CN117677404A - Gadolinium-based compounds and MRI contrast agents comprising the same - Google Patents
Gadolinium-based compounds and MRI contrast agents comprising the same Download PDFInfo
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- CN117677404A CN117677404A CN202280051261.9A CN202280051261A CN117677404A CN 117677404 A CN117677404 A CN 117677404A CN 202280051261 A CN202280051261 A CN 202280051261A CN 117677404 A CN117677404 A CN 117677404A
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Landscapes
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Abstract
The invention discloses a gadolinium-based compound and an MRI contrast agent comprising the same. The gadolinium-based compound may be a DO 3A-based gadolinium compound to which 4-hydroxybenzoic acid is bound. The MRI contrast agent may comprise the compound. In addition, the present invention discloses a pharmaceutical composition for preventing or treating neuroinflammatory disorders comprising the compound or a pharmaceutically acceptable salt thereof.
Description
Technical Field
The present invention relates to gadolinium-based compounds and MRI contrast agents comprising the compounds.
Background
Today, as the population ages, patients suffering from degenerative brain diseases continue to grow, and the need for early detection of these diseases is becoming increasingly prominent. Neurodegenerative brain diseases including parkinson's disease, vascular dementia, alzheimer's disease, etc., neurotoxicity caused by excessive accumulation of beta-amyloid polymer (oligo aβ) are considered to be one of the causes of these diseases.
Beta-amyloid (aβ) is the major component of amyloid plaques found in the brains of alzheimer's patients, meaning a 36 to 43 amino acid peptide closely related to alzheimer's disease. The peptides are induced from Amyloid Precursor Protein (APP).
The beta-amyloid molecules can aggregate to form soluble polymers that can exist in a variety of forms, and the beta-amyloid polymers (oligometric aβ) formed are toxic to nerve cells and are well known to be directly involved in the progression of alzheimer's disease if excessively accumulated in the brain. Thus, it is envisioned that detecting changes in the concentration of β -amyloid polymer will enable early diagnosis of degenerative brain diseases.
In addition, magnetic resonance imaging (Magnetic Resonance Image, MRI below) is a method for obtaining human anatomy, physiology, and biochemistry information images by utilizing the phenomenon that hydrogen atoms are relaxed in a magnetic field due to the difference in distribution of hydrogen atoms among tissues in the body. Unlike CT or PET, MRI does not use radiation harmful to the human body, but generates an image in vivo using magnetic field gradients and radio waves under a strong magnetic field, and thus is non-invasive, high in resolution, and excellent for soft tissue examination.
In order to more precisely utilize such an MRI apparatus, a contrast agent (contrast agent) is injected into a subject to obtain an MRI image. Contrast (contrast) between tissues on MRI images is a phenomenon that occurs due to the difference in relaxation (effect) of nuclear spins of water molecules in the tissues to return to an equilibrium state on each tissue. The contrast agent influences the relaxation by using paramagnetic or superparamagnetic materials, pulls the relaxation difference between tissues, causes MRI signal change and makes the contrast between tissues clearer.
At present, the most commonly used in clinicIs a gadolinium (Gd) chelate-based contrast agent. Currently, gd-DTPA is usedGd-DOTA/>Gd(DTPA-BMA)/>Gd(DO3A-HP)Gd(BOPTA)/>Etc. However, most commonly used contrast agents are non-specific contrast agents distributed in the extracellular space (extracellular fluide, ECF). As specific contrast agents only special liver specific contrast agents are used.
Recent studies have driven the development of contrast agents with specific targeting or exhibiting signal enhancement by physiological activity (pH change, enzymatic activity), but to date, MRI contrast agents with specific targeting, in particular specific MRI contrast agents for degenerative brain have not achieved adequate results.
Disclosure of Invention
It is an object of the present invention to provide a compound that specifically binds to a β -amyloid polymer.
It is another object of the present invention to provide an MRI contrast agent containing the above compound.
It is still another object of the present invention to provide a pharmaceutical composition for preventing or treating neuroinflammatory disorders, which contains the above-mentioned compound.
According to one aspect, the present invention provides a compound having the following formula (1):
in the method, in the process of the invention,
l is- (CH) 2 ) x -A 1 -(CH 2 ) y -A 2 -(CH 2 ) z -*，
x, y and z are each independently selected from any integer from 0 to 5,
A 1 a is a 2 Is independently selected from the group consisting of single bond, -COO-, -CO-, -NH-, -CH 2 One or more structures in the group of-CONH-and-O-,
x is a structure having the following formula (2):
* Is a binding site.
In one embodiment, the A 2 Can be-NH-.
In one embodiment, the A 1 Can be, -CONH-.
In one embodiment, x may be 1.
In one embodiment, y may be 2.
In one embodiment, z may be 0.
In one embodiment, the compound may have the following formula (3).
In one embodiment, the gadolinium (Gd) may coordinate with more than one water molecule.
In one embodiment, the compound may specifically bind to mammalian β -amyloid polymers (oligomera).
In one embodiment, the compound may have a relaxation rate (relaxation) of 3.5 to 4.2s -1 。
In one embodiment, the compound may cross the Blood Brain Barrier (BBB) when injected by intravenous injection.
According to another aspect, the present invention provides an MRI contrast agent comprising a compound as described above.
In one embodiment, the MRI contrast agent may be used to diagnose degenerative brain diseases.
In one embodiment, the MRI contrast agent is used to diagnose Alzheimer's (Alzheimer's) disease.
According to still another aspect, the present invention provides a pharmaceutical composition for preventing or treating neuroinflammatory disorders, comprising the above-described compound or a pharmaceutically acceptable salt thereof.
In one embodiment, the neuroinflammatory disorder may be an inflammatory neurodegenerative brain disorder.
In one embodiment, the inflammatory neurodegenerative brain disease may be a disease selected from Alzheimer's disease or parkinson's disease.
Effects of the invention
According to the embodiment of the invention, the compound can be specifically combined with the beta-amyloid polymer, so that the MRI contrast agent containing the compound can be used for diagnosing degenerative brain diseases including Alzheimer's disease.
In addition, the compound according to the embodiment of the present invention, by having an anti-inflammatory function to reduce an inflammatory factor expressed in a pathway causing neuroinflammation, NLRP3, may be used as an active ingredient in a pharmaceutical composition for preventing or treating neuroinflammatory diseases.
Drawings
Fig. 1 to 7 are diagrams showing experimental results of experimental examples according to the present invention.
Detailed Description
Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings. The invention is susceptible to various modifications and alternative forms, and specific embodiments thereof have been shown by way of example in the drawings and are herein described in detail. It should be understood, however, that there is no intention to limit the invention to the specific forms disclosed, but on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention. In describing the drawings, like reference numerals are given to like components. In the drawings, the size of the structures is shown exaggerated in comparison with actual ones for the sake of clarity of the invention.
The terminology used in the present application is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The singular reference includes the plural reference unless the context clearly indicates otherwise. In this application, the terms "comprises" and "comprising" are used to specify the presence of stated features, integers, steps, actions, components or groups thereof, but do not preclude the presence or addition of one or more other features or integers, steps, actions, components or groups thereof.
Unless defined otherwise, all terms used in this application, including technical and scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Terms defined in commonly used dictionaries should be interpreted as having meanings consistent with their meanings in the context of the relevant art and should not be interpreted in an idealized or overly formal sense unless expressly so defined herein.
The compound according to an embodiment of the present invention may have the following formula (1).
In the above formula (1), gadolinium ion (Gd) 3+ ) Can be combined with a carboxylate (carboxylate; COO-) groups coordinate to form complexes.
In the above formula (1), L may be- (CH) 2 ) x -A 1 -(CH 2 ) y -A 2 -(CH 2 ) z And x, y and z may each be independently selected from any integer from 0 to 5. A is that 1 A is a 2 Can be each independently selected from the group consisting of single bond, -COO, -CO, -NH, -CH 2 -CONH-, and-O-. * Is a binding site.
The L may be a linker (linker) linking the nitrogen in the cyclic structure of the compound and the X. The A is 1 A is a 2 The method of connecting nitrogen in the cyclic structure of the compound and the X through the linking group or the functional group determined by the method may be determined. The x, y and z may determine the linking of the A in the linker 1 And A 2 Is a chain length of the chain. In one embodiment, the A 2 Can be-NH-. In one embodiment, the A 1 Can be, -CONH-. In one embodiment, x may be 1. In one embodiment, y may be 2. In one embodiment, z may be 0.
As long as the compound according to an embodiment of the present invention actually has the structure of the above formula (1), bonding or removal of bonding acceptable to those of ordinary skill in the art is not excluded in the scope of the present invention. As an example, in one embodiment, the gadolinium (Gd) may be coordinated with more than one water molecule in the compound.
In the above formula (1), X may have a structure of the following formula (2).
* Is a binding site.
In one embodiment, the compound may have the following formula (3).
In one embodiment, the compound may specifically bind to mammalian β -amyloid polymers (oligomera). In one embodiment, the compound may have a length of 3.5 to 4.2s -1 Relaxation rate (relaxation) of (c). In one embodiment, the compound may cross the Blood Brain Barrier (BBB) when injected by intravenous injection.
As described above, the compounds according to embodiments of the present invention may specifically bind to β -amyloid polymer.
An MRI contrast agent according to an embodiment of the present invention may comprise the compound. In one embodiment, the MRI contrast agent may be used to diagnose degenerative brain diseases. In one embodiment, the MRI contrast agent may be used to diagnose Alzheimer's disease.
As described above, the MRI contrast agent according to the embodiment of the present invention may be used to diagnose degenerative brain diseases including alzheimer's disease.
A pharmaceutical composition for preventing or treating neuroinflammatory disorders according to an embodiment of the present invention may comprise the above-described compound or a pharmaceutically acceptable salt thereof. In one embodiment, the neuroinflammatory disorder may be an inflammatory neurodegenerative brain disorder. In one embodiment, the inflammatory neurodegenerative brain disease may be a disease selected from Alzheimer's disease or parkinson's disease.
In one embodiment, the "pharmaceutically acceptable salt" is not limited as long as it forms an addition salt with the compound, and includes salts derived from pharmaceutically acceptable inorganic acids, organic acids, or bases. The compound according to the present invention may be converted into a salt thereof by a conventional method, and a person of ordinary skill in the art can easily prepare a salt according to the structure of the compound without additional explanation.
The pharmaceutical composition of the present invention may contain the compound represented by formula 1 above or a pharmaceutically acceptable salt thereof alone, but may further contain a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier may be one commonly used in the pharmaceutical field, and may be an excipient (e.g., starch, calcium carbonate, sucrose, lactose, sorbitol, mannitol, cellulose, etc.) or a diluent (e.g., physiological saline solution, purified water, etc.).
In the present invention, the term "preventing" is to inhibit the occurrence of a neuroinflammatory condition or disease in an individual who is not diagnosed as having such condition or disease, but who is susceptible to such condition or disease. In addition, in the present invention, the term "treating" refers to inhibiting the development of, alleviating, and eliminating a neuroinflammatory condition or disease.
The pharmaceutical compositions of the present invention may be prepared in various dosage forms for parenteral or oral administration according to well-known methods. In one embodiment, the pharmaceutical composition may be administered intravenously.
Hereinafter, embodiments of the present invention will be described in detail. However, the examples described below are only partial examples of the present invention, and the scope of the present invention is not limited to the following examples.
< Synthesis of Gd-DO3A-Hba >
Gd-DO3A-Hba compounds were prepared by stepwise synthesis of material 1 to final material 5.
(1) Synthesis of tri-tert-butyl 2,2 '- (10- (2-ethoxy-2-oxoethyl) -1,4,7,10-tetraazacyclododecane-1,4, 7-triyl) triacetate (tri-tert-butyl 2,2' - (10- (2-ethoxy-2-oxoethyl) -1,4,7, 10-tetrazacyclodecane-1, 4, 7-yl) triacetate), 1
Tri-tert-butyl 2,2 '-1, 4,7,10-tetraazacyclododecane-1,4, 7-triyl) triacetate (tri-tert-butyl 2,2' - (1, 4,7, 10-tetraazacyclodecane-1, 4, 7-yl) triacetate) (9.72 mmol) was dissolved in 160mL of acetonitrile, followed by addition of potassium hydrogencarbonate (29.69 mmol) and stirring for 30 minutes. Then, ethyl bromoacetate (10.69 mmol) was added thereto, followed by stirring at 60℃for 24 hours. After 24 hours, the product was filtered with a filter and the solvent was removed by filtration under reduced pressure. The product was dissolved in dichloromethane, the insoluble material was removed, and after all solvents were removed, vacuum drying was performed to give a yellowish solid. Yield: 99 percent of
(2) Synthesis of tri-tert-butyl 2,2 '- (10- (2-oxo-2- ((2- (3, 4, 5-trihydroxybenzoylamino) ethyl) amino) ethyl) -1,4,7,10-tetraazacyclododecane-1,4, 7-triyl) triacetate 2,2' - (10- (2-oxo-2- ((2- (3, 4, 5-trihydroxybenzamiddo) ethyl) amino) ethyl) -1,4,7, 10-tetraazacyclodecane-1, 4, 7-yl) triacylate, 2
After 1 (5.33 mmol) was dissolved in 7mL of methanol, 6mL of ethylenediamine was added and reacted at room temperature for 4 days. The solvent was removed after heating to 55 ℃ in vacuo to give an oily solid which was washed multiple times with diethyl ether. After drying in vacuo, insoluble matter dissolved in methanol was removed by filtration, and then a pale yellow solid was purified by column chromatography under a mixed solvent of methylene chloride/methanol. Yield: 57%
(3) Synthesis of tri-tert-butyl 2,2 '- (10- (2- ((2- (4-hydroxybenzoylamino) ethyl) amino) -2-oxoethyl) -1,4,7,10-tetraazacyclododecane-1,4, 7-triyl) triacetate (tri-tert-butyl 2,2' - (10- (2- ((2- (4-hydroxybenzomido) ethyl) amino) -2-oxoethyl) -1,4,7, 10-tetraazacyclodecane-1, 4, 7-yl) triacetate), 3
4-hydroxybenzoic acid (6.97 mmol) was dissolved in dimethylformamide and stirred at 0 ℃. Then, EDC. HCl (7.67 mmol) and HOBt hydrate (7.67 mmol) dissolved in dimethylformamide were added to the gallic acid solution and stirred for 30 minutes. Then, 2 (4.88 mmol) dissolved in dimethylformamide was added to the reaction mass, DIPEA (13.94 mmol) was added, and stirred at room temperature for 24 hours. Then, after concentrating dimethylformamide to the maximum by filtration under reduced pressure, extraction was performed with methylene chloride and brine (brine), dehydration was performed with sodium sulfate, and filtration under reduced pressure was performed. Then, the solid was separated by column chromatography under a mixed solvent of methylene chloride/methanol. The next reaction can be carried out without additional isolation and purification.
(4) Synthesis of 2,2 '- (10- (2- ((2- (4-hydroxybenzoamino) ethyl) amino) -2-oxoethyl) -1,4,7,10-tetraazacyclododecane-1,4, 7-triyl) triacetate (2, 2' - (10- (2- ((2- (4-hydroxybenzomido) ethyl) amino) -2-oxoethyl) -1,4,7, 10-tetraazacyclodecane-1, 4, 7-triyl) triacetic acid), 4
After adding excess trifluoroacetic acid to 3 at a temperature of 0 ℃, the reaction was stirred at room temperature for 20 hours. Then, methylene chloride was added and filtration under reduced pressure was repeated. Next, high performance liquid chromatography was performed with the addition of 0.1% trifluoroacetic acid in water/acetonitrile mixed solvent to obtain a purified solid. Yield (2→4): 51%
(5) Synthesis of Gd-DO3A-Hba,5
4 (0.82 mmol) was dissolved in water, then the pH was adjusted to 3 using 1M sodium hydroxide, and GdCl dissolved in water was added 3 ·6H 2 O (0.58 mmol). Then, after the pH was adjusted to 7 using 1M sodium hydroxide, the mixture was stirred at room temperature for 20 hours. The solid obtained by the filtration under reduced pressure was separated and purified by high performance liquid chromatography with the addition of a water/acetonitrile mixed solvent of 10mM ammonium acetate to obtain a solid. Yield: 73%
HR-MS and purity analysis results of Gd-DO3A-Hba ]
Gd-DO3A-Hba was analyzed by HR-MS. Fig. 1 is a graph showing the result. Referring to FIG. 1, it was confirmed that a peak (722.1788 m/z) corresponding to the peak predicted for Gd-DO3A-Hba (722.1785 m/z) occurred.
Further, the result of analyzing the purity of Gd-DO3A-Hba using HPLC is shown in FIG. 2. Referring to FIG. 2, it was confirmed that the purity of Gd-DO3A-Hba was about 98%.
< Gd-DO3A-Hba Performance evaluation method and results >
1) Measurement of relaxation Rate (relaxation)
Using synthetic Gd-DO3A-Hba and cyclic conventional contrast agentsAnd->As a control group, the relaxation rate (r 1 、r 2 ). Specifically, after preparing a model by diluting gadolinium complex with triple distilled water to 5 concentrations (0.0625, 0.125, 0.25, 0.5, 1 mM), T was measured in 3T MRI 1 And T 2 Relaxation time (Relaxation time). From this, R (Relaxation rate=1/T) at each concentration was calculated, and the Relaxation rate (R) of gadolinium complex was obtained by linear regression analysis (see fig. 3) 1 、r 2 ) The results of (2) are shown in the following table1。
[ Table 1 ]
Referring to Table 1 above, it can be seen that r of Gd-DO3A-Hba 1 Has a value of 3.6.+ -. 0.1, r 2 Having a value of 4.1.+ -. 0.1 is a relaxation rate value sufficient for clinical use, and thus, it was confirmed that Gd-DO3A-Hba can be used as a contrast agent.
2) Evaluation of kinetic stability (Kinetic stability)
After preparing the model by diluting Gd-DO3A-Hba and various conventional contrast agents to a concentration of 2.5mM in PBS (pH 7.4), 1 equivalent of 250mM zinc chloride (ZnCl) was added 2 ) The binding stability of DO3A ligand and Gd metal ion was evaluated. This can be confirmed by measuring the metal exchange reaction (transition) of zinc ions to gadolinium ions as a change in relaxation rate.
From the observation of FIG. 4 showing the results, it was confirmed that the Gd-DO3A-Hba of the present invention was due to R 2 The rate of change remains close to a value of 1 and therefore has sufficient stability to be used as an MRI contrast agent.
3) Evaluation of pH stability
1mM Gd-DO3A-Hba and conventional contrast agent as control groupDiluted in buffer solution of pH1, 3, 5, 7, 9, 11, then photographed on MRI 2 Weighted image 3 week measurement R 2 Values. By measuring R over time 2 The value, the change in value after dilution can be confirmed, and the more constant the value is, the higher the pH stability can be evaluated.
From FIG. 5 showing the results, the Gd-DO3A-Hba of the present invention has R in a range of pH3 to 11 for 3 weeks 2 The values did not change, although slightly under strong acid conditions at pH 1. From this result, it was confirmed that Gd-DO3A-Hba was stable under in vivo pH conditions and remained stable even under strong acid-base conditions.
4) Beta-amyloid polymer targeting evaluation
4-1) model experimental methods for confirming targeting of beta-amyloid polymers
(1) 221.5uL of HFIP was added to 1mg of beta amyloid protein at 1mM concentration, and then shaken at room temperature using a shake flask for 1 hour to remove pre-aggregation (Preaggregation).
(2) After drying the pre-aggregated β -amyloid removed, 221.5uL of DMSO was added to prepare a 1mM concentration, and a suspension was formed by a mixer and sonicator, followed by 878.5uL of PBS (1 x, ph 7.4) to prepare a 0.2mM concentration.
(3) After 4 days of incubation at 37℃using shake flasks, the polymerized beta-amyloid polymer was partitioned into 200uL each and Gd-DO3A-Hba and conventional contrast media dissolved in PBS at a concentration of 2mMAfter 20uL addition, the cells were cultured at 37℃for 24 hours using a shake flask.
(4) After 24 hours, the supernatant was removed by centrifugation, and then after washing the β -amyloid polymer with PBS, 200uL of a solution of PBS: dmso=9:1 was added to the precipitate (Pellet) to prepare an MRI model sample. As a control, a model sample was used that only cultures the β -amyloid polymer.
4-2) analysis results of targeting effect of beta-amyloid Polymer
Using the model samples, gd-DO3A-Hba and conventional contrast agents according to an embodiment of the invention were evaluated on a 9.4T MR deviceIs targeted by the beta-amyloid polymer.
Referring to FIG. 6 showing the results, only the model of the beta-amyloid polymer (Abeta) was cultured and cultured togetherThere is little contrast enhancement effect difference between models (Abeta+Gadovist), thereforeAnalysis was no targeting ability. However, the model treated with Gd-DO3A-Hba (Abeta+Gd-DO 3A-Hba) showed a 2-fold increase in signal intensity compared to the model in which the beta-amyloid polymer alone was cultured. From this, it was confirmed that the gadolinium contrast agent of the present invention has a targeting effect on β -amyloid polymer.
Beta-amyloid aggregates from monomers into highly toxic polymers or plaques in the brain, which can produce toxicity and destroy nerve cells when accumulated in the brain for long periods of time, resulting in degenerative brain diseases, i.e., alzheimer's disease. The Gd-DO3A-Hba according to an embodiment of the present invention has a function of targeting β -amyloid polymer (toxic protein), and thus, can be used as a reagent for diagnosing alzheimer's disease.
5) Evaluation of in vivo (in vivo) efficacy
LPS (lipopolysaccharide from Escherichia coli O127: B8 (Lipopolysaccharides), 50ug/2 uL) was used to induce brain inflammation in the small brain medullary pool (cisterna magna) of Balb/c mice (10 weeks old, male, 23-25 g) with a Hamiltonian syringe. The kit is divided into a control group, namely a physiological saline injection group, an LPS group and a Gd-DO3A-Hba (0.1 mmol Gd/kg) group injected by tail vein after LPS injection. Here, gd-DO3A-Hba was injected twice, and Hippocampus (Hippocampus) and Cortex (Cortex) were extracted at 6 hours and 12 hours after LPS injection, respectively, and the expression level of inflammatory factor (NLRP 3) was quantitatively analyzed by immunoblotting (western blot), and the results are shown in FIG. 7.
It is known that degenerative brain diseases such as Alzheimer's disease and Parkinson's disease are closely related to inflammatory cytokines secreted by activated encephalitis and inflammatory mechanisms centered on various proteins. The NLRP3 inflammatory body pathway (inflammasome pathway) is one of the mechanisms of encephalitis that is being actively studied. In the present invention, it was confirmed from the experimental results shown in FIG. 7 that Gd-DO3A-Hba decreased the main inflammatory factor NLRP3 in the above mechanism. From these results, it was confirmed that Gd-DO3A-Hba of the present invention can be used as an MRI agent, i.e., targeted treatment of neuroinflammation through anti-inflammatory function, and diagnosis of brain diseases caused by neuroinflammation.
Although the invention has been described with reference to preferred embodiments thereof, it will be understood by those skilled in the art that various modifications and changes may be made thereto without departing from the spirit and scope of the invention as set forth in the appended claims.
Claims (15)
1. A compound, wherein, having the following formula (1):
in the method, in the process of the invention,
l is- (CH) 2 ) x -A 1 -(CH 2 ) y -A 2 -(CH 2 ) z -*，
x, y and z are each independently selected from any integer from 0 to 5,
A 1 a is a 2 Is independently selected from the group consisting of single bond, -COO-, -CO-, -NH-, -CH 2 One or more structures in the group of-CONH-and-O-,
x is a structure having the following formula (2):
* Is a binding site.
2. The compound of claim 1, wherein the a 2 is-NH-.
3. The compound of claim 2, wherein the a 1 is-CONH-.
4. A compound according to claim 3, wherein x is 1, y is 2 and z is 0.
5. The compound according to claim 1, wherein the compound has the following formula (3).
6. The compound of claim 1, wherein the gadolinium (Gd) coordinates with more than one water molecule.
7. The compound of claim 1, wherein the compound specifically binds to mammalian β -amyloid polymer (oligo aβ).
8. The compound of claim 1, wherein the compound has a relaxation rate of 3.5 to 4.2s -1 。
9. The compound of claim 1, wherein the compound crosses the blood brain barrier when injected by intravenous injection.
10. An MRI contrast agent comprising a compound according to any one of claims 1 to 9.
11. The MRI contrast agent of claim 10, wherein the MRI contrast agent is used to diagnose degenerative brain diseases.
12. The MRI contrast agent of claim 11, wherein the MRI contrast agent is used to diagnose alzheimer's disease.
13. A pharmaceutical composition for preventing or treating a neuroinflammatory disorder, comprising a compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof.
14. The pharmaceutical composition of claim 13, wherein the neuroinflammatory disorder is an inflammatory neurodegenerative brain disorder.
15. The pharmaceutical composition of claim 14, wherein the inflammatory neurodegenerative brain disease is a disease selected from alzheimer's disease or parkinson's disease.
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| KR1020220089920A KR102659248B1 (en) | 2021-07-21 | 2022-07-20 | Gadolinium-based compound, mri contrast agent comprising the same |
| PCT/KR2022/010744 WO2023003412A1 (en) | 2021-07-21 | 2022-07-21 | Gadolinium-based compound, and mri contrast agent including same |
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