Cyclic polypeptide compounds and their use

Abstract

This invention provides cyclic polypeptide compounds and their uses, specifically disclosing cyclic polypeptide compound A and cyclic polypeptide compound B. Cyclic polypeptide compound A is a compound formed by chelating compound X with a therapeutic radionuclide ion. Cyclic polypeptide compound B is a compound formed by chelating compound X with a diagnostic radionuclide ion. These compounds can be used for the diagnosis and treatment of tumors associated with or mediated by FAP, exhibiting high tumor uptake, long residence times, and broad applicability. JPEG2026513316000414.jpg50104

Description

[Technical Field]

[0001] This invention relates to cyclic polypeptide compounds and their uses. [Background technology]

[0002] Chemotherapy is still widely used to treat cancer patients and other diseases. Conventional anti-cancer chemotherapy drugs act on the basic mechanisms of cell survival and cannot effectively distinguish between healthy and malignant cells. Furthermore, these drugs do not effectively reach and accumulate at the disease site after systemic administration. Nonspecific mechanisms of action and inefficient localization to tumor sites are causes of side effects and reduced therapeutic efficacy.

[0003] In recent years, the development of targeted drugs has become a hot topic in new drug research and development to more effectively treat diseases. These drugs selectively localize to the disease site after systemic administration and exert their effects. These drugs are substances in which a chemical substance with a typical therapeutic effect (e.g., a cytotoxic drug or radionuclide) is conjugated with a ligand that has target cell specificity. Disease-specific monoclonal antibodies, peptides, and small molecule ligands are ideal ligands for the development of targeted drugs. In targeted use, using small molecule ligands instead of large molecules (e.g., peptides and antibodies) allows for faster and more effective penetration into tumors, lower immunogenicity, and lower manufacturing costs.

[0004] A tumor is a complex composed of tumor cells and the surrounding matrix cells and non-cellular components. Tumor development is a dynamic process in which tumor cells and their tumor microenvironment (TME) mutually promote and evolve together. The tumor microenvironment consists of multiple heterogeneous cell lines, including endothelial cells, fibroblasts (cancer-associated fibroblasts, CAFs), and their extracellular products, as well as immune cells. Among these, cancer-associated fibroblasts (CAFs) are the most important stromal cells in the tumor microenvironment, accounting for approximately 50% of the total number of tumor tissue cells. CAFs play a crucial role in tumor growth, metastasis, drug resistance, and treatment resistance, making them one of the hot topics in recent tumor diagnosis and treatment research.

[0005] A prominent feature of CAFs is the high expression of seprase or fibroblast activation protein (FAP). Both are cell surface membrane serine proteases that possess both dipeptidyl peptidase (DPP) and collagenase activity, and can degrade dipeptides and type I collagen. FAP has a similar structural domain and dipeptidyl peptidase activity to dipeptidyl peptidase IV (PPIV) and belongs to the same serine protease family. However, FAP has a unique endopeptidase activity that allows it to cleave gelatin, denatured type I collagen, and α2-antifibrotic proteins, while DPPIV lacks this function, thus distinguishing them. FAP is selectively expressed on the surface of stromal fibroblasts in over 90% of epithelial malignancies, including breast cancer, ovarian cancer, lung cancer, colorectal cancer, gastric cancer, pancreatic cancer, and cutaneous melanoma. FAP is not typically expressed in benign and precancerous intraepithelial neoplasias such as colorectal adenomas, mammary phyllodes tumors, and fibroadenomas. FAP is not normally expressed in normal human tissues, being present only in the cervix and endometrium, and is expressed for a short period during embryonic development. Numerous studies have shown that high expression of FAP in epithelial tumor CAFs is associated with poor patient prognosis, and that its activity levels are linked to cancer development and the metastasis and spread of cancer cells.

[0006] Radioactive radionuclides are pharmaceuticals consisting of radioisotopes and molecular reagents that target specific organs and tissues. They are radiopharmaceuticals that can be used in diagnostic imaging and clinical treatment. Depending on their intended use, they are classified into diagnostic radioactive radionuclides and therapeutic radioactive radionuclides.

[0007] Diagnostic radionuclides are classified into two types: organ imaging agents and functional measurement agents. By combining them with SPECT or PET, they enable molecular-level research into the function and metabolic processes of drugs in vivo, achieving rapid, non-destructive, real-time imaging of physiological and pathological processes, and providing a means to enable truly early diagnosis and rapid treatment.

[0008] Therapeutic radionuclide medicines can be administered orally or by injection to patients, and then highly selectively concentrated in diseased tissue. The radiation emitted from the radioisotopes produces a localized ionizing radiobiological effect, inhibiting or destroying diseased tissue and thus providing a therapeutic effect.

[0009] In recent years, methods using FAP as a target for tumor diagnosis and treatment have attracted widespread attention. Diagnostically, compared to FDG imaging, FAP-targeted imaging exhibits lower background noise in organs such as the brain and liver, and a higher detection rate of tumor lesions. However, so far, this type of probe has not shown particularly favorable results in treatment. The main reasons for this are that the biological activity of these compounds is often relatively low, resulting in poor absorption at the lesion site and a short residence time in the body. Furthermore, from the perspective of ligand selection, the binding of monomers to receptors exhibits a one-to-one correspondence, leading to poor stability of binding to the receptor and low absorption at the lesion, thus significantly limiting diagnostic and therapeutic efficacy. Therefore, using this as a target for nuclear medicine imaging presents a promising strategy for early diagnosis of malignant tumors, tumor staging, or as a companion diagnostic tool for tumor treatment and efficacy evaluation. [Overview of the project]

[0010] This application claims priority to Chinese patent application 202310307579.5, filed on March 27, 2023. This application incorporates the full text of the aforementioned Chinese patent application.

[0011] This application claims priority to Chinese patent application 202310934748.8, filed on 27 July 2023. This application incorporates the full text of the aforementioned Chinese patent application. The object of the present invention is to provide a cyclic polypeptide compound and its use in order to solve existing problems in the art, such as low affinity of the compound to FAP, too short residence time at the target, or too low uptake by the lesion. The cyclic polypeptide compound has advantages such as being easy to manufacture, having good stability, high uptake by tumors, and a long residence time, making it suitable for clinical use.

[0012] The present invention provides compound X or a pharmaceutically acceptable salt thereof. [ka] Here, -X1- is [ka] R 1 The group is a C1-C4 alkylene group, a C3-C6 cycloalkylene group, a C1-C4 alkylene-C3-C6 cycloalkylene group, or a C1-C4 alkylene-C3-C6 heterocycloalkylene group, wherein the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and it contains at least one N. R 2 is hydrogen or a C1-C4 alkyl group, R 3 The group is a C1-C4 alkylene group, a C1-C4 alkylene-3-6 member heterocycloalkylene group, a 3-6 member heterocycloalkylene group, or a 6-12 member heteroarylene group, wherein the heteroatoms of the 3-6 member heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, and includes at least one N, and the heteroatoms of the 6-12 member heteroarylene group are selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, and includes at least one N, R 4is a 3- to 6-member heterocycloalkylene group, and the heteroatoms of the 3- to 6-member heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and at least one N is included. -X2- is -X 2-1 -Y1-, and -X 2-1 - is a chemical bond, a non-natural amino acid residue, or a natural amino acid residue, and Y1 is

Chemical formula

Chemical formula

Chemical formula

[0013] In one embodiment, the definition of a particular substituent of compound X may be as follows, and the definition of substituents not mentioned is as described in any of the embodiments above.

[0014] In one embodiment, R 1 In the C1-C4 alkylene group, the C1-C4 alkylene-C3-C6 cycloalkylene group, and the C1-C4 alkylene-C3-C6 heterocycloalkylene group, the C1-C4 alkylene-C3-C6 heterocycloalkylene group are each independently a methylene group, an ethylene group, an n-propylene group, or an isopropylene group, for example, a methylene group.

[0015] In one embodiment, R 1 And the C3-C6 cycloalkylene group in the aforementioned C1-C4 alkylene-C3-C6 cycloalkylene group is a cyclobutylene group (for example, [ka] ) or a cyclopropylene group.

[0016] In one embodiment, R 1 In the C1-C4 alkylene-C3-C6 heterocycloalkylene group, the C3-C6 heterocycloalkylene group is a C4-C6 heterocycloalkylene group, and in the C3-C6 heterocycloalkylene group, the heteroatom is preferably N, the number of heteroatoms is preferably 1, and the C3-C6 heterocycloalkylene group is, for example, an azoxycyclohexylene group (for example, [ka]

[0017] ) In one embodiment, R 2 The C1-C4 alkyl group is a methyl group, an ethyl group, an n-propyl group, or an isopropyl group. In one embodiment, R 3 In the C1-C4 alkylene group and the C1-C4 alkylene-3-6 membered heterocycloalkylene group, the C1-C4 alkylene group is independently a methylene group, an ethylene group, an n-propylene group, and an isopropylene group, respectively.

[0018] In one embodiment, R 3 In the C1-C4 alkylene-3-6 membered heterocycloalkylene group and the 3-6 membered heterocycloalkylene group, each is independently a 4-6 membered heterocycloalkylene group, and in the 3-6 membered heterocycloalkylene group, the heteroatom is preferably N, and the number of heteroatoms is preferably 1, for example, the 3-6 membered heterocycloalkylene group is an azoxycyclobutylene group (for example, [ka] )

[0019] In one embodiment, R 3 The 6-12 membered heteroarylene group is a 6-10 membered heteroarylene group, and in the 6-12 membered heteroarylene group, the heteroatom is preferably N, and the number of heteroatoms is preferably 1. In one embodiment, R 4 The 3-6 member heterocycloalkylene group is a 4-6 member heterocycloalkylene group, and in the 3-6 member heterocycloalkylene group, the heteroatom is preferably N, the number of heteroatoms is preferably 1, and the 3-6 member heterocycloalkylene group is, for example, an azoxycyclohexylene group (for example, [ka] )

[0020] In one embodiment, -X 2-1 -Then the aforementioned non-natural amino acid residue is D-alanine (for example, [ka] ) or [ka] That is the case.

[0021] In one embodiment, -X 2-1 -Then the aforementioned natural amino acid residue is glycine (for example, [ka] ) or L-alanine (for example, [ka] )

[0022] In one embodiment, R 5 The C1-C4 alkylene group and one, two or three R 5-1 The C1-C4 alkylene groups substituted by are each independently a methylene group, an ethylene group, an n-propylene group, or an isopropylene group, for example, an ethylene group or an n-propylene group. In one embodiment, -X 3-1 -The aforementioned non-natural amino acid residue is [ka]

[0023] In one embodiment, -X 3-1 -Then the aforementioned natural amino acid residue is glycine (for example, [ka] For example, the aforementioned natural amino acid residue is [ka] That is the case.

[0024] In one embodiment, R 6 And the C1-C4 alkyl group and one, two or two R 6-1 The C1-C4 alkylene groups of the C1-C4 alkyl group substituted by are each independently a methylene group, an ethylene group, an n-propylene group, or an isopropylene group, for example, a methylene group.

[0025] In one embodiment, R 6 The C3-C6 cycloalkyl group is a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group. In one embodiment, R 6-1 The C3-C6 cycloalkyl group is a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group, for example, a cyclohexyl group (for example, [ka] )

[0026] In one embodiment, R 6-1 So, the above C6~C 10 An aryl group, and one or more R 6-1-1 C6~C substituted by 10 C6~C of aryl group 10 Each aryl group is independently either a phenyl group or a naphthyl group; for example, it is a phenyl group. In one embodiment, R 6-1-1 The halogen is fluorine, chlorine, or bromine.

[0027] In one embodiment, R 7The 3-6 membered heterocycloalkylene group is a 4-6 membered heterocycloalkylene group, and in the 3-6 membered heterocycloalkylene group, the heteroatom is preferably N, the number of heteroatoms is preferably 1, and the 3-6 membered heterocycloalkylene group is, for example, an azoxycyclopentylene group (for example, [ka] )

[0028] In one embodiment, R 8 And the aforementioned C 1-10 The alkyl group is a methyl group, ethyl group, n-propyl group, n-butyl group, n-pentyl group, n-hexyl group, n-heptyl group, n-octyl group, or n-nonyl group, for example, a methyl group, n-pentyl group, n-nonyl group, n-heptyl group, or n-butyl group.

[0029] In one embodiment, R 9 The C1-C4 alkyl group is a methyl group, an ethyl group, an n-propyl group, or an isopropyl group, for example, an ethyl group (for example, [ka] )

[0030] In one embodiment, in L1 and L2, the C1-C4 alkylene group is a methylene group, an ethylene group, an n-propylene group, or an isopropylene group, for example, an n-propylene group.

[0031] In one embodiment, the 3-6 membered heterocycloalkylene group is a 5-6 membered heterocycloalkylene group, the heteroatom of the 3-6 membered heterocycloalkylene group is preferably N, and the number of heteroatoms is preferably 3.

[0032] In one embodiment, Cy, the heteroatom of the 5- or 6-membered heteroarylene group is N, and the number of heteroatoms is preferably 1 or 3. For example, the 5- or 6-membered heteroarylene group is a heteroarylene group such as a pyridyl group (e.g., [Chemical formula] ) or 1H-1,2,3-triazole (e.g., [Chemical formula] ).

[0033] In one embodiment, Cy, the C6-C 10 [[ID=​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​The alkylene group is a methyl group, an ethyl group, an n-propyl group, an n-butyl group, an n-pentyl group or an n-hexyl group, and for example, it is a methyl group, an ethyl group or an n-propyl group. In one embodiment, L 3-3 wherein the 6- to 12-membered heteroarylene group is a 12-membered heteroarylene group, and in the 6- to 12-membered heteroarylene group, the heteroatom is preferably N, the number of heteroatoms is preferably 1, and for example, the 6- to 12-membered heteroarylene group is

Chemical formula

[0036] In one embodiment, L 3-3 wherein the carbonyl-C 1-6 alkylene-3- to 6-membered heterocycloalkylene group, NH-C 1-6 alkylene-3- to 6-membered heterocycloalkylene group and the 3- to 6-membered heterocycloalkylene group of the 3- to 6-membered heterocycloalkylene group are each independently a 4- to 6-membered heterocycloalkylene group, the heteroatom is preferably N, the number of heteroatoms is preferably 1 or 2, and the 3- to 6-membered heterocycloalkylene group is, for example, an azoxycyclohexylene group (for example,

Chemical formula

[0037] In one embodiment, L 3-3 wherein the carbonyl-C 1-6 alkylene-3- to 6-membered heterocycloalkylene group and NH-C 1-6 the C of the alkylene-3- to 6-membered heterocycloalkylene group of the alkylene-3- to 6-membered heterocycloalkylene group 1-6 alkylene groups are each independently a methyl group, an ethyl group, an n-propyl group, an n-butyl group, an n-pentyl group or an n-hexyl group, and for example, they are a methyl group, an ethyl group or an n-propyl group.

[0038] [[ID=4…]] In one embodiment, -L3-1- in, [ka]

[0039] In one embodiment, -L 3-1 -in, [ka]

[0040] In one embodiment, -X1- is [ka] [ka] It is connected to X4.

[0041] In one embodiment, -X2- is -X 2-1 -Y1-, where X 2-1 It is connected to X4. In one embodiment, -X3- is -X 3-1 -Y2-, where X 3-1 is-NH-( [ka] (NH-) or carbonyl group ( [ka] It is linked to the carbonyl group.

[0042] In one embodiment, -X4- is [ka] And here, [ka] It is connected to X2.

[0043] In one embodiment, W is -NH-CO-* or -NH-CO-NH-*, where -* is R 8 It is connected to. In one embodiment, L1 and L2 are each independently a chemical bond, a C1-C4 alkylene group, or -S-(CH2) k -*, where * is concatenated to Cy.

[0044] In one embodiment, -L3- is -L 3-1 -L 3-2 -L 3-3 -* is where -* is R 11 It is connected to.

[0045] In one embodiment, -L 3-1 - is a chemical bond, [ka] And here, [ka] ha-L 3-2 - is linked to

[0046] In one embodiment, -L 3-2 - is *-X5-Y3-, where *- is -L 3-1 - is linked to In one embodiment, -L 3-3 - represents a chemical bond, -NH-, -carbonyl-6~12 member heteroarylene-*, -carbonyl-C 1-6 Alkylene-3 to 6-membered heterocycloalkylene-*,-NH-C 1-6 Alkylene-3-6 member heterocycloalkylene-* or a 3-6 member heterocycloalkylene group, where -* is R 11 It is connected to.

[0047] In one embodiment, -L4- is

Chemical formula

Chemical formula

[0048] In one embodiment, -X1- is

Chemical formula

[0049] In one embodiment, R 1 is a C3-C6 cycloalkylene group or a C1-C4 alkylene-C3-C6 heterocycloalkylene group, the heteroatom of the 3- to 6-membered heterocycloalkylene group is selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and at least one N is included.

[0050] In one embodiment, R 2 is hydrogen. In one embodiment, R 3 is a 3- to 6-membered heterocycloalkylene group, the heteroatom of the 3- to 6-membered heterocycloalkylene group is selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and at least one N is included,

[0051] In one embodiment, -X 2-1 - is a chemical bond, a non-natural amino acid residue or a natural amino acid residue, and the non-natural amino acid residue is [ka] The aforementioned natural amino acid residues are [ka] And for example, -X 2-1 - represents a chemical bond.

[0052] In one embodiment, -X 2-1 - is -X 2-1 -Y1- and -X 2-1 - is a chemical bond, and Y1 is [ka] That is the case.

[0053] In one embodiment, R 5 Each of these is independently one, two, or three R 5-1 These are C1-C4 alkylene groups substituted by [the specified agent]. In one embodiment, each R 5-1 Each of these is independently a halogen, a hydroxyl group, a guanidine group (-NHC(=NH)NH2), or an amide group, for example a hydroxyl group, a guanidine group (-NHC(=NH)NH2), or an amide group, for example a hydroxyl group.

[0054] In one embodiment, -X 3-1 - represents a chemical bond or a natural amino acid residue, and the natural amino acid residue is, for example, [ka] And for example, -X 3-1 - represents a chemical bond.

[0055] In one embodiment, -X3- is -X 3-1 -Y2- and -X 3-1- is a chemical bond, and Y2 is [Chem.] as follows.

[0056] In one embodiment, R 6 is a C1-C4 alkyl group substituted by one or two R 6-1 . In one embodiment, each R 6-1 is independently halogen, a C3-C6 cycloalkyl group or a C6-C 10 aryl group, for example, a C3-C6 cycloalkyl group or a C6-C 10 aryl group.

[0057] In one embodiment, R 9 is a C1-C4 alkyl group substituted by one or two R 9-1 , R 9-1 is an amide group (-CONH2), for example, R 9 is a C1-C4 alkyl group substituted by one R 9-1 , and R 9-1 is an amide group (-CONH2). In one embodiment, L1 and L2 are -S-(CH2) k -, and k is 1.

[0058] In one embodiment, k is 0 or 1, for example, 1. In one embodiment, Cy is a chemical bond, a 5-6 member heteroarylene group, a C6-C 10 arylene group, or a C6-C 10 arylene-L4-R 12 , wherein the 5-6 member heteroarylene group has heteroatoms selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and at least one N is included, for example, a C6-C 10 arylene group (for example, a phenylene group).

[0059] In one embodiment, Cy is a chemical bond, a 3-6 membered heterocycloalkylene group, a 5-6 membered heteroarylene group, or C6-C 10 The arylene group is characterized in that the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and at least one N is included, and the 5-6 membered heteroarylene group is characterized in that the heteroatoms are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and at least one N is included, R 11 It is a chelating group, Preferably, Cy is C6~C 10 Arylene group (for example, [ka] ) and R 11 It is a chelating group.

[0060] In one embodiment, T1 and T2 are independently 0 or 1. In one embodiment, T3 and T4 are each independently 0, 1, or 3, for example, 0 or 1. In one embodiment, -L 3-2 - is -X5-Y3-, where -X5- is a chemical bond, or a polypeptide formed from 2 to 6 natural amino acids, and -Y3- is a chemical bond. [ka] For example, -X5- is a chemical bond, and -Y3- is [ka] Alternatively, -X5- is a polypeptide formed from 2 to 6 natural amino acids, and -Y3- is a chemical bond or [ka] And, for example, -X5- is a chemical bond, and -Y3- is a chemical bond. [ka] A is a chemical bond or -NH-.

[0061] In one embodiment, -L 3-1 teeth [ka] That is the case.

[0062] In one embodiment, -L 3-2 - is -X5-Y3-, where -X5- is a chemical bond and -Y3- is a chemical bond. [ka] T5 and T6 are independently 0, 1, 2, or 4, and E and Q are independently C 1-6 It is an alkylene group, and A is either a chemical bond or -NH-.

[0063] In one embodiment, -L 3-3 - represents a chemical bond, -NH-, -carbonyl-C 1-6 Alkylene-3 to 6-membered heterocycloalkylene-,-NH-C 1-6 Alkylene-3 to 6-membered heterocycloalkylene-, for example, -L 3-3 - is -NH-, -carbonyl-C 1-6 Alkylene-3 to 6-membered heterocycloalkylene-,-NH-C 1-6 The alkylene is a 3- to 6-membered heterocycloalkylene, where the heteroatoms of the 3- to 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and it contains at least one N.

[0064] In one embodiment, -L 3-1 teeth [ka] And T1 and T2 are independently 0, 1, 2, 3, or 4. -L 3-2 - is -X5-Y3-, where -X5- is a chemical bond and -Y3- is [ka] T6 is 0, 1, 2, 3 or 4, and E is C 1-6 Alkylene group or (OCH2CH2) j’ - is -, j' is 1, 2, 3, 4, 5 or 6 (for example, 1), and A is a chemical bond or -NH-, -L 3-3 - represents a chemical bond.

[0065] In one embodiment, -L 3-1 teeth [ka] And T1 and T2 are independently 0, 1, 2, 3, or 4. -L 3-2 - is -X5-Y3-, where -X5- is a chemical bond and -Y3- is a chemical bond. -L 3-3 - is -NH-C 1-6 The molecule is an alkylene-3-6 membered heterocycloalkylene- or a 3-6 membered heterocycloalkylene group, wherein the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and it contains at least one N.

[0066] In one embodiment, -L3- is -L 3-1 -L 3-2 -L 3-3 -and, -L 3-1 teeth [ka] And T3 and T4 are independently 0, 1, 2, 3, or 4, -L 3-2 - is -X5-Y3-, where -X5- is a chemical bond and -Y3- is [ka] T5 is 0, 1, 2, 3 or 4, and Q is C 1-6 Alkylene group or (OCH2CH2) j’ - and j' is 1, 2, 3, 4, 5, or 6. -L 3-3 - is -NH-

[0067] In one embodiment, -L 3-1 teeth [ka] And T3 and T4 are independently 0, 1, 2, 3, or 4, -L 3-2 - is -X5-Y3-, where -X5- is a chemical bond and -Y3- is a chemical bond. -L 3-3 - is -carbonyl-6~12 member heteroarylene-, -carbonyl-C 1-6 Alkylene-3 to 6-membered heterocycloalkylene-(e.g., -carbonyl-C) 1-6 The alkylene (3-6 member heterocycloalkylene), wherein the heteroatoms of the 3-6 member heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N; and the heteroatoms of the 6-12 member heteroarylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N.

[0068] In one embodiment, -L 3-1 teeth [ka] And T1 and T2 are independently 0, 1, 2, 3, or 4. -L 3-2 - is -X5-Y3-, where -X5- is a natural amino acid residue, or a polypeptide formed from 2 to 6 natural amino acid residues (for example, [ka] ) and Y3 is a chemical bond, -L 3-3 - represents a chemical bond.

[0069] In one embodiment, E and Q are each independently C 1-6 It is an alkylene group. In one embodiment, T5 and T6 are each independently 0, 1, 2, or 4, for example, 0, 1, or 2.

[0070] In one embodiment, j' is 1, 2, or 3. In one embodiment, R 10 It is a hydroxyl group. In one embodiment, -L4- is [ka] And L 4-1 It is a chemical bond.

[0071] In one embodiment, the chelate group is [ka] That is the case.

[0072] In one embodiment, R 11 is a chelating group, and the chelating group is [ka] That is the case.

[0073] In one embodiment, the compound X is (1)-X1- is [ka] And R 3 The group is a 4-membered or 6-membered heterocycloalkylene group, and the heteroatoms of the 4-membered or 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and it contains at least one N. (2)R 6 is one or two R 6-1 A C1-C4 alkyl group substituted by, and each R 6-1 Each element independently satisfies one or more of the conditions for being a C3-C6 cycloalkyl group. In one technical solution, compound X is compound X-1, compound X-2, compound X-3, or compound X-4, [ka] Z is either N or CH. X1, X2, X3, X4, R 9 , R 8 , L1, W, L2, L3 and R 11 The definition is as described in any one of the present inventions.

[0074] In one technical solution, compound X is compound X-5, [ka] X1, X2, X3, R 9 , R 8 W, L1, L2, Cy, L3 and R 11 The definition is as described in any one of the present inventions.

[0075] In one technical solution, compound X is compound X-6, compound X-7, compound X-8, or compound X-9, [ka] Here, X1, X2, R 9 , R 8 , L1, L2, Cy, L3 and R 11 The definition is as described in any one of the present inventions.

[0076] In one technical solution, with compound X, -X1- is [ka] R 1 The group is a C3-C6 cycloalkylene group or a C1-C4 alkylene-C3-C6 heterocycloalkylene group, and the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and it contains at least one N. R 2 It is hydrogen, R 3 This is a 3-6 membered heterocycloalkylene group, where the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and it contains at least one N. R 4 This is a 3-6 membered heterocycloalkylene group, where the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and it contains at least one N. -X2- is -X 2-1 -Y1- and -X 2-1 - represents a chemical bond, a non-natural amino acid residue, or a natural amino acid residue. The aforementioned non-natural amino acid residues are [ka] The aforementioned natural amino acid residues are [ka] [ka] And, R 5 Each of these is independently one, two, or three R 5-1 A C1-C4 alkylene group substituted by, R 5-1 Each of these is independently a hydroxyl group, a guanidino group, or an amide group. -X3- is -X 3-1 -Y2- and -X 3-1 - represents a chemical bond or a natural amino acid residue. The aforementioned natural amino acid residues are [ka] And Y2 is [ka] And, R 6 is one or two R 6-1 A C1-C4 alkyl group substituted by, and each R 6-1 These are independently halogens, C3-C6 cycloalkyl groups, or C6-C6 10 It is an aryl group, -X4- is [ka] And R 7 This is a 3-6 membered heterocycloalkylene group, where the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and it contains at least one N. W is -NH-CO- or -NH-CO-NH-, R 8 is a straight chain C 1-10 It is an alkyl group, R 9 is H or one or two R 9-1 A C1-C4 alkyl group substituted by R 9-1 This is a carboxyl group (-COOH) or an amide group (-CONH2), L1 and L2 are each independently chemically bonded, C1-C4 alkylene groups, or -S-(CH2) k - and k is 0 or 1, Cy is a chemical bond, a 5-6 membered heteroarylene group, C6-C 10 Arylene group, or C6~C 10 Arirene-L4-R 12 The 5-6 membered heteroarylene group is such that the heteroatoms are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and it contains at least one N. -L3- is -L 3-1 -L 3-2 -L 3-3 -and, -L 3-1 is a chemical bond, [ka] T1 and T2 are independently 0 or 1, and T3 and T4 are independently 0, 1 or 3. -L 3-2 - is -X5-Y3-, where -X5- is a chemical bond, or a polypeptide formed from 2 to 6 natural amino acids, and -Y3- is a chemical bond. [ka] T5 and T6 are independently 0, 1, 2, or 4, and E and Q are independently C 1-6 Alkylene group or -(OCH2CH2) j’- is -, j' is 1, 2 or 3, and A is a chemical bond or -NH-, -L 3-3 - is a chemical bond, -NH-, -carbonyl-6~12 member heteroarylene-, -carbonyl-C 1-6 Alkylene-3 to 6-membered heterocycloalkylene-,-NH-C 1-6 The alkylene-3-6 membered heterocycloalkylene- or 3-6 membered heterocycloalkylene group, wherein the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, and includes at least 1 N; and the heteroatoms of the 6-12 membered heteroarylene group are selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3, and includes at least 1 N. R 10 is a hydroxyl group or an amino group, -L4- is [ka] And L 4-1 It is a chemical bond, R 12 and R 11 Each of them is independently either H or a chelating group, and R 11 When H, R 12 is a chelating group, or R 12 When H, R 11 It is a chelating group, The aforementioned chelate group [ka] , NOTA, HBED-CC, NODAGA, NOTAGA, DOTAGA, TRAP, NOPO, PCTA, DFO, DTPA, CHX-DTPA, AAZTA or DEDPA, The aforementioned compound X is (1)-X1- is [ka] R 1 This is a C3-C6 cycloalkylene group, or a C1-C4 alkylene-C3-C6 heterocycloalkylene group. R 2 It is hydrogen, R 3 is a 4-membered or 6-membered heterocycloalkylene group, wherein the heteroatoms of the 4-membered or 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and includes at least one N. R 4 This is a 3-6 membered heterocycloalkylene group, where the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and it contains at least one N. (2)-X 2-1 - is a condition that it is either a natural amino acid or a non-natural amino acid. (3)-X 3-1 - is a natural amino acid, or R 6 is one or two R 6-1 A C1-C4 alkyl group substituted by, and each R 6-1 The conditions are that it is independently a C3-C6 cycloalkyl group or halogen, (4)-X4- is [ka] And R 7 The group is a four-membered heterocycloalkylene group, the heteroatoms of the four-membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and the group satisfies one or more of the following conditions: it contains at least one N.

[0077] In one embodiment, with compound X, -X1- is [ka] And, R 3 This is a 3-6 membered heterocycloalkylene group, where the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and it contains at least one N. -X2- is -X 2-1 -Y1- and -X 2-1 - is a chemical bond, and Y1 is [ka] And, R 5 Each of these is independently one, two, or three R 5-1 These are C1-C4 alkylene groups substituted by [the specified agent]. Each R 5-1 Each of these is independently a hydroxyl group, -X3- is -X 3-1 -Y2- and -X 3-1 - is a chemical bond, and Y1 is [ka] And, R 6 is one or two R 6-1 A C1-C4 alkyl group substituted by, and each R 6-1 Each is independently a C3-C6 cycloalkyl group or a C6-C6 10 It is an aryl group, -X4- is [ka] And R 7 This is a 3-6 membered heterocycloalkylene group, where the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and it contains at least one N. W is -NH-CO- or -NH-CO-NH-, R 8 is a straight chain C1-10 It is an alkyl group, R 9 is H or one or two R 9-1 A C1-C4 alkyl group substituted by R 9-1 It is an amide group (-CONH2), L1 and L2 are independently -S-(CH2) k - and k is 1, Cy is C6~C 10 It is an arylene group, -L3- is -L 3-1 -L 3-2 -L 3-3 -and, -L 3-1 is a chemical bond, [ka] T1 and T2 are independently 0 or 1, and T3 and T4 are independently 0 or 1. -L 3-2 - is -X5-Y3-, where -X5- is a chemical bond and -Y3- is a chemical bond. [ka] T5 and T6 are independently 0, 1, or 2, and E and Q are independently C 1-6 It is an alkylene group, and A is either a chemical bond or -NH-. -L 3-3 - represents a chemical bond, -NH-, -carbonyl-C 1-6 Alkylene-3 to 6-membered heterocycloalkylene-,-NH-C 1-6 The alkylene-3-6 membered heterocycloalkylene- or 3-6 membered heterocycloalkylene group, wherein the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and it contains at least one N. R 10 It is a hydroxyl group, R 11is a chelating group, and the chelating group is [ka] And, The aforementioned compound X is (1)-X1- is [ka] And R 3 The group is a 4-membered or 6-membered heterocycloalkylene group, and the heteroatoms of the 4-membered or 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and it contains at least one N. (2)R 6 is one or two R 6-1 A C1-C4 alkyl group substituted by, and each R 6-1 Each of these independently satisfies one or more of the conditions of being a C3-C6 cycloalkyl group.

[0078] In one embodiment, with compound X, -X1- is [ka] And, R 3 This is a 3-6 membered heterocycloalkylene group, where the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and it contains at least one N. -X2- is -X 2-1 -Y1- and -X 2-1 - is a chemical bond, and Y1 is [ka] And, R 5 Each of these is independently one, two, or three R 5-1A C1-C4 alkylene group substituted by, Each R 5-1 Each of these is independently a hydroxyl group, -X3- is -X 3-1 -Y2- and -X 3-1 - is a chemical bond, and Y2 is [ka] And, R 6 is one or two R 6-1 A C1-C4 alkyl group substituted by, and each R 6-1 Each is independently a C3-C6 cycloalkyl group or a C6-C6 10 It is an aryl group, -X4- is [ka] And R 7 This is a 3-6 membered heterocycloalkylene group, where the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and it contains at least one N. W is -NH-CO- or -NH-CO-NH-, R 8 is a straight chain C 1-10 It is an alkyl group, R 9 is one R 9-1 A C1-C4 alkyl group substituted by R 9-1 It is an amide group (-CONH2), L1 and L2 are independently -S-(CH2) k - and k is 1, Cy is C6~C 10 It is an arylene group, -L3- is -L 3-1 -L 3-2 -L 3-3 -and, -L 3-1 teeth [ka] T1 and T2 are independently 0 or 1, and T3 and T4 are independently 0 or 1. -L 3-2 - is -X5-Y3-, where -X5- is a chemical bond and -Y3- is a chemical bond. [ka] T5 and T6 are independently 0, 1, or 2, and E and Q are independently C 1-6 Alkylene group or -(OCH2CH2) j’ -, j' is 1, A is a chemical bond or -NH-, -L 3-3 - represents a chemical bond, -NH-, -carbonyl-C 1-6 Alkylene-3 to 6-membered heterocycloalkylene-,-NH-C 1-6 The alkylene is a 3- to 6-membered heterocycloalkylene, where the heteroatoms of the 3- to 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and it contains at least one N. R 10 is a hydroxyl group or an amino group, R 11 It is a chelating group, The aforementioned chelate group [ka] , NOTA, HBED-CC, NODAGA, NOTAGA, DOTAGA, TRAP, NOPO, PCTA, DFO, DTPA, CHX-DTPA, AAZTA or DEDPA.

[0079] In one embodiment, with compound X, -X1- is [ka] And, R 3 This is a 3-6 membered heterocycloalkylene group, where the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and it contains at least one N. -X2- is -X 2-1 -Y1- and -X 2-1 - is a chemical bond, and Y1 is [ka] And, R 5 Each of these is independently one, two, or three R 5-1 A C1-C4 alkylene group substituted by, Each R 5-1 Each of these is independently a hydroxyl group, -X3- is -X 3-1 -Y2- and -X 3-1 - is a chemical bond, and Y2 is [ka] And, R 6 is one or two R 6-1 A C1-C4 alkyl group substituted by, and each R 6-1 These are independently C3-C6 cycloalkyl groups or C6-C 10 It is an aryl group, -X4- is [ka] And R 7 This is a 3-6 membered heterocycloalkylene group, where the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and it contains at least one N. W is -NH-CO- or -NH-CO-NH-, R8 is a straight chain C 1-10 It is an alkyl group, R 9 is one or two R 9-1 A C1-C4 alkyl group substituted by R 9-1 It is an amide group (-CONH2), L1 and L2 are independently -S-(CH2) k - and k is 1, Cy is C6~C 10 It is an arylene group, -L3- is -L 3-1 -L 3-2 -L 3-3 -and, -L 3-1 teeth [ka] T1 and T2 are independently 0 or 1, and T3 and T4 are independently 0 or 1. -L 3-2 - is -X5-Y3-, where -X5- is a chemical bond and -Y3- is a chemical bond. [ka] T5 and T6 are independently 0, 1, 2, or 4, and E and Q are independently C 1-6 It is an alkylene group, and A is either a chemical bond or -NH-. -L 3-3 - is -NH-, -carbonyl-C 1-6 Alkylene-3 to 6-membered heterocycloalkylene-,-NH-C 1-6 The alkylene is a 3- to 6-membered heterocycloalkylene, where the heteroatoms of the 3- to 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and it contains at least one N. R 10 It is a hydroxyl group, R 11 It is a chelating group, The aforementioned chelate group [ka] , NOTA, HBED-CC, NODAGA, NOTAGA, DOTAGA, TRAP, NOPO, PCTA, DFO, DTPA, CHX-DTPA, AAZTA or DEDPA.

[0080] In one embodiment, -X1- is [ka] Preferably, -X1- is [ka] And here, [ka] It is connected to X4.

[0081] In one embodiment, -X4- is [ka] Preferably, X4- is [ka] And here, [ka] It is connected to X2.

[0082] In one embodiment, -X2- is [ka] Preferably, -X2- is [ka] And here, [ka] is-NH-( [ka] It is linked to -NH-).

[0083] In one embodiment, -X3- is [ka] And, Preferably, -X3- is [ka] And here, [ka] is a carbonyl group ( [ka] It is linked to -CO-).

[0084] In one embodiment, -L4- is [ka] Preferably, -L4- is [ka] And here, [ka] is R 11 It is connected to.

[0085] In one embodiment, -L 3-1 - is a chemical bond, [ka] Preferably, -L 3-1 - is a chemical bond, [ka] And here, [ka] ha-L 3-2 - is linked to

[0086] In one embodiment, -L 3-2 - is a chemical bond, [ka] Preferably, -L 3-2 - is a chemical bond, [ka] [ka] ha-L 3-3 - is linked to

[0087] In one embodiment, -L 3-3 - is a chemical bond, -NH-, [ka] And preferably, -L 3-3 - is a chemical bond, [ka] And here, [ka] is R 11 It is connected to.

[0088] In one embodiment, R 8 is a straight chain C 1-10 It is an alkyl group, such as a methyl group, n-pentyl group, n-nonyl group, n-heptyl group, or n-butyl group. In one embodiment, R 9 H, [ka] That is the case.

[0089] In one embodiment, R 10 It is -OH or -NH2. In one embodiment, L1 and L2 are independently -S-methylene-, n-propylene-, a chemical bond, or -S-.

[0090] In one embodiment, Cy is [ka] [ka] (is linked to L1), chemical bond or [ka] That is the case.

[0091] In one embodiment, the structure of compound X is represented by one of the following formulas: [ka]

[0092]

change

[0093]

change

[0094]

change

[0095]

change

[0096]

change

[0097]

change

[0098]

change

[0099]

change

[0100]

change

[0101]

change

[0102] [ka]

[0103] [ka]

[0104] [ka]

[0105] [ka]

[0106] [ka]

[0107] [ka]

[0108] [ka]

[0109] [ka]

[0110] The present invention also provides a cyclic polypeptide compound A, which is a compound formed by chelating compound X with a therapeutic radionuclide ion.

[0111] In some embodiments, the therapeutic radionuclide is 177 Lu, 90 Y, 89 Sr, 188 Re, 225 Ac, 213 Bi or 212 It is Pb. In some embodiments, the valence state of the therapeutic radionuclide ion is monovalent, divalent, trivalent, or tetravalent, for example, trivalent.

[0112] In some embodiments, the therapeutic radionuclide is 177 Lu 3+ , 225 Ac 3+ , 90 Y 3+ , 212 Pb 2+ or 213 Bi 3+ For example, 177 Lu 3+ That is the case. In some embodiments, the cyclic polypeptide compound A is compound X and 177 Lu 3+ The compound is formed by chelating the two, and the structure of compound X is as described above.

[0113] The present invention also provides a cyclic polypeptide compound B, which is a compound formed by chelating compound X with a diagnostic radionuclide ion, wherein the structure of compound X is as described above. In some embodiments, the diagnostic radionuclide is 18 F, 68 Ga, 111 In or 64 It is Cu.

[0114] In some embodiments, the valence state of the diagnostic radionuclide ion is monovalent, divalent, trivalent, or tetravalent, for example, trivalent. In some embodiments, the diagnostic radioactive metal ion is 68 Ga 3+ or 64 Cu 2+ That is the case.

[0115] In some embodiments, the cyclic polypeptide compound B is compound X and 68 Lu 3+The compound is formed by chelating the two, and the structure of compound X is as described above. The present invention also provides a cyclic polypeptide compound C, which is selected from any one of the above compounds X.

[0116] The present invention also provides a pharmaceutical composition comprising substance Y and a pharmaceutical excipient, wherein substance Y is the above-mentioned cyclic polypeptide compound A or the above-mentioned cyclic polypeptide compound B. The present invention also provides the use of the cyclic polypeptide compound A in the manufacture of a pharmacopoeia for the treatment of tumors. The tumor may be a FAP-related tumor such as breast cancer, ovarian cancer, lung cancer, colorectal cancer, gastric cancer, pancreatic cancer, prostate cancer, liver cancer, or cutaneous melanoma. Preferably, the tumor may be a solid tumor that expresses FAP positively, such as breast cancer, ovarian cancer, lung cancer, colorectal cancer, gastric cancer, pancreatic cancer, prostate cancer, liver cancer, or cutaneous melanoma.

[0117] The present invention also provides the use of the cyclic polypeptide compound B in the manufacture of a pharmaceutical for diagnosing tumors. The tumor may be a FAP-related tumor such as breast cancer, ovarian cancer, lung cancer, colorectal cancer, gastric cancer, pancreatic cancer, prostate cancer, liver cancer, or cutaneous melanoma. Preferably, the tumor may be a solid tumor that expresses FAP positively, such as breast cancer, ovarian cancer, lung cancer, colorectal cancer, gastric cancer, pancreatic cancer, prostate cancer, liver cancer, or cutaneous melanoma. Unless otherwise specified, the terms used in this invention have the following meanings:

[0118] The term "pharmaceutically acceptable salt" refers to a salt obtained by reacting a compound with a pharmaceutically acceptable (relatively non-toxic, safe, and suitable for patient use) acid or base. When a compound contains relatively acidic functional groups, a base addition salt can be obtained by contacting a sufficient amount of a pharmaceutically acceptable base with the free form of the compound in a suitable inert solvent. pharmaceutically acceptable base addition salts include, but are not limited to, sodium salts, potassium salts, calcium salts, aluminum salts, magnesium salts, bismuth salts, and ammonium salts. When a compound contains relatively basic functional groups, an acid addition salt can be obtained by contacting a sufficient amount of a pharmaceutically acceptable acid with the free form of the compound in a suitable inert solvent. pharmaceutically acceptable acid addition salts include, but are not limited to, hydrochloride salts, sulfate salts, methanesulfonates, acetate salts, and trifluoromethanesulfonates. For specifics, refer to Handbook of Pharmaceutical Salts: Properties, Selection, and Use (P. Heinrich Stahl, 2002).

[0119] term [ka]

[0120] The term "alkyl group" refers to a group with a specific number of carbon atoms (for example, C1-C1). 30 , C1~C 20 This refers to a linear or branched alkyl group having C1-C6. Alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, and sec-butyl groups.

[0121] The term "alkylene group" refers to a divalent group that is linked to the rest of a molecule by two single bonds, and the rest of its definition is the same as that of the term "alkyl group". The term "cycloalkyl group" refers to a saturated cyclic group consisting solely of carbon atoms, having a specific number of carbon atoms (e.g., C3-C8 or C3-C6), and can be monocyclic, bridging, or spirocyclic. Cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups.

[0122] The term "cycloalkylene group" refers to a divalent group that is attached to the rest of a molecule by two single bonds, and the rest of its definition is the same as that of the term "cycloalkyl group." The term "heterocycloalkyl group" refers to a cyclic group having a specific number of ring atoms (e.g., 3-10 membered or 3-6 membered), a specific number of heteroatoms (e.g., one, two, or three), and a specific type of heteroatom (e.g., one or more of N, O, and S), and which can be monocyclic, bridging, or spirocyclic, with each ring being saturated. Heterocycloalkyl groups include, but are not limited to, zetidinyl, tetrahydropyrrolyl, tetrahydrofuranyl, morpholinyl, piperidinyl, azocyclopentanyl, and azacyclohexanyl groups.

[0123] The term "heterocycloalkylene group" refers to a divalent group that is attached to the rest of a molecule by two single bonds, and the rest of its definition is the same as that of the term "heterocycloalkyl group". The term "aryl group" refers to a group with a specific number of carbon atoms (for example, C6-C6). 10 An aryl group is a cyclic group consisting only of carbon atoms, which is monocyclic or fused, and at least one ring is aromatic (according to Hückel's rule). Aryl groups are attached to other fragments within the molecule via aromatic or non-aromatic rings. Aryl groups include, but are not limited to, phenyl and naphthyl groups.

[0124] The term "arylene group" refers to a divalent group that is attached to the rest of a molecule by two single bonds, and the rest of its definition is the same as that of the term "aryl group." The term "heteroaryl group" refers to a cyclic group having a specific number of ring atoms (e.g., 6-12 members), a specific number of heteroatoms (e.g., one, two, or three), and a specific type of heteroatom (one or more of N, O, and S), which may be monocyclic, bridging, or spirocyclic, and which has at least one ring that is aromatic (according to Hückel's rule). Heteroaryl groups are linked to other parts of the molecule via non-aromatic rings within aromatic or fused rings. Heteroaryl groups include pyridinyl groups, pyrimidinyl groups, indolyl groups, [ka] This includes, but is not limited to, the following.

[0125] The term "heteroarylene group" refers to a divalent group that is attached to the rest of a molecule by two single bonds, and the rest of its definition is the same as that of the term "heteroaryl group". In fragments [ka] This indicates that the fragment is linked to other fragments within the molecule via that site. For example, [ka] This refers to a cyclohexyl group.

[0126] The term "pharmaceutical excipients" refers to excipients and additives used in the manufacture and formulation of pharmaceuticals, encompassing all substances contained in drug preparations excluding the active ingredient. For further details, refer to the Pharmacopoeia of the People's Republic of China (2020 edition) or the Handbook of Pharmaceutical Excipients (Raymond C Rowe, 2009).

[0127] The term "therapeutic dose" refers to the amount of compound or radiation administered to a patient that is sufficient to effectively treat the disease. While the therapeutic dose varies depending on the compound, the type of disease, the severity of the disease, and the patient's age, those skilled in the art can adjust it as needed.

[0128] The term "patient" refers to any animal that has received or is about to receive treatment, preferably a mammal, most preferably a human. Mammals include, but are not limited to, cattle, horses, sheep, pigs, cats, dogs, mice, rats, rabbits, guinea pigs, monkeys, and humans.

[0129] The term “treatment” refers to any of the following situations: (1) improving one or more biological expressions of a disease; (2) disrupting one or more points in the biological cascade leading to the disease; or (3) slowing the progression of the development of one or more biological expressions of a disease.

[0130] The aforementioned preferred conditions can be combined in any way, without violating the ordinary knowledge of the art, to obtain each preferred embodiment of the present invention. The reagents and raw materials used in this invention are commercially available.

[0131] Positive progressive effects of the present invention: The present invention provides a cyclic polypeptide compound having high affinity for FAP, which can be used for the diagnosis and treatment of FAP-related tumors, exhibiting high uptake into tumors, long residence time, and promising a wide range of applications. [Brief explanation of the drawing]

[0132] [Figure 1] This shows the in vivo distribution of 177Lu-labeled compounds in tumor-bearing mice. [Figure 2] These are PET-CT images of 68Ga-FAP-2286 in tumor-bearing mice. [Figure 3] These are PET-CT images of 68Ga-JHDC16 in tumor-bearing mice. [Figure 4]This is a PET-CT image of 68Ga-JHDC06 in tumor-bearing mice. [Figure 5] This involves the inhibition of tumor growth by 177Lu-labeled compounds in a tumor-bearing mouse model. [Figure 6] This describes the effect of 177Lu-labeled compounds on body weight in a tumor-bearing mouse model. [Modes for carrying out the invention]

[0133] The present invention will be further described below with reference to embodiments, but this does not limit the present invention to the scope of the above embodiments. In the following embodiments, experimental methods for which specific conditions are not described are selected according to conventional methods and conditions or according to the product description.

[0134] Explanation of structural abbreviations: Abbreviation for natural amino acids: [Table 1-1]

[0135] Abbreviation for unnatural amino acids [Table 1-2]

[0136] [Table 1-3]

[0137] Abbreviation for intermediate [Table 1-4]

[0138] [Table 1-5]

[0139] Abbreviation for chelate group: [Table 1-6]

[0140] [Table 1-7]

[0141] The above chelating group is linked to L via a carbonyl group (CO) through an amidation reaction, for example, via an amide group.

[0142] The amino acid skeleton sequence of the compounds in the examples is as follows. [Table 1-8]

[0143] [Table 1-9]

[0144] Example 1 Compound Synthesis Method 1 for synthesizing general compounds: Taking compound JHDC23 as an example, it is produced by solid-phase synthesis in the following steps. [ka]

[0145] Hex[Cys(3MeBn)-hhy39-Pro-Thr-Gln-Phe-Cys]-Glu-(EDA-DOTA)-OH was synthesized using the following steps. 1. Weigh the CTC resin (SUNRESIN, 1g, 0.65 mmol) and add it to the synthesis tube. Allow it to swell, then close the lid. Sequentially couple Fmoc-Glu(OAll)-OH, Fmoc-Cys(Trt)-OH, Fmoc-Phe-OH, Fmoc-Gln(Trt)-OH, Fmoc-Thr(tBu)OH, Fmoc-Pro-OH, hhy39, Fmoc-Cys(Trt)-OH, and Hex. After removing the Alloc protecting group, couple Fmoc-ethylenediamine with DOTA-(OtBu)3. Condensation was performed using a PyBOP / DIEA system, and the Fmoc protection was removed with 20% pip / DMF. Solid-phase synthesis was completed using the Fmoc method. The peptide was cleaved in a TFA:DTT:Tis:H2O (90:5:2.5:2.5) solution for 3-6 hours, the cleavage solution was added dropwise to 10 times the volume of isopropyl ether, a solid precipitated, the solid was washed three times with isopropyl ether and dried to obtain 550 mg of naked peptide (JHD00130-A1) [M / 2+H]. + We obtained = 719.20, which was used directly in the next step of the reaction.

[0146] 2. JHD00130-A1 (550 mg, 382 mmol) and 1,3-bis(bromomethyl)benzene (131.4 mg, 497.7 mmol) were dissolved in H2O (250 mL) and acetonitrile (250 mL). NH4HCO3 (aq.) solution was added to adjust the pH to 8, and the reaction was carried out with stirring. The completion of the reaction was confirmed by LC-MS detection. The mixture was freeze-dried and purified by pre-HPLC to obtain 148 mg of crude product and 16.56 mg of pure product. [M+H] + =1540.45 (JHDC23).

[0147] Common preparative liquid purification methods: Chromatography column: Bonnasil-BS C18 (21.2 x 250 mm, 5 μm) Mobile phase: H2O (0.01% TFA) (A) / Acetonitrile (0.01% TFA) (B) Flow rate: 10mL / min Detection wavelength: 220nm Dissolution program: 15-45% B, 0-60 minutes.

[0148] Analysis method 1: Chromatography column: Shim-pack VP-ODS (4.6 × 150 mm, 5 μm) Mobile phase: H2O (0.01% TFA) (A) / Acetonitrile (0.01% TFA) (B) Flow rate: 1.0mL / min Elution program: At a rate of 1.0 mL / min, B reached a gradient from 10% to 40% within 20 minutes, then from 20 to 24 minutes B reached a gradient from 40% to 70%, from 24 to 24.1 minutes B reached a gradient from 70% to 10%, and from 24.1 to 30 minutes B remained at 10%. Column temperature: 30℃ Detection: Ultraviolet light (214, 4 nm).

[0149] Analysis method 2: Chromatography column: XBridge Peptide BEH C18 (4.6 × 150 mm, 3.5 μm) Mobile phase: A: 0.05% TFA in water, B: 0.05% TFA in ACN Elution program: 5% B for 1 min, 5-65% B within 20 min Flow rate: 1.0mL / min Column temperature: 40℃ Detection wavelength: 220 nM.

[0150] Analysis method 3: Chromatography column: Phenomenex Luna 3u C18(2), (4.6×150mm×3um) Mobile phase: A: 0.1% TFA in 100% water, B: 0.1% TFA in 100% acetonitrile Flow rate: 0.8mL / min Detection wavelength: 220nm Elution program: 15% B, 0.01 minutes; 15-60% B, 0.01-25.0 minutes; 60-90% B, 25-30 minutes.

[0151] Analysis method 4: Chromatography column: SHIMADZU Inertsil ODS-SP (4.6 × 250 mm × 5 μm) Mobile phase A: 0.1% TFA in 100% Water, B: 0.1% TFA in 100% acetonitrile Flow rate: 1mL / min Detection wavelength: 220nm Dissolution program: B: 20%, 0 minutes; B: 20-80%, 0-25 minutes; B: 100%, 25.01-30 minutes.

[0152] Analysis method 5: Chromatography column: LSepaxGP-C18 (4.6 × 150 mm × 5 μm) Mobile phase A: 0.1% TFA in 100% Water, B: 0.09% TFA in (80% Acetone / 20% Water) Flow rate: 1mL / min Detection wavelength: 220nm Dissolution program: B: 39-49%, 0-20 minutes.

[0153] Analysis method 6: Chromatography column: SHIMADZU Inertsil ODS-SP (4.6 × 250 mm × 5 μm) Mobile phase A: 0.1% TFA in 100% Water, B: 0.1% TFA in 100% Acetolite Flow rate: 1mL / min Detection wavelength: 220nm Dissolution program: B: 25%, 0 minutes; B: 25-65%, 0-20 minutes; B: 100%, 20.01-23 minutes; B: 100%, 23-38 minutes; B: 100-25%, 38-40 minutes.

[0154] The following compounds were prepared using the general synthesis method 1 described above. [ka] JHDC01 Ac[Cys(3MeBn)-hhy42-Pro-Ala-Thr-Glu-Nal-Cys]-Lys-(DOTA)-OH, Synthesis Method 1, Analytical Method 4

[0155]

change

[0156]

change

[0157]

change

[0158]

change

[0159]

change

[0160]

change

[0161]

change

[0162]

change

[0163]

change

[0164]

change

[0165]

change

[0166]

change

[0167]

change

[0168]

change

[0169]

change

[0170]

change

[0171]

change

[0172]

change

[0173]

change

[0174]

change

[0175]

change

[0176]

change

[0177]

change

[0178]

change

[0179]

change

[0180]

change

[0181]

change

[0182]

change

[0183]

change

[0184]

change

[0185]

change

[0186]

change

[0187]

change

[0188]

change

[0189]

change

[0190]

change

[0191]

change

[0192]

change

[0193]

change

[0194]

change

[0195]

change

[0196]

change

[0197]

change

[0198]

change

[0199]

change

[0200]

change

[0201]

change

[0202]

change

[0203]

change

[0204]

change

[0205]

change

[0206]

change

[0207]

change

[0208]

change

[0209]

change

[0210]

change

[0211]

change

[0212]

change

[0213]

change

[0214]

change

[0215] [ka] JHDC62 Hex-[Cys(3MeBn)-hhy39-Pro-Thr-Gln-hhy34-Cys]-2,4-diamino-BA-(DOTA)-OH, Synthesis Method 1, Analysis Method 1.

[0216] [ka] JHDC63 Hex-[Cys(3MeBn)-hhy39-Pro-Thr-Gln-Phe-Cys]-Glu-(piperazine-DOTA)-OH, Synthesis method 1, Analysis method 1.

[0217] [ka] JHDC64 Hex-[Cys(3MeBn)-hhy39-Pro-Thr-Gln-Phe-Cys]-Glu-(aminopropylpiperidine-DOTA)-OH, Synthesis method 1, Analysis method 1.

[0218] The HPLC peak times and mass spectra of the above compounds are shown in Table 1. Table 1 [Table 1-10]

[0219] [Table 1-11]

[0220] [Table 1-12]

[0221] [Table 1-13]

[0222] [Table 1-14]

[0223] [Table 1-15]

[0224] [Table 1-16]

[0225] [Table 1-17]

[0226] [Table 1-18]

[0227] [Table 1-19]

[0228] Example 2: Compound 175 Cold labeling: JHDC23 is used as an example. [ka]

[0229] 2.66 mg of precursor JHDC23 was accurately weighed and dissolved in 1.9 mL of sodium acetate buffer (pH: 5.0). 100 μL of lutetium chloride aqueous solution (50 mg / mL) was added. The solution was placed in a reactor at 95°C and reacted for 20 minutes. After cooling the reaction solution, it was purified by prep-HPLC (15-45%, acetonitrile / water) to obtain a white solid product (1.5 mg). HPLC: 11.21 min, purity: 99.83%; MS: [M / 2+H] + : 895.95.

[0230] Example 3: Compound affinity test: Ligand binding of FAP protein (Sinobiological) was detected using a Biacore 8K (Cytiva) instrument. FAP protein was captured on an SA chip. Before ligand immobilization (channels 1 and 2, flow rate: 10 μL / min), FAP protein (10 μL / mL, flow rate: 5 μL / min, injection time: 600 s) was immobilized in channel 2 using rannin buffer, and the sensor surface was prepared by injecting 1 M NaCl into 50 mM NaOH three times in succession. After each ligand injection, additional washing with isopropanol in 1 M NaCl and 50 mM NaOH was performed (channels 1 and 2, flow rate: 10 μL / min, injection time: 60 s).

[0231] The test compound was dissolved in 100% dimethyl sulfoxide, diluted to 10 mM, and then diluted to the appropriate maximum concentration with analytical buffer (PBS, pH 7.4, 1 mM TCEP (tris(2-carboxyethyl)phosphine), 0.05% P20, 2% dimethyl sulfoxide). The analyte was analyzed using the following conditions: analytical temperature of 15°C, analytical step = all set to LMW dynamics, cycle type = single cycle (contact time: 90 s, separation time: 1800 s, flow rate: 30 μL / min, channels 1, 2), channel detection = 2-1). Data evaluation was performed using Biacore Insight evaluation software, and the data were fitted to a 1:1 coupling model.

