COMPOUNDS CONTAINING FIBROBLAST ACTIVATION PROTEIN LIGANDS AND USES THEREOF - Patent application

Abstract

The present invention relates to a compound comprising a cyclic peptide of formula (I) and an N-terminal modification group A attached to Xaa1, wherein each and any one of Xaa1, Xaa2, Xaa3, Xaa4, Xaa5, Xaa6, and Xaa7 is an amino acid residue, and Yc is a structure of formula (X). [Formula 1] TIFF2024503637000377.tif2051 [C2] TIFF2024503637000378.tif2051

Description

[Technical Field]

[0001] The present invention relates to compounds; inhibitors of fibroblast activation proteins (FAPs); compositions comprising the compounds and inhibitors, respectively; compounds, inhibitors, and compositions, respectively, for use in methods for the diagnosis of disease; compounds, inhibitors, and compositions, respectively, for use in methods for the treatment of disease; compounds, inhibitors, and compositions, respectively, for use in methods for the diagnosis and treatment of disease, also referred to as "thera(g)nosis" or "thera(g)nostics"; compounds, inhibitors, and compositions, respectively, for use in methods for delivering effectors to FAP-expressing tissue; methods for the diagnosis of disease using the compounds, inhibitors, and compositions, respectively; methods for the treatment of disease using the compounds, inhibitors, and compositions, respectively; methods for the diagnosis and treatment of disease, also referred to as "thera(g)nosis" or "thera(g)nostics" using the compounds, inhibitors, and compositions, respectively; and methods for the delivery of effectors to FAP-expressing tissue using the compounds, inhibitors, and compositions, respectively. [Background technology]

[0002] Despite the increasing availability of therapeutic options, cancer remains the second leading cause of death worldwide. Treatment strategies primarily focus on targeting malignant cancer cells themselves, ignoring the ever-present surrounding tumor microenvironment (TME), which limits the access of therapeutic cancer cell agents (Valkenburg et al., Nat Rev Clin Oncol, 2018, 15:366). The TME is part of the tumor mass and consists of not only a heterogeneous population of cancer cells but also various resident and infiltrating host cells, secreted factors, and extracellular matrix proteins (Quail et al., Nat Med, 2013, 19:1423). The predominant cell type found in the TME is cancer-associated fibroblasts (CAFs) (Kalluri, Nat Rev Cancer, 2016, 16:582). Many different cell types have been described as sources and origins for CAFs, such as fibroblasts, mesenchymal stem cells, smooth muscle cells, cells of epithelial origin, or endothelial cells (Madar et al., Trends Mol Med, 2013, 19:447). CAFs exhibit mesenchymal-like characteristics and are often the predominant cell type within solid tumor masses. CAFs have attracted increasing interest as players in tumor progression and homeostasis (Gascard et al., Genes Dev, 2016, 30:1002; LeBleu et al., Dis Model Mech, 2018, 11).

[0003] In recent years, fibroblast activation protein (FAP) has lost its reputation as a marker of CAFs (Shiga et al., Cancers (Basel), 2015, 7:2443; Pure et al., Oncogene, 2018, 37:4343; Jacob et al., Curr Mol Med, 2012, 12:1220). Due to the ubiquitous presence of CAFs in tumors and stroma, FAP has been identified as a suitable marker for radiopharmaceutical diagnosis and a suitable target for radiopharmaceutical therapy (Siveke, J Nucl Med, 2018, 59:1412).

[0004] Fibroblast activation protein alpha (FAP) is a type II transmembrane serine protease and a member of the S9 prolyl oligopeptidase family (Park et al., J Biol Chem, 1999, 274:36505). The closest family member, DPP4, shares 53% homology with FAP. Like other DPP enzymes (DPP4, DPP7, DPP8, and DPP9), FAP possesses post-proline exopeptidase activity. Furthermore, FAP possesses endopeptidase activity, similar to prolyl oligopeptidase / endopeptidase (POP / PREP). The FAP gene is highly conserved across various species. The extracellular domain of human FAP shares 90% amino acid sequence identity with mouse and rat FAP. Mouse FAP shares 97% sequence identity with rat FAP.

[0005] Structurally, FAP is a 760-amino acid transmembrane protein composed of a short N-terminal cytoplasmic tail (6 amino acids), a single transmembrane domain (20 amino acids), and a 734-amino acid extracellular domain (Aertgeerts et al., J Biol Chem, 2005, 280:19441). This extracellular domain consists of an eight-bladed β-propeller domain and an α / β-hydrolase domain. The catalytic triad, consisting of Ser624, Asp702, and His734, is located at the interface between the β-propeller and hydrolase domains. The active site is accessible through the central hole of the β-propeller domain or through a narrow cavity between the β-propeller and hydrolase domains. FAP is not active as a monomer, but forms active homodimers and heterodimers with DPP4 (Ghersi et al., Cancer Res, 2006, 66:4652). Soluble homodimeric FAPs have also been described (Keane et al., FEBS Open Bio, 2013, 4:43; Lee et al., Blood, 2006, 107:1397).

[0006] FAP has dual enzymatic activity (Hamson et al., Proteomics Clin Appl, 2014, 8:454). Its dipeptidyl peptidase activity cleaves two amino acids N-terminal to the proline residue. FAP substrates rapidly cleaved by its dipeptidyl peptidase activity include neuropeptide Y, peptide YY, substance P, and B-type natriuretic peptide. Collagens I and III, fibroblast growth factor 21 (FGF21), and α2-antiplasmin have been shown to be cleaved by FAP's endopeptidase activity. Although FAP cannot cleave native collagens, predigestion with other proteases, such as matrix metalloproteinases, facilitates further collagen cleavage by FAP. Collagen processing can affect the migration ability of cancer cells. In addition to increasing cancer cell invasiveness through extracellular matrix remodeling, several other FAP-mediated tumor-promoting roles have been proposed, including increased proliferation and angiogenesis. Furthermore, stromal expression of FAP is associated with escape from immune surveillance in various cancers, suggesting a role in antitumor immunity (Pure et al., Oncogene, 2018, 37:4343).

[0007] FAP is transiently expressed during normal development but is only rarely expressed in healthy adult tissues. In transgenic mice, FAP has been shown to be expressed by adipose tissue, skeletal muscle, skin, bone, and pancreas (Pure et al., Oncogene, 2018, 37: 4343; Roberts et al., J Exp Med, 2013, 210: 1137). However, FAP knockout mice have a healthy phenotype, suggesting a redundant role under normal conditions (Niedermeyer et al., Mol Cell Biol, 2000, 20: 1089). At sites of active tissue remodeling, including wound healing, fibrosis, arthritis, atherosclerosis, and cancer, FAP becomes highly upregulated in stromal cells (Pure et al., Oncogene, 2018, 37: 4343).

[0008] FAP expression in the tumor stroma of 90% of epithelial cancers was first reported in 1990 using the monoclonal antibody F19 (Garin-Chesa et al., Proc Natl Acad Sci USA, 1990, 87:7235; Rettig et al., Cancer Res, 1993, 53:3327). FAP-expressing stromal cells were further characterized as cancer-associated fibroblasts (CAFs) and cancer-associated pericytes (Cremasco et al., Cancer Immunol Res, 2018, 6:1472). FAP expression on malignant epithelial cells has also been reported, although its significance remains uncertain (Pure et al., Oncogene, 2018, 37:4343). Table 1 below, taken from Busek et al. (Busek et al., Front Biosci (Landmark Ed), 2018, 23:1933), summarizes the expression of FAP in various malignancies showing tumor type and cellular expression.

[0009] [Table 1-1]

[0010] [Table 1-2]

[0011] FAP expression in CAFs has been demonstrated in nearly all carcinomas and sarcomas (Pure et al., Oncogene, 2018, 37:4343; Busek et al., Front Biosci (Landmark Ed), 2018, 23:1933). Furthermore, CAFs are present in hematological malignancies (Raffaghello et al., Oncotarget, 2015, 6:2589). Therefore, the use of FAP as a therapeutic target is not limited to any particular tumor entity.

[0012] The abundance of FAP-expressing CAFs has been reported to correlate with poor prognosis. Across various human tumor indications, FAP expression has been reported to correlate with higher tumor grade and worse overall survival (Pure et al., Oncogene, 2018, 37:4343).

[0013] As mentioned above, FAP and FAP-expressing cells present in tumor microenvironment have been shown to significantly affect tumor progression (Hanahan et al., Cancer Cell, 2012, 21:309).In addition, due to its relatively selective expression in tumors, FAP is considered as a suitable target for therapeutic and diagnostic agents, as described below (Siveke, J Nucl Med, 2018, 59:1412; Christiansen et al., Neoplasia, 2013, 15:348; Zi et al., Mol Med Rep, 2015, 11:3203).

[0014] Shortly after their discovery, FAPs were exploited as therapeutic targets in cancer, and to date, various strategies have been explored, including, for example, inhibition of FAP enzymatic activity, elimination of FAP-positive cells, or targeted delivery of cytotoxic compounds.

[0015] In 2007, talabostat (Val-boro-Pro, PT-100), an inhibitor of FAP and DPP4, was developed by Point Therapeutics (e.g., as described in U.S. Patent No. 6,890,904 or published international patent application WO9916864). Pennisi et al. (Pennisi et al., Br J Haematol, 2009, 145:775) observed a reduction in tumor growth in multiple myeloma animal models as well as in cancer syngeneic mouse models. In addition, several other prolylboronic acid derivatives have been developed and reported as putative selective inhibitors of FAP. These derivatives exhibit instability in aqueous environments at physiological pH (Coutts et al., J Med Chem, 1996, 39:2087) and nonspecific reactivity with other enzymes.

[0016] WO2008 / 116054 disclosed hexapeptide derivatives in which the compounds contain a C-terminal bisamino or boronic acid functionality. US2017 / 0066800 disclosed pseudopeptide inhibitors, such as M83, that are effective against FAP. These inhibitors were evaluated in lung and colon cancer xenografts in immunodeficient mice. Tumor growth inhibition was observed (Jackson et al., Neoplasia, 2015, 17:43). These pseudopeptides inhibit the activity of both prolyl oligopeptidase (POP / PREP) and FAP, thereby precluding their use as specific therapeutic FAP inhibitors.

[0017] US2008 / 280856 disclosed nanomolar concentrations of boronic acid-based inhibitors that exhibit dual specific inhibition of FAP and PREP, thereby precluding their use as specific therapeutic FAP inhibitors.

[0018] Cyclic peptide-based FAP inhibitors have been disclosed, for example, in WO2016 / 146174 and WO2006 / 042282. WO2016 / 146174 discloses a peptide for the diagnosis and treatment of FAP-expressing tumors that exhibits specificity for FAP, and the closely related homolog DPP4 is not recognized by the peptide. WO2006 / 042282 discloses a polypeptide for the treatment of melanoma. In nude mice, inhibition of melanoma growth and melanoma metastasis was demonstrated.

[0019] WO99 / 75151 and WO01 / 68708 disclosed a humanized FAP monoclonal antibody, F19 (sibrotuzumab). Furthermore, the anti-FAP antibody F19 and its humanized versions were disclosed in WO99 / 57151 and WO01 / 68708. Development approaches included, for example, the generation of high-affinity, species-cross-reactive, FAP-specific scFvs, which were converted into bivalent derivatives (Brocks et al., Mol Med, 2001, 7:461). In phase I and II clinical trials, sibrotuzumab demonstrated specific tumor enrichment but failed to demonstrate measurable therapeutic activity in patients with metastatic colorectal cancer, with only 2 of 17 patients achieving stable disease (Hofheinz et al., Onkologie, 2003, 26:44). The F19 antibody was shown not to block any cellular or protease functions of FAP, which may explain the lack of therapeutic efficacy (Hofheinz et al., Onkologie, 2003, 26:44; Scott et al., Clin Cancer Res, 2003, 9:1639).

[0020] US2018 / 022822 disclosed novel molecules that specifically bind to human FAP and its epitopes as human-derived antibodies and chimeric antigen receptors (CARs) useful in the treatment of diseases and conditions induced by FAP. Treatment of mice bearing orthotopic MC38 colorectal tumors with anti-FAP antibodies reduced tumor diameter and the number of metastases. WO2012 / 020006 disclosed glycoengineered antibodies carrying modified oligosaccharides in the Fc region. Subsequently, bispecific antibodies specific for FAP and DR5 were developed as the subject of WO2014 / 161845. These antibodies induced tumor cell apoptosis in in vitro and in vivo preclinical tumor models with FAP-positive stroma (Brunker et al., Mol Cancer Ther, 2016, 15:946). Antibody-drug conjugates and immunotoxins targeting FAP are described in WO2015 / 118030. In vitro toxicity as well as in vivo inhibition of tumor growth was demonstrated after application of anti-hu / moFAP hu36:cytolysin ADC candidates. It is unclear whether these antibodies were able to inhibit FAP activity.

[0021] A small molecule FAP inhibitor based on (4-quinolinol)glycyl-2-cyanopyrrolidine, which exhibits low nanomolar inhibitory potency and high selectivity against related DPPs and PREPs, was described by Jansen et al. (Jansen et al., J Med Chem, 2014, 57:3053; Jansen et al., ACS Med Chem Lett, 2013, 4:491) and disclosed in WO2013 / 107820. However, that compound is not structurally related to the compounds of the present invention and contains a warhead that provides covalent binding to FAP.

[0022] Recently, several FAP-targeted radiopharmaceutical approaches have been developed, which are illustratively described herein. WO2010 / 036814 disclosed small molecule inhibitors of FAP for use as therapeutic agents by inhibiting FAP enzymatic activity or as radiopharmaceuticals by binding to FAP.

[0023] WO2019 / 083990 disclosed imaging and radiotherapeutic agents based on small molecule FAP inhibitors described by Jansen et al. (Jansen et al., J Med Chem, 2014, 57:3053; Jansen et al., ACS Med Chem Lett, 2013, 4:491). Furthermore, several authors have described the selective uptake in tumors of cancer patients of imaging and radiotherapeutic agents based on FAP inhibitors, as described by Jansen et al. (Jansen et al., J Med Chem, 2014, 57:3053; Jansen et al., ACS Med Chem Lett, 2013, 4:491) (Lindner et al., J Nucl Med, 2018, 59:1415; Loktev et al., J Nucl Med, 2018, 59:1423; Giesel et al., J Nucl Med, 2019, 60:386; Loktev et al., J Nucl Med, 2019, Mar 8 (Electronic ahead of print); Giesel et al., Eur J Nucl Med Mol Imaging, 2019, 46:1754; Kratochwil et al., J Nucl Med, 2019, 60:801).

[0024] 131 Clinical evaluation of an I-labeled, humanized form of the F19 antibody (sibrotuzumab) demonstrated selective uptake by tumors, but not normal tissues, in patients with colorectal cancer or non-small cell lung cancer (Scott, et al., Clin Cancer Res, 2003, 9:1639). This may be due to the long circulation time of the antibody, making it unsuitable for diagnostic, therapeutic, or diagnostic-therapeutic procedures involving radionuclides.

[0025] WO2011 / 040972 disclosed a high-affinity antibody that recognizes both human and mouse FAP antigens as a potent radioimmunoconjugate. ESC11 IgG1 induces down-modulation and internalization of surface FAP (Fischer et al., Clin Cancer Res, 2012, 18:6208). WO2017 / 211809 disclosed a tissue-targeted thorium-227 complex in which the targeting moiety has specificity for FAP. However, the long circulation time of antibodies makes them unsuitable for diagnostic, therapeutic, or diagnostic-therapeutic procedures involving radionuclides.

[0026] FAP has also been described to be involved in diseases other than oncological indications, examples of which are given below. Fibroblast-like synoviocytes in rheumatoid arthritis joints of patients show significantly increased expression of FAP (Bauer et al., Arthritis Res Ther, 2006, 8:R171; Milner et al., Arthritis Res Ther, 2006, 8:R23). In rheumatoid arthritis, stromal cells play a key role in organizing the structure of the synovial tissue of the joint by producing extracellular matrix components, recruiting infiltrating immune cells, and secreting inflammatory mediators. Considerable evidence supports the role of these cells in driving the persistence of inflammation and joint damage (Bartok et al., Immunol Rev, 2010, 233:233; Turner et al., Curr Opin Rheumatol, 2015, 27:175). In rheumatoid arthritis, FAP plays a pathological role in cartilage turnover, at least by promoting proteoglycan loss and subsequent cartilage degradation (Bauer et al., Arthritis Res Ther, 2006, 8:R171; Waldele et al., Arthritis Res Ther, 2015, 17:12).Therefore, it can serve as a marker for patient stratification, or as a therapeutic target for the evaluation and follow-up of treatment success (Bauer et al., Arthritis Res Ther, 2006, 8:R171).In mice, treatment response is 99mThis has been demonstrated using SPECT / CT imaging with Tc-labeled anti-FAP antibodies (van der Geest et al., Rheumatology (Oxford), 2018, 57:737; Laverman et al., J Nucl Med, 2015, 56:778; van der Geest et al., J Nucl Med, 2017, 58:151).

[0027] Furthermore, FAP has been recognized not only as a marker of activated fibroblasts in the injury response (Tillmanns et al., Int J Cardiol, 2013, 168:3926) but also as an important player in the wound healing process (Ramirez-Montagut et al., Oncogene, 2004, 23:5435). Jing et al. demonstrated a time-dependent course of changes in FAP expression after burn wound injury in rats (Jing et al., Nan Fang Yi Ke Da Xue Xu Bao, 2013, 33:615). Inhibition of FAP activity in reactive wound fibroblasts in keloid scars, a common benign fibroproliferative reticular skin lesion, may provide a therapeutic option for preventing disease progression (Dienus et al., Arch Dermatol Res, 2010, 302:725).

[0028] In fibrosis, for example, in idiopathic pulmonary fibrosis, Crohn's disease, and liver fibrosis, upregulated expression of FAP has been observed. In an ex vivo model of Crohn's disease, a chronic inflammatory bowel disease characterized by excessive and unbalanced extracellular matrix (ECM) deposition, upregulated FAP expression was observed. FAP inhibition reconstituted extracellular matrix homeostasis (Truffi et al., Inflamm Bowel Dis, 2018, 24:332). A similar observation was made by Egger et al. (Egger et al., Eur J Pharmacol, 2017, 809:64) using a mouse model of pulmonary fibrosis. Inhibition of FAP results in a reduction of fibrotic pathology. FAP is also expressed in areas of tissue remodeling in chronically injured livers (Wang et al., Front Biosci, 2008, 13:3168), and FAP expression by hepatic stellate cells correlates with the histological severity of liver disease (Gorrell et al., Adv Exp Med Biol, 2003, 524:235). Therefore, FAP is also a promising target for the treatment of liver fibrosis (Lay et al., Front Biosci (Landmark Ed), 2019, 24:1).

[0029] FAP is expressed in atherosclerotic lesions and is upregulated in activated vascular smooth muscle cells (Monslow et al., Circulation, 2013, 128:A17597). Monslow et al. demonstrated that targeted inhibition of FAP in atherosclerotic lesions can reduce overall lesion volume, inhibit inflammatory cell homing, and increase lesion stability through its ability to alter lesion structure by favoring matrix-rich lesions over inflammation. More importantly, many atherosclerotic pathologies share a common pathological feature: the rupture of atherosclerotic plaques, which leads to atherosclerotic lesions (Davies et al., Br Heart J, 1985, 53:363; Falk, Am J Cardiol, 1989, 63:114e). Rupture of the fibrous cap in advanced atherosclerotic plaques is an important precipitating factor for acute coronary syndromes, which can result in myocardial infarction and sudden cardiac death. One of the key events in promoting plaque instability is the degradation of the fibrous cap, which exposes the underlying thrombogenic plaque core to blood flow, leading to thrombosis and subsequent vascular occlusion (Farb et al., Circulation, 1996, 93:1354; Virmani et al., J Am Coll Cardiol, 2006, 47:C13). Brokopp et al. showed that FAP contributes to type I collagen disruption in the fibrous cap (Brokopp et al., Eur Heart J, 2011, 32:2713). Radiolabeled tracers have been developed and their applicability for atherosclerosis imaging has been demonstrated (Meletta et al., Molecules, 2015, 20:2081). DETAILED DESCRIPTION OF THE INVENTION

[0030] The problem underlying the present invention is to provide compounds suitable as diagnostic and / or therapeutic agents, particularly when conjugated to a diagnostically and / or therapeutically active effector. A further problem underlying the present invention is to provide compounds suitable as diagnostic and / or therapeutic agents, particularly when conjugated to a diagnostically and / or therapeutically active effector, such that the compounds are potent inhibitors of FAP activity, preferably with a pIC50 of greater than or equal to 6.0. A further problem underlying the present invention is to provide compounds suitable as diagnostic and / or therapeutic agents in the diagnosis and / or treatment of diseases in which diseased cells and / or diseased tissues express FAP, particularly when conjugated to a diagnostically and / or therapeutically active effector. A further problem underlying the present invention is to provide compounds suitable for delivering diagnostically and / or therapeutically effective agents to diseased cells and / or diseased tissues, respectively, more particularly to diseased cells and / or diseased tissues expressing FAP, preferably diseased tissues that include or contain cancer-associated fibroblasts. The present invention also provides methods for diagnosing, treating, and / or preventing diseases, as well as methods for the combined diagnosis and treatment of diseases, preferably diseases involving cells and / or tissues expressing FAP, more particularly diseased cells and / or tissues expressing FAP, and preferably diseased tissues including or containing cancer-associated fibroblasts. A further object of the present invention is to provide methods for identifying subjects likely to respond or not respond to disease treatment, and methods for selecting subjects likely to respond or not respond to disease treatment from a group of subjects. A further object of the present invention is to provide pharmaceutical compositions comprising compounds having the characteristics outlined above. A further object of the present invention is to provide kits suitable for use in any of the above methods.

[0031] There is a need for compounds that are suitable as diagnostic and / or therapeutic agents, particularly when conjugated to a diagnostically and / or therapeutically active effector. There is also a need for compounds that are suitable as diagnostic and / or therapeutic agents, particularly when conjugated to a diagnostically and / or therapeutically active effector, such that the compound is a potent inhibitor of FAP activity, preferably where the compound has a pIC50 of equal to or greater than 6.0. There is also a need for compounds that are suitable as diagnostic and / or therapeutic agents in the diagnosis and / or treatment of diseases in which diseased cells and / or diseased tissues express FAP, particularly when conjugated to a diagnostically and / or therapeutically active effector. There is also a need for compounds that are suitable for delivering diagnostically and / or therapeutically effective agents to diseased cells and / or diseased tissues, respectively, more particularly to diseased cells and / or diseased tissues that express FAP, preferably where the diseased tissues include or contain cancer-associated fibroblasts. There is also a need for methods for the diagnosis of disease, for the treatment and / or prevention of disease, and for the combined diagnosis and treatment of disease, preferably wherein such diseases involve cells and / or tissues expressing FAP, more particularly diseased cells and / or diseased tissues expressing FAP, and preferably wherein the diseased tissues include or contain cancer-associated fibroblasts. Furthermore, there is a need for methods for identifying subjects likely to respond or not respond to disease treatment, and for selecting subjects likely to respond or not respond to disease treatment from a group of subjects. Furthermore, there is a need for pharmaceutical compositions comprising compounds having the characteristics outlined above. Furthermore, there is a need for kits suitable for use in any of the above methods. The present invention satisfies these needs.

