Compounds targeting cxcr4 and uses thereof

Abstract

The present application discloses a kind of compound for targeting CXCR4 and purposes thereof.The compound is shown in structure of formula (I) or its isotopic variant, hydrate, ester or solvate, tautomer, stereoisomer or pharmaceutically acceptable salt.The compound of the present application connects ligand group (Ra and Rb) for targeting CXCR4 and chelating group Z by linker (L1-X-L2), which has good CXCR4 targeting and specificity, can be quickly imaged in a short time after administration, and can be used for diagnosing and treating CXCR4 overexpression diseases.

Description

Technical Field

[0001] This application belongs to the field of biomedical technology, specifically relating to compounds targeting CXCR4 and their uses, and more specifically to compounds, complexes, imaging agents, pharmaceutical compositions, and their uses that target CXCR4. Background Technology

[0002] Chemokines are a class of small secretory proteins with a molecular weight of 8–10 kDa, primarily responsible for regulating cell migration. Based on the arrangement of N-terminal cysteine ​​residues, chemokines are classified into four main categories: CC, CXC, C, and CX3C. They are produced by different cell types and exert their biological functions by activating their respective G protein-coupled receptors (GPCRs).

[0003] Chemokine CXCL12α belongs to the CXC subfamily and is composed of 68 amino acids. Chemokine receptor CXCR4 is one of the main receptors for CXCL12. It is widely distributed in organs such as lymphoid tissue, brain, thymus and spleen, and has an important influence on physiological processes such as development, hematopoiesis, organogenesis and angiogenesis.

[0004] Under pathological conditions, abnormal expression of CXCR4 is closely related to the occurrence and development of various diseases, especially in the field of oncology. Studies have shown that the biological axis formed by CXCL12 and CXCR4 plays a crucial role in the initiation, progression, invasion, and metastasis of tumors, and is overexpressed in more than 23 types of human cancers, including lymphoma, leukemia, breast cancer, prostate cancer, lung cancer, and colorectal cancer. Furthermore, CXCR4 can promote angiogenesis, cell metastasis, growth, or survival, and is involved in HIV infection. These biological functions determine that CXCR4-targeted drugs can be used to treat diseases such as cancer, hematopoietic stem cell mobilization, and HIV.

[0005] Given the crucial role of CXCR4 in the development and progression of various diseases, developing novel radionuclide conjugates with higher affinity and selectivity has become an important direction that urgently needs to be explored in order to meet the clinical needs for the diagnosis and treatment of diseases with high CXCR4 expression. Summary of the Invention

[0006] This application aims to at least partially address one of the technical problems existing in the prior art. To this end, this application provides a compound targeting CXCR4, which exhibits good CXCR4 targeting and specificity, and allows for rapid imaging shortly after administration, making it suitable for the diagnosis and treatment of CXCR4 overexpression diseases.

[0007] In a first aspect of this application, a compound is provided, characterized in that the compound comprises a structure of formula (I) or an isotopic variant thereof, a hydrate, an ester or solvate, a tautomer or stereoisomer, or a pharmaceutically acceptable salt: (I); in: Z is selected from a chelating group; Ra and Rb are each independently selected from ligand groups targeting CXCR4; X is selected from ** indicates that it is connected to Z; L1 and L2 are each independently selected from *-C(O)-phenyl-R8-R9-, *-C(O)-R 10 -R9-, or *-C(O)-phenyl-R8-NH-C(O)-R 10 -R9-, * indicates connection to Ra or Rb; R1 is selected from CH, N, phenyl, or 1,3,5-triazine alkyl groups; R2, R3, and R4 are each independently selected from empty, -R8-C(O)-, C 1~6 Alkylene; R5 and R6 are each independently selected as -N(R7)- or -C(O)-; R7 is selected from H or C. 1~6 alkyl; R8 is selected from C 1~6 Alkylene; R9 is selected from -N(R7)- or -C(O)-; R 10 Selected from C 3~10 Alkylene; Z and X, X and L1 or L2, Ra and L1, and Rb and L2 are all connected by amide bonds.

[0008] In a second aspect of this application, a complex is provided. According to an embodiment of this application, the complex comprises the compound described in the first aspect and M, wherein M is complexed with the compound; M is selected from radioactive nuclides or non-radioactive elements.

[0009] In a third aspect, this application provides an imaging agent. According to embodiments of this application, the imaging agent comprises the compound described in the first aspect or the complex described in the second aspect.

[0010] In a fourth aspect, this application provides a pharmaceutical composition. According to embodiments of this application, the pharmaceutical composition comprises the compound described in the first aspect, the complex described in the second aspect, or the imaging agent described in the third aspect.

[0011] In a fifth aspect of this application, the use of the compound described in the first aspect, the complex described in the second aspect, the imaging agent described in the third aspect, or the pharmaceutical composition described in the fourth aspect in the preparation of a medicament for diagnosing and / or treating CXCR4 overexpression diseases is proposed.

[0012] Beneficial effects: The compound of this application has a high affinity for CXCR4. The complex obtained by radiolabeling the compound molecule with radionuclides has good CXCR4 targeting, rapid imaging capability and target retention capability, and can be applied to the diagnosis and treatment of CXCR4 overexpression diseases.

[0013] Additional aspects and advantages of this application will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of this application. Attached Figure Description

[0014] The above and / or additional aspects and advantages of this application will become apparent and readily understood from the description of the embodiments taken in conjunction with the following drawings, in which: Figure 1 The chromatogram of compound 1 in Preparation Example 1 of this application is shown. Figure 2 The chromatogram of compound 2 in Preparation Example 2 of this application; Figure 3 This is a PET / CT imaging result of compound 1 in test example 2 of this application on a Daudi tumor model mouse. Detailed Implementation

[0015] The embodiments of this application are described in detail below. The embodiments described below are exemplary and are only used to explain this application, and should not be construed as limiting this application.

[0016] It should be noted that the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Therefore, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. Furthermore, in the description of this application, unless otherwise stated, "multiple" means two or more.

[0017] It should be noted that the structural and chemical formula descriptions in the embodiments or implementations of this application are intended to cover all alternatives, modifications, and equivalent technical solutions, all of which are within the scope of this application as defined in the claims. Those skilled in the art will recognize that many similar or equivalent methods and materials can be used to practice this application. This application is by no means limited to the methods and materials described herein. In the event that one or more of the cited documents, patents, and similar materials differ from or contradict this application (including but not limited to defined terminology, application of terminology, described techniques, etc.), this application shall prevail.

[0018] It should be further appreciated that some features of this application, for clarity, have been described in multiple independent embodiments or implementations, but may also be provided in combination in a single embodiment or implementation. Conversely, various features of this application, for the sake of brevity, have been described in a single embodiment or implementation, but may also be provided individually or in any suitable sub-combination.

[0019] Unless otherwise stated, the technical and scientific terms used in this application have the same meaning as commonly understood by one of ordinary skill in the art to which this application pertains, and unless otherwise stated, all patent publications cited in the entirety of this application are incorporated herein by reference.

[0020] This application will apply the following definitions unless otherwise indicated. For the purposes of this application, chemical elements are defined according to the periodic table, CAS version, and Chemical Handbook, 75, 1994. Furthermore, general principles of organic chemistry are found in "Organic Chemistry," Thomas Sorrell, University Science Books, Sausalito: 1999, and "March's Advanced Organic Chemistry," by Michael B. Smith and Jerry March, John Wiley & Sons, New York: 2007; therefore, all contents of this application incorporate the references.

[0021] In this document, the terms “comprising” or “including” are open-ended expressions, meaning that they include the contents specified in this application but do not exclude other contents.

[0022] In this document, the compounds of this application also include isotopically labeled compounds of this application that are identical to those compounds described herein except that one or more atoms are replaced by atoms with atomic masses or mass numbers different from those of naturally common atomic masses or mass numbers. Exemplary isotopes that may also be introduced into the compounds of this application include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, and chlorine, such as... 2 H, 3 H, 13 C 14 C 15 N、 16 O、 17 O、 31 P, 32 P, 36 S, 18 F and 37 Cl.

[0023] Compounds of this application containing other isotopes of the aforementioned isotopes and / or other atoms, as well as pharmaceutically acceptable salts of said compounds, are included within the scope of this application. Isotope-labeled compounds of this application, such as radioactive isotopes, are also included. 3 H and 14 The incorporation of tritium into the compounds of this application can be used for drug and / or substrate tissue distribution analysis. Due to its ease of preparation and detection, tritium-substituted compounds... 3 H, and carbon-14, i.e. 14 C isotopes are particularly preferred. In addition, heavier isotopes, such as deuterium, are used. 2 H substitution can offer therapeutic advantages stemming from greater metabolic stability, such as increased in vivo half-life or reduced dose requirements. Therefore, it may be preferred in some cases.

[0024] In this document, the term "pharmaceutically acceptable" means that a substance or composition must be chemically and / or toxicologically compatible with other components of the formulation and / or the mammals to which it is treated.

[0025] As used herein, the term "pharmaceutically acceptable salt" refers to carboxylates and amino acid addition salts of the compounds of this application that are suitable for contact with patient tissues within the bounds of reliable medical judgment, without producing undue toxicity, irritation, allergic reactions, etc., and are effective for their intended use in proportion to a reasonable benefit / risk ratio, including (where possible) zwitterionic forms of the compounds of this application.

[0026] Pharmaceutically acceptable base addition salts are those formed with metals or amines, such as alkali metal and alkaline earth metal hydroxides or organic amines. Examples of metals used as cations include sodium, potassium, magnesium, and calcium. Suitable amines include N,N'-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, N-methylglucosamine, and procaine.

[0027] The base addition salts of acidic compounds can be prepared by contacting the free acid form with a sufficient amount of the required base in a conventional manner to form a salt. The free acid can be regenerated by contacting the salt form with an acid in a conventional manner and then separating the free acid. The free acid forms differ somewhat from their respective salt forms in certain physical properties, such as solubility in polar solvents; however, for the purposes of this application, the salts are equivalent to their respective free acids.

[0028] Salts can be sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, nitrates, phosphates, monohydrogen phosphates, dihydrogen phosphates, metaphosphates, pyrophosphates, chlorides, bromides, and iodides prepared from inorganic acids, such as hydrochloric acid, nitric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, and phosphoric acid. Representative salts include: hydrobromide, hydrochloride, sulfate, bisulfate, nitrate, acetate, oxalate, valerate, oleate, palmitate, stearate, laurate, borate, benzoate, lactate, phosphate, toluenesulfonate, citrate, maleate, fumarate, succinate, tartrate, naphthate, methanesulfonate, gluconate, lactobionate, laurylsulfonate, and hydroxyethanesulfonate. Salts can also be prepared from organic acids, such as aliphatic monocarboxylic and dicarboxylic acids, phenyl-substituted alkyl acids, hydroxyalkyl acids, alkyl diacids, aromatic acids, and aliphatic and aromatic sulfonic acids. Representative salts include acetates, propionates, octanoates, isobutyrates, oxalates, malonates, succinates, octanoates, sebacic acid salts, fumarates, maleates, mandelates, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, naphthates, benzenesulfonates, toluenesulfonates, phenylacetates, citrates, lactates, maleates, tartrates, and methanesulfonates. Pharmaceutically acceptable salts may include alkali metal and alkaline earth metal-based cations, such as sodium, lithium, potassium, calcium, and magnesium, as well as non-toxic ammonium, quaternary ammonium, and amine cations, including but not limited to ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, and ethylamine. It also covers amino acid salts, such as arginine salts, gluconates, galacturons, etc. (see, for example, Berge SM et al., "Pharmaceutical Salts," J. Pharm. Sci., 1977; 66: 1-19, incorporated herein by reference).

[0029] In this document, the terms “optionally,” “optionally,” or “optionally” generally refer to an event or condition that may, but may not, occur, and the description includes both cases in which the event or condition occurs and cases in which the event or condition does not occur.

[0030] When listing a range of values, it is assumed that each value and the subranges within that range are included. For example, "C 1-6 Alkyl groups include C1, C2, C3, C4, C5, C6, and C6. 1-6 C 1-5 C 1-4 C 1-3 C 1-2 C 2-6 C 2-5 C 2-4 C 2-3 C 3-6 C 3-5 C 3-4 C 4-6 C 4-5 and C 5-6 Alkyl group. For example, "C 5-10 Alkyl groups include C5, C6, C7, C8, C9, and C6 alkyl groups. 10 C 5-10 C 5-9 C 5-8 C 5-7 C 5-6 C 6-10 C 6-8 C 6-7 alkyl.

[0031] In this document, "alkyl" refers to a straight-chain or branched saturated hydrocarbon group having a carbon atom. In some embodiments, "C 1-6 "alkyl" includes C 1-4 Alkyl, C 1-3 Alkyl and C 1-2 Alkyl groups are preferred. C 1-6 Examples of alkyl groups include: methyl (C1), ethyl (C2), n-propyl (C3), isopropyl (C3), n-butyl (C4), tert-butyl (C4), sec-butyl (C4), isobutyl (C4), n-pentyl (C5), 3-pentyl (C5), pentyl (C5), neopentyl (C5), 3-methyl-2-butyl (C5), tert-pentyl (C5), and n-hexyl (C6). The term "C" is used in conjunction with the preceding text. 1-6"Alkyl" also includes heteroalkyl groups, wherein one or more (e.g., 1, 2, 3, or 4) carbon atoms are replaced by heteroatoms (e.g., oxygen, sulfur, nitrogen, boron, silicon, phosphorus). The alkyl group may be optionally substituted with one or more substituents, for example, substituted with 1 to 5 substituents, 1 to 3 substituents, or 1 substituent. Common alkyl abbreviations include: Me(-CH3), Et(-CH2CH3), iPr(-CH(CH3)2), nPr(-CH2CH2CH3), n-Bu(-CH2CH2CH2CH3), or i-Bu(-CH2CH(CH3)2). In some embodiments, straight-chain alkyl groups are preferred. In some embodiments, "C 5-10 "alkyl" includes C 5-9 Alkyl, C 5-8 Alkyl and C 5-7 Alkyl groups are preferred.

[0032] In this article, "C 1-6 "Alkylene" refers to the removal of C 1-6 The alkyl group is a divalent group formed by another hydrogen atom, and can be substituted or unsubstituted. In some embodiments, C 1-4 Alkylene, C 1-3 Alkylene, C 1-2 Alkylenes and methylene groups are preferred. Unsubstituted alkylenes include, but are not limited to: methylene (-CH2-), ethylene (-CH2CH2-), propylene (-CH2CH2CH2-), butylene (-CH2CH2CH2CH2-), pentylene (-CH2CH2CH2CH2CH2-), hexylene (-CH2CH2CH2CH2CH2-), and so on. Exemplary substituted alkylenes, for example, those substituted with one or more alkyl (methyl) groups, include, but are not limited to: substituted methylene (-CH(CH3)-, -C(CH3)2-), substituted ethylene (-CH(CH3)CH2-, -CH2CH(CH3)-, -C(CH3)2CH2-, -CH2C(CH3) 2- ), substituted propylidenes (-CH(CH3)CH2CH2-, -CH2CH(CH3)CH2-, -CH2CH2CH(CH3)-, -C(CH3)2CH2CH2-, -CH2C(CH3)2CH2-, -CH2CH2C(CH3)2-), etc. In some embodiments, straight-chain alkylene groups are preferred.

[0033] As used herein, the term “treatment” refers to reversing, alleviating, inhibiting, or preventing the progression of an obstacle or condition to which the term applies, or one or more symptoms of such an obstacle or condition. The noun “treatment” as used herein also refers to the action of the verb “to treat,” as defined above.

[0034] The "group description in this application" "" is used to describe the position of the substituent group.

[0035] In this application, the chemical structure of the compound contains the bond " "" indicates that the configuration is not specified. If chiral isomerism exists in the chemical structure, the bond " "can be " " ", or both contain " "and" "Two configurations. Although all the above structural formulas are drawn in some isomer form for simplicity, this article may include all isomers, such as: tautomers, rotational isomers, geometric isomers, diastereomers, racemates and enantiomers."

[0036] In the chemical structure of the ligands or compounds described in this article, the bond " "" indicates that the configuration is not specified. If cis-trans isomerism exists in the chemical structure, the bond " The configuration of “” can be E type, Z type, or both E and Z types.

[0037] In this document, the term "pharmaceuticalally acceptable excipient" includes any solvent, salt, pharmaceutical stabilizer, or combination thereof, all of which are known to those skilled in the art (as described in Remington's Pharmaceutical Sciences, 18th Ed. Mack Printing Company, 1990, pp. 1289-1329). Except in cases where any conventional excipient is incompatible with the active ingredient, it covers its use in therapeutic or pharmaceutical compositions.

[0038] In this document, the term "subject" as used to administer the drug includes, but is not limited to: humans (i.e., men or women of any age group, e.g., pediatric subjects (e.g., infants, children, adolescents) or adult subjects (e.g., young adults, middle-aged adults, or older adults)) and / or non-human animals, such as mammals, e.g., primates (e.g., cynomolgus monkeys, rhesus monkeys), cattle, pigs, horses, sheep, goats, rodents, cats, and / or dogs. In some embodiments, the subject is a human. In some embodiments, the subject is a non-human animal. The terms "human," "patient," and "subject" are used interchangeably herein.

[0039] Generally, the "effective amount" of a compound refers to the amount sufficient to elicit a target biological response. As will be understood by those skilled in the art, the effective amount of the compounds in this application can vary depending on factors such as the biological target, the pharmacokinetics of the compound, the disease being treated, the administration method, and the age, health status, and symptoms of the subject. Effective amounts include therapeutic effective amounts and prophylactic effective amounts.

[0040] Unless otherwise stated, the term "therapeuticly effective amount" of a compound as used herein is an amount sufficient to provide therapeutic benefit in the treatment of a disease, disorder, or condition, or to delay or minimize one or more symptoms associated with the disease, disorder, or condition. Therapeuticly effective amount of a compound refers to the amount of a therapeutic agent, used alone or in combination with other therapies, that provides therapeutic benefit in the treatment of a disease, disorder, or condition. The term "therapeuticly effective amount" may include amounts that improve overall treatment, reduce or prevent symptoms or causes of a disease or condition, or enhance the therapeutic effects of other therapeutic agents.

[0041] Unless otherwise stated, the “preventively effective amount” of a compound as used herein is an amount sufficient to prevent a disease, disorder, or condition, or an amount sufficient to prevent one or more symptoms associated with a disease, disorder, or condition, or an amount sufficient to prevent recurrence of a disease, disorder, or condition. The preventively effective amount of a compound refers to the amount of a therapeutic agent, used alone or in combination with other agents, that provides preventive benefit in the prevention of a disease, disorder, or condition. The term “preventively effective amount” may include amounts that improve overall prevention or enhance the preventive effect of other preventive agents.

[0042] In this document, the term "administration" refers to the introduction of a predetermined amount of a substance into a patient in a suitable manner. The compounds or pharmaceutical compositions of this application may be administered via any common route, as long as it can reach the intended tissue. Various routes of administration are foreseeable, including peritoneal, intravenous, intramuscular, subcutaneous, etc., but this application is not limited to these exemplified routes of administration. Preferably, the compositions of this application are administered via intravenous or subcutaneous injection.

[0043] In this document, the term "treatment" refers to the administration of a drug or compound to an individual to achieve a desired pharmacological and / or physiological effect. This effect may be preventative in terms of complete or partial prevention of a disease or its symptoms, and / or therapeutic in terms of partial or complete cure of a disease and / or adverse effects caused by the disease. As used herein, "treatment" encompasses diseases in mammals, particularly humans, including: (a) prevention of disease or the onset of a condition in an individual who is susceptible but has not yet been diagnosed with the disease; (b) inhibition of disease, such as blocking disease progression; or (c) relief of disease, such as reducing symptoms associated with the disease. As used herein, "treatment" encompasses any administration of a drug or compound to an individual to treat, cure, relieve, improve, reduce, or inhibit the individual's disease, including but not limited to administration of a drug containing a compound described herein to an individual in need.

[0044] In this article, the terms “disease,” “disorder,” and “symptom” are used interchangeably.

[0045] In this article, the terms "cancer" or "tumor" can refer to any unregulated cell growth. For example, cancers expressing CXCR4 are selected from breast cancer, lung cancer, prostate cancer, pancreatic cancer, colorectal cancer, ovarian cancer, neuroblastoma, glioblastoma, leukemia, multiple myeloma, head and neck squamous cell carcinoma, gastric cancer, melanoma, renal cell carcinoma, B-cell lymphoma, T-cell lymphoma, Hodgkin's lymphoma, Burkitt's lymphoma, and so on.

[0046] The term "combination" and related terms refer to the simultaneous or sequential administration of the compound of this application and other therapeutic agents. For example, the compound of this application may be administered simultaneously or sequentially with other therapeutic agents in separate unit dosage forms, or simultaneously with other therapeutic agents in a single unit dosage form.

[0047] This application discloses a compound, complex, imaging agent, pharmaceutical composition, and their uses that target CXCR4, which will be described in detail below.

[0048] compound In a first aspect of this application, a compound is provided, characterized in that the compound comprises a structure of formula (I) or an isotopic variant thereof, a hydrate, an ester or solvate, a tautomer or stereoisomer, or a pharmaceutically acceptable salt: (I); in: Z is selected from a chelating group; Ra and Rb are each independently selected from ligand groups targeting CXCR4; X is selected from ** indicates that it is connected to Z; L1 and L2 are each independently selected from *-C(O)-phenyl-R8-R9-, *-C(O)-R 10 -R9-, or *-C(O)-phenyl-R8-NH-C(O)-R 10 -R9-, * indicates connection to Ra or Rb; R1 is selected from CH, N, phenyl, or 1,3,5-triazine alkyl groups; R2, R3, and R4 are each independently selected from empty, -R8-C(O)-, C 1~6 Alkylene; R5 and R6 are each independently selected as -N(R7)- or -C(O)-; R7 is selected from H or C. 1~6 alkyl; R8 is selected from C 1~6 Alkylene; R9 is selected from -N(R7)- or -C(O)-; R 10 Selected from C 3~10 Alkylene; Z and X, X and L1 or L2, Ra and L1, and Rb and L2 are all connected by amide bonds.

[0049] The compound of this application connects the CXCR4-targeting ligand groups (Ra and Rb) and the chelating group Z via a linking group (L1-X-L2), which can improve the tumor tissue targeting and uptake of the compound, and rapidly form clear tumor images shortly after administration. Therefore, the compound of this application has good CXCR4 targeting and specificity, and can be rapidly imaged shortly after administration, making it suitable for the diagnosis and treatment of CXCR4 overexpression diseases.

[0050] According to embodiments of this application, the above-mentioned compound may further include at least one of the following technical features: According to the embodiments of this application, R1 is selected from phenyl, and R2, R3 and R4 are all empty.

[0051] According to embodiments of this application, R1 is selected from 1,3,5-triazine alkyl groups, R2 is selected from -N(R7)-R8-C(O)-, and R3 and R4 are each independently selected from C 1~6 Alkylene.

[0052] According to embodiments of this application, R1 is selected from 1,3,5-triazine alkyl groups, R2 is selected from -R8-C(O)-, and R8 is selected from C 1~3 Alkylenes, R3 and R4 are each independently selected from C10. 1~6 Alkylene.

[0053] According to an embodiment of this application, R1 is selected from CH, R2 is empty, and one of R3 and R4 is empty while the other is C. 1~6 Alkylene.

[0054] According to embodiments of this application, R1 is selected from N, and R2, R3, and R4 are each independently selected from C. 1~6 Alkylene.

[0055] According to embodiments of this application, R5 and R6 are each independently selected from -NH- or -C(O)-.

[0056] According to an embodiment of this application, R7 is selected from H.

[0057] According to embodiments of this application, X is selected from... , , , ,or .

[0058] According to embodiments of this application, X is selected from... , , , , ,or .

[0059] According to embodiments of this application, X is selected from... , , , , , ,or .

[0060] In a preferred embodiment, X is selected from... .

[0061] According to embodiments of this application, in L1 and L2, R8 is selected from C. 1~3 Alkylene.

[0062] According to embodiments of this application, R9 is selected from -NH- or -C(O)-.

[0063] According to an embodiment of this application, R 10 Selected from C 4~8 Alkylene.

[0064] According to embodiments of this application, R 10 Selected from C 5~8 Alkylene.

[0065] According to embodiments of this application, L1 and L2 are each independently selected from... , , , , .

[0066] According to embodiments of this application, L1 and L2 are each independently selected from... , , , , , , , , , .

[0067] According to embodiments of this application, -L1-X-L2- is selected from... , , , , , , , , , , .

[0068] According to embodiments of this application, the chelating group is derived from a chelating agent; The chelating agent is selected from 1,4,7,10-tetraazacyclododecane-N,N',N",N'''-tetraacetic acid (DOTA). N,N"-Bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N"-diacetic acid (HBED-CC) 1,4,7-Triazacyclononane-1,4,7-triacetic acid (NOTA) 2-(4,7-bis(carboxymethyl)-1,4,7-triazonon-1-yl)glutaric acid (NODAGA), 2-(4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane-1-yl)glutaric acid (DOTAGA), 1,4,7-Triazacyclononanephosphonic acid (TRAP) 1,4,7-Triazacyclononane-1-[methyl(2-carboxyethyl)phosphonic acid]-4,7-bis[methyl(2-hydroxymethyl)phosphonic acid] (NOPO), 3,6,9,15-Tetraazabicyclo[9.3.1.]pentadecan-1(15),11,13-triene-3,6,9-triacetic acid (PCTA), N'-{5-[acetyl(hydroxy)amino]pentyl}-N-[5-({4-[(5-aminopentyl)(hydroxy)amino]-4-oxobutyryl}amino)pentyl]-N-hydroxysuccinamide (DFO) Diethyltriaminepentaacetic acid (DTPA) trans-cyclohexyl-diethylenetriaminepentaacetic acid (CHX-DTPA) 1-Oxa-4,7,10-triazacyclododecane-4,7,10-triacetic acid (O-Do3A) p-Isocyanothiobenzyl-DTPA (SCN-Bz-DTPA), 1-(p-isocyanothiobenzyl)-3-methyl-DTPA (1B3M), 2-(p-isocyanothiobenzyl)-4-methyl-DTPA (1M3B), 1-(2)-Methyl-4-isocyanothiobenzyl-DTPA (MX-DTPA), [(R)-2-amino-3-(4-isothiocyanophenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diaminepentaacetic acid (p-SCN-Bn-CHX-A"-DTPA), 6-Hydroxypyridine-3-carboxylic acid (HYNIC) 2-(4-Isothiocyanophenyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA), or 2-[(4-isothiocyanophenyl)methyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (p-SCN-Bn-DOTA).

[0069] According to embodiments of this application, Z is selected from... DOTA NOTA、 NODAGA、 DOTAGA, HBED-CC, p-SCN-Bn-CHX-A"-DTPA、 p-SCN-Bn-NOTA and p-SCN-Bn-DOTA.

[0070] According to embodiments of this application, Z is selected from... DOTA, or NOTA.

[0071] According to embodiments of this application, the ligand group targeting CXCR4 is selected from... ,or .

[0072] According to embodiments of this application, the ligand group targeting CXCR4 is selected from... ,or .

[0073] According to embodiments of this application, Ra and Rb may be the same or different; According to embodiments of this application, Ra and Rb are the same.

[0074] According to embodiments of this application, the compound has the structure of formula (I-1): (I-1); Among them, Z, R3, and R8 are as shown in any of the above items.

[0075] According to embodiments of this application, in the structure of formula (I-1), Z is selected from a chelating group, and R3 is selected from C. 1~6 Alkylene, R8 is selected from C 1~6 Alkylene.

[0076] According to an embodiment of this application, in the structure of formula (I-1), R3 is selected from C 1~4 Alkylene.

[0077] According to an embodiment of this application, in the structure of formula (I-1), R8 is selected from C 1~3 Alkylene.

[0078] According to an embodiment of this application, in the structure of formula (I-1), Z is selected from... DOTA NOTA.

[0079] According to an embodiment of this application, in formula (I-1), R3 is selected from C 1~3 Alkylene, R8 is selected from C 1~3 Alkylene.

[0080] According to embodiments of this application, the compound has the structure of formula (I-2): (I-2); Among them, Z, R3, and R8 are as shown in any of the above items.

[0081] According to embodiments of this application, in the structure of formula (I-2), Z is selected from a chelating group, and R3 is selected from C. 1~6 Alkylene, R8 is selected from C 1~6 Alkylene.

[0082] According to an embodiment of this application, in the structure of formula (I-2), R3 is selected from C 1~4 Alkylene.

[0083] According to an embodiment of this application, in the structure of formula (I-2), R8 is selected from C 1~3 Alkylene.

[0084] According to an embodiment of this application, in the structure of formula (I-2), Z is selected from... DOTA NOTA.

[0085] According to an embodiment of this application, in formula (I-2), R3 is selected from C 1~3 Alkylene, R8 is selected from C 1~3 Alkylene.

[0086] According to embodiments of this application, the compound has the structure of formula (I-3): (I-3); Among them, Z and R8 are as shown in any of the above items.

[0087] According to embodiments of this application, in the structure of formula (I-3), Z is selected from a chelating group, and R8 is selected from C. 1~6 Alkylene.

[0088] According to an embodiment of this application, in the structure of formula (I-3), R8 is selected from C 1~3 Alkylene.

