Novel compound and MRI contrast agent comprising same

Abstract

The invention discloses a novel compound based on Pyclin and an MRI (Magnetic Resonance Imaging) contrast agent containing the same. The novel compound and the MRI contrast agent of the present invention are represented by Chemical Formula 1-1, have a structure in which one selected from the group consisting of an alicyclic compound and an aromatic cyclic compound is introduced into the cycle of the skeleton, and exhibit a stable cyclic structure. In addition, the present invention has the effect of providing a high self-relaxation rate and targeting to the liver in a subject.

Description

Technical Field

[0001] The present invention relates to a novel compound and an MRI contrast agent containing the same, and more particularly to a novel compound having a high self-relaxation rate and being able to effectively target the liver even in a small amount, and an MRI contrast agent containing the same. Background Art

[0002] Magnetic resonance imaging (MRI), which is evaluated as a common diagnostic medical device in image diagnosis, uses electromagnetic waves and uses the water content of the human body as an image. Therefore, unlike X-rays, it has attracted attention as a non-invasive diagnostic device. When performing MRI examinations or operations, MRI contrast agents are used together to facilitate the visualization of tissues or blood vessels in the body. When using MRI contrast agents, the time to obtain images can be shortened by the rapid relaxation of water hydrogen, and the tissue contrast in the image is excellent, so the accuracy of diagnosis can be improved.

[0003] In recent years, gadolinium (Gd)-based contrast agents (GBCAs) have been widely used. Gadolinium-based contrast agents include compounds with structures in which chelated ligands surround and bind gadolinium elements, such as DO3A (1,4,7,10-tetraazacyclododecane 1,4,7-triacetic acid) and PCTA (3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15), 11,13-triene-3,6,9-triacetic acid). According to the structure of the ligand, they are divided into linear contrast agents (linear-GBCA) and cyclic contrast agents (ocyclic-GBCA). Since linear contrast agents have stability issues, cyclic contrast agents are preferred. Summary of the invention

[0004] One object of the present invention is to provide a novel compound based on a stable cyclic pyclen, and an MRI contrast agent containing the same.

[0005] Another object of the present invention is to provide a compound with high targeting property to the liver, and an MRI contrast agent comprising the same.

[0006] At present, the gadolinium contrast agents based on DO3A are mainly used as extracellular contrast agents in the market, especially those used as liver contrast agents. Most of them have linear structures and poor stability. Therefore, the present invention provides a stable compound based on cyclic pyclen and targeting the liver.

[0007] A novel compound for achieving one object of the present invention is represented by the following formula 1. Specifically, the compound has a structure in which pyclen is used as a back bone and an alicyclic compound or an aromatic compound is introduced.

[0008] [Chemical formula 1]

[0009]

[0010] In the chemical formula 1, R may be one selected from an alicyclic compound or an aromatic compound.

[0011] In one embodiment, in the compound represented by Chemical Formula 1, R may be an alicyclic compound, and the alicyclic compound may be one selected from cyclohexane or cyclopentane.

[0012] Preferably, the compound may be a compound represented by the following Formula 1-1.

[0013] [Chemical formula 1-1]

[0014]

[0015] The compound represented by the chemical formula 1-1 may have a structure in which 2-aminocyclohexanol having a cyclic structure is introduced into a compound based on Piclene bonded to gadolinium. Since the cyclohexane in the 2-aminocyclohexanol has lipophilic properties, it is judged to have a specific targeting effect on the liver. The Log P value of 2-aminocyclohexanol is 0.45, showing lipophilicity.

[0016] In one embodiment, the compound can specifically target the liver. When the compound is used as a contrast agent and injected into a blood vessel, the compound enters the liver cells and exhibits a long-term contrast enhancement effect, and also exhibits a strong contrast enhancement effect on the bile duct. That is, the compound exhibits specificity for the hepatobiliary system.

[0017] To achieve another object of the present invention, an MRI contrast agent comprises a compound represented by the above formula 1. The MRI contrast agent of the present invention is a T1 contrast agent, which has excellent contrast around a tumor or lesion and is easy to diagnose.

[0018] In one embodiment, the MRI contrast agent can be used to diagnose liver metastasis of cancer, liver cysts, liver cancer or biliary obstruction.

[0019] Effects of the Invention

[0020] According to the present invention, there is an advantage that an image with improved quality can be provided due to a high self-relaxation rate, and further, an effect of targeting the liver can be provided even when a small amount of T1 MRI contrast agent is used. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 This is a diagram for explaining a novel compound, a method for producing the same, and an MRI contrast agent containing the same according to one embodiment of the present invention.

[0022] Figure 2 This is a graph used to compare and evaluate the kinetic stability of the compound Gd-PCTA-Ach according to one embodiment of the present invention with commercially available contrast agents (Gd-DOTA, Gd-HP-DO3A, Gd-DTPA, Gd-EOB-DTPA, Gd-BOPTA).

[0023] FIG3 is a graph for comparing and evaluating the pH stability of the compound Gd-PCTA-Ach according to one embodiment of the present invention with the commercially available contrast agent Gd-DO3A-buttrol, wherein (a) represents the pH stability of 0.5 mM Gd-PCTA-Ach and (b) represents the pH stability of 1 mM Gd-DO3A-buttrol.

[0024] Figure 4 It shows whether there is free Gd in the compound Gd-PCTA-Ach according to one embodiment of the present invention. 3+ The experimental results.

[0025] Figure 5 This is a graph for evaluating the absorbance and fluorescence of 1 mM and 0.5 mM Gd-PCTA-Ach, a compound according to one example of the present invention.

[0026] Figure 6 Graphs showing the survival rates of (A) liver cells (AML-12), (B) brain cells (C8-D1A), and (C) kidney cells (Hek-293) of mice in various concentrations of Gd-PCTA-Ach and Gd-DO3A-butrol, respectively, according to an embodiment of the present invention.

[0027] Figure 7 The figure shows the content of Gd in various organs when Gd-PCTA-Ach according to one embodiment of the present invention is intravenously injected into normal mice.

[0028] FIG. 8 shows (a) MR images according to the injected contents of Gd-PCTA-Ach and Gd-DO3A-buttrol in the brain cancer model and (b) CNR graphs according to the MR images.

[0029] FIG9 is for comparing Gd-PCTA-Ach according to an embodiment of the present invention and commercially available contrast agents (Gd-BOPTA, GD-EOB-DTPA), showing (a) MRI images and (b) CNR graphs of each contrast agent flowing into the liver of a normal mouse at 3.0 T.

[0030] FIG10 shows images of normal mice using Gd-PCTA-Ach at (a) 3.0-T and (b) 9.4-T according to an embodiment of the present invention. Yellow arrows indicate the liver and gallbladder. Data are mean ± SD, n = 3.

[0031] 11 shows (a, c) 3.0-T MRI results of liver cancer mice analyzed using Gd-PCTA-Ach according to an embodiment of the present invention, and (b) a CNR distribution diagram for analyzing MRI. DETAILED DESCRIPTION

[0032] Below, embodiments of the present invention are described in detail with reference to the accompanying drawings. The present invention may be subjected to various modifications and may have various forms, so specific embodiments are illustrated in the accompanying drawings and described in detail in this specification. However, it should be understood that this does not limit the present invention to a specific disclosure method, but includes all modifications, equivalent technical solutions and alternative solutions included in the concept and technical scope of the present invention. When describing the drawings, similar components are marked with similar reference numerals.

[0033] The terms used in this application are only used to illustrate specific embodiments and are not intended to limit the present invention. Unless the context clearly indicates a different meaning, a singular expression includes a plural expression. In this application, terms such as "including" or "having" are used to specify the existence of features, steps, actions, constituent elements, parts, or combinations thereof recorded in the specification, and shall not be understood as excluding in advance the existence or additional possibility of one or more other features or steps, actions, constituent elements, parts, or combinations thereof.

[0034] Unless otherwise defined, all terms used in this application, including technical and scientific terms, have the same meaning as those generally understood by those skilled in the art to which the present invention belongs. Terms defined in commonly used dictionaries should be interpreted as having the same meaning as that in the context of the relevant technology, and, unless explicitly defined in this application, should not be interpreted in an ideal or overly chemical sense.

[0035] The novel compound of the present invention and the MRI contrast agent comprising the same are described in more detail below through specific examples and experimental examples. However, the embodiments of the present invention are only some embodiments of the present invention, and the scope of the present invention is not limited to the following embodiments.

[0036] Figure 1 1 is a diagram for illustrating a novel compound according to an embodiment of the present invention, a method for producing the same, and an MRI contrast agent comprising the same. Figure 1 The novel compounds of the present invention and examples thereof are described.

[0037] Example

[0038] Compound 1 (2-bromoglutaric acid)

[0039] L-Glutamic acid (10 g, 67.9 mmol) and NaBr (24.40 g, 237 mmol) were dissolved in 2N HBr solution. NaNO2 (8.485 g, 123 mmol) was slowly added to the solution in small portions as a solid at 0°C over 1 hour. After 2 hours and 30 minutes, concentrated sulfuric acid was slowly added dropwise to the yellow mixture at room temperature, and the orange-brown solution was stirred for 20 minutes. The solution was extracted with diethyl ether (4×100 mL), and the collected organic layer was extracted with brine (2×100 mL) and dried over Na2SO4. Then, the solvent was removed under reduced pressure, and compound 1 was obtained without further purification. Yield: 36%.

[0040] Compound 2 (Diethyl-2-bromopentanedioate)

[0041] The solution of compound 1 prepared above (5.14g, 24.48mmol) was dissolved in EtOH (200mL, excessive). At 0°C, thionyl chloride (3.55mL) was slowly added dropwise to the solution. The light yellow solution was stirred at room temperature for 2 days. The solution was evaporated, and the oil obtained was dissolved in DCM (100mL). The mixture was extracted with 5% NaHCO (4×100mL), and the organic layer collected was extracted with brine (2×100mL), and dehydrated with Na2SO4. The solvent was removed under reduced pressure. Then, the product obtained by column chromatography was purified using petroleum ether and ethyl acetate to obtain compound 2. Yield: 49.2%.

[0042] Compound 3 (3,6,9,15-Tetraazabicyclo[9,3,1]pentadeca-1(15),11,13-triene)

[0043] Compound 3 was used and provided by ACG-PHARM.

[0044] Compound 4 (Hexaethyl 2,2',2"-(3,6,9-triaza-1(2,6)-pyridinacyclodecaphane-3,6,9-triyl)trigluatrate)

[0045] A solution of compound 2 (5.98 g, 22.47 mmol) of ACN (acetonitrile) was added together with K2CO3 (4.12 g, 29.88 mmol) to a solution of compound 3 (0.77 g, 3.735 mmol) of ACN and the mixed solution prepared was refluxed at a temperature of 65°C for 24 hours. Then, K2CO3 was removed using a paper filter. After the filtered solvent was evaporated with an evaporator, the concentrated solution was added to ethyl acetate (100 mL) and extracted with 0.1 M HCl (4×100 mL). The collected aqueous layer was added to 5% NaHCO3 and the pH was adjusted to 7 to 8 in an ice bath. The solution was then extracted with DCM (3×400 mL) and the organic layer was dried with Na2SO4. The solvent was then evaporated and compound 4 was obtained without further purification. Yield: 65%.

[0046] Compound 5 (2,2',2"-(3,6,9-triaza-1(2,6)-pyridinylcyclodecaphane-3,6,9-triyl)triglutaric acid)

[0047] Compound 4 prepared above was dissolved in EtOH and added to 5M NaOH. Then, refluxed at 80°C for 23 hours. The solvent was evaporated and the pH of the mixed solution was adjusted to 7 using HCl (conc HCL) at 0°C. The product was then purified by ion chromatography, eluent and ACN under unbuffered conditions. After syringe filtration, the solvent was blown off and freeze-dried to obtain yellow compound 5 without further purification. Yield: 69%

[0048] Compound 6 (GdL)

[0049] Compound 5 (0.51 g, 0.855 mmol) obtained above was dissolved in HPLC water and adjusted to pH 7 with 1 M NaOH. Then, the GdCl dissolved in water was slowly added dropwise to the solution. Then, 1 M NaOH was used to adjust the solution to pH 7, and stirred at room temperature for 24 hours. Then, the dark yellow solution was filtered through paper. The product obtained by semi-preparative liquid chromatography (prep HPLC) purification was used under the following conditions, i.e., Hydrosphere C18 column, elution (flow velocity: 8 mL / min), neutral water, neutral CAN conditions:

[0050] 0 min 5% solvent B, 3 min 40% solvent B, 28 min 80% solvent B, 31 min 100% solvent B, 34 min 100% solvent B, 37 min 5% solvent B.

[0051] Then, after syringe filtration, the product solvent was evaporated and lyophilized to give compound 6 (GdL) of the present invention.

[0052] Compound 7 (Gd-PCTA-Ach)

[0053] Compound 6 (1 g, 1.331 mmol) obtained above was dissolved in HPLC water. HOBt (0.359 g, 2.662 mmol) dissolved in dioxane and EDC·HCl (1.27 g, 6.655 mmol) dissolved in water were slowly added dropwise in sequence and stirred for 10 minutes. 2-Aminocyclohexanol (0.91 g, 7.986 mmol) dissolved in water was slowly added dropwise, the pH was adjusted to 6 with 1 M HCl, and stirred at room temperature for 24 hours. Then, the mixed solution was filtered through paper. The product obtained was purified by semi-preparative liquid chromatography (prep HPLC) using a Triart C18 column in the next 2 steps.

[0054] First, elution (flow rate: 12 mL / min) with water, MeOH conditions were as follows: 0 min 0% solvent B, 5 min 0% solvent B, 60 min 90% solvent B, 70 min 90% solvent B, 75 min 0% solvent B, second elution (flow rate: 12 mL / min), ACN conditions were as follows: 0 min 0% solvent B, 5 min 0% solvent B, 60 min 90% solvent B, 70 min 90% solvent B, 75 min 0% solvent B.

[0055] Then, after syringe filtration, the product solvent was evaporated and freeze-dried to obtain the compound Gd-PCTA-Ach of the present invention. Yield: 10%.

[0056] Comparative Example

[0057] In order to compare and evaluate the performance of Gd-PCTA-Ach of the present invention, commercially available contrast agents were used. (Gd-DOTA), (Gd-HP-DO3A), (Gd-DTPA), (Gd-EOB-DTPA), (Gd-BOPTA), (Gd-DO3A-buttrol) and Gadopiclenol were used as comparative examples.

[0058] Figure 2 to Figure 1 1 is a diagram showing the results of various experimental examples of the present invention. Figure 2 to Figure 1 1. The characteristics of the novel compound of the present invention and the effect as an MRI contrast agent are described.

[0059] Experimental example

[0060] Experimental Example 1 Relaxivity and HSA Combination Evaluation

[0061] The relaxivity (r1 and r2), hydrophilicity (Log P) and HSA binding affinity of the compound Gd-PCTA-Ach of the present invention and commercially available contrast agents were compared and evaluated. The relaxivity (r1 and r2) was measured in water and HSA at 3.0T and 9.4T magnetic fields, respectively. The HSA binding affinity was measured using ultrafiltration analysis. The measurement results are summarized in Table 1 below.

[0062]

Table 1

[0063]

[0064] Referring to Table 1, the Gd-PCTA-Ach of the present invention has higher relaxation rates (r1 and r2) than commercially available contrast agents under all conditions.

[0065] The Log P value is a value for evaluating hydrophilicity. If the P value is less than 1, the Log P value becomes negative, indicating hydrophilicity, and if the P value is greater than 1, the Log P value becomes positive, indicating lipophilicity. Since the Log P value is -1.0, which is negative, it is confirmed that the Gd-PCTA-Ach of the present invention has hydrophilicity.

[0066] In addition, the binding percentage value of Gd-PCTA-Ach was shown to be 3 times higher than that of Gd-BOPTA and Gd-EOB-DTPA. Based on the hydrophilicity results, the log P value indicates a strong interaction with blood proteins such as HSA, which is supported by the HSA binding analysis data. As a result, it can be judged that Gd-PCTA-Ach stays in the blood for a long time based on the high HSA binding value of 30. In the HSA binding analysis, Gd-PCTA-Ach may have a longer blood residual half-life, but whether there is a greater interaction in HSA or transport protein in hepatocytes, actual hepatocyte accumulation in vivo needs to be investigated. Additional data on stem cell accumulation was demonstrated by in vivo MRI experiments.

[0067] Experimental Example 2: Stability Evaluation

[0068] (1) Kinetic stability evaluation

[0069] Kinetic stability is an important factor in understanding the ligand-bound Gd 3+ The exchange rate experiment with zinc, which is abundant in the human body, shows that free Gd replaced by zinc 3+ (Free Gd 3+ ) is toxic and therefore may be harmful to the human body. Therefore, it is important not to exchange for a long time. In the kinetic stability experiment, commercial contrast agents (Gd-DOTA, Gd-HP-DO3A, Gd-DTPA, Gd-EOB-DTPA, Gd-BOPTA, Gd-DO3A-buttrol) were compared with two concentrations of Gd-PCTA-Ach (1.5mM, 1mM), and the results are shown in Figure 2 .

[0070] refer to Figure 2 , showing that Gd in the drug 3+ The change of metal exchange degree with zinc over time. The results of 72-hour follow-up observation showed that Gd-PCTA-Ach showed a similar trend to Gd-DOTA, Gd-HP-DO3A, and Gd-DO3A-buttrol, and was higher than Gd-DTPA, Gd-EOB-DTPA, and Gd-BOPTA.

[0071] (2) pH stability evaluation

[0072] The pH stability test is an experiment to confirm the stability of the drug at each pH. The pH value of the human body is usually maintained at about 7.4, but since the pH value of each part is slightly different, it is important to confirm the stability at each pH value. In the pH stability test, the stability is confirmed at pH 1, 4, 7, and 10 for 72 hours in the same manner as the kinetic stability evaluation. The results are shown in Figure 3.

[0073] With reference to Fig. 3, it can be confirmed that the pH value remains constant within 72 hours. Although this value is different according to each pH, ​​it is observed to be stable, and the Gd-PCTA-Ach of the present invention shows that the higher the pH is, the higher the stability is, and, when the pH is more than 7, it shows a lower stability than the commercially available contrast agent Gd-DOTA.

[0074] Experimental Example 3 Evaluation of other chemical properties

[0075] (1) Whether there is free Gd 3+ (Free Gd 3+ )'s review

[0076] Due to free Gd 3+ Therefore, experiments were performed to determine whether free Gd existed in the synthesized Gd-PCTA-Ach. 3 + The free Gd was confirmed by mapping with the dye Arsenazo III. 3+ The existence of Figure 4 .

[0077] refer to Figure 4 The Gd-PCTA-Ach of the present invention reacts with Arsenazo III and free Gd 3+ Different from the above, the color was purple and red, so it was confirmed that there was no free Gd 3+ .

[0078] (2) Absorption and fluorescence evaluation

[0079] Experiments were conducted to determine the absorption and emission wavelengths of the Gd-PCTA-Ach synthesized by the present invention. The concentrations of Gd-PCTA-Ach were 1 mM and 0.5 mM, respectively, and the results are shown in Figure 5 .

[0080] refer to Figure 5 The absorption wavelength is highest at 270nm and the emission wavelength is highest at 315nm.

[0081] Experimental Example 4 Cytotoxicity

[0082] Figure 6The results of the cytotoxicity experiments of Gd-PCTA-Ach and Gd-DO3A-buttrol in mouse (A) liver cells (AML-12), (B) brain cells (C8-D1A), and (C) kidney cells (Hek-293) are shown. Gd-DO3A-buttrol was used as the positive group, and the cells were incubated with the drug for 24 hours.

[0083] refer to Figure 6 When the Gd-PCTA-Ach of the present invention and Gd-DO3A-butol were compared, it was confirmed that the Gd-PCTA-Ach of the present invention did not have the cytotoxicity as the commercially available Gd-DO3A-butol.

[0084] Experimental Example 5 Biodistribution Evaluation

[0085] In order to confirm the biodistribution, the compound of the present invention (Gd-PCTA-Ach) was intravenously injected into normal mice, and the organs in which the compound was detected were confirmed by ICP after 15 minutes, 30 minutes, 2 hours, and 24 hours.

[0086] Figure 7 The content of Gd in each organ is shown. Among the organs, the intensity of liver and kidney is higher, confirming that Gd-PCTA-Ach flows into the liver. In addition, it is also confirmed in gallbladder (GB) and blood vessels (Blood). According to these results, it is shown that the present invention has a characteristic similar to the commercially available contrast agent Gd-BOPTA used as a hepatobiliary specific contrast agent.

[0087] Experimental Example 6 Image Evaluation

[0088] After preparing a brain cancer model using C6 glioma of brain cancer cells, 0.1 mmol / kg of Gd-PCTA-Ach, 0.05 mmol / kg of Gd-PCTA-Ach, and 0.1 mmol / kg of Gd-DO3A-buttrol were injected respectively to obtain (a) MRI images and (b) CNR graphs based on the MRI images. The results are shown in Figure 8.

[0089] Referring to Figure 8, it is observed that (a) the brain cancer area appears brighter under 0.1mmol / kg of Gd-PCTA-Ach of the present invention than under 0.1mmol / kg of Gd-DO3A-butrol. In addition, 0.1mmol / kg of Gd-DO3A-buttrol shows a brightness similar to that of 0.05mmol.kg of Gd-PCTA-Ach with a concentration halved. Referring to (b), it can be seen that the CNR changes of 0.1mmol / kg of Gd-DO3A-buttrol and 0.05mmol / kg of Gd-PCTA-Ach are almost similar. Therefore, it can be seen that when using the Gd-PCTA-Ach of the present invention, images of similar brightness can be provided even at a lower concentration than the commercially available contrast agent Gd-DO3A-butol.

[0090] 9 is an (a) MR image and (b) CNR chart of each contrast agent flowing into the liver of a normal mouse at 3.0 T for comparison between Gd-PCTA-Ach and commercially available contrast agents (Gd-BOPTA, GD-EOB-DTPA) according to an embodiment of the present invention.

[0091] Referring to Figure 9, liver parenchyma was observed 5 minutes after all three MR contrast agents were injected, and a slow decrease was observed. On the one hand, the observation of gallbladder was slightly different. In the case of Gd-BOPTA and Gd-EOB-DTPA, CA was observed to increase initially and then slowly decrease, while in the case of Gd-PCTA-Ach, CA was observed to gradually increase from 5 minutes to 120 minutes. All three MR CAs were confirmed to be cleared 24 hours after intravascular injection. Compared with other drugs, Gd-PCTA-Ach uniquely exhibits a temporary blood enhancement compared with other agents, and the following results show that the enhancement effect of Gd-PCTA-Ach entering the liver is slightly lower than that of Gd-BOPTA and Gd-EOB-DTPA.

[0092] 10 shows images of normal mice treated with Gd-PCTA-Ach at (a) 3.0-T and (b) 9.4-T according to an embodiment of the present invention. The mice were intravenously injected with 0.1 mmol / kg of Gd-PCTA-Ach.

[0093] Referring to FIG. 10 , it is well known that the relaxivity decreases as the MHz increases. From the MR image pattern of the Gd-PCTA-Ach of the present invention according to the change of the magnetic field (3.0T (64MHz) -> 9.4T (400MHz)), it can be confirmed that the relaxivity r1 and r2 of the Gd-PCTA-Ach decrease as the magnetic field change increases. Therefore, the improvement in contrast indicates that the image quality at 3T is brighter than that at 9.4T.

[0094] Figure 11 shows (a, c) 3.0-TMRI results of liver cancer mice analyzed using Gd-PCTA-Ach according to an embodiment of the present invention, and (b) CNR distribution for analyzing MRI results. The HepG2 cell line was injected into orthotopic HCC mice and allowed to proliferate until the tumor size was large enough. After tumor formation, HCC experimental mice were intravenously injected with 0.1mmol / kg of Gd-PCTA-Ach.

[0095] Referring to Figure 11, T2-weighted images were used to confirm the location of the tumor before Gd-PCTA-Ach injection. No clear tumor was seen on the T1-weighted images before injection (a). In liver cancer, 5 minutes after the injection of Gd-PCTA-Ach, not only did the boundary between the normal group and the tumor group become clear, but the tumor itself was also slightly enhanced and then gradually shrank (A and c). HCC is known to promote angiogenic tumors. It can be assumed that Gd-PCTA-Ach enters the blood vessels of the tumor and shows contrast enhancement between tumors. As shown in (b), the contrast effect of Gd-PCTA-Ach showed a significant improvement at 5 minutes and then gradually decreased.

[0096] Although the present invention has been described above with reference to preferred embodiments thereof, it will be appreciated by those skilled in the art that various modifications and variations may be made to the present invention without departing from the spirit and scope of the invention as described in the appended claims.

Claims

1. A compound, characterized in that It is represented by the following formula 1: [Chemical formula 1] In the chemical formula 1, R represents one selected from an alicyclic compound or an aromatic ring compound.

2. The compound according to claim 1, characterized in that In the chemical formula 1, R is an alicyclic compound, The alicyclic compound is one selected from cyclohexane or cyclopentane.

3. The compound according to claim 2, characterized in that The compound is represented by the following formula 1-1. [Chemical formula 1-1] 4. The compound according to claim 1, characterized in that The compounds specifically target the liver. 5 . An MRI contrast agent comprising the compound according to claim 1 .

6. The MRI contrast agent according to claim 5, characterized in that The MRI contrast agent is used to diagnose liver metastasis of cancer, liver cysts, liver cancer or bile duct obstruction.

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