
35% ethanol, 95% ethanol gradient elution, collect each eluent respectively, are concentrated under reduced pressure into no alcohol taste, obtain water elution component,
25%-35%% ethanol elutions component, 95% ethanol elution component；
(2) the 95% ethanol elution component that step (1) obtains is taken, is separated through silica gel column chromatography, is mixed with chloroform-methanol molten
Agent gradient elution, it is 9 to collect chloroform-methanol ratio:1 component, obtain product 2.2g.
Then component obtained above, with Methanol+Water gradient elution, is collected into first through ODS pillar layer separations
Alcohol-water ratio is 5:5 component, obtain product 85mg.
The component of above-mentioned collection prepares liquid phase HPLC separation through half, using ratio as 25:75 acetonitrile-water is mobile phase, inspection
Survey wavelength is 254nm and 220nm, flow velocity 4mL/min, and it is 21.4min to prepare the retention time in liquid phase half, separating obtained molten
Liquid and drying, compound 11.6mg shown in formula (I) is obtained, purity 98%, it is yellow gummy solid.
The structure detection of embodiment 2
Structural Identification is carried out to compound obtained above, as a result referring to Fig. 1~Fig. 8, wherein, Fig. 1 provides for the present invention
Formula (I) shown in compound HR-ESI-Q-TOF-MS (ultra high efficiency liquid phase high resolution mass spectrum) figure, Fig. 2 is provided by the invention
The nucleus magnetic hydrogen spectrum figure of compound shown in formula (I), Fig. 3 be the nuclear-magnetism carbon spectrogram of compound shown in formula provided by the invention (I) with
DEPT-135 spectrograms, Fig. 4 be the nucleus magnetic hydrogen spectrum figure of compound shown in formula provided by the invention (I) and disconnected oxygen loganic acid and
The ratio of (1S, 7R, 8R.10S) -7,8,11-trihydroxy-1-hydroperoxy-4-guaien-3-one nucleus magnetic hydrogen spectrum figure
Right, Fig. 5 is the HMBC spectrograms of compound shown in formula provided by the invention (I), and Fig. 6 is chemical combination shown in formula provided by the invention (I)
The H of thing1-H1COSY spectrograms；Fig. 7 is the ROSEY spectrograms of compound shown in formula provided by the invention (I), and Fig. 8 provides for the present invention
Formula (I) shown in compound hsqc spectrum figure.
By Fig. 1 HR-ESI-Q-TOF-MS, display compound has absworption peak m/z 625.2866 [M+H]+(calculate
It is worth 625.2860), to determine that compound molecule formula is C31H44O13, it is 10 to calculate degree of unsaturation.
Compound shown in the formula of analysis chart 2 (I)1H-NMR(600MHz,in CD3OD), its high field region is observed that 4
Obvious methyl signals：δ 1.05 (3H, d, J=7.1Hz), 1.31 (3H, s), 1.42 (3H, s) and 1.68 (3H, d, J=
2.2Hz) and 1 typical iridoid 3 goes up proton signal：δ 7.41 (1H, s) and 1 upper hemiacetal proton signal：
5.54 (1H, d, J=6.9Hz), 1 glucose anomeric proton signal：δ 4.70 (3H, d, J=7.9Hz).
Compound shown in Fig. 3 formulas (I)13C-NMR(150MHz,in CD3OD) combine DEPT-135 to compose, show 31 altogether
Carbon signal, including 4 methyl (δ 23.9,21.0,20.6,8.8), 6 methylene (δ 119.2,62.8,38.5,36.2,33.4,
31.4), 7 quaternary carbon signals [2 carbonyls (δ 211.5,171.8), 2 company oxygen SP3Hydridization quaternary carbon (δ 80.7,74.0), 1 pair four
Substitute double bond (δ 141.9,174.8)] and 14 methine carbon signals.
Hydrogen, the carbon nuclear magnetic data of compound show two groups of signals, one of structure fragment A and Secologanic
Acid (disconnected oxygen loganic acid) is closely similar, another structure fragment B then with (1S, 7R, 8R.10S) -7,8,11-
Trihydroxy-1-hydroperoxy-4-guaien-3-one similar (see Fig. 4), structure fragment A nuclear magnetic data with
Secologanic acid compare, it is found that the carboxyl (- COOH) on only 7 substitutes [δ by oxygen containing methineH 5.07(IH,d,
), J=5.4,3.6Hz δC96.2].And another structure decision B then remaining 15 carbon signals, with reference to NMR data, can speculate
Structure fragment B is 1 sesquiterpenoids, contains 4 methoxyl groups, 2 rings, 1 ketone carbonyl and 1 double bond in structure.