[0089] According to an embodiment of this application, in the structure of formula (I-3), Z is selected from... DOTA NOTA.

[0090] According to embodiments of this application, the compound has the structure of formula (I-4): (I-4); Among them, Z and R8 are as shown in any of the above items.

[0091] According to embodiments of this application, in the structure of formula (I-4), Z is selected from a chelating group, and R8 is selected from C. 1~6 Alkylene.

[0092] According to an embodiment of this application, in the structure of formula (I-4), R8 is selected from C 1~3 Alkylene.

[0093] According to an embodiment of this application, in the structure of formula (I-4), Z is selected from... DOTA NOTA.

[0094] According to embodiments of this application, the compound has the structure of formula (I-5): (I-5); Among them, Z, R3, R4, and R8 are as shown in any of the above items.

[0095] According to embodiments of this application, in the structure of formula (I-5), Z is selected from chelating groups, and R3 and R4 are each independently selected from C. 1~6 Alkylene, R8 is selected from C 1~6 Alkylene.

[0096] According to an embodiment of this application, in the structure of formula (I-5), R3 and R4 are each independently selected from C. 1~4 Alkylene.

[0097] According to an embodiment of this application, in the structure of formula (I-5), R8 is selected from C 1~3 Alkylene.

[0098] According to an embodiment of this application, in the structure of formula (I-5), Z is selected from... DOTA NOTA.

[0099] According to embodiments of this application, the compound has the structure of formula (I-6): (I-6); Among them, Z, R3, R4, and R8 are as shown in any of the above items.

[0100] According to embodiments of this application, in the structure of formula (I-6), Z is selected from chelating groups, and R3 and R4 are each independently selected from C 1~6 Alkylene, R8 is selected from C 1~6 Alkylene.

[0101] According to an embodiment of this application, in the structure of formula (I-6), R3 and R4 are each independently selected from C. 1~4 Alkylene.

[0102] According to an embodiment of this application, in the structure of formula (I-6), R8 is selected from C 1~3 Alkylene.

[0103] According to an embodiment of this application, in the structure of formula (I-6), Z is selected from... DOTA NOTA.

[0104] According to embodiments of this application, the compound has the structure of formula (I-7): (I-7); Among them, Z, R2, R3, R4, R 10 As shown in any of the above items.

[0105] According to embodiments of this application, in the structure of formula (I-7), Z is selected from chelating groups, and R2, R3, and R4 are each independently selected from C. 1~6 Alkylene, R 10 Selected from C 3~10 Alkylene.

[0106] According to an embodiment of this application, in the structure of formula (I-7), R2, R3, and R4 are each independently selected from C. 1~4 Alkylene.

[0107] According to an embodiment of this application, in the structure of formula (I-7), R 10 Selected from C 4~8 Alkylene.

[0108] According to an embodiment of this application, in the structure of formula (I-7), Z is selected from... DOTA NOTA.

[0109] According to embodiments of this application, the compound has the structure of formula (I-8): (I-8); Among them, Z, R2, R3, R4, R 10 As shown in any of the above items.

[0110] According to embodiments of this application, in the structure of formula (I-8), Z is selected from chelating groups, and R2, R3, and R4 are each independently selected from C. 1~6 Alkylene, R 10 Selected from C 3~10 Alkylene.

[0111] According to an embodiment of this application, in the structure of formula (I-8), R2, R3, and R4 are each independently selected from C. 1~4 Alkylene.

[0112] According to an embodiment of this application, in the structure of formula (I-8), R 10 Selected from C 4~8 Alkylene.

[0113] According to an embodiment of this application, in the structure of formula (I-8), Z is selected from... DOTA NOTA.

[0114] According to embodiments of this application, the compound has the structure of formula (I-9): (I-9); Among them, Z, R2, R3, R4, R8, R 10 As shown in any of the above items.

[0115] According to embodiments of this application, in the structure of formula (I-9), Z is selected from chelating groups, and R2, R3, and R4 are each independently selected from C. 1~6 Alkylene, R8 is selected from C 1~6 Alkylene, R 10 Selected from C 3~10 Alkylene.

[0116] According to an embodiment of this application, in the structure of formula (I-9), R2, R3, and R4 are each independently selected from C. 1~4 Alkylene.

[0117] According to an embodiment of this application, in the structure of formula (I-9), R8 is selected from C 1~3 Alkylene.

[0118] According to an embodiment of this application, in the structure of formula (I-9), R 10 Selected from C 4~8 Alkylene.

[0119] According to an embodiment of this application, in the structure of formula (I-9), Z is selected from... DOTA NOTA.

[0120] According to embodiments of this application, the compound has the structure of formula (I-10): (I-10); Among them, Z, R2, R3, R4, R8, R 10 As shown in any of the above items.

[0121] According to embodiments of this application, in the structure of formula (I-10), Z is selected from a chelating group, and R2, R3, and R4 are each independently selected from C. 1~6 Alkylene, R8 is selected from C 1~6 Alkylene, R 10 Selected from C 3~10 Alkylene.

[0122] According to an embodiment of this application, in the structure of formula (I-10), R2, R3, and R4 are each independently selected from C. 1~4 Alkylene.

[0123] According to an embodiment of this application, in the structure of formula (I-10), R8 is selected from C 1~3 Alkylene.

[0124] According to an embodiment of this application, in the structure of formula (I-10), R 10 Selected from C 4~8 Alkylene.

[0125] According to an embodiment of this application, in the structure of formula (I-10), Z is selected from... DOTA NOTA.

[0126] According to embodiments of this application, the compound has the structure of formula (I-11): (I-11); Among them, Z, R3, R 10 As shown in any of the above items.

[0127] According to embodiments of this application, in the structure of formula (I-11), Z is selected from a chelating group, and R3 is selected from C. 1~6 Alkylene, R 10 Selected from C 3~10 Alkylene.

[0128] According to an embodiment of this application, in the structure of formula (I-11), R3 is selected from C 1~4 Alkylene.

[0129] According to an embodiment of this application, in the structure of formula (I-11), R 10 Selected from C 4~8 Alkylene.

[0130] According to an embodiment of this application, in the structure of formula (I-11), Z is selected from... DOTA NOTA.

[0131] According to embodiments of this application, the compound has the structure of formula (I-12): (I-12); Among them, Z, R3, R 10 As shown in any of the above items.

[0132] According to embodiments of this application, in the structure of formula (I-12), Z is selected from a chelating group, and R3 is selected from C. 1~6 Alkylene, R 10 Selected from C 3~10 Alkylene.

[0133] According to an embodiment of this application, in the structure of formula (I-12), R3 is selected from C 1~4 Alkylene.

[0134] According to an embodiment of this application, in the structure of formula (I-12), R 10 Selected from C 4~8 Alkylene.

[0135] According to an embodiment of this application, in the structure of formula (I-12), Z is selected from... DOTA NOTA.

[0136] According to embodiments of this application, the compound has the structure of formula (I-13): (I-13); Among them, Z, R3, R8, R 10 As shown in any of the above items.

[0137] According to embodiments of this application, in the structure of formula (I-13), Z is selected from a chelating group, and R3 is selected from C. 1~6 Alkylene, R8 is selected from C 1~6 Alkylene, R 10 Selected from C 3~10 Alkylene.

[0138] According to an embodiment of this application, in the structure of formula (I-13), R3 is selected from C 1~4 Alkylene.

[0139] According to an embodiment of this application, in the structure of formula (I-13), R8 is selected from C 1~3 Alkylene.

[0140] According to an embodiment of this application, in the structure of formula (I-13), R 10 Selected from C 4~8 Alkylene.

[0141] According to an embodiment of this application, in the structure of formula (I-13), Z is selected from... DOTA NOTA.

[0142] According to embodiments of this application, the compound has the structure of formula (I-14): (I-14); Among them, Z, R3, R8, R 10 As shown in any of the above items.

[0143] According to embodiments of this application, in the structure of formula (I-14), Z is selected from a chelating group, and R3 is selected from C. 1~6 Alkylene, R8 is selected from C 1~6 Alkylene, R 10 Selected from C 3~10 Alkylene.

[0144] According to an embodiment of this application, in the structure of formula (I-14), R3 is selected from C 1~4 Alkylene.

[0145] According to an embodiment of this application, in the structure of formula (I-14), R8 is selected from C 1~3 Alkylene.

[0146] According to an embodiment of this application, in the structure of formula (I-14), R 10 Selected from C 4~8 Alkylene.

[0147] According to an embodiment of this application, in the structure of formula (I-14), Z is selected from... DOTA NOTA.

[0148] According to embodiments of this application, the compound has the structure of formula (I-15): (I-15); Among them, Z and R 10 As shown in any of the above items.

[0149] According to embodiments of this application, in the structure of formula (I-15), Z is selected from chelating groups, and R... 10 Selected from C 3~10 Alkylene.

[0150] According to an embodiment of this application, in the structure of formula (I-15), R 10 Selected from C 4~8 Alkylene.

[0151] According to an embodiment of this application, in the structure of formula (I-15), Z is selected from... DOTA NOTA.

[0152] According to embodiments of this application, the compound has the structure of formula (I-16): (I-16); Among them, Z and R 10 As shown in any of the above items.

[0153] According to embodiments of this application, in the structure of formula (I-16), Z is selected from chelating groups, and R 10 Selected from C 3~10 Alkylene.

[0154] According to an embodiment of this application, in the structure of formula (I-16), R 10 Selected from C 4~8 Alkylene.

[0155] According to an embodiment of this application, in the structure of formula (I-16), Z is selected from... DOTA NOTA.

[0156] According to embodiments of this application, the compound has the structure of formula (I-17): (I-17); Among them, Z, R3, R4, R8, R 10 As shown in any of the above items.

[0157] According to embodiments of this application, in the structure of formula (I-17), Z is selected from chelating groups, and R3 and R4 are each independently selected from C. 1~6 Alkylene, R8 is selected from C 1~6 Alkylene, R 10 Selected from C 3~10 Alkylene.

[0158] According to an embodiment of this application, in the structure of formula (I-17), R3 and R4 are each independently selected from C. 1~4 Alkylene.

[0159] According to an embodiment of this application, in the structure of formula (I-17), R8 is selected from C 1~3 Alkylene.

[0160] According to an embodiment of this application, in the structure of formula (I-17), R 10 Selected from C 4~8 Alkylene.

[0161] According to an embodiment of this application, in the structure of formula (I-17), Z is selected from... DOTA NOTA.

[0162] According to embodiments of this application, the compound has the structure of formula (I-18): (I-18); Among them, Z, R3, R4, R8, R 10 As shown in any of the above items.

[0163] According to embodiments of this application, in the structure of formula (I-18), Z is selected from chelating groups, and R3 and R4 are each independently selected from C. 1~6 Alkylene, R8 is selected from C 1~6 Alkylene, R 10 Selected from C 3~10 Alkylene.

[0164] According to an embodiment of this application, in the structure of formula (I-18), R3 and R4 are each independently selected from C. 1~4 Alkylene.

[0165] According to an embodiment of this application, in the structure of formula (I-18), R8 is selected from C 1~3 Alkylene.

[0166] According to an embodiment of this application, in the structure of formula (I-18), R 10 Selected from C 4~8 Alkylene.

[0167] According to an embodiment of this application, in the structure of formula (I-18), Z is selected from... DOTA NOTA.

[0168] According to embodiments of this application, the compound has the following structure:

[0169]

[0170]

[0171]

[0172]

[0173]

[0174]

[0175]

[0176]

[0177]

[0178]

[0179]

[0180]

[0181]

[0182]

[0183] .

[0184] Metal complexes In a second aspect of this application, a complex is proposed. According to embodiments of this application, the complex comprises the compound described in the first aspect and M, wherein M is complexed with the compound; M is selected from radionuclides or non-radioactive elements. The complex of this application can be used as a radioactive tracer.

[0185] According to embodiments of this application, the complex may further include at least one of the following technical features: According to embodiments of this application, the radionuclide is selected from at least one of diagnostic radionuclides and therapeutic radionuclides.

[0186] According to embodiments of this application, the radionuclide is selected from... 67 / 68 Ga、 18 F, 99 mTc, 89 Zr、 124 I, 76 Br、 43 Sc、 111 In、 45 Ti、 52 Mn, 59 Fe、 94m Tc, 71 / 72 / 74 As、 82m Rb、 86 Y、 177 Lu、 90 Y、 131 I, 153 Sm、 60 / 61 / 62 / 64 / 67 Cu、 89 Sr、 166 Ho、 177 Yb、 47 Sc、 186 / 188 Re、 212 / 213 Bi、 149 Pm, 212 Pb, 211 At、 223 Ra、 161 Tb, 225 Ac or 227 Th.

[0187] According to embodiments of this application, the radionuclide is selected from... 68 Ga、18 F, 89 Zr、 99m Tc, 177 Lu、 225 Ac、 161 Tb.

[0188] According to embodiments of this application, the radionuclide 18 F is through 18 FAl is formed by complexing with the compound.

[0189] According to embodiments of this application, the radionuclide is selected from... 68 Ga、 18 F or 177 Lu.

[0190] According to embodiments of this application, the radionuclide is selected from... 68 Ga or 177 Lu.

[0191] Furthermore, those skilled in the art will understand that the features and advantages described above for the compound also apply to this complex, and will not be repeated here.

[0192] Imaging agent In a third aspect, this application provides an imaging agent. According to embodiments of this application, the imaging agent comprises the compound described in the first aspect or the complex described in the second aspect.

[0193] Furthermore, those skilled in the art will understand that the features and advantages described above for the compounds and complexes also apply to this imaging agent, and will not be repeated here.

[0194] Pharmaceutical Composition In a fourth aspect, this application provides a pharmaceutical composition. According to embodiments of this application, the pharmaceutical composition comprises the compound described in the first aspect, the complex described in the second aspect, or the imaging agent described in the third aspect.

[0195] According to embodiments of this application, the above-described pharmaceutical composition may further include at least one of the following technical features: In an optional embodiment of this application, the pharmaceutical composition may further include pharmaceutically acceptable excipients, carriers, or mediators.

[0196] In one optional embodiment of this application, pharmaceutically acceptable excipients refer to pharmaceutical excipients that are conventional in the pharmaceutical field, such as absorption enhancers, isotonic agents, stabilizers, regulators, etc.

[0197] In one alternative embodiment of this application, a pharmaceutically acceptable carrier refers to a drug carrier conventional in the pharmaceutical field.

[0198] In one alternative embodiment of this application, pharmaceutically acceptable mediators refer to pharmaceutical mediators conventional in the pharmaceutical field, such as solutions (e.g., water).

[0199] In one alternative embodiment of this application, examples of suitable pharmaceutically acceptable carriers, excipients, and mediators are well known in the art. Pharmaceutical compositions comprising such carriers, excipients, and mediators can be formulated using known conventional methods.

[0200] In some alternative embodiments, the pharmaceutical composition of this application may also contain other active ingredients for treatment.

[0201] The pharmaceutical composition of this application can be administered via various routes (e.g., orally or intravenously). Preferably, the pharmaceutical composition of this application is in solution form. Clinical dosing regimens are determined by the attending physician and clinical factors. As is known in the medical field, the dosage for any given patient depends on many factors, including patient size, body surface area, age, the drug to be administered, sex, time and route of administration, general health, and other concurrently administered medications. The pharmaceutical composition of this application can be administered topically or systemically. Preferably, it can be administered intravenously or subcutaneously. The pharmaceutical composition of this application can also be administered directly to the target site, for example, by targeted delivery to internal or external target sites.

[0202] Furthermore, those skilled in the art will understand that the features and advantages described above for the compounds and complexes also apply to this pharmaceutical composition, and will not be repeated here.

[0203] use In a fifth aspect of this application, the use of the compound described in the first aspect, the complex described in the second aspect, the imaging agent described in the third aspect, or the pharmaceutical composition described in the fourth aspect is provided.

[0204] In one aspect, this application provides for the use of the compound described in the first aspect, the complex described in the second aspect, the imaging agent described in the third aspect, or the pharmaceutical composition described in the fourth aspect in the preparation of a medicament for the diagnosis and / or treatment of CXCR4 overexpression diseases.

[0205] On the other hand, this application proposes the use of the compound described in the first aspect, the complex described in the second aspect, the imaging agent described in the third aspect, or the pharmaceutical composition described in the fourth aspect in the diagnosis and / or treatment of CXCR4 overexpression diseases.

[0206] In another aspect, this application proposes the compounds described in the first aspect, the complexes described in the second aspect, the imaging agents described in the third aspect, or the pharmaceutical compositions described in the fourth aspect for the diagnosis and / or treatment of CXCR4 overexpression diseases.

[0207] According to embodiments of this application, the above-described uses may further include at least one of the following technical features: According to embodiments of this application, the CXCR4 overexpression disease is selected from at least one of cancers, viral infectious diseases, immune-related diseases, or inflammatory and fibrotic diseases that express CXCR4.

[0208] According to embodiments of this application, the CXCR4 overexpression disease is selected from at least one of the following neoplastic diseases: breast cancer, lung cancer, prostate cancer, pancreatic cancer, colorectal cancer, ovarian cancer, neuroblastoma, glioblastoma, gastric cancer, melanoma, renal cell carcinoma, hepatocellular carcinoma, cholangiocarcinoma, esophageal cancer, cervical cancer, endometrial cancer, head and neck squamous cell carcinoma, and subtypes of the above tumors that are highly invasive, easily metastatic, or resistant to conventional treatment.

[0209] According to embodiments of this application, the CXCR4 overexpression disease is selected from at least one of the following hematologic malignancies: leukemia, acute myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, multiple myeloma, myelodysplastic syndrome, primary myelofibrosis, B-cell lymphoma, T-cell lymphoma, Hodgkin's lymphoma, and Burkitt's lymphoma.

[0210] According to embodiments of this application, the CXCR4 overexpression disease is selected from at least one of the infectious diseases: human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS), monkeypox virus infection, cytomegalovirus infection, hepatitis B virus infection, hepatitis C virus infection, and other viral infectious diseases associated with CXCR4-mediated immune cell recruitment or tissue damage.

[0211] According to embodiments of this application, the CXCR4 overexpression disease is selected from at least one of immunodeficiency diseases or autoimmune diseases: WHIM syndrome, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease, systemic sclerosis, and graft-versus-host disease.

[0212] According to embodiments of this application, the CXCR4 overexpression disease is selected from at least one of inflammatory or fibrosis-related diseases: atherosclerosis, acute lung injury, acute respiratory distress syndrome, pulmonary fibrosis, liver fibrosis, cirrhosis, renal fibrosis, cardiac fibrosis, pulmonary hypertension, and ischemia-reperfusion injury-related diseases.

[0213] The CXCR4 overexpression diseases also include those associated with adrenal dysfunction: primary aldosteronism, aldosterone-producing adenoma, adrenocortical tumors, and adrenal nodular hyperplasia.

[0214] According to embodiments of this application, the diagnostic method is selected from radionuclide imaging.

[0215] According to embodiments of this application, the diagnostic method is selected from positron emission tomography (PET) or single-photon emission computed tomography (SPECT).

[0216] According to an embodiment of this application, the treatment is selected from radiotherapy.

[0217] Furthermore, those skilled in the art will understand that the features and advantages described above for the compounds, complexes and pharmaceutical compositions also apply to this use, and will not be repeated here.

[0218] method In a sixth aspect of this application, a method for diagnosing and / or treating CXCR4 overexpression diseases is provided. According to embodiments of this application, the method comprises administering to a subject a pharmaceutically acceptable dose of the compound of the first aspect, the complex of the second aspect, the imaging agent of the third aspect, or the pharmaceutical composition of the fourth aspect.

[0219] According to embodiments of this application, the CXCR4 overexpression disease is selected from at least one of cancers, viral infectious diseases, immune-related diseases, or inflammatory and fibrotic diseases that express CXCR4.

[0220] According to embodiments of this application, the CXCR4 overexpression disease is selected from at least one of the following neoplastic diseases: breast cancer, lung cancer, prostate cancer, pancreatic cancer, colorectal cancer, ovarian cancer, neuroblastoma, glioblastoma, gastric cancer, melanoma, renal cell carcinoma, hepatocellular carcinoma, cholangiocarcinoma, esophageal cancer, cervical cancer, endometrial cancer, head and neck squamous cell carcinoma, and subtypes of the above tumors that are highly invasive, easily metastatic, or resistant to conventional treatment.

[0221] According to embodiments of this application, the CXCR4 overexpression disease is selected from at least one of the following hematologic malignancies: leukemia, acute myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, multiple myeloma, myelodysplastic syndrome, primary myelofibrosis, B-cell lymphoma, T-cell lymphoma, Hodgkin's lymphoma, and Burkitt's lymphoma.

[0222] According to embodiments of this application, the CXCR4 overexpression disease is selected from at least one of the infectious diseases: human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS), monkeypox virus infection, cytomegalovirus infection, hepatitis B virus infection, hepatitis C virus infection, and other viral infectious diseases associated with CXCR4-mediated immune cell recruitment or tissue damage.

[0223] According to embodiments of this application, the CXCR4 overexpression disease is selected from at least one of immunodeficiency diseases or autoimmune diseases: WHIM syndrome, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease, systemic sclerosis, and graft-versus-host disease.

[0224] According to embodiments of this application, the CXCR4 overexpression disease is selected from at least one of inflammatory or fibrosis-related diseases: atherosclerosis, acute lung injury, acute respiratory distress syndrome, pulmonary fibrosis, liver fibrosis, cirrhosis, renal fibrosis, cardiac fibrosis, pulmonary hypertension, and ischemia-reperfusion injury-related diseases.

[0225] The CXCR4 overexpression diseases also include those associated with adrenal dysfunction: primary aldosteronism, aldosterone-producing adenoma, adrenocortical tumors, and adrenal nodular hyperplasia.

[0226] According to embodiments of this application, the diagnostic method is selected from radionuclide imaging.

[0227] According to embodiments of this application, the diagnostic method is selected from positron emission tomography (PET) or single-photon emission computed tomography (SPECT).

[0228] According to an embodiment of this application, the treatment is selected from radiotherapy.

[0229] In one alternative embodiment of this application, the pharmaceutically acceptable dose may be selected from the effective dose (or effective amount).

[0230] The effective amount of the compound described in this application may vary depending on the administration method and the severity of the disease to be treated. A preferred effective amount can be determined by those skilled in the art based on various factors (e.g., through clinical trials). These factors include, but are not limited to: pharmacokinetic parameters of the active ingredient, such as bioavailability, metabolism, and half-life; the severity of the disease to be treated, the patient's weight, the patient's immune status, and the route of administration. For example, due to the urgency of the treatment condition, several separate doses may be administered daily, or the dose may be reduced proportionally.

[0231] The compounds or pharmaceutical compositions of this application may be incorporated into suitable pharmaceuticals, which may be prepared in various forms, such as liquids. Various routes of administration of the compounds, pharmaceutical compositions, or pharmaceuticals of this application are contemplated, including intravenous, intramuscular, and subcutaneous injection, but this application is not limited to these exemplified routes of administration.

[0232] Furthermore, those skilled in the art will understand that the features and advantages described above for compounds, metal complexes, and pharmaceutical compositions also apply to this method, and will not be repeated here.

[0233] The present application's solution will be explained below with reference to embodiments. Those skilled in the art will understand that the following embodiments are for illustrative purposes only and should not be construed as limiting the scope of the application. Where specific techniques or conditions are not specified in the embodiments, they are performed according to the techniques or conditions described in the literature in the field or according to the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be obtained commercially.

[0234] Unless otherwise specified, the experimental methods used in the following examples are conventional methods in the art; the reagents, raw materials, instruments, equipment, etc. used in the following examples are all commercially available.

[0235] The abbreviations of chemical reagent names and their corresponding full names are as follows:

[0236] Amino acids used in peptide synthesis:

[0237] Preparation Example 1: Preparation of Compound 1 The structure of compound 1 is as follows:

[0238] The synthesis steps are as follows: 1. Synthesizing Int 1-1:

[0239] 1.1 Peptide synthesis: The peptide was synthesized using standard Fmoc chemical methods.

[0240] 1) Weigh 2-CTC resin (Sub = 0.50 mmol / g, 0.50 mmol, 1.00 eq) and Fmoc-Pen-OH (0.50 mmol, 1.00 eq) into the reaction column. Add 30.0 mL of DCM and then add DIEA (2.00 mmol, 4.00 eq). Purge with nitrogen to make the resin swell evenly. After reacting at 20 °C for 2 h, add MeOH (1.00 mL) dropwise into the reaction column. Purge with nitrogen for 30 min, then purge until no liquid flows out. Add DMF to wash, then purge again until no liquid flows out.

[0241] 2) Deprotection: Add piperidine / DMF (20%, v / v, 30.0 mL) to the resin, agitate with nitrogen for 15 min, wash the resin with DMF, and dry it to obtain the resin.

[0242] 3) Coupling of amino acids: Weigh Fmoc-His(Trt)-OH (1.50 mmol, 3.00 eq) and HATU (1.42 mmol, 2.85 eq) into the above resin, add 30.0 mL of DMF, and then add DIEA (3.00 mmol, 6.00 eq) dropwise into the reaction column. Purge with nitrogen to make the resin bulge evenly. After reacting at 20 °C for 30 min, remove the reaction solution, add DMF to wash, and discharge waste until no liquid flows out.

[0243] 4) Repeat steps 2-3 above to couple the following amino acids / coupling substrates (3-8): Table 5

[0244] Shrink the resin with MeOH, discharge the waste until no more liquid flows out, pour out the resin and dry it for later use.

[0245] 1.2 Peptide cleavage: At room temperature, the dried resin was added to the prepared cutting solution (92.5% TFA / 2.5% H2O / 2.5% TIS / 2.5% 3-Mpr, 30.0 mL) for cutting. The solution was filtered, and the filtrate was added to ice-cold isopropyl ether for sedimentation and centrifugation. The solution was then washed with isopropyl ether and dried under vacuum.

[0246] 1.3 Peptide cyclization: At room temperature, the dried product was dissolved in a water / acetonitrile mixture (1:1, v / v, 500 mL), and 0.1 M I2 / MeOH was added dropwise until the solution turned pale yellow. The reaction was carried out at room temperature for 30 min. After the reaction was completed, the reaction solution was adjusted with 0.5 M sodium thiosulfate until the pale yellow color disappeared. The reaction solution was then freeze-dried to obtain the crude compound Int 1-1.

[0247] 1.4 Peptide purification: The crude compound Int 1-1 was purified by preparative high performance liquid chromatography (A: 0.075% TFA in H2O, B: acetonitrile) to obtain compound Int 1-1.

[0248] 2. Synthesize Int 1-2:

[0249] Compound 1-a (1.00 mmol, 1.0 eq) was dissolved in DMF, and DIPEA (1.50 mmol, 1.5 eq) was added, followed by compound 1-b (1.10 mmol, 1.1 eq). The mixture was stirred overnight at room temperature. The reaction solution was poured into water, extracted with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and purified to obtain compound 1-c.

[0250] Compound 1-c (0.5 mmol, 0.5 eq), DCC, DMAP, and N-hydroxysuccinimide (1.10 mmol, 1.1 eq) were added to DMF and reacted overnight. The reaction solution was diluted with ethyl acetate, washed with saturated NaHCO3 solution, and the organic layer was washed with saturated brine. The mixture was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude compound Int 1-2.

[0251] 3. Synthesize compound 1:

[0252] Compounds Int 1-1 (0.04 mmol, 0.02 eq), Int 1-2 (0.02 mmol, 0.01 eq), and DIPEA (0.06 mmol, 0.025 eq) were dissolved in DMF and reacted overnight. The solvent was removed by vacuum evaporation. A cleavage solution (TFA: H2O: TIS = 90:5:5, v / v) was added to the product, and the mixture was stirred at 30 °C for 3 h. The reaction mixture was poured into anhydrous diethyl ether, filtered, and the filter cake was washed with cold anhydrous diethyl ether and dried to give crude compound 1.

[0253] The crude compound 1 was purified by preparative high-performance liquid chromatography (C18, A: 100% H2O / 0.1% TFA, B: 100% ACN / 0.1% TFA) to obtain compound 1 (7 mg, purity 96.7%, TFA salt). The detection results are shown in [reference needed]. Figure 1 . MS cal.: 2593.1, MS observed: [M / 5+H] + = 519.5.

[0254] Preparation Example 2: Preparation of Compound 2 The structure of compound 2 is as follows:

[0255] The synthesis steps are as follows: 1. Synthesizing Int 2-1:

[0256] 1.1 Synthesis of polypeptides: The peptide was synthesized using standard Fmoc chemical methods.

[0257] 1) Weigh 2-CTC resin (Sub = 0.70 mmol / g, 1.00 mmol, 1.00 eq) and Fmoc-2-Nal-OH (1.00 mmol, 1.00 eq) into the reaction column. Add 100.0 mL of DCM, then add DIEA (4.00 mmol, 4.00 eq) dropwise. Purge with nitrogen to make the resin bulge evenly. After reacting at 20 °C for 2 h, add MeOH (3.00 mL) dropwise into the reaction column. Purge with nitrogen for 30 min, then purge until no liquid flows out. Add DMF to wash, then purge again until no liquid flows out.

[0258] 2) Deprotection: Add 20% piperidine (50.0 mL) to the resin and agitate with nitrogen for 15 min. Wash the resin with DMF and dry it under vacuum to obtain the final resin.

[0259] 3) Coupling of amino acids: Weigh Fmoc-Arg(Pbf)-OH (3.00 mmol, 3.00 eq) and HBTU (2.85 mmol, 2.85 eq) into the above resin. Add 80.0 mL of DMF and then add DIEA (6.00 mmol, 6.00 eq) dropwise into the reaction column. Purge with nitrogen to make the resin bulge evenly. After reacting at 20 °C for 50 min, remove the reaction solution, add DMF to wash, and discharge waste until no liquid flows out.

[0260] 4) Repeat steps 2-3 above to couple the following amino acids / coupling substrates (1-3): surface

[0261] Shrink the resin with MeOH, discharge the waste until no more liquid flows out, pour out the resin and dry it for later use.

[0262] 1.2 Peptide cleavage: At room temperature, the dried resin was added to the prepared cutting fluid (20% HFIP / 80% DCM) for cutting, filtered, the filtrate was evaporated to dryness, and then acetonitrile and water were added for lyophilization to obtain compound Int 2-1.

[0263] 2. Synthesizing Int 2-2:

[0264] To a DMF solution containing 700 mg of compound Int 2-1, 398 mg of TBTU and 167 mg of HOBt were added and stirred until dissolved. DIEA was then added until the pH of the reaction solution reached 7-8, and the reaction was carried out at 20 °C for 1 h. After the reaction was complete, the reaction solution was evaporated to dryness, and then 5.00 mL of 80% TFA / 20% DCM solution was added. The reaction was carried out at 20 °C for 1 h. After the reaction was complete, the reaction solution was evaporated to dryness to obtain compound Int 2-2.

[0265] 3. Synthesize Int 2-3:

[0266] Compounds 2-a (0.6 mmol, 1.50 eq), TBTU (0.48 mmol, 1.20 eq), and HOBt (0.48 mmol, 1.20 eq) were added to a DMF solution containing compound Int 2-2 (0.4 mmol, 1.00 eq) and stirred until dissolved. DIEA was added until the pH of the reaction solution reached 7-8, and the reaction was carried out at 20 °C for 1 h. After the reaction was complete, the reaction solution was evaporated to dryness, and then 80% TFA / 20% DCM (5.00 mL) solution was added. The reaction was carried out at 20 °C for 1 h. After the reaction was complete, the reaction solution was evaporated to dryness to obtain compound Int 2-3.

[0267] 4. Synthesizing Int 2-4:

[0268] Compound 2-b (1.00 mmol, 1.00 eq) was dissolved in DMF, and DIPEA (3.00 mmol, 3.00 eq) was added, followed by compound 2-c (1.20 mmol, 1.20 eq). The mixture was stirred overnight at room temperature, and then the reaction solution was poured into water. After extraction with ethyl acetate, the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and purified to obtain compound 2-d.

[0269] Compound 2-d (0.70 mmol, 1.00 eq), DCC (1.50 mmol, 2.00 eq), DMAP (1.50 mmol, 2.00 eq), and N-hydroxysuccinimide (3.50 mmol, 5.00 eq) were added to DMF and reacted overnight. The mixture was diluted with ethyl acetate, washed with saturated NaHCO3 solution, and the organic layer was washed with saturated brine. The mixture was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain the crude compound Int 2-4.

[0270] 5. Synthesize compound 2:

[0271] Compounds Int 2-3 (0.10 mmol, 2.00 eq), Int 2-4 (0.05 mmol, 1.00 eq), and DIPEA (0.20 mmol, 4.00 eq) were dissolved in DMF and reacted overnight. The solvent was removed by vacuum evaporation. A cleavage solution (trifluoroacetic acid:water:triisopropylsilane = 90:5:5, v / v) was added to the product, and the mixture was stirred at 30 °C for 3 h. The reaction mixture was poured into anhydrous diethyl ether, filtered, and the filter cake was washed with cold anhydrous diethyl ether and dried to give crude compound 2.

[0272] The crude compound 2 was purified by preparative high-performance liquid chromatography (C18, A: 100% H2O / 0.1% TFA, B: 100% ACN / 0.1% TFA) to obtain compound 2 (11 mg, purity 98.3%, TFA salt). The detection results are shown in [reference needed]. Figure 2 . MS cal.: 2066.3, MS observed: [M / 3+H] + = 689.7.

[0273] Preparation Example 3: The preparation of other compounds is the same as in Preparation Example 1 and Preparation Example 2. Specific compounds are listed in the table below:

[0274] Example 1: Radiolabeling of compounds Add 1 mL of sodium acetate / acetic acid buffer solution (pH=7.2) to the reaction flask, then add 60 μL of an aqueous solution containing one compound (containing 60 μg of the compound), mix thoroughly, and then add 1 mL of... 68 The GaCl3 was mixed thoroughly with 0.1 M hydrochloric acid solution and the labeling reaction was carried out under the conditions shown in the table below. After the reaction was complete, the reaction solution was purified using a C18 column, and the eluent was collected and filtered through a sterile filter membrane to obtain the labeled product.

[0275] Sampling and testing were performed using HPLC. 68 Ga-compound 1, 68 The radiochemical purities of Ga-compound 2 were 95.09% and 94.72%, respectively, as detailed in Table 1.

[0276] Table 1

[0277] Test Example 1: Compound Affinity Experiment The binding affinity of the compounds prepared in Example 1 was determined using an experimental method based on radioligand competitive binding.

[0278] CXCR4 / CHO-K1 cells were loaded at 1×10 5 Cells were seeded at a density of 10 cells / well into 96-well plates (96-well ClearRound Bottom Ultra-Low Attachment Microplate, 7007, purchased from Corning). DMSO solutions of the test compound, serially diluted 3-fold, were added to the 96-well plates, followed by the addition of radioactive ligands. 125 I-SDF-1α (NEX346, purchased from Revvity) was incubated at 25 °C for 180 min.

[0279] After incubation, the liquid in the 96-well plate was filtered, washed, and dried. Then, scintillation solution (purchased from Revvity) was added, and the plate was used in TopCount mode on the MicroBeta counter (MicroBeta2, 2450-0060). 125 I. The procedure reads the plate and determines the compound concentration required for 50% inhibition rate (IC50) using a four-parameter logistic dose-response model. 50The test results are shown in Table 2, indicating that the compound has a certain affinity for the CXCR4 receptor.

[0280] Table 2: Results of Compound Affinity Tests

[0281] Test Example 2: MicroPET / CT scan tissue distribution and targeting of drugs in Daudi tumor model mice Experimental materials: The Daudi tumor model mice used in this experiment were obtained from Biocytogen Jiangsu Gene Biotechnology Co., Ltd.

[0282] Experimental steps: The Daudi tumor model mice were selected for grouped experiments. Mice in each group were given the same drug, with each mouse receiving 80 μCi of the compound (e.g., 68 Ga-compound 1, 68 Ga-compound 2).

[0283] Mice that had been pre-anesthetized were placed in a MicroPET / CT imaging chamber (SNPC-303 Super Nova, Ping Sheng Medical Technology (Kunshan) Co., Ltd.) and kept under anesthesia. MicroPET / CT scans were performed at 30 min, 1 h and 2 h after drug administration.

[0284] After reconstruction using the equipment software, scanned images were obtained. Regions of interest (ROIs) were analyzed to determine the uptake of the radioactive tracer, yielding %ID / g values. Results are shown below. Figure 3 And Table 3.

[0285] Results analysis: The present invention discloses 68 Ga-compounds show radioactive uptake at the tumor site shortly after administration, and this uptake level remains stable over time. For a period after administration, there is still a significant radioactive uptake at the tumor site, while the radioactive uptake in most normal tissues continues to decrease, which is beneficial for achieving rapid and clear tumor imaging in clinical practice. Specifically, when administering... 68 Ga-compound 1 was enriched at the tumor site (indicated by the arrow) within 30 minutes after administration, and tumor uptake continued to increase over time; 2 hours after administration, high uptake was maintained at the tumor site, with tumor uptake still exceeding 5. Meanwhile, 68 The ratio of tumor uptake to muscle uptake in Ga-compound 1 gradually increases, reaching 17% two hours after administration, indicating a high target-to-supply ratio and clear tumor imaging, providing a sufficient imaging window for clinical use. Experimental results demonstrate that the method disclosed in this invention… 68Ga-compounds exhibit good tumor targeting, specificity, and retention capabilities, demonstrating their potential as radiotracers.

[0286] Table 3: 68 Radioactive uptake of Ga-compound 1 in different tissues of a mouse tumor model

[0287] Table 4: 68 Radioactive uptake of Ga-compound 2 in different tissues of tumor model mice

[0288] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of this application. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples.

[0289] Although embodiments of this application have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting this application. Those skilled in the art can make changes, modifications, substitutions and variations to the above embodiments within the scope of this application.

Claims

1. A compound, characterized in that, The compound comprises the structure shown in formula (I) or its isotopic variants, hydrates, esters or solvates, tautomers or stereoisomers, or pharmaceutically acceptable salts: (I)； in: Z is selected from a chelating group; Ra and Rb are each independently selected from ligand groups targeting CXCR4; X is selected from ** indicates that it is connected to Z; L1 and L2 are each independently selected from *-C(O)-phenyl-R8-R9-, *-C(O)-R 10 -R9-, or *-C(O)-phenyl-R8-NH-C(O)-R 10 -R9-, * indicates connection to Ra or Rb; R1 is selected from CH, N, phenyl, or 1,3,5-triazine alkyl groups; R2, R3, and R4 are each independently selected from empty, -R8-C(O)-, C 1~6 Alkylene; R5 and R6 are each independently selected as -N(R7)- or -C(O)-; R7 is selected from H or C. 1~6 alkyl; R8 is selected from C 1~6 Alkylene; R9 is selected from -N(R7)- or -C(O)-; R 10 Selected from C 3~10 Alkylene; Z and X, X and L1 or L2, Ra and L1, and Rb and L2 are all connected by amide bonds.

2. The compound according to claim 1, characterized in that, The compound satisfies one or more of the following conditions: 1) R1 is selected from phenyl, and R2, R3 and R4 are all empty; 2) R1 is selected from 1,3,5-triazine alkyl groups, R2 is selected from -R8-C(O)-, and R3 and R4 are each independently selected from C 1~6 Alkylene; Optionally, R1 is selected from 1,3,5-triazine alkyl groups, R2 is selected from -R8-C(O)-, and R8 is selected from C 1~3 Alkylenes, R3 and R4 are each independently selected from C10. 1~6 Alkylene; 3) R1 is selected from CH, R2 is empty, and one of R3 and R4 is empty while the other is C. 1~6 Alkylene; 4) R1 is selected from N, and R2, R3, and R4 are each independently selected from C. 1~6 Alkylene; 5) R5 and R6 are each independently selected from -NH- or -C(O)-; 6) R7 is selected from H.

3. The compound according to any one of claims 1 to 2, characterized in that, X is selected from , , , ,or ; Optionally, X is selected from , , , , ,or ; Optional, X is selected from , , , , , ,or .

4. The compound according to claim 1, characterized in that, The compound satisfies one or more of the following conditions: 1) In L1 and L2, R8 is selected from C. 1~3 Alkylene; 2) R9 is selected from -NH- or -C(O)-; 3) R 10 Selected from C 4~8 Alkylene.

5. The compound according to claim 1 or 4, characterized in that, L1 and L2 are each independently selected , , , , ; Optionally, L1 and L2 are each selected independently. , , , , , , , , , .

6. The compound according to claims 1-5, characterized in that, -L1-X-L2- Selected from 、 、 、 、 、 、 、 、 、 、 。 7. The compound according to claims 1-6, characterized in that, The ligand group targeting CXCR4 is selected from... ,or ; Optionally, the ligand group targeting CXCR4 is selected from... ,or ; Optionally, Ra and Rb may be the same or different; Optionally, Ra and Rb are the same.

8. The compound according to claims 1-7, characterized in that, The chelating group is derived from a chelating agent; The chelating agent is selected from 1,4,7,10-tetraazacyclododecane-N,N',N",N'''-tetraacetic acid (DOTA). N,N"-Bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N"-diacetic acid (HBED-CC) 1,4,7-Triazacyclononane-1,4,7-triacetic acid (NOTA) 2-(4,7-bis(carboxymethyl)-1,4,7-triazonon-1-yl)glutaric acid (NODAGA), 2-(4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane-1-yl)glutaric acid (DOTAGA), 1,4,7-Triazacyclononanephosphonic acid (TRAP) 1,4,7-Triazacyclononane-1-[methyl(2-carboxyethyl)phosphonic acid]-4,7-bis[methyl(2-hydroxymethyl)phosphonic acid] (NOPO), 3,6,9,15-Tetraazabicyclo[9.3.1.]pentadecan-1(15),11,13-triene-3,6,9-triacetic acid (PCTA), N'-{5-[acetyl(hydroxy)amino]pentyl}-N-[5-({4-[(5-aminopentyl)(hydroxy)amino]-4-oxobutyryl}amino)pentyl]-N-hydroxysuccinamide (DFO) Diethyltriaminepentaacetic acid (DTPA) trans-cyclohexyl-diethylenetriaminepentaacetic acid (CHX-DTPA) 1-Oxa-4,7,10-triazacyclododecane-4,7,10-triacetic acid (O-Do3A) p-Isocyanothiobenzyl-DTPA (SCN-Bz-DTPA), 1-(p-isocyanothiobenzyl)-3-methyl-DTPA (1B3M), 2-(p-isocyanothiobenzyl)-4-methyl-DTPA (1M3B), 1-(2)-Methyl-4-isocyanothiobenzyl-DTPA (MX-DTPA), [(R)-2-amino-3-(4-isothiocyanophenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diaminepentaacetic acid (p-SCN-Bn-CHX-A"-DTPA), 6-Hydroxypyridine-3-carboxylic acid (HYNIC) 2-(4-Isothiocyanophenyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA), or 2-[(4-isothiocyanophenyl)methyl]-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (p-SCN-Bn-DOTA); Preferably, Z is selected from DOTA NOTA、 NODAGA、 DOTAGA, HBED-CC, p-SCN-Bn-CHX-A"-DTPA、 p-SCN-Bn-NOTA and p-SCN-Bn-DOTA; Optionally, Z is selected from DOTA, or NOTA.

9. The compound according to claim 1, characterized in that, The compound has the following structures: formula (I-1), formula (I-2), formula (I-3), formula (I-4), formula (I-5), formula (I-6), formula (I-7), formula (I-8), formula (I-9), formula (I-10), formula (I-11), formula (I-12), formula (I-13), formula (I-14), formula (I-15), formula (I-16), formula (I-17), and formula (I-18). (I-1)； (I-2)； (I-3)； (I-4)； (I-5)； (I-6)； (I-7)； (I-8)； (I-9)； (I-10)； (I-11)； (I-12)； (I-13)； (I-14)； (I-15)； (I-16)； (I-17)； (I-18)； Among them, Z, R2, R3, R4, R8, R 10 As described in any one of claims 1 to 9; Optionally, R2, R3, and R4 are each independently selected from C. 1~6 Alkylene; Optionally, R2, R3, and R4 are each independently selected from C. 1~4 Alkylene; Optionally, R8 is selected from C. 1~6 Alkylene; Optionally, R8 is selected from C. 1~3 Alkylene; Optional, R 10 Selected from C 3~10 Alkylene; Optional, R 10 Selected from C 4~8 Alkylene; Optionally, Z is selected from chelating groups; Optionally, Z is selected from DOTA NOTA; Optionally, in equation (I-16), R 10 Selected from C 4~8 Alkylene; Optionally, in equation (I-1), R3 is selected from C 1~3 Alkylene, R8 is selected from C 1~3 Alkylene.

10. The compound according to any one of claims 1 to 9, characterized in that, The compound has the following structure: 。 11. A complex, characterized in that, It includes the compound according to any one of claims 1 to 10 and M, wherein M is complexed with the compound; M is selected from radioactive nuclides or non-radioactive elements; Optionally, the radionuclide is selected from... 67 / 68 Ga、 18 F, 99m Tc, 89 Zr、 124 I, 76 Br、 43 Sc、 111 In、 45 Ti、 52 Mn, 59 Fe、 94m Tc, 71 / 72 / 74 As、 82m Rb、 86 Y、 177 Lu、 90 Y、 131 I, 153 Sm、 60 / 61 / 62 / 64 / 67 Cu、 89 Sr、 166 Ho、 177 Yb、 47 Sc、 186 / 188 Re、 212 / 213 Bi、 149 Pm, 212 Pb, 211 At、 223 Ra、 161 Tb, 225 Ac or 227 Th; Optionally, the radionuclide is selected from... 68 Ga、 18 F, 89 Zr、 99m Tc, 177 Lu、 225 Ac、 161 Tb; Optionally, the radionuclide 18 F is through 18 Formed by the complexation of FAl with the compound; Optionally, the radionuclide is selected from... 68 Ga、 18 F or 177 Lu; Optionally, the radionuclide is selected from... 68 Ga.

12. An imaging agent, characterized in that, Includes the compound according to any one of claims 1 to 10 or the complex according to claim 11.

13. A pharmaceutical composition, characterized in that, It includes the compound according to any one of claims 1 to 10, the complex according to claim 11, or the imaging agent according to claim 12, and optionally pharmaceutically acceptable excipients, carriers, or mediators.

14. Use of the compound of any one of claims 1 to 10, the complex of claim 11, the imaging agent of claim 12, or the pharmaceutical composition of claim 13 in the preparation of a medicament for diagnosing and / or treating CXCR4 overexpression diseases; The CXCR4 overexpression disease is selected from at least one of the following: neoplastic diseases, infectious diseases, immune-related diseases, or inflammatory and fibrotic diseases that express CXCR4. The CXCR4 overexpression diseases are selected from at least one of the following neoplastic diseases: breast cancer, lung cancer, prostate cancer, pancreatic cancer, colorectal cancer, ovarian cancer, neuroblastoma, glioblastoma, gastric cancer, melanoma, renal cell carcinoma, hepatocellular carcinoma, bile duct cancer, esophageal cancer, cervical cancer, endometrial cancer, head and neck squamous cell carcinoma, and subtypes of the above tumors that are highly aggressive, easily metastatic, or resistant to conventional treatment. The CXCR4 overexpression diseases are selected from at least one of the following hematologic malignancies: leukemia, acute myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, multiple myeloma, myelodysplastic syndrome, primary myelofibrosis, B-cell lymphoma, T-cell lymphoma, Hodgkin's lymphoma, and Burkitt's lymphoma; The CXCR4 overexpression diseases are selected from at least one of the following infectious diseases: human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS), monkeypox virus infection, cytomegalovirus infection, hepatitis B virus infection, hepatitis C virus infection, and other viral infectious diseases associated with CXCR4-mediated immune cell recruitment or tissue damage. The CXCR4 overexpression diseases are selected from at least one of the following: immunodeficiency diseases or autoimmune diseases: WHIM syndrome, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease, systemic sclerosis, and graft-versus-host disease; The CXCR4 overexpression diseases are selected from at least one of the following inflammatory or fibrosis-related diseases: atherosclerosis, acute lung injury, acute respiratory distress syndrome, pulmonary fibrosis, liver fibrosis, cirrhosis, renal fibrosis, cardiac fibrosis, pulmonary hypertension, and ischemia-reperfusion injury-related diseases. The CXCR4 overexpression diseases also include those associated with adrenal dysfunction: primary aldosteronism, aldosterone-producing adenoma, adrenocortical tumors, and adrenal nodular hyperplasia. Optionally, the diagnostic method is selected from radionuclide imaging; Optionally, the diagnostic method is selected from positron emission tomography or single-photon emission computed tomography. Optionally, the treatment is selected from radiotherapy.

Images