[0032] These and other problems are solved by the subject matter of the appended claims. These and other problems underlying the present invention are also solved by the following embodiments. Embodiment 1. Formula (I)

[0033] [ka]

[0034] Cyclic peptides and an N-terminal modification group A attached to Xaa1, the peptide sequence is drawn from left to right in the N-terminal to C-terminal direction; Xaa1 is a compound represented by formula (II)

[0035] [ka]

[0036] is a residue of an amino acid R 1a is -NH-, R 1b is H or CH3, n=0 or 1, the N-terminal modification group A is covalently bound to the nitrogen atom of Xaa1; The carbonyl group of Xaa1 is covalently bonded to the nitrogen of Xaa2, The sulfur atom of Xaa1 is covalently bonded to Yc as a thioether, Xaa2 is represented by formula (III), (IV), or (XX)

[0037] [ka]

[0038] is a residue of an amino acid R 2a , R 2b , R 2care each independently selected from the group consisting of (C1-C2)alkyl and H, and the (C1-C2)alkyl is optionally substituted with a substituent selected from the group consisting of OH, NH2, halogen, and (C5-C7)cycloalkyl; p=0, 1, or 2; v=1 or 2, w=1, 2, or 3, the amino acid of formula (IV) is optionally substituted at positions 3 and 4 of the indicated ring with one or two substituents selected from the group consisting of methyl, OH, NH, and F; Xaa3 is a compound of formula (V) or (XX)

[0039] [ka]

[0040] is a residue of an amino acid X 3 CH2, CF2, CH-R 3b , S, O, and NH; p=1 or 2, v=1 or 2, w=1, 2, or 3, R 3a is H, methyl, OH, NH2, or F, R 3b is methyl, OH, NH2, or F, Xaa4 is a compound represented by formula (VI)

[0041] [ka]

[0042] is a residue of an amino acid R 4a H, OH, COOH, CONH2, X 4 , and -NH-CO-X 4 and X is selected from the group consisting of 4is selected from the group consisting of (C1-C6) alkyl, (C5-C6) aryl, and (C5-C6) heteroaryl; and X 4 is optionally substituted by one or two substituents selected from the group consisting of methyl, CONH2, halogen, NH2, and OH; q=1, 2, or 3; one or two hydrogen atoms of said one, two, or three CH— groups are optionally and independently replaced by methyl, ethyl, (C-C)aryl, or (C-C)heteroaryl; R 4b is methyl or H, Xaa5 is structure (VII)

[0043] [ka]

[0044] is a residue of an amino acid R 5 is selected from the group of OH and NH; r=1, 2, or 3, Xaa6 is an amino acid selected from the group consisting of aromatic L-α-amino acids and heteroaromatic L-α-amino acids, Xaa7 is a compound represented by formula (IX)

[0045] [ka]

[0046] is an aminothiol or amino acid residue of R 7a -CO-, -COOH, -CONH2, -CH2-OH, -(CO)-NH-R 7b , -(CO)-(NR 7c )-R 7b , or H and R 7b and R 7c are each independently (C1-C4) alkyl; t is 1 or 2, Yc is the formula (X)

[0047] [ka]

[0048] and connecting the S atom of Xaa1 with the S atom of Xaa7 under the formation of two thioether linkages, thereby forming a compound of formula (XXI)

[0049] [ka]

[0050] forming a ring structure of the substitution pattern of the aromatic group of formula (X) is ortho, meta, or para; n=0 or 1, t=1 or 2, Y 1 is CH or N, Y 2 is N or CR c1 and R c1 is H or CH2-R c2 and R c2 is of formula (XI), (XII), or (XXII)

[0051] [ka]

[0052] The structure is R c3 and R c4 are each independently selected from the group consisting of H and (C1-C4) alkyl; u=1, 2, 3, 4, 5, or 6, x and y are each independently 1, 2, or 3; X=O or S, In formulas (XI) and (XXII), one of the nitrogen atoms is R c1In formula (XII), -X- is bonded to -CH2- in R c1 is bonded to -CH2- The N-terminal modification group A is a blocking group Ab1, and the blocking group Ab1 is R a1 -NH-C(O)-, and R a1 is selected from the group consisting of C3 alkyl, C4 alkyl, or C5 alkyl, each independently optionally substituted with up to two substituents independently selected from the group consisting of OH, F, COOH, (C3-C8)cycloalkyl, aryl, heteroaryl, and (C3-C8)heterocycle, wherein one of the -CH2- groups in the (C1-C8)alkyl is optionally replaced by -S- or -O-. Embodiment 2. R a1 is selected from the group consisting of C3 alkyl, C4 alkyl, or C5 alkyl. Embodiment 3. R a1 The compound of any one of embodiments 1 and 2, wherein is C4 alkyl. Embodiment 4. R a1 is n-butyl. Embodiment 5. The compound of any one of embodiments 1 to 4, wherein Xaa1 is a D-amino acid residue selected from the group consisting of cys, hcy, and pen, or Xaa1 is an L-amino acid residue selected from the group consisting of Cys, Hcy, and Pen. Embodiment 6 The compound of embodiment 5, wherein Xaa1 is Cys. Embodiment 7 The compound of any one of embodiments 1, 2, 3, 4, 5, and 6, wherein Xaa2 is an amino acid residue selected from the group consisting of Pro, Gly, Nmg, and derivatives thereof. Embodiment 8 The compound of embodiment 7, wherein Xaa2 is an amino acid residue selected from the group consisting of Pro and Nmg. Embodiment 9 The compound of any one of embodiments 7 and 8, wherein Xaa2 is an amino acid residue of Pro. Embodiment 10 The compound of any one of embodiments 1, 2, 3, 4, 5, 6, 7, 8, and 9, wherein Xaa3 is an amino acid residue selected from the group consisting of Pro, Hyp, Tfp, Cfp, Dmp, Aze, and Pip, and derivatives thereof. Embodiment 11 The compound of embodiment 10, wherein Xaa3 is an amino acid residue of Pro. Embodiment 12 The compound of any one of embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11, wherein Xaa4 is an amino acid residue selected from the group consisting of Thr, Hse, Asn, Gln, and Ser, and derivatives thereof. Embodiment 13 The compound of embodiment 12, wherein Xaa4 is Thr. Embodiment 14 The compound of any one of embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13, wherein Xaa5 is an amino acid residue selected from the group consisting of Gln and Glu, and derivatives thereof. Embodiment 15 The compound of embodiment 14, wherein Xaa5 is an amino acid residue selected from the group consisting of Gln and Glu. Embodiment 16 The compound of embodiment 15, wherein Xaa5 is an amino acid residue of Gln. Embodiment 17 The compound of embodiment 15, wherein Xaa5 is an amino acid residue of Glu. Embodiment 18. Xaa6 is selected from the group consisting of formulas (VIIIa), (VIIIb), (VIIIc), and (VIIId)

[0053] [ka]

[0054] is any one of the amino acid residues R 6a and R 6b are each independently selected from the group consisting of H, methyl, ethyl, propyl, and isopropyl; R 6crepresents 0 to 3 substituents, each of which is independently Cl, F, Br, NO2, NH2, CN, CF3, OH, OR 6d and C1-C4 alkyl; R 6d is selected from the group consisting of methyl, ethyl, propyl, and isopropyl; The compound of any one of embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, and 17, wherein s is 0 or 1. Embodiment 19. Xaa6 is selected from the group consisting of formulas (VIIIa), (VIIIb), (VIIIc), and (VIIId)

[0055] [ka]

[0056] is any one of the amino acid residues R 6a and R 6b are H, respectively, R 6c represents 0 to 2 substituents, each of which is independently Cl, F, Br, NO2, NH2, CN, CF3, OH, OR 6d and methyl; R 6d is selected from the group consisting of methyl, ethyl, propyl, and isopropyl; The compound of embodiment 18, wherein s is 0. Embodiment 20 The compound of any one of Embodiments 18 to 19, wherein Xaa6 is an amino acid residue selected from the group consisting of Phe, Ocf, Ppa, Thi, 1Ni, Otf, and Mpa, and derivatives thereof. Embodiment 21 The compound of embodiment 20, wherein Xaa6 is an amino acid residue of Phe. Embodiment 22. The compound of any one of embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, and 21, wherein Xaa7 is an aminothiol residue selected from the group consisting of Cys, Cys-OH, Cys-NH2, Cysol, AET, Hcy, cys, cys-OH, cys-NH2, and hcy. Embodiment 23 The compound of embodiment 22, wherein Xaa7 is an aminothiol residue selected from the group consisting of Cys, Cys-OH, Cys-NH2, Cysol, and AET. Embodiment 24 The compound of embodiment 23, wherein Xaa7 is an aminothiol residue of Cys, Cys-OH, or Cys-NH2, preferably Cys-OH. Embodiment 25. Xaa1 is an amino acid residue of Cys; Xaa2 is an amino acid residue of Pro or Nmg, preferably an amino acid residue of Pro; Xaa3 is an amino acid residue of Pro, Xaa4 is an amino acid residue of Thr; Xaa5 is an amino acid residue of Gln or Glu, preferably an amino acid residue of Gln; Xaa6 is an amino acid residue of Phe; The compound according to any one of embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24, preferably any one of embodiments 1, 2, 3, and 4, wherein Xaa7 is an amino acid residue of Cys. compound. Embodiment 26. Xaa1 is an amino acid residue of Cys; Xaa2 is an amino acid residue of Pro, Xaa3 is an amino acid residue of Pro, Xaa4 is an amino acid residue of Thr; Xaa5 is an amino acid residue of Gln, Xaa6 is an amino acid residue of Phe; The compound according to any one of embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24, preferably any one of embodiments 1, 2, 3, and 4, wherein Xaa7 is an amino acid residue of Cys. Embodiment 27. Xaa1 is an amino acid residue of Cys, Xaa2 is an amino acid residue of Pro, Xaa3 is an amino acid residue of Pro, Xaa4 is an amino acid residue of Thr; Xaa5 is an amino acid residue of Glu, Xaa6 is an amino acid residue of Phe; The compound according to any one of embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24, preferably any one of embodiments 1, 2, 3, and 4, wherein Xaa7 is an amino acid residue of Cys. Embodiment 28. Xaa1 is an amino acid residue of Cys; Xaa2 is an amino acid residue of Nmg; Xaa3 is an amino acid residue of Pro, Xaa4 is an amino acid residue of Thr; Xaa5 is an amino acid residue of Gln, Xaa6 is an amino acid residue of Phe; The compound according to any one of embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, and 24, preferably any one of embodiments 1, 2, 3, and 4, wherein Xaa7 is an amino acid residue of Cys. Embodiment 29. Yc

[0057] [ka]

[0058] The structure is Rc1 CH2-R c2 or H, CH2-R c2 is represented by formula (XIId) or formula (XXIIb)

[0059] [ka]

[0060] The structure is Z is a chelator, optionally including a linker; R c4 is H or methyl, 29. The compound of any one of embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, and 28, wherein u=1, 2, 3, 4, or 5. Embodiment 30. R c2 is represented by formula (XIId)

[0061] [ka]

[0062] 30. The compound of embodiment 29, wherein the compound has the structure: Embodiment 31. R c2 is represented by formula (XIId)

[0063] [ka]

[0064] The structure is u=1, R c4 The compound of any one of embodiments 29 and 30, wherein is H. Embodiment 32. R c2 is represented by formula (XXIIc)

[0065] [ka]

[0066] 30. The compound of embodiment 29, wherein the compound has the structure: Embodiment 33 The compound of any one of embodiments 29, 30, 31, and 32, wherein Z is a chelator lacking a linker. Embodiment 34 The compound of any one of embodiments 29, 30, 31, and 32, wherein Z is a chelator that includes a linker. Embodiment 35. The linker is covalently bonded to the chelator and has Formula (XIId)

[0067] [ka]

[0068] The compound of embodiment 34, wherein the N atom of the structure: Embodiment 36. The linker is covalently bonded to the chelator and has Formula (XXIIc)

[0069] [ka]

[0070] The compound of embodiment 34, wherein the N atom of the structure: Embodiment 37 The compound of any one of Embodiments 34, 35, and 36, wherein the linker is selected from the group consisting of Ttds and O2Oc. Embodiment 38 The compound of embodiment 37, wherein the linker is Ttds. Embodiment 39 The compound of embodiment 37, wherein the linker is O2Oc. Embodiment 39. R c1 is H. Embodiment 40. The compound of any one of embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, and 39, wherein an amino acid or peptide is attached to Xaa7, a majority of the amino acids of the peptide are charged or polar, and the net charge of the peptide is -2, -1, 0, +1, or +2. Embodiment 41 The compound of embodiment 40, wherein the amino acid is attached to Xaa7. Embodiment 42 The compound of embodiment 41, wherein the amino acid attached to Xaa7 is selected from the group consisting of Asp, asp, Bal, Gly, Gab, Ser, Nmg, Bhf, Lys, Ape, Ttds, and Bhk. Embodiment 43 The compound of embodiment 42, wherein the amino acid attached to Xaa7 is selected from the group consisting of Bhk, Ape, and Lys. Embodiment 44 The compound of embodiment 43, wherein the amino acid attached to Xaa7 is Bhk. Embodiment 45 The compound of any one of embodiments 41, 42, 43, and 44, wherein chelator Z is covalently attached to the amino acid attached to Xaa7. Embodiment 46. R c1 is H. Embodiment 47. Z is 99m Tc(CO)3-chelators, CB-TE2A, CHX-A”-DTPA, DTPA, DATA, DFO, HBED, Crown, DOTAGA, DOTAM (also known as TCMC), FSC, H4octapa, Macropa, HEHA, HOPO, Hynic, PCTA, PSC, NETA, DOTA, NODA-MPAA, NODAGA, NOTP, N x S 4-xThe compound of any one of embodiments 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, and 46, wherein the chelator is selected from the group consisting of (N4, N2S2, N3S), NOPO, NOTA, Pycup, RESCA, sarcofagin, TETA, THP, and TRAP. Embodiment 48. The compound of embodiment 47, wherein Z is a chelator selected from the group consisting of DOTAM, Macropa, PCTA, DOTA, N4Ac, NODAGA, NOPO, and NOTA. Embodiment 49:

[0071] [ka]

[0072] The compound nBu-CAyl-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3940), The following formula

[0073] [ka]

[0074] The compound nBu-CAyl-[Cys(tMeBn(N4Ac-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4533), The following formula

[0075] [ka]

[0076] The compound nBu-CAyl-[Cys(tMeBn(N4Ac-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4534), The following formula

[0077] [ka]

[0078] The compound nBu-CAyl-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-NH2 (3BP-4560), The following formula

[0079] [ka]

[0080] The compound nBu-CAyl-[Cys(tMeBn(DOTA-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4564), The following formula

[0081] [ka]

[0082] The compound nBu-CAyl-[Cys(tMeBn(DOTA-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-NH2 (3BP-4565), The following formula

[0083] [ka]

[0084] The compound nBu-CAyl-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Bhk(N4Ac)-OH (3BP-4589), The following formula

[0085] [ka]

[0086] the compound nBu-CAyl-[Cys(tMeBn(DOTA-AET))-Nmg-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4607), and The following formula

[0087] [ka]

[0088] The compound nBu-CAyl-[Cys(tMeBn(DOTA-AET))-Nmg-Pro-Thr-Gln-Phe-Cys]-NH2 (3BP-4621), The following formula

[0089] [ka]

[0090] The compound nBu-CAyl-[Cys(tMeBn(NODAGA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH(3BP-4723), The following formula

[0091] [ka]

[0092] The compound nBu-CAyl-[Cys(tMeBn(NODAGA-AET))-Pro-Pro-Thr-Glu-Phe-Cys]-OH(3BP-4724), The following formula

[0093] [ka]

[0094] The compound nBu-CAyl-[Cys(tMeBn(NOPO-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4768), The following formula

[0095] [ka]

[0096] the compound nBu-CAyl-[Cys(tMeBn(NOPO-AET))-Pro-Pro-Thr-Glu-Phe-Cys]-OH (3BP-4778), and The following formula

[0097] [ka]

[0098] The compound nBu-CAyl-[Cys(tMeBn(NOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-5210) 49. The compound of any one of embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, and 48, selected from the group consisting of: Embodiment 50:

[0099] [ka]

[0100] The compound nBu-CAyl-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3940), The following formula

[0101] [ka]

[0102] The compound nBu-CAyl-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-NH2 (3BP-4560), The following formula

[0103] [ka]

[0104] The compound nBu-CAyl-[Cys(tMeBn(NOPO-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4768) 50. The compound of embodiment 49, selected from the group consisting of: Embodiment 51. The compound of any one of embodiments 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, and 50, wherein the chelator comprises a nuclide, preferably wherein the nuclide is coordinatively bonded to the chelator. Embodiment 52 The compound of embodiment 51, wherein the nuclide is a diagnostically active nuclide or a therapeutically active nuclide. Embodiment 53 The compound of embodiment 52, wherein the diagnostically active nuclide is a diagnostically active radionuclide. Embodiment 54. The diagnostically active radionuclide is 18 F, 43 Sc, 44 Sc, 51 Mn, 52 Mn, 64 Cu, 67 Ga, 68 Ga, 76 Br, 77 Br, 86 Y, 89 Zr, 94m Tc, 99m Tc, 111 In, 123 I, 124 I, 125 I, 152 Tb, 155 Tb, 177 Lu, 201 Tl, and203 Pb. Embodiment 55. The diagnostically active radionuclide is: 18 F, 68 Ga, 99m Tc, 111 In, and 203 Pb. Embodiment 56 The compound of embodiment 52, wherein the therapeutically active nuclide is a therapeutically active radionuclide. Embodiment 57. The therapeutically active radionuclide is 47 Sc, 67 Cu, 89 Sr, 90 Y, 131 I, 111 In, 153 Sm, 149 Tb, 161 Tb, 177 Lu, 186 Re, 188 Re, 211 At, 212 Pb, 213 Bi, 223 Ra, 224 Ra, 225 Ac, 226 Th, and 227 The compound of embodiment 56, selected from the group consisting of Th. Embodiment 58. The therapeutically active radionuclide is 90 Y, 177 Lu, 212 Pb, and 225 The compound of embodiment 57, wherein said compound is Ac. Embodiment 59. Formula (I)

[0105] [ka]

[0106] Cyclic peptides and an N-terminal modification group A attached to Xaa1, the peptide sequence is drawn from left to right in the N-terminal to C-terminal direction; Xaa1 is a compound represented by formula (II)

[0107] [ka]

[0108] is a residue of an amino acid R 1a is -NH-, R 1b is H or CH3, n=0 or 1, the N-terminal modification group A is covalently bound to the nitrogen atom of Xaa1; The carbonyl group of Xaa1 is covalently bonded to the nitrogen of Xaa2, The sulfur atom of Xaa1 is covalently bonded to Yc as a thioether, Xaa2 is represented by formula (III), (IV), or (XX)

[0109] [ka]

[0110] is a residue of an amino acid R 2a , R 2b , R 2c are each independently selected from the group consisting of (C1-C2)alkyl and H, and the (C1-C2)alkyl is optionally substituted with a substituent selected from the group consisting of OH, NH2, halogen, and (C5-C7)cycloalkyl; p=0, 1, or 2; v=1 or 2, w=1, 2, or 3, the amino acid of formula (IV) is optionally substituted at positions 3 and 4 of the indicated ring with one or two substituents selected from the group consisting of methyl, OH, NH, and F; Xaa3 is a compound of formula (V) or (XX)

[0111] [ka]

[0112] is a residue of an amino acid X 3 CH2, CF2, CH-R 3b , S, O, and NH; p=1 or 2, v=1 or 2, w=1, 2, or 3, R 3a is H, methyl, OH, NH2, or F, R 3b is methyl, OH, NH2, or F, Xaa4 is a compound represented by formula (VI)

[0113] [ka]

[0114] is a residue of an amino acid R 4a H, OH, COOH, CONH2, X 4 , and -NH-CO-X 4 and X is selected from the group consisting of 4 is selected from the group consisting of (C1-C6) alkyl, (C5-C6) aryl, and (C5-C6) heteroaryl; and X 4 is optionally substituted by one or two substituents selected from the group consisting of methyl, CONH2, halogen, NH2, and OH; q=1, 2, or 3; one or two hydrogen atoms of said one, two, or three CH— groups are optionally and independently replaced by methyl, ethyl, (C-C)aryl, or (C-C)heteroaryl; R 4b is methyl or H, Xaa5 is structure (VII)

[0115] [ka]

[0116] is a residue of an amino acid R 5 is selected from the group of OH and NH; r=1, 2, or 3, Xaa6 is an amino acid selected from the group consisting of aromatic L-α-amino acids and heteroaromatic L-α-amino acids, Xaa7 is a compound represented by formula (IX)

[0117] [ka]

[0118] is an aminothiol or amino acid residue of R 7a -CO-, -COOH, -CONH2, -CH2-OH, -(CO)-NH-R 7b , -(CO)-(NR 7c )-R 7b , or H, R 7b and R 7c are each independently (C1-C4) alkyl; t is 1 or 2, Yc is the formula (X)

[0119] [ka]

[0120] and connecting the S atom of Xaa1 with the S atom of Xaa7 under the formation of two thioether linkages, thereby forming a compound of formula (XXI)

[0121] [ka]

[0122] forming a ring structure of the substitution pattern of the aromatic group of formula (X) is ortho, meta, or para, preferably meta; n=0 or 1, t=1 or 2, Y 1 is CH, Y 2 is CR c1 and R c1 CH2-R c2 or H, R c2 is represented by formula (XIId) or (XXIIc)

[0123] [ka]

[0124] The structure is u=1, R c4 is H, Z is a chelator, optionally including a linker; The N-terminal modification group A is a blocking group Ab1, and the blocking group Ab1 is R a1 -NH-C(O)-, and R a1 is (C1-C8)alkyl optionally substituted with up to two substituents each independently selected from the group consisting of OH, F, COOH, (C3-C8)cycloalkyl, aryl, heteroaryl, and (C3-C8)heterocycle, wherein one of the -CH2- groups in the (C1-C8)alkyl is optionally replaced by -S- or -O-. Embodiment 60. R c2 is represented by formula (XIId)

[0125] [ka]

[0126] The structure is u=1, R c4is H, The compound of embodiment 59, wherein Z is a chelator, optionally including a linker. Embodiment 61 The compound of embodiment 60, wherein Z is a chelator lacking a linker. Embodiment 62 The compound of embodiment 60, wherein Z comprises a linker. Embodiment 63. The compound of embodiment 62, wherein the linker covalently connects the chelator to the N atom of the structure of formula (XIId). Embodiment 64. The compound of any one of embodiments 62 to 63, wherein the linker is selected from the group consisting of Ttds, O2Oc, and PEG6, preferably Ttds and O2Oc. Embodiment 65. R c2 is represented by formula (XXIIc)

[0127] [ka]

[0128] The structure is The compound of embodiment 59, wherein Z is a chelator, optionally including a linker. Embodiment 66 The compound of embodiment 65, wherein Z is a chelator lacking a linker. Embodiment 67 The compound of embodiment 65, wherein Z comprises a linker. Embodiment 68. The compound of embodiment 67, wherein the linker covalently connects the chelator to the N atom of the structure of formula (XXIIc). Embodiment 69. The compound of any one of embodiments 67 to 68, wherein the linker is selected from the group consisting of Ttds, O2Oc, and PEG6, preferably the linker is selected from the group consisting of Ttds and O2Oc. Embodiment 70. R c1 is H. Embodiment 71. R a1is selected from the group consisting of C alkyl, C alkyl, or C alkyl, each independently optionally substituted with up to two substituents independently selected from the group consisting of OH, F, COOH, (C3-C8)cycloalkyl, aryl, heteroaryl, and (C3-C8)heterocycle, wherein in the (C1-C8)alkyl one of the -CH2- groups is optionally replaced by -S- or -O-. Embodiment 72. R a1 is selected from the group consisting of C3 alkyl, C4 alkyl, or C5 alkyl. Embodiment 73. R a1 The compound of any one of embodiments 71 and 72, wherein is C4 alkyl. Embodiment 74. R a1 The compound of embodiment 73, wherein is n-butyl. Embodiment 75. The compound of any one of embodiments 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, and 74, wherein Xaa1 is a D-amino acid residue selected from the group consisting of cys, hcy, and pen, or Xaa1 is an L-amino acid residue selected from the group consisting of Cys, Hcy, and Pen. Embodiment 76 The compound of embodiment 75, wherein Xaa1 is Cys. Embodiment 77 The compound of any one of embodiments 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, and 76, wherein Xaa2 is an amino acid residue selected from the group consisting of Pro, Gly, Nmg, and derivatives thereof. Embodiment 78 The compound of embodiment 77, wherein Xaa2 is an amino acid residue selected from the group consisting of Pro and Nmg. Embodiment 79 The compound of any one of embodiments 77 and 78, wherein Xaa2 is the amino acid residue of Pro. Embodiment 80 The compound of any one of embodiments 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, and 79, wherein Xaa3 is an amino acid residue selected from the group consisting of Pro, Hyp, Tfp, Cfp, Dmp, Aze, and Pip, and derivatives thereof. Embodiment 81 The compound of embodiment 80, wherein Xaa3 is an amino acid residue of Pro. Embodiment 82 The compound of any one of embodiments 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, and 81, wherein Xaa4 is an amino acid residue selected from the group consisting of Thr, Hse, Asn, Gln, and Ser, and derivatives thereof. Embodiment 83 The compound of embodiment 82, wherein Xaa4 is Thr. Embodiment 84 The compound of any one of embodiments 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, and 83, wherein Xaa5 is an amino acid residue selected from the group consisting of Gln and Glu, and derivatives thereof. Embodiment 85 The compound of embodiment 84, wherein Xaa5 is an amino acid residue selected from the group consisting of Gln and Glu. Embodiment 86 The compound of embodiment 85, wherein Xaa5 is an amino acid residue of Gln. Embodiment 87 The compound of embodiment 85, wherein Xaa5 is an amino acid residue of Glu. Embodiment 88. Xaa6 is selected from the group consisting of formulas (VIIIa), (VIIIb), (VIIIc), and (VIIId)

[0129] [ka]

[0130] is any one of the amino acid residues R 6a and R 6b are each independently selected from the group consisting of H, methyl, ethyl, propyl, and isopropyl; R 6c represents 0 to 3 substituents, each of which is independently Cl, F, Br, NO2, NH2, CN, CF3, OH, OR 6d and C1-C4 alkyl; R 6d is selected from the group consisting of methyl, ethyl, propyl, and isopropyl; The compound of any one of embodiments 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, and 86, wherein s is 0 or 1. Embodiment 89. Xaa6 is selected from the group consisting of formulas (VIIIa), (VIIIb), (VIIIc), and (VIIId)