(see Fig. 5) in HMBC spectrums, relevant peaks H-15 "/C-3 ", 4 ", 5 " and H-2 "/C-1 ", 3 ", 5 ", release α, β-no
The structure fragment a of saturation cyclopentanone.1H-1(see Fig. 6) in H COSY spectrums, it is seen that H-8 ＂/H-9 "/H-10 "/H-1 ", H-10 "/
CH3- 14 " relevant peaks, with reference to H-6 "/C-1 ", 4 ", HMBC 5 ", 7 " is remotely related；CH3- 14 "/C-1 ", 10 ", 9 " and H-
8 "/C-7 ", 9 ", HMBC 10 " is remotely related, builds the structure fragment b of cycloheptane.Two unimodal methyl CH3- 12 ＂ and CH3-
It is remotely related that 13 " to C-7 " and C-11 " are respectively provided with HMBC, thus it is speculated that contains fragment c in structure.It had been assumed that 3 structure pieces
Duan Zhong, we can be found that 1,5,7 carbon atoms are public carbon, so as to connect it as the sequiterpene skeleton of 1 guainane type
B.Visible H-8 "/C-7 in HMBC spectrums；CH3- 12 "/C-7 long-range correlation, binding molecule formula C31H44O13And degree of unsaturation, push away
Disconnected structure fragment A and B is connected by C (C-7)-O-C (C-8 "), C (C-7)-O-C (C-11 ").
Atom numbering is as follows：
The relative configuration of above-claimed cpd provided by the invention determined by ROESY spectrums, in ROSEY spectrums (see
Fig. 7), it is seen that H-7/H3- 12 ", H-8 ", H-5；H-5/H-9,H-8″/H3- 14 ", H-1 "；H-1/H-10 prompts H-7, H-5, H-9,
H3- 12 ", H-8 ", H3- 14 ", H-1 " coplines, are beta comfiguration, and H-1 is α configurations.
Integrated use 1D and hsqc spectrum (see Fig. 8), the whole carbon signals and hydrogen signal of the compound are belonged to (see
Table 1).By SciFinder Scholar network retrievals, relevant report is not found, it is a noval chemical compound to show the compound,
It is named as japonicaside C.
The compound of table 1 nuclear magnetic data (deuterated methanol,1H-NMR 600MHz,13C-NMR 150MHz)
Above testing result shows that compound provided by the invention has structure shown in formula (I).
The activity experiment of embodiment 3
1. material
1.1 strain hand-foot-mouth disease EV 71 virus and Respiratory Syncytial Virus(RSV) RSV, laboratory passage preserve.
1.2 cell model MK cells system Vero and Hep-2 cells, preserved by this laboratory passage.Condition of culture point
It is not:DMEM+10% hyclones, the hyclone of RPMI-1640 culture mediums+10%, 37 DEG C, 5%CO2。
2. principle and method
The cytotoxicity detection of 2.1 medicines
Employ(Invitrogen) toxic action of the kit detection medicine to cell.
Experimental principle：It is a kind of oxidation-reduction indicator, absorbance can be produced according to metabolic activity and become
Change and fluorescence signal.Soluble in water, its oxidised form can be surveyed after entering cell through cyclophorase reduction generation
The fluorescence and color change of amount, the quantitative analysis bred for cytoactive and cell and vitro cytotoxicity research.It is this
Measure is that reagent is converted into the ability of fluorescence and colorimetric indicator based on the cell with metabolic activity, is damaged and inactive thin
Born of the same parents have relatively low native metabolic active, and corresponding signal is relatively low.Therefore fluorescence signal is strong and weak, can reflect the height of cytoactive
It is low.
Method and step：Vero cells and Hep-2 cells are inoculated in 96 porocyte culture plates respectively, cell attachment standby
With.Medicine is originated from 2 times with cell maintenance medium (DMEM+5% serum and the hyclone of RPMI-1640 culture mediums+2%) respectively
Continuous 3 times of gradient dilutions, 6 gradients of concentration (100 μm of ol), per the detection of concentration gradient single hole.After dosing culture 48h, add37 DEG C of incubation 2h, fluoroscopic examinationReduction situation, exciting light 570nm, launch light
595nm。
Cytoactive (%)=(sample well-blank control)/(cell controls-blank control) * 100%
Suppression of 2.2 medicines to EV71 and RSV viruses is tested
2.2.1 suppression of the medicine to EV-71 viruses is tested
After the EV71 vero cells infections of the GFP containing reporter gene, infection cell meeting expressing green fluorescent protein, by glimmering
Viewed under light microscopy expresses the cell number of GFP green fluorescences, it is possible to reflects the proliferative conditions of EV71 viruses.
Method and step：
Vero cells are inoculated in 96 porocyte culture plates, standby after cell attachment.Medicine is from 4 times of highest test concentrations
(100 μm of ol) plays continuous 3 times of gradient dilutions, 6 gradients；Enter vial supernatant is added in the medicine adding hole diluted, after 4h
Row infection, is placed in 37 DEG C of cell culture incubator culture 24h, is taken pictures under fluorescence microscope, fluorecyte is counted.
Experiment sets no medicine control wells (non-dosing thing hole after virus infection), positive drug control hole (guanidine hydrochloride GuHCl).
Inhibiting rate (%)=(no medicine control wells-sample well)/without medicine control wells × 100%
2.2.2 suppression of the medicine to RSV viruses is tested
Hep-2 cells are inoculated in 96 porocyte culture plates, standby after cell attachment.After cells grow up to the individual layer adds
The virus liquid for maintaining culture medium and the dilution of 100 μ l RPMI-1640 culture mediums of 100 μ l medicines containing 2x, 37 DEG C of cultures.See daily
Examine and record cell and specific C PE situations occur, (lesion of virus control wells 75%~100%) detection cell is lived after cultivating 5d
Power.
Experiment sets cell controls group (virus-free infection), virus control group (non-dosing thing hole after virus infection) and positive drug
Thing (Ribavirin) control wells.
Inhibiting rate (%)=(medicine group-virus control group)/(cell controls group-virus control group) × 100%
3. result
3.1 drug samples detect to the toxicity detection of Vero cells and to EV71 inhibitory activity
Drug sample dilutes solvent for use, highest concentration of ordinary dissolution, highest test concentrations, CC50, EC50And (selection refers to SI
Number) as shown in table 2.
Table 2EV71 inhibitory activity test experience results
3.2 drug samples detect to the toxicity detection of Hep-2 cells and to RSV inhibitory activity
Drug sample dilutes solvent for use, highest concentration of ordinary dissolution, highest test concentrations, CC50, EC50And (selection refers to SI
Number) as shown in table 3.
Table 3RSV inhibitory activity test experience results
4. conclusion
Experiment is as can be seen that compound shown in formula (I) provided by the invention is viral without overt toxicity, its anti-EV-71 above
And the SI values of RSV viruses are respectively 10.1 and 19.5, show that it has to hand-foot-mouth disease EV 71 virus and Respiratory Syncytial Virus(RSV) RSV
Certain inhibitory action.
The explanation of above example is only intended to help the method and its core concept for understanding the present invention.It should be pointed out that pair
For those skilled in the art, under the premise without departing from the principles of the invention, the present invention can also be carried out
Some improvement and modification, these are improved and modification is also fallen into the protection domain of the claims in the present invention.
Claims (10)
- A kind of 1. compound shown in formula (I)：
- 2. the preparation method of compound shown in a kind of formula (I), including：A Reduning injection) is subjected to pillar layer separation, successively using water, 25%~35% ethanol, 90%~100% ethanol Gradient elution, collect 90%~100% ethanol eluate；B 90%~100% ethanol eluate) is subjected to pillar layer separation, uses chloroform-methanol mixed solvent as elution Agent, it is 9 to collect chloroform-methanol ratio:1 component；C) by step B) collect component carry out pillar layer separation, use Methanol+Water for eluant, eluent progress gradient wash De-, it is 1 to collect methanol-water ratio:1 component；D) by step C) collect component separated through semi-preparative liquid chromatography, obtain compound shown in formula (I)；
- 3. preparation method according to claim 2, it is characterised in that the semi-preparative liquid chromatography is specially：With ratio For 25:75 acetonitrile-water is mobile phase, and Detection wavelength is 254nm and 220nm, flow velocity 4mL/min, is prepared half in liquid phase Retention time is 21.4min.
- 4. preparation method according to claim 2, it is characterised in that the step A) in pillar layer separation be macropore inhale Attached resin.
- 5. preparation method according to claim 2, it is characterised in that the step B) in pillar layer separation be silicagel column Chromatographic isolation.
- 6. preparation method according to claim 2, it is characterised in that the step C) in pillar layer separation be ODS posts Chromatographic isolation.
- 7. application of the compound shown in formula (I) in the medicine for preparing anti-EV71 viruses and/or RSV viruses,
- 8. application of the compound shown in formula (I) in the medicine of preventing and treating hand-foot-and-mouth disease and/or respiratory tract infection is prepared,
- 9. a kind of medicine, including compound shown in formula (I),
- 10. application of the medicine in the product of preventing and treating hand-foot-and-mouth disease and/or respiratory tract infection is prepared described in claim 9.
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