Peptoid compound and complex thereof, pharmaceutical composition, and use

Abstract

Disclosed in the present invention are a peptoid compound and a complex thereof, and a pharmaceutical composition comprising the peptoid compound. The peptoid compound can target integrin proteins such as αvβ5, α5β1 or αvβ3, and are enriched in integrin highly expressed tumor cells, and the peptoid compound and the complex thereof, and the pharmaceutical composition can be used for diagnosis and / or treatment of tumors.

Description

A peptide-like compound, its complex, pharmaceutical composition and application

[0001] This application claims priority to the Chinese patent application filed with the China Patent Office on June 21, 2023, with application number 2023107486486 and invention name “A peptoid compound and its complex, pharmaceutical composition and application”, the entire contents of which are incorporated by reference into this application. Technical Field

[0002] The present invention belongs to the technical field of pharmaceutical chemical synthesis, and specifically relates to a peptoid compound and its complex, a pharmaceutical composition containing the same, and its medical use. The peptoid compound is specifically a compound with integrin inhibitory activity. Background Art

[0003] Integrins are transmembrane glycoproteins ubiquitously present in cells. They are members of the cell adhesion molecule family and are the primary mediators of cell-extracellular matrix (ECM) interactions. They are a class of cell membrane receptors that recognize and bind to corresponding ligands in the ECM, providing attachment points for cell adhesion, regulating cell motility, proliferation, and apoptosis. They mediate mutual recognition and adhesion between cells and between cells and the ECM, and serve to bridge external cellular processes with internal cellular structures. Integrins are heterodimers composed of two subunits, α and β, linked by non-covalent bonds in a 1:1 ratio. They consist of an extracellular domain, a transmembrane domain, and an intracellular domain. The extracellular domain is connected to form a globular region and contains a divalent cation-binding domain. Based on the specificity of their ligand recognition, integrins can be broadly classified as those that recognize the arginase-glycinase-aspartase peptide (RGD tripeptide) sequence, laminin-binding integrins, leukocyte integrins, and collagen-binding integrins. Integrins bind to ECM proteins—collagen, laminin, vitronectin, fibronectin—or some cell surface molecules through their extracellular domains. Integrins are involved in many important physiological processes, including embryogenesis, blood coagulation, and maintaining the integrity of tissues and organs in the body. Many pathological processes, such as inflammation, thrombosis, angiogenesis, and the growth, infiltration, and metastasis of malignant tumors, are associated with abnormal integrin regulation.

[0004] Dysregulation of integrin expression on cancer cells has been extensively studied in cell and animal models, and targeting integrins has been shown to inhibit tumor growth, reduce resistance to chemotherapy or radiotherapy, and mitigate invasion and metastasis. Studies using transgenic mouse models or immunodeficient mouse xenograft models have demonstrated that the loss of integrins in cancer cells or the inhibition of integrin function using blocking antibodies or peptides interferes with tumor growth, metastasis, and resistance to chemotherapy or radiotherapy. β1 integrins have dual roles in growth and metastasis, suggesting them as potential therapeutic targets. Integrins, such as αvβ3, αvβ5, and α5β1, are not only expressed on tumor cells but are also induced on endothelial cells during angiogenesis. These integrins have been shown to be targets for anti-angiogenic cancer therapy.

[0005] Recent studies have revealed that a range of other integrin subtypes are involved in the development of cancer, including the establishment of pre-metastatic niches, epithelial-mesenchymal transition (EMT), metabolic reprogramming, and the development of cancer cell stemness and dormancy. The involvement of integrin αvβ6 in TGFβ activation is associated with SOX4-mediated cancer immune evasion: αvβ6-blocking antibodies can inhibit SOX4 expression and sensitize triple-negative breast cancer mouse models to T cell-mediated killing responses induced by immune checkpoint inhibitors. Integrin αvβ8 can be used as a target for regulating anti-tumor immunity. αvβ8-blocking antibodies or specific blockade of integrin αvβ8 on the surface of regulatory T cells can attenuate TGFβ-mediated suppression of CD8+ T cells, thereby restoring the tumor-killing capacity of CD8+ T cells and synergizing with radiation or immunotherapy.

[0006] Expression of the integrin αvβ3 is broadly associated with the progression of melanoma from the early radial growth stage to invasive vertical growth and metastasis. Studies have found that αvβ3 is significantly upregulated in malignant primary neuroendocrine prostate cancer and its lung metastatic lesions, suggesting that αvβ3 may serve as a biomarker for early detection of malignant transformation in prostate cancer. Expression of the integrin αvβ5 has been suggested as a predictive biomarker in several cancer types, including breast, liver, and gastric cancers. Elevated levels of αvβ5 have been detected in patients with glioblastoma or colorectal cancer, and overexpression of αvβ5 is associated with poor overall survival. Integrin α5β1 is involved in tumor-promoting processes such as angiogenesis, proliferation, and metastasis. In patients with early-stage breast cancer, expression of α5β1 in primary tumors correlates with the presence of disseminated tumor cells in bone marrow aspirates and poor metastasis-free survival. Similarly, studies have shown that genetic silencing of α5 or pharmacological inhibition of α5β1 with woximab attenuates bone colonization in mice following intravenous injection of tumor cells. Integrin α5β1 has also been found to be upregulated in some gastrointestinal tumors, among which enhanced expression of ITGA5 corresponds to poor prognosis.

[0007] The abnormal expression of integrins such as αvβ3, αvβ5, and α5β1 in various tumors and their role in tumor development and progression make them promising drug targets for targeted tumor therapy. Drug molecules targeting integrins can either directly kill tumor cells or serve as targeted vectors to precisely deliver cytotoxins and radionuclides to tumor cells, thereby achieving tumor killing. Furthermore, combining radionuclides and fluorescent molecules with integrin-targeting molecules has applications in tumor diagnosis, surgical navigation, and other fields.

[0008] Summary of the Invention

[0009] Based on the above background, the present invention provides a peptoid compound and its complex, as well as a pharmaceutical composition comprising the peptoid compound, wherein the compound can target integrin proteins such as αvβ5, α5β1 or αvβ3, and is used for the diagnosis and / or treatment of tumors.

[0010] The present invention includes the following technical solutions:

[0011] In a first aspect, the present invention provides a peptoid compound, and pharmaceutically acceptable salts, esters, stereoisomers, tautomers, polymorphs, solvates, nitrogen oxides, isotope labels, metabolites and prodrugs thereof, wherein the compound has the following structural formula:

[0012] ZT-PD, or ZT-Linker-PD;

[0013] Among them, the ZT structure is one of ZT1 to ZT4:

[0014] na is an integer selected from 1 to 8.

[0015] The Linker structure is as follows:

[0016] X L Selected from N-alkyl substituted D- or L-amino acids, or one of the structures X1-X8:

[0017] LL is selected from one of the following structures:

[0018] LR does not exist or is selected from one of the following structures:

[0019] The absence of LR indicates that the carbonyl group on the left side of LR is directly connected to PD.

[0020] m and n are independently selected from integers between 0 and 16;

[0021] R 1Lselected from hydrogen, hydrocarbon or substituted hydrocarbon, alkene or alkene derivatives, alkyne or alkene derivatives, aryl and substituted aryl, heteroaryl or substituted heteroaryl, alkoxy, methylenedioxy, ethylenedioxy, alkylthio (or seleno) group, haloalkylthio (or seleno) group, thiol (or seleno) group, alkylthio (or seleno) ether, arylthio (or seleno) ether, hydroxyl, cyano, nitro, carboxyl derivative group, aryloxy, amide, acylamine, amino, hydroxylamine, alkylamine, dialkylamine, trifluoroalkoxy, trifluoromethyl , ester group, sulfonyl group, alkylsulfonyl group, halogenated alkylsulfonyl group, sulfonic acid group, sulfonamide group, phosphoric acid group, phosphate ester group, unsubstituted aromatic group, aromatic heterocyclic group, monocyclic heterocyclic group, carboxyl group, -CHF2, -CF3, -NHOH, -SO3H, -SOMe, -SO2Me, -SOEt, -SO2Et, -CONH2, -COOMe, -COOEt, -NHOCH, -NHOCCH3, -NHSO2Me, p-toluenesulfonamide group, sulfonic acid ester group.

[0022] R 2L Selected from -OH, -NH2, -NHMe, -N(Me)2, -N(Et)2.

[0023] Y L It has a diamine structure, one end of which is connected to Z L The fragment is coupled to form urea, and the other end forms an amide bond, carbonate bond or urea with ZT. L One selected from the Y1-Y4 structures:

[0024] Z L With Y L The urea structure formed by coupling is selected from one of Z1-Z4:

[0025] In a preferred embodiment of the present invention, the Linker structure is shown as L1 to L10:

[0026] m, n, R 1L 、R 2L 、X L 、Y L , Z L The groups are as described above.

[0027] In a specific embodiment of the present invention, Linker is selected from the following structure:

[0028] PD is a polypeptide compound, a compound and / or its derivatives prepared by amino condensation of one or more of the compounds of formula 1 to formula 6:

[0029] The amino group in the PD compound is condensed and connected with the linker. For the convenience of description, the PD compound described below is a reaction raw material without forming a linker.

[0030] In Formulas 1 to 6:

[0031] m, n, and n1 are independently selected from integers between 0 and 5;

[0032] R is selected from hydrogen, -OH, -NH2, a hydrocarbon group or a substituted hydrocarbon group; preferably, R is an alkyl group with a carbon number of 1 to 20, more preferably an alkyl group with a carbon number of 1 to 15, more preferably an alkyl group with a carbon number of 1 to 10, more preferably an alkyl group with a carbon number of 1 to 5, and most preferably a methyl group or an ethyl group.

[0033] R1, R2, R3, R4, R5, R6 are independently selected from hydrogen, hydrocarbon or substituted hydrocarbon, alkene or alkene derivatives, alkyne or alkyne derivatives, aryl and substituted aryl, heteroaryl or substituted heteroaryl; wherein the substituent group is selected from halogen, haloalkyl, lower alkyl, alkoxy, methylenedioxy, ethylenedioxy, alkylthio (or selenium), haloalkylthio (or selenium), sulfhydryl (or selenium), alkylthio (or selenium) ether, arylthio (or selenium) ether, hydroxyl, cyano, nitro, carboxyl derivatives, aryloxy, amide, acylamine, amino alkyl, -S02Me, -CONH2, -COOMe, -COOEt, -NHOCH, -NHOCCH3, -NHSO2Me, p-toluenesulfonamide, and sulfonate.

[0034] Preferably, the hydrocarbon group in R1, R2, R3, R4, R5, and R6 is selected from hydrocarbon groups with 1 to 20 carbon atoms, more preferably hydrocarbon groups with 1 to 10 carbon atoms; the hydrocarbon group is an alkyl group, an alkynyl group, an alkenyl group, or a fatty chain.

[0035] The substituent in the substituted hydrocarbon group in R1, R2, R3, R4, R5, and R6 is preferably N, O, S, or Se.

[0036] The aryl group in R1, R2, R3, R4, R5, and R6 is preferably selected from an aliphatic ring or an aromatic ring.

[0037] The substituents in the substituted aryl or substituted heteroaryl in R1, R2, R3, R4, R5 and R6 are preferably -F, -Cl, -Br, -I, -OH, -NH2, -NHOH, -COOH, -COH, -SO3H, -SH, -SMe, -SEt, -OPO3H, -NO2, -NO, -SOMe, -SO2Me, -SOEt, -SO2Et, -CONH2, -COOMe, -COOEt, -NHOCH, -NHOCCH3, -NHSO2Me, -OSO2Ph, phosphate group and sulfonate group.

[0038] If R1, R2, R3, R4, R5, and R6 are selected from hydrogen, X, Y, and Z are absent;

[0039] When R1, R2, R3, R4, R5, and R6 are selected from non-hydrogen substituents, X, Y, and Z are independently selected from hydrogen, amino, carboxyl, sulfhydryl, -SMe, -SEt, phosphate, nitro, -F, -Cl, -Br, -I, -CHF2, -CF3, -NHOH, -SO3H, -SOMe, -SO2Me, -SOEt, -SO2Et, -CONH2, -COOMe, -COOEt, -NHOCH, -NHOCCH3, -NHSO2Me, -SeMe, -SeEt, p-toluenesulfonamide, phosphate, sulfonic acid ester group, halogen, haloalkyl group, lower alkyl group, alkoxy group, methylenedioxy group, ethylenedioxy group, alkylthio (or seleno) group, haloalkylthio (or seleno) group, thiol (or seleno) group, alkylthio (or seleno) ether, arylthio (or seleno) ether, hydroxyl group, cyano group, carboxyl derivative group, aryloxy group, amide group, acylamine group, hydroxylamine group, alkylamine group, dialkylamine group, trifluoroalkoxy group, trifluoromethyl group, ester group, sulfonyl group, alkylsulfonyl group, haloalkylsulfonyl group, sulfonic acid group, sulfonamide group, phosphoric acid group, unsubstituted aryl group, aryl heterocyclic group, monocyclic heterocyclic group, methylthio (or seleno) group, ethylthio (or seleno) group, -NHOH.

[0040] In the present invention, the PD polypeptide compound is preferably synthesized by condensing one or more amino acids or amino acid-like compounds in Formulas 1 to 6 into an amide bond through the amino end and the carboxyl end, and / or by condensing the amino group and the sulfonic acid group into a sulfonamide bond; and / or by condensing the amino group and the sulfinic acid group into a sulfinamide bond.

[0041] Preferably, the PD polypeptide compound is preferably formed by condensing 5 amino acids or amino acid-like compounds, forming 4 amide bonds, sulfonamide bonds, and sulfenamide bonds, and the left end of the amino acid or amino acid-like structure is the nitrogen end and the right end is the carbon end.

[0042] In a preferred embodiment of the present invention, the compounds of Formula 1 to Formula 6 (amino acids or amino acid-like compounds) are selected from one or more of Gln, Glu, Asn, Asp, homoaspartic acid, homoasparagine, homoglutamine, homoglutamic acid, Arg-Gly-Asp, Gly, Ala, Leu, Val, Leu, Phe, Ser, Thr, Phe, Tyr, Tyr(OMe) and Tyr(OEt); the amino acids in the compounds of Formula 1 to Formula 6 preferably include one or both of L-configuration and D-configuration structures.

[0043] More preferably, PD is selected from one of the compounds of formula II to formula VII:

[0044] In formula II, m, n, n1, n2, n3, n4, m1, m2, m3, and m4 are selected from integers between 0 and 5;

[0045] R1 is selected from -H, -OH, -NH2, -NHNZ 1 Z 2 、-NHZ 1 、-NZ 1 Z 2 、-OZ 1 、-NHOZ 1 、-SH、-SeH、-SZ 1 、-SeZ 1 ,-Arg-Gly-Asp-Z 3 , connected with carbonyl to form lipid derivative groups, amine derivative groups, Z 1 , Z 2 Independently selected from alkyl, Z 3 Selected from hydrogen, hydroxyl, amino, ester derivative group formed with the carbon end of Asp amino acid, amine derivative group, hydrocarbon group or substituted hydrocarbon;

[0046] R2 is selected from hydrogen, -OH, -NH2, a hydrocarbon group or a substituted hydrocarbon group, an acyl derivative group, a sulfonyl derivative group, X5-Arg-Gly-Asp-;

[0047] R3, R4, R5, R6, R7, R8, R9, R 10 、R 11 、R 12 independently selected from hydrogen, hydrocarbyl or substituted hydrocarbyl, heteroatom-substituted hydrocarbyl, alkene or alkene derivative, alkynyl or alkynyl derivative, aryl and substituted aryl, heteroaryl or substituted heteroaryl;

[0048] X, X1, X2, X3, X4, and X5 are independently selected from hydrogen, hydroxy, amino, hydrocarbon, or substituted hydrocarbon.

[0049] In the present invention, the PD is a polypeptide compound preferably having the structure of formula III:

[0050] In formula III, k1 and k2 are independently selected from integers between 0 and 16;

[0051] R', R'1, R'2 and R'3 are independently selected from hydrogen, hydroxy, amino, hydrocarbon or substituted hydrocarbon;

[0052] X1, X2 and X3 are independently selected from -H, -OH, -NH2, -NHNZ 1 Z 2 、-NHZ 1 、-NZ 1 Z 2 、-OZ 1 、-NHOZ 1 、-SH、-SeH、-SZ 1 、-SeZ 1 ,-Arg-Gly-Asp-Z 3 , connected with carbonyl to form lipid derivative groups, amine derivative groups, Z 1 , Z 2 Independently selected from alkyl, Z 3 Selected from hydrogen, hydroxyl, amino, ester derivative group formed with the carbon end of Asp, amine derivative group, hydrocarbon group or substituted hydrocarbon;

[0053] AA1 is selected from one of the structures of Formula 7 to Formula 12:

[0054] In formulas 7 to 12: the acyl end of the general formula AA3 is coupled to the nitrogen end of the main chain;

[0055] m, n, and n1 are independently selected from integers between 0 and 5;

[0056] R, Z' are independently selected from hydrogen, -OH, -NH2, hydrocarbon or substituted hydrocarbon, acyl derivative group, sulfonyl derivative group;

[0057] R1, R2, R3, R4, R5, and R6 are independently selected from hydrogen, hydrocarbon or substituted hydrocarbon, alkene or alkene derivatives, alkynyl or alkynyl derivatives, aryl and substituted aryl, heteroaryl or substituted heteroaryl;

[0058] If R1, R2, R3, R4, R5, and R6 are selected from hydrogen, X, Y, and Z are absent;

[0059] When R1, R2, R3, R4, R5, and R6 are selected from non-hydrogen substitutions, X, Y, and Z are independently selected from hydrogen, halogen, haloalkyl, lower alkyl, alkoxy, methylenedioxy, ethylenedioxy, alkylthio (or seleno), haloalkylthio (or seleno), mercapto (or seleno), alkylthio (or seleno) ether, arylthio (or seleno) ether, hydroxyl, cyano, nitro, carboxyl derivative group, aryloxy, amide, acylamine, amino, hydroxylamine, alkylamine, dialkylamine, trifluoroalkoxy, trifluoromethyl, ester group, sulfonyl, alkylsulfonyl, haloalkylsulfonyl, sulfonic acid, sulfonamide, phosphate, phosphate ester group, unsubstituted aryl, aryl heterocyclic group, and monocyclic heterocyclic group.