[0131] [ka]

[0132] is any one of the amino acid residues R 6a and R 6b are H, respectively, R 6c represents 0 to 2 substituents, each of which is independently Cl, F, Br, NO2, NH2, CN, CF3, OH, OR 6d and methyl; R 6d is selected from the group consisting of methyl, ethyl, propyl, and isopropyl; The compound of embodiment 88, wherein s is 0. Embodiment 90 The compound of any one of Embodiments 88 to 89, wherein Xaa6 is an amino acid residue selected from the group consisting of Phe, Ocf, Ppa, Thi, 1Ni, Otf, and Mpa, and derivatives thereof. Embodiment 91 The compound of embodiment 90, wherein Xaa6 is an amino acid residue of Phe. Embodiment 92. The compound of any one of embodiments 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, and 81, wherein Xaa7 is an aminothiol residue selected from the group consisting of Cys, Cys-OH, Cys-NH2, Cysol, AET, Hcy, cys, cys-OH, cys-NH2, and hcy. Embodiment 93 The compound of embodiment 92, wherein Xaa7 is an aminothiol residue selected from the group consisting of Cys, Cys-OH, Cys-NH2, Cysol, and AET. Embodiment 94 The compound of embodiment 93, wherein Xaa7 is an aminothiol residue of Cys, Cys-OH, or Cys-NH2, preferably Cys-OH. Embodiment 95. Xaa1 is an amino acid residue of Cys, Xaa2 is an amino acid residue of Pro or Nmg, preferably an amino acid residue of Pro; Xaa3 is an amino acid residue of Pro, Xaa4 is an amino acid residue of Thr; Xaa5 is an amino acid residue of Gln or Glu, preferably an amino acid residue of Gln; Xaa6 is an amino acid residue of Phe; 95. The compound of any one of embodiments 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, and 94, wherein Xaa7 is an amino acid residue of Cys. Embodiment 96. Xaa1 is an amino acid residue of Cys, Xaa2 is an amino acid residue of Pro, Xaa3 is an amino acid residue of Pro, Xaa4 is an amino acid residue of Thr; Xaa5 is an amino acid residue of Gln, Xaa6 is an amino acid residue of Phe; 95. The compound of any one of embodiments 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, and 94, wherein Xaa7 is an amino acid residue of Cys. Embodiment 97. Xaa1 is the amino acid residue Cys, Xaa2 is an amino acid residue of Pro, Xaa3 is an amino acid residue of Pro, Xaa4 is an amino acid residue of Thr; Xaa5 is an amino acid residue of Glu, Xaa6 is an amino acid residue of Phe; 95. The compound of any one of embodiments 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, and 94, wherein Xaa7 is an amino acid residue of Cys. Embodiment 98. Xaa1 is an amino acid residue of Cys, Xaa2 is an amino acid residue of Nmg; Xaa3 is an amino acid residue of Pro, Xaa4 is an amino acid residue of Thr; Xaa5 is an amino acid residue of Gln, Xaa6 is an amino acid residue of Phe; 95. The compound of any one of embodiments 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, and 94, wherein Xaa7 is an amino acid residue of Cys. Embodiment 99. The compound of any one of embodiments 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, and 98, wherein an amino acid or peptide is attached to Xaa7, a majority of the amino acids of the peptide are charged or polar, and the net charge of the peptide is -2, -1, 0, +1, or +2. Embodiment 100 The compound of embodiment 99, wherein the amino acid is attached to Xaa7. Embodiment 101 The compound of embodiment 100, wherein the amino acid attached to Xaa7 is selected from the group consisting of Asp, asp, Bal, Gly, Gab, Ser, Nmg, Bhf, Lys, Ape, Ttds, and Bhk. Embodiment 102 The compound of embodiment 101, wherein the amino acid attached to Xaa7 is selected from the group consisting of Bhk, Ape, and Lys. Embodiment 103 The compound of embodiment 102, wherein the amino acid attached to Xaa7 is Bhk. Embodiment 104 The compound of any one of embodiments 100, 101, 192, and 103, wherein a chelator Z is covalently attached to the amino acid attached to Xaa7. Embodiment 105. R c1 The compound of embodiment 104, wherein Embodiment 106. Z is 99m Tc(CO)3-chelators, CB-TE2A, CHX-A”-DTPA, DTPA, DATA, DFO, HBED, Crown, DOTAGA, DOTAM (also known as TCMC), FSC, H4octapa, Macropa, HEHA, HOPO, Hynic, PCTA, PSC, NETA, DOTA, NODA-MPAA, NODAGA, NOTP, N x S 4-x106. The compound of any one of embodiments 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, and 105, wherein the chelator is selected from the group consisting of (N4, N2S2, N3S), NOPO, NOTA, Pycup, RESCA, sarcofagin, TETA, THP, and TRAP. Embodiment 107. The compound of embodiment 106, wherein Z is a chelator selected from the group consisting of DOTAM, Macropa, PCTA, DOTA, N4Ac, NODAGA, NOPO, and NOTA. Embodiment 108: The following formula

[0133] [ka]

[0134] The compound nBu-CAyl-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3940), The following formula

[0135] [ka]

[0136] The compound nBu-CAyl-[Cys(tMeBn(N4Ac-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4533), The following formula

[0137] [ka]

[0138] The compound nBu-CAyl-[Cys(tMeBn(N4Ac-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4534), The following formula

[0139] [ka]

[0140] The compound nBu-CAyl-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-NH2 (3BP-4560), The following formula

[0141] [ka]

[0142] The compound nBu-CAyl-[Cys(tMeBn(DOTA-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4564), The following formula

[0143] [ka]

[0144] The compound nBu-CAyl-[Cys(tMeBn(DOTA-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-NH2 (3BP-4565), The following formula

[0145] [ka]

[0146] The compound nBu-CAyl-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Bhk(N4Ac)-OH (3BP-4589), The following formula

[0147] [ka]

[0148] the compound nBu-CAyl-[Cys(tMeBn(DOTA-AET))-Nmg-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4607), and The following formula

[0149] [ka]

[0150] The compound nBu-CAyl-[Cys(tMeBn(DOTA-AET))-Nmg-Pro-Thr-Gln-Phe-Cys]-NH2 (3BP-4621), The following formula

[0151] [ka]

[0152] The compound nBu-CAyl-[Cys(tMeBn(NODAGA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH(3BP-4723), The following formula

[0153] [ka]

[0154] The compound nBu-CAyl-[Cys(tMeBn(NODAGA-AET))-Pro-Pro-Thr-Glu-Phe-Cys]-OH(3BP-4724), The following formula

[0155] [ka]

[0156] The compound nBu-CAyl-[Cys(tMeBn(NOPO-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4768), The following formula

[0157] [ka]

[0158] the compound nBu-CAyl-[Cys(tMeBn(NOPO-AET))-Pro-Pro-Thr-Glu-Phe-Cys]-OH (3BP-4778), and The following formula

[0159] [ka]

[0160] The compound nBu-CAyl-[Cys(tMeBn(NOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-5210) 106, and 107. The compound of any one of embodiments 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, and 107, selected from the group consisting of: Embodiment 109:

[0161] [ka]

[0162] The compound nBu-CAyl-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3940), The following formula

[0163] [ka]

[0164] the compound nBu-CAyl-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-NH2 (3BP-4560), and The following formula

[0165] [ka]

[0166] The compound nBu-CAyl-[Cys(tMeBn(NOPO-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4768) The compound of embodiment 108, selected from the group consisting of: Embodiment 110. The compound of any one of embodiments 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, and 109, wherein the chelator comprises a nuclide, preferably wherein the nuclide is coordinatively bonded to the chelator. Embodiment 111 The compound of embodiment 110, wherein the nuclide is a diagnostically active nuclide or a therapeutically active nuclide. Embodiment 112 The compound of embodiment 111, wherein the diagnostically active nuclide is a diagnostically active radionuclide. Embodiment 113. The diagnostically active radionuclide is 18 F, 43 Sc, 44 Sc, 51 Mn, 52 Mn, 64 Cu, 67 Ga,68 Ga, 76 Br, 77 Br, 86 Y, 89 Zr, 94m Tc, 99m Tc, 111 In, 123 I, 124 I, 125 I, 152 Tb, 155 Tb, 177 Lu, 201 Tl, and 203 The compound of embodiment 112, wherein the compound is selected from the group consisting of: Pb. Embodiment 114. The diagnostically active radionuclide is: 18 F, 68 Ga, 99m Tc, 111 In, and 203 The compound of embodiment 113, wherein the compound is selected from the group consisting of Pb. Embodiment 115. The compound of embodiment 111, wherein the therapeutically active nuclide is a therapeutically active radionuclide. Embodiment 116. The therapeutically active radionuclide is 47 Sc, 67 Cu, 89 Sr, 90 Y, 131 I, 111 In, 153 Sm, 149 Tb, 161 Tb, 177 Lu, 186 Re, 188 Re, 211 At, 212 Pb, 213 Bi, 223 Ra, 224 Ra, 225 Ac, 226 Th, and 227 The compound of embodiment 115, selected from the group consisting of Th. Embodiment 117. The therapeutically active radionuclide is 90 Y, 177 Lu, 212 Pb, and 225 The compound of embodiment 116, wherein the compound is Ac. Embodiment 118: Formula (I)

[0167] [ka]

[0168] Cyclic peptides and an N-terminal modification group A attached to Xaa1, the peptide sequence is drawn from left to right in the N-terminal to C-terminal direction; Xaa1 is a compound represented by the formula (II)

[0169] [ka]

[0170] is a residue of an amino acid R 1a is -NH-, R 1b is H or CH3, n=0 or 1, the N-terminal modification group A is covalently bound to the nitrogen atom of Xaa1; The carbonyl group of Xaa1 is covalently bonded to the nitrogen of Xaa2, The sulfur atom of Xaa1 is covalently bonded to Yc as a thioether, Xaa2 is represented by formula (III), (IV), or (XX)

[0171] [ka]

[0172] is a residue of an amino acid R 2a , R 2b , R 2c are each independently selected from the group consisting of (C1-C2)alkyl and H, and the (C1-C2)alkyl is optionally substituted with a substituent selected from the group consisting of OH, NH2, halogen, and (C5-C7)cycloalkyl; p=0, 1, or 2; v=1 or 2, w=1, 2, or 3, the amino acid of formula (IV) is optionally substituted at positions 3 and 4 of the indicated ring with one or two substituents selected from the group consisting of methyl, OH, NH, and F; Xaa3 is a compound of formula (V) or (XX)

[0173] [ka]

[0174] is a residue of an amino acid X 3 CH2, CF2, CH-R 3b , S, O, and NH; p=1 or 2, v=1 or 2, w=1, 2, or 3, R 3a is H, methyl, OH, NH2, or F, R 3b is methyl, OH, NH2, or F, Xaa4 is a compound represented by formula (VI)

[0175] [ka]

[0176] is a residue of an amino acid R 4a H, OH, COOH, CONH2, X 4 , and -NH-CO-X 4 and X is selected from the group consisting of 4 is selected from the group consisting of (C1-C6) alkyl, (C5-C6) aryl, and (C5-C6) heteroaryl; and X 4 is optionally substituted by one or two substituents selected from the group consisting of methyl, CONH2, halogen, NH2, and OH; q=1, 2, or 3; one or two hydrogen atoms of said one, two, or three CH— groups are optionally and independently replaced by methyl, ethyl, (C-C)aryl, or (C-C)heteroaryl; R 4b is methyl or H, Xaa5 is structure (VII)

[0177] [ka]

[0178] is a residue of an amino acid R 5 is selected from the group of OH and NH; r=1, 2, or 3, Xaa6 is an amino acid selected from the group consisting of aromatic L-α-amino acids and heteroaromatic L-α-amino acids, Xaa7 is a compound represented by formula (IX)

[0179] [ka]

[0180] is an aminothiol or amino acid residue of R 7a -CO-, -COOH, -CONH2, -CH2-OH, -(CO)-NH-R 7b , -(CO)-(NR 7c )-R 7b , or H, R 7b and R 7c are each independently (C1-C4) alkyl; t is 1 or 2, Yc is the formula (X)

[0181] [ka]

[0182] and connecting the S atom of Xaa1 with the S atom of Xaa7 under the formation of two thioether linkages, thereby forming a compound of formula (XXI)

[0183] [ka]

[0184] forming a ring structure of the substitution pattern of the aromatic group of formula (X) is meta; n=0 or 1, t=1 or 2, Y 1 is CH or N, Y 2 is CR c1 and R c1 is H, the N-terminal modification group A is the amino acid Aaa, The amino acid Aaa has the structure (XIV)

[0185] [ka]

[0186] is an L-amino acid residue of R a2 is selected from the group consisting of (C1-C6) alkyl and modified (C1-C6) alkyl, in which one -CH2- group is replaced by -S- or -O-; the amino acid Aaa is covalently attached to a linker, the linker is covalently attached to a chelator Z, the linker consisting of (a) a first linker or (b) a first linker and a second linker; when the linker consists of the first linker, the first linker is covalently attached to the chelator and to the amino acid Aaa; when the first linker consists of a first linker and a second linker, the first linker is covalently bonded to the amino acid Aaa and the second linker, and the second linker is covalently bonded to the chelator; the first linker is selected from the group consisting of Ttds and PEG6, preferably the first linker is Ttds; The compound, wherein said second linker is selected from the group consisting of PPAc and PEG6, preferably said second linker is PPAc. Embodiment 119. R a2 is C4 alkyl. Embodiment 120 The compound of embodiments 118 and 119, wherein the amino acid Aaa is a residue of Nle. Embodiment 121. Y 1 The compound of any one of embodiments 118, 119, and 120, wherein is CH. Embodiment 122. Y 1 The compound of any one of embodiments 118, 119, and 120, wherein is N. Embodiment 123. The compound of any one of embodiments 118, 119, 120, 121, and 122, preferably any one of embodiments 120 to 122, wherein the linker consists of a first linker, and the first linker is selected from the group consisting of Ttds and PEG6. Embodiment 124. The compound of embodiment 123, wherein the first linker is Ttds, and preferably the amino acid Aaa is a residue of Nle. Embodiment 125. The compound of embodiment 123, wherein the first linker is PEG6 and preferably the amino acid Aaa is a residue of Nle. Embodiment 126. The compound of any one of embodiments 118, 119, 120, 121, and 122, preferably any one of embodiments 120, 121, and 122, wherein the linker consists of a first linker and a second linker, wherein the first linker is selected from the group consisting of Ttds and PEG6, and the second linker is selected from the group consisting of PPAc and PEG6, preferably PPAc. Embodiment 127. The compound of embodiment 126, wherein the first linker is Ttds and the second linker is PPAc, and preferably the amino acid Aaa is a residue of Nle. Embodiment 128. The compound of embodiment 126, wherein the first linker is Ttds and the second linker is PEG6, and preferably the amino acid Aaa is a residue of Nle. Embodiment 129. The compound of any one of embodiments 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, and 128, wherein Xaa1 is a D-amino acid residue selected from the group consisting of cys, hcy, and pen, or Xaa1 is an L-amino acid residue selected from the group consisting of Cys, Hcy, and Pen. Embodiment 130 The compound of embodiment 129, wherein Xaa1 is Cys. Embodiment 131 The compound of any one of embodiments 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, and 130, wherein Xaa2 is an amino acid residue selected from the group consisting of Pro, Gly, Nmg, and derivatives thereof. Embodiment 132 The compound of embodiment 131, wherein Xaa2 is an amino acid residue selected from the group consisting of Pro and Nmg. Embodiment 133 The compound of any one of embodiments 131 and 132, wherein Xaa2 is the amino acid residue of Pro. Embodiment 134 The compound of any one of embodiments 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, and 133, wherein Xaa3 is an amino acid residue selected from the group consisting of Pro, Hyp, Tfp, Cfp, Dmp, Aze, and Pip, and derivatives thereof. Embodiment 135 The compound of embodiment 134, wherein Xaa3 is an amino acid residue of Pro. Embodiment 136 The compound of any one of embodiments 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, and 135, wherein Xaa4 is an amino acid residue selected from the group consisting of Thr, Hse, Asn, Gln, and Ser, and derivatives thereof. Embodiment 137 The compound of embodiment 136, wherein Xaa4 is Thr. Embodiment 138 The compound of any one of embodiments 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, and 137, wherein Xaa5 is an amino acid residue selected from the group consisting of Gln and Glu, and derivatives thereof. Embodiment 139 The compound of embodiment 138, wherein Xaa5 is an amino acid residue selected from the group consisting of Gln and Glu. Embodiment 140 The compound of embodiment 139, wherein Xaa5 is an amino acid residue of Gln. Embodiment 141 The compound of embodiment 140, wherein Xaa5 is an amino acid residue of Glu. Embodiment 142. Xaa6 is selected from the group consisting of formulas (VIIIa), (VIIIb), (VIIIc), and (VIIId)

[0187] [ka]

[0188] is any one of the amino acid residues R 6a and R 6b are each independently selected from the group consisting of H, methyl, ethyl, propyl, and isopropyl; R 6c represents 0 to 3 substituents, each of which is independently Cl, F, Br, NO2, NH2, CN, CF3, OH, OR 6d and C1-C4 alkyl; R 6d is selected from the group consisting of methyl, ethyl, propyl, and isopropyl; 132, 133, 134, 135, 136, 137, 138, 139, 140, and 141, wherein s is 0 or 1. Embodiment 143. Xaa6 is selected from the group consisting of formulas (VIIIa), (VIIIb), (VIIIc), and (VIIId)

[0189] [ka]

[0190] is any one of the amino acid residues R 6a and R 6b are H, respectively, R 6c represents 0 to 2 substituents, each of which is independently Cl, F, Br, NO2, NH2, CN, CF3, OH, OR 6d and methyl; R 6d is selected from the group consisting of methyl, ethyl, propyl, and isopropyl; The compound of embodiment 142, wherein s is 0. Embodiment 144 The compound of any one of Embodiments 142 to 143, wherein Xaa6 is an amino acid residue selected from the group consisting of Phe, Ocf, Ppa, Thi, 1Ni, Otf, and Mpa, and derivatives thereof. Embodiment 145 The compound of embodiment 144, wherein Xaa6 is an amino acid residue of Phe. Embodiment 146. The compound of any one of embodiments 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, and 145, wherein Xaa7 is an aminothiol residue selected from the group consisting of Cys, Cys-OH, Cys-NH2, Cysol, AET, Hcy, cys, cys-OH, cys-NH2, and hcy. Embodiment 147 The compound of embodiment 146, wherein Xaa7 is an aminothiol residue selected from the group consisting of Cys, Cys-OH, Cys-NH2, Cysol, and AET. Embodiment 148 The compound of embodiment 147, wherein Xaa7 is an aminothiol residue of Cys, Cys-OH, or Cys-NH2, preferably Cys-OH. Embodiment 149. Xaa1 is an amino acid residue of Cys, Xaa2 is an amino acid residue of Pro or Nmg, preferably an amino acid residue of Pro; Xaa3 is an amino acid residue of Pro, Xaa4 is an amino acid residue of Thr; Xaa5 is an amino acid residue of Gln or Glu, preferably an amino acid residue of Gln; Xaa6 is an amino acid residue of Phe; 149. The compound of any one of embodiments 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, and 148, wherein Xaa7 is an amino acid residue of Cys. Embodiment 150. Xaa1 is an amino acid residue of Cys, Xaa2 is an amino acid residue of Pro, Xaa3 is an amino acid residue of Pro, Xaa4 is an amino acid residue of Thr; Xaa5 is an amino acid residue of Gln, Xaa6 is an amino acid residue of Phe; 149. The compound of any one of embodiments 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, and 148, wherein Xaa7 is an amino acid residue of Cys. Embodiment 151. Xaa1 is an amino acid residue of Cys, Xaa2 is an amino acid residue of Pro, Xaa3 is an amino acid residue of Pro, Xaa4 is an amino acid residue of Thr; Xaa5 is an amino acid residue of Glu, Xaa6 is an amino acid residue of Phe; 149. The compound of any one of embodiments 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, and 148, wherein Xaa7 is an amino acid residue of Cys. Embodiment 152. Xaa1 is an amino acid residue of Cys, Xaa2 is an amino acid residue of Nmg; Xaa3 is an amino acid residue of Pro, Xaa4 is an amino acid residue of Thr; Xaa5 is an amino acid residue of Gln, Xaa6 is an amino acid residue of Phe; 149. The compound of any one of embodiments 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, and 148, wherein Xaa7 is an amino acid residue of Cys. Embodiment 153. The compound of any one of embodiments 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, and 152, wherein an amino acid or peptide is attached to Xaa7, a majority of the amino acids of the peptide are charged or polar, and the net charge of the peptide is −2, −1, 0, +1, or +2. Embodiment 154 The compound of embodiment 153, wherein the amino acid is attached to Xaa7. Embodiment 155 The compound of embodiment 154, wherein the amino acid attached to Xaa7 is selected from the group consisting of Asp, asp, Bal, Gly, Gab, Ser, Nmg, Bhf, Lys, Ape, Ttds, and Bhk. Embodiment 156 The compound of embodiment 155, wherein the amino acid attached to Xaa7 is Bal or Asp. Embodiment 157. Z is 99mTc(CO)3-chelators, CB-TE2A, CHX-A”-DTPA, DTPA, DATA, DFO, HBED, Crown, DOTAGA, DOTAM (also known as TCMC), FSC, H4octapa, Macropa, HEHA, HOPO, Hynic, PCTA, PSC, NETA, DOTA, NODA-MPAA, NODAGA, NOTP, N x S 4-x 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, wherein the compound is a chelator selected from the group consisting of (N4, N2S2, N3S), NOPO, NOTA, Pycup, RESCA, sarcofagin, TETA, THP, and TRAP. Embodiment 158. The compound of embodiment 157, wherein Z is a chelator selected from the group consisting of DOTAM, Macropa, PCTA, DOTA, N4Ac, NODAGA, NOPO, and NOTA. Embodiment 159:

[0191] [ka]

[0192] The compound N4Ac-PPAc-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-OH(3BP-4541), The following formula

[0193] [ka]

[0194] The compound N4Ac-Ttds-Nle-[Cys(3Lut)-Pro-Pro-Thr-Gln-Phe-Cys]-OH(3BP-4549), The following formula

[0195] [ka]

[0196] the compound N4Ac-PEG6-Nle-[Cys(3Lut)-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4550), The following formula

[0197] [ka]

[0198] the compound N4Ac-PEG6-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-4551), The following formula

[0199] [ka]

[0200] The compound N4Ac-PEG6-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-OH(3BP-4552), The following formula

[0201] [ka]

[0202] The compound NODAGA-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-OH(3BP-4713), The following formula

[0203] [ka]

[0204] The compound NODAGA-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-OH(3BP-4714), The following formula

[0205] [ka]

[0206] The compound NODAGA-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-NH2(3BP-4743), The following formula

[0207] [ka]

[0208] the compound N4Ac-PEG6-Nle-[Cys(3Lut)-Pro-Pro-Thr-Glu-Phe-Cys]-OH (3BP-4773), The following formula

[0209] [ka]

[0210] The compound N4Ac-PPAc-Ttds-Nle-[Cys(3Lut)-Pro-Pro-Thr-Gln-Phe-Cys]-OH(3BP-4774), The following formula

[0211] [ka]

[0212] The compound N4Ac-PPAc-Ttds-Nle-[Cys(3Lut)-Pro-Pro-Thr-Glu-Phe-Cys]-OH(3BP-4775), The following formula

[0213] [ka]

[0214] The compound N4Ac-PEG6-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-OH(3BP-4780), The following formula

[0215] [ka]

[0216] the compound N4Ac-PPAc-PEG6-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-OH (3BP-4781), The following formula

[0217] [ka]

[0218] The compound N4Ac-PPAc-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-OH(3BP-4782), The following formula

[0219] [ka]

[0220] The compound N4Ac-PPAc-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Bal-OH(3BP-4784), The following formula

[0221] [ka]

[0222] The compound N4Ac-PPAc-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-Asp-OH(3BP-4785), The following formula

[0223] [ka]

[0224] The compound N4Ac-PPAc-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-Bal-OH(3BP-4960), The following formula

[0225] [ka]

[0226] the compound N4Ac-PPAc-Ttds-Nle-[Cys(3Lut)-Pro-Pro-Thr-Gln-Phe-Cys]-Bal-OH (3BP-4961), and The following formula

[0227] [ka]

[0228] The compound NOTA-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-OH(3BP-5201) 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, and 158, selected from the group consisting of: Embodiment 160. The following formula:

[0229] [ka]

[0230] The compound N4Ac-PPAc-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-OH(3BP-4541), The following formula

[0231] [ka]

[0232] The compound NODAGA-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-OH(3BP-4713), The following formula

[0233] [ka]

[0234] the compound N4Ac-PPAc-Ttds-Nle-[Cys(3Lut)-Pro-Pro-Thr-Gln-Phe-Cys]-Bal-OH (3BP-4961), and The following formula

[0235] [ka]

[0236] The compound NOTA-Ttds-Nle-[Cys(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-OH(3BP-5201) 160. The compound of embodiment 159, selected from the group consisting of: Embodiment 161. The compound of any one of embodiments 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, and 160, wherein the chelator comprises a nuclide, preferably wherein the nuclide is coordinatively bonded to the chelator. Embodiment 162. The compound of embodiment 161, wherein the nuclide is a diagnostically active nuclide or a therapeutically active nuclide. Embodiment 163 The compound of embodiment 162, wherein the diagnostically active nuclide is a diagnostically active radionuclide. Embodiment 164. The diagnostically active radionuclide is 18 F, 43 Sc, 44 Sc, 51 Mn, 52 Mn, 64 Cu, 67 Ga, 68 Ga, 76 Br, 77 Br, 86 Y, 89 Zr, 94m Tc, 99m Tc, 111 In, 123 I, 124 I, 125 I, 152 Tb, 155 Tb, 177 Lu, 201 Tl, and 203The compound of embodiment 163, wherein the compound is selected from the group consisting of Pb. Embodiment 165. The diagnostically active radionuclide is: 18 F, 68 Ga, 99m Tc, 111 In, and 203 The compound of embodiment 164, wherein the compound is selected from the group consisting of Pb. Embodiment 166 The compound of embodiment 162, wherein the therapeutically active nuclide is a therapeutically active radionuclide. Embodiment 167. The therapeutically active radionuclide is 47 Sc, 67 Cu, 89 Sr, 90 Y, 131 I, 111 In, 153 Sm, 149 Tb, 161 Tb, 177 Lu, 186 Re, 188 Re, 211 At, 212 Pb, 213 Bi, 223 Ra, 224 Ra, 225 Ac, 226 Th, and 227 The compound of embodiment 166, selected from the group consisting of Th. Embodiment 168. The therapeutically active radionuclide is 90 Y, 177 Lu, 212 Pb, and 225 The compound of embodiment 167, wherein said compound is Ac. Embodiment 169. Formula (I)

[0237] [ka]

[0238] Cyclic peptides and an N-terminal modification group A attached to Xaa1, the peptide sequence is drawn from left to right in the N-terminal to C-terminal direction; Xaa1 is a compound represented by the formula (II)

[0239] [ka]

[0240] is a residue of an amino acid R 1a is -NH-, R 1b is H or CH3, n=0 or 1, the N-terminal modification group A is covalently bound to the nitrogen atom of Xaa1; The carbonyl group of Xaa1 is covalently bonded to the nitrogen of Xaa2, The sulfur atom of Xaa1 is covalently bonded to Yc as a thioether, Xaa2 is represented by formula (III), (IV), or (XX)

[0241] [ka]

[0242] is a residue of an amino acid R 2a , R 2b , R 2c are each independently selected from the group consisting of (C1-C2)alkyl and H, and the (C1-C2)alkyl is optionally substituted with a substituent selected from the group consisting of OH, NH2, halogen, and (C5-C7)cycloalkyl; p=0, 1, or 2; v=1 or 2, w=1, 2, or 3, the amino acid of formula (IV) is optionally substituted at positions 3 and 4 of the indicated ring with one or two substituents selected from the group consisting of methyl, OH, NH, and F; Xaa3 is a compound represented by formula (V) or (XX)

[0243] [ka]

[0244] is a residue of an amino acid X 3 CH2, CF2, CH-R 3b , S, O, and NH; p=1 or 2, v=1 or 2, w=1, 2, or 3, R 3a is H, methyl, OH, NH2, or F, R 3b is methyl, OH, NH2, or F, Xaa4 is a compound represented by formula (VI)

[0245] [ka]

[0246] is a residue of an amino acid R 4a H, OH, COOH, CONH2, X 4 , and -NH-CO-X 4 and X is selected from the group consisting of 4 is selected from the group consisting of (C1-C6) alkyl, (C5-C6) aryl, and (C5-C6) heteroaryl; and X 4 is optionally substituted by one or two substituents selected from the group consisting of methyl, CONH2, halogen, NH2, and OH; q=1, 2, or 3; one or two hydrogen atoms of said one, two, or three CH— groups are optionally and independently replaced by methyl, ethyl, (C-C)aryl, or (C-C)heteroaryl; R 4b is methyl or H, Xaa5 is structure (VII)

[0247] [ka]

[0248] is a residue of an amino acid R 5 is selected from the group of OH and NH; r=1, 2, or 3, Xaa6 is an amino acid selected from the group consisting of aromatic L-α-amino acids and heteroaromatic L-α-amino acids, Xaa7 is a compound represented by formula (IX)

[0249] [ka]

[0250] is an aminothiol or amino acid residue of R 7a -CO-, -COOH, -CONH2, -CH2-OH, -(CO)-NH-R 7b , -(CO)-(NR 7c )-R 7b , or H, R 7b and R 7c are each independently (C1-C4) alkyl; t is 1 or 2, Yc is the formula (X)

[0251] [ka]

[0252] and connecting the S atom of Xaa1 with the S atom of Xaa7 under the formation of two thioether linkages, thereby forming a compound of formula (XXI)

[0253] [ka]

[0254] forming a ring structure of the substitution pattern of the aromatic group of formula (X) is meta; n=0 or 1, t=1 or 2, Y 1 is CH, Y 2 is CR c1 and R c1 CH2-R c2 and R c2 is represented by formula (XIId)

[0255] [ka]

[0256] The structure is u=1, 2, 3, 4, 5, or 6, preferably 1; R c4 is H or methyl, Z is a chelator, optionally including a linker; The N-terminal modification group A is a blocking group Ab1, and the blocking group Ab1 is R a11 -C(O)-, and R a11 is a C4 alkyl or a C5 alkyl, and in each and any one of the C4 alkyl and C5 alkyl individually and independently one of said -CH2- groups is optionally replaced by -O- or -S-. Embodiment 170. R a11 is C5 alkyl. Embodiment 171. R a11 The compound according to embodiment 170, wherein is n-pentyl. Embodiment 172. R a11 Structure (XXX)

[0257] [ka]

[0258] 171. The compound of embodiment 170, wherein Embodiment 173. R a11 is C4 alkyl. Embodiment 174. R a11 The compound of embodiment 173, wherein is n-butyl. Embodiment 175. R a11 Structure (XXXI)

[0259] [ka]

[0260] 170. The compound of embodiment 169, wherein Embodiment 176. R a11 Structure (XXXII)

[0261] [ka]

[0262] 170. The compound of embodiment 169, wherein Embodiment 177. R a11 Structure (XXXIII)

[0263] [ka]

[0264] 170. The compound of embodiment 169, wherein Embodiment 178. The chelator Z is of Formula (XIId)

[0265] [ka]

[0266] The compound of any one of embodiments 169 to 177, wherein the N atom of the structure: Embodiment 179. The compound of embodiment 170, wherein u=1. Embodiment 180. Rc4 The compound according to any one of embodiments 178 and 179, wherein is H. Embodiment 181. The compound of any one of embodiments 169, 170, 171, 172, 173, 174, 175, 176, and 177, wherein the chelator Z comprises a linker. Embodiment 182. The linker is covalently bonded to the chelator and has Formula (XIId)

[0267] [ka]

[0268] The compound of embodiment 181, wherein the N atom of the structure: Embodiment 183 The compound of embodiment 182, wherein u=1. Embodiment 184. R c4 The compound according to any one of embodiments 182 and 183, wherein is H. Embodiment 185 The compound of any one of embodiments 181, 182, 183, and 184, wherein the linker is selected from the group consisting of Ttds and O2Oc. Embodiment 186 The compound of any one of embodiments 181, 182, 183, and 184, wherein the linker is Ttds. Embodiment 187 The compound of any one of embodiments 181, 182, 183, and 184, wherein the linker is O2Oc. Embodiment 188. The compound of any one of embodiments 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, and 187, wherein Xaa1 is a D-amino acid residue selected from the group consisting of cys, hcy, and pen, or Xaa1 is an L-amino acid residue selected from the group consisting of Cys, Hcy, and Pen. Embodiment 189 The compound of embodiment 188, wherein Xaa1 is Cys. Embodiment 190. The compound of any one of embodiments 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 187, 188, and 189, wherein Xaa2 is an amino acid residue selected from the group consisting of Pro, Gly, Nmg, and derivatives thereof. Embodiment 191 The compound of embodiment 190, wherein Xaa2 is an amino acid residue selected from the group consisting of Pro and Nmg. Embodiment 192 The compound of any one of embodiments 190 and 191, wherein Xaa2 is the amino acid residue of Pro. Embodiment 193 The compound of any one of embodiments 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 187, 188, 189, 190, 191, and 192, wherein Xaa3 is an amino acid residue selected from the group consisting of Pro, Hyp, Tfp, Cfp, Dmp, Aze, and Pip, and derivatives thereof. Embodiment 194 The compound of embodiment 193, wherein Xaa3 is an amino acid residue of Pro. Embodiment 195. The compound of any one of embodiments 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 187, 188, 189, 190, 191, 192, 193, and 194, wherein Xaa4 is an amino acid residue selected from the group consisting of Thr, Hse, Asn, Gln, and Ser, and derivatives thereof. Embodiment 196 The compound of embodiment 195, wherein Xaa4 is Thr. Embodiment 197. The compound of any one of embodiments 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 187, 188, 189, 190, 191, 192, 193, 194, 195, and 196, wherein Xaa5 is an amino acid residue selected from the group consisting of Gln and Glu, and derivatives thereof. Embodiment 198 The compound of embodiment 197, wherein Xaa5 is an amino acid residue selected from the group consisting of Gln and Glu. Embodiment 199 The compound of embodiment 198, wherein Xaa5 is an amino acid residue of Gln. Embodiment 200. A compound according to embodiment 199, wherein Xaa5 is an amino acid residue of Glu. Embodiment 201. Xaa6 is selected from the group consisting of formulas (VIIIa), (VIIIb), (VIIIc), and (VIIId)

[0269] [ka]

[0270] is any one of the amino acid residues R 6a and R 6b are each independently selected from the group consisting of H, methyl, ethyl, propyl, and isopropyl; R 6c represents 0 to 3 substituents, each of which is independently Cl, F, Br, NO2, NH2, CN, CF3, OH, OR 6d and C1-C4 alkyl; R 6d is selected from the group consisting of methyl, ethyl, propyl, and isopropyl; The compound of any one of embodiments 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, and 200, wherein s is 0 or 1. Embodiment 202. Xaa6 is selected from the group consisting of formulas (VIIIa), (VIIIb), (VIIIc), and (VIIId)

[0271] [ka]

[0272] is any one of the amino acid residues R 6a and R 6b are H, respectively, R 6c represents 0 to 2 substituents, each of which is independently Cl, F, Br, NO2, NH2, CN, CF3, OH, OR 6d and methyl; R 6d is selected from the group consisting of methyl, ethyl, propyl, and isopropyl; The compound of embodiment 201, wherein s is 0. Embodiment 203 The compound of any one of Embodiments 201 to 202, wherein Xaa6 is an amino acid residue selected from the group consisting of Phe, Ocf, Ppa, Thi, 1Ni, Otf, and Mpa, and derivatives thereof. Embodiment 204 The compound of embodiment 203, wherein Xaa6 is an amino acid residue of Phe. Embodiment 205. The compound of any one of embodiments 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, and 204, wherein Xaa7 is an aminothiol residue selected from the group consisting of Cys, Cys-OH, Cys-NH2, Cysol, AET, Hcy, cys, cys-OH, cys-NH2, and hcy. Embodiment 206 The compound of embodiment 205, wherein Xaa7 is an aminothiol residue selected from the group consisting of Cys, Cys-OH, Cys-NH2, Cysol, and AET. Embodiment 207 The compound of embodiment 206, wherein Xaa7 is an aminothiol residue of Cys or Cys-NH2, preferably Cys-OH. Embodiment 208. Xaa1 is an amino acid residue of Cys, Xaa2 is an amino acid residue of Pro or Nmg, preferably an amino acid residue of Pro; Xaa3 is an amino acid residue of Pro, Xaa4 is an amino acid residue of Thr; Xaa5 is an amino acid residue of Gln or Glu, preferably an amino acid residue of Gln; Xaa6 is an amino acid residue of Phe; 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, and 207. The compound of any one of embodiments 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, and 207, wherein Xaa7 is an amino acid residue of Cys. Embodiment 209. Xaa1 is an amino acid residue of Cys, Xaa2 is an amino acid residue of Pro, Xaa3 is an amino acid residue of Pro, Xaa4 is an amino acid residue of Thr; Xaa5 is an amino acid residue of Gln, Xaa6 is an amino acid residue of Phe; 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, and 207. The compound of any one of embodiments 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, and 207, wherein Xaa7 is an amino acid residue of Cys. Embodiment 210. Xaa1 is an amino acid residue of Cys, Xaa2 is an amino acid residue of Pro, Xaa3 is an amino acid residue of Pro, Xaa4 is an amino acid residue of Thr; Xaa5 is an amino acid residue of Glu, Xaa6 is an amino acid residue of Phe; 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, and 207. The compound of any one of embodiments 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, and 207, wherein Xaa7 is an amino acid residue of Cys. Embodiment 211. Xaa1 is an amino acid residue of Cys, Xaa2 is an amino acid residue of Nmg; Xaa3 is an amino acid residue of Pro, Xaa4 is an amino acid residue of Thr; Xaa5 is an amino acid residue of Gln, Xaa6 is an amino acid residue of Phe; 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, and 207. The compound of any one of embodiments 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, and 207, wherein Xaa7 is an amino acid residue of Cys. Embodiment 212. Z is 99m Tc(CO)3-chelators, CB-TE2A, CHX-A”-DTPA, DTPA, DATA, DFO, HBED, Crown, DOTAGA, DOTAM (also known as TCMC), FSC, H4octapa, Macropa, HEHA, HOPO, Hynic, PCTA, PSC, NETA, DOTA, NODA-MPAA, NODAGA, NOTP, N x S 4-x 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, and 211, wherein the compound is a chelator selected from the group consisting of (N4, N2S2, N3S), NOPO, NOTA, Pycup, RESCA, sarcofagin, TETA, THP, and TRAP. Embodiment 213. The compound of embodiment 212, wherein Z is a chelator selected from the group consisting of DOTAM, Macropa, PCTA, DOTA, N4Ac, NODAGA, NOPO, and NOTA. Embodiment 214: The following formula

[0273] [ka]

[0274] The compound iHex-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3907), The following formula

[0275] [ka]

[0276] The compound Pent-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3910), The following formula

[0277] [ka]

[0278] The compound EtOPr-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3918), The following formula

[0279] [ka]

[0280] The compound MeOBut-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3937), The following formula

[0281] [ka]

[0282] The compound PrOAc-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3938), The following formula

[0283] [ka]

[0284] The compound nBu-COyl-[Cys(tMeBn(DOTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-3941), The following formula

[0285] [ka]

[0286] The compound Hex-[Cys(tMeBn(DATA-Ttds-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH(3BP-4384), The following formula

[0287] [ka]

[0288] The compound Hex-[Cys(tMeBn(NODAGA-AET))-Pro-Pro-Thr-Glu-Phe-Cys]-OH (3BP-4695), The following formula

[0289] [ka]

[0290] The compound Hex-[Cys(tMeBn(NODAGA-O2Oc-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-NH2(3BP-4708), The following formula

[0291] [ka]

[0292] The compound Hex-[Cys(tMeBn(NOPO-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-NH2 (3BP-4729), The following formula

[0293] [ka]

[0294] The compound Hex-[Cys(tMeBn(NOPO-AET))-Pro-Pro-Thr-Glu-Phe-Cys]-OH (3BP-4818), The following formula

[0295] [ka]

[0296] the compound Hex-[Cys(tMeBn(AcPCTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-5273), The following formula

[0297] [ka]

[0298] the compound Hex-[Cys(tMeBn(LSC-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-5288), and The following formula

[0299] [ka]

[0300] The compound Hex-[Cys(tMeBn(DOTAM-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (3BP-5323) 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, and 213, wherein the compound is selected from the group consisting of: Embodiment 215. The compound of any one of embodiments 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, and 214, wherein the chelator comprises a nuclide, preferably wherein the nuclide is coordinatively bonded to the chelator. Embodiment 216 The compound of embodiment 215, wherein the nuclide is a diagnostically active nuclide or a therapeutically active nuclide. Embodiment 217 The compound of embodiment 216, wherein the diagnostically active nuclide is a diagnostically active radionuclide. Embodiment 218. The diagnostically active radionuclide is 18 F, 43 Sc, 44 Sc, 51 Mn, 52 Mn, 64 Cu, 67 Ga, 68 Ga, 76 Br, 77 Br, 86 Y, 89 Zr, 94m Tc, 99m Tc, 111 In, 123 I, 124 I, 125 I, 152 Tb, 155 Tb, 177 Lu, 201 Tl, and203 218. The compound of embodiment 217, selected from the group consisting of Pb. Embodiment 219. The diagnostically active radionuclide is: 18 F, 68 Ga, 99m Tc, 111 In, and 203 219. The compound of embodiment 218, wherein the compound is selected from the group consisting of: Pb. Embodiment 220 The compound of embodiment 216, wherein the therapeutically active nuclide is a therapeutically active radionuclide. Embodiment 221. The therapeutically active radionuclide is 47 Sc, 67 Cu, 89 Sr, 90 Y, 131 I, 111 In, 153 Sm, 149 Tb, 161 Tb, 177 Lu, 186 Re, 188 Re, 211 At, 212 Pb, 213 Bi, 223 Ra, 224 Ra, 225 Ac, 226 Th, and 227 The compound of embodiment 220, selected from the group consisting of Th. Embodiment 222. The therapeutically active radionuclide is 90 Y, 177 Lu, 212 Pb, and 225 The compound of embodiment 221, wherein the compound is Ac. Embodiment 223. A method of interacting with a fibroblast activation protein (FAP), preferably a human FAP having the amino acid sequence of SEQ ID NO: 1, or a homolog thereof, wherein the amino acid sequence of the homolog has at least 85% identity with the amino acid sequence of SEQ ID NO: 1, as described in any one of embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 2, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 1 13, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169 , 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, and 222. Embodiment 224 The compound of embodiment 223 which is an inhibitor of fibroblast activation protein (FAP). Embodiment 225. pIC against human FAP of SEQ ID NO: 1 50 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 23, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175 , 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, and 224. Embodiment 226. The method of any of embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68 for use in a method for diagnosing a disease. , 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131 , 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, and 225, preferably a compound according to any one of embodiments 5 to 55, 110 to 114, 161 to 165, and 215 to 219. Embodiment 227. A compound for use according to embodiment 226, wherein the disease is a disease involving upregulated expression of fibroblast activation protein (FAP), preferably fibroblast activation protein (FAP). Embodiment 228. A compound for use according to any one of embodiments 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, and 227, wherein the disease involves diseased tissue comprising cells exhibiting upregulated expression of fibroblast activation protein (FAP), preferably cells exhibiting upregulated expression of fibroblast activation protein (FAP), more preferably a disease involving fibroblasts associated with a tumor. Embodiment 229. A compound for use according to any one of embodiments 226, 227, and 228, wherein the disease is a neoplasm, preferably a cancer or tumor. Embodiment 230. The compound for use according to embodiment 229, wherein the neoplasms, cancers, and tumors are each individually selected from the group comprising solid tumors, epithelial tumors, bladder cancer, breast cancer, cervical cancer, colorectal cancer, cholangiocarcinoma, endometrial cancer, esophageal cancer, gastric cancer, gastrointestinal stromal tumors, head and neck cancer, liver cancer, lung cancer, melanoma, mesothelioma, neuroendocrine tumors and carcinomas, ovarian cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, salivary gland cancer, sarcoma, squamous cell carcinoma, and thyroid cancer. Embodiment 231. The compound for use according to embodiment 230, wherein the neoplasms, cancers, and tumors are each individually selected from the group comprising breast cancer, colorectal cancer, cholangiocarcinoma, head and neck cancer, lung cancer, mesothelioma, neuroendocrine tumors and carcinomas, ovarian cancer, pancreatic cancer, prostate cancer, sarcoma, and squamous cell carcinoma. Embodiment 232. A compound for use according to any one of embodiments 226, 227, and 228, wherein the disease is selected from the group comprising inflammatory diseases, cardiovascular diseases, autoimmune diseases, and fibrotic diseases. Embodiment 233 The compound for use according to embodiment 232, wherein the disease is an inflammatory disease. Embodiment 234. A compound for use according to embodiment 233, wherein the disease is atherosclerosis, arthritis, or rheumatoid arthritis. Embodiment 235 The compound for use according to embodiment 232, wherein the disease is a cardiovascular disease. Embodiment 236. A compound for use according to embodiment 235, wherein the disease is a cardiovascular disease associated with atherosclerotic plaques. Embodiment 237. A compound for use according to embodiment 236, wherein the disease is an atherosclerotic lesion caused by plaque rupture, acute coronary syndrome, myocardial infarction, thrombosis, or vascular occlusion. Embodiment 238 The compound for use according to embodiment 232, wherein the disease is a fibrotic disease. Embodiment 239. A compound for use according to embodiment 238, wherein the disease is selected from the group comprising idiopathic pulmonary fibrosis, Crohn's disease, and hepatic fibrosis. Embodiment 240. A compound for use according to any one of embodiments 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, and 239, comprising a diagnostically active nuclide, preferably a diagnostically active radionuclide. Embodiment 241. The diagnostically active radionuclide is 18 F, 43 Sc, 44 Sc, 51 Mn, 52 Mn, 64 Cu, 67 Ga, 68 Ga, 76 Br, 77 Br, 86 Y, 89 Zr, 94m Tc, 99m Tc, 111 In, 123 I, 124 I, 125 I, 152 Tb, 155 Tb, 177 Lu, 201 Tl, and 203 Pb, preferably 18 F, 68 Ga, 99m Tc, 111 In, and 203241. The compound for use according to embodiment 240, selected from the group consisting of Pb. Embodiment 242. The compound for use according to any one of embodiments 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, and 241, wherein the method for diagnosis is an imaging method. Embodiment 243. The compound for use according to embodiment 242, wherein the imaging method is selected from the group consisting of scintigraphy, single photon emission computed tomography (SPECT), and positron emission tomography (PET). Embodiment 244. The compound for use according to any one of embodiments 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, and 243, wherein the method comprises administering a diagnostically effective amount of the compound to a subject, preferably a mammal, wherein the mammal is selected from the group comprising humans, companion animals, pets, and livestock, more preferably the subject is selected from the group comprising humans, dogs, cats, horses, and cows, and most preferably the subject is a human. Embodiment 245. The compound of any of embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 1 1, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135 , 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 187, 188, 189, 190, 191, 192, 193 , 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, and 225, preferably a compound according to any one of embodiments 51, 52, 56 to 58, 110, 111, 115 to 117, 161, 162, 166 to 168, 215, 216, and 220 to 222. Embodiment 246. A compound for use according to embodiment 245, wherein the disease is a disease involving upregulated expression of fibroblast activation protein (FAP), preferably fibroblast activation protein (FAP). Embodiment 247. A compound for use according to any one of embodiments 245 to 246, wherein the disease involves diseased tissue comprising cells exhibiting upregulated expression of fibroblast activation protein (FAP), preferably cells exhibiting upregulated expression of fibroblast activation protein (FAP), more preferably a disease involving fibroblasts associated with a tumor. Embodiment 248. A compound for use according to any one of embodiments 245, 246, and 247, wherein the disease is a neoplasm, preferably a cancer or tumor. Embodiment 249. The compound for use according to embodiment 248, wherein the neoplasms, cancers, and tumors are each individually selected from the group comprising solid tumors, epithelial tumors, bladder cancer, breast cancer, cervical cancer, colorectal cancer, cholangiocarcinoma, endometrial cancer, esophageal cancer, gastric cancer, gastrointestinal stromal tumors, head and neck cancer, liver cancer, lung cancer, melanoma, mesothelioma, neuroendocrine tumors and carcinomas, ovarian cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, salivary gland cancer, sarcoma, squamous cell carcinoma, and thyroid cancer. Embodiment 250. The compound for use according to embodiment 249, wherein the neoplasms, cancers, and tumors are each individually selected from the group comprising breast cancer, colorectal cancer, cholangiocarcinoma, head and neck cancer, lung cancer, mesothelioma, neuroendocrine tumors and carcinomas, ovarian cancer, pancreatic cancer, prostate cancer, sarcoma, and squamous cell carcinoma. Embodiment 251. A compound for use according to any one of embodiments 245, 246, and 247, wherein the disease is selected from the group comprising inflammatory diseases, cardiovascular diseases, autoimmune diseases, and fibrotic diseases. Embodiment 252 The compound for use according to embodiment 251, wherein the disease is an inflammatory disease. Embodiment 253. A compound for use according to embodiment 252, wherein the disease is atherosclerosis, arthritis, or rheumatoid arthritis. Embodiment 254 The compound for use according to embodiment 251, wherein the disease is a cardiovascular disease. Embodiment 255. A compound for use according to embodiment 254, wherein the disease is a cardiovascular disease associated with atherosclerotic plaques. Embodiment 256. A compound for use according to embodiment 255, wherein the disease is an atherosclerotic lesion caused by plaque rupture, acute coronary syndrome, myocardial infarction, thrombosis, or vascular occlusion. Embodiment 257 The compound for use according to embodiment 251, wherein the disease is a fibrotic disease. Embodiment 258. A compound for use according to embodiment 257, wherein the disease is selected from the group comprising idiopathic pulmonary fibrosis, Crohn's disease, and hepatic fibrosis. Embodiment 259. A compound for use according to any one of embodiments 245, 246, 247, and 248, comprising a therapeutically active nuclide, preferably a therapeutically active radionuclide. Embodiment 260. The therapeutically active nuclide is 47 Sc, 67 Cu, 89 Sr, 90 Y, 131 I, 111 In, 153 Sm, 149 Tb, 161 Tb, 177 Lu, 186 Re, 188 Re, 211 At, 212 Pb, 213 Bi, 223 Ra, 224 Ra, 225 Ac, 226 Th, and 227 Th, preferably 90 Y, 177 Lu, 212 Pb, and 225 The compound for use according to embodiment 259, selected from the group consisting of Ac. Embodiment 261. The compound for use according to any one of embodiments 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, and 260, wherein the method comprises administering a therapeutically effective amount of the compound to a subject, preferably a mammal, wherein the mammal is selected from the group comprising humans, companion animals, pets, and livestock, more preferably the subject is selected from the group comprising humans, dogs, cats, horses, and cattle, and most preferably the subject is a human. Embodiment 262. Any of embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, for use in a method for identifying a subject. 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114 4, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 1 5, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 1 6, 177, 178, 179, 180, 181, 182, 183, 184, 185, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336,243, and 244. Embodiment 263. The method of any one of embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 5, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112 2, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144 3, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 1 74, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 2 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334,32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 10 2, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 21 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, and 225, preferably comprising performing a method for the diagnosis of a disease as described in any one of embodiments 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, and 244. Embodiment 264. Any of embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62 for use in a method for stratifying a group of subjects into subjects likely to respond to treatment of a disease and subjects not likely to respond to treatment of a disease. , 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164 , 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332,33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 209, 2010, 2011, 201 6, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, and 225, preferably comprising performing a method for the diagnosis of a disease as described in any one of embodiments 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, and 244. Embodiment 265. A compound for use according to any one of embodiments 262, 263, and 264, wherein the disease is a disease associated with upregulated expression of fibroblast activation protein (FAP), preferably fibroblast activation protein (FAP). Embodiment 266. A compound for use according to any one of embodiments 262, 263, 264, and 265, wherein the disease involves diseased tissue comprising cells exhibiting upregulated expression of fibroblast activation protein (FAP), preferably cells exhibiting upregulated expression of fibroblast activation protein (FAP), more preferably a disease involving fibroblasts associated with a tumor. Embodiment 267. A compound for use according to any one of embodiments 262, 263, 264, 165, and 266, wherein the disease is a neoplasm, preferably a cancer or tumor. Embodiment 268. The compound for use according to embodiment 267, wherein the neoplasms, cancers, and tumors are each individually selected from the group comprising solid tumors, epithelial tumors, bladder cancer, breast cancer, cervical cancer, colorectal cancer, cholangiocarcinoma, endometrial cancer, esophageal cancer, gastric cancer, gastrointestinal stromal tumors, head and neck cancer, liver cancer, lung cancer, melanoma, mesothelioma, neuroendocrine tumors and carcinomas, ovarian cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, salivary gland cancer, sarcoma, squamous cell carcinoma, and thyroid cancer. Embodiment 269. The compound for use according to embodiment 268, wherein the neoplasms, cancers, and tumors are each individually selected from the group comprising breast cancer, colorectal cancer, cholangiocarcinoma, head and neck cancer, lung cancer, mesothelioma, neuroendocrine tumors and carcinomas, ovarian cancer, pancreatic cancer, prostate cancer, sarcoma, and squamous cell carcinoma. Embodiment 270. A compound for use according to any one of embodiments 262, 263, 264, 265, and 266, wherein the disease is selected from the group comprising inflammatory diseases, cardiovascular diseases, autoimmune diseases, and fibrotic diseases. Embodiment 271. A compound for use according to embodiment 270, wherein the disease is an inflammatory disease. Embodiment 272. A compound for use according to embodiment 271, wherein the disease is atherosclerosis, arthritis, or rheumatoid arthritis. Embodiment 273. A compound for use according to embodiment 272, wherein the disease is a cardiovascular disease. Embodiment 274. A compound for use according to embodiment 273, wherein the disease is a cardiovascular disease associated with atherosclerotic plaques. Embodiment 275. A compound for use according to embodiment 274, wherein the disease is an atherosclerotic lesion caused by plaque rupture, acute coronary syndrome, myocardial infarction, thrombosis, or vascular occlusion. Embodiment 276 The compound for use according to embodiment 270, wherein the disease is a fibrotic disease. Embodiment 277. A compound for use according to embodiment 276, wherein the disease is selected from the group comprising idiopathic pulmonary fibrosis, Crohn's disease, and hepatic fibrosis. Embodiment 278. The compound for use according to any one of embodiments 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, and 277, wherein the method of diagnosis is an imaging method. Embodiment 279. The compound for use according to embodiment 278, wherein the imaging method is selected from the group comprising scintigraphy, single photon emission computed tomography (SPECT), and positron emission tomography (PET). Embodiment 280. The compound for use according to any one of embodiments 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, and 279, comprising a diagnostically active nuclide, preferably a diagnostically active radionuclide. Embodiment 281. The diagnostically active nuclide is: 18 F, 43 Sc, 44 Sc, 51 Mn, 52 Mn, 64 Cu, 67 Ga, 68 Ga, 76 Br, 77 Br, 86 Y, 89 Zr, 94m Tc, 99m Tc, 111 In, 123 I, 124I, 125 I, 152 Tb, 155 Tb, 177 Lu, 201 Tl, and 203 Pb, preferably 18 F, 68 Ga, 99m Tc, 111 In, and 203 281. The compound for use according to embodiment 280, selected from the group consisting of Pb. Embodiment 282. The method of any one of embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, for use in a method for delivering an effector to a fibroblast activation protein (FAP), preferably a human fibroblast activation protein (FAP). 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 1 25, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 2 216, 217, 218, 219, 220, 221, 222, 223, 224, and 225, wherein the effector is selected from the group comprising diagnostically active agents and therapeutically active agents. Embodiment 283. The compound for use according to embodiment 282, wherein the effector is selected from the group comprising diagnostically active nuclides and therapeutically active nuclides. Embodiment 284 The compound for use according to embodiment 283, wherein the diagnostically active nuclide is a diagnostically active radionuclide. Embodiment 285. The diagnostically active nuclide is: 18 F, 43 Sc, 44 Sc, 51 Mn, 52 Mn, 64 Cu, 67 Ga, 68 Ga, 76 Br, 77 Br, 86 Y, 89 Zr, 94m Tc, 99m Tc, 111 In, 123 I, 124 I, 125 I, 152 Tb, 155 Tb, 177 Lu, 201 Tl, and 203 Pb, preferably 18 F, 68 Ga, 99m Tc, 111 In, and 203 285. The compound for use according to embodiment 284, selected from the group consisting of Pb. Embodiment 286. The compound for use according to any one of embodiments 282, 283, 284, and 285, wherein the fibroblast activation protein (FAP) is expressed by a cell, preferably a fibroblast, mesenchymal stem cell, smooth muscle cell, cell of epithelial origin, or endothelial cell, more preferably a human fibroblast, mesenchymal stem cell, smooth muscle cell, cell of epithelial origin, or endothelial cell, most preferably a human fibroblast, mesenchymal stem cell, smooth muscle cell, cell of epithelial origin, or endothelial cell, each of which exhibits upregulated expression of fibroblast activation protein (FAP). Embodiment 287. The compound for use according to embodiment 286, wherein the cell is contained in or is part of a tissue, preferably a diseased tissue of a subject suffering from a disease. Embodiment 288. A compound for use according to embodiment 287, wherein the disease involves diseased tissue comprising cells exhibiting upregulated expression of fibroblast activation protein (FAP), preferably cells exhibiting upregulated expression of fibroblast activation protein (FAP), more preferably a disease involving fibroblasts associated with a tumor. Embodiment 289. A compound for use according to any one of embodiments 287 to 288, wherein the disease is a neoplasm, preferably a cancer or tumor. Embodiment 290. The compound for use according to embodiment 289, wherein the neoplasms, cancers, and tumors are each individually selected from the group comprising solid tumors, epithelial tumors, bladder cancer, breast cancer, cervical cancer, colorectal cancer, cholangiocarcinoma, endometrial cancer, esophageal cancer, gastric cancer, gastrointestinal stromal tumors, head and neck cancer, liver cancer, lung cancer, melanoma, mesothelioma, neuroendocrine tumors and carcinomas, ovarian cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, salivary gland cancer, sarcoma, squamous cell carcinoma, and thyroid cancer. Embodiment 291. The compound for use according to embodiment 290, wherein the neoplasms, cancers, and tumors are each individually selected from the group comprising breast cancer, colorectal cancer, cholangiocarcinoma, head and neck cancer, lung cancer, mesothelioma, neuroendocrine tumors and carcinomas, ovarian cancer, pancreatic cancer, prostate cancer, sarcoma, and squamous cell carcinoma. Embodiment 292. A compound for use according to any one of embodiments 287 to 288, wherein the disease is selected from the group comprising inflammatory diseases, cardiovascular diseases, autoimmune diseases, and fibrotic diseases. Embodiment 293 The compound for use according to embodiment 292, wherein the disease is an inflammatory disease. Embodiment 294. A compound for use according to embodiment 293, wherein the disease is atherosclerosis, arthritis, or rheumatoid arthritis. Embodiment 295 The compound for use according to embodiment 292, wherein the disease is a cardiovascular disease. Embodiment 296. A compound for use according to embodiment 295, wherein the disease is a cardiovascular disease associated with atherosclerotic plaques. Embodiment 297. A compound for use according to embodiment 296, wherein the disease is an atherosclerotic lesion caused by plaque rupture, acute coronary syndrome, myocardial infarction, thrombosis, or vascular occlusion. Embodiment 298. The compound for use according to embodiment 292, wherein the disease is a fibrotic disease. Embodiment 299. A compound for use according to embodiment 298, wherein the disease is selected from the group comprising idiopathic pulmonary fibrosis, Crohn's disease, and hepatic fibrosis. Embodiment 300. The compound for use according to embodiment 283, wherein the therapeutically active nuclide is a therapeutically active radionuclide. Embodiment 301. The therapeutically active radionuclide is 47 Sc, 67 Cu, 89 Sr, 90 Y, 131 I, 111 In, 153 Sm, 149 Tb, 161 Tb, 177 Lu, 186 Re, 188 Re, 211 At, 212 Pb, 213 Bi, 223 Ra, 224 Ra, 225 Ac, 226 Th, and 227 Th, preferably 90 Y, 177 Lu, 212 Pb, and 225 The compound for use according to embodiment 300, selected from the group consisting of Ac. Embodiment 302. The compound for use according to any one of embodiments 300 to 301, wherein the fibroblast activation protein (FAP) is expressed by a cell, preferably a fibroblast, mesenchymal stem cell, smooth muscle cell, cell of epithelial origin, or endothelial cell, more preferably a human fibroblast, mesenchymal stem cell, smooth muscle cell, cell of epithelial origin, or endothelial cell, most preferably a human fibroblast, mesenchymal stem cell, smooth muscle cell, cell of epithelial origin, or endothelial cell that exhibits upregulated expression of fibroblast activation protein (FAP). Embodiment 303. The compound for use according to embodiment 302, wherein the cell is contained in or is part of a tissue, preferably a diseased tissue of a subject suffering from a disease. Embodiment 304. A compound for use according to embodiment 303, wherein the disease involves cells that exhibit upregulated expression of fibroblast activation protein (FAP), preferably diseased tissue comprising cells that exhibit upregulated expression of fibroblast activation protein (FAP), more preferably a disease involving fibroblasts associated with a tumor. Embodiment 305. A compound for use according to any one of embodiments 302, 303, and 304, wherein the disease is a neoplasm, preferably a cancer or tumor. Embodiment 306. The compound for use according to embodiment 305, wherein the neoplasms, cancers, and tumors are each individually selected from the group comprising solid tumors, epithelial tumors, bladder cancer, breast cancer, cervical cancer, colorectal cancer, cholangiocarcinoma, endometrial cancer, esophageal cancer, gastric cancer, gastrointestinal stromal tumors, head and neck cancer, liver cancer, lung cancer, melanoma, mesothelioma, neuroendocrine tumors and carcinomas, ovarian cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, salivary gland cancer, sarcoma, squamous cell carcinoma, and thyroid cancer. Embodiment 307. Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72 , 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 1 32, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, and 225, and a pharmaceutically acceptable excipient. Embodiment 308. The composition of embodiment 307 for use in any method defined in any of the preceding claims. Embodiment 309. A method for diagnosing a disease in a subject, comprising administering to a subject a diagnostically effective amount of any one of Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63 , 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126 6, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 22 80, 181, 182, 183, 184, 185, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, and 225 to the subject. Embodiment 310 The method of embodiment 309, wherein the compound comprises a diagnostically active agent, the agent preferably being a radionuclide. Embodiment 311. A method for treating a disease in a subject, comprising administering a therapeutically effective amount of any one of embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64 , 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, and 225 to the subject. Embodiment 312 The method of embodiment 311, wherein the compound comprises a therapeutically active agent, the agent preferably being a radionuclide. Embodiment 313 The method of any one of embodiments 309, 310, 311, and 312, wherein the disease is a disease associated with fibroblast activation protein (FAP), preferably upregulated expression of fibroblast activation protein (FAP). Embodiment 314. The method of any one of embodiments 309, 310, 311, 312, and 313, wherein the disease involves diseased tissue containing cells that exhibit upregulated expression of fibroblast activation protein (FAP), preferably cells that exhibit upregulated expression of fibroblast activation protein (FAP), more preferably a disease involving tumor-associated fibroblasts. Embodiment 315. The method of any one of embodiments 309, 310, 311, 312, 313, and 314, wherein the disease is selected from the group comprising neoplasia, preferably cancer or tumor, and inflammatory diseases, cardiovascular diseases, autoimmune diseases, and fibrotic diseases. Embodiment 316. Embodiments 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 43, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202 20. A kit comprising a compound according to any one of claims 2, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, optionally one or more excipients, and optionally one or more devices, wherein the device is selected from the group comprising a labeling device, a purification device, a handling device, a radiation protection device, an analytical device, or an administration device. Embodiment 317. The kit of embodiment 316 for use in any method defined in any of the preceding embodiments.

[0301] More specifically, the problem underlying the present invention is, in a first aspect, to provide a compound of formula (I)

[0302] [ka]

[0303] Cyclic peptides and an N-terminal modification group A attached to Xaa1, the peptide sequence is drawn from left to right in the N-terminal to C-terminal direction; Xaa1 is a compound represented by formula (II)

[0304] [ka]

[0305] is a residue of an amino acid R 1a is -NH-, R 1b is H or CH3, n=0 or 1, the N-terminal modification group A is covalently bound to the nitrogen atom of Xaa1; The carbonyl group of Xaa1 is covalently bonded to the nitrogen of Xaa2, The sulfur atom of Xaa1 is covalently bonded to Yc as a thioether, Xaa2 is represented by formula (III), (IV), or (XX)

[0306] [ka]

[0307] is a residue of an amino acid R 2a , R 2b , R 2care each independently selected from the group consisting of (C1-C2)alkyl and H, and the (C1-C2)alkyl is optionally substituted with a substituent selected from the group consisting of OH, NH2, halogen, and (C5-C7)cycloalkyl; p=0, 1, or 2; v=1 or 2, w=1, 2, or 3, the amino acid of formula (IV) is optionally substituted at positions 3 and 4 of the indicated ring with one or two substituents selected from the group consisting of methyl, OH, NH, and F; Xaa3 is a compound of formula (V) or (XX)

[0308] [ka]

[0309] is a residue of an amino acid X 3 CH2, CF2, CH-R 3b , S, O, and NH; p=1 or 2, v=1 or 2, w=1, 2, or 3, R 3a is H, methyl, OH, NH2, or F, R 3b is methyl, OH, NH2, or F, Xaa4 is a compound represented by formula (VI)

[0310] [ka]

[0311] is a residue of an amino acid R 4a H, OH, COOH, CONH2, X 4 , and -NH-CO-X 4 and X is selected from the group consisting of 4is selected from the group consisting of (C1-C6) alkyl, (C5-C6) aryl, and (C5-C6) heteroaryl; and X 4 is optionally substituted by one or two substituents selected from the group consisting of methyl, CONH2, halogen, NH2, and OH; q=1, 2, or 3; one or two hydrogen atoms of said one, two, or three CH— groups are optionally and independently replaced by methyl, ethyl, (C-C)aryl, or (C-C)heteroaryl; R 4b is methyl or H, Xaa5 is structure (VII)

[0312] [ka]

[0313] is a residue of an amino acid R 5 is selected from the group of OH and NH; r=1, 2, or 3, Xaa6 is an amino acid selected from the group consisting of aromatic L-α-amino acids and heteroaromatic L-α-amino acids, Xaa7 is a compound represented by formula (IX)

[0314] [ka]

[0315] is an aminothiol or amino acid residue of R 7a -CO-, -COOH, -CONH2, -CH2-OH, -(CO)-NH-R 7b , -(CO)-(NR 7c )-R 7b , or H and R 7b and R 7c are each independently (C1-C4) alkyl; t is 1 or 2, Yc is the formula (X)

[0316] [ka]

[0317] and connecting the S atom of Xaa1 with the S atom of Xaa7 under the formation of two thioether linkages, thereby forming a compound of formula (XXI)

[0318] [ka]

[0319] forming a ring structure of the substitution pattern of the aromatic group of formula (X) is ortho, meta, or para; n=0 or 1, t=1 or 2, Y 1 is CH or N, Y 2 is N or CR c1 and R c1 is H or CH2-R c2 and R c2 is of formula (XI), (XII), or (XXII)

[0320] [ka]

[0321] The structure is R c3 and R c4 are each independently selected from the group consisting of H and (C1-C4) alkyl; u=1, 2, 3, 4, 5, or 6, x and y are each independently 1, 2, or 3; X=O or S, In formulas (XI) and (XXII), one of the nitrogen atoms is R c1In formula (XII), -X- is bonded to -CH2- in R c1 is bonded to -CH2- The N-terminal modification group A is a blocking group Ab1, and the blocking group Ab1 is R a1 -NH-C(O)-, and R a1 is selected from the group consisting of C3 alkyl, C4 alkyl, or C5 alkyl, each independently substituted with up to two substituents independently selected from the group consisting of OH, F, COOH, (C3-C8)cycloalkyl, aryl, heteroaryl, and (C3-C8)heterocycle, wherein one of the -CH2- groups in the (C1-C8)alkyl is optionally replaced by -S- or -O-.

[0322] More specifically, the problem underlying the present invention is, in a second aspect, to provide a compound of formula (I)

[0323] [ka]

[0324] and an N-terminal modification group A attached to Xaa1, the peptide sequence is drawn from left to right in the N-terminal to C-terminal direction; Xaa1 is a compound represented by formula (II)

[0325] [ka]

[0326] is a residue of an amino acid R 1a is -NH-, R 1b is H or CH3, n=0 or 1, the N-terminal modification group A is covalently bound to the nitrogen atom of Xaa1; The carbonyl group of Xaa1 is covalently bonded to the nitrogen of Xaa2, The sulfur atom of Xaa1 is covalently bonded to Yc as a thioether, Xaa2 is represented by formula (III), (IV), or (XX)

[0327] [ka]

[0328] is a residue of an amino acid R 2a , R 2b , R 2c are each independently selected from the group consisting of (C1-C2)alkyl and H, and the (C1-C2)alkyl is optionally substituted with a substituent selected from the group consisting of OH, NH2, halogen, and (C5-C7)cycloalkyl; p=0, 1, or 2; v=1 or 2, w=1, 2, or 3, the amino acid of formula (IV) is optionally substituted at positions 3 and 4 of the indicated ring with one or two substituents selected from the group consisting of methyl, OH, NH, and F; Xaa3 is a compound represented by formula (V) or (XX)

[0329] [ka]

[0330] is a residue of an amino acid X 3 CH2, CF2, CH-R 3b , S, O, and NH; p=1 or 2, v=1 or 2, w=1, 2, or 3, R 3a is H, methyl, OH, NH2, or F, R 3b is methyl, OH, NH2, or F, Xaa4 is a compound represented by formula (VI)

[0331] [ka]

[0332] is a residue of an amino acid R 4a H, OH, COOH, CONH2, X 4 , and -NH-CO-X 4 and X is selected from the group consisting of 4 is selected from the group consisting of (C1-C6) alkyl, (C5-C6) aryl, and (C5-C6) heteroaryl; and X 4 is optionally substituted by one or two substituents selected from the group consisting of methyl, CONH2, halogen, NH2, and OH; q=1, 2, or 3; one or two hydrogen atoms of said one, two, or three CH— groups are optionally and independently replaced by methyl, ethyl, (C-C)aryl, or (C-C)heteroaryl; R 4b is methyl or H, Xaa5 is structure (VII)

[0333] [ka]

[0334] is a residue of an amino acid R 5 is selected from the group of OH and NH; r=1, 2, or 3, Xaa6 is an amino acid selected from the group consisting of aromatic L-α-amino acids and heteroaromatic L-α-amino acids, Xaa7 is a compound represented by formula (IX)

[0335] [ka]

[0336] is an aminothiol or amino acid residue of R 7a -CO-, -COOH, -CONH2, -CH2-OH, -(CO)-NH-R 7b , -(CO)-(NR 7c )-R 7b , or H and R 7b and R 7c are each independently (C1-C4) alkyl; t is 1 or 2, Yc is the formula (X)

[0337] [ka]

[0338] and connecting the S atom of Xaa1 with the S atom of Xaa7 under the formation of two thioether linkages, thereby forming a compound of formula (XXI)

[0339] [ka]

[0340] forming a ring structure of the substitution pattern of the aromatic group of formula (X) is ortho, meta, or para, preferably meta; n=0 or 1, t=1 or 2, Y 1 is CH, Y 2 is CR c1 and R c1 CH2-R c2 or H, R c2 is represented by formula (XIId) or (XXIIc)

[0341] [ka]

[0342] The structure is u=1, R c4 is H, Z is a chelator, optionally including a linker; The N-terminal modification group A is a blocking group Ab1, and the blocking group Ab1 is R a1 -NH-C(O)-, and R a1 is (C1-C8)alkyl optionally substituted with up to two substituents each independently selected from the group consisting of OH, F, COOH, (C3-C8)cycloalkyl, aryl, heteroaryl, and (C3-C8)heterocycle, and in the (C1-C8)alkyl one of the -CH2- groups is optionally replaced by -S- or -O-.

[0343] More specifically, the problem underlying the present invention is, in a third aspect, to provide a compound of formula (I)

[0344] [ka]

[0345] and an N-terminal modification group A attached to Xaa1, the peptide sequence is drawn from left to right in the N-terminal to C-terminal direction; Xaa1 is a compound represented by formula (II)

[0346] [ka]

[0347] is a residue of an amino acid R 1a is -NH-, R 1b is H or CH3, n=0 or 1, the N-terminal modification group A is covalently bound to the nitrogen atom of Xaa1; The carbonyl group of Xaa1 is covalently bonded to the nitrogen of Xaa2, The sulfur atom of Xaa1 is covalently bonded to Yc as a thioether, Xaa2 is represented by formula (III), (IV), or (XX)

[0348] [ka]

[0349] is a residue of an amino acid R 2a , R 2b , R 2c are each independently selected from the group consisting of (C1-C2)alkyl and H, and the (C1-C2)alkyl is optionally substituted with a substituent selected from the group consisting of OH, NH2, halogen, and (C5-C7)cycloalkyl; p=0, 1, or 2; v=1 or 2, w=1, 2, or 3, the amino acid of formula (IV) is optionally substituted at positions 3 and 4 of the indicated ring with one or two substituents selected from the group consisting of methyl, OH, NH, and F; Xaa3 is a compound represented by formula (V) or (XX)

[0350] [ka]

[0351] is a residue of an amino acid X 3 CH2, CF2, CH-R 3b , S, O, and NH; p=1 or 2, v=1 or 2, w=1, 2, or 3, R 3a is H, methyl, OH, NH2, or F, R 3bis methyl, OH, NH2, or F, Xaa4 is a compound represented by formula (VI)

[0352] [ka]

[0353] is a residue of an amino acid R 4a H, OH, COOH, CONH2, X 4 , and -NH-CO-X 4 and X is selected from the group consisting of 4 is selected from the group consisting of (C1-C6) alkyl, (C5-C6) aryl, and (C5-C6) heteroaryl; and X 4 is optionally substituted by one or two substituents selected from the group consisting of methyl, CONH2, halogen, NH2, and OH; q=1, 2, or 3; one or two hydrogen atoms of said one, two, or three CH— groups are optionally and independently replaced by methyl, ethyl, (C-C)aryl, or (C-C)heteroaryl; R 4b is methyl or H, Xaa5 is structure (VII)

[0354] [ka]

[0355] is a residue of an amino acid R 5 is selected from the group of OH and NH; r=1, 2, or 3, Xaa6 is an amino acid selected from the group consisting of aromatic L-α-amino acids and heteroaromatic L-α-amino acids, Xaa7 is a compound represented by formula (IX)

[0356] [ka]

[0357] is an aminothiol or amino acid residue of R 7a -CO-, -COOH, -CONH2, -CH2-OH, -(CO)-NH-R 7b , -(CO)-(NR 7c )-R 7b , or H and R 7b and R 7c are each independently (C1-C4) alkyl; t is 1 or 2, Yc is the formula (X)

[0358] [ka]

[0359] and connecting the S atom of Xaa1 with the S atom of Xaa7 under the formation of two thioether linkages, thereby forming a compound of formula (XXI)

[0360] [ka]

[0361] forming a ring structure of the substitution pattern of the aromatic group of formula (X) is meta; n=0 or 1, t=1 or 2, Y 1 is CH or N, Y 2 is CR c1 and R c1 is H, the N-terminal modification group A is the amino acid Aaa, Amino acid Aaa is structure (XIV)

[0362] [ka]

[0363] is an L-amino acid residue of R a2 is selected from the group consisting of (C1-C6) alkyl and modified (C1-C6) alkyl; In the modified (C1-C6) alkyl, one -CH2- group is replaced by -S- or -O-; the amino acid Aaa is covalently attached to a linker, the linker is covalently attached to a chelator Z, the linker consisting of (a) a first linker or (b) a first linker and a second linker; when the linker consists of the first linker, the first linker is covalently attached to the chelator and to the amino acid Aaa; when the first linker consists of a first linker and a second linker, the first linker is covalently bonded to the amino acid Aaa and the second linker, and the second linker is covalently bonded to the chelator; the first linker is selected from the group consisting of Ttds and PEG6, preferably the first linker is Ttds; The problem is solved by a compound, wherein said second linker is selected from the group consisting of PPAc and PEG6, preferably said second linker is PPAc.

[0364] More specifically, the problem underlying the present invention is, in a fourth aspect, to provide a compound of formula (I)

[0365] [ka]

[0366] and an N-terminal modification group A attached to Xaa1, the peptide sequence is drawn from left to right in the N-terminal to C-terminal direction; Xaa1 is a compound represented by the formula (II)

[0367] [ka]

[0368] is a residue of an amino acid R 1a is -NH-, R 1b is H or CH3, n=0 or 1, the N-terminal modification group A is covalently bound to the nitrogen atom of Xaa1; The carbonyl group of Xaa1 is covalently bonded to the nitrogen of Xaa2, The sulfur atom of Xaa1 is covalently bonded to Yc as a thioether, Xaa2 is represented by formula (III), (IV), or (XX)

[0369] [ka]

[0370] is a residue of an amino acid R 2a , R 2b , R 2c are each independently selected from the group consisting of (C1-C2)alkyl and H, and the (C1-C2)alkyl is optionally substituted with a substituent selected from the group consisting of OH, NH2, halogen, and (C5-C7)cycloalkyl; p=0, 1, or 2; v=1 or 2, w=1, 2, or 3, the amino acid of formula (IV) is optionally substituted at positions 3 and 4 of the indicated ring with one or two substituents selected from the group consisting of methyl, OH, NH, and F; Xaa3 is a compound of formula (V) or (XX)

[0371] [ka]

[0372] is a residue of an amino acid X 3 CH2, CF2, CH-R 3b , S, O, and NH; p=1 or 2, v=1 or 2, w=1, 2, or 3, R 3a is H, methyl, OH, NH2, or F, R 3b is methyl, OH, NH2, or F, Xaa4 is a compound represented by formula (VI)

[0373] [ka]

[0374] is a residue of an amino acid R 4a H, OH, COOH, CONH2, X 4 , and -NH-CO-X 4 and X is selected from the group consisting of 4 is selected from the group consisting of (C1-C6) alkyl, (C5-C6) aryl, and (C5-C6) heteroaryl; and X 4 is optionally substituted by one or two substituents selected from the group consisting of methyl, CONH2, halogen, NH2, and OH; q=1, 2, or 3; one or two hydrogen atoms of said one, two, or three CH— groups are optionally and independently replaced by methyl, ethyl, (C-C)aryl, or (C-C)heteroaryl; R 4b is methyl or H, Xaa5 is structure (VII)

[0375] [ka]

[0376] is a residue of an amino acid R 5 is selected from the group of OH and NH; r=1, 2, or 3, Xaa6 is an amino acid selected from the group consisting of aromatic L-α-amino acids and heteroaromatic L-α-amino acids, Xaa7 is a compound represented by formula (IX)

[0377] [ka]

[0378] is an aminothiol or amino acid residue of R 7a -CO-, -COOH, -CONH2, -CH2-OH, -(CO)-NH-R 7b , -(CO)-(NR 7c )-R 7b , or H and R 7b and R 7c are each independently (C1-C4) alkyl; t is 1 or 2, Yc is the formula (X)

[0379] [ka]

[0380] and connecting the S atom of Xaa1 with the S atom of Xaa7 under the formation of two thioether linkages, thereby forming a compound of formula (XXI)

[0381] [ka]

[0382] forming a ring structure of the substitution pattern of the aromatic group of formula (X) is meta; n=0 or 1, t=1 or 2, Y 1 is CH, Y 2 is CR c1 and R c1 CH2-R C2 and R C2 is represented by formula (XIId)

[0383] [ka]

[0384] The structure is u=1, 2, 3, 4, 5, or 6, preferably u=1; R c4 is H or methyl, Z is a chelator, optionally including a linker; The N-terminal modification group A is a blocking group Ab1, and the blocking group Ab1 is R a11 -C(O)-, and R a11 is a C4 alkyl or a C5 alkyl, and in each and any one of the C4 alkyl and C5 alkyl individually and independently one of said -CH2- groups is optionally replaced by -O- or -S-.

[0385] More specifically, in a fifth aspect the problem underlying the present invention is solved by a compound according to the first, second, third and fourth aspects, including any embodiment, for use in a method for the diagnosis of a disease.

[0386] More specifically, in a sixth aspect the problem underlying the present invention is solved by a compound according to the first, second, third and fourth aspects, including any embodiment, for use in a method for the treatment of a disease.

[0387] More particularly, in a seventh aspect the problem underlying the present invention is solved by a compound according to the first, second, third and fourth aspect, including any of its embodiments, for use in a method for identifying a subject, wherein the subject is likely to respond or not to respond to treatment of a disease, the method for identifying a subject comprising performing a method of diagnosis using a compound according to the first, second, third and fourth aspect, including any of its embodiments.

[0388] More particularly, in an eighth aspect the problem underlying the present invention is solved by a compound according to the first, second, third and fourth aspect, including any embodiment thereof, for use in a method of selecting subjects from a population of subjects, wherein the subjects are likely to respond or not to respond to treatment of a disease, the method of selecting subjects from a population of subjects comprising performing a method of diagnosis using a compound according to the first, second, third and fourth aspect, including any embodiment.

[0389] More particularly, in a ninth aspect the problem underlying the present invention is solved by a compound according to the first, second, third and fourth aspect, including any embodiment thereof, for use in a method of stratifying a population of subjects into those likely to respond to a disease treatment and those unlikely to respond to a disease treatment, wherein the method for stratifying subjects comprises performing a method of diagnosis using a compound according to the first, second, third and fourth aspect, including any embodiment.

[0390] More specifically, in a tenth aspect, the problem underlying the present invention is solved by a composition, preferably a pharmaceutical composition, comprising a compound according to the first, second, third and fourth aspects, including any of their embodiments, and a pharmaceutically acceptable excipient.

[0391] More specifically, in an eleventh aspect the problem underlying the present invention is solved by a method for diagnosing a disease in a subject, the method comprising administering to the subject a diagnostically effective amount of a compound according to the first, second, third and fourth aspects, including any embodiment thereof.

[0392] More specifically, in a twelfth aspect the problem underlying the present invention is solved by a method for the treatment of a disease in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound according to the first, second, third and fourth aspects, including any of their embodiments.

[0393] More specifically, in a thirteenth aspect the problem underlying the present invention is solved by a kit comprising a compound according to the first, second, third and fourth aspects including any embodiment, one or more optional excipient(s), and optionally one or more device(s), wherein the device(s) are selected from the group comprising a labelling device, a purification device, a manipulation device, a radioprotection device, an analytical device or an administration device.

[0394] One of ordinary skill in the art will recognize that a compound or compounds of the present invention is any compound disclosed herein, including, but not limited to, any compound described in any of the above embodiments and any of the following embodiments.

[0395] One of ordinary skill in the art will recognize that a method or methods of the present invention is any method disclosed herein, including, but not limited to, any method described in any of the above embodiments and any of the following embodiments.

[0396] Those of ordinary skill in the art will recognize that a composition or compositions of the present invention is any composition disclosed herein, including, but not limited to, any composition described in any of the above embodiments and any of the following embodiments.

[0397] Those skilled in the art will recognize that a kit or kits of the present invention is any kit disclosed herein, including, but not limited to, any kit described in any of the above embodiments and any of the following embodiments.

[0398] It is recognized that in the context of the present invention, any embodiment of any aspect of the invention may be an embodiment of any other aspect of the invention, including any embodiment thereof. Because no cyclic peptide-based inhibitors specific for fibroblast activation proteins (FAPs) with nanomolar affinity have been previously described, the present invention is based on the inventors' surprising discovery that the compounds of the present invention, and more particularly the cyclic peptides thereof, provide highly specific binding of compounds comprising such cyclic peptides to FAPs.

[0399] Furthermore, the present invention is based on the surprising discovery that a chelator can be attached to the cyclic peptide at three different positions, directly or indirectly, i.e., using a linker. The first position is Yc having the structure of formula (X), which connects the S atom of Xaa1 and the S atom of Xaa7, thus forming two thioether linkages; the second position is Aaa attached to Xaa1 of the cyclic peptide of formula (I), and the third position is an amino acid or peptide attached to Xaa7. Surprisingly, the attachment of such a chelator does not significantly affect the binding of the compound of the present invention to FAPs and the inhibitory properties of the compound of the present invention against FAPs, respectively. In one embodiment, the present invention relates to a cyclic peptide of formula (I) in which a chelator (Z group) is attached to only one of the first, second, or third positions defined above. It is also within the scope of the present invention that a chelator is attached to the cyclic peptide of formula (I) at any combination of the first, second, and third positions defined above. More specifically, the present invention also relates to compounds of formula (I) in which a Z group is attached to both the first and second positions as defined above, compounds of formula (I) in which a Z group is attached to both the first and third positions as defined above, compounds of formula (I) in which a Z group is attached to both the second and third positions as defined above, and compounds of formula (I) in which a Z group is attached to the first, second, and third positions as defined above. These compounds containing two or three Z groups can be realized in any embodiment of the invention disclosed herein.

[0400] Finally, the present inventors have found that the compounds of the present invention are surprisingly stable in plasma, surprisingly useful as imaging agents, and effective in shrinking tumors. The term "alkyl" as used herein preferably refers to saturated, straight-chain or branched hydrocarbon groups, and is usually accompanied by a modifier that designates the number of carbon atoms that it may contain.For example, the term (C1-C6) alkyl refers to methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 1-methyl-butyl, 1-ethyl-propyl, 3-methyl-butyl, 1,2-dimethyl-propyl, 2-methyl-butyl, 1,1-dimethyl-propyl, 2,2-dimethylpropyl, n-hexyl, 1,1-dimethyl-butyl, and any other isoform of alkyl groups containing 6 saturated carbon atoms.

[0401] In certain embodiments, as preferably used herein, (C1-C2) alkyl refers independently to either methyl or ethyl. In certain embodiments, as preferably used herein, (C1-C3) alkyl refers to each and individually methyl, ethyl, n-propyl, and isopropyl.

[0402] In certain embodiments, and as preferably used herein, (C1-C4) alkyl refers to each and independently any of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and tert-butyl.

[0403] In certain embodiments, as preferably used herein, (C1-C6)alkyl means each and individually methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-pentyl, 2-methyl-butyl, 3-methyl-butyl, 3-pentyl, 3-methyl-but-2-yl, 2-methyl-but-2-yl, 2,2-dimethylpropyl, n-hexyl, 2-hexyl, 2-methyl-pent ...hexyl, 2-hexyl, 2-hexyl, 2-hexyl, 2-hexyl, 2-hexyl, 2-hexyl, 2-hexyl, 2-hexyl, 2-hexyl, 2-hexyl, 2-hexyl, 2-hexyl, 2-hexyl, 2-hexyl, 2-hexyl, 2-hexyl, 2-hexyl, 2-hexyl, butyl, 3-methyl-pentyl, 4-methyl-pentyl, 3-hexyl, 2-ethyl-butyl, 2-methyl-pent-2-yl, 2,2-dimethyl-butyl, 3,3-dimethyl-butyl, 3-methyl-pent-2-yl, 4-methyl-pent-2-yl, 2,3-dimethyl-butyl, 3-methyl-pent-3-yl, 2-methyl-pent-3-yl, 2,3-dimethyl-but-2-yl and 3,3-dimethyl-but-2-yl.

[0404] In certain embodiments, as preferably used herein, (C1-C8) alkyl refers to a saturated or unsaturated, straight or branched chain hydrocarbon group having from 1 to 8 carbon atoms. Representative (C1-C8) alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-pentyl, 2-methyl-butyl, 3-methyl-butyl, 3-pentyl, 3-methyl-but-2-yl, 2-methyl-but-2-yl, 2,2-dimethylpropyl, n-hexyl, 2-hexyl, 2-methyl-pentyl, 3-methyl-pentyl, 4-methyl-pentyl , 3-hexyl, 2-ethyl-butyl, 2-methyl-pent-2-yl, 2,2-dimethyl-butyl, 3,3-dimethyl-butyl, 3-methyl-pent-2-yl, 4-methyl-pent-2-yl, 2,3-dimethyl-butyl, 3-methyl-pent-3-yl, 2-methyl-pent-3-yl, 2,3-dimethyl-but-2-yl, 3,3-dimethyl-but-2-yl, n-heptyl, 2-heptyl, 2-methyl-hexyl, 3-methyl-hexyl, 4-methyl hexyl, 5-methylhexyl, 3-heptyl, 2-ethylpentyl, 3-ethylpentyl, 4-heptyl, 2-methylhex-2-yl, 2,2-dimethylpentyl, 3,3-dimethylpentyl, 4,4-dimethylpentyl, 3-methylhex-2-yl, 4-methylhex-2-yl, 5-methylhex-2-yl, 2,3-dimethylpentyl, 2,4-dimethyl ethyl-pentyl, 3,4-dimethyl-pentyl, 3-methyl-hex-3-yl, 2-ethyl-2-methyl-butyl, 4-methyl-hex-3-yl, 5-methyl-hex-3-yl, 2-ethyl-3-methyl-butyl, 2,3-dimethyl-pent-2-yl, 2,4-dimethyl-pent-2-yl, 3,3-dimethyl-pent-2-yl, 4,4-dimethyl-pent-2-yl, 2,2,3-trimethyl-butyl, 2,3,3-trimethyl-butyl, 2,3,3-trimethyl-but-2-yl, n-octyl, 2-octyl, 2-methyl-heptyl, 3-methyl-heptyl, 4-methyl-heptyl, 5-methyl-heptyl, 6-methyl-heptyl, 3-octyl, 2-ethyl-hexyl, 3-ethyl-hexyl, 4-ethyl-hexyl, 4-octyl, 2-propyl-pentyl, 2-methyl-hept-2-yl, 2,2-dimethyl-hexyl, 3,3-dimethyl-hexyl, 4,4-dimethyl-hexyl, 5,5-dimethyl-hexyl, 3-methyl-hept-2-yl, 4-methyl-hept-2-yl, 5 -Methyl-hept-2-yl, 6-methyl-hept-2-yl, 2,3-dimethyl-hex-1-yl, 2,4-dimethyl-hex-1-yl, 2,5-dimethyl-hex-1-yl, 3,4-dimethyl-hex-1-yl, 3,5-dimethyl-hex-1-yl, 3,5-dimethyl-hex-1-yl, 3-methyl-hept-3-yl, 2-ethyl-2-methyl-1-yl, 3-ethyl-3-methyl-1-yl, 4-methyl-hept-3-yl, 5-methyl-hept-3-yl, 6-methyl-hept-3-yl, 2-ethyl-3-methyl-pentyl , 2-ethyl-4-methyl-pentyl, 3-ethyl-4-methyl-pentyl, 2,3-dimethyl-hex-2-yl, 2,4-dimethyl-hex-2-yl, 2,5-dimethyl-hex-2-yl, 3,3-dimethyl-hex-2-yl, 3,4-dimethyl-hex-2-yl, 3,5-dimethyl-hex-2-yl, 4,4-dimethyl-hex-2-yl, 4,5-dimethyl-hex-2-yl, 5,5-dimethyl-hex-2-yl, 2,2,3-trimethyl-pentyl, 2,2,4-trimethyl-pentyl, 2,3,3-trimethyl-pentyl butyl, 2,3,4-trimethylpentyl, 2,4,4-trimethylpentyl, 3,3,4-trimethylpentyl, 3,4,4-trimethylpentyl, 2,3,3-trimethylpent-2-yl, 2,3,4-trimethylpent-2-yl, 2,4,4-trimethylpent-2-yl, 3,4,4-trimethylpent-2-yl, 2,2,3,3-tetramethylbutyl, 3,4-dimethylhex-3-yl, 3,5-dimethylhex-3-yl, 4,4-dimethylhex-3-yl, 4,5-dimethylhex-3-yl, 5,and any of 5-dimethyl-hex-3-yl, 3-ethyl-3-methyl-pent-2-yl, 3-ethyl-4-methyl-pent-2-yl, 3-ethyl-hex-3-yl, 2,2-diethyl-butyl, 3-ethyl-3-methyl-pentyl, 4-ethyl-hex-3-yl, 5-methyl-hept-3-yl, 2-ethyl-3-methyl-pentyl, 4-methyl-hept-4-yl, 3-methyl-hept-4-yl, 2-methyl-hept-4-yl, 3-ethyl-hex-2-yl, 2-ethyl-2-methyl-pentyl, 2-isopropyl-pentyl, 2,2-dimethyl-hex-3-yl, 2,2,4-trimethyl-pent-3-yl, and 2-ethyl-3-methyl-pentyl. The (C-C) alkyl group can be unsubstituted or substituted with one or more groups including, but not limited to, (C-C) alkyl, -O-[(C-C) alkyl], -aryl, -CO-R', -O-CO-R', -CO-OR', -CO-NH, -CO-NHR', -CO-NR', -NH-CO-R', -SO-R', -SO-R', -OH, -halogen, -N, -NH, -NHR', -NR' and -CN, where each R' is independently selected from -(C-C) alkyl and aryl.

[0405] The term "alkylidene" as used herein preferably refers to a saturated straight or branched hydrocarbon group in which two substitution points are specified. Simple alkyl chains in which the two substitution points are at the maximum distance from each other, such as methane-1,1-diyl, ethane-1,2-diyl, propane-1,3-diyl, butane-1,4-diyl and pentane-1,5-diyl, are also called methylene (also called methane-1,1-diyl), ethylene (also called ethane-1,2-diyl), propylene (also called propane-1,3-diyl), butylene (also called butane-1,4-diyl) and pentylene (also called pentane-1,5-diyl).

[0406] In an embodiment, preferably as used herein, (C1-C 10)Alkylidene means, individually, methylene, ethane-1,2-diyl, propane-1,3-diyl, propane-1,2-diyl, butane-1,4-diyl, butane-1,3-diyl, butane-1,2-diyl, 2-methyl-propane-1,2-diyl, 2-methyl-propane-1,3-diyl, pentane-1,5-diyl, pentane-1,4-diyl, pentane-1,3-diyl, pentane-1,2-diyl, pentane-2,3-diyl, pentane hexane-1,6-diyl, any other isomer having 6 carbon atoms, heptane-1,7-diyl, any other isomer having 7 carbon atoms, octane-1,8-diyl, any other isomer having 8 carbon atoms, nonane-1,9-diyl, any other isomer having 9 carbon atoms, decane-1,10-diyl and any other isomer having 10 carbon atoms, preferably (C1-C 10 ) Alkylidene means, each independently, any of methylene, ethane-1,2-diyl, propane-1,3-diyl, butane-1,4-diyl, pentane-1,5-diyl, hexane-1,6-diyl, heptane-1,7-diyl, octane-1,8-diyl, nonane-1,9-diyl, and decane-1,10-diyl. (C1-C 10 ) Alkylidene groups can be unsubstituted or substituted with one or more groups including, but not limited to, (C1-C8) alkyl, -O-[(C1-C8) alkyl], -aryl, -CO-R', -O-CO-R', -CO-OR', -CO-NH, -CO-NHR', -CO-NR'2, -NH-CO-R', -SO2-R', -SO-R', -OH, -halogen, -N3, -NH2, -NHR', -NR'2 and -CN, where each R' is independently selected from -(C1-C8) alkyl and aryl.

[0407] In certain embodiments, as preferably used herein, (C3-C8)cycloalkyl means each and independently any of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.

[0408] In certain embodiments, as preferably used herein, (C5-C7)cycloalkyl refers independently to any of cyclopentyl, cyclohexyl, and cycloheptyl.

[0409] In certain embodiments, as preferably used herein, a (C3-C8)carbocycle refers to a 3-, 4-, 5-, 6-, 7-, or 8-membered saturated or unsaturated non-aromatic carbon ring. Representative (C3-C8)carbocycles include, but are not limited to, any of -cyclopropyl, -cyclobutyl, -cyclopentyl, -cyclopentadienyl, -cyclohexyl, -cyclohexenyl, -1,3-cyclohexadienyl, -1,4-cyclohexadienyl, -cycloheptyl, -1,3-cycloheptadienyl, -1,3,5-cycloheptatrienyl, -cyclooctyl, and -cyclooctadienyl. A (C3-C8) carbocyclic group can be unsubstituted or substituted with one or more groups including, but not limited to, (C1-C8) alkyl, -O-[(C1-C8) alkyl], -aryl, -CO-R', -O-CO-R', -CO-OR', -CO-NH2, -CO-NHR', -CO-NR'2, -NH-CO-R', -SO2-R', -SO-R', -OH, -halogen, -N3, -NH2, -NHR', -NR'2 and -CN, where each R' is independently selected from -(C1-C8) alkyl and aryl.

[0410] In certain embodiments, and as preferably used herein, (C-C)carbocyclo refers to a (C-C)carbocyclic group as defined above, in which one of the carbocyclic group hydrogen atoms is replaced with a bond.

[0411] In certain embodiments, and as preferably used herein, "aryl" refers to a carbocyclic aromatic group. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, and anthracenyl.

[0412] In certain embodiments, as preferably used herein, (C5-C6)aryl refers to a carbocyclic aromatic group containing 5 or 6 carbon atoms. The carbocyclic aromatic group can be unsubstituted or substituted with, but not limited to, -(C1-C8)alkyl, -O-[(C1-C8)alkyl], -aryl, -CO-R', -O-CO-R', -CO-OR', -CO-NH2, -CO-NHR', -CO-NR'2, -NH-CO-R', -SO2-R', -SO-R', -OH, -halogen, -N3, -NH2, -NHR', -NR'2 and -CN, where each R' is independently selected from -(C1-C8)alkyl and aryl.

[0413] In certain embodiments, and as preferably used herein, "heteroaryl" refers to a heterocyclic aromatic group. Examples of heteroaryl groups include, but are not limited to, furan, thiophene, pyridine, pyrimidine, benzothiophene, benzofuran, and quinoline.

[0414] In certain embodiments, as preferably used herein, (C5-C6)heteroaryl refers to a heteroaromatic group consisting of 5 or 6 ring atoms, at least one of which is different from carbon, preferably nitrogen, sulfur, or oxygen. The heteroaromatic group can be unsubstituted or substituted with one or more groups, including but not limited to -(C1-C8)alkyl, -O-[(C1-C8)alkyl], aryl, -CO-R', -O-CO-R', -CO-OR', -CO-NH2, -CO-NHR', -CO-NR'2, -NH-CO-R', -SO2-R', -SO-R', -OH, -halogen, -N3, -NH2, -NHR', -NR'2, and -CN, where each R' is independently selected from -(C1-C8)alkyl and aryl.

[0415] In certain embodiments, as preferably used herein, (C-C)heterocyclo refers to a (C-C)heterocyclic group as defined above, in which one of the hydrogen atoms of the carbocyclic group is replaced with a bond. The (C-C)heterocyclo can be unsubstituted or substituted with up to six groups, including (C-C)alkyl, -O-[(C-C)alkyl], -aryl, -CO-R', -O-CO-R', -CO-OR', -CO-NH, -CO-NHR', -CO-NR', -NH-CO-R', -SO-R', -SO-R', -OH, -halogen, -N, -NH, -NHR', -NR', and -CN, where each R' is independently selected from -(C-C)alkyl and aryl.

[0416] In certain embodiments, as preferably used herein, arylene refers to a group having two covalent bonds and having the following structure:

[0417] [ka]

[0418] wherein the phenyl group can be unsubstituted or substituted with up to four groups including, but not limited to, (C-C) alkyl, -O-[(C-C) alkyl], -aryl, -CO-R', -O-CO-R', -CO-OR', -CO-NH, -CO-NHR', -CO-NR', -NH-CO-R', -SO-R', -SO-R', -OH, -halogen, -N, -NH, -NHR', -NR' and -CN, where each R' is independently selected from -(C-C) alkyl and aryl.

[0419] In an embodiment of each and any aspect, including any embodiment, any S atom that can be oxidized, preferably an S atom of a thioether group, is present as -S-, -S(O)-, or -S(O)-, or a mixture thereof.

[0420] In some embodiments, as used herein, preferably, in any structural formula or in any context of this specification, including claims, an atom with an unspecified atomic mass number is either an unspecified isotopic composition, a naturally occurring isotopic mixture, or an individual isotope.This particularly applies to carbon, oxygen, nitrogen, sulfur, phosphorus, halogen and metal atoms, such as, but not limited to, C, O, N, S, F, P, Cl, Br, At, Sc, Cr, Mn, Co, Fe, Cu, Ga, Sr, Zr, Y, Mo, Tc, Ru, Rh, Pd, Pt, Ag, In, Sb, Sn, Te, I, Pr, Pm, Dy, Sm, Gd, Tb, Ho, Dy, Er, Yb, Tm, Lu, Sn, Re, Rd, Os, Ir, Au, Pb, Bi, Po, Fr, Ra, Ac, Th and Fm.

[0421] In certain embodiments, as preferably used herein, a chelator is a compound capable of forming a chelate, whereby the chelator is a compound, preferably a cyclic compound, in which a metal or moiety having an electron gap or lone pair participates in the formation of a ring. More preferably, the chelator is a compound of this type in which a single ligand occupies more than one coordination site at the central atom.

[0422] In certain embodiments, as preferably used herein, a diagnostically active compound is a compound that is suitable or useful in the diagnosis of disease. In certain embodiments, as preferably used herein, a diagnostic agent or diagnostically active agent is a compound that is suitable or useful in the diagnosis of disease.

[0423] In certain embodiments, as preferably used herein, a therapeutically active compound is a compound that is suitable or useful in the treatment of a disease. In certain embodiments, a therapeutic agent or therapeutically active agent, as preferably used herein, is a compound suitable or useful in the treatment of a disease.

[0424] In certain embodiments, as preferably used herein, a diagnostically therapeutically active compound is a compound that is suitable or useful for both the diagnosis and treatment of a disease. In certain embodiments, as preferably used herein, a diagnostic therapeutic agent or diagnostic therapeutically active agent is a compound that is suitable or useful for both the diagnosis and treatment of a disease.

[0425] In certain embodiments, diagnostic therapeutics, as preferably used herein, is a method for the combined diagnosis and treatment of a disease, preferably wherein the combined diagnostically and therapeutically active compounds used in the diagnostic therapeutics are radiolabeled.

[0426] In certain embodiments, treatment of a disease, as used herein, is treatment and / or prevention of a disease. In certain embodiments, as preferably used herein, a disease involving a FAP refers to a disease in which cells, including but not limited to fibroblasts, that express a FAP, preferably in an upregulated manner, and tissues containing or comprising cells, such as fibroblasts, that express a FAP, or that express a FAP, preferably in an upregulated manner, respectively, are the sole cause of the disease and / or symptoms of the disease, or are part of the underlying pathology of the disease. A preferred FAP-expressing cell is a cancer-associated fibroblast (CAF). In disease embodiments, preferably when used in connection with disease treatment, treating, and / or therapy, the effect on the cells, tissue, and pathology, respectively, results in a cure, treatment, or amelioration of the disease and / or symptoms of the disease. In disease embodiments, preferably when used in connection with disease diagnosis and / or therapy, labeling of FAP-expressing cells and / or FAP-expressing tissues can distinguish or differentiate the cells and / or tissues from healthy or non-FAP-expressing cells and / or healthy or non-FAP-expressing tissues. More preferably, such discrimination or differentiation forms the basis of the above-mentioned diagnosis and diagnosing, respectively. In that embodiment, labeling refers to the interaction of a detectable label, directly or indirectly, with FAP-expressing cells and / or FAP-expressing tissues or tissues containing such FAP-expressing cells, and more preferably, such interaction involves or is based on the interaction of a label or a compound bearing such a label with the FAP.

[0427] In one embodiment, as preferably used herein, a target cell is a cell that expresses a FAP and is the sole or sole cause of a disease and / or symptoms of a disease, or is part of the underlying pathology of a disease.

[0428] In one embodiment, and preferably as used herein, a non-target cell is a cell that does not express a FAP and / or is not the sole or sole cause of the disease and / or symptoms of the disease, or is not part of the underlying pathology of the disease.

[0429] In certain embodiments, as preferably used herein, a neoplasm is an abnormal new growth of cells. Cells in a neoplasm proliferate more rapidly than normal cells and continue to proliferate if not treated. Neoplasms can be benign or malignant.

[0430] In certain embodiments, a tumor, as preferably used herein, is a mass lesion that can be benign or malignant. In certain embodiments, cancer, as preferably used herein, is a malignant neoplasm.

[0431] In some embodiments, as preferably used herein, a linkage is a bond between two atoms of two independent moieties. A preferred linkage is a chemical bond or multiple chemical bonds. More preferably, the chemical bond is a covalent bond or multiple chemical bonds. Most preferably, the linkage is a covalent bond or a coordinate bond. As preferably used herein, an embodiment of a coordinate bond is the bond or bonds realized when a metal is bound by a chelator. Depending on the type of atoms connected and their atomic environment, different types of linkages are created. These types of linkages are defined by the type of atomic arrangement created by the linkage. For example, the linkage between an amine-containing moiety and a carboxylic acid-containing moiety results in a linkage called an amide (also called an amide linkage, -CO-N-, -N-CO-). Those skilled in the art will recognize that the following examples of creating this and other linkages are merely prototypical examples and in no way limit the scope of this application. Those skilled in the art will recognize that the combination of an amine-containing moiety with an isothiocyanate-containing moiety results in a thiourea (also referred to as a thiourea linkage, -N-CS-N-), and the combination of a C-atom-containing moiety with a thiol group (-C-SH) results in a thioether (also referred to as a thioether linkage, -CSC-). A non-limiting list of linkages preferably used in connection with the chelators and linkers of the present invention, and their characteristic types of atomic arrangements, is provided in Table 2.

[0432] [Table 2]

[0433] In some embodiments of the present invention, examples of reactive groups used to form linkages between chelators and linkers, or to form direct bonds between chelators and compounds of the present invention, are summarized in Table 3. However, it will be understood by those skilled in the art that the linkages that can be achieved in embodiments for forming conjugates of the present invention are not limited to those in Table 3, nor are the reactive groups that form such linkages limited.

[0434] [Table 3]

[0435] The following are reactive groups and functional groups that are utilized or suitable for forming linkages between moieties or structures used in embodiments of the conjugates of the present invention. Primary or secondary amino, carboxylic acid, activated carboxylic acid, chloro, bromo, iodo, sulfhydryl, hydroxyl, sulfonic acid, activated sulfonic acid, sulfonate esters like mesylate or tosylate, Michael acceptors, trans cyclooctene, isocyanate, isothiocyanate, azide, alkyne and strained alkenes like tetrazine.

[0436] As preferably used herein, the term "activated carboxylic acid" refers to a carboxylic acid group having the general formula -CO-X, where X is a leaving group. For example, activated forms of the carboxylic acid group can include, but are not limited to, acyl chlorides, symmetrical or asymmetrical anhydrides, and esters. In some embodiments, the activated carboxylic acid group is an ester with pentafluorophenol, nitrophenol, benzotriazole, azabenzotriazole, thiophenol, or N-hydroxysuccinimide (NHS) as the leaving group.

[0437] As preferably used herein, the term "activated sulfonic acid" refers to a sulfonic acid group having the general formula -SO2-X, where X is a leaving group. For example, activated forms of sulfonic acid can include, but are not limited to, sulfonyl chloride or sulfonic acid anhydride. In some embodiments, the activated sulfonic acid group is a sulfonyl chloride containing chloride as a leaving group.

[0438] In an embodiment, as preferably used herein, the term "mediate linkage" means that a linkage or linkage type is established, preferably a linkage between two moieties. In preferred embodiments, the linkage and linkage type are as defined herein.

[0439] In this application, where a range is referred to as being represented by a lower integer and an upper integer, such as 1 to 4, such a range is a representation of the lower integer, the higher integer, and any integer between the lower and higher integers. To that extent, the range is actually a separate disclosure of the integers. In the above example, the range 1 to 4 means 1, 2, 3, and 4.

[0440] The compounds of the present invention typically comprise the amino acid sequences provided herein. Conventional amino acids, also called natural amino acids, are identified according to their standard three-letter and one-letter abbreviations, as set forth in Table 4.

[0441] [Table 4]

[0442] Unconventional amino acids, also called unnatural amino acids, are any type of non-oligomeric compound that contains an amino group and a carboxyl group and is not a conventional amino acid. Examples of unconventional amino acids and other building blocks used in constructing compounds of the present invention are identified according to their abbreviations or names found in Table 5. The structures of some building blocks are described with exemplary reagents for introducing the building blocks into peptides (e.g., carboxylic acids), or these building blocks are shown as residues fully attached to another structure, such as a peptide or amino acid. Amino acid structures are shown as explicit amino acids, not as residues of amino acids, as they will appear after implementation into a peptide sequence. Some larger chemical moieties consisting of more than one moiety are also shown for clarity.

[0443] [Table 5-1]

[0444] [Table 5-2]

[0445] [Table 5-3]

[0446] [Table 5-4]

[0447] [Table 5-5]

[0448] [Table 5-6]

[0449] [Table 5-7]

[0450]

Table 5-8

[0451] Table 5-9

[0452] Table 5-10

[0453]

Table 5-11

[0454]

Table 5-12

[0455] Table 5-13

[0456] Table 5-14

[0457]

Table 5-15

[0458] Table 5-16

[0459] The amino acid sequence of peptide provided herein is written in typical peptide sequence format, as understood by those skilled in the art.For example, the three-letter designation of conventional amino acid, or the designation of unconventional amino acid, or the abbreviation of additional building block, indicates that amino acid or building block exists at a specific position in peptide sequence.Each amino acid designation or building block is connected to the designation or building block of the next and / or previous amino acid in sequence by a hyphen (typically representing amide linkage).

[0460] Where an amino acid contains more than one amino acid and / or carboxy group, all orientations of this amino acid are in principle possible, although in α-amino acids, utilization of the α-amino and α-carboxy groups is preferred; otherwise, the preferred orientation is explicitly specified.

[0461] For amino acids, in their abbreviations, the first letter indicates the stereochemistry of the C-α atom, if applicable, e.g., a capitalized first letter indicates that the L-form of the amino acid is present in the peptide sequence, while a lowercase first letter indicates that the D-form of the corresponding amino acid is present in the peptide sequence.

[0462] In one embodiment, as preferably used herein, an aromatic L-α-amino acid is any type of L-α-amino acid that contains an aryl group. In one embodiment, as preferably used herein, a heteroaromatic L-α-amino acid is any type of L-α-amino acid that contains a heteroaryl group.

[0463] Those skilled in the art will recognize whether a stereocenter exists in the compounds disclosed herein, regardless of whether such stereocenter is part of an amino acid moiety or any other part or moiety of the compound of the present invention. Thus, the present invention encompasses both possible stereoisomers, including not only racemates but also individual enantiomers and / or diastereomers. If a compound is desired as a single enantiomer or diastereomer, it can be obtained by stereospecific synthesis or by resolution of the final product or any convenient intermediate. The ability to resolve the final product, intermediate, or starting material can be affected by any suitable method known in the art. For example, see "Stereochemistry of Organic Compounds" by EL Eliel, SH Wilen, and LN Mander (Wiley-Interscience, 1994).

[0464] In this application, the structural formula of a compound may, in some cases, for convenience, represent a certain type of isomer, but the present invention includes all isomers such as geometric isomers, optical isomers based on asymmetric carbons, stereoisomers, tautomers, etc. In this specification, the structural formula of a compound may, in some cases, for convenience, represent a certain type of isomer, but the present invention includes all isomers such as geometric isomers, optical isomers based on asymmetric carbons, stereoisomers, tautomers, etc.

[0465] Unless otherwise indicated, amino acid sequences are presented herein in an N-terminal to C-terminal direction. Derivatives of the amino acids that make up the peptides of the present invention may be listed in Table 6. In any embodiment, one or more amino acids of the compounds of the present invention are substituted with a derivative of the corresponding preferred amino acid.

[0466] [Table 6-1]

[0467] [Table 6-2]

[0468] Linear peptides A typical linear peptide is typically written from N- to C-terminus as shown below: NT-Xaa1-Xaa2-Xaa3-Xaa4-...Xaan-CT; There, 1. Xaax is the abbreviation, descriptor or symbol for the amino acid or building block at a particular sequence position x, as shown in Table 5; 2. NT is the N-terminal group, e.g., "H" (hydrogen for the free N-terminal amino group), or an abbreviation for a particular terminal carboxylic acid, such as "Ac" for acetic acid, or other chemical group or structural formula of a chemical group linked via a hyphen to the N-terminal amino acid designation (Xaa1), and 3. CT is an abbreviation for the C-terminal group, typically "OH" or "NH2" (as the terminal carboxylic acid or amide), or a specific terminal amine (Xaan) linked to the C-terminal amino acid designation via a hyphen. Branched peptides with side chains modified by specific building blocks or peptides A typical linear branched peptide is described from N- to C-terminus as follows: NT-Xaa1-Xaa2-Xaa3(NT-Xab1-Xab2-......Xabn)-......Xaan-CT There, the explanations 1.-3. for the description of linear peptides apply to the specification of Xaax, NT and CT in the backbone of branched peptides.

[0469] The position of the branching is specified in parentheses after the Xaax abbreviation. The branching typically occurs at a lysine (Lys) residue (or similar), which means that the branching is attached to the ε-amino function of the lysine side chain via an amide bond.

[0470] The contents in brackets describe the sequence / structure of the peptide branch "NT-Xab1-Xab2-......Xabn", where: 1. Xabx is the abbreviation, descriptor or symbol for the amino acid or building block at a particular sequence position x of the branch, as shown in Table 3; 2. NT is the N-terminal group, e.g., an abbreviation for a particular terminal carboxylic acid, such as "Ac" for acetic acid, or another chemical group or structural formula of a chemical group linked via a hyphen to the N-terminal amino acid designation (Xab1); and 3. The final building block of a branched Xabn, which connects the branch to the backbone by forming an amide bond with the side chain amino function of a lysine (or similar residue) and its own carboxyl function. Cyclic peptides An exemplary generic cyclic peptide, written from N- to C-terminal, is shown below: NT-Xaa1-[Xaa2-Xaa3-Xaa4-...Xaan]-CT; The specifications of Xaax, NT, and CT in the backbone of cyclic peptides are as described in 1.-3. above for the description of linear peptides. The characteristics of the peptide cycle are indicated in square brackets.

[0471] 1. The open square bracket indicates the building block with the side chain where the cycle begins (cycle-start residue), 2. The closed square bracket indicates the building block with the side chain that ends the cycle (cycle-ending residue).

[0472] The chemical nature of the connection between these two residues is as follows: 1. an amide bond, where one of the residues shown contains an amino function in its side chain (e.g., Lys) while the other contains a carboxyl function in its side chain (e.g., Glu), or 2. Disulfide bonds when the indicated residue / amino acid contains a sulfhydryl moiety (e.g., Cys). Cyclic peptides containing cycloaddition elements (Yc) A typical extended cyclic peptide, written from N- to C-terminal, is shown below: NT-Xaa1-[Xaa2(Yc)-Xaa3-Xaa4-...Xaan]-CT; The specifications of Xaax, NT, and CT in the backbone of a cyclic peptide are as described in 1.-3. for the description of linear peptides. Additionally, Yc is the cyclization element. As in cyclic peptides, the cycle features are identified by square brackets indicating the cycle start and cycle end residues.

[0473] The brackets adjacent to the cycle-starting residue identify the cyclization element Yc in the extended peptide cycle. The Yc element is linked to the side chain of that residue. In turn, the Yc element is linked to the side chain of the cycle-ending residue. The chemical nature of the linkage between either of these residues and the Yc element depends on the side chain functionality of the corresponding amino acid Xaan. If the side chain of Xaan contains a sulfhydryl group (e.g., Cys), the linkage is a thioether.

[0474] As a non-limiting example, the structure of Ac-[Cys(tMeBn(DOTA-PP))-Pro-Pro-Thr-Gln-Phe-Cys]-OH is depicted below.

[0475] [ka]

[0476] There, 1. Ac corresponds to NT in the general formula. 2. Cys, Pro, Pro, Thr, Gln, Phe, and Cys correspond to Xaa1 to Xaa7 in the general formula.

[0477] 3.OH corresponds to CT in the general formula. 4. An open square bracket (,[') adjacent to the N-terminal cysteine ​​in the sequence indicates that the cycle begins at this residue (cycle start residue).

[0478] 5. A closed square bracket (,]') adjacent to the N-terminal cysteine ​​in the sequence indicates that the cycle ends at this residue (cycle-ending residue). 6. The tMeBn in parentheses adjacent to the Cys indicated as the start residue identifies the cyclization element Yc, which in turn binds to the Cys indicated as the cycle end residue. The Yc element is linked to the above residue via a thioether linkage.

[0479] 7. The remaining attachment point of the tMeBn residue is the DOTA chelator via a PP linker. Explicit terms such as "Cys(tMeBn(DOTA-PP)" are included in the list of chemical structures in Table 2.

[0480] In an embodiment of the invention, an amino acid or peptide is attached to Xaa7, the majority of the amino acids of the peptide are charged or polar, and the net charge of the peptide is −2, −1, 0, +1 or +2.

[0481] In calculating peptide net charge, negatively charged amino acids are those that have an acidic group such as -COOH or -SO3H in their side chain, and their net charge corresponds to the number of acidic groups; for example, Asp or Glu have a net charge of -1.

[0482] In this calculation, positively charged amino acids are those that have a basic group, such as amino or -guanidino, in their side chain, and their net charge corresponds to the number of basic groups, e.g., Lys or Arg have a net charge of +1.

[0483] Polar amino acids are amino acids that have polar groups in their side chains, such as CONH, OH, F, Cl, CN, and heterocycles such as imidazole in histidine.

[0484] Polar amino acids have a net charge of 0. It is recognized that some nitrogen-containing heterocycles are protonated at equilibrium and therefore carry a degree of positive charge depending on the pH of the environment, but are considered to have a net charge of 0 for calculation purposes.

[0485] The majority of the amino acids in this peptide (over 50%) are charged or polar. Preferably, the positive or negative charges may be separated by polar or non-polar amino acids.

[0486] In some embodiments, the presence of a negatively charged amino acid is preferred at XaalO. In some embodiments, the presence of a positively charged amino acid is preferred at Xaa13, preferably Arg and arg.

[0487] According to the present invention, the compound of the present invention can comprise a Z group. The Z group comprises a chelator and optionally a linker. When preferably used, the linker is an element, moiety, or structure that separates two parts of a molecule. In the present invention, the linker group forms a covalent bond with both the chelator group and the respective part of the compound of the present invention to which Z is attached. In principle, the linker group can be any chemical group that can form a bond at a specific position with both the chelator group and a part of the compound of the present invention.

[0488] An important property or characteristic of the linker is that it separates the chelator and cyclic peptide portions of the compounds of the invention. This is particularly important when the target binding ability of the cyclic peptide is compromised by the proximity of the chelator. However, the overall linker length in its most extended conformer should not exceed 200 Å, preferably 150 Å or less, and most preferably 100 Å or less.

[0489] In a preferred embodiment, the linker is -[X] a-, where a is an integer from 1 to 10, and each X is an individual building block independently connected to its neighbors in the sequence by a functional group selected from those including an amide linkage, a urea linkage, a carbamate linkage, an ester linkage, an ether linkage, a thioether linkage, a sulfonamide, a triazole, and a disulfide linkage.

[0490] X1 is connected to a chelator, if present, to X2, or to a compound of the invention at a specific position. a If present, X a-1 and is connected to the compound of the present invention at a specific position.

[0491] A more preferred class of linker groups is -[X] a -, where a is an integer from 1 to 10, preferably 1 to 8, 1 to 6, 1 to 5, 1 to 4, or 1 to 3, and each X is an individual building block independently connected to its neighbors in the sequence by a functional group selected from the group including an amide linkage, a urea linkage, a carbamate linkage, an ester linkage, an ether linkage, a thioether linkage, a sulfonamide linkage, a triazole linkage, and a disulfide linkage.

[0492] In certain embodiments, the building block X has the general formula (8):

[0493] [ka]

[0494] wherein: Fragment Lin if present 2 , and the fragment Lin if present 3 are, individually and independently, -CO-, -NR 10 -, -S-, -CO-NR 10 -,-CS-NR 10 -, -O-, -succinimide and -CH2-CO-NR10 -; with the proviso that Lin 2 or Lin 3 At least one of R has a carbon atom 9 and the nitrogen atoms of all nitrogen-containing fragments are linked to R 9 Concatenated to; R 10 is selected from the group consisting of hydrogen and (C1-C4) alkyl; and R 9 is -(C1-C 10 ) alkylidene-, -(C3-C8) carbocyclo-, -arylene-, -(C1-C 10 ) alkylidene-arylene-, -arylene-(C1-C 10 ) alkylidene-, -(C1-C 10 ) alkylidene-arylene-(C1-C 10 ) alkylidene-, -(C1-C 10 ) alkylidene-(C3-C8)carbocyclo-, -(C3-C8)carbocyclo-(C1-C 10 ) alkylidene-, -(C1-C 10 )Alkylidene-(C3-C8)carbocyclo-(C1-C 10 ) alkylidene-, -(C3-C8) heterocyclo-, (C1-C 10 ) alkylidene-(C3-C8)heterocyclo-, -(C3-C8)heterocyclo-(C1-C 10 ) alkylidene-, -(C1-C 10 ) alkylidene-(C3-C8)heterocyclo-(C1-C 10 ) Alkylidene-, -(CH2CH2O) r - and -(CH2) s -(CH2CH2O) r -(CH2) t -Selected from; r is any integer from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; s is any integer from 0, 1, 2, 3, and 4; t is any integer from 0, 1, 2, 3, and 4.

[0495] Preferably, apart from the linkage between X1 and the chelator, the linkages are amide linkages. More preferably, the building blocks X2 to X a are independently selected from the group consisting of amino acids, dicarboxylic acids and diamines, and each linkage is an amide.

[0496] In one embodiment, the building blocks X2 to X a is preferably an amino acid, selected from the group comprising conventional and unconventional amino acids. In one embodiment, the amino acid is selected from the group comprising β-amino acids, γ-amino acids, δ-amino acids, ε-amino acids, and ω-amino acids. In a further embodiment, the amino acid is a cyclic amino acid or a linear amino acid. It will be understood by those skilled in the art that in the case of amino acids with asymmetric centers, all stereoisomeric forms can be used in building block X.

[0497] In one embodiment, the building blocks X2 to X a is preferably an amino acid, which is selected from a group comprising amino acids that differ in terms of the distance of the amino group from the carboxyl group. Amino acids of this type are generally

[0498] [ka]

[0499] It can be expressed as follows. It is within the scope of the present invention that such amino acids are not further substituted. However, it is also within the scope of the present invention that such amino acids are further substituted, preferably where such substitutions are CO-NH and / or Ac-NH-.

[0500] Representatives of this type of amino acid (structure 32) that can be used as building block X are glycine (Gly), β-alanine (Bal), γ-aminobutyric acid (GABA), aminopentanoic acid, aminohexanoic acid, and homologues with up to 10 CH groups.

[0501] Representatives of this type of amino acid (structure 33) which are more preferably used as building block X are 3-aminomethylbenzoic acid, 4-aminomethylbenzoic acid, anthranilic acid, 3-aminobenzoic acid and 4-aminobenzoic acid.

[0502] Related building blocks are diamines derived from amino acids (structures 32+33) by replacing NH2 with COOH, which are preferably used as building block X: diaminoethane, 1,3-diaminopropane, 1,4-diaminobutane, 1,5-diaminopentane, 3-aminomethyl-aniline, 4-aminomethyl-aniline, 1,2-diaminobenzene, 1,3-diaminobenzene and 1,4-diaminobenzene.

[0503] Related building blocks are dicarboxylic acids derived from amino acids (structures 32+33) by replacing COOH with NH2, with those more preferably used as building block X being malonic acid, succinic acid, glutaric acid, adipic acid, phthalic acid, terephthalic acid, isophthalic acid and 2, 3 or 4 carboxyphenylacetic acid.

[0504] In a further embodiment, the amino acid is preferably an amino acid containing a polyether as a backbone. Preferably, such a polyether is polyethylene glycol and consists of up to 30 monomer units. Preferably, such polyether-containing amino acids exhibit increased hydrophilicity compared to amino acids that do not contain such polyether. The building block X, and ultimately the linker group [X] aIncorporation into typically results in increased hydrophilicity. Preferred embodiments of this type of amino acid are described below, and such amino acids may contain 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 ethylene oxide moieties:

[0505] [ka]

[0506] It is recognized that the Preferred ethylene glycol containing amino acids are Ttds (N-(3-{2-[2-[2-(3-amino-propoxy)-ethoxy]-ethoxy}-propyl)-succinic acid) and OOc ([2-(2-(2-amino-ethoxy)-ethoxy]-acetic acid), the formula of which is as follows:

[0507] [ka]

[0508] In a preferred embodiment, the linker comprises an oligomer or monomer of only one specific amino acid selected from the group Ttds, O2Oc, Apac, Gly, Bal, Gab, Mamb, Pamb, Ppac, 4Amc, Inp, Sni, Rni, Nmg, Cmp, PEG6, PEG12, PEG-amino acid, more preferably the linker is monomeric.

[0509] In another preferred embodiment, the linker comprises one building block X2 selected from the group consisting of Ttds, O2Oc, Apac, Gly, Bal, Gab, Mamb Pamb, PEG6, PEG12, and PEG-amino acid, and a second building block X1 directly attached to the amino nitrogen of X2 and directly linked to the chelator by a linkage selected from the group consisting of amide linkage, urea linkage, carbamate linkage, ester linkage, ether linkage, thioether linkage, sulfonamide linkage, triazole linkage, and disulfide linkage. X1 in this case acts as an adapter mediating the linkage of different types of binding functional groups provided by the chelator to the nitrogen atom of the amino acid X2, in the sense that X1 provides a complementary functional group related to the linkage of the chelator.

[0510] However, the use of a linker usually depends on the purpose. In some situations, it is necessary to free up a larger portion of the molecule separate from the biologically active molecule to maintain high biological activity. In other situations, the introduction of a linker opens up the opportunity to adjust the physicochemical properties of the molecule by introducing polarity or multiple charges. In certain situations, it can be advantageous and rewarding if a chelator can be combined with a biologically active compound without the need for such a linker. In particular, the compounds of the present invention in which a chelator is attached to Yc of formula (X) through the formation of two thioether linkages, which connect the S atom of Xaa1 and the S atom of Xaa7, typically exhibit excellent performance without the use of any dedicated linker.

[0511] In some embodiments, the compounds of the present invention include a chelator. Preferably, the chelator is part of the compound of the present invention, whereby the chelator is directly or indirectly attached, such as by a linker, to the compound of the present invention. Preferred chelators are those that form metal chelates, preferably containing at least one radiometal. The at least one radiometal is preferably useful in diagnostic and / or therapeutic and / or diagnostic therapeutic uses, or more preferably useful or suitable for imaging and / or radiotherapy.

[0512] In principle, chelators useful and / or suitable for the practice of the present invention, including the diagnosis and / or treatment of diseases, are known to those skilled in the art. A wide variety of individual chelators are available, as reviewed, for example, by Banerjee et al. (Banerjee et al., Dalton Trans, 2005, 24:3886) and references therein (Price et al., Chem Soc Rev, 2014, 43:260; Wadas et al., Chem Rev, 2010, 110:2858). Such chelators include, but are not limited to, linear, cyclic, macrocyclic, tetrapyridine, N3S, N2S2 and N4 chelators disclosed in U.S. Patent No. 5,367,080A, U.S. Patent No. 5,364,613A, U.S. Patent No. 5,021,556A, U.S. Patent No. 5,075,099A and U.S. Patent No. 5,886,142A.

[0513] Representative chelating agents and their derivatives, also referred to herein as chelators, suitable for the practice of the present invention include, but are not limited to, 99mTc(CO)3-chelators, AAZTA, BAT, CDTA, DTA, DTPA, CY-DTA, DTCBP, CHX-A"-DTPA, CTA, cyclam, cyclen, TETA, sarcofagin, CPTA, TEAMA, Crown, Cyclen, DO3A, DO2A, TRITA, DATA, DFO, DATA(M), DATA(P), DATA(Ph), DATA(PPh), DEDPA, H4octapa, H2dedpa, H5decapa, H2azapa, H2CHX, DEDPA, DFO-Chx-MAL, DFO-p-SCN, DFO-1AC, DFO-BAC, p-SCN-Bn-DFO, DFO-pPhe-NCS, DFO-HOPO, DFC, diphosphine, DOTA, DOTAGA, DOTA-MFCO, DOTAM-monoacid, nitro-DOTA, nitro-PA-DOTA, p-NCS-Bz- DOTA, PA-DOTA, DOTA-NCS, DOTA-NHS, CB-DO2A, PCTA, p-NH2-Bn-PCTA, p-SCN-Bn-PCTA, p-SCN-Bn-DOTA, DOTMA, NB-DOTA, H4NB-DOTA, H4TCE-DOTA, 3,4,3-(Li-1,2-HOPO), TREN(Me-3,2-HOPO), TCE-DOTA, DOTP, DOXP, p-NCS-DOTA, p-NCS-TRITA, TRITA, TETA, 3p-C-DEPA, 3p-C-DEPA-NCS, p-NH2-BN-OXO-DO 3A, p-SCN-BN-TCMC, TCMC, 4-aminobutyl-DOTA, azido-mono-amide-DOTA, BCN-DOTA, butyne-DOTA, BCN-DOTA-GA, DOA3P, DO2a2p, DO2A lance-H2do2a), DO3A, DO3A-thiol, DO3AtBu-N-(2-aminoethyl)ethanamide, DO2AP, CB-DO2A, C3B-DO2A, HP-DO3A, DOTA-NHS-ester, maleimido-DOTA-GA, maleimido-mono-amide-DOTA, maleimido-DOTA, NH2-DOTA-GA, NH2-PEG4-DOTA-GA, p-N H2-Bn-DOTA, p-NO2-Bn-DOTA, p-SCN-Bn-DOTA, p-SCN-Bz-DOTA, TA-DOTA, TA-DOTA-GA, OTTA, DOXP, TSC, DTC, DTCBP, PTSM, ATSM, FSC, H2ATSM, H2PTSM, Dp44mT, DpC, Bp44mT, QT, hybrid thiosemicarbazone-benzothiazole, thiosemicarbazone-styrylpyridine tetradentate ligands H2 L2-4, HBED, HBED-CC, dmHBED, dmEHPG, HBED-nn, SHBED, Br-Me2HBED, BPCA, HEHA, BF-HEHA, Deferiprone, THP, HOPO, HYNIC (2-hydrazinonicotinamide), NHS-HYNIC, HYNIC-Kp-DPPB, HYNIC-Ko-DPPB, (HYNIC)(tricine)2, (HYNIC)(EDDA)Cl, p-EDDHA, AIM, AIM A,IAM B, MOTHER, MOTHER-DGal, MOTHER-MGal, MOTHER-DA, MOTHER-HAD, Macropa, Macropaquin, Macroquin-SO3, NxS4-x, N2S2, N3S. N4, MAG3B, NOTE, NODAGA, SCN-Bz-NOTE-R, NOT-P(NOTMP), NOTAM, p-NCS-NOTE, TACN, TACN-TM, NETA, NETA-モノアミン, p SCN-PhPr-NE3TA, C-NE3TA-NCS, C-NETA-NCS, 3p-C-NETA, NODASE, NOPO, NODA, NO2A, N-ベンル-NODA, NODA-MPAA, C-NO TA, BCNOT-NOT, NO2A-NO2A-NOTAチン, NO2AP, NO3AP, N-NOTE, Oxo-DO3A, p-NH2-Bn-NOTE, p-NH 2-Bn-oxo-DO3A, p-NO2-Bn-Cyclen, PSC, p-SCN-Bn-NOTE, NOTP, p-SCN-Bn-オキソ-DO3A, TRAP, PAPER, BF-PAPER, Pycup, P ycup2A, pycup1A1Bn, pycup2Bn, RESCA, SarAr-R, Diamsar, AmBaSar-R, siamSar, Sar, Tachpyr, tachpyr-(6-Me) TAM A、TAM B, TAME, TAME-Hex, THP-Ph-NCS, THP-NCS, THP-TATE, NTP, H3THP, THPN, CB-TE 2A、PCB-TE1A1P、TETA-NHS、CPTA、CPTA-NHS、CB-TE1K1P、CB-TE2A、TE2A、H2CB -TE2A、TE2P、CB-TE2P、MM-TE2A、DM-TE2A、2C-TETA、6C-TETA、BAT、BAT-6、NHS -BAT, SSBAT, SCN-CHX-A-DTPA-P, SCN-TETA, TMT-アン, p-BZ-HTCPP,

[0514] HYNIC, DTPA, EDTA, DOTA, TETA, bisaminobisthiol (BAT) based chelators as disclosed in U.S. Pat. No. 5,720,934; desferrioxamine (DFO) as disclosed in (Doulias et al., Free Radic Biol Med, 2003, 35:719); tetrapyridine and N3S, N2S2 and N4 chelators as disclosed in U.S. Pat. No. 5,367,080A, U.S. Pat. No. 5,364,613A, U.S. Pat. No. 5,021,556A, U.S. Pat. No. 5,075,099A, U.S. Pat. No. 5,886,142A, all of which references are incorporated herein by reference in their entireties; 6-amino-6-methylperhydro-1,4-diazepine-N,N',N'',N'''-tetraacetic acid (AAZTA) as disclosed in Pfister et al. (Pfister et al., EJNMI Res 2015, 5:74), Deferiprone, 1,2-dimethyl-3,4-hydroxypyridinone, and hexadentate tris(3,4-hydroxypyridinone)THP are disclosed by Cusnir et al. (Cusnir et al., Int J Mol Sci 2017, 18), monoamine-monoamide dithiol (MAMA)-based chelators are disclosed by Demoin et al. (Demoin et al., Nucl Med Biol 2016, 43:802), and MACROPA and analogs are disclosed by Thieler et al. (Thiele et al., Angew Chem Int Ed Engl 2017, 56:14712), 1,4,7,10,13,16-hexaazacyclohexadecane-N,N',N'',N''',N'''',N'''-hexaacetic acid (HEHA) and PEPA analogs are disclosed by Price and Orvig (Price et al., Chem Soc Rev 2014, 43:260), and Pycup and analogs are disclosed by Boros et al. (Boros et al., Mol Pharm, 2014, vol. 11:617) and contains N,N-bis(2-hydroxybenzyl)ethylenediamine-N,N-diacetic acid (HBED), 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane (TCM), 2-[(carboxymethyl)]-[5-(4-nitrophenyl)-1-[4,7,10-Tris-(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl]pentan-2-yl)-amino]acetic acid (3p-C-DEPA), CB-TE2A, TE2A, TE1A1P, Diamsar, 1-N-(4-aminobenzyl)-3,6,10,13,16,19-hexaazabicyclo[6.6.6]-eicosane-1,8-diamine (SarAr), NETA, N,N0,N00, tris(2-mercaptoethyl)-1,4,7-triazacyclononane (TACN-TM), {4-[2-(bis-carboxymethyl-amino)-ethyl]-7-carboxymethyl-[1,4,7]triazonan-1-yl}-acetic acid ( NETA), diethylenetriaminepentaacetic acid (DTP), 3-({4,7-bis-[(2-carboxy-ethyl)-hydroxy-phosphinoylmethyl]-[1,4,7]triazonan-1-ylmethyl}-hydroxy-phosphinoyl)-propionic acid (TRAP), NOPO, H4octapa, SHBED, BPCA, 3,6,9,15-tetraazabicyclo[9.3.1]-pentadeca-1(15),11,13-triene-3,6,9,-triacetic acid (PCTA), 1,4,7,10,13-pentaazacyclopentadecane-N,N',N'',N''',N''''-pentaacetic acid (PEPA) were obtained from Price and Orvig (Price et al., Chem. Soc Rev, 2014, 43:260), 1-hydroxy-2-pyridone ligands (HOPO) were disclosed by Allott et al. (Allott et al., Chem Commun (Camb), 2017, 53:8529), [4-carboxymethyl-6-(carboxymethyl-methyl-amino)-6-methyl-[1,4]diazepam-1-yl]-acetic acid (DATA) was disclosed by Tornesello et al. (Tornesello et al., Molecules, 2017, 22:1282), tetrakis(aminomethyl)methane (TAM) and analogs were disclosed by McAuley 1988 (McAuley et al., Canadian Journal of Chemistry, 1989, 67:1657), and hexadentate tris(3,4-hydroxypyridinone (THP) and analogs are disclosed in Ma et al. (Ma et al., Dalton Trans, 2015, 44:4884).

[0515] The diagnostic and / or therapeutic uses of some of the above chelators have been described in the prior art. For example, 2-hydrazinonicotinamide (HYNIC) 99m Tc and 186,188 It has been widely used in the presence of co-ligands for the incorporation of Re (Schwartz et al., Bioconjug Chem, 1991, 2:333; Babich et al., J Nucl Med, 1993, 34:1964; Babich et al., Nucl Med Biol, 1995, 22:25); DTPA 111 It has been used in Octreoscan® for complexing In, and several modifications have been described in the literature (Li et al., Nucl Med Biol, 2001, 28:145; Brechbiel et al., Bioconjug Chem, 1991, 2:187); DOTA-type chelators for radiotherapy applications have been reported by Tweedle et al. (U.S. Pat. No. 4,885,363); other polyazamacrocycles for complexing trivalent isotope metals have been reported by Eisenwiener et al. (Eisenwiener et al., Bioconjug Chem, 2002, 13:530); and 99m N4-chelators, such as Tc-N4-chelators, have been used to label peptides, such as minigastrins, to target the CCK-2 receptor (Nock et al., J Nucl Med 2005, 46:1727).

[0516] In certain embodiments, the metal chelator may be, but is not limited to, DOTA, DOTAGA, NOTA, NODAGA, NODA-MPAA, HBED, TETA, CB-TE2A, DTPA, DFO, Macropa, HOPO, TRAP, THP, DATA, NOTP, sarcofadin, FSC, NETA, H4octapa, Pycup, N x S4-x (N4, N2S2, N3S), Hynic, 99m selected from the group comprising Tc(CO)3-chelators, and analogs thereof; DOTA stands for 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; DOTAGA stands for 1,4,7,10-tetraazacyclodosecane, 1-(glutaric acid)-4,7,10-triacetic acid; NOTA represents 1,4,7-triazacyclononanetriacetic acid, NODAGA stands for 1,4,7-triazacyclononane-N-glutaric acid-N',N''-diacetic acid; NODA-MPAA stands for 1,4,7-triazacyclononane-1,4-diacetate-methylphenylacetic acid; HBED stands for bis(2-hydroxybenzyl)ethylenediaminediacetic acid; TETA represents 1,4,8,11-tetraazacyclododecane-1,4,8,11-tetraacetic acid; CB-TE2A represents 4,11-bis-(carboxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]-hexadecane; DTPA stands for diethylenetriaminepentaacetic acid, DFO represents a desferal or desferrioxamine type group of chelators, a non-limiting example chemical name is N-[5-({3-[5-(acetyl-hydroxy-amino)-pentylcarbamoyl]-propionyl}-hydroxy-amino)-pentyl]-N'-(5-amino-pentyl)-N'-hydroxy-succinamide.

[0517] Macropa represents N,N'-bis[(6-carboxy-2-pyridyl)methyl]-4,13-diaza-18-crown; HOPO represents an octadentate hydroxypyridinone type group of the chelator, and the structure of a non-limiting example is shown below.

[0518] TRAP stands for 3-({4,7-bis-[(2-carboxy-ethyl)-hydroxy-phosphinoylmethyl]-[1,4,7]triazonan-1-ylmethyl}-hydroxy-phosphinoyl)-propionic acid; THP stands for hexadentate tris(3,4-hydroxypyridinone); DATA stands for [4-carboxymethyl-6-(carboxymethyl-methyl-amino)-6-methyl-[1,4]diazepan-1-yl]-acetic acid; NOTP stands for 1,4,7-triazacyclononane-N,N',N''-tris(methylenephosphonic) acid; Sarcofazine represents 3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane; FSC stands for 3,15,27-triamino-7,19,31-trihydroxy-10,22,34-trimethyl-1,13,25-trioxa-7,19,31-triaza-cyclohexatriaconta-9,21,33-triene-2,8,14,20,26,32-hexaone; NETA represents {4-[2-(bis-carboxymethyl-amino)-ethyl]-7-carboxymethyl-[1,4,7]triazonan-1-yl}-acetic acid; H4octapa represents N,N'-(6-carboxy-2-pyridylmethyl)-N,N'-diacetic acid-1,2-diaminoethane; Pycup represents 1,8-(2,6-pyridinedimethylene)-1,4,8,11-tetraazacyclotetradecane; N x S 4-x (N4, N2S2, N3S) represent a group of tetradentate chelators with an N atom (basic amine or non-basic amide) and a thiol as donors to stabilize Tc complexes, especially Tc(V)-oxo complexes. The structure of one representative, non-limiting example, MAG3, is shown below.

[0519] MAG3 represents {2-[2-(3-mercapto-propionylamino)-acetylamino]-acetylamino}-acetic acid; HYNIC stands for 6-hydrazino-nicotinic acid; 99m Tc(CO)3-chelators represent bi- or tridendate chelators capable of forming stable complexes with technetium tricarbonyl fragments; Their chemical structures are as follows:

[0520] [ka]

[0521] [ka]

[0522] In preferred embodiments, the metal chelator is selected from the group consisting of DOTA, DOTAGA, NOTA, NODAGA, NODA-MPAA, HBED, CB-TE2A, DFO, THP, N4 and analogs thereof.

[0523] In a more preferred embodiment, the metal chelator is selected from the group consisting of DOTA, DOTAGA, NOTA, N4Ac and NODAGA, and analogs thereof. Those skilled in the art will recognize that chelators can in principle be used regardless of whether the compounds of the invention are used or suitable for diagnosis or therapy, and such principles are outlined, inter alia, in WO 2009 / 109332 A1.

[0524] Furthermore, those skilled in the art will recognize that the presence of a chelator in a compound of the present invention, unless otherwise stated, includes the possibility that the chelator may be complexed to any metal complex partner, i.e., in principle, any metal that can be complexed by a chelator. The explicitly described chelator of a compound of the present invention or the general term chelator in connection with a compound of the present invention refers to a chelator that is not complexed in this way, or a chelator to which any metal complex partner is bound, and the metal complex partner is any radioactive or non-radioactive metal complex partner. Preferably, the metal chelator complex, i.e., the chelator to which the metal complex partner is bound, is a stable metal chelator complex.

[0525] Non-radioactive metal chelator complexes have several uses, for example, for assessing properties such as stability or activity that are otherwise difficult to determine. One aspect is that cold variants of radioactive versions of metal complex partners (e.g., non-radioactive gallium, lutetium, or indium complexes described in the Examples) can serve as surrogates for radioactive compounds. Furthermore, they are valuable tools for identifying metabolites in vitro or in vivo, as well as for assessing the toxicity properties of compounds of the invention. In addition, metal chelator complexes can be used in binding assays that take advantage of the fluorescent properties of some metal complexes with different ligands (e.g., europium salts).

[0526] Chelators can be synthesized with a wide variety of (possibly already activated) groups for conjugation to peptides or amino acids, or are commercially available. Direct conjugation of a chelator to the amino-nitrogen of each compound of the present invention is fully possible for chelators selected from the group consisting of DOTA, DOTAGA, NOTA, NODAGA, NODA-MPAA, HBED, TETA, CB-TE2A, DTPA, DFO, DATA, sarcofadin, N4, MAG3, and Hynic, preferably DOTA, DOTAGA, NOTA, NODAGA, NODA-MPAA, CB-TE2A, and N4. In this regard, the preferred linkage is an amide linkage.

[0527] Functional groups on chelators that are ideal precursors for direct conjugation to the amino-nitrogen of a chelator are known to those skilled in the art and include, but are not limited to, carboxylic acids, activated carboxylic acids, such as active esters, e.g., NHS-esters, pentafluorophenol-esters, HOBt-esters and HOAt-esters, isothiocyanates.

[0528] Functional groups on chelators that are ideal precursors for direct conjugation of the chelator to the carboxyl group of a peptide are known to those skilled in the art and include, but are not limited to, alkylamino and arylamino nitrogens. Each chelator reagent is commercially available for several chelators, such as DOTA, which has either an alkylamino or arylamino nitrogen.

[0529] It will be appreciated by those skilled in the art that the radionuclide attached or to be attached to the compounds of the present invention will be selected having regard to the particularities of the disease to be treated and / or diagnosed, respectively, and / or the patient population and patient group to be treated and diagnosed, respectively.

[0530] In embodiments of the present invention, radioactive nuclei are also referred to as radionuclides. Radioactive decay is the process by which the nuclei of unstable atoms lose energy by emitting ionizing particles (ionizing radiation). There are various types of radioactive decay. Decay, i.e., energy loss, occurs when an atom with one type of nucleus, called the parent radionuclide, is transformed into an atom with a different nucleus state or into a different nucleus containing a different number of protons and neutrons. Both of these products are called daughter nuclei. In some decays, the parent and daughter are different chemical elements, and therefore, the decay process results in nuclear transmutation (the creation of atoms of new elements). For example, radioactive decay can be alpha decay, beta decay, and gamma decay. Alpha decay occurs when a nucleus emits an alpha particle (helium nucleus). This is the most common process of emitting nucleons, but in rarer types of decay, the nucleus emits protons or specific nuclei of other elements (in a process called cluster decay). Beta decay occurs when a nucleus loses electrons (β - -decay) or positron (β + Radioactive decay occurs when an excited nucleus undergoes a nuclear transformation (gamma decay) and releases a type of neutrino. In contrast, there are radioactive decay processes that do not produce mutations. The energy of an excited nucleus can be emitted as gamma rays in gamma decay, or used to eject orbital electrons by interaction with the excited nucleus in a process called internal conversion, or used to absorb inner atomic electrons from their electron shells, thereby converting nuclear protons into neutrons, which can cause the emission of electron neutrinos in a process called electron capture (EC), or can be emitted without changing the number of protons and neutrons in a process called isomeric transition (IT). Another form of radioactive decay, spontaneous fission (SF), is found only in very heavy chemical elements, resulting in their spontaneous decomposition into smaller nuclei and a small number of isolated nuclear particles.

[0531] In a preferred embodiment of the present invention, radionuclides may be used to label the compounds of the present invention. In an embodiment of the present invention, the radionuclide is suitable for complexation with a chelator to provide a radionuclide chelate complex.

[0532] In further embodiments, one or more atoms of the compounds of the invention are of non-natural isotopic composition, preferably these atoms are radionuclides, more preferably radionuclides of carbon, oxygen, nitrogen, sulfur, phosphorus and the halogens; these radioactive atoms are typically part of amino acids, optionally halogen-containing amino acids, and / or building blocks, optionally halogenated building blocks of each of the compounds of the invention.

[0533] In a preferred embodiment of the invention, the radionuclide has a half-life that allows for diagnostic and / or therapeutic medical use, specifically a half-life of between 1 minute and 100 days. In a preferred embodiment of the present invention, the radionuclides have decay energies that allow for diagnostic and / or therapeutic medical use. Specifically, for gamma-emitting isotopes, the decay energies are 0.004 to 10 MeV, preferably 0.05 to 4 MeV, for diagnostic use. For positron-emitting isotopes, the decay energies are 0.6 to 13.2 MeV, preferably 1 to 6 MeV, for diagnostic use. For particle-emitting isotopes, the decay energies are 0.039 to 10 MeV, preferably 0.4 to 6.5 MeV, for therapeutic use.

[0534] In a preferred embodiment of the present invention, the radionuclide is industrially produced for medical use, specifically the radionuclide is available in GMP quality. In a preferred embodiment of the present invention, the daughter nuclide(s) after radioactive decay of the radionuclide are compatible with diagnostic and / or therapeutic medical use. Furthