CN109400615A - It is a kind of target beta-amyloid protein coumarin kind compound and its preparation and application - Google Patents
It is a kind of target beta-amyloid protein coumarin kind compound and its preparation and application Download PDFInfo
- Publication number
- CN109400615A CN109400615A CN201710713030.0A CN201710713030A CN109400615A CN 109400615 A CN109400615 A CN 109400615A CN 201710713030 A CN201710713030 A CN 201710713030A CN 109400615 A CN109400615 A CN 109400615A
- Authority
- CN
- China
- Prior art keywords
- compound
- amyloid protein
- preparation
- coumarin
- targeting beta
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/052—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0453—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/002—Heterocyclic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
Abstract
The present invention relates to a kind of coumarin kind compound and its preparation method and application for targeting beta-amyloid protein, the structural formula for targeting the coumarin kind compound of beta-amyloid protein is as follows:Wherein, R1For CH3Or CF3；R2For C2H4Or C3H6Straight chained alkyl.The compound uses compound B for labelled precursor, with18F‑It carries out nucleophilic substitution to be made, compared with prior art, the present invention can fill up China and early diagnose AD using radiopharmaceutical and the blank in curative effect evaluation field.And as a species specificity Alzheimer's disease PET Imaging probe.Preparation method of the present invention is simple, is suitble to radiopharmaceuticals clinical application, is prepared18F labeled compound radiochemical purity is greater than 95%.
Description
Technical field
The present invention relates to coumarin kind compounds, more particularly, to a kind of Coumarins chemical combination for targeting beta-amyloid protein
Object and its preparation and application.
Background technique
Intracerebral beta-amyloid protein ((β-amyloid protein, A β)) derives from its precursor substance beta-amyloyd precursor egg
White (amyloid precursor protein, APP).Have been acknowledged that A β derives from the APP of gene coding, molecular weight is about
4kD is transmembrane glycoprotein, and is in a three-dimensional structure in β-pleated sheet, therefore claims " amyloid beta ".A β by APP cell membrane outside
12 amino acid of 28 amino acid and transmembrane segment composition, positioned at the hydrophobic part of APP.With very strong aggregation, easy shape
At extremely poorly soluble precipitating.A β is the main component of senile plaque, is neuropathologic hallmark (Glenner G G.Wong C
W.Alzheimer's disease:initial report of the purification and characterization
of a novel cerebrovascular amyloid protein[J]. Biochem Biophys Res Commun,
1984,120(3):855-900.Toreilles F,Touchon J. Pathogenic theories and
intrathecal analysis of the sporadic form of Alzheimer's disease[J].Prog
Neurobiol,2002,66(3):191-203.Lambert M P,Barlow A K,Chromy B A,
etal.Diffusible,non fibrillar ligands derived from Abeta1-42 are potent
central nervous system neurotoxins[J].Pro Natl Acad Sci USA,1998,95(11):6448-
6453.).There are many theories for the pathogenesis of Alzheimer's disease (Alzheimer's disease, AD), and wherein Hardy etc. is mentioned
The A β cascade hypothesis for having gone out AD is of greatest concern, which thinks that the AD that is gathered in of A β occurs, plays the role of a nucleus in development process, A β
Nerve cell dysfunction and death are resulted in, dementia (HARDY J, SELKOE DJ.The amyloid hypo is finally caused
thesis of Alzheimer's disease:progress and problems on the road to
therapeutics[J].Science,2002,297(5580):353-356.)。
Positron emission tomography (PET) (Positron Emission is carried out using the specific molecular probes of targeting A β
Tomograph, PET) it is optimum AD early stage to make a definite diagnosis means.The major drugmaker in the whole world is all selectively targeted in research and development always
The PET imaging agent of A β, until 2012, gift carried out the product of (Eli Lilly) company,18F-Florbetapir(US7687052/
US8506929 U.S. FDA approval) is obtained；Later, U.S. FDA has approved two marketing drugs in succession again, and General Electric's medical treatment is public
Take charge of (GE HEALTHCARE)18F-Flutemetamol(US7270800/US7351401/US8236282/US8691185/
) and PIRAMAL IMAGING company US891613118F-Florbetaben(US7807135).The country there is no targeting A at present
The PET imaging agent of β gets the Green Light listing, domestic to make a definite diagnosis AD early stage and curative effect evaluation is the available situation of no medicine, researches and develops novel
The PET imaging medicament of targeting A β can fill up China's Bio-pharmaceutical Industry in the blank in the field.