[0060] In the present invention, the PD is a polypeptide compound preferably having the structure of Formula IV:

[0061] In formula IV, k1 and k2 are independently selected from integers between 0 and 16;

[0062] R', R'1, R'2 and R'3 are independently selected from hydrogen, hydroxy, hydrocarbon or substituted hydrocarbon;

[0063] X' is selected from hydrogen, hydrocarbyl or substituted hydrocarbyl;

[0064] X1, X2 and X3 are independently selected from -H, -OH, -NH2, -NHNZ 1 Z 2 、-NHZ 1 、-NZ 1 Z 2 、-OZ 1 、-NHOZ 1 、-SH、-SeH、-SZ 1 、-SeZ 1 ,-Arg-Gly-Asp-Z 3 , connected with carbonyl to form lipid derivative groups, amine derivative groups, Z 1 , Z 2 Independently selected from alkyl, Z 3 Selected from hydrogen, hydroxyl, amino, ester derivative group formed with the carbon end of Asp, amine derivative group, hydrocarbon group or substituted hydrocarbon;

[0065] AA2 is selected from one of the structures of Formula 13 to Formula 18:

[0066] In formulas 13 to 18: the acyl end of the general formula AA2 is coupled to the nitrogen end of the main chain, and the acyl end of the main chain is coupled to the nitrogen end of the general formula AA2;

[0067] m, n, and n1 are independently selected from 0 to 5;

[0068] R is selected from hydrogen, -OH, -NH2, hydrocarbon or substituted hydrocarbon;

[0069] R1, R2, R3, R4, R5, and R6 are independently selected from hydrogen, hydrocarbon or substituted hydrocarbon, alkene or alkene derivatives, alkynyl or alkynyl derivatives, aryl and substituted aryl, heteroaryl or substituted heteroaryl;

[0070] If R1, R2, R3, R4, R5, and R6 are selected from hydrogen, X, Y, and Z are absent;

[0071] When R1, R2, R3, R4, R5, and R6 are selected from non-hydrogen substitutions, X, Y, and Z are independently selected from hydrogen, halogen, haloalkyl, lower alkyl, alkoxy, methylenedioxy, ethylenedioxy, alkylthio (or seleno), haloalkylthio (or seleno), mercapto (or seleno), alkylthio (or seleno) ether, arylthio (or seleno) ether, hydroxyl, cyano, nitro, carboxyl derivative group, aryloxy, amide, acylamine, amino, hydroxylamine, alkylamine, dialkylamine, trifluoroalkoxy, trifluoromethyl, ester group, sulfonyl, alkylsulfonyl, haloalkylsulfonyl, sulfonic acid, sulfonamide, phosphate, phosphate ester group, unsubstituted aryl, aryl heterocyclic group, and monocyclic heterocyclic group.

[0072] In the present invention, the PD is a polypeptide compound preferably having the structure of Formula V:

[0073] In formula V, k, k1 and k2 are independently selected from integers between 0 and 16;

[0074] R', R'1, R'2 and R'3 are independently selected from hydrogen, hydroxy, amino, hydrocarbon or substituted hydrocarbon;

[0075] X' is selected from hydrogen, hydrocarbyl or substituted hydrocarbyl;

[0076] X1, X2 and X3 are independently selected from -H, -OH, -NH2, -NHNZ 1 Z 2 、-NHZ 1 、-NZ 1 Z 2 、-OZ 1 、-NHOZ 1 、-SH、-SeH、-SZ 1 、-SeZ 1 ,-Arg-Gly-Asp-Z 3 , connected with carbonyl to form lipid derivative groups, amine derivative groups, Z 1 , Z 2 Independently selected from alkyl, Z 3Selected from hydrogen, hydroxyl, amino, ester derivative group formed with the carbon end of Asp, amine derivative group, hydrocarbon group or substituted hydrocarbon;

[0077] The selection range of AA3 is consistent with the selection range of AA2 in formula III described in the above technical solution.

[0078] In the present invention, the PD is a polypeptide compound preferably having the structure of Formula VI:

[0079] In Formula VI, k, k1 and k2 are independently selected from integers between 0 and 16;

[0080] R', R'1, R'2 and R'3 are independently selected from hydrogen, hydroxy, amino, hydrocarbon or substituted hydrocarbon;

[0081] X' is selected from hydrogen, hydrocarbyl or substituted hydrocarbyl;

[0082] X1, X2 and X3 are independently selected from -H, -OH, -NH2, -NHNZ 1 Z 2 、-NHZ 1 、-NZ 1 Z 2 、-OZ 1 、-NHOZ 1 、-SH、-SeH、-SZ 1 、-SeZ 1 ,-Arg-Gly-Asp-Z 3 , connected with carbonyl to form lipid derivative groups, amine derivative groups, Z 1 , Z 2 Independently selected from alkyl, Z 3 Selected from hydrogen, hydroxyl, amino, ester derivative group formed with the carbon end of Asp, amine derivative group, hydrocarbon group or substituted hydrocarbon;

[0083] The selection range of AA4 is consistent with the selection range of AA2 in formula III described in the above technical solution.

[0084] In the present invention, the PD is a polypeptide compound preferably having the structure of Formula VII:

[0085] In Formula VII, k and k1 are independently selected from integers between 0 and 16;

[0086] R', R'1, R'2 are independently selected from hydrogen, hydroxy, amino, hydrocarbon or substituted hydrocarbon;

[0087] X' is selected from hydrogen, hydrocarbyl or substituted hydrocarbyl;

[0088] X1, X2 and X3 are independently selected from -H, -OH, -NH2, -NHNZ 1 Z 2 、-NHZ 1 、-NZ 1 Z 2 、-OZ 1 、-NHOZ 1 、-SH、-SeH、-SZ 1 、-SeZ 1 ,-Arg-Gly-Asp-Z 3 , connected with carbonyl to form lipid derivative groups, amine derivative groups, Z 1 , Z 2 Independently selected from alkyl, Z 3 Selected from hydrogen, hydroxyl, amino, ester derivative group formed with the carbon end of Asp, amine derivative group, hydrocarbon group or substituted hydrocarbon;

[0089] AA5 is selected from one of the structures of Formula 19 to Formula 24:

[0090] In Formulas 19 to 24: the main chain acyl end is coupled to the general nitrogen end of AA5;

[0091] m, n, and n1 are independently selected from integers between 0 and 5;

[0092] R is selected from hydrogen, -OH, -NH2, hydrocarbon or substituted hydrocarbon;

[0093] R1, R2, R3, R4, R5, and R6 are independently selected from hydrogen, hydrocarbon or substituted hydrocarbon, alkene or alkene derivatives, alkynyl or alkynyl derivatives, aryl and substituted aryl, heteroaryl or substituted heteroaryl;

[0094] If R1, R2, R3, R4, R5, and R6 are selected from hydrogen, X, Y, and Z are absent;

[0095] When R1, R2, R3, R4, R5, and R6 are selected from non-hydrogen substituted groups, X, Y, and Z are independently selected from hydrogen, halogen, haloalkyl, lower alkyl, alkoxy, methylenedioxy, ethylenedioxy, alkylthio (or seleno), haloalkylthio (or seleno), mercapto (or seleno), alkylthio (or seleno) ether, arylthio (or seleno) ether, hydroxyl, cyano, nitro, carboxyl derivative, aryloxy, amide, acylamine, amino, hydroxylamine, alkylamine, dialkylamine, trifluoroalkoxy, trifluoromethyl, ester, sulfonyl, alkylsulfonyl, haloalkylsulfonyl, sulfonic acid, sulfonamide, phosphate, phosphate ester, unsubstituted aryl, aryl heterocyclic group, and monocyclic heterocyclic group;

[0096] R xSelected from -H, -OH, -NH2, -NHNZ 1 Z 2 、-NHZ 1 、-NZ 1 Z 2 、-OZ 1 、-NHOZ 1 、-SH、-SeH、-SZ 1 、-SeZ 1 ,-Arg-Gly-Asp-Z 3 , connected with the carbonyl group to form a lipid derivative group, an amine derivative group, an olefin group or an olefin derivative, an alkyne group or an alkyne derivative, an aryl group and a substituted aryl group, a heteroaryl group or a substituted heteroaryl group, Z 1 , Z 2 Independently selected from alkyl, Z 3 It is selected from hydrogen, hydroxyl, amino, an ester derivative group formed with the carbon end of Asp, an amine derivative group, a hydrocarbon group or a substituted hydrocarbon.

[0097] In a specific embodiment of the present invention, the PD polypeptide compound has the following structure:

[0098] Preferably, the peptoid compound provided by the present invention has the following structure:

[0099] In a second aspect, the present invention provides a complex of a peptoid compound, wherein the complex is formed by reacting the peptoid compound, and pharmaceutically acceptable salts, esters, stereoisomers, tautomers, polymorphs, solvates, nitrogen oxides, isotope labels, metabolites and prodrugs thereof with a metal; the metal is selected from rare earth elements, Cu, Ga, In, Bi, Al 18 One of F, At, Ac, Bi or an isotope thereof.

[0100] The “rare earth elements” mentioned above include lanthanum (La), cerium (Ce), rhodium (Pr), neodymium (Nd), promethium (Pm), samarium (Sm), europium (Eu), gadolinium (Gd), terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er), thulium (Tm), ytterbium (Yb), lutetium (Lu), yttrium (Y), and scandium (Sc).

[0101] Preferably, the metal is Gd, 177 Lu,64 Cu, 68 Ga, 111 In, 211 At 225 Ac, 90 Y. 213 Bi、Al 18 F or its isotopes.

[0102] In a specific embodiment of the present invention, the complex structure of the peptoid compound is as follows:

[0103] In a third aspect, the present invention provides a pharmaceutical composition comprising the above-mentioned peptoid compound, and pharmaceutically acceptable salts, esters, stereoisomers, tautomers, polymorphs, solvates, nitrogen oxides, isotope labels, metabolites and prodrugs and / or complexes of the peptoid compound.

[0104] Preferably, the pharmaceutical composition further comprises pharmaceutically acceptable excipients and / or carriers.

[0105] In a fourth aspect, the present invention provides a peptidomimetic compound, and its pharmaceutically acceptable salts, esters, stereoisomers, tautomers, polymorphs, solvates, nitrogen oxides, isotope labels, metabolites and prodrugs and / or complexes of the peptidomimetic compound and / or the use of the above-mentioned pharmaceutical compositions in the preparation of drugs for diagnosing and / or treating diseases related to integrin αvβ5, and / or integrin α5β1, and / or integrin αvβ3, and / or integrin αvβ6.

[0106] The diagnosis includes but is not limited to PET / CT and magnetic resonance imaging.

[0107] The diseases associated with integrin αvβ5, and / or integrin α5β1, and / or integrin αvβ3, and / or integrin αvβ6 described in the present invention include one or more of lung adenocarcinoma, breast cancer, pancreatic cancer, melanoma, malignant primary neuroendocrine prostate cancer and its lung metastatic lesions, breast cancer, ovarian cancer, and gastrointestinal tumors.

[0108] The peptidyl ...

[0109] In the structural formula of the compound of the present invention Indicates the bond between two groups.

[0110] In the present invention, the term "pharmaceutically acceptable salt" refers to a salt of the compound of the present invention that is substantially non-toxic to organisms. In the present invention, pharmaceutically acceptable salts generally include (but are not limited to) salts formed by reacting the compound of the present invention with a pharmaceutically acceptable inorganic / organic acid or inorganic / organic base. Such salts are also called acid addition salts or base addition salts.

[0111] In the present invention, the term "pharmaceutically acceptable ester" refers to an ester that is substantially non-toxic to organisms and is hydrolyzed in vivo to form the compound of the present invention or a salt thereof. In the present invention, pharmaceutically acceptable esters generally include (but are not limited to) esters formed between the compound of the present invention and a pharmaceutically acceptable carboxylic acid or sulfonic acid, such esters being also referred to as carboxylate esters or sulfonate esters.

[0112] In the present invention, the term "isomer" refers to a compound having the same molecular weight due to having the same number of atoms and atom types, but different spatial arrangements or configurations of atoms. The term "stereoisomer" (or "optical isomer") refers to a stable isomer that has a vertical asymmetric plane due to having at least one chiral factor (including chiral center, chiral axis, chiral plane, etc.), thereby being able to rotate plane-polarized light. Since the compounds of the present invention have asymmetric centers and other chemical structures that may lead to stereoisomerism, the present invention also includes these stereoisomers and mixtures thereof. Since the compounds of the present invention (or pharmaceutically acceptable salts thereof) include asymmetric carbon atoms, they can exist in the form of single stereoisomers, racemates, enantiomers, and mixtures of diastereomers. Typically, these compounds can be prepared in the form of racemates. However, if desired, such compounds can be prepared or isolated to obtain pure stereoisomers, i.e., single enantiomers or diastereomers, or mixtures enriched in a single stereoisomer (purity ≥98%, ≥95%, ≥93%, ≥90%, ≥88%, ≥85%, or ≥80%). Single stereoisomers of a compound can be synthesized from optically active starting materials containing the desired chiral center, or by preparing a mixture of enantiomeric products followed by separation or resolution, for example, by conversion to a mixture of diastereomers followed by separation or recrystallization, chromatography, use of a chiral resolving agent, or direct separation of the enantiomers on a chiral chromatographic column. Starting compounds of a particular stereochemistry can be obtained commercially or prepared by methods well known in the art and resolved by methods well known in the art. The term "enantiomers" refers to a pair of stereoisomers that are non-superimposable mirror images of each other. The term "diastereomer" or "diastereomers" refers to optical isomers that are not mirror images of one another. The term "racemic mixture" or "racemate" refers to a mixture containing equal parts of a single enantiomer (i.e., an equimolar mixture of two R and S enantiomers). The term "non-racemic mixture" refers to a mixture containing unequal parts of a single enantiomer. Unless otherwise indicated, all stereoisomeric forms of the compounds of the present invention are within the scope of the present invention. The term "tautomer" (or "tautomeric form") refers to structural isomers with different energies that are interconvertible across a low energy barrier. If tautomerism is possible (e.g., in solution), chemical equilibrium of the tautomers can be achieved. For example, proton tautomers (or prototropic tautomers) include, but are not limited to, interconversions via proton migration, such as keto-enol isomerization, imine-enamine isomerization, and amide-iminoalcohol isomerization. Unless otherwise indicated, all tautomeric forms of the compounds of the present invention are within the scope of the present invention.

[0113] As used herein, the term "polymorph" (or "polymorphic form") refers to a solid crystalline form of a compound or complex. Polymorphs of a molecule can be obtained by a variety of methods known to those skilled in the art. These methods include, but are not limited to, melt recrystallization, melt cooling, solvent recrystallization, desolvation, rapid evaporation, rapid cooling, slow cooling, vapor diffusion, and sublimation.

[0114] In the present invention, the term "solvate" refers to a substance formed by the combination of a compound of the present invention (or a pharmaceutically acceptable salt thereof) and at least one solvent molecule through non-covalent intermolecular forces. Common solvates include (but are not limited to) hydrates (including hemihydrates, monohydrates, dihydrates, trihydrates, etc.), ethanolates, acetonides, etc.

[0115] In the present invention, the term "nitrogen oxide" refers to a compound formed by oxidation of a nitrogen atom in a tertiary amine or nitrogen-containing (aromatic) heterocyclic compound structure. For example, a nitrogen atom in a parent core structure can form a corresponding nitrogen oxide.

[0116] In the present invention, the term "isotopically labeled" refers to a derivative compound formed by replacing a specific atom in the compound of the present invention with an isotope thereof. Unless otherwise indicated, the compounds of the present invention include various isotopes of H, C, N, O, F, P, S, and Cl, such as 2 H(D), 3 H(T), 13 C. 14 C. 15 N. 17 O. 18 O. 18 F. 31 P. 32 P. 35 S. 36 S and 37 Cl.

[0117] In the present invention, the term "metabolite" refers to a derivative compound formed after metabolism of the compound of the present invention. Further information on metabolism can be found in Goodman and Gilman's: The Pharmacological Basis of Therapeutics (9th ed.) [M], McGraw-Hill International Editions, 1996.

[0118] In the present invention, the term "prodrug" refers to a derivative compound that is capable of providing a compound of the present invention directly or indirectly upon administration to an individual. Particularly preferred derivative compounds or prodrugs are compounds that can increase the bioavailability of the compound of the present invention when administered to an individual (e.g., more readily absorbed into the bloodstream), or compounds that promote delivery of the parent compound to the site of action (e.g., the lymphatic system). Unless otherwise indicated, all prodrug forms of the compounds of the present invention are within the scope of the present invention, and various prodrug forms are well known in the art.

[0119] As used herein, the terms "comprises," "including," "having," or "contains" or any other variations thereof are intended to cover a non-exclusive or open-ended inclusion. For example, a composition, method, or apparatus comprising a list of elements is not necessarily limited to only the elements specifically listed but may also include other elements not specifically listed or inherent to such composition, method, or apparatus.

[0120] The present invention has no special restrictions on the preparation method of the peptoid compound. The solid phase piece-by-piece, fragment synthesis, and liquid phase synthesis of polypeptide compounds by a person skilled in the art can be adopted, and the desired amino acids, quasi-amino acids, or polypeptide substances can be used for synthesis according to the compound structure; the general steps in the preparation process of the polypeptide compound preferably include: initial resin synthesis, deprotection group (Fmoc protecting group), coupling amino acids, and the desired polypeptide compound is gradually synthesized by repeating the deprotection group and amino acid coupling operations. BRIEF DESCRIPTION OF THE DRAWINGS

[0121] Figure 1 HPLC spectrum of compound TM1;

[0122] Figure 2 HPLC spectrum of compound TM13;

[0123] FIG3 HPLC spectrum of compound Ga-TM2;

[0124] FIG4 PET / CT imaging of Experimental Example 2. DETAILED DESCRIPTION

[0125] The following is a clear and complete description of the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only some embodiments of the present invention, not all. All other embodiments obtained by ordinary technicians in this field based on the embodiments of the present invention without making any creative efforts are within the scope of protection of the present invention.

[0126] Synthesis of peptoid compounds

[0127] Example 1 Synthesis of TM1 compound

[0128] The structural formula of TM1 compound is as follows:

[0129] Step 1: Synthesis of Fmoc-Asn(Trt)-resin

[0130] 2-CTC Resin (1 g, 1 mmol) was placed in a peptide synthesis tube and swelled with dichloromethane (DCM) (10 mL) at room temperature for 15 minutes, and the solvent was drained. Fmoc-Asn(Trt)-OH (715 mg, 1.2 mmol), DCM (10 mL) and diisopropylethylamine (DIEA) (310 mg, 2.4 mmol) were added, and the reaction was allowed to proceed with nitrogen purging at room temperature for 2 hours, and the solvent was drained. The resin was washed three times with DCM (10 mL). A mixed solution of methanol (MeOH) and DIEA in DCM (15 mL, V DCM :V MeOH :V DIEA =75:25:5) and continued the reaction for 15 min. The reaction solution was drained and washed three times with DCM (5 mL). Finally, it was washed three times with N,N-dimethylformamide (DMF) (5 mL). The solvent was drained to obtain Fmoc-Asn(Trt)-resin, which was directly used in the next reaction.

[0131] Step 2:

[0132] Synthesis of tBuO-DOTA-PEG3-Asp(OtBu)-Pro-Val-PEG4-Asn(Trt)-Asp(OtBu)-Aib-Ile-Asn(Trt)-resin

[0133] Removal of Fmoc protecting group: Add piperidine DMF solution (10 mL, V 哌啶 :V DMF =1:4), react at room temperature for 5 minutes, drain, and add piperidine DMF solution (10 mL, V 哌啶 :V DMF =1:4) at room temperature for 10 minutes. Upon completion, the reaction mixture was drained and washed three times with DMF (10 mL). The solvent was then drained. A small amount of resin was heated with 5% ninhydrin in ethanol at 110°C for 3 minutes. The resin turned dark blue, indicating that Fmoc had been removed, and was used directly in the next reaction.

[0134] Coupling: Fmoc-Ile-OH (1 g, 3 mmol, 3 eq) and 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) (0.96 g, 3 mmol, 3 eq) were dissolved in DMF (15 mL). DIEA (1 mL, 6 mmol, 6 eq) was added to the reaction mixture under ice-cooling and stirred for 10 minutes for activation. The activated solution was added to the Fmoc-removed resin and reacted at room temperature for 1 hour. A small amount of the resin was added to 5% ninhydrin in ethanol and heated at 110°C for 3 minutes. The resin turned colorless. The reaction mixture was drained and washed three times with DMF (10 mL). The resulting resin was used directly in the next reaction.

[0135] The coupling cycle was repeated, and the above operation was repeated to couple amino acids Fmoc-Aib-OH (0.97 g, 3 mmol, 3 eq), Fmoc-Asp(OtBu)-OH (1.23 g, 3 mmol, 3 eq), Fmoc-Asn(Trt)-OH (1.79 g, 3 mmol, 3 eq), Fmoc-PEG4-OH (0.73 g, 1.5 mmol, 1.5 eq), Fmoc-Val-OH (1 g, 3 mmol, 3 eq), Fmoc-Pro-OH (1 g, 3 mmol, 3 eq), Fmoc-Asp(OtBu)-OH (1.2 g, 3 mmol, 3 eq), Fmoc-PEG3-OH (0.66 g, 1.5 mmol, 1.5 eq), and DOTA(tBu)3 (1 g, 2 mmol, 2 eq). The mixture was washed alternately with 10 mL of DCM and MeOH for 3 times, dried, transferred to a vacuum oven, and dried in vacuo at 35 °C for 2 h to obtain 3.4 g of DOTA(OtBu)3-PEG3-Asp(OtBu)-Pro-Val-PEG4-Asn(Trt)-Asp(OtBu)-Aib-Ile-Asn(Trt)-resin, which was directly used in the next reaction.

[0136] Step 3:

[0137] Synthesis of DOTA-PEG3-Asp-Pro-Val-PEG4-Asn-Asp-Aib-Ile-Asn-OH(TM1)

[0138] To 1.7 g of resin was added cleavage solution (17 mL, 10 mL / g resin, TFA:TIS:H2O volume ratio of 95:2.5:2.5). The mixture was allowed to react for 2.5 hours, filtered, and the resin washed with cleavage solution (1 mL). The combined filtrates were dropwise added with methyl tert-butyl ether (MTBE) (50 mL), allowed to settle in an ice bath for 1 hour, and centrifuged. The mixture was washed three times with methyl tert-butyl ether (40 mL) to obtain a white solid. The solid was transferred to a vacuum drying oven and dried under vacuum at 35°C for 2 hours to obtain 690 mg of crude peptide. The purified solution was purified by Pre-HPLC, concentrated, and lyophilized to obtain 340 mg of a white solid with a purity of 97.6%, as shown in Figure 1, for a yield of 40%.

[0139] The product prepared in Example 1 was subjected to mass spectrometry detection; the detection results were: MS (ESI): m / z [M+2H] 2+ / 2=847.6,[M+3H] 3+ / 3=565.5.

[0140] According to the similar operation method described in Example 1, the compounds (TM2-TM12) with the following structures were synthesized.

[0141] TM2 compounds

[0142] TM3 compounds

[0143] TM4 compounds

[0144] TM5 compounds

[0145] TM6 compounds

[0146] TM7 compounds

[0147] TM8 compounds

[0148] TM9 compounds

[0149] TM10 compound

[0150] TM11 compound

[0151] TM12 compound

[0152] Example 2 Synthesis of TM13 compound

[0153] The structural formula of TM13 compound is as follows:

[0154] Step 1: Synthesis of Fmoc-Asn(Trt)-resin (M1)

[0155] 2-CTC Resin (1 g, 1 mmol) was placed in a peptide synthesis tube and swelled with DCM (10 mL) at room temperature for 15 minutes. The solvent was then drained. Fmoc-Asn(Trt)-OH (715 mg, 1.2 mmol), DCM (10 mL), and DIEA (310 mg, 2.4 mmol) were added and the mixture was allowed to react at room temperature with nitrogen for 2 hours. The solvent was then drained. The resin was washed three times with DCM (10 mL). A mixture of MeOH and DIEA in DCM (15 mL, V DCM :V MeOH :V DIEA =75:25:5) and continued the reaction for 15 min. The reaction solution was drained and washed three times with DCM (5 mL). Finally, it was washed three times with N,N-dimethylformamide (DMF) (5 mL). The solvent was drained to obtain Fmoc-Asn(Trt)-resin (M1), which was directly used in the next reaction.

[0156] Step 2: Synthesis of Fmoc-PEG3-Asp(OtBu)-Pro-Val-Asn(Trt)-Asp(OtBu)-Aib-Ile-Asn(Trt)-resin (M2)

[0157] Removal of Fmoc protecting group: Add piperidine DMF solution (10 mL, V 哌啶 :V DMF =1:4), react at room temperature for 5 minutes, drain, and add piperidine DMF solution (10 mL, V 哌啶 :V DMF =1:4) at room temperature for 10 minutes. Upon completion, the reaction mixture was drained and washed three times with DMF (10 mL). The solvent was then drained. A small amount of resin was heated with 5% ninhydrin in ethanol at 110°C for 3 minutes. The resin turned dark blue, indicating that Fmoc had been removed, and was used directly in the next reaction.

[0158] Coupling: Fmoc-Ile-OH (1 g, 3 mmol, 3 eq) and 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) (0.96 g, 3 mmol, 3 eq) were dissolved in DMF (15 mL). DIEA (1 mL, 6 mmol, 6 eq) was added to the reaction mixture under ice-cooling and stirred for 10 minutes for activation. The activated solution was added to the Fmoc-removed resin and reacted at room temperature for 1 hour. A small amount of the resin was added to 5% ninhydrin in ethanol and heated at 110°C for 3 minutes. The resin turned colorless. The reaction mixture was drained and washed three times with DMF (10 mL). The resulting resin was used directly in the next reaction.

[0159] The coupling cycle was repeated, and the above operation was repeated to couple amino acids Fmoc-Aib-OH (0.97 g, 3 mmol, 3 eq), Fmoc-Asp(OtBu)-OH (1.23 g, 3 mmol, 3 eq), Fmoc-Asn(Trt)-OH (1.79 g, 3 mmol, 3 eq), Fmoc-Val-OH (1 g, 3 mmol, 3 eq), Fmoc-Pro-OH (1 g, 3 mmol, 3 eq), Fmoc-Asp(OtBu)-OH (1.2 g, 3 mmol, 3 eq), and Fmoc-PEG3-OH (0.86 g, 2 mmol, 2 eq). The mixture was washed alternately three times with 10 mL each of DCM and MeOH, dried, transferred to a vacuum oven, and dried in vacuo at 35°C for 2 hours to obtain 2.9 g of Fmoc-PEG3-Asp(OtBu)-Pro-Val-Asn(Trt)-Asp(OtBu)-Aib-Ile-Asn(Trt)-resin (M2).

[0160] Step 3: Synthesis of NH2-Ph-NH-CO-PEG3-Asp(OtBu)-Pro-Val-Asn(Trt)-Asp(OtBu)-Aib-Ile-Asn(Trt)-resin (M3)

[0161] 1.5 g of the above resin was subjected to Fmoc removal in a peptide synthesis tube. After washing, a DMF solution (5 mL) of N,N'-disuccinimidyl carbonate (DSC) (0.64 g, 2.5 mmol, 5 eq) and DIEA (0.87 mL, 5 mmol, 10 eq) were added to the peptide resin. After reacting under nitrogen bubbling for 2 hours, the mixture was washed three times with DMF and dried. p-Diphenylamine (0.27 g, 2.5 mmol, 5 eq) and DIEA (0.87 mL, 5 mmol, 10 eq) were added to the peptide resin. After reacting under nitrogen bubbling for 2 hours, the mixture was washed three times with DMF and dried.

[0162] Step 4: Synthesis of DOTA-XX-PEG3-Asp-Pro-Val-Asn-Asp-Aib-Ile-Asn-OH (M4)

[0163] DOTA(tBu)3 (0.57 g, 1 mmol, 2 eq) and TBTU (0.32 g, 1 mmol, 2 eq) were dissolved in DMF (15 mL). DIEA (1 mL, 6 mmol, 6 eq) was added to the reaction mixture under ice-cooling and stirred for 10 minutes for activation. The activated solution was added to the Fmoc-depleted resin and allowed to react at room temperature overnight. A small amount of the resin was added to a 5% ninhydrin ethanol solution and heated at 110°C for 3 minutes until the resin turned colorless. The reaction mixture was drained and washed three times with DMF (10 mL). The mixture was then condensed with DCM and MeOH alternately to yield 1.7 g of resin (M4).

