Novel compound as well as preparation method and application thereof in tumor marker detection

Abstract

The invention provides a compound shown as a formula (I), and the compound can be used for recognizing a prostate specific antigen, can efficiently detect prostate cancer, and has a relatively high application value. # imgabs0 #

Description

Technical Field

[0001] The present invention belongs to the field of tumor marker detection, and particularly relates to a novel compound, a preparation method thereof, and an application thereof in tumor marker detection. Background Art

[0002] Prostate cancer is the second most common cancer among men globally and the sixth leading cause of cancer death. Early cancer screening and accurate cancer diagnosis are the keys to cancer prevention and treatment. Among them, prostate-specific antigen (PSA) is a marker for the early diagnosis and monitoring of prostate cancer, and its estimated sensitivity for prostate cancer can reach 0.88. Prostate cancer markers such as complex PSA (cPSA), free PSA (fPSA), and PSA isoform [-2] proprostate-specific antigen (p2PSA) have received increasing attention.

[0003] PSA is a serine protease secreted by prostatic epithelial cells and is a glycoprotein with 237 amino acid residues. Prostate-specific antigen is also a normal component of semen, and its main function is to help hydrolyze and liquefy semen clots, thereby releasing sperm. PSA has become the primary tumor marker for the diagnosis, detection, and prognosis of prostate cancer. The application of comprehensive evaluation criteria such as the Prostate Health Index (PHI) that combines multiple indicators of cPSA, fPSA, and p2PSA has improved the detection rate of prostate cancer. However, PSA is also the only recognized tumor marker with organ specificity, and there are differences in PSA levels among different patients, which can lead to different treatment effects when the same therapeutic drug is used in different patients, making it difficult to treat patients specifically.

[0004] Long-term survival after cancer depends extremely on early detection and treatment. The ability to detect different patterns of protein expression in healthy and abnormal prostate tissues can help classify early prostate changes that may lead to cancer. The ability to detect and quantify the levels of mature prostate-specific antigen more accurately and effectively will contribute to understanding the pathogenesis and prognosis of prostate cancer and help determine the most suitable treatment methods. Currently, there are various PSA detection chips and kits on the market, mostly based on the specific recognition of antigen-antibody. The antibodies are expensive, require low-temperature preservation, and the detection costs are relatively high. At the same time, cPSA, fPSA, and p2PSA have high amino acid sequence homology, and cross-reaction of antibodies is likely to occur when using these chips and kits for detection. PSA has some specific cavities. It is a feasible research route to specifically bind small molecule compounds to the cavities to identify the PSA target of patients and then administer targeted drugs for treatment. Therefore, it is necessary to develop new compounds with high binding affinity for the specific cavities of prostate-specific antigen, so as to detect prostate cancer at low cost and with high efficiency. Summary of the Invention

[0005] To achieve the above object, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof:

[0006]

[0007] Wherein each R1 and R2 is the same or different and independently selected from H, halogen, C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkyl, halo C 1-6 alkoxy, C 3-10 cycloalkyl or C 3-10 cycloalkyloxy;

[0008] R3 and R4 are the same or different and independently selected from H, C 1-6 alkyl or halo C 1-6 alkyl;

[0009] R5 is selected from H;

[0010] R6 and R7 are the same or different and independently selected from H, C 1-6 alkyl or halo C 1-6 alkyl;

[0011] m is selected from 0, 1, 2, 3, 4, 5, 6 or 7;

[0012] n is selected from 0, 1, 2 or 3;

[0013] p is selected from 1, 2, 3, 4, 5, 6, 7 or 8.

[0014] According to an embodiment of the present invention, each of R1 and R2, which are the same or different, is independently selected from H, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, and isopropoxy.

[0015] According to an embodiment of the present invention, R3, R4, and R5, which are the same or different, are independently selected from H, methyl, ethyl, propyl, and isopropyl.

[0016] According to an embodiment of the present invention, each of R6 and R7, which are the same or different, is independently selected from H, methyl, ethyl, propyl, and isopropyl.

[0017] According to an embodiment of the present invention, m is selected from 0, 1, or 2.

[0018] According to an embodiment of the present invention, n is selected from 0 or 1.

[0019] According to an embodiment of the present invention, p is selected from 1, 2, or 3.

[0020] According to an embodiment of the present invention, the present invention provides a compound represented by formula (II):

[0021]

[0022] wherein each of R1 and R2, which are the same or different, is independently selected from H, halogen, C 1-6 alkyl, C 1-6 alkoxy, halo-C 1-6 alkyl, halo-C 1-6 alkoxy, C 3-10 cycloalkyl, or C 3-10 cycloalkyloxy;

[0023] n is selected from 1, 2, or 3.

[0024] According to an embodiment of the present invention, each of R1 and R2, which are the same or different, is independently selected from H, C 1-3 alkoxy, halo-C 1-3 alkoxy, C 3-6 cycloalkyloxy;

[0025] According to an embodiment of the present invention, each of R1 and R2, which are the same or different, is independently selected from H, methyl, ethyl, isopropyl, methoxy, and ethoxy.

[0026] According to an embodiment of the present invention, n is selected from 1 or 2.

[0027] According to an embodiment of the present invention, the compound represented by formula (I) is selected from the structures shown below:

[0028]

[0029] The present invention also provides a method for preparing the compound represented by formula (I), which includes the following steps: reacting compound a with compound b to obtain the compound represented by formula (I);

[0030]

[0031] Wherein, R1, R2, R3, R4, R5, R6, R7, m, n, p independently of one another have the definitions described above; L is selected from leaving groups, such as OH, halogen.

[0032] The present invention also provides the use of the compound represented by formula (I) or a pharmaceutically acceptable salt thereof in identifying prostate specific antigen, and the identification is the specific binding of the compound represented by formula (I) or a pharmaceutically acceptable salt thereof to the cavity in prostate specific antigen.

[0033] According to an embodiment of the present invention, the compound represented by formula (I) or a pharmaceutically acceptable salt thereof can be further introduced with a fluorescent group, such as the Fmoc group.

[0034] The present invention also provides a method for preventing and / or treating prostate cancer, which includes the following steps:

[0035] (1) Using the compound represented by formula (I) or a pharmaceutically acceptable salt thereof to identify the prostate specific antigen of a patient;

[0036] (2) Administering to the patient a prophylactically and / or therapeutically effective amount of an anti-prostate cancer drug according to the identified prostate specific antigen.

[0037] The present invention also provides the use of the compound represented by formula (I) or a pharmaceutically acceptable salt thereof in detecting prostate specific antigen (PSA) or prostate cancer, and the use is not directly aimed at the diagnosis or treatment of a disease.

[0038] The present invention also provides the use of the compound represented by formula (I) or a pharmaceutically acceptable salt thereof in preparing a reagent, protein chip or kit for detecting prostate specific antigen.

[0039] The present invention also provides a method for detecting prostate specific antigen, which includes:

[0040] (a) Under conditions sufficient to cause an antibody / antigen binding reaction, contacting the prostate specific antigen with the compound represented by formula (I) or a pharmaceutically acceptable salt thereof to obtain a PSA-Drug complex; and

[0041] (b) Detecting the presence of the PSA-Drug complex, and the presence of the PSA-Drug complex indicates the presence of the prostate specific antigen in the test sample;

[0042] The method is not directly aimed at the diagnosis or treatment of diseases.

[0043] According to an embodiment of the present invention, the presence of the prostate-specific antigen indicates the presence of prostate cancer.

[0044] The present invention also provides a reagent comprising the compound represented by formula (I) or a pharmaceutically acceptable salt thereof.

[0045] The present invention also provides a protein chip comprising the compound represented by formula (I) or a pharmaceutically acceptable salt thereof.

[0046] According to an embodiment of the present invention, the chip is composed of a substrate and a protein detection index and a control detection index coating distributed in an array on the substrate. The protein detection index includes the PSA tumor marker and is fixed on the substrate by covalent or non-covalent bonds.

[0047] The present invention also provides a kit comprising the compound represented by formula (I) or a pharmaceutically acceptable salt thereof.

[0048] The kit according to the present invention is characterized in that the kit includes a chip, a standard product and a quality control product.

[0049] In the kit according to the present invention, the chip comprises the compound represented by formula (I) or a pharmaceutically acceptable salt thereof.