Cumarin (Coumarin), also known as bifuran and cumarin are the black tonka-bean of south China endemic plant, perfume (or spice)
The effective component of prairie pine etc..The present invention is innovative to carry out F-18 label to coumarin derivative, and development one is species specific
PET Imaging probe, makes a definite diagnosis the early stage of AD and curative effect evaluation, has highly important application prospect.
Summary of the invention
It is an object of the present invention to overcome the above-mentioned drawbacks of the prior art and provide a kind of high-purities to target β-
The coumarin kind compound of amyloid protein and its preparation and application.
The purpose of the present invention can be achieved through the following technical solutions: a kind of Coumarins targeting beta-amyloid protein
Compound, which is characterized in that its structural formula is as follows:
Wherein, R1For CH3Or CF3；R2For C2H4Or C3H6Straight chained alkyl.
The preparation method of the coumarin kind compound of above-mentioned targeting beta-amyloid protein, which is characterized in that be by compound B
Labelled precursor, with18F-Nucleophilic substitution is carried out, the structural formula of the compound B is as follows:
Wherein, R1For CH3Or CF3；R2For C2H4Or C3H6Straight chained alkyl, TsO be octadecyl trichlorosilane alkane base.
The method is specifically includes the following steps: in organic solvent, under inert gas shielding, containing phase transfer catalysis (PTC)
Agent, sylvite and18F-Mixture under the action of with compound B carry out nucleophilic substitution, 40 DEG C~120 DEG C of reaction temperature, instead
5-30min is between seasonable to get the coumarin kind compound for targeting beta-amyloid protein.
The coumarin kind compound of gained targeting beta-amyloid protein is post-processed, post-processing approach are as follows: select radiation
Property HPLC the coumarin kind compound for targeting beta-amyloid protein is isolated and purified, then diluted with pure water, cross silicagel column enrichment,
It is eluted with the normal saline solution containing 45% ethyl alcohol, is collected in physiological saline cillin bottle, is finally prepared into containing 10% ethyl alcohol
Normal saline solution is filtered through sterilised membrane filter, is obtained18F marks coumarin compound preparation.It is isolated and purified with radioactivity HPLC
Before, can also first it be purified with Sep-Pak C18 column to product.
The organic solvent includes anhydrous acetonitrile, anhydrous tetrahydro furan, anhydrous DMF (N,N-dimethylformamide), nothing
One of water DMSO (dimethyl sulfoxide) or a variety of, preferably anhydrous DMF.
The sylvite is potassium carbonate or saleratus；
The phase transfer catalyst is cyclic crown ether class catalyst, and the cyclic crown ether class catalyst is selected from 4,7,
Six oxygen -1,10- diaza-bicyclo [8.8.8] hexacosane (K of 13,16,21,24-222)。
The inert gas is nitrogen and/or argon gas and/or helium.
It is described containing phase transfer catalyst, sylvite and18F-Mixture in each component substance amount ratio are as follows: phase transfer
Catalyst: sylvite=1:3.5~7.5:1,18F-Activity be 40 μ Ci~2Ci.Concentration of the compound B in reaction solution
For 0.01~2mol/L；The mass ratio of phase transfer catalyst and compound B be 1:1~7.5:1 wherein18F-Selected from convolution plus
Fast device bombards H2 18Obtained by O target.
It is described containing K222, potassium carbonate and18F-Mixture can be made by following methods: it is rich with the elution of K222 solution
Collection18F-QMA column, solvent evaporated.