[0164] Step 5: Synthesis of DOTA-XX-PEG3-Asp-Pro-Val-Asn-Asp-Aib-Ile-Asn-OH (TM13)

[0165] To 1.7 g of the above resin was added cleavage solution (17 mL, 10 mL / g resin, TFA:TIS:H2O volume ratio of 95:2.5:2.5). The mixture was allowed to react for 2.5 hours, filtered, and the resin washed with cleavage solution (1 mL). The combined filtrates were dropwise added with methyl tert-butyl ether (MTBE) (80 mL), allowed to settle in an ice bath for 1 hour, and centrifuged. The mixture was washed three times with methyl tert-butyl ether (40 mL) to obtain a white solid. The solid was transferred to a vacuum drying oven and dried under vacuum at 35°C for 2 hours to obtain 594 mg of crude peptide. The purified solution was purified by pre-HPLC, concentrated, and lyophilized. 126 mg of a white solid was obtained with a purity of 96.3%, as shown in Figure 2. The yield was 16%.

[0166] The product prepared in Example 2 was subjected to mass spectrometry detection; the detection results were: MS (ESI): m / z [M+2H + ] / 2=791.0,[M+3H + ] / 3=527.9.

[0167] In this embodiment

[0168] According to the operation method similar to that described in Example 2, the compounds (TM14-TM18) with the following structures were synthesized.

[0169] TM14 compound

[0170] TM15 compound

[0171] TM16 compound

[0172] TM17 compound

[0173] TM18 compound

[0174] TM19 compound

[0175] Synthesis of complexes of peptoid compounds

[0176] Example 3 Synthesis of Ga-TM2

[0177] The synthetic route is as follows:

[0178] Weigh TM2 (150 mg, 0.1 mmol) and add it to the reaction tube. Add ultrapure water (1 mL) to dissolve it, add it to GaCl3 solution (0.5 mL, 0.2 M), and add NaOAc aqueous solution (1 M) to adjust the pH to 4-6. After stirring and reacting for 1 hour, take 1 drop of the reaction solution, dilute and filter it, and send it to HPLC for control. After the reaction of the raw material is completed, filter it and send it for purification. After freeze-drying, 107 mg of white solid was obtained with 98.8% HPLC purity, as shown in Figure 3. LC-MS results showed m / z: [M+2H + ] / 2=757.6 is the target molecule.

[0179] According to the similar operation method described in Example 3, the compound with the following structure was synthesized.

[0180] Ga-TM3 compound

[0181] LC-MS results showed m / z: [M+2H + ] / 2=741.8; 15 mg; 98.2% HPLC purity.

[0182] Ga-TM9 compound

[0183] LC-MS results showed m / z: [M+2H + ] / 2=780.3; 21 mg; 96.6% HPLC purity.

[0184] Ga-TM1 compound

[0185] LC-MS results showed m / z: [M+2H + ] / 2=873.4; 7 mg; 92.7% HPLC purity.

[0186] Ga-TM7 compound

[0187] LC-MS results showed m / z: [M+2H + ] / 2=778.8; 67 mg; 93.5% HPLC purity.

[0188] Ga-TM17 compound

[0189] LC-MS results showed m / z: [M+2H + ] / 2=857.8; 21 mg; 97.8% HPLC purity.

[0190] Ga-TM16 compound

[0191] LC-MS results showed m / z: [M+2H + ] / 2=830.8; 17 mg; 98.7% HPLC purity.

[0192] Ga-TM13 compound

[0193] LC-MS results showed m / z: [M+2H + ] / 2=823.8; 15 mg; 91.5% HPLC purity.

[0194] Ga-TM18 compound

[0195] LC-MS results showed m / z: [M+2H + ] / 2=947.4; 8 mg; 95.8% HPLC purity.

[0196] Ga-TM19 compound

[0197] LC-MS results showed m / z: [M+2H + ] / 2=954.4; 67 mg; 99.3% HPLC purity.

[0198] Gd-TM8 compounds

[0199] LC-MS results showed m / z: [M+2H + ] / 2=796.3; 23 mg; 99.3% HPLC purity.

[0200] Lu-TM19 compound

[0201] LC-MS results showed m / z: [M+2H + ] / 2=1007.4; 16 mg; 96.5% HPLC purity.

[0202] Test Example 1 Target Affinity Test

[0203] Surface Plasmon Resonance (SPR) technology was used to test the affinity of the example compounds with the target proteins integrin α5β1, αvβ3, αvβ5, and αvβ6. The specific steps are as follows:

[0204] Recombinant integrin α5β1, αvβ3, αvβ5, and αvβ6 proteins were immobilized on a CM5 chip (Biacore). An SPR instrument (Biacore T200) was used to measure the binding constants (Ka) and dissociation constants (Kd) of the compounds with integrin α5β1, αvβ3, αvβ5, and αvβ6 at 25°C with an injection volume of 30 μL of the test solution and a flow rate of 30 μL / min. The affinity constants KD of the compounds for the target proteins integrin α5β1, αvβ3, αvβ5, and αvβ6 were calculated according to the formula KD = Kd / Ka (the lower the KD value, the higher the affinity of the example compound for the target protein).

[0205] The in vitro affinity data are shown in Table 1:

[0206] Table 1 KD values ​​of compounds for integrin α5β1, αvβ3, αvβ5 or αvβ6

[0207] Experimental Example 2 Radioactive compound labeling experiment

[0208] Radioactivity of compound TM1 68 Ga labeling

[0209] The aqueous solution of TM1 (20 μg) was added to the prepared 68 The GaCl3 solution is then adjusted to a pH of 3-5 with sodium acetate aqueous solution and acetic acid, and reacted at 70-95°C for 15 minutes. After the reaction is complete, the product is purified to obtain the labeled product. 68 Solution of Ga-TM1.

[0210] All compounds in the examples of the present invention 68 The Ga labeling method is the same as the above method, and the Ga labeling is continued as described above. 68 Ga-TM2, 68 Ga-TM13, 68 Ga-TM18.

[0211] PET / CT experiments

[0212] 1) Evaluation of lung adenocarcinoma model

[0213] M-NSG mice inoculated with H1975 were injected with about 100 μCi of the above-mentioned 68 The Ga-labeled compound solution was injected and PET / CT imaging was performed 1 h and 2 h later. The experimental data in Table 2 were obtained through image post-processing.

[0214] Table 2 PET / CT experimental results

[0215] The animal experiment results in the table above demonstrate significant tumor accumulation in M-NSG mice inoculated with H1975. TM1, TM2, TM13, and TM18 exhibited the highest tumor uptake at 1 and 2 hours, with the exception of the kidney (the primary clearance pathway for the compound). Furthermore, the tumor / tissue ratio (excluding tumor / kidney) in the imaging data at both 1 and 2 hours was greater than 2, indicating specific tumor targeting. At 1 hour, drug uptake in all tissues (excluding the tumor and kidney) was less than 0.5% ID / g, indicating rapid clearance from all tissues. Furthermore, the 1-hour imaging results shown in Figure 4 demonstrate primary drug accumulation in the tumor, bladder, and kidney, resulting in clear images suitable for PET / CT diagnosis.

[0216] The present invention lists 68 Ga chelated TM1, TM2, TM13, and TM18 compounds were subjected to PET / CT imaging in a mouse model of lung adenocarcinoma. The data showed that they were specifically taken up in the tumor site and had low uptake in normal tissues. The above data indicate that the compounds mentioned in the present invention have tumor targeting specificity and can be used for the treatment of 177 Lu, 64 Cu, 111 In、Al 18 F. 211 At 225 Ac, 90 Y. 213 Targeted compounds of radioactive substances such as Bi and Gd or their isotopes are expected to be used in the diagnosis and / or treatment of various tumors, including lung adenocarcinoma, breast cancer, pancreatic cancer, melanoma, malignant primary neuroendocrine prostate cancer and its lung metastatic lesions, breast cancer, ovarian cancer, gastrointestinal tumors, etc.

[0217] The results of PET / CT imaging animal experiments show that the peptoid compounds and their complexes prepared by the present invention can directly target tumor cells and can be used as targeting carriers to accurately deliver cytotoxins, radionuclides, etc. to tumor cells.

[0218] The results of in vitro enzymology experiments show that the peptoid compounds prepared by the present invention and their complexes can be used for the diagnosis and / or treatment of various tumors such as lung adenocarcinoma, breast cancer, pancreatic cancer, melanoma, malignant primary neuroendocrine prostate cancer and its lung metastatic lesions, breast cancer, ovarian cancer, gastrointestinal tumors, etc.

[0219] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the above embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A peptoid compound, and its pharmaceutically acceptable salts, esters, stereoisomers, tautomers, polymorphs, solvates, nitrogen oxides, isotope labels, metabolites and prodrugs, wherein the compound has the following structural formula: ZT-PD, or ZT-Linker-PD; in, The ZT structure is one of ZT1 to ZT4: na is an integer selected from 1 to 8; PD is a polypeptide compound, a compound and / or its derivatives prepared by amino condensation of one or more of the compounds of formula 1 to formula 6: In Formulae 1 to 6, m, n, and n1 are independently selected from integers between 0 and 5; R is selected from hydrogen, -OH, -NH2, a hydrocarbon group or a substituted hydrocarbon group; R1, R2, R3, R4, R5, R6 are independently selected from hydrogen, hydrocarbon or substituted hydrocarbon, olefin or olefin derivative, alkynyl or alkynyl derivative, aryl and substituted aryl, heteroaryl or substituted heteroaryl; wherein the substituent is selected from halogen, haloalkyl, lower alkyl, alkoxy, methylenedioxy, ethylenedioxy, alkylthio (or selenium), haloalkylthio (or selenium), thiol (or selenium), alkylthio (or selenium) ether, arylthio (or selenium) ether, hydroxyl, cyano, nitro, carboxyl derivative, aryloxy, amide, acylamine, amino, hydroxylamine, alkylamine, dialkylamine, tris(thio)amine, thio ... Fluoroalkoxy, trifluoromethyl, ester, sulfonyl, alkylsulfonyl, halogenated alkylsulfonyl, sulfonic acid, sulfonamide, phosphoric acid, phosphate ester, unsubstituted aryl, aryl heterocyclic group, monocyclic heterocyclic group, N, O, S, Se, hydrogen, carboxyl, methylthio (or seleno) ether, ethylthio (or seleno) ether, -SOMe, -SO2Me, -CONH2, -COOMe, -COOEt, -NHOCH, -NHOCCH3, -NHSO2Me, p-toluenesulfonamide, sulfonic acid ester; When R1, R2, R3, R4, R5, and R6 are selected from hydrogen substitution, X, Y, and Z are absent; When R1, R2, R3, R4, R5, and R6 are selected from non-hydrogen substitutions, X, Y, and Z are independently selected from hydrogen, amino, carboxyl, thiol, -SMe, -SEt, phosphate, nitro, -F, -Cl, -Br, -I, -CHF2, -CF3, -NHOH, -SO3H, -SOMe, -SO2Me, -SOEt, -SO2Et, -CONH2, -COOMe, -COOEt, -NHOCH, -NHOCCH3, -NHSO2Me, -SeMe, -SeEt, p-toluenesulfonamide, phosphate, sulfonic acid ester group, halogen, haloalkyl, lower alkyl, alkoxy, methylenedioxy, ethylenedioxy, alkylthio (or seleno), haloalkylthio (or seleno), thiol (or seleno), alkylthio (or seleno) ether, arylthio (or seleno) ether, hydroxyl, cyano, carboxyl derivative group, aryloxy, amide, acylamine, hydroxylamine, alkylamine, dialkylamine, trifluoroalkoxy, trifluoromethyl, ester group, sulfonyl, alkylsulfonyl, haloalkylsulfonyl, sulfonic acid, sulfonamide, phosphoric acid, unsubstituted aryl, aryl heterocyclic group, monocyclic heterocyclic group, methylthio (or seleno), ethylthio (or seleno), -NHOH; The Linker structure is as follows: X L Selected from N-alkyl substituted D- or L-amino acid, or one of the structures X1-X8: LL is selected from one of the following structures: LR does not exist or is selected from one of the following structures: m and n are independently selected from integers between 0 and 16; R 1L is selected from hydrogen, hydrocarbon or substituted hydrocarbon, alkene or alkene derivatives, alkynyl or alkynyl derivatives, aryl and substituted aryl, heteroaryl or substituted heteroaryl, alkoxy, methylenedioxy, ethylenedioxy, alkylthio (or seleno) group, haloalkylthio (or seleno) group, thiol (or seleno) group, alkylthio (or seleno) ether, arylthio (or seleno) ether, hydroxyl, cyano, nitro, carboxyl derivative group, aryloxy, amide, acylamine, amino, hydroxylamine, alkylamine, dialkylamine, trifluoroalkoxy, trifluoromethyl , ester group, sulfonyl group, alkylsulfonyl group, halogenated alkylsulfonyl group, sulfonic acid group, sulfonamide group, phosphoric acid group, phosphate ester group, unsubstituted aryl group, aryl heterocyclic group, monocyclic heterocyclic group, carboxyl group, -CHF2, -CF3, -NHOH, -SO3H, -SOMe, -SO2Me, -SOEt, -SO2Et, -CONH2, -COOMe, -COOEt, -NHOCH, -NHOCCH3, -NHSO2Me, p-toluenesulfonamide group, sulfonic acid ester group; R 2L Selected from -OH, -NH2, -NHMe, -N(Me)2, -N(Et)2; Y L Selected from one of the structures Y1-Y4: Z L With Y L The urea structure formed by coupling is selected from one of Z1-Z4:

2. The peptoid compound according to claim 1, and its pharmaceutically acceptable salts, esters, stereoisomers, tautomers, polymorphs, solvates, nitrogen oxides, isotope labels, metabolites and prodrugs, characterized in that: The Linker structure is shown in L1 to L10: m, n, R 1L , R 2L , X L , Y L , Z L The group is as described in claim 1.

3. The peptoid compound according to claim 1, and its pharmaceutically acceptable salts, esters, stereoisomers, tautomers, polymorphs, solvates, nitrogen oxides, isotope labels, metabolites and prodrugs, characterized in that: Linker is selected from the structure shown below:

4. The peptoid compound according to claim 1, and its pharmaceutically acceptable salts, esters, stereoisomers, tautomers, polymorphs, solvates, nitrogen oxides, isotope labels, metabolites and prodrugs, characterized in that: The compounds of Formulas 1 to 6 in the PD structure are selected from one or more of Gln, Glu, Asn, Asp, homoaspartic acid, homoasparagine, homoglutamine, homoglutamic acid, Arg-Gly-Asp, Gly, Ala, Leu, Val, Leu, Phe, Ser, Thr, Phe, Tyr, Tyr(OMe) and Tyr(OEt); the amino acids in the compounds of Formulas 1 to 6 include one or both of L-configuration and D-configuration structures.

5. The peptoid compound according to claim 4, and its pharmaceutically acceptable salts, esters, stereoisomers, tautomers, polymorphs, solvates, nitrogen oxides, isotope labels, metabolites and prodrugs, characterized in that: PD is formed by condensing five compounds in Formulae 1 to 6, forming four amide bonds, sulfonamide bonds and / or sulfenamide bonds. The left end of the amino acid or amino acid-like structure is the nitrogen end, and the right end is the carbon end.

6. The peptoid compound according to claim 5, and its pharmaceutically acceptable salts, esters, stereoisomers, tautomers, polymorphs, solvates, nitrogen oxides, isotope labels, metabolites and prodrugs, characterized in that: PD is selected from one of the compounds of formula II to formula VII: In formula II, m, n, n1, n2, n3, n4, m1, m2, m3, and m4 are selected from integers between 0 and 5; R1 is selected from -H, -OH, -NH2, -NHNZ 1 Z 2 、-NHZ 1 、-NZ 1 Z 2 、-OZ 1 、-NHOZ 1 , -SH, -SeH, -SZ 1 、-SeZ 1 ,-Arg-Gly-Asp-Z 3 , connected with the carbonyl group to form lipid derivative groups, amine derivative groups, Z 1 , Z 2 independently selected from alkyl, Z 3 Selected from hydrogen, hydroxyl, amino, ester derivative group formed with the carbon end of Asp amino acid, amine derivative group, hydrocarbon group or substituted hydrocarbon; R2 is selected from hydrogen, -OH, -NH2, a hydrocarbon group or a substituted hydrocarbon group, an acyl derivative group, a sulfonyl derivative group, X5-Arg-Gly-Asp-; R3, R4, R5, R6, R7, R8, R9, R 10 , R 11 , R 12 independently selected from hydrogen, hydrocarbon or substituted hydrocarbon, heteroatom substituted hydrocarbon, alkene or alkene derivative, alkynyl or alkynyl derivative, aryl and substituted aryl, heteroaryl or substituted heteroaryl; X, X1, X2, X3, X4, and X5 are independently selected from hydrogen, hydroxyl, amino, hydrocarbon or substituted hydrocarbon; In formula III, k1 and k2 are independently selected from integers between 0 and 16; R', R'1, R'2 and R'3 are independently selected from hydrogen, hydroxyl, amino, hydrocarbon or substituted hydrocarbon; X1, X2 and X3 are independently selected from -H, -OH, -NH2, -NHNZ 1 Z 2 、-NHZ 1 、-NZ 1 Z 2 、-OZ 1 、-NHOZ 1 , -SH, -SeH, -SZ 1 、-SeZ 1 ,-Arg-Gly-Asp-Z 3 , connected with the carbonyl group to form lipid derivative groups, amine derivative groups, Z 1 , Z 2 independently selected from alkyl, Z 3 Selected from hydrogen, hydroxyl, amino, ester derivative group formed with the carbon end of Asp, amine derivative group, hydrocarbon group or substituted hydrocarbon; AA1 is selected from one of the structures of Formula 7 to Formula 12: In Formulae 7 to 12: the acyl end of the general formula AA3 is coupled to the nitrogen end of the main chain; m, n, and n1 are independently selected from integers between 0 and 5; R, Z' are independently selected from hydrogen, -OH, -NH2, hydrocarbon or substituted hydrocarbon, acyl derivative groups, sulfonyl derivative groups; R1, R2, R3, R4, R5, and R6 are independently selected from hydrogen, hydrocarbon or substituted hydrocarbon, olefin or olefin derivatives, alkynyl or alkynyl derivatives, aryl and substituted aryl, heteroaryl or substituted heteroaryl; When R1, R2, R3, R4, R5, and R6 are selected from hydrogen substitution, X, Y, and Z are absent; When R1, R2, R3, R4, R5, and R6 are selected from non-hydrogen substitutions, X, Y, and Z are independently selected from hydrogen, halogen, haloalkyl, lower alkyl, alkoxy, methylenedioxy, ethylenedioxy, alkylthio (or seleno), haloalkylthio (or seleno), mercapto (or seleno), alkylthio (or seleno) ether, arylthio (or seleno) ether, hydroxyl, cyano, nitro, carboxyl derivative group, aryloxy, amide, acylamine, amino, hydroxylamine, alkylamine, dialkylamine, trifluoroalkoxy, trifluoromethyl, ester, sulfonyl, alkylsulfonyl, haloalkylsulfonyl, sulfonic acid, sulfonamide, phosphoric acid, phosphoric acid ester, unsubstituted aryl, aryl heterocyclic group, and monocyclic heterocyclic group; In formula IV, k1 and k2 are independently selected from integers between 0 and 16; R', R'1, R'2 and R'3 are independently selected from hydrogen, hydroxyl, hydrocarbon or substituted hydrocarbon; X' is selected from hydrogen, hydrocarbyl or substituted hydrocarbyl; X1, X2 and X3 are independently selected from -H, -OH, -NH2, -NHNZ 1 Z 2 、-NHZ 1 、-NZ 1 Z 2 、-OZ 1 、-NHOZ 1 , -SH, -SeH, -SZ 1 、-SeZ 1 ,-Arg-Gly-Asp-Z 3 , connected with the carbonyl group to form lipid derivative groups, amine derivative groups, Z 1 , Z 2 independently selected from alkyl, Z 3 Selected from hydrogen, hydroxyl, amino, and ester derivative groups formed with the carbon end of Asp, Amine derivative groups, hydrocarbon groups or substituted hydrocarbons; AA2 is selected from one of the structures of Formula 13 to Formula 18: In Formulae 13 to 18: the acyl end of the general formula AA2 is coupled to the nitrogen end of the main chain, and the acyl end of the main chain is coupled to the nitrogen end of the general formula AA2; m, n, n1 are independently selected from 0 to 5; R is selected from hydrogen, -OH, -NH2, a hydrocarbon group or a substituted hydrocarbon group; R1, R2, R3, R4, R5, and R6 are independently selected from hydrogen, hydrocarbon or substituted hydrocarbon, olefin or olefin derivatives, alkynyl or alkynyl derivatives, aryl and substituted aryl, heteroaryl or substituted heteroaryl; When R1, R2, R3, R4, R5, and R6 are selected from hydrogen substitution, X, Y, and Z are absent; When R1, R2, R3, R4, R5, and R6 are selected from non-hydrogen substitutions, X, Y, and Z are independently selected from hydrogen, halogen, haloalkyl, lower alkyl, alkoxy, methylenedioxy, ethylenedioxy, alkylthio (or seleno), haloalkylthio (or seleno), mercapto (or seleno), alkylthio (or seleno) ether, arylthio (or seleno) ether, hydroxyl, cyano, nitro, carboxyl derivative group, aryloxy, amide, acylamine, amino, hydroxylamine, alkylamine, dialkylamine, trifluoroalkoxy, trifluoromethyl, ester, sulfonyl, alkylsulfonyl, haloalkylsulfonyl, sulfonic acid, sulfonamide, phosphoric acid, phosphoric acid ester, unsubstituted aryl, aryl heterocyclic group, and monocyclic heterocyclic group; In formula V, k, k1 and k2 are independently selected from integers between 0 and 16; R', R'1, R'2 and R'3 are independently selected from hydrogen, hydroxyl, amino, hydrocarbon or substituted hydrocarbon; X' is selected from hydrogen, hydrocarbyl or substituted hydrocarbyl; X1, X2 and X3 are independently selected from -H, -OH, -NH2, -NHNZ 1 Z 2 、-NHZ 1 、-NZ 1 Z 2 、-OZ 1 、-NHOZ 1 , -SH, -SeH, -SZ 1 、-SeZ 1 ,-Arg-Gly-Asp-Z 3 , connected with the carbonyl group to form lipid derivative groups, amine derivative groups, Z 1 , Z 2 independently selected from alkyl, Z 3 Selected from hydrogen, hydroxyl, amino, and ester derivative groups formed with the carbon end of Asp, Amine derivative groups, hydrocarbon groups or substituted hydrocarbons; The selection range of AA3 is consistent with the selection range of AA2 in Formula III described in the above technical solution; In Formula VI, k, k1 and k2 are independently selected from integers between 0 and 16; R', R'1, R'2 and R'3 are independently selected from hydrogen, hydroxyl, amino, hydrocarbon or substituted hydrocarbon; X' is selected from hydrogen, hydrocarbyl or substituted hydrocarbyl; X1, X2 and X3 are independently selected from -H, -OH, -NH2, -NHNZ 1 Z 2 、-NHZ 1 、-NZ 1 Z 2 、-OZ 1 、-NHOZ 1 , -SH, -SeH, -SZ 1 、-SeZ 1 ,-Arg-Gly-Asp-Z 3 , connected with the carbonyl group to form lipid derivative groups, amine derivative groups, Z 1 , Z 2 independently selected from alkyl, Z 3 Selected from hydrogen, hydroxyl, amino, ester derivative group formed with the carbon end of Asp, amine derivative group, hydrocarbon group or substituted hydrocarbon; The selection range of AA4 is consistent with the selection range of AA2 in Formula III described in the above technical solution; In Formula VII, k and k1 are independently selected from integers between 0 and 16; R', R'1, R'2 are independently selected from hydrogen, hydroxyl, amino, hydrocarbon or substituted hydrocarbon; X' is selected from hydrogen, hydrocarbyl or substituted hydrocarbyl; X1, X2 and X3 are independently selected from -H, -OH, -NH2, -NHNZ 1 Z 2 、-NHZ 1 、-NZ 1 Z 2 、-OZ 1 、-NHOZ 1 , -SH, -SeH, -SZ 1 、-SeZ 1 ,-Arg-Gly-Asp-Z 3 , connected with the carbonyl group to form lipid derivative groups, amine derivative groups, Z 1 , Z 2 independently selected from alkyl, Z 3 Selected from hydrogen, hydroxyl, amino, ester derivative group formed with the carbon end of Asp, amine derivative group, hydrocarbon group or substituted hydrocarbon; AA5 is selected from one of the structures of Formula 19 to Formula 24: In Formulas 19 to 24: the main chain acyl end is coupled to the general nitrogen end of AA5; m, n, and n1 are independently selected from integers between 0 and 5; R is selected from hydrogen, -OH, -NH2, a hydrocarbon group or a substituted hydrocarbon group; R1, R2, R3, R4, R5, and R6 are independently selected from hydrogen, hydrocarbon or substituted hydrocarbon, olefin or olefin derivatives, alkynyl or alkynyl derivatives, aryl and substituted aryl, heteroaryl or substituted heteroaryl; When R1, R2, R3, R4, R5, and R6 are selected from hydrogen substitution, X, Y, and Z are absent; When R1, R2, R3, R4, R5, and R6 are selected from non-hydrogen substitutions, X, Y, and Z are independently selected from hydrogen, halogen, haloalkyl, lower alkyl, alkoxy, methylenedioxy, ethylenedioxy, alkylthio (or seleno), haloalkylthio (or seleno), mercapto (or seleno), alkylthio (or seleno) ether, arylthio (or seleno) ether, hydroxyl, cyano, nitro, carboxyl derivative group, aryloxy, amide, acylamine, amino, hydroxylamine, alkylamine, dialkylamine, trifluoroalkoxy, trifluoromethyl, ester, sulfonyl, alkylsulfonyl, haloalkylsulfonyl, sulfonic acid, sulfonamide, phosphoric acid, phosphoric acid ester, unsubstituted aryl, aryl heterocyclic group, and monocyclic heterocyclic group; R x Selected from -H, -OH, -NH2, -NHNZ 1 Z 2 、-NHZ 1 、-NZ 1 Z 2 、-OZ 1 、-NHOZ 1 , -SH, -SeH, -SZ 1 、-SeZ 1 ,-Arg-Gly-Asp-Z 3 , connected with the carbonyl group to form a lipid derivative group, an amine derivative group, an olefin group or an olefin derivative, an alkynyl group or an alkynyl derivative, an aryl group and a substituted aryl group, a heteroaryl group or a substituted heteroaryl group, Z 1 , Z 2 independently selected from alkyl, Z 3 It is selected from hydrogen, hydroxyl, amino, an ester derivative group formed with the carbon end of Asp, an amine derivative group, a hydrocarbon group or a substituted hydrocarbon.

7. The peptoid compound according to claim 5, and its pharmaceutically acceptable salts, esters, stereoisomers, tautomers, polymorphs, solvates, nitrogen oxides, isotope labels, metabolites and prodrugs, characterized in that: The PD compound has the following structure:

8. A complex of a peptoid compound, the complex being formed by reacting the peptoid compound according to any one of claims 1 to 7, and its pharmaceutically acceptable salts, esters, stereoisomers, tautomers, polymorphs, solvates, nitrogen oxides, isotope labels, metabolites and prodrugs with a metal; the metal being selected from rare earth elements, Cu, Ga, In, Bi, Al 18 One of F, At, Ac, Bi or an isotope thereof.

9. A pharmaceutical composition comprising the peptidomimetic compound according to any one of claims 1 to 7, and pharmaceutically acceptable salts, esters, stereoisomers, tautomers, polymorphs, solvates, nitrogen oxides, isotope labels, metabolites and prodrugs thereof and / or complexes of the peptidomimetic compound according to claim 8.

10. Use of a peptidomimetic compound according to any one of claims 1 to 7, and pharmaceutically acceptable salts, esters, stereoisomers, tautomers, polymorphs, solvates, nitrogen oxides, isotope labels, metabolites and prodrugs thereof, and / or a complex of the peptidomimetic compound according to claim 8, and / or a pharmaceutical composition according to claim 9 in the preparation of drugs for diagnosing and / or treating diseases associated with integrin αvβ5, and / or integrin α5β1, and / or integrin αvβ3, and / or integrin αvβ6.

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