[0232] The Biacore results are shown in Table 2 below, and pKD =-LogK D Here, K D This is the binding affinity of the compound to the FAP protein, as measured by Biacore. D (M=K) d (1 / s) / K a It is expressed as (1 / Ms). Within that, A:pK D >8, B:7 <pK D <8, C:6 <pK D <7, D:pK D <6. Furthermore, FAPi-46 (CAS: 2374782-04-2) and FAP-2286 (CAS: 2581741-18-4) were used as positive reference compounds.

[0233] Example 4: Selectivity test of the compound: The specificity of the synthesized compound against recombinant human dipeptidyl peptidase IV (DPPIV), fibroblast-activating protein (FAP), or prolyl oligopeptidase (PREP) is such that the half-inhibitory IC2 level inhibits the protease. 50 It is represented by: Specific steps:

[0234] 1) The synthesized compound was dissolved in DMSO, and the final concentration was 100 mM. a) For the FAP test: The test compound was diluted to a 1 mM solution in 50 mM Tris and 140 mM NaCl buffer with a pH of 7.5. b) For the DPPIV test: The test compound was diluted to a 1 mM solution in 25 mM Tris and 250 mM NaCl buffer with a pH of 7.5. c) For the PREP test: The test compound was diluted to a 1 mM solution in a 140 mM NaCl buffer solution with a pH of 8.0. 2) The 1 mM test compound solutions prepared above were gradient diluted (1:10) with the corresponding buffer solutions and placed in the first row of a 96-well plate. 3) The substrates were prepared in DMSO stock solution (FAP and PREP: 2.5 mM Z-Gly-Pro-AMC (VWR, catalog number: I-1145.0050BA) in DMSO, DPPIV: 100 mM Gly-Pro-AMC (VWR, catalog number: 100042-646) in DMSO), and then diluted 20-fold with the corresponding buffers mentioned above to obtain the substrate stock solution. 4) The enzymes were diluted in appropriate analytical buffer. The final enzyme concentrations of DPPIV, FAP, and PREP were 0.1, 1.2, and 0.6 nM, respectively. 180 μL was added to each of the desired wells in columns 2 through 10. Column 1 (A, B, C) required the preparation of controls with 200 μL of appropriate analytical buffer. Column 1 (D, E, F, G, H) required the preparation of inhibitor-free controls with 20 μL of appropriate analytical buffer and 180 μL of enzyme. 5) If necessary, add 20 μL of the test compound from the diluted plate prepared in Step 2 to rows 2-10 of the test plate. Each sample needed to be tested three times. Incubate at room temperature for 10 minutes, shaking the plate for the first 2 minutes. 6) Add 10 μL of the 20× matrix prepared in step 3 to each well and incubate at room temperature for 15 minutes, shaking the plate for the first 2 minutes. 7) Fluorescence was read at λex:380 and λem:460. The results of the above tests showed that the synthesized compound had excellent selectivity for FAP. However, pIC 50 =-Log(IC 50 ), here, A:pIC 50 >8, B:7 <pIC 50 <8, C:6 <pIC 50 <7, D:pIC 50 <6

[0235] Table 2 [Table 2-1]

[0236] [Table 2-2] "-" means it has not been tested.

[0237] Example 5: Compound 177 Lu thermal label 1. The precursor compound (1 mg) was weighed and dissolved in a 0.45 M ascorbic acid buffer (pH 4.5) to a solution of 0.1 mg / mL. 2. Nuclide:Precursor = Labeled according to a molar ratio of 1:7~10: 2mCi 177 The amount of precursor calculated based on LuCl3 and real-time specific activity was added to the labeled buffer system (0.5 M, pH 4.0 ascorbic acid buffer) to bring the reaction system volume to 0.15 mL. 3. The mixture was incubated in a constant temperature incubator at 95°C for 30 minutes. Once the reaction was complete, the product was subjected to iTLC and radio-HPLC. 4. iTLC developing agent: 1% EDTA, stationary phase: silica gel 254. Development to 1 cm on the stationary phase took approximately 20 minutes, and the sample volume was 0.5 μL. 5. If the iTLC and Radio-HPLC results reached 95%, the labeled product was considered acceptable. 6. Transfer the reaction solution to the cylinder, wash the reaction tube with 0.15 mL of physiological saline solution, and add the washing solution to the cylinder as well. 7.6.7 μL of DTPA solution (0.25 mM) was added, mixed uniformly, and stored for later use. 1.0 mg of DTPA was added to 10 mL of physiological saline to prepare a DTPA stock solution (concentration: 0.25 mM), mixed uniformly, and stored for later use. The final formulation is a clear solution, ready for immediate use after manufacturing, and only usable on the day of manufacture.

[0238] Example 6: Experiment on cell binding of compounds (1) Prepare HT1080 8# cells (GENEWIZ) in the logarithmic growth phase into a cell suspension and set the cell density to 1 × 10⁻⁶ 4 The solution was adjusted to the required concentration ( / mL), and 1 mL was inoculated into a 24-well cell culture plate. The cells were incubated overnight at 37°C. (2) The cell culture medium was aspirated, the cells were washed once with PBS, and 975 μL of additive-free medium was added. (3) Each well contains a fixed concentration of radioactive material 177 25 μL of Lu-labeled FAPi-46 (CAS: 2374782-04-2) ligand (final concentration in medium: 1.35 μCi / ml) was added to unlabeled test compounds at different concentrations (final concentrations in medium: 1000 ng / mL, 100 ng / mL, 10 ng / mL, 1 ng / mL, 0.1 ng / mL, 0.01 ng / mL, 0.001 ng / mL, 0 ng / mL). (4) The cells were cultured on and off ice for 2 hours. (5) The cells were washed three times with ice-cold PBS. (6) The cells were lysed with 0.5 mL of 1 M sodium hydroxide, washed twice with 0.5 mL of PBS, and the sodium hydroxide (0.5 mL) and PBS (0.5 mL x 2) solutions were collected and the number of cells taken up was measured. The results are shown in Table 3.

[0239] Table 3. Results of cell binding experiments for compounds [Table 3]

[0240] Example 7: Measurement of ClogP The following 177 A predetermined amount of Lu-labeled compound solution was taken, ultrapure water was added and mixed uniformly, and the activity after mixing was measured. Prepare two EP tubes, add 100 μL of saturated n-octanol aqueous solution and 80 μL of pure water to each, and then add the above to each tube. 177 20 μL of Lu-labeled compound solution was added, and the mixture was shaken for 2 hours. Then, the mixture was centrifuged at room temperature at 2000 rpm / min for 5 minutes. 20 μL was taken from both the upper layer (lipid layer) and the lower layer (aqueous layer) of each tube, and the gamma-ray count was measured. The results are shown in Table 4.

[0241] Table 4. Ratio of lipophilicity to hydrophilicity (ClogP) of compounds [Table 4]

[0242] Example 8: Binding rate between labeled compound and plasma protein Marked 177 1 μCi of Lu compound was taken and 50 μL of PBS was added to obtain a 20 μCi / mL reaction solution. 50 μL of the 20 μCi / mL reaction solution was added to 200 μL of plasma, mixed uniformly, and incubated at room temperature for 10 minutes. The sample was then added to a 30K ultrafiltration tube (PALL), centrifuged at 13000 rpm for 45 minutes, then 50 μL of physiological saline was added, and centrifugation was continued for 15 minutes. The upper chamber and filtrate were counted separately.

[0243] PPB = [(Upper Chamber Count - Background Count)] / (Filtrate Count + Upper Chamber Count - 2 × Background Count)] × 100%.

[0244] Example 9: In tumor-carrying mice 177 In vivo distribution of Lu-labeled compounds Tissue distribution of FAP-positive tumor-bearing mice: HT1080 2# FAP (50% Matrigel, Corning) was placed in 2x10⁻¹⁶ mice approximately 6-9 weeks old (Balb / c nude) on the right shoulder. 6 Cells were inoculated subcutaneously. The tumor was approximately 150-350 mm in size. 3 When they grew up, 177 Lu radiolabeled compounds were injected into the tail vein of mice (approximately 3.7 MBq / mouse). 24 hours after administration, the animals were euthanized by carbon dioxide inhalation. After euthanasia, the animals' blood and organs (liver, kidney, muscle, tumor) were collected.

[0245] Blood was collected from the inferior vena cava and immediately after collection, 100 μL was weighed into a designated centrifuge tube. After organ collection, the organs were washed twice with deionized water, wiped dry, placed in pre-weighed test tubes, weighed again to calculate the sample weight, and the sample weight was measured on the day of collection. The radioactivity of all blood and tissue samples was measured using a gamma counter. The results of the tissue distribution test are shown in Table 5 and Figure 1.

[0246] Table 5. Distribution of compounds in tumor-bearing mice (@24h, %ID / g) [Table 5-1]

[0247] Example 10: In tumor-carrying mice 68 Image results of Ga-labeled compounds A.JHD compound was dissolved in ascorbic acid buffer to prepare a solution with a concentration of 0.1 mg / mL. The germanium-gallium generator was partially washed with 5 mL of 0.1 M HCl, and the most active portion (0.5 mL) was removed. 0.5 mL of pH=4.5 metal-free 0.1 M sodium ascorbate buffer was added, and a predetermined amount of precursor [1000 (molecular weight) / 14.94 μL (precursor solution) / mCi (nuclide)] was added to a 1.5 mL centrifuge tube used as the reaction tube. The mixture was vortexed for 10 seconds and heated at 95°C and 800 rpm for 15 minutes. The C.C18 column was activated with anhydrous ethanol, washed with pure water, and then dried. D. The solution after the reaction was passed through a C18 column, washed with pure water, dried, washed with ethanol, and three drops were attached to each tube, resulting in a total of about 10 tubes. E. The final formulation is a clear solution, and the formulation should be used immediately after manufacture and only on the day of manufacture.

[0248] PCT / CT scan 1) I powered on the PET / CT scanner according to its operating procedure, opened the scanning software, and performed the daily calibration. 2) Preparation for animal anesthesia: Tumor-bearing mice were anesthetized with isoflurane. 3) After the righting reflex disappeared in tumor-bearing mice, a contrast agent was injected into the tail vein. 4) A 10-minute dynamic scan was performed 1 hour after drug administration, and a 10-minute static scan was performed 3 hours later. 5) During the process, the animal's weight, injection volume, injection time, and residual dose were recorded according to the record sheet, and the injection volume measurement time and residual dose measurement time were also recorded. 6) Using PMOD software, animal tumors, muscle tissue, and other organs were taken.

[0249] The PET-CT results showed that the tail vein of tumor-bearing mice was 68 The results showed that after injection of Ga-labeled compounds, they were rapidly distributed to various organs and tumors in animals, rapidly metabolized, and excreted from the body by the kidneys. The uptake of the labeled compounds in tumors changed over time, with some compounds showing longer residence times in tumors compared to reference compounds. The results are shown in Tables 5-9 and Figures 2-4.

[0250] Table 5. Mouse heart 68 Changes in the distribution of Ga-labeled compounds over time [Table 5-2]

[0251] Table 6. Mouse liver 68 Changes in the distribution of Ga-labeled compounds over time [Table 6]

[0252] Table 7. In mouse kidneys 68 Changes in the distribution of Ga-labeled compounds over time [Table 7]

[0253] Table 8. Mouse muscle 68 Changes in the distribution of Ga-labeled compounds over time [Table 8]

[0254] Table 9. Mouse tumors68 Changes in the distribution of Ga-labeled compounds over time [Table 9]

[0255] Example 11: In tumor-carrying mice 177 Treatment results of Lu-labeled compounds Approximately 6-8 weeks old (Balb / c Nude) mice had 2 x 10¹⁶ granules in the right scapula. 6 Cells were subcutaneously inoculated with HT1080 2# (50% Matrigel, Corning). Once the tumors grew to the size required for the experiment, the animals were randomly divided into 13 experimental groups of 5 animals each, according to tumor volume. The weight and tumor size of the animals were measured, and administration was started on the day of group division, with the control group receiving saline solution and groups 1-12 receiving administration according to the group order. General health and appearance were observed daily after the start of the experiment, and the weight and tumor size of the animals were measured before each sample collection. All abnormal observations found throughout the study must be recorded in the raw data.

[0256] The experimental results are shown in 10, Table 11, Figure 5, and Figure 6. Table 10. 177 Time course of animal tumors after injection of Lu-labeled compounds

[0257] [Table 10]

[0258] Table 11. 177 Changes in animal body weight over time after injection of Lu-labeled compound [Table 11]

[0259] The experimental results were synthesized 177When the Lu-labeled compound was injected into tumor-bearing mice via the tail vein, it showed an inhibitory effect on tumor growth over time. Compared to the reference compound, the synthetic compound demonstrated superior efficacy at the same dose. Furthermore, no significant changes in the animals' body weight were observed at the same dose.

[0260] While the above describes specific embodiments of the present disclosure, those skilled in the art should understand that these are provided only as examples, and that various modifications or alterations may be made to these embodiments without departing from the principles and essence of the present disclosure. Accordingly, the scope of protection of the present disclosure is defined by the appended claims.

