A compound targeting chemokine receptor 4 and use thereof

Abstract

The present application relates to the technical field of pharmaceutical chemistry, and particularly relates to a compound targeting chemokine receptor 4 and application thereof.The chemical structural formula of the compound is shown as formula I.The present application provides a novel compound targeting chemokine receptor 4, which has high affinity to CXCR4, and obvious tumor uptake; compared with existing compounds, the compound can effectively prolong the residence time in vivo.The compound can be used as a drug after being labeled with a radionuclide, and is used for diagnosing CXCR4-positive tumor-related diseases.The compound targeting chemokine receptor 4 provided by the present application has important value in the fields of diagnosis and prevention and treatment of CXCR4-positive tumor-related diseases.

Description

Technical Field

[0001] The present invention relates to the technical field of medicinal chemistry, and in particular to a compound targeting chemokine receptor 4 and application thereof. Background Art

[0002] Radiopharmaceutical research has received increasing attention in the scientific research field in recent years. Its core mechanism is generally to give it diagnostic or therapeutic functions by introducing specific targeting groups or fragments containing radionuclides.

[0003] Currently, a large number of molecules have been designed for targets such as prostate-specific membrane antigen (PSMA) and fibroblast activation protein inhibitor (FAPI). Researchers have selected several radiopharmaceuticals, such as PSMA-617 and FAPI-04, with excellent target specificity and a high tumor-to-nontarget ratio. However, the development of radiopharmaceuticals targeting chemokine receptor 4 (CXCR4) remains relatively slow. Currently, only two or three radiopharmaceuticals based on structures such as Pentixafor and Pentixather have entered clinical trials. Apart from Pentixafor and Pentixather, no other radiopharmaceuticals have entered clinical trials. Only a few have demonstrated promising animal imaging results in preclinical studies. For example, molecules BL08 and BL09, developed based on the LY2510924 structure, are currently under investigation.

[0004] Therefore, there is an urgent need to develop more molecular structures targeting CXCR4, which will help to promote the marketing of radiopharmaceuticals targeting CXCR4 more quickly. Summary of the Invention

[0005] In order to solve the problems existing in the prior art, the present invention provides a compound targeting chemokine receptor 4 and its application.

[0006] In a first aspect, the present invention provides a compound or a pharmaceutically acceptable salt thereof (referred to as DOTA-HTA-741), wherein the chemical structure of the compound is shown in Formula I:

[0007] .

[0008] The compound provided by the present invention is a dimer based on the monomer H-Gly-Arg-Ala-DCys-Arg-2Nal-His-Pen-OH. H-Gly-Arg-Ala-DCys-Arg-2Nal-His-Pen-OH is a CXCR4 antagonist with the ability to target CXCR4. However, it has a short retention time in vivo. According to the metabolism of the drug by the organism, after the drug enters the body, the uptake of the liver or kidney will experience a peak value and then gradually decrease. However, the one-hour data of existing research show that the amount of liver uptake and kidney uptake is very low, that is, the peak values ​​of the liver and kidney are within one hour, indicating that the drug has been substantially metabolized in less than one hour after injection. Obviously, if it is prepared into a PET probe, it is necessary to complete the detection within one hour, which is extremely difficult to achieve in practical applications.

[0009] The present invention, based on a specific linker site, designed and synthesized a dimer compound of H-Gly-Arg-Ala-DCys-Arg-2Nal-His-Pen-OH. Experimental data confirmed that the compound remained metabolized and significantly uptaken by tumors after 240 minutes, ensuring sufficient imaging time after drug injection. Furthermore, the resulting dimer compound exhibited excellent affinity, effectively targeting CXCR4.

[0010] In a second aspect, the present invention provides a compound or a pharmaceutically acceptable salt thereof, wherein the compound has the following structure: H-Gly-Arg-Ala-DCys-Arg-2Nal-His-Pen-OH.

[0011] In a third aspect, the present invention provides a method for preparing the aforementioned compound, comprising:

[0012]

[0013] (1) H-Gly-Arg-Ala-DCys-Arg-2Nal-His-Pen-OH undergoes oxidation reaction to form a disulfide bond between Gly and Pen to obtain compound 2;

[0014] (2) Compound 2 and compound 3 undergo dimerization reaction to obtain compound 4;

[0015] (3) Compound 4 and compound 5 undergo amidation reaction to obtain compound 6;

[0016] (4) Compound 6 and compound 7 are subjected to amidation reaction to obtain the compound shown in formula I.