[0050] According to an embodiment of the present invention, the reagent, chip or kit further comprises a pharmaceutically acceptable carrier or excipient.

[0051] According to an embodiment of the present invention, the reagent, chip or kit further comprises at least one of a buffer, a stabilizer or a diluent.

[0052] Beneficial effects

[0053] The conventional antibody-based detection method for prostate cancer has problems such as the need for low temperature, high cost, and possible cross-reaction with antibodies. By analyzing the protein structure of PSA, analyzing the residue characteristics of the PSA binding cavity, the inventors screened out a compound with a high binding affinity for a specific cavity of prostate-specific antigen, and the compound has a small molecular weight. This compound can be used to identify prostate-specific antigen and for the prevention and / or treatment of prostate cancer.

[0054] At the same time, the fluorescence labeling group used in the antibody detection of PSA and the detection using streptavidin, biotin and colloidal gold as a combination will further increase the detection cost of PSA. The compound designed by the present invention can introduce fluorescent groups such as Fmoc in the further modification process to achieve low-cost and efficient detection of prostate cancer, and has high application value. Brief description of the drawings

[0055] Figure 1 For compound 1's 1 H NMR.

[0056] Figure 2 For compound 2's 1 H NMR.

[0057] Figure 3 Is the interaction map of compound 1 with the protein. The white part on the left indicates that the protein wraps compound 1, and the right side shows the amino acid residues and their numbers where compound 1 interacts with the protein.

[0058] Figure 4 Is the interaction map of compound 2 with the protein. The white part on the left indicates that the protein wraps compound 2, and the right side shows the amino acid residues and their numbers where compound 2 interacts with the protein.

[0059] Figure 5 Is the surface plasmon resonance SPR experiment to test the binding affinity of the compound with PSA and the fitting curves: (a) and (c) are respectively the binding affinity test results and fitting curves of compound 1; (b) and (d) are respectively the binding affinity test results and fitting curves of compound 2.

[0060] Figure 6 Is the microscale thermophoresis experiment to test the binding affinity of the compound with PSA and the fitting curves: (a) and (c) are respectively the binding affinity test results and fitting curves of compound 1; (b) and (d) are respectively the binding affinity test results and fitting curves of compound 2.

[0061] Term Definitions and Explanations

[0062] Unless otherwise specified, the definitions of groups and terms recorded in the specification and claims of this application, including their definitions as examples, exemplary definitions, preferred definitions, definitions recorded in tables, definitions of specific compounds in the examples, etc., can be combined and combined with each other arbitrarily. The group definitions and compound structures after such combinations and combinations should be understood to be within the scope recorded in the specification and / or claims of this application.

[0063] The term "C 1-6"Alkyl" refers to straight-chain and branched-chain saturated hydrocarbon groups having 1, 2, 3, 4, 5 or 6 carbon atoms. Examples of said alkyl groups are methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neopentyl, 1,1-dimethylpropyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 2-ethylbutyl, 1-ethylbutyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 2,3-dimethylbutyl, 1,3-dimethylbutyl or 1,2-dimethylbutyl, etc., or their isomers.

[0064] The term "C 3-10 Cycloalkyl" refers to saturated monovalent monocyclic, bicyclic (such as fused rings, bridged rings, spiro rings) hydrocarbon rings or tricyclic alkanes having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms. The C 3-10 Cycloalkyl includes C 3-8 Cycloalkyl, C 3-5 Cycloalkyl, C 6-8 Cycloalkyl, C 3-4 Cycloalkyl, C 5-6 Cycloalkyl, C6 cycloalkyl, etc. The C 3-10 Cycloalkyl can be a monocyclic hydrocarbon group, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl or cyclodecyl, or a bicyclic hydrocarbon group such as bornyl, indolyl, hexahydroindolyl, tetrahydronaphthyl, decahydronaphthyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.1]heptenyl, 6,6-dimethylbicyclo[3.1.1]heptyl, 2,6,6-trimethylbicyclo[3.1.1]heptyl, bicyclo[2.2.2]octyl, 2,7-diazaspiro[3,5]nonyl, 2,6-diazaspiro[3,4]octyl, or a tricyclic hydrocarbon group such as adamantyl.

[0065] The term "C 1-6 Alkoxy" refers to the group -O-R X , where R X is an alkyl group as defined above.

[0066] The term "halogen" or "hal" refers to fluorine, chlorine, bromine and iodine.

[0067] Those skilled in the art can understand that the compounds shown in formula (I) can exist in the form of various pharmaceutically acceptable salts. If these compounds have a basic center, they can form acid addition salts; if these compounds have an acidic center, they can form base addition salts; if these compounds contain both an acidic center (such as a carboxyl group) and a basic center (such as an amino group), they can also form internal salts. Detailed Embodiments

[0068] The technical solutions of the present disclosure will be further described in detail below in conjunction with specific embodiments. It should be understood that the following embodiments are only illustrative explanations of the present disclosure and should not be construed as limiting the protection scope of the present disclosure. All technologies implemented based on the above content of the present disclosure are covered within the scope of protection intended by the present disclosure.

[0069] Unless otherwise specified, the raw materials and reagents used in the following embodiments are all commercially available products or can be prepared by known methods.

[0070] Example 1 Synthesis of Compound 1

[0071]

[0072] Under an ice bath, 0.74 g (3.69 mmol) of 3-naphthalen-2-ylpropanoic acid was dissolved in 30 mL of N,N-dimethylformamide, and 0.87 g (4.43 mmol) of EDCI and 0.59 g (4.43 mmol) of HOBt were added and stirred for 1 hour. Under this condition, 0.55 g (3.69 mmol) of 5-aminobenzimidazolone and 0.45 g (4.50 mmol) of triethylamine were successively added to the reaction system. After stirring for another 1 hour, the temperature was raised to room temperature and stirred for 12 hours. After the reaction was completed, 30 mL of water was added to the reaction solution for dilution. The solid product was filtered, washed with water, and dried to obtain 0.85 g of white solid Compound 1, with a yield of 66.4%. 1 H NMR (400 MHz, DMSO-d6) δ 10.52 (s, 1H), 10.45 (s, 1H), 9.78 (s, 1H), 7.85 - 7.80 (m, 3H), 7.73 (s, 1H), 7.47 - 7.41 (m, 4H), 6.97 (dd, 1H, J1 = 1.68 Hz, J2 = 8.36 Hz), 6.80 (d, 1H, J = 8.32 Hz), 3.08 (t, 2H, J = 7.4 Hz), 2.69 (t, 2H, J = 7.88 Hz).

[0073] Example 2 Synthesis of Compound 2

[0074]

[0075] Under an ice bath, 0.50 g (2.68 mmol) of 2-naphthaleneacetic acid was dissolved in 30 mL of N,N-dimethylformamide, and 0.51 g (2.68 mmol) of EDCI and 0.36 g (2.68 mmol) of HOBt were added and stirred for 1 hour. Under these conditions, 0.40 g (2.68 mmol) of 5-aminobenzimidazolone and 0.45 g (4.50 mmol) of triethylamine were successively added to the reaction system, and after stirring for 1 hour, the temperature was raised to room temperature and stirred for 12 hours. After the reaction was completed, the resulting solid product was filtered, washed with water, and dried to obtain 0.62 g of white solid compound 2, with a yield of 72.9%. 1 H NMR (400 MHz, DMSO-d6) δ 10.55 (s, 1H), 10.49 (s, 1H), 10.11 (s, 1H), 7.88 - 7.82 (m, 4H), 7.51 - 7.48 (m, 4H), 7.05 (d, 1H, J = 8.04 Hz), 6.84 (d, 1H, J = 8.24 Hz), 3.78 (s, 2H).

[0076] Example 3 Molecular Recognition Results

[0077] In order to explore the interaction and mode of action of Compound 1 and Compound 2 with PSA (PSA protein was purchased from Nanjing Oakai Biotechnology Co., Ltd., product number: C1551, concentration: 0.3 mg / ml, pH 7.4, molecular weight approximately 33 kDa), the recognition results of the compounds of the present invention are summarized in the following table, and the docking recognition poses are respectively as Figure 3 and Figure 4 shown. Among them, Compound 1 forms hydrogen bonds with Thr 190, Ser 226, and Ser 217, with distances of 2.88 Å, 3.17 Å, and 3.01 Å respectively, and forms hydrophobic interactions with amino acids such as His 57, Leu 95, Cys191, Ser 192, Gly 216, and Cys 220. Compound 2 forms hydrogen bonds with Thr 190, Gly 193, and Ser217, with distances of 3.14 Å, 3.26 Å, and 3.20 Å respectively. It forms hydrophobic interactions with amino acids such as His 57, Leu 95, Asp 102, Cys 191, Cys 220, and Gly216. From the docking scores, the scores of Compound 1 and 2 are -10.8 and -10.3 respectively, indicating a very high binding force.

[0078]

[0079] Example 4 Interaction Tests of Compounds 1 and 2

[0080] 1) Surface Plasmon Resonance SPR

[0081] In this experiment, the Biacore T200 system (GE Healthcare Life Sciences, Uppsala, Sweden) was used to quantitatively measure the interaction between compounds and target proteins. The purified target protein was directly immobilized on a carboxymethylated 5 (CM5) sensor chip, and then different concentrations of small molecules were used as analytes for multi-cycle kinetic detection. The carboxylic acid groups on the CM5 chip (Cytiva) were first activated with a mixture of EDC and NHS solutions (Cytiva) at a flow rate of 10 μL / min at 25 °C for 7 minutes; subsequently, the target protein dissolved in sodium acetate buffer (10 mM; pH 4.5) was injected until the protein content immobilized on the chip reached 2500 - RU; finally, the chip was blocked with ethanolamine. For multi-cycle kinetics, the target protein was directly immobilized on the CM5 chip first, and then gradient-diluted analytes were detected sequentially, 1 concentration / cycle, while performing DMSO solvent correction to detect affinity and kinetics. Small molecule concentrations: 0, 1.25, 2.5, 5, 10, 20 nM. Temperature: 25 °C, injection: 30 uL / min, binding time 90 s, dissociation time 60 s, running buffer: 5% DMSO PBS-P.

[0082] All results were analyzed by kinetics / affinity fitting according to the 1:1 model, and the data was analyzed using Biacore evaluation software (version T200 2.0), and the results are shown in Figure 5 ... The results showed that the binding affinity between compound 1 and PSA was 59.33 nM, and the binding affinity between compound 2 and PSA was 144 nM, indicating that both compound 1 and compound 2 had strong binding affinities with PSA.

[0083] The values of 59.33 nM and 144 nM represent the dissociation constant (abbreviated as KD value) of the small molecule and the protein. The KD value is the equilibrium dissociation constant between the protein and the small molecule substance (which can also be a protein molecule), representing the concentration of the small molecule at which half of the protein is bound. A lower KD value means that at a lower concentration of the small molecule, half of the protein is already bound to the small molecule, indicating very tight binding. Therefore, the smaller the value, the stronger the binding between the protein and the ligand, that is, the greater the affinity.

[0084] 2) Microscale Thermophoresis (MST) experiment

[0085] MST is an optical method for characterizing biomolecular properties and is the directional movement of particles in a microscopic temperature gradient. One of the interacting molecules (mostly proteins) is labeled with a fluorescent dye or fused with a GFP tag. The labeled protein and ligand molecules are placed in a capillary according to a specific concentration gradient. Infrared laser heating generates a microscopic temperature gradient field for thermophoresis. Molecular properties such as its hydration layer, molecular size, and charge will change with thermophoresis, which in turn causes changes in the fluorescence distribution in the reaction system. The MST instrument records the fluorescence changes in the infrared laser irradiation area inside the sample in the temperature gradient before, during, and after the laser is turned on, thereby achieving measurement in a relatively short time. In this experiment, a Monolith NT.115 instrument was used to detect the interaction between the compound and the target protein. First, a purified protein was labeled using the MonolithTM RED-NHS second-generation protein labeling kit. Among them, the NHS-ester carried by the RED dye can covalently bind to the primary amino group (lysine residue) of the target protein. Then, 16 gradient concentration solutions of the compound to be tested were prepared, and 20 μL of the RED-NHS-labeled target protein of equal volume was taken and mixed evenly with each of them. A capillary was used to aspirate the mixed sample for the MST experiment. The MO.Affinity Analysis X86 software was used to fit the MST curve to obtain the binding Kd value. The results are shown in Figure 6 。

[0086] Different from the SPR principle, MST is based on the influence of the temperature gradient on the molecular diffusion behavior in the solution. When two molecules bind or dissociate, their diffusion behavior in the temperature gradient will change. The present invention provides more comprehensive and reliable results based on the verification of the binding of PSA to its ligand in multiple systems. The MST results show that between 0.15 nM and 5 μM, as the concentrations of Compound 1 and Compound 2 increase, the fluorescence signal gradually increases, indicating that both Compound 1 and Compound 2 can bind to the PSA protein. The binding affinity between Compound 1 and the PSA protein is 78.91 nM, and the binding affinity between Compound 2 and the PSA protein is 103.31 nM, indicating that both Compound 1 and Compound 2 have strong binding affinities, and the binding affinity of Compound 1 with the PSA protein is stronger.

[0087] The above has given an exemplary description of the implementation manner of the technical solution of the present disclosure. It should be understood that the protection scope of the present disclosure is not limited to the above implementation manner. Any modifications, equivalent replacements, improvements, etc. made by those skilled in the art within the spirit and principle of the present disclosure shall be included within the protection scope of the claims of this application.

Claims

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof: Among them, Each of R1 and R2, which may be the same or different, is independently selected from H, halogen, C 1-6 alkyl, C 1-6 alkoxy, halo-C 1-6 alkyl, halo-C 1-6 alkoxy, C 3-10 cycloalkyl or C 3-10 cycloalkyloxy; R3 and R4 are the same or different and are each independently selected from H, C 1-6 alkyl or halo C 1-6 alkyl; R5 is selected from H; R6 and R7 are the same or different and are each independently selected from H, C 1-6 alkyl or halo C 1-6 alkyl; m is selected from 0, 1, 2, 3, 4, 5, 6 or 7; n is selected from 0, 1, 2 or 3; p is selected from 1, 2, 3, 4, 5, 6, 7 or 8.

2. The compound or a pharmaceutically acceptable salt thereof according to claim 1, wherein Each R1 and R2, which may be the same or different, are independently selected from H, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy, isopropoxy; Preferably, R3, R4, and R5, which may be the same or different, are independently selected from H, methyl, ethyl, propyl, isopropyl; Preferably, each R6 and R7, which may be the same or different, are independently selected from H, methyl, ethyl, propyl, isopropyl; Preferably, m is selected from 0, 1 or 2; Preferably, n is selected from 0 or 1; Preferably, p is selected from 1, 2 or 3.

3. The compound or a pharmaceutically acceptable salt thereof according to claim 1 or 2, which is selected from the structure shown in the following formula (II): Among them, Each R1, R2, and n has the definition as defined in claim 1 or 2.

4. The compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-3, which is selected from the following compounds:

5. A method for preparing the compound according to any one of claims 1-4, comprising the following steps: Compound a reacts with compound b to obtain the compound of formula (I); Wherein, R1, R2, R3, R4, R5, R6, R7, m, n, and p independently have the definition as defined in any one of claims 1-4; L is selected from leaving groups such as OH, halogen.

6. Use of the compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-4 in the recognition of prostate-specific antigen, wherein the recognition is the specific binding of the compound or a pharmaceutically acceptable salt thereof to the cavity in prostate-specific antigen; Preferably, the compound or a pharmaceutically acceptable salt thereof can be further introduced with a fluorescent group such as the Fmoc group.

7. Use of the compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-4 in the detection of prostate-specific antigen (PSA) or prostate cancer, and the use is not directly for the diagnosis or treatment of diseases.

8. Use of the compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-4 in the preparation of a reagent, protein chip or kit for detecting prostate-specific antigen.

9. A method for detecting prostate-specific antigen, comprising: (a) contacting the prostate-specific antigen with the compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-4 under conditions sufficient for an antibody / antigen binding reaction to obtain a PSA-Drug complex; and (b) detecting the presence of the PSA-Drug complex, and the presence of the PSA-Drug complex indicates the presence of the prostate-specific antigen in the test sample; The method is not directly for the diagnosis or treatment of diseases.

10. A reagent comprising the compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-4; and / or, a protein chip comprising the compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-4; and / or, a kit comprising the compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-4.

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