Claims

1. Compound X or a pharmaceutically acceptable salt thereof. 【Chemistry 1】 (Here, -X １ -teeth 【Chemistry 2】 And, R １ is C １ to C ４ an alkylene group, C ３ to C ６ a cycloalkylene group, C １ to C ４ an alkylene-C ３ to C ６ a cycloalkylene group or C １ to C ４ an alkylene-C ３ to C ６ a heterocycloalkylene group, wherein the heteroatom of the 3- to 6-membered heterocycloalkylene group is selected from one or more of N, O and S, the number of heteroatoms is one, two or three, and at least one N is included, R ２ is hydrogen or C １ ~C ４ It is alkyl, R ３ is C １ ~C ４ Alkylene group, C １ ~C ４ The alkylene is a 3-6 membered heterocycloalkylene group, a 3-6 membered heterocycloalkylene group, or a 6-12 membered heteroarylene group, wherein the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N; the heteroatoms of the 6-12 membered heteroarylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N. R ４ This is a 3- to 6-membered heterocycloalkylene group, and the heteroatoms of the 3- to 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N. -X ２ - is -X ２－１ -Y １ - and -X ２－１ - represents a chemical bond, a non-natural amino acid residue, or a natural amino acid residue, Y １ teeth 【Transformation 3】 And, R ５ Each is independently C １ ~C ４ Alkylene group or one, two or three R ５－１ C replaced by １ ~C ４ It is an alkylene group, R ５－１ Each of these is independently a halogen, a hydroxyl group, a guanidino group, a carboxyl group, or an amide group. -X ３ - is -X ３－１ -Y ２ - and -X ３－１ - represents a chemical bond, a non-natural amino acid residue, or a natural amino acid residue, Y ２ teeth 【Chemistry 4】 And, R ６ is C １ ~C ４ Alkyl group, one or two R ６－１ C replaced by １ ~C ４ Alkyl alkyl group or C ３ ~C ６ It is a cycloalkyl group, and each R ６－１ These are halogens and C ３ ~C ６ Cycloalkyl groups, C ６ ~C １０ aryl group or one or more R ６－１－１ C replaced by ６ ~C １０ It is an aryl group, R ６－１－１ Each of them is an independent halogen, -X ４ -teeth 【Transformation 5】 And R ７ This is a 3- to 6-membered heterocycloalkylene group, and the heteroatoms of the 3- to 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N. W is -NH-CO- or -NH-CO-NH-, R ８ is a straight chain C １－１０ It is an alkyl group, R ９ is H or one or two R ９－１ C replaced by １ ~C ４ It is an alkyl group, R ９－１ is a carboxyl group or an amide group, L １ and L ２ Each is independently a chemical bond, C １ ~C ４ Alkylene group or -S-(CH) ２ ) ｋ - and k is 0, 1, 2, 3 or 4, Cy is a chemical bond, a 3-6 member heterocycloalkylene group, a 5-6 member heteroarylene group, C ６ ~C １０ Arylene group or C ６ ~C １０ Arielene-L ４ -R １２ The heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N. The heteroatoms of the 5-6 membered heteroarylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N. -L ３ - is -L ３－１ -L ３－２ -L ３－３ - and -L ３－１ is a chemical bond, 【Transformation 6】 And, T １ and T ２ Each of these is independently 0, 1, 2, 3, or 4, and T ３ and T ４ Each of these is independently 0, 1, 2, 3, or 4. -L ３－２ - is -X ５ -Y ３ - is, -X ５ - is a chemical bond, a natural amino acid residue or a polypeptide formed of 2 to 6 natural amino acids, -Y ３ - is a chemical bond, 【Transformation 7】 and T ５ and T ６ is each independently 0, 1, 2, 3 or 4, and E and Q are each independently C １－６ alkylene group or -(OCH ２ CH ２ ) ｊ’ -, j' is 1, 2, 3, 4, 5 or 6, and A is a chemical bond or -NH- -L ３－３ - represents a chemical bond, -NH-, -carbonyl-6-12 member heteroarylene-, -carbonyl-C １－６ Alkylene-3 to 6-membered heterocycloalkylene-,-NH-C １－６ The alkylene-3-6 membered heterocycloalkylene- or 3-6 membered heterocycloalkylene group, wherein the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N; and the heteroatoms of the 6-12 membered heteroarylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N. R １０ is a hydroxyl group or an amino group, -L ４ -teeth 【Transformation 8】 And L ４－１ is a chemical bond, 【Chemistry 9】 And, T ５ and T ６ Each of these is an independent natural number between 0 and 10. M is a 6-12 membered heteroarylene group, and the heteroatoms of the 6-12 membered heteroarylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N. R １１ and R １２ Each is independently either H or a chelating group, and R １１ When H, R １２ is a chelating group, or R １２ When H, R １１ It is a chelating group, The aforementioned chelate group 【Chemistry 10】 , NOTA, HBED-CC, NODAGA, NOTAGA, DOTAGA, TRAP, NOPO, PCTA, DFO, DTPA, CHX-DTPA, AAZTA or DEDPA, The aforementioned compound X is (1) -X １ -teeth 【Chemistry 11】 And, R １ is C １ ~C ４ Alkylene group, C ３ ~C ６ Cycloallene group, C １ ~C ４ Alkylene-C ３ ~C ６ Cycloallene group or C １ ~C ４ Alkylene-C ３ ~C ６ It is a heterocycloalkylene group, R ２ is hydrogen or C １ ~C ４ It is alkyl, R ３ is C １ ~C ４ Alkylene group, C １ ~C ４ The alkylene is a 3- to 6-membered heterocycloalkylene group, a 4- or 6-membered heterocycloalkylene group, or a 6- to 12-membered heteroarylene group, wherein the heteroatoms of the 3- to 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N; the heteroatoms of the 4- or 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N; the heteroatoms of the 6- to 12-membered heteroarylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N. R ４ The group is a 3-6 membered heterocycloalkylene group, and the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and the group contains at least one N. (2) -X ２－１ - indicates the condition that it is a natural amino acid or a non-natural amino acid. (3) -X ３－１ - is a natural amino acid or a non-natural amino acid, or R ６ is C １ ~C ４ Alkyl alkyl group, or one or two R ６－１ C replaced by １ ~C ４ Alkyl alkyl group or C ３ ~C ６ It is a cycloalkyl group, and each R ６－１ These are halogens and C ３ ~C ６ Cycloalkyl groups, or mono-tera R ６－１－１ C replaced by ６ ~C １０ The condition is that it is an aryl group, (4)-X ４ -teeth 【Chemistry 12】 And R ７ This is a four-membered heterocycloalkylene group, and the heteroatoms of the four-membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and it contains at least one N. (5) L ４－１ teeth 【Chemistry 13】 The condition, (Saves one or more of the following conditions.)

2. The aforementioned compound X is (1) R １ In the case of C １ ~C ４ Alkylene group, C １ ~C ４ Alkylene-C ３ ~C ６ Cycloalkylene group and C １ ~C ４ Alkylene-C ３ ~C ６ C of the heterocycloalkylene group １ ~C ４ The alkylene groups are independently a methylene group, an ethylene group, an n-propylene group, and an isopropylene group. For example, under the condition that it is a methylene group, (2) R １ In the case of C １ ~C ４ Alkylene-C ３ ~C ６ C of the cycloalkylene group ３ ~C ６ The cycloalkylene group is a cyclobutylene group or a cyclopropylene group, and the cyclobutylene group is, for example, 【Chemistry 14】 The condition, (3) Caution １ In the case of C １ ~C ４ Alkylene-C ３ ~C ６ C of the heterocycloalkylene group ３ ~C ６ The heterocycloalkylene group is C ４ ~C ６ It is a heterocycloalkylene group, and the C ３ ~C ６ The heteroatom of the heterocycloalkylene group is N, and the number of heteroatoms is preferably one, and the C ３ ~C ６ The heterocycloalkylene group is, for example, an azoxycyclohexylene group, and the azoxycyclohexylene group is, for example, 【Chemistry 15】 The condition, (4) R ２ In the case of C １ ~C ４ The alkyl group is a methyl group, an ethyl group, an n-propyl group, or an isopropyl group. (5) Caution ３ In the case of C １ ~C ４ Alkylene group, and C １ ~C ４ Alkylene - 3- to 6-membered heterocycloalkylene group C １ ~C ４ Each alkylene group is independently a methylene group, an ethylene group, an n-propylene group, or an isopropylene group. (6) R ３ In the case of C １ ~C ４ The alkylene-3-6 membered heterocycloalkylene group and the 3-6 membered heterocycloalkylene group are each independently 4-6 membered heterocycloalkylene groups, and in the 3-6 membered heterocycloalkylene group, the heteroatom is preferably N, and the number of heteroatoms is preferably 1, for example, the 3-6 membered heterocycloalkylene group is an azoxycyclobutylene group, and the azoxycyclobutylene group is, for example, 【Chemistry 16】 The condition, (7) R ３ In this case, the 6-12 membered heteroarylene group is a 6-10 membered heteroarylene group, and in the 12 membered heteroarylene group, the heteroatom is preferably N, and the number of heteroatoms is preferably 1. (8) R ４ The 3-6 membered heterocycloalkylene group is a 4-6 membered heterocycloalkylene group, and in the 3-6 membered heterocycloalkylene group, the heteroatom is preferably N, the number of heteroatoms is preferably 1, and the 3-6 membered heterocycloalkylene group is, for example, an azoxycyclohexylene group, and the azoxycyclohexylene is, for example, 【Chemistry 17】 The condition, (9)-X ２－１ -In this case, the non-natural amino acid residue is D-alanine or [Chemistry 18] And the D-alanine is, for example, 【Chemistry 19】 The condition, (10)-X ２－１ -In this, the natural amino acid residue is a glycine residue or an L-alanine residue, and the glycine residue is, for example, 【Chemistry 20】 The L-alanine residue is, for example, 【Chemistry 21】 The condition, (11) R ５ In the case of C １ ~C ４ Alkylene group and one, two or three R ５－１ C replaced by １ ~C ４ C of the alkylene group １ ~C ４ Each alkylene group is independently a methylene group, an ethylene group, an n-propylene group, or an isopropylene group. For example, under the condition that it is an ethylene group or an n-propylene group, (12)-X ３－１ - In this case, the non-natural amino acid residue is 【Chemistry 22】 The condition, (13)-X ３－１ -In this case, the natural amino acid residue is a glycine residue, 【Chemistry 23】 For example, the aforementioned natural amino acid residue is 【Chemistry 24】 The condition, (14) R ６ In the case of C １ ~C ４ Alkyl alkyl group, and one or two R ６－１ C replaced by １ ~C ４ C of alkyl group １ ~C ４ Each alkylene group is independently a methylene group, an ethylene group, an n-propylene group, or an isopropylene group. For example, under the condition that it is a methylene group, (15) R ６ In the case of C ３ ~C ６ The cycloalkyl group is defined as a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group. (16) R ６－１ In the case of C ３ ~C ６ The cycloalkyl group is a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group, for example, a cyclohexyl group, and the cyclohexyl group is, for example, 【Chemistry 25】 The condition, (17) R ６－１ In the case of C ６ ~C １０ An aryl group, and one or more R ６－１―１ C replaced by ６ ~C １０ C of the aryl group ６ ~C １０ Each aryl group is independently either a phenyl group or a naphthyl group, for example, under the condition that it is a phenyl group, (18) R ６－１－１ In this case, the halogen is fluorine, chlorine, or bromine, (19) R ７ In this, the 3-6 membered heterocycloalkylene group is a 4-6 membered heterocycloalkylene group, and in the 3-6 membered heterocycloalkylene group, the heteroatom is preferably N, the number of heteroatoms is preferably 1, and the 3-6 membered heterocycloalkylene group is, for example, an azoxycyclopentylene group, and the azoxycyclopentylene group is, for example, 【Chemistry 26】 The condition, (20) R ８ In the case of C １－１０ The alkyl group is a methyl group, ethyl group, n-propyl group, n-butyl group, n-pentyl group, n-hexyl group, n-heptyl group, n-octyl group, or n-nonyl group, for example, under the condition that it is a methyl group, n-pentyl group, n-nonyl group, n-heptyl group, or n-butyl group. (21) R ９ In the case of C １ ~C ４ The alkyl group is a methyl group, an ethyl group, an n-propyl group, or an isopropyl group, for example, an ethyl group, and the ethyl group is, for example, 【Chemistry 27】 The condition, (22) L １ and L ２ In the case of C １ ~C ４ The alkylene group is a methylene group, an ethylene group, an n-propylene group, or an isopropylene group. For example, under the condition that it is an n-propylene group, (23) In Cy, the 3-6 membered heterocycloalkylene group is a 5-6 membered heterocycloalkylene group, the heteroatom of the 3-6 membered heterocycloalkylene group is preferably N, and the number of heteroatoms is preferably 3. (24) In Cy, the heteroatom of the 5-6 membered heteroarylene group is N, and the number of heteroatoms is preferably one or three, for example the 5-6 membered heteroarylene group is a pyridyl group or 1H-1,2,3-triazole, and the pyridyl group is, for example 【Chemistry 28】 The 1H-1,2,3-triazole is, for example, 【Chemistry 29】 The condition, (25) In Cy, the C ６ ~C １０ Arylene group or C ６ ~C １０ Arielene-L ４ -R １２ C ６ ~C １０ Each allerene group is independently a phenyl group or a naphthyl group, for example, a phenyl group, and the phenyl group is, for example, 【Transformation 30】 The condition, (26) L ３－２ In the above, the natural amino acids of the natural amino acid residue or the polypeptide formed from 2 to 6 natural amino acids are selected from one or more of glutamic acid, arginine, glycine, and aspartic acid, preferably the polypeptide is formed from 3 natural amino acids, and more preferably the polypeptide is 【Chemistry 31】 The condition, (27) Y ３ In the case of C １－６ The alkylene group is a straight chain C １－６ It is an alkylene group, preferably the C １－６ The alkylene group is a methyl group, ethyl group, n-propyl group, n-butyl group, n-pentyl group, or n-hexyl group, for example, under the condition that it is a methyl group, ethyl group, or n-propyl group, (28) L ３－３ In this, the 6-12 membered heteroarylene group is a 12 membered heteroarylene group, and in the 6-12 membered heteroarylene group, the heteroatom is preferably N, and the number of heteroatoms is preferably 1, for example, the 6-12 membered heteroarylene group is 【Chemistry 32】 The condition, (29) L ３－３ In the above carbonyl-C １－６ Alkylene-3 to 6-membered heterocycloalkylene group, NH-C １－６ The alkylene-3-6 membered heterocycloalkylene group and the 3-6 membered heterocycloalkylene group are each independently 4-6 membered heterocycloalkylene groups, the heteroatom is preferably N, the number of heteroatoms is preferably 1 or 2, and the 3-6 membered heterocycloalkylene group is, for example, an azoxycyclohexylene group, and the azoxycyclohexylene group is, for example, 【Transformation 33】 The condition, (30) L ３－３ In the above carbonyl-C １－６ Alkylene-3 to 6-membered heterocycloalkylene group and NH-C １－６ Alkylene - 3- to 6-membered heterocycloalkylene group C １－６ The alkylene group is independently a methyl group, an ethyl group, an n-propyl group, an n-butyl group, an n-pentyl group, or an n-hexyl group, for example, under the condition that it is a methyl group, an ethyl group, or an n-propyl group, (31)-L ３ - １ - in 【Transformation 34】 The condition, (32)-L ３ - １ - in 【Chemistry 35】 Conditions A compound X according to claim 1 or a pharmaceutically acceptable salt thereof that satisfies one or more of the following conditions.

3. The aforementioned compound X is (1) -X １ -teeth 【Transformation 36】 And here, 【Chemistry 37】 is X ４ Conditions linked to, (2) -X ２ - is -X ２－１ -Y １ - and here, X ２－１ is X ４ Conditions linked to, (3) -X ３ - is -X ３－１ -Y ２ - and here, X ３－１ The condition is that it is linked to an -NH- or carbonyl group. (4)-X ４ -teeth 【Transformation 38】 And here, 【Chemistry 39】 is X ２ Conditions linked to, (5) W is -NH-CO-* or -NH-CO-NH-*, where -* is R ８ Conditions linked to, (6) L １ and L ２ Each is independently a chemical bond, C １ ~C ４ Alkylene group or -S-(CH) ２ ) ｋ -*, where * is the condition for being linked to Cy. (7)-L ３ - is -L ３－１ -L ３－２ -L ３－３ -* is R １１ Conditions linked to, (8)-L ３－１ - is a chemical bond. 【Chemistry 40】 And here, 【Chemistry 41】 Ha-L ３－２ - Conditions that are linked to (9)-L ３－２ - is * - X ５ -Y ３ - and here, *- is -L ３－１ - Conditions that are linked to (10)-L ３－３ - represents a chemical bond, -NH-, -carbonyl-6-12 member heteroarylene-*, -carbonyl-C １－６ Alkylene-3 to 6-membered heterocycloalkylene-*,-NH-C １－６ Alkylene-3-6 membered heterocycloalkylene-* or a 3-6 membered heterocycloalkylene group, where -* is R １１ Conditions linked to, (11)-L ４ -teeth 【Chemistry 42】 And here, 【Chemistry 43】 This is the condition for being linked to Cy. A compound X according to claim 1 or a pharmaceutically acceptable salt thereof that satisfies one or more of the following conditions.

4. The aforementioned compound X is (1) -X １ -teeth 【Chemistry 44】 The condition, (2) R １ is C ３ ~C ６ Cycloalkylene group or C １ ~C ４ Alkylene-C ３ ~C ６ A heterocycloalkylene group, wherein the heteroatoms of the 3- to 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and the group contains at least one N. (3) Caution ２ The condition is that it is hydrogen. (4) R ３ The group is a 3-6 membered heterocycloalkylene group, and the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and the group contains at least one N. (5)-X ２－１ - represents a chemical bond, a non-natural amino acid residue, or a natural amino acid residue, and the non-natural amino acid residue is 【Chemistry 45】 The aforementioned natural amino acid residues are 【Chemistry 46】 And for example, -X ２－１ - is a condition for a chemical bond, (6) R ５ Each of these is independently one, two, or three R ５－１ C replaced by １ ~C ４ The condition is that it is an alkylene group, (7) Each R ５－１ Each of these is independently a halogen, a hydroxyl group, a guanidine group, or an amide group, for example, a hydroxyl group, a guanidine group, or an amide group, and also, for example, a hydroxyl group, (8)-X ３－１ - represents a chemical bond or a natural amino acid residue, and the natural amino acid residue is, for example, 【Chemistry 47】 And for example, -X ３－１ - is a condition for a chemical bond, (9) Caution ６ is one or two R ６－１ C replaced by １ ~C ４ Conditions for being an alkyl group, (10) Each R ６－１ These are halogens and C ３ ~C ６ Cycloalkyl groups or C ６ ~C １０ It is an aryl group, for example, C ３ ~C ６ Cycloalkyl groups or C ６ ~C １０ The condition is that it is an aryl group, (11) R ９ is one or two R ９－１ C replaced by １ ~C ４ It is an alkyl group, R ９－１ The condition is that it is an amide group. (12) k is 0 or 1, for example, the condition that k is 1, (13) Cy is a chemical bond, a 5-6 member heteroarylene group, C ６ ~C １０ Arylene group, or C ６ ~C １０ Arielene-L ４ -R １２ The 5-6 membered heteroarylene group is such that the heteroatoms are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and it contains at least one N, for example, C ６ ~C １０ Conditions for being an arylene group, (14) T １ and T ２ Each of these conditions is independently either 0 or 1. (15) T ３ and T ４ Each is independently 0, 1, or 3, for example, the condition is 0 or 1, (16)-L ３－２ - is -X ５ -Y ３ - and -X ５ - is a chemical bond or a polypeptide formed from 2 to 6 natural amino acids, and -Y ３ - is a chemical bond. 【Chemistry 48】 And for example, -X ５ - represents a chemical bond, -Y ３ -teeth 【Chemistry 49】 And, or, -X ５ - is a polypeptide formed from 2 to 6 natural amino acids, and -Y ３ - is a chemical bond or [Transformation 50] And, for example, -X ５ - represents a chemical bond, -Y ３ - is a chemical bond. 【Chemistry 51】 The condition is that A is a chemical bond or -NH-, (17) E and Q are each independent of C １－６ The condition is that it is an alkylene group, (18) T ５ and T ６ Each is independently 0, 1, 2, or 4, for example, the condition is 0, 1, or 2. (19) The condition that j' is 1, 2 or 3, (20) R １０ The condition is that it is a hydroxyl group. (21)-L ４ -teeth 【Chemistry 52】 And L ４－１ The condition is that it is a chemical bond. (22) The chelate group is 【Chemistry 53】 The condition, (23) R １１ is a chelating group, and the chelating group is 【Chemistry 54】 The condition, (24) The compound X is (1) -X １ -teeth 【Transformation 55】 And R ３ The group is a four-membered or six-membered heterocycloalkylene group, and the heteroatoms of the four-membered or six-membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and it contains at least one N. (2) R ６ is one or two R ６－１ C replaced by １ ~C ４ Each R is an alkyl group. ６－１ C is independent ３ ~C ６ Conditions that satisfy one or more of the conditions for being a cycloalkyl group, A compound X according to claim 1 or a pharmaceutically acceptable salt thereof that satisfies one or more of the following conditions.

5. The aforementioned compound X is (1) -X ２－１ - is -X ２－１ -Y １ - and -X ２－１ - is a chemical bond, Y １ teeth 【Transformation 56】 The condition, (2) -X ３ - is -X ３－１ -Y ２ - and -X ３－１ - is a chemical bond, Y ２ teeth 【Chemistry 57】 It is, Preferably, -L ３－１ teeth 【Transformation 58】 And, For example, -L ３－１ teeth 【Chemistry 59】 And, T １ and T ２ Each of these is independently 0, 1, 2, 3, or 4. -L ３－２ - is -X ５ -Y ３ - and -X ５ - represents a chemical bond, -Y ３ -teeth 【Transformation 60】 And, T ６ is 0, 1, 2, 3 or 4, and E is C １－６ Alkylene group or (OCH ２ CH ２ ) ｊ’ - and j' is 1, 2, 3, 4, 5 or 6, for example, j' is 1 and A is a chemical bond or -NH-, -L ３－３ - is a chemical bond, For example, -L ３－１ teeth 【Chemistry 61】 And, T １ and T ２ Each of these is independently 0, 1, 2, 3, or 4. -L ３－２ - is -X ５ -Y ３ - and -X ５ - represents a chemical bond, -Y ３ - is a chemical bond, -L ３－３ - is - NH-C １－６ The alkylene-3-6 membered heterocycloalkylene- or 3-6 membered heterocycloalkylene group, wherein the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and includes at least one N. For example, -L ３－１ teeth 【Transformation 62】 And, T ３ and T ４ Each of these is independently 0, 1, 2, 3, or 4. -L ３－２ - is -X ５ -Y ３ - and -X ５ - represents a chemical bond, -Y ３ -teeth 【Transformation 63】 And, T ５ Q is 0, 1, 2, 3 or 4, and Q is C １－６ Alkylene group or (OCH ２ CH ２ ) ｊ’ - and j' is 1, 2, 3, 4, 5 or 6, -L ３－３ - is -NH-, For example, -L ３－１ teeth 【Chemistry 64】 And, T ３ and T ４ Each of these is independently 0, 1, 2, 3, or 4. -L ３－２ - is -X ５ -Y ３ - and -X ５ - represents a chemical bond, -Y ３ - is a chemical bond, -L ３－３ - is -carbonyl-6-12 member heteroarylene-, -carbonyl-C １～６ The alkylene is a 3- to 6-membered heterocycloalkylene, where the heteroatoms of the 3- to 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N; the heteroatoms of the 6- to 12-membered heteroarylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N; For example, -L ３－１ teeth 【Transformation 65】 And, T １ and T ２ Each of these is independently 0, 1, 2, 3, or 4. -L ３－２ - is -X ５ -Y ３ - and -X ５ - is a natural amino acid residue, or a polypeptide formed from 2 to 6 natural amino acid residues, Y ３ It is a chemical bond, -L ３－３ - is a condition for a chemical bond, (3) Caution ９ is one R ９－１ C replaced by １ ~C ４ It is an alkyl group, R ９－１ The condition is that it is an amide group. (4) L １ and L ２ ha-S-(CH ２ ) ｋ - and the condition that k is 1, (5) Cy is a chemical bond, a 3-6 member heterocycloalkylene group, a 5-6 member heteroarylene group, or C ６ ~C １０ The arylene group is characterized in that the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and at least one N is included. The 5-6 membered heteroarylene group is characterized in that the heteroatoms are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and at least one N is included. R １１ It is a chelating group, Preferably, Cy is C ６ ~C １０ It is an arylene group, R １１ is a chelating group, for example, in Cy, the C ６ ~C １０ The arylene group 【Chemical Formula 66】 The condition, (6)-L ３－２ - is -X ５ -Y ３ - and -X ５ - represents a chemical bond, -Y ３ - is a chemical bond. 【Transformation 67】 And, T ５ and T ６ Each is independently 0, 1, 2, or 4, and E and Q are independently C １－６ The condition is that it is an alkylene group and A is a chemical bond or -NH-, (7)-L ３－３ The hyphen represents a chemical bond, -NH-, -carbonyl-C １－６ Alkylene-3 to 6-membered heterocycloalkylene-,-NH-C １－６ Alkylene-3 to 6-membered heterocycloalkylene-, for example, -L ３－３ - is -NH-, -carbonyl-C １－６ Alkylene-3 to 6-membered heterocycloalkylene-,-NH-C １－６ The alkylene is a 3- to 6-membered heterocycloalkylene, wherein the heteroatoms of the 3- to 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and the group contains at least one N. A compound X according to claim 1 or a pharmaceutically acceptable salt thereof that satisfies one or more of the following conditions.

6. The aforementioned compound X is compound X-1, compound X-2, compound X-3, compound X-4, or compound X-5. 【Transformation 68】 Z is N or CH, X １ , X ２ , X ３ , X ４ , R ９ , R ８ , L １ W, L ２ , L ３ and R １１ The definition of is as described in claim 1, the compound X described in claim 1 or a pharmaceutically acceptable salt thereof.

7. The aforementioned compound X is compound X-6, compound X-7, compound X-8, or compound X-9. 【Transformation 69】 However, X １ , X ２ , X ３ , R ９ , R ８ W, L １ , L ２ ,Cy,L ３ and R １１ The definition of is as described in claim 1, the compound X described in claim 1 or a pharmaceutically acceptable salt thereof.

8. The compound X is one of the following schemes: Scheme 1: In compound X, -X １ -teeth 【Transformation 70】 And, R １ is C ３ ~C ６ Cycloalkylene group or C １ ~C ４ Alkylene-C ３ ~C ６ A heterocycloalkylene group, wherein the heteroatoms of the 3- to 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and includes at least one N. R ２ It is hydrogen, R ３ This is a 3- to 6-membered heterocycloalkylene group, and the heteroatoms of the 3- to 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N. R ４ This is a 3- to 6-membered heterocycloalkylene group, and the heteroatoms of the 3- to 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N. -X ２ - is -X ２－１ -Y １ - and -X ２－１ - represents a chemical bond, a non-natural amino acid residue, or a natural amino acid residue. The aforementioned non-natural amino acid residues are 【Chemistry 71】 The aforementioned natural amino acid residues are 【Chemistry 72】 Y １ teeth 【Transformation 73】 And, R ５ Each of these is independently one, two, or three R ５－１ C replaced by １ ~C ４ It is an alkylene group, Each R ５－１ Each of these is independently a hydroxyl group, a guanidino group, or an amide group. -X ３ - is -X ３－１ -Y ２ - and -X ３－１ - represents a chemical bond or a natural amino acid residue. The aforementioned natural amino acid residues are 【Chemistry 74】 Y ２ teeth 【Chemistry 75】 And, R ６ is one or two R ６－１ C replaced by １ ~C ４ Each R is an alkyl group. ６－１ These are halogens and C ３ ~C ６ Cycloalkyl groups or C ６ ~C １０ It is an aryl group, -X ４ -teeth 【Transformation 76】 And R ７ This is a 3- to 6-membered heterocycloalkylene group, and the heteroatoms of the 3- to 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N. W is -NH-CO- or -NH-CO-NH-, R ８ is a straight chain C １－１０ It is an alkyl group, R ９ is H or one or two R ９－１ C replaced by １ ~C ４ It is an alkyl group, R ９－１ is a carboxyl group (-COOH) or an amide group (-CONH ２ ) and L １ and L ２ Each is independently a chemical bond, C １ ~C ４ Alkylene group or -S-(CH) ２ ) ｋ - and k is 0 or 1, Cy is a chemical bond, a 5-6 membered heteroarylene group, C ６ ~C １０ Arylene group, or C ６ ~C １０ Arielene-L ４ -R １２ The 5-6 membered heteroarylene group is such that the heteroatoms are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and it contains at least one N. -L ３ - is -L ３－１ -L ３－２ -L ３－３ - and -L ３－１ is a chemical bond, 【Chemical 77】 And, T １ and T ２ Each of these is independently either 0 or 1, and T ３ and T ４ Each of these is independently 0, 1, or 3. -L ３－２ - is -X ５ -Y ３ - and -X ５ - is a chemical bond or a polypeptide formed from 2 to 6 natural amino acids, and -Y ３ - is a chemical bond. 【Transformation 78】 And, T ５ and T ６ Each is independently 0, 1, 2, or 4, and E and Q are independently C １－６ Alkylene group or -(OCH) ２ CH ２ ) ｊ’ -, j' is 1, 2 or 3, and A is a chemical bond or -NH-, -L ３－３ - represents a chemical bond, -NH-, -carbonyl-6-12 member heteroarylene-, -carbonyl-C １－６ Alkylene-3 to 6-membered heterocycloalkylene-,-NH-C １－６ The alkylene-3-6 membered heterocycloalkylene- or 3-6 membered heterocycloalkylene group, wherein the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N; and the heteroatoms of the 6-12 membered heteroarylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N. R １０ is a hydroxyl group or an amino group, -L ４ -teeth 【Chemistry 79】 And L ４－１ It is a chemical bond, R １２ and R １１ Each is independently either H or a chelating group, and R １１ When H, R １２ is a chelating group, or R １２ When H, R １１ It is a chelating group, The aforementioned chelate group 【Chemistry 80】 , NOTA, HBED-CC, NODAGA, NOTAGA, DOTAGA, TRAP, NOPO, PCTA, DFO, DTPA, CHX-DTPA, AAZTA or DEDPA, The aforementioned compound X is (1) -X １ -teeth 【Chemistry 81】 R １ C ３ ~C ６ Cycloalkylene group, or C １ ~C ４ Alkylene-C ３ ~C6 heterocycloalkylene group, R ２ It is hydrogen, R ３ This is a four-membered or six-membered heterocycloalkylene group, where the heteroatoms of the four-membered or six-membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and it contains at least one N. R ４ The group is a 3-6 membered heterocycloalkylene group, and the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and the group contains at least one N. (2) -X ２－１ - indicates the condition that it is a natural amino acid or a non-natural amino acid. (3) -X ３－１ - is a natural amino acid, or R ６ is one or two R ６－１ C replaced by １ ~C ４ Each R is an alkyl group. ６－１ Each is independently C ３ ~C ６ The condition is that it is a cycloalkyl group or halogen, (4)-X ４ -teeth 【Chemistry 82】 And R ７ is a four-membered heterocycloalkylene group, wherein the heteroatoms of the four-membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and one or more of the following conditions are met: Scheme 2: In the aforementioned compound X, -X １ -teeth 【Chemistry 83】 And, R ３ This is a 3- to 6-membered heterocycloalkylene group, and the heteroatoms of the 3- to 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N. -X ２ - is -X ２－１ -Y １ - and -X ２－１ - is a chemical bond, Y １ teeth 【Chemical 84】 And, R ５ Each of these is independently one, two, or three R ５－１ C replaced by １ ~C ４ It is an alkylene group, Each R ５－１ Each of these is independently a hydroxyl group, -X ３ - is -X ３－１ -Y ２ - and -X ３－１ - is a chemical bond, Y ２ teeth 【Chemical 85】 And, R ６ is one or two R ６－１ C replaced by １ ~C ４ Each R is an alkyl group. ６－１ Each is independently C ３ ~C ６ Cycloalkyl groups or C ６ ~C １０ It is an aryl group, -X ４ -teeth 【Chemical 86】 And R ７ This is a 3- to 6-membered heterocycloalkylene group, and the heteroatoms of the 3- to 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N. W is -NH-CO- or -NH-CO-NH-, R ８ is a straight chain C １－１０ It is an alkyl group, R ９ is H or one or two R ９－１ C replaced by １ ~C ４ It is an alkyl group, R ９－１ is an amide group (-CONH ２ ) and L １ and L ２ Each of them independently represents -S-(CH ２ ) ｋ - and k is 1, Cy is C ６ ~C １０ It is an arylene group, -L ３ - is -L ３－１ -L ３－２ -L ３－３ - and -L ３－１ is a chemical bond, 【Transformation 87】 And, T １ and T ２ Each of these is independently either 0 or 1, and T ３ and T ４ Each of these is independently either 0 or 1, -L ３－２ - is -X ５ -Y ３ - and -X ５ - represents a chemical bond, -Y ３ - is a chemical bond. 【Chemical 88】 And, T ５ and T ６ Each is independently 0, 1, or 2, and E and Q are independently C １－６ It is an alkylene group, and A is a chemical bond or -NH-. -L ３－３ The hyphen represents a chemical bond, -NH-, -carbonyl-C １－６ Alkylene-3 to 6-membered heterocycloalkylene-,-NH-C １－６ The alkylene-3-6 membered heterocycloalkylene- or 3-6 membered heterocycloalkylene group, wherein the heteroatoms of the 3-6 membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and includes at least one N. R １０ It is a hydroxyl group, R １１ is a chelating group, and the chelating group is 【Chemical 89】 And, The aforementioned compound X is (1) -X １ -teeth 【Chemistry 90】 And R ３ The group is a four-membered or six-membered heterocycloalkylene group, and the heteroatoms of the four-membered or six-membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and it contains at least one N. (2) R ６ is one or two R ６－１ C replaced by １ ~C ４ Each R is an alkyl group. ６－１ C is independent ３ ~C ６ Satisfying one or more of the conditions for being a cycloalkyl group, Scheme 3: In the aforementioned compound X, -X １ -teeth 【Chemistry 91】 And, R ３ This is a 3- to 6-membered heterocycloalkylene group, and the heteroatoms of the 3- to 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N. -X ２ - is -X ２－１ -Y １ - and -X ２－１ - is a chemical bond, Y １ teeth 【Chemistry 92】 And, R ５ Each of these is independently one, two, or three R ５－１ C replaced by １ ~C ４ It is an alkylene group, Each R ５－１ Each of these is independently a hydroxyl group, -X ３ - is -X ３－１ -Y ２ - and -X ３－１ - is a chemical bond, Y ２ teeth 【Chemistry 93】 And, R ６ is one or two R ６－１ C replaced by １ ~C ４ Each R is an alkyl group. ６－１ Each is independently C ３ ~C ６ Cycloalkyl groups or C ６ ~C １０ It is an aryl group, -X ４ -teeth 【Chemical 94】 And R ７ This is a 3- to 6-membered heterocycloalkylene group, and the heteroatoms of the 3- to 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N. W is -NH-CO- or -NH-CO-NH-, R ８ is a straight chain C １－１０ It is an alkyl group, R ９ is one R ９－１ C replaced by １ ~C ４ It is an alkyl group, R ９－１ It is an amide group, L １ and L ２ Each of them independently represents -S-(CH ２ ) ｋ - and k is 1, Cy is C ６ ~C １０ It is an arylene group, -L ３ - is -L ３－１ -L ３－２ -L ３－３ - and -L ３－１ teeth 【Chemical 95】 And, T １ and T ２ Each of these is independently either 0 or 1, and T ３ and T ４ Each of these is independently either 0 or 1, -L ３－２ - is -X ５ -Y ３ - and -X ５ - represents a chemical bond, -Y ３ - is a chemical bond. 【Chemistry 96】 And, T ５ and T ６ Each is independently 0, 1, or 2, and E and Q are independently C １－６ Alkylene group or -(OCH) ２ CH ２ ) ｊ’ -, j' is 1, A is a chemical bond or -NH-, -L ３－３ The hyphen represents a chemical bond, -NH-, -carbonyl-C １－６ Alkylene-3 to 6-membered heterocycloalkylene-,-NH-C １－６ The alkylene is a 3- to 6-membered heterocycloalkylene, where the heteroatoms of the 3- to 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and it contains at least one N. R １０ is a hydroxyl group or an amino group, R １１ It is a chelating group, The aforementioned chelate group 【Chemistry 97】 , NOTA, HBED-CC, NODAGA, NOTAGA, DOTAGA, TRAP, NOPO, PCTA, DFO, DTPA, CHX-DTPA, AAZTA or DEDPA, Scheme 4: In the aforementioned compound X, -X １ -teeth 【Chem.98】 And, R ３ This is a 3- to 6-membered heterocycloalkylene group, and the heteroatoms of the 3- to 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N. -X ２ - is -X ２－１ -Y １ - and -X ２－１ - is a chemical bond, Y １ teeth 【Chem.99】 And, R ５ Each of these is independently one, two, or three R ５－１ C replaced by １ ~C ４ It is an alkylene group, Each R ５－１ Each of these is independently a hydroxyl group, -X ３ - is -X ３－１ -Y ２ - and -X ３－１ - is a chemical bond, Y ２ teeth 【Chemistry 100】 And, R ６ is one or two R ６－１ C replaced by １ ~C ４ Each R is an alkyl group. ６－１ C is independent ３ ~C ６ Cycloalkyl groups or C ６ ~C １０ It is an aryl group, -X ４ -teeth 【Chemistry 101】 And R ７ This is a 3- to 6-membered heterocycloalkylene group, and the heteroatoms of the 3- to 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, and the number of heteroatoms is one, two, or three, and includes at least one N. W is -NH-CO- or -NH-CO-NH-, R ８ is a straight chain C １－１０ It is an alkyl group, R ９ is one or two R ９－１ C replaced by １ ~C ４ It is an alkyl group, R ９－１ is an amide group (-CONH ２ ) and L １ and L ２ Each of them independently represents -S-(CH ２ ) ｋ - and k is 1, Cy is C ６ ~C １０ It is an arylene group, -L ３ - is -L ３－１ -L ３－２ -L ３－３ - and -L ３－１ teeth 【Chemical Engineering 102】 And, T １ and T ２ Each of these is independently either 0 or 1, and T ３ and T ４ Each of these is independently either 0 or 1, -L ３－２ - is -X ５ -Y ３ - and -X ５ - represents a chemical bond, -Y ３ - is a chemical bond. 【Chemistry 103】 And, T ５ and T ６ Each is independently 0, 1, 2, or 4, and E and Q are independently C １－６ It is an alkylene group, and A is a chemical bond or -NH-. -L ３－３ - is -NH-, -carbonyl-C １－６ Alkylene-3 to 6-membered heterocycloalkylene-,-NH-C １－６ The alkylene is a 3- to 6-membered heterocycloalkylene, where the heteroatoms of the 3- to 6-membered heterocycloalkylene group are selected from one or more of N, O, and S, the number of heteroatoms is one, two, or three, and it contains at least one N. R １０ It is a hydroxyl group, R １１ It is a chelating group, The aforementioned chelate group 【Chemical 104】 Compound X according to claim 1, or a pharmaceutically acceptable salt thereof, which is NOTA, HBED-CC, NODAGA, NOTAGA, DOTAGA, TRAP, NOPO, PCTA, DFO, DTPA, CHX-DTPA, AAZTA, or DEDPA.

9. The aforementioned compound X is (1) -X １ -teeth 【Chemistry 105】 Preferably, -X １ -teeth 【Chemistry 106】 【Chemistry 107】 is X ４ Conditions linked to, (2) -X ４ -teeth 【Chemistry 108】 For example, 【Chemistry 109】 And, Preferably, -X ４ -teeth 【Chemical 110】 And here, 【Chemistry 111】 is X ２ Conditions linked to, (3) -X ２ -teeth 【Chemistry 112】 Preferably, -X ２ -teeth 【Chemistry 113】 And here, 【Chemical 114】 The condition for being linked to -NH- (4)-X ３ -teeth 【Chemical 115】 Preferably, -X ３ -teeth 【Chemistry 116】 And here, 【Chemistry 117】 The conditions for being linked to a carbonyl group are (5)-L ４ -teeth 【Chemistry 118】 Preferably, -L ４ -teeth 【Chemical 119】 And here, 【Chemical 120】 is R １１ Conditions linked to, (6)-L ３－１ - is a chemical bond. 【Chemistry 121】 Preferably, -L ３－１ - is a chemical bond. 【Chemistry 122】 And here, 【Chemical 123】 Ha-L ３－２ - Conditions that are linked to (7)-L ３－２ - is a chemical bond. 【Chemistry 124】 Preferably, -L ３－２ - is a chemical bond. 【Chemistry 125】 Here, 【Chemistry 126】 Ha-L ３－３ - Conditions that are linked to (8)-L ３－３ - represents a chemical bond, -NH-, 【Chemistry 127】 Preferably, -L ３－３ - is a chemical bond. 【Chemistry 128】 And here, 【Chemistry 129】 is R １１ Conditions linked to, (9) Caution ８ The condition is that it is a methyl group, an n-pentyl group, an n-nonyl group, an n-heptyl group, or an n-butyl group. (10) R ９ H, 【Chemistry 130】 The condition, (11) L １ and L ２ Each of these independently has the conditions of being -S-methylene-, n-propylene-, a chemical bond, or -S-. (12) Cy is 【Chemistry 131】 Chemical bond or 【Chemistry 132】 And here, 【Chemistry 133】 For example, 【Chemistry 134】 And here, 【Chemistry 135】 is L １ Conditions linked to A compound X according to claim 1 or a pharmaceutically acceptable salt thereof that satisfies one or more of the following conditions.

10. The compound X described in claim 1 or a pharmaceutically acceptable salt thereof, wherein the structure of the compound X is represented by any one of the following formulas. 【Transformation 136】 【Chemistry 137】 【Chemistry 138】 【Chemistry 139】 [Chemical 140] 【Chemistry 141】 【Chemistry 142】 【Chemistry 143】 【Chemistry 144】 【Chemistry 145】 【Chemistry 146】 【Chemistry 147】 【Chemistry 148】 【Chemistry 149】 [Chemical 150] 【Chemistry 151】 【Chemistry 152】 【Chemistry 153】 【Chemistry 154】

11. A cyclic polypeptide compound A is a compound formed by chelating compound X according to any one of claims 1 to 10 with a therapeutic radionuclide ion.

12. The aforementioned cyclic polypeptide compound A is (1) The radioactive nuclide for therapeutic purposes is １７７ Lu, ９０ Y, ８９ Sr, １８８ Re, ２２５ Ac, ２１３ Bi or ２１２ The condition for Pb, (2) The condition that the valence state of the therapeutic radionuclide ion is monovalent, divalent, trivalent, or tetravalent, (3) The therapeutic radioactive nuclide ions, １７７ Lu ３＋ , ２２５ Ac ３＋ , ９０ Y ３＋ , ２１２ Pb ２＋ or ２１３ Bi ３＋ Conditions A cyclic polypeptide compound A according to claim 11, satisfying one or more of the following conditions.

13. The cyclic polypeptide compound A is compound X and １７７ Lu ３＋ The cyclic polypeptide compound A according to claim 11, which is a compound formed by chelating the two.

14. The compound is formed by chelating compound X with a radioactive nuclide ion for diagnostics, and the structure of compound X A cyclic polypeptide compound B, wherein the compound is as described in any one of claims 1 to 10.

15. The aforementioned cyclic polypeptide compound B is (1) The diagnostic radionuclide is １８ F, ６８ Ga, １１１ In or ６４ Conditions for being Cu, (2) The condition that the valence state of the diagnostic radionuclide ion is monovalent, divalent, trivalent, or tetravalent, (3) The diagnostic radioactive metal ions ６８ Ga ３＋ or ６４ Cu ２＋ Conditions A cyclic polypeptide compound B according to claim 14, satisfying one or more of the following conditions.

16. The aforementioned cyclic polypeptide compound B is compound X and ６８ Ga ３＋ The compound is formed by chelating and the structure of compound X The cyclic polypeptide compound B according to claim 14, wherein the compound is as described in any one of claims 1 to 10.

17. A pharmaceutical composition comprising substance Y and a pharmaceutical excipient, wherein substance Y is a cyclic polypeptide compound A according to any one of claims 11 to 13 or a cyclic polypeptide compound B according to any one of claims 14 to 16.

18. Use of cyclic polypeptide compound A according to any one of claims 11 to 13 in the manufacture of a pharmaceutical product for treating a tumor, wherein the tumor may be a solid tumor expressing FAP, such as breast cancer, ovarian cancer, lung cancer, colorectal cancer, gastric cancer, pancreatic cancer, prostate cancer, liver cancer, or cutaneous melanoma.

19. Use of cyclic polypeptide compound B according to any one of claims 14 to 16 in the manufacture of a pharmaceutical product for diagnosing a tumor, wherein the tumor may be a solid tumor expressing FAP, such as breast cancer, ovarian cancer, lung cancer, colorectal cancer, gastric cancer, pancreatic cancer, prostate cancer, liver cancer, or cutaneous melanoma.

Images