[0017] Furthermore, the above oxidation reaction uses ACN solution as solvent and adds NaHCO3 to react.

[0018] Furthermore, the dimerization reaction and the amidation reaction are carried out using DMF as solvent.

[0019] Furthermore, the dimerization reaction is as follows: compound 3 is first reacted with DCC and HOSu for 5 to 7 hours, compound 2 and DIEA are then added to react for 2 to 4 hours, TFA is then added to react for 5 to 10 minutes, and ether is then added to precipitate a solid, and finally the solid is purified by centrifugation, drying, and reverse phase preparative liquid phase.

[0020] Furthermore, (3) is that compound 5 is first reacted with DCC and HOSu for 5-7 hours, then compound 4 and DIEA are added to react for 2-4 hours, then TFA is added to react for 5-10 minutes, and then ether is added to precipitate the solid, and finally the solid is purified by centrifugation, drying, and reverse phase preparative liquid phase.

[0021] Furthermore, (4) is that compound 7 is first reacted with DCC and HOSu for 5-7 hours, then compound 6 and DIEA are added to react for 2-4 hours, then TFA is added to react for 5-10 minutes, and then ether is added to precipitate the solid, and finally the solid is purified by centrifugation, drying, and reverse phase preparative liquid phase.

[0022] Furthermore, the molar ratio of compound 2, compound 3, DCC, HOSu and DIEA in (2) is (2~4):1:(2~4):(2~4):(5~8).

[0023] Furthermore, the molar ratio of compound 4, compound 5, DCC, HOSu and DIEA in (3) is 1:(1.5~3):(1.5~4):(1.5~4):(2~5).

[0024] Furthermore, the molar ratio of compound 6, compound 7, DCC, HOSu and DIEA in (4) is 1: (1.5~3): (1.5~4): (1.5~4): (2~5).

[0025] In a fourth aspect, the present invention provides a drug comprising the aforementioned compound or a pharmaceutically acceptable salt thereof.

[0026] Furthermore, it also includes: a radioactive nuclide that forms a complex with the aforementioned compound, preferably Ga-68.

[0027] Furthermore, the drug is a diagnostic reagent or a preventive and therapeutic drug for CXCR4-positive tumor diseases.

[0028] In a fifth aspect, the present invention provides use of the aforementioned compound or a pharmaceutically acceptable salt thereof in targeting chemokine receptor 4 or in the preparation of a drug for targeting chemokine receptor 4.

[0029] In a sixth aspect, the present invention provides use of the aforementioned compound or a pharmaceutically acceptable salt thereof in the preparation of a medicament for diagnosing or preventing or treating CXCR4-positive tumor diseases.

[0030] Furthermore, the CXCR4-positive tumor disease includes one or more of: multiple myeloma, non-Hodgkin's lymphoma, acute myeloid leukemia, chronic lymphocytic leukemia, breast cancer, prostate cancer, lung cancer, gastric cancer, pancreatic cancer, colorectal cancer, glioma, esophageal cancer or neuroendocrine tumors.

[0031] The present invention has the following beneficial effects:

[0032] The present invention synthesizes a compound molecule DOTA-HTA-741 with a new structure targeting CXCR4, which has a high affinity for CXCR4. The molecule obtained by radioactive nucleic acid labeling of the compound molecule [ 68 Ga]DOTA-HTA-741 has high stability, reaching a radiochemical purity of more than 98% (without purification) and still more than 95% radiochemical purity after 3 hours.

[0033] The present invention provides 68 Ga]DOTA-HTA-741 can be used in PET / CT imaging, and tumor uptake is obvious, so it can be used for the diagnosis of CXCR4-positive tumor-related diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] In order to more clearly illustrate the technical solutions in the present invention or the prior art, a brief introduction is given below to the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0035] Figure 1 This is a synthetic route for compound 1 (H-Gly-Arg-Ala-DCys-Arg-2Nal-His-Pen-OH) provided in Example 1 of the present invention.

[0036] Figure 2 This is a synthetic route for the compound DOTA-HTA-741 provided in Example 1 of the present invention.

[0037] Figure 3 This is the high performance liquid chromatography (HPLC) data of DOTA-HTA-741 provided in Example 1 of the present invention.

[0038] Figure 4This is the low-resolution mass spectrum (ESI) of DOTA-HTA-741 provided in Example 1 of the present invention.

[0039] Figure 5 This is the high-resolution mass spectrum (ESI) of DOTA-HTA-741 provided in Example 1 of the present invention.

[0040] Figure 6 The embodiment of the present invention provides [ 68 Ga]DOTA-HTA-741 ITLC data.

[0041] Figure 7 The embodiment of the present invention provides [ 68 In vitro stability data of [Ga]DOTA-HTA-741 (0 h).

[0042] Figure 8 The embodiment of the present invention provides [ 68 In vitro stability data of [Ga]DOTA-HTA-741 (3 h).

[0043] Figure 9 This is the PET / CT imaging of mice 2 hours after administration provided in Example 2 of the present invention.

[0044] Figure 10 The DOTA-HTA-741 provided in Example 2 of the present invention is blocked and then injected [ 68 PET / CT imaging of mice with [Ga]DOTA-HTA-741.

[0045] Figure 11 This is the PET / CT imaging of mice 4 hours after administration provided in Example 2 of the present invention. DETAILED DESCRIPTION

[0046] To make the objectives, technical solutions, and advantages of the present invention more clear, the technical solutions of the present invention will be clearly and completely described below in conjunction with the accompanying drawings. Obviously, the embodiments described are only some of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts shall fall within the scope of protection of the present invention.

[0047] Unless otherwise specified, the experimental methods involved in the following examples are all conventional methods in the art. For example, reference can be made to experimental manuals in the art, or the conditions recommended by the manufacturer's instructions.

[0048] Unless otherwise specified, the experimental materials and reagents involved in the following examples can be obtained from commercial sources.

[0049] In the following examples, the "(eq)" after a compound refers to the equivalent level (in mol) of the compound used relative to the reactant, i.e., (1 eq) means 1 mol of reactant corresponds to 1 mol of the compound, and (3 eq) means 1 mol of reactant corresponds to 3 mol of the compound.

[0050] Example 1 Synthesis and characterization of compounds

[0051] 1. Synthesis of Compound 1

[0052] like Figure 1 As shown, Fmoc-Pen(Trt)-OH was first attached to CTC resin under alkaline conditions. Fmoc-His(Trt)-OH, Fmoc-2Nal-OH, Fmoc-Arg(Pbf)-OH, Fmoc-DCys(Trt)-OH, Fmoc-Arg(Pbf)-OH, Fmoc-Ala-OH, Fmoc-Arg(Pbf)-OH, and Fmoc-Gly-OH were then coupled sequentially. All amino acid couplings were performed in DMF using DIC (3 eq) and HOBt (3 eq) as coupling reagents, with Fmoc as the protecting group. The coupling was cleaved using a 20% Pip / DMF solution. Finally, the peptide was cleaved from the resin using TFA at room temperature for 2 h to obtain the crude peptide compound 1. The crude peptide was then purified by HPLC on a C18 preparative column to obtain pure compound 1 (yield: 25.7%).

[0053] 2. Synthesis of the molecule DOTA-HTA-741

[0054] like Figure 2 As shown, the synthesis of the molecule DOTA-HTA-741 includes the following process:

[0055] (1) Synthesis of compound 2

[0056] Compound 1 (1 eq) was dissolved in 2.2 L ACN / H2O (volume ratio 1:1), 1 M NaHCO3 solution (22 mL) was added, and the mixture was stirred at room temperature overnight. The reaction solution was directly used to prepare compound 2 (yield: 62%).

[0057] (2) Synthesis of compound 4

[0058] Compound 3 (1 eq) was dissolved in 20 mL of DMF, and DCC (2.5 eq) and HOSu (2.5 eq, 158 mg) were added. The reaction was carried out at room temperature for 6 h. Compound 2 (2.4 eq) and DIEA (6 eq) were then added. The reaction was carried out at room temperature for 2 h. The solvent was dried by spin drying, and 10 mL of TFA was added. The reaction was carried out for 5 min. 50 mL of icy ether was poured into the solution, and a large amount of solid precipitated. The product was centrifuged and dried. The product was purified by reverse phase preparative liquid chromatography to obtain compound 4 (yield: 55%).

[0059] (3) Synthesis of compound 6

[0060] Compound 5 (2 eq) was dissolved in 10 mL DMF, and DCC (2 eq) and HOSu (2 eq) were added and reacted at room temperature for 6 h. Compound 4 (1 eq) and DIEA (3 eq) were then added and reacted at room temperature for 2 h. The solvent was dried by spin drying, and 10 mL TFA was added and reacted for 5 min. 50 mL of icy ether was poured into the solution, and a large amount of solid precipitated. The solution was centrifuged and dried, and purified by reverse phase preparative liquid chromatography to obtain compound 6 (yield: 72%).

[0061] (4) Synthesis of the molecule DOTA-HTA-741 (final product)

[0062] Compound 7 (2 eq) was dissolved in 10 mL DMF, and DCC (2 eq) and HOSu (2 eq) were added and reacted at room temperature for 6 h. Then, compound 6 (1 eq) and DIEA (3 eq) were added and reacted at room temperature for 2 h. The solvent was dried by spin drying, and 10 mL TFA was added and reacted for 5 min. 50 mL of icy ether was poured into the solution, and a large amount of solid precipitated. The solution was centrifuged and dried, and purified by reverse phase preparative liquid chromatography to obtain the molecule: DOTA-HTA-741 (yield: 32%).

[0063] 3. Peptide structure characterization

[0064] 3.1 Purity

[0065] The molecule DOTA-HTA-741 was purified by preparative liquid chromatography followed by lyophilization to obtain a highly pure white powder. The purified molecule was analyzed for purity by high-performance liquid chromatography (HPLC), as shown in Table 1.

[0066] Table 1 HPLC mobile phase composition of DOTA-HTA-741

[0067]

[0068] Through analysis, the HPLC data of the molecule DOTA-HTA-741 were obtained as follows Figure 3 As shown. Figure 3The results show that after purification and freeze-drying, the purity of the molecule DOTA-HTA-741 can reach 99.95%.

[0069] 3.2 Low-resolution mass spectrometry

[0070] As can be seen from Section 3.1, the purity of the molecule DOTA-HTA-741 can reach 99.95%. In order to determine the accuracy of the product structure, the present invention performed ESI low-resolution and high-resolution mass spectrometry detection on the molecule.

[0071] The low-resolution mass spectrometry results of the molecule DOTA-HTA-741 are as follows Figure 4 As shown in the molecular formula, the theoretical average relative molecular mass of the molecule DOTA-HTA-741 is 2661.10, and the theoretical value of its most abundant isotope peak is 2660.20; according to Figure 4 From the data, we can see that the measured value of the most abundant isotope peak of the molecule DOTA-HTA-741 is 2660.8 (1331.3×2-2), which is 0.2% different from the theoretical value, which basically determines the correctness of its structure.

[0072] 3.3 High-resolution mass spectrometry

[0073] In order to further confirm the accuracy of its molecular mass, the present invention conducted a high-resolution mass spectrometry test on this basis. The high-resolution mass spectrometry (ESI) spectrum of the molecule DOTA-HTA-741 is shown in Figure 5 .

[0074] Calculated by Chemdraw software, the theoretical value of the most abundant isotope peak of the molecule DOTA-HTA-741 is 2660.1963, and the actual measured value is 1331.1075×2-2 = 2660.215. The deviation between the measured value and the theoretical value is 0.0007%, which can be used to determine the accuracy of the actual molecule DOTA-HTA-741.

[0075] 4. Ga-68 labeling

[0076] 4.1 Development of labeling methods

[0077] The marking method is as follows:

[0078] (1) Prepare sodium acetate buffer solution (0.25 M, pH 4.5. Preparation method: dissolve 4.1059 g of sodium acetate in 200 mL of deionized water to obtain a 0.25 M sodium acetate aqueous solution; then take 4000 μL of it and add 80 μL of acetic acid to obtain a buffer solution with a pH of 4.5). Take 200 μL and add 60 μL of the reconstituted 5 mg / 2 mL polypeptide aqueous solution;

[0079] (2) Rinse the generator and use a negative pressure bottle to receive68 The GaCl3 eluent was washed for at least 3 minutes to obtain 68 The GaCl3 eluent is about 22MCi (about 1.1mL); dilute it to 0.05M with an equal amount of water (1.1mL);

[0080] (3) Take 800 μL of the diluted eluent and add it to the sodium acetate buffer solution containing the peptide, add a stopper, roll the cap, and measure the activity;

[0081] (4) Open the incubator and control the temperature to 95°C for 10 minutes;

[0082] (5) Cool for 7 minutes;

[0083] (6) Perform HPLC and ITLC (both in test tubes and display tanks) to check for radiochemical purity.

[0084] The HPLC mobile phase composition was 14%-34% of B (acetonitrile) for 20 min. The ITLC developing solvent composition was methanol: 1 M ammonium acetate = 1:1.

[0085] Finally, the Ga-68 labeled molecule was obtained. 68 Ga]DOTA-HTA-741.

[0086] 4.2 ITLC data

[0087] The labeling results can be preliminarily judged by thin layer chromatography: when the ITLC developing solvent is a mixture of methanol and 1M ammonium acetate, the uncomplexed free 68 Ga ions (including 68 Ga ions formed colloid) at the baseline, while 68 Organic compounds that have undergone complexation with Ga ions can diffuse as the developing solvent rises. This study used mixtures of methanol and 1M ammonium acetate at varying concentrations (methanol:1M ammonium acetate = 1:2, 1:1, and 2:1) as developing solvents. Results showed that when the mixed solvent ratio was 1:1, the Rf value of the radioactive complex was approximately 0.4; when the methanol:1M ammonium acetate ratio was 1:2 and 2:1, the Rf value of the radioactive complex was approximately 0.3. Therefore, this study ultimately selected a 1:1 methanol:1M ammonium acetate mixture as the iTLC mobile phase for labeling the product.

[0088] Figure 6 Shows the molecule [ 68 ITLC data of Ga]DOTA-HTA-741. The short peak at 20 μm is the origin, which belongs to the colloidal form. 68 The radioactive peak of Ga. The peak at 60 mm belongs to the product [ 68Ga]DOTA-HTA-741 radioactive peak. According to the integrated data, [ 68 The radiochemical purity (labeling rate) of [Ga]DOTA-HTA-741 was 92.26%. Since the two peaks overlapped to some extent in the figure, HPLC analysis was further performed.

[0089] 4.3hPLC data

[0090] After radioactive labeling, the present invention tested the radiochemical purity of the product by high performance liquid chromatography. The composition of the mobile phase used is shown in Table 2.

[0091] Table 2 68 HPLC mobile phase composition of [Ga]DOTA-HTA-741

[0092]

[0093] molecular[ 68 The HPLC data of Ga]DOTA-HTA-741 showed that the peak with a retention time of 10.96 min was the peak of the labeled product, which also corresponded to the corresponding UV absorption peak in the UV spectrum. The retention time of this peak was also consistent with that of the labeled precursor. The results showed that the radiochemical purity of the product was 97.93%.

[0094] 5. In vitro stability data

[0095] [ 68 The in vitro stability data of [Ga]DOTA-HTA-741 are as follows:

[0096] In terms of in vitro stability, the present invention selected PBS buffer solution as the system for testing radiochemical stability. 68 0.5 mL of Ga]DOTA-HTA-741 was placed in 0.5 mL of phosphate buffer (pH = 7.4) and incubated at 37 o The cells were incubated at 4 °C for 1 h, 2 h, and 3 h, and the radiochemical purity was determined by HPLC to determine the in vitro stability.

[0097] 0h data see Figure 7 When the labeling was completed, the radiochemical purity was 98.72%. Figure 8 As shown in the HPLC data, the radiochemical purity dropped from 98.72% to 94.65% after 3 hours. The impurity with a retention time of 15 minutes increased from 0.58% at 0 hours to 3.7% at 3 hours.

[0098] From the stability data of 0h and 3h, it can be seen that [ 68The stability of Ga]DOTA-HTA-741 can still maintain close to 95% radiochemical purity after 3 h, which fully demonstrates that this compound is stable in PBS buffer in vitro.

[0099] 6. Fat-water partition coefficient

[0100] After obtaining the Ga-68 labeled compound, the present invention tested its lipid-water partition coefficient. The test process is as follows:

[0101] The labeled compound was dissolved in an EP tube (100 μL) using equal volumes (0.5 mL:0.5 mL) of n-octanol (organic phase) and phosphate buffer (aqueous phase, pH 7.4). The mixture was shaken thoroughly for 5 minutes and separated by centrifugation at 2000 rpm for 5 minutes. 200 μL of each of the organic and aqueous phases was transferred to a 1.5 mL EP tube and the radioactivity count rate was measured in a well-type gamma detector. The lipid-water partition coefficient (P) was calculated from the ratio of the radioactivity count rates in the organic and aqueous phases.

[0102] P=log(N o / N aq ).

[0103] Where: N o and N aq are the radioactivity counting rates of the organic and aqueous phase samples, s -1 .

[0104] The fat-water partition coefficient obtained by the above method is shown in the following table:

[0105] Table 3 Calculation results of lipid-water partition coefficient

[0106]

[0107] From the above data on the lipid-water partition coefficient, it can be seen that [ 68 Ga]DOTA-HTA-741 has good water solubility, and its distribution content in the aqueous phase is about twelve times that in the organic phase.

[0108] Example 2

[0109] This example further uses the [ 68 Small animal PET imaging experiments using Ga]DOTA-HTA-741 include the following:

[0110] The present invention will mark the drug [ 68 Ga]DOTA-HTA-741 was diluted with normal saline and administered into B-NDG tumor-bearing mice (Daudi) via tail vein injection. Figure 9This is a PET / CT image taken 2 hours after administration. The image shows that the drug is clearly taken up by the tumor. In another set of experiments, the present invention pre-injected 0.91 mg of DOTA-HTA-741 molecules (dissolved in 100 μl of sodium chloride injection) into mice, and then injected [ 68 Ga]DOTA-HTA-741, PET / CT imaging was performed two hours after injection, and the images obtained were as follows Figure 10 shown. Figure 11 PET / CT images taken 4 hours after drug administration.

[0111] Depend on Figure 9 and Figure 10 It can be seen that after pre-injection of DOTA-HTA-741, [ 68 Ga]DOTA-HTA-741 is almost no longer taken up by tumors in mice. Figure 11 It can be seen that 4 hours after administration, the imaging results are still better.

[0112] The above data and images show that the [ 68 Ga]DOTA-HTA-741 can be used as a drug for diagnosing CXCR4-positive tumors such as multiple myeloma and non-Hodgkin's lymphoma. Its retention time in the body is suitable for imaging examinations.

[0113] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the various embodiments of the present invention.

Claims

1. A compound or a pharmaceutically acceptable salt thereof, characterized in that: The chemical structural formula of the compound is shown in Formula I: Formula I.

2. The method for preparing the compound according to claim 1, characterized in that include: ； (1) The compound with the following structure: H-Gly-Arg-Ala-DCys-Arg-2Nal-His-Pen-OH is subjected to an oxidation reaction to form a disulfide bond between Gly and Pen to obtain compound 2; (2) Compound 2 and compound 3 undergo amidation reaction to obtain compound 4; (3) Compound 4 and compound 5 undergo amidation reaction to obtain compound 6; (4) Compound 6 and Compound 7 are subjected to amidation reaction to obtain the compound according to claim 1.

3. A drug, characterized in that The drug comprises the compound according to claim 1 or a pharmaceutically acceptable salt thereof.

4. The drug according to claim 3, characterized in that Also includes: A radionuclide that forms a complex with the compound of claim 1.

5. The drug according to claim 3, characterized in that The drug is a diagnostic reagent or a preventive and therapeutic drug for CXCR4-positive tumor diseases. 6 . Use of the compound according to claim 1 or a pharmaceutically acceptable salt thereof in the preparation of a medicament for targeting chemokine receptor 4.

7. Use of the compound according to claim 1 or a pharmaceutically acceptable salt thereof in the preparation of a medicament for diagnosing or preventing or treating CXCR4-positive tumor diseases.

8. The use according to claim 7, characterized in that The CXCR4-positive tumor diseases include: one or more of multiple myeloma, non-Hodgkin's lymphoma, acute myeloid leukemia, chronic lymphocytic leukemia, breast cancer, prostate cancer, lung cancer, gastric cancer, pancreatic cancer, colorectal cancer, glioma, esophageal cancer or neuroendocrine tumors.

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