The application of the coumarin kind compound of above-mentioned targeting beta-amyloid protein, which is characterized in that it is as a kind of special
Property Alzheimer's disease PET Imaging probe, for AD early diagnosis and curative effect evaluation.
Used labelled precursor compound B such as wads a quilt with cotton Biotechnology Co., Ltd purchased from Shanghai in the present invention, used in remaining
To reagent be commercial reagents.
Compared with prior art, the present invention has the following advantages and beneficial effects:
1, the present invention obtains18F marks the selectively targeted intracerebral beta-amyloid protein of coumarin compound energy, intracerebral β-shallow lake
The aggregation of powder sample albumen be lead to one of AD Producing reason, and18F label coumarin compound can image characterization by PET
Its intracerebral dense poly- degree, to characterize the aggregation extent of beta-amyloid protein to carry out the early diagnosis of AD.
2, preparation method of the present invention is simple, is suitble to radiopharmaceuticals clinical application, is prepared18F marks cumarin chemical combination
Object radiochemical purity is greater than 95%.
3, the present invention can fill up the sky that China carries out early diagnosis and curative effect evaluation field using radiopharmaceutical to AD
It is white.
Detailed description of the invention
Fig. 1 present invention prepares the HPLC detection figure of products obtained therefrom；
Fig. 2 present invention prepares the analysis HPLC detection figure of products obtained therefrom；
Fig. 3 present invention prepares products obtained therefrom and carries out the experiment micro-PET imaging of AD model mouse applied to PET Imaging probe
Figure, wherein a is APP/PS1 double transgenic AD rat model micro-PET 30min static image figure, and b is normal rat
Micro-PET 30min static image figure.
Specific embodiment
The present invention is described in detail with specific embodiment below in conjunction with the accompanying drawings.
Embodiment 1
Compound A (R1For CH3；R2For C2H4) coumarin compound preparation
Take K222The acetonitrile solution of (10-12mg) and potassium carbonate (1-2mg) cross enrichment [18F]F-QMA column (2mCi), receive
Collection into reaction flask, set at 90 DEG C by reaction flask, is passed through nitrogen (1mL/min) drying, adds anhydrous acetonitrile solvent and be evaporated to dryness,
In triplicate, 0.6mL anhydrous DMF is added.0.3mL precursor compound containing 2mg B (R is added in reaction flask1For CH3；R2For C2H4)
Anhydrous DMF solution, confined reaction 30min, is cooled to room temperature after reaction at 120 DEG C.
Reaction product is added 5mL pure water and first passes through sep-pak C18 column in advance, then separate with half preparation C18 column pure
Change, as shown in Figure 1, the peak of t=8.1min is unreacted18F-Characteristic peak, the peak of t=25.5min is product peak, is collected
The product of 25-27min, the product being collected into are diluted with 100mL pure water, cross silicagel column enrichment, then contain the life of 45% ethyl alcohol with 2mL
Saline solution elution is managed, is collected in the cillin bottle of physiological saline containing 8mL, it is water-soluble to be finally prepared into the physiology salt containing 10% ethyl alcohol
Liquid is filtered through sterilised membrane filter, is obtained18F marks coumarin compound preparation, measures through activity meter, obtains not corrected putting
Yield is 10%, is detected through HPLC, HPLC condition: analytical column is Agilent ZORBAX EclipseXDB C18 column
(4.6mm×250mm)；Mobile phase is the water (a) and acetonitrile (b) for being added to 0.1% trifluoroacetic acid, gradient condition are as follows: 0-
60min, 30% → 50%b；Flow velocity is 1.0mL/min；UV (220nm) detection and radiological measuring.It obtains18F marks cumarin
Radiochemicsl purity > 98% of compound formulation.
Reference compound structure C is as follows:
Wherein, R1For CH3Or CF3；R2For C2H4Or C3H6Straight chained alkyl.The synthetic method of reference compound C uses and this
Identical method is invented, F element is18The stable isotope of F.
Take above-mentioned preparation A (hot) (R1For CH3；R2For C2H4) and its reference compound C (cold) (R1For CH3；R2For
C2H4) HPLC of common sample introduction checks map as shown in Fig. 2, HPLC condition is same as above.The retention time for obtaining above-mentioned preparation A is
The retention time of 7.51min, reference compound C are 7.63min.
Reference compound C (R1For CH3；R2For C2H4) warp1HNMR and MS identification, Structural Identification result are as follows:
1HNMR (DMSO-d6): δ 7.92 (d, 3JHH=8.4Hz, 2H, Ar-H), 7.86 (s, 1H, Ar-H), 7.75 (d,
3JHH=8.4Hz, 2H, Ar-H), 7.59 (s, 1H, Ar-H), 7.40 (d, 3JHH=1.6Hz, 8.0Hz, 2H, Ar-H), 6.72
(d, 3JHH=1.6Hz, 8.8Hz, 2H, Ar-H), 6.38 (s, 1H, Ar-H), 4.14-4.11 (t, 3JHH=5.2Hz, 2H,
), CH2 3.47-3.45 (t, 3JHH=4.4Hz, 2H, CH2), 2.54 (s, CH3), 2.34 (s, CH3)
TOF-ESI-MS:M (C19H16FN3O2)=337.12 (m/z), 338.2 (M+1)+
Raw material in this preparation method, precursor compound B are Shanghai such as wadding Biotechnology Co., Ltd's product, remaining chemistry
Reagent is traditional Chinese medicines chemical reagents corporation product, [18F]F-It is by C-30 cyclotron small size18O-H2O target occurs18O(p,
n)18F nuclear reaction obtains.
2 PET of embodiment imaging
By above method preparation18F marks coumarin compound A to carry out micro-PET imaging
Prepared by AD model mouse and the normal control tail vein injection above method18F marks coumarin compound A, different fluorine
Keep its body temperature at 37 DEG C or so using heating module after alkane inhalation anesthesia, using R4micro-PET dynamic scan 2h, data are adopted
Framing after collection (preceding half an hour, 2 minutes/frame；Every 10 minutes/frame below), image reconstruction is carried out using OSEM3D method,
Each region of interest of brain area is selected manually using Inveon Research Workplace 2.2 (IRW, Siemens) software
(ROI), SUV is calculated.It images as shown in Figure 3.It can be seen that pair of the AD rat model in intracerebral18F marks cumarin
Closing object A has obvious concentration, compares in normal mice without concentration.
Embodiment 2
A kind of coumarin kind compound targeting beta-amyloid protein, structural formula are as follows:
Wherein, R1For CH33；R2For C2H4Straight chained alkyl.
The coumarin kind compound of above-mentioned targeting beta-amyloid protein is made by the following method: being label by compound B
Precursor, with18F-Nucleophilic substitution is carried out, the structural formula of the compound B is as follows:
Wherein, R1For CH3；R2For C2H4Straight chained alkyl, TsO be octadecyl trichlorosilane alkane base.
The above method specifically the following steps are included:
1. by containing for acquisition18F-H2 18O solution crosses the enrichment of QMA column18F-, use the solution containing phase transfer catalyst, sylvite
Elution QMA column obtain containing phase transfer catalyst, sylvite and18F-Mixed solution, it is described containing phase transfer catalyst, sylvite and18F-Mixture in each component substance amount ratio are as follows: phase transfer catalyst: sylvite=1:3.5,18F-Activity be 40 μ
Ci.Wherein18F-Selected from cyclotron bombard H2 18Obtained by O target.
2. under inert gas (nitrogen) protection, phase transfer catalyst will be contained in organic solvent (anhydrous tetrahydro furan)
K222, potassium carbonate and18F-H2 18O solution and compound B progress nucleophilic substitution, 40 DEG C of reaction temperature, the reaction time
30min is to get the coumarin kind compound for targeting beta-amyloid protein.Concentration of the compound B in reaction solution is
0.01mol/L；The mass ratio of phase transfer catalyst and compound B are 1:1.
3. radioactivity HPLC is selected to isolate and purify the coumarin kind compound for targeting beta-amyloid protein, pure water is then used
Dilution crosses silicagel column enrichment, is eluted, be collected in physiological saline cillin bottle, finally with the normal saline solution containing 45% ethyl alcohol
It is prepared into the normal saline solution containing 10% ethyl alcohol, filters, obtains through sterilised membrane filter18F marks coumarin compound preparation.With
Before radioactivity HPLC is isolated and purified, can also first it be purified with Sep-Pak C18 column to product.
Embodiment 3
A kind of preparation method for the coumarin kind compound targeting beta-amyloid protein, comprising the following steps:
1. by containing for acquisition18F-H2 18O solution crosses the enrichment of QMA column18F-, use the solution containing phase transfer catalyst, sylvite
Elution QMA column obtain containing phase transfer catalyst, sylvite and18F-Mixed solution, it is described containing phase transfer catalyst, sylvite and18F-Mixture in each component substance amount ratio are as follows: phase transfer catalyst: sylvite=7.5:1,18F-Activity be 2Ci.
Wherein18F-Selected from cyclotron bombard H2 18Obtained by O target.
2. under inert gas (nitrogen) protection, phase transfer catalyst will be contained in organic solvent (anhydrous tetrahydro furan)
K222, potassium carbonate and18F-H2 18O solution and compound B progress nucleophilic substitution, 120 DEG C of reaction temperature, the reaction time
5min is to get the coumarin kind compound for targeting beta-amyloid protein.Concentration of the compound B in reaction solution is
2mol/L；The mass ratio of phase transfer catalyst and compound B are 7.5:1.
3. radioactivity HPLC is selected to isolate and purify the coumarin kind compound for targeting beta-amyloid protein, pure water is then used
Dilution crosses silicagel column enrichment, is eluted, be collected in physiological saline cillin bottle, finally with the normal saline solution containing 45% ethyl alcohol
It is prepared into the normal saline solution containing 10% ethyl alcohol, filters, obtains through sterilised membrane filter18F marks coumarin compound preparation.With
Before radioactivity HPLC is isolated and purified, can also first it be purified with Sep-Pak C18 column to product.
Gained targets the coumarin kind compound of beta-amyloid protein, and structural formula is as follows:
Wherein, R1For CF3；R2For C3H6Straight chained alkyl.
The coumarin kind compound of above-mentioned targeting beta-amyloid protein is made by the following method: being label by compound B
Precursor, with18F-Nucleophilic substitution is carried out, the structural formula of the compound B is as follows:
Wherein, R1For CF3；R2For C3H6Straight chained alkyl, TsO be octadecyl trichlorosilane alkane base.
Claims (10)
1. a kind of coumarin kind compound for targeting beta-amyloid protein, which is characterized in that its structural formula is as follows:
Wherein, R1For CH3Or CF3；R2For C2H4Or C3H6Straight chained alkyl.
2. a kind of preparation method of the coumarin kind compound of targeting beta-amyloid protein as described in claim 1, feature
It is, is labelled precursor by compound B, with18F-Nucleophilic substitution is carried out, the structural formula of the compound B is such as
Under:
Wherein, R1For CH3Or CF3；R2For C2H4Or C3H6Straight chained alkyl, TsO be octadecyl trichlorosilane alkane base.
3. the preparation method of the coumarin kind compound of targeting beta-amyloid protein according to claim 2, feature exist
In the method is specifically includes the following steps: containing acquisition18F-H2 18O solution crosses the enrichment of QMA column18F-, using containing phase
Transfer catalyst, sylvite solution elution QMA column obtain containing phase transfer catalyst, sylvite and18F-Mixed solution, organic molten
In agent, under inert gas shielding, will contain phase transfer catalyst, sylvite and18F-Mixture and compound B carry out nucleophilic displacement of fluorine it is anti-
It answers, 100 DEG C~120 DEG C of reaction temperature, reaction time 30-60min is to get the Coumarins chemical combination for targeting beta-amyloid protein
Object.
4. the preparation method of the coumarin kind compound of targeting beta-amyloid protein according to claim 3, feature exist
In the coumarin kind compound of gained targeting beta-amyloid protein is post-processed, post-processing approach are as follows: select radioactivity HPLC
The coumarin kind compound for targeting beta-amyloid protein is isolated and purified, is then diluted with pure water, silicagel column enrichment is crossed, with containing
The normal saline solution of 45% ethyl alcohol elutes, and is collected in physiological saline cillin bottle, is finally prepared into the physiology containing 10% ethyl alcohol
Saline solution is filtered through sterilised membrane filter, is obtained18F marks coumarin compound preparation.
5. the preparation method of the coumarin kind compound of targeting beta-amyloid protein according to claim 3, feature exist
In the organic solvent includes anhydrous acetonitrile, anhydrous tetrahydro furan, anhydrous DMF (n,N-Dimethylformamide), anhydrous DMSO
It is one of (dimethyl sulfoxide) or a variety of, preferred anhydrous DMF.
6. the preparation method of the coumarin kind compound of targeting beta-amyloid protein according to claim 3, feature exist
In the sylvite is potassium carbonate or saleratus.
7. the preparation method of the coumarin kind compound of targeting beta-amyloid protein according to claim 3, feature exist
In, the phase transfer catalyst is cyclic crown ether class catalyst, and the cyclic crown ether class catalyst is selected from 4,7,13,16,
21,24- six oxygen -1,10- diaza-bicyclo [8.8.8] hexacosane.
8. the preparation method of the coumarin kind compound of targeting beta-amyloid protein according to claim 3, feature exist
In the inert gas is nitrogen and/or argon gas and/or helium.
9. the preparation method of the coumarin kind compound of targeting beta-amyloid protein according to claim 3, feature exist
In, it is described containing phase transfer catalyst, sylvite and18F-Mixture in each component substance amount ratio are as follows: phase transfer catalysis (PTC)
Agent: sylvite=1:3.5~7.5:1,18F-Activity be 40 μ Ci~2Ci；Concentration of the compound B in reaction solution is
0.01~2mol/L；The mass ratio of phase transfer catalyst and compound B are 1:1~7.5:1, wherein18F-Selected from convolution accelerate
Device bombards H2 18Obtained by O target.
10. a kind of application of the coumarin kind compound of targeting beta-amyloid protein as described in claim 1, feature exist
In as a species specificity Alzheimer's disease PET Imaging probe.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710713030.0A CN109400615B (en) | 2017-08-18 | 2017-08-18 | Beta-amyloid targeted coumarin compound and preparation and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710713030.0A CN109400615B (en) | 2017-08-18 | 2017-08-18 | Beta-amyloid targeted coumarin compound and preparation and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109400615A true CN109400615A (en) | 2019-03-01 |
| CN109400615B CN109400615B (en) | 2021-07-16 |
Family
ID=65462669
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710713030.0A Active CN109400615B (en) | 2017-08-18 | 2017-08-18 | Beta-amyloid targeted coumarin compound and preparation and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109400615B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112552272A (en) * | 2020-12-22 | 2021-03-26 | 四川大学 | Coumarin compound, preparation method and application thereof, and pharmaceutical composition |
Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1519242A (en) * | 2003-01-24 | 2004-08-11 | 中国科学院上海原子核研究所 | Compound of benzopyran category marked by fluorin [*F] as well as preparation method and its application of developing agent for D4 receptor of dopamine |
| US7270800B2 (en) * | 2000-08-24 | 2007-09-18 | University Of Pittsburgh | Thioflavin derivatives for use in antemortem diagnosis of Alzheimer's disease and in vivo imaging and prevention of amyloid deposition |
| WO2009059214A1 (en) * | 2007-11-02 | 2009-05-07 | The Regents Of The University Of California | Abeta-binding small molecules |
| US7687052B2 (en) * | 2006-03-30 | 2010-03-30 | The Trustees Of The University Of Pennsylvania | Styrylpyridine derivatives and their use for binding and imaging amyloid plaques |
| US20100135906A1 (en) * | 2007-03-30 | 2010-06-03 | Barrio Jorge R | In vivo imaging of sulfotransferases |
| CN102532055A (en) * | 2003-03-14 | 2012-07-04 | 匹兹堡大学联邦制高等教育 | Benzothiazole derivative compounds, compositions and uses |
| US8236282B2 (en) * | 2003-08-22 | 2012-08-07 | University of Pittsburgh—of the Commonwealth System of Higher Education | Benzothiazole derivative compounds, compositions and uses |
| CN103254203A (en) * | 2012-06-01 | 2013-08-21 | 四川大学 | Five-membered urea ring-coumarin derivative or pharmaceutical salt and application thereof |
| US8916131B2 (en) * | 2007-08-30 | 2014-12-23 | Ge Healthcare Limited | Radiopharmaceutical composition |
| CN104710817A (en) * | 2013-12-17 | 2015-06-17 | 中国科学院大连化学物理研究所 | Small molecular weight coumarins near infrared fluorescent dye with large Stokes shift and synthesis method thereof |
| CN105622625A (en) * | 2016-03-09 | 2016-06-01 | 河南师范大学 | Synthesis method of benzopyrone and imidazopyridine compound |
-
2017
- 2017-08-18 CN CN201710713030.0A patent/CN109400615B/en active Active
Patent Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7270800B2 (en) * | 2000-08-24 | 2007-09-18 | University Of Pittsburgh | Thioflavin derivatives for use in antemortem diagnosis of Alzheimer's disease and in vivo imaging and prevention of amyloid deposition |
| CN1519242A (en) * | 2003-01-24 | 2004-08-11 | 中国科学院上海原子核研究所 | Compound of benzopyran category marked by fluorin [*F] as well as preparation method and its application of developing agent for D4 receptor of dopamine |
| CN102532055A (en) * | 2003-03-14 | 2012-07-04 | 匹兹堡大学联邦制高等教育 | Benzothiazole derivative compounds, compositions and uses |
| US8236282B2 (en) * | 2003-08-22 | 2012-08-07 | University of Pittsburgh—of the Commonwealth System of Higher Education | Benzothiazole derivative compounds, compositions and uses |
| US7687052B2 (en) * | 2006-03-30 | 2010-03-30 | The Trustees Of The University Of Pennsylvania | Styrylpyridine derivatives and their use for binding and imaging amyloid plaques |
| US20100135906A1 (en) * | 2007-03-30 | 2010-06-03 | Barrio Jorge R | In vivo imaging of sulfotransferases |
| US8916131B2 (en) * | 2007-08-30 | 2014-12-23 | Ge Healthcare Limited | Radiopharmaceutical composition |
| WO2009059214A1 (en) * | 2007-11-02 | 2009-05-07 | The Regents Of The University Of California | Abeta-binding small molecules |
| CN103254203A (en) * | 2012-06-01 | 2013-08-21 | 四川大学 | Five-membered urea ring-coumarin derivative or pharmaceutical salt and application thereof |
| CN104710817A (en) * | 2013-12-17 | 2015-06-17 | 中国科学院大连化学物理研究所 | Small molecular weight coumarins near infrared fluorescent dye with large Stokes shift and synthesis method thereof |
| CN105622625A (en) * | 2016-03-09 | 2016-06-01 | 河南师范大学 | Synthesis method of benzopyrone and imidazopyridine compound |
Non-Patent Citations (3)
| Title |
|---|
| T. SHESHASHENA REDDY，ET AL.: "Synthesis and fluorescence study of 6,7-diaminocoumarin and its imidazolo derivatives", 《DYES AND PIGMENTS》 * |
| YANPING YANG,ET AL.: "Synthesis and Monkey-PET Study of (R)- and (S)-18F-Labeled 2-Arylbenzoheterocyclic Derivatives as Amyloid Probes with Distinctive in Vivo Kinetics", 《MOLECULAR PHARMACEUTICS》 * |
| 尹立 等: "异香豆素对老年痴呆小鼠β淀粉样蛋白的影响", 《当代医学》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112552272A (en) * | 2020-12-22 | 2021-03-26 | 四川大学 | Coumarin compound, preparation method and application thereof, and pharmaceutical composition |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109400615B (en) | 2021-07-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100422180C (en) | Amyloid plaque aggregation inhibitors and diagnostic imaging agents | |
| Kuhnast et al. | [18F] DPA-714,[18F] PBR111 and [18F] FEDAA1106—Selective radioligands for imaging TSPO 18 kDa with PET: Automated radiosynthesis on a TRACERLAb FX-FN synthesizer and quality controls | |
| CN112043838B (en) | ACE2 receptor targeted nuclide polypeptide probe, and preparation method and application thereof | |
| JP2009532328A (en) | 5-HT1B receptor radioligand | |
| Yang et al. | Synthesis and evaluation of 68Ga-labeled DOTA-2-deoxy-D-glucosamine as a potential radiotracer in μPET imaging | |
| Campoy et al. | [18F] Nifene PET/CT imaging in mice: Improved methods and preliminary studies of α4β2* nicotinic acetylcholinergic receptors in transgenic A53T mouse model of α-synucleinopathy and post-mortem human Parkinson’s disease | |
| Kumata et al. | [18F] DAA1106: Automated radiosynthesis using spirocyclic iodonium ylide and preclinical evaluation for positron emission tomography imaging of translocator protein (18 kDa) | |
| Shah et al. | Radiosynthesis and biological evaluation of the 99mTc-tricarbonyl moxifloxacin dithiocarbamate complex as a potential Staphylococcus aureus infection radiotracer | |
| KR20150010742A (en) | Kit and Method for Producing a Radiopharmaceutical | |
| CN109400615A (en) | It is a kind of target beta-amyloid protein coumarin kind compound and its preparation and application | |
| CN105579454A (en) | Compounds and their use for preparation of Tau imaging agents and Tau imaging formulations | |
| Shah et al. | Radiosynthesis and characterization of the 99m Tc-fleroxacin complex: a novel Escherichia coli infection imaging agent | |
| Shah et al. | Radiosynthesis and biological evolution of 99m Tc (CO) 3–sitafloxacin dithiocarbamate complex: a promising Staphylococcus aureus infection radiotracer | |
| CN103497217A (en) | 2-aryl benzothiazole compound with high affinity with A(beta) plaque and preparation method and application thereof | |
| CN106902363A (en) | Radioactive composition, its single fraction preparation method and use | |
| CN101891791B (en) | Derivate for labeling bile acid and reference compound, preparation method and application thereof | |
| CN107118097A (en) | 2-18F- fluoropropionic acids isomers, its synthetic method and its application | |
| CN101020698A (en) | Benzothiazole aniline compound marked with Tc-99m and its prepn process and application | |
| CN113024542B (en) | Deuterated tropane derivative and application thereof | |
| CN101486734B (en) | 99Tcm(CO)3 ciprofloxacin dithiocarbamate complexes, as well as preparation method and application | |
| CN102993243B (en) | 99mTc marked glucose derivative and preparation method and application thereof | |
| CN112250680B (en) | Novel berberine derivative and synthesis method and application thereof | |
| CN207243786U (en) | A kind of synthesis module for the coumarin kind compound for targeting amyloid beta | |
| CN110577478A (en) | Positron probe and preparation method and application thereof | |
| BR102018006679A2 (en) | PHARMACEUTICAL FORMULATION AND ITS METHOD OF PREPARATION |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |