CN107325809B - A kind of fluorescent chemicals and preparation and application with A β plaque block with affinity - Google Patents
A kind of fluorescent chemicals and preparation and application with A β plaque block with affinity Download PDFInfo
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- CN107325809B CN107325809B CN201710347238.5A CN201710347238A CN107325809B CN 107325809 B CN107325809 B CN 107325809B CN 201710347238 A CN201710347238 A CN 201710347238A CN 107325809 B CN107325809 B CN 107325809B
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- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical group N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 abstract description 6
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
- A61K49/0032—Methine dyes, e.g. cyanine dyes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an alkyl or cycloalkyl radical attached to the ring nitrogen atom
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- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1029—Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom
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Abstract
The invention belongs to specific molecular identifying and diagnosing reagent fields, disclose a kind of fluorescent chemicals and preparation and application with A β plaque block with affinity.The fluorescent chemicals have general structure shown in formula (I), wherein R is malononitrile substituent group or cyan-acetic ester substituent group.Fluorescent chemicals of the invention have good photoluminescent property, and launch wavelength has reached near infrared region.Gained fluorescent chemicals are tested in vitro shows have affinity to A β plaque block, can be used successfully to the near-infrared fluorescent imaging of A β plaque block, has many advantages, such as that safety is "dead", low in cost, background fluorescence interference is lower, penetration power is strong in biological tissues.
Description
Technical field
The invention belongs to specific molecular identifying and diagnosing reagent fields, and in particular to a kind of to have affinity with A β plaque block
Fluorescent chemicals and preparation and application.
Background technique
Alzheimer's disease (Alzheimer ' s disease, AD) is a kind of neurodegenerative disease.According to 2016 one
Item latest survey data are shown, have more than 47,000,000 patients AD in global range at present.And China enters aging society in advance
Meeting, investigation display China have had more than 8,000,000 AD patients, and quantity occupies first of the world, and number of patients is with annual 300000 or more
Speed increase.AD not only seriously affects the health of the elderly, and brings heavy burden to society and family.Currently,
The drug that can be clinically used for treatment AD cannot delay, terminate or reverse the development of the AD state of an illness, can only partially improve clinical condition
Shape.Moreover, because the AD cause of disease is complicated, exact pathogenesis be it is not immediately clear, clinically main recognizing by evaluation patient
Impairment is known to diagnose, and patient diagnosed more has entered the middle and advanced stage of the course of disease and delayed treatment.Lack effective detection means
Have become the major obstacles of AD getting up early diagnosing and treating.
In AD patient's brain, it is AD pathologic mark the most significant that beta-amyloid protein (Amyloid, A β) deposits in brain
One of will.Many decades of A β plaque block before the onset of AD have started to occur, and are the earliest nerve fiber degeneration mark of AD and important disease
Feature of science.In recent years, the prevention and reverse one of the target for becoming treatment AD that A β plaque block is formed, inhibit A β plaque block to produce in intracerebral
Raw and accumulation drug and therapy have obtained extensive research.
Other than AD, A β plaque block is existed in other diseases, such as cerebral amyloid angiopathy, amyloidosis, shallow lake
Powder sample polyneuropathy, systemic senile amyloidosis and with hereditary cerebral hemorrhage of amyloidosis etc..Therefore, research and development tool
There is the A beta molecule probe of specific binding A β plaque block noticeable.A β plaque block is carried out using A beta molecule probe and Molecular imaging techniques
Imaging, it can be achieved that noninvasive, real-time A β plaque block tracing in vivo and detection, and then carry out early stage for the Diseases such as AD and examine
Disconnected, examination of curative effect and therapeutic agent research etc. provides great convenience.
Between the past several years, have more radioactivity A beta molecule probe and enter clinical experimental stage, and there is related PET to be imaged
Reagent listing, but the application of Radionuclide imaging method is also limited by some factors, such as penetrating of being issued of radiological imaging agent
Line has certain radiation injury to human body, medical institutions is needed to be configured with the cyclotron of production radionuclide, radiation
Property imaging agent need professional technician mark prepare etc..Under comparing, optical imagery has safe "dead", data acquisition
Time is short and equal many advantages low in cost, in recent years in medical diagnosis etc. using in widespread attention.It is especially close red
Outer Imaging-PAM, because the interference of its background fluorescence is lower, penetration power is strong in biological tissues, and therefore, research and development have A β plaque block
There is the near-infrared fluorescent imaging agent (molecular probe) of affinity, it will be with important scientific meaning and real value.
Summary of the invention
In place of the above shortcoming and defect of the existing technology, the primary purpose of the present invention is that providing a kind of and A β
Patch has the fluorescent chemicals of affinity.
Another object of the present invention is to provide the preparation methods of the above-mentioned fluorescent chemicals with A β plaque block with affinity.
A further object of the present invention is to provide the applications of the above-mentioned fluorescent chemicals with A β plaque block with affinity.
The object of the invention is achieved through the following technical solutions:
A kind of fluorescent chemicals with A β plaque block with affinity, the fluorescent chemicals have structure shown in formula (I)
General formula:
Wherein, R is(fluorescent chemicals are referred to as DCSC-1) or(the fluorescence chemical combination
Object is referred to as DCSC-7).
The preparation method of above-mentioned fluorescent chemicals, including following preparation step:
(1) 2,3,3- tri-methyl indoles and iodomethane are added to ethyl alcohol to be mixed evenly, are heated in pressure vessel
It is reacted to 60~100 DEG C, is cooled to room temperature precipitation solid after the reaction was completed, filtered, obtain intermediate 1:
(2) DMF and methylene chloride are uniformly mixed, ice bath and nitrogen protection, are then added dropwise phosphorus oxychloride, stirring 20~
Cyclohexanone is added after 40min, is warming up to 50~100 DEG C of back flow reactions, is cooled to room temperature after the reaction was completed, ice is added in reaction solution
In water, solid is precipitated, filters, obtains intermediate 2:
(3) intermediate 1 and intermediate 2 are dissolved in organic solvent, are warming up to 80~130 DEG C of back flow reactions, reaction is completed
Solvent is evaporated off in back spin, and column chromatography for separation obtains intermediate 3:
(4) intermediate 3 and malononitrile are dissolved in organic solvent, piperidines or potassium carbonate methanol saturated solution, room temperature is added
Solid is precipitated in stirring, filters, and obtains the fluorescent chemicals DCSC-1 for having affinity with A β plaque block；Or by intermediate 3 and cyano
Ethyl acetate is dissolved in organic solvent, piperidines or saturated solution of potassium carbonate is added, after reaction is stirred at room temperature, column chromatography for separation is obtained
To the fluorescent chemicals DCSC-7 with A β plaque block with affinity.
Preferably, organic solvent described in step (3) is the mixed solvent of n-butanol and toluene.
Preferably, organic solvent described in step (4) is methanol.
Preferably, the molar ratio of intermediate 3 described in step (4) and malononitrile or cyan-acetic ester is 1:(5~15).
The synthetic route chart of above-mentioned preparation method is as shown in Figure 1.
It is above-mentioned that there is application of the fluorescent chemicals of affinity in preparation A β plaque block localization diagnosis composition with A β plaque block,
The composition includes fluorescent chemicals and pharmaceutically acceptable carrier shown in formula (I), " the pharmaceutically acceptable load
Body " includes various excipient and diluent." pharmaceutically acceptable carrier " may include liquid, such as water, physiological saline, sweet
Oil or ethyl alcohol.
It is above-mentioned have to A β plaque block the fluorescent chemicals of affinity preparation A β plaque block diagnostic reagent or with A β deposition it is related
Application in the therapeutic agent of disease.
Further, described to refer to Alzheimer's disease or cerebral amyloid angiopathy with A β deposition related disease.
Fluorescent chemicals of the invention have the following advantages that and the utility model has the advantages that
Fluorescent chemicals of the invention, electron donating group and electron-withdrawing group in structure form push-pull electronics work
Conjugated structure, and by the conjugated system of carbon-carbon double bond increase transition, make the fluorescence of compound molecule generation to near-infrared
Area is mobile, while this class compound all has good photoluminescent property, and launch wavelength has reached near infrared region.Gained fluorescence chemical combination
Object is tested in vitro shows have affinity to A β plaque block, can be used successfully to the near-infrared fluorescent imaging of A β plaque block, have
The advantages that safety is "dead", low in cost, background fluorescence interference is lower, penetration power is strong in biological tissues.
Detailed description of the invention
Fig. 1 is the synthetic route chart of fluorescent chemicals of the present invention (I)；
Fig. 2 is fluorescent chemicals DCSC-1 obtained by the embodiment of the present invention1H-NMR spectrum；
Fig. 3 is fluorescent chemicals DCSC-1 obtained by the embodiment of the present invention13C-NMR spectrogram；
Fig. 4 is fluorescent chemicals DCSC-7 obtained by the embodiment of the present invention1H-NMR spectrum；
Fig. 5 is fluorescent chemicals DCSC-7 obtained by the embodiment of the present invention13C-NMR spectrogram；
Fig. 6 is the probe (I) and A β of the preparation of fluorescent chemicals DCSC-1 and DCSC-7 obtained by the present invention1-42Aggregation mixing
The fluorescence emission spectrogram of compound of front and back；
Fig. 7 is fluorescent chemicals DCSC-1 solution probe obtained by the present invention by tail vein injection AD transgenic mice and normal
Different time points brain living imaging figure in 60min after mouse.
Specific embodiment
Present invention will now be described in further detail with reference to the embodiments and the accompanying drawings, but embodiments of the present invention are unlimited
In this.
Following embodiment can refer to routine techniques progress for not specifically specified parameter.Nuclear-magnetism spectrum uses Switzerland
Bruker company Avance III 400MHz nmr determination, deuterated chloroform or deuterated DMSO make solvent.
The developing method of present invention offer A β plaque block.In the first step of this developing method, by formula (I) institute of detectable amount
The compound shown is introduced into tissue or patient.Compound is usually the part of diagnosis composition and passes through those skilled in the art
Well known method is administered to tissue or patient.Patient is such as introduced with the formula of detectable amount (I) compound represented and is being enough
After the time for closing compound and A β plaque agllutination, atraumatic ground detection compound.Or formula (I) compound represented is introduced
Patient takes tissue sample from patient through the enough time so that compound and A β plaque agllutination are closed, and is detached from patient and detects in tissue
Compound.Or tissue sample is taken from patient and formula (I) compound represented is introduced into the tissue sample.It is being enough to make the change
It closes object to be bound to after the time of A β plaque block, detection compound.
Formula (I) compound represented can be administered to patient by whole or local administration route.For example, can be with
Compound is administered to patient so that it is delivered to whole body.It is alternatively possible to which compound to be administered to the specific organ of concern
Or tissue.For example, needing the amyloid plaques of positioning and quantitative intracerebral to diagnose or track the process of the AD of patient.
Term " patient " refers to the mankind and other animals.Also known how to determine is enough to make compound those skilled in the art
The time closed with A β plaque agllutination.By the way that formula (I) compound represented of detectable amount is introduced patient, then upon administration each
The required time can be easily determined in detection compound at time.
Term " in conjunction with " refers to the chemical interaction between compound and A β plaque block.In conjunction with example include covalent bond,
Ionic bond, hydrophilic-hydrophilic interaction, hydrophobic-hydrophobic interaction and complex compound.
Imaging means of the present invention are optics imaging.
Embodiment 1
A kind of synthesis of fluorescent chemicals (I) of the present embodiment, specific synthesis step are as follows:
(1) synthetic intermediate 1
By the 2,3,3- tri-methyl indole (30mmol) of 4.77g and 3.22ml iodomethane (7.08g, 50mmol) in 60ml second
It is stirred evenly in alcohol, sealed pressure vessel, 80 DEG C of reaction 12h.After the reaction was completed, it is cooled to room temperature, solid is precipitated, filters, obtain
Solid 7.7g is precipitated to get intermediate 1；
(2) synthetic intermediate 2
17.5ml DMF (16.54g, 225mmol) is uniformly mixed with 18ml methylene chloride, under ice bath and nitrogen protection,
15ml phosphorus oxychloride (24.68g, 160mmol) slowly is added dropwise dropwise, after stirring 20-40min, 4.6ml cyclohexanone is added
(4.37g, 45mmol) is cooled to room temperature, reaction solution is poured slowly into ice water after being warming up to 80 DEG C of back flow reaction 4h, is precipitated solid
Body filters, obtains 7.5g solid, i.e. intermediate 2；
(3) synthetic intermediate 3
7.5g intermediate 1 (25mmol) and 7g intermediate 2 (40mmol) are dissolved in 140ml n-butanol to mix with 60ml toluene
In solvent, after being warming up to 80-130 DEG C of reaction 4h, solvent is removed, column chromatography for separation obtains 2.5g intermediate 3；
(4) fluorescent chemicals DCSC-1 is synthesized
400mg intermediate 3 (1.2mmol) and 800 μ L malononitrile (12mmol) are dissolved in 32ml methanol, 320 μ are added
The potassium carbonate methanol solution of L saturation, is stirred at room temperature 3h, filters, and obtains 202mg and solid is precipitated to get DCSC-1, yield
44.9%.Nucleus magnetic hydrogen spectrum figure and carbon the spectrogram difference of products therefrom are as shown in Figures 2 and 3.Product appraising datum is as follows:
1H NMR (400MHz, DMSO) δ 8.00 (d, J=13.8Hz, 1H), 7.82 (s, 1H), 7.48 (d, J=6.9Hz,
1H), 7.33 (t, J=7.7Hz, 1H), 7.20 (d, J=7.6Hz, 1H), 7.10 (t, J=7.4Hz, 1H), 5.90 (d, J=
12.9Hz, 1H), 3.47 (s, 3H), 2.81 (t, J=8.7Hz, 2H), 2.60 (t, J=9.3Hz, 2H), 1.85-1.73 (m,
2H),1.60(s,6H)；
13C NMR(101MHz,CDCl3)δ166.28,153.40,148.14,143.74,139.64,137.59,
128.17,124.81,123.96,122.35,121.94,117.37,115.59,107.87,95.15,72.11,47.32,
29.82,29.71,28.34,27.49,25.86,20.96。
(5) fluorescent chemicals DCSC-7 is synthesized
400mg intermediate 3 (1.2mmol) and 1.28mL cyan-acetic ester (12mmol) are dissolved in 32ml methanol, then
100 μ L piperidines are added, after 12h is stirred at room temperature, DCSC-7 of the column chromatography for separation to get 126mg, yield 24.9%.Products therefrom
Nucleus magnetic hydrogen spectrum figure and carbon spectrogram difference it is as shown in Figure 4 and Figure 5.Product appraising datum is as follows:
1H NMR (400MHz, DMSO) δ 8.45 (s, 1H), 7.86 (d, J=14.1Hz, 1H), 7.42 (d, J=7.6Hz,
1H), 7.28 (t, J=8.2Hz, 1H), 7.09 (d, J=8.7Hz, 1H), 7.02 (t, J=7.1Hz, 1H), 5.75 (d, J=
12.9Hz, 1H), 4.25 (q, J=14.5,7.5Hz, 2H), 3.37 (s, 3H), 2.88 (t, J=5.8Hz, 2H), 2.60 (t, J=
8.3Hz, 2H), 1.79 (m, 2H), 1.59 (s, 6H), 1.26 (t, J=7.5Hz, 3H)；
13C NMR(101MHz,CDCl3)δ165.13,164.59,164.31,164.12,151.40,147.50,
147.22,144.13,139.45,134.67,134.38,128.00,125.24,124.41,121.85,121.55,107.26,
94.28,61.93,52.85,46.85,29.71,29.58,28.32,26.02,21.25,14.29。
Embodiment 2
A kind of synthesis of fluorescent chemicals (I) of the present embodiment, specific synthesis step are as follows:
(1) synthetic intermediate 1
By the 2,3,3- tri-methyl indole (30mmol) of 4.77g and 3.22ml iodomethane (7.08g, 50mmol) in 60ml second
It is stirred evenly in alcohol, sealed pressure vessel, 80 DEG C of reaction 12h.After the reaction was completed, it is cooled to room temperature, solid is precipitated, filters, obtain
Solid 7.7g is precipitated to get intermediate 1；
(2) synthetic intermediate 2
17.5ml DMF (16.54g, 225mmol) is uniformly mixed with 18ml methylene chloride, under ice bath and nitrogen protection,
15ml phosphorus oxychloride (24.68g, 160mmol) slowly is added dropwise dropwise, after stirring 20-40min, 4.6ml cyclohexanone is added
(4.37g, 45mmol) is cooled to room temperature, reaction solution is poured slowly into ice water after being warming up to 80 DEG C of back flow reaction 4h, is precipitated solid
Body filters, obtains 7.5g solid, i.e. intermediate 2；
(3) synthetic intermediate 3
7.5g intermediate 1 (25mmol) and 7g intermediate 2 (40mmol) are dissolved in 140ml n-butanol to mix with 60ml toluene
In solvent, after being warming up to 80-130 DEG C of reaction 4h, solvent is removed, column chromatography for separation obtains 2.5g intermediate 3；
(4) fluorescent chemicals DCSC-1 is synthesized
400mg intermediate 3 (1.2mmol) and 800 μ L malononitrile (6mmol) are dissolved in 16ml methanol, 160 μ L are added
The potassium carbonate methanol solution of saturation, is stirred at room temperature 3h, filters, and obtains 184mg and solid is precipitated to get DCSC-1, yield 40.9%.
Product appraising datum is the same as embodiment 1.
(5) fluorescent chemicals DCSC-7 is synthesized
400mg intermediate 3 (1.2mmol) and 1.28mL cyan-acetic ester (6mmol) are dissolved in 16ml methanol, then plus
Enter 50 μ L piperidines, after 12h is stirred at room temperature, column chromatography for separation is to get 121mg DCSC-7, yield 23.7%.Product appraising datum
With embodiment 1.
Embodiment 3
A kind of synthesis of fluorescent chemicals (I) of the present embodiment, specific synthesis step are as follows:
(1) synthetic intermediate 1
By the 2,3,3- tri-methyl indole (30mmol) of 4.77g and 3.22ml iodomethane (7.08g, 50mmol) in 60ml second
It is stirred evenly in alcohol, sealed pressure vessel, 80 DEG C of reaction 12h.After the reaction was completed, it is cooled to room temperature, solid is precipitated, filters, obtain
Solid 7.7g is precipitated to get intermediate 1；
(2) synthetic intermediate 2
17.5ml DMF (16.54g, 225mmol) is uniformly mixed with 18ml methylene chloride, under ice bath and nitrogen protection,
15ml phosphorus oxychloride (24.68g, 160mmol) slowly is added dropwise dropwise, after stirring 20-40min, 4.6ml cyclohexanone is added
(4.37g, 45mmol) is cooled to room temperature, reaction solution is poured slowly into ice water after being warming up to 80 DEG C of back flow reaction 4h, is precipitated solid
Body filters, obtains 7.5g solid, i.e. intermediate 2；
(3) synthetic intermediate 3
7.5g intermediate 1 (25mmol) and 7g intermediate 2 (40mmol) are dissolved in 140ml n-butanol to mix with 60ml toluene
In solvent, after being warming up to 80-130 DEG C of reaction 4h, solvent is removed, column chromatography for separation obtains 2.5g intermediate 3；
(4) fluorescent chemicals DCSC-1 is synthesized
400mg intermediate 3 (1.2mmol) and 800 μ L malononitrile (18mmol) are dissolved in 48ml methanol, 150 μ are added
The potassium carbonate methanol solution of L saturation, is stirred at room temperature 3h, filters, and obtains 196mg and solid is precipitated to get DCSC-1, yield
43.6%.Product appraising datum is the same as embodiment 1.
(5) fluorescent chemicals DCSC-7 is synthesized
400mg intermediate 3 (1.2mmol) and 1.28mL cyan-acetic ester (18mmol) are dissolved in 48ml methanol, then
150 μ L piperidines are added, after 12h is stirred at room temperature, column chromatography for separation is to get 115mg DCSC-7, yield 22.7%.Product identifies number
According to same embodiment 1.
Gained fluorescent chemicals (I) application performance test of the invention:
(1) probe and A β of fluorescent chemicals preparation1-42The vitro binding assay of aggregation:
Experimental method: it takes fluorescent chemicals DCSC-1 or DCSC-7 obtained by the present invention to be dissolved in dimethyl sulfoxide, is configured to
10mM stock solution is diluted to 1 μM of prepare liquid (probe (I) with PBS solution.First measure the excitation and emission spectra of probe (I)
Matter.Select A β1-42Albumen cultivates A beta-aggregation body in 37 DEG C of water-baths, for simulating the aβ protein aggregation in human brain.By probe
(I) with A β1-42(5 μM) of aggregation mixing carry out fluorescence detection using sepectrophotofluorometer.Gained probe (I) and A β1-42It is poly-
The fluorescence spectra of collective's mixing front and back is shown in Fig. 6.As seen from Figure 6, the near-infrared fluorescent of fluorescent chemicals of the invention (I)
It is well-behaved, reach near infrared region.Wherein, after fluorescent chemicals DCSC-1 is in conjunction with A beta-aggregation body, maximum emission wavelength is
685nm or so.Fluorescent chemicals DCSC-1 and A β1-42The mixed fluorescence intensity of aggregation substantially enhances.
(2) fluorescent chemicals (I) probe application is in AD transgenic mice living imaging:
Experimental procedure: by fluorescent chemicals DCSC-1 be prepared into solution probe (4mg/kg, 10% Tween 80,20%DMSO,
70%PBS) by tail vein injection enter AD transgenic mice (Tg, APP/PS1 bis- turn, 10 monthly ages) and normal mouse (WT,
C57BL6,10 monthly ages) in vivo, under the continuous narcosis of isoflurane respectively 10min, 30min, 60min carry out mouse species at
As (Caliper Life Science, IVIS Lumina XR, excitation wavelength take 630nm to Image Acquisition, and launch wavelength takes
685nm), result is analyzed.Imaging results analysis is carried out using Living Imaging Software.Gained imaging experiment result
As shown in Figure 7.The results show that fluorescent chemicals (I) can penetrate blood-brain barrier, the fluorescence signal of brain was reached at 10 minutes or so
To peak value.After 10 minutes, the brain fluorescence signal intensity of AD transgenic mice is better than normal mouse.Fluorescent chemicals
Clearance rate of the DCSC-1 in AD transgenic mice body will obviously be slower than normal mouse, show the A β plaque in probe and mouse brain
Agllutination is trapped in mouse brain after closing, and so that the fluorescence signal of AD mouse brain is apparently higher than normal mouse, suitable for the glimmering of living body
Light imaging.
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, other any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present invention,
It should be equivalent substitute mode, be included within the scope of the present invention.
Claims (2)
1. a kind of have application of the fluorescent chemicals of affinity in preparation A β plaque block localization diagnosis composition with A β plaque block,
Be characterized in that: the composition includes the fluorescent chemicals and pharmaceutically acceptable carrier of formula (I) structure；
Wherein, R isOr
2. a kind of have application of the fluorescent chemicals of affinity in preparation A β plaque block diagnostic reagent with A β plaque block, feature exists
In: the fluorescent chemicals have general structure shown in formula (I):
Wherein, R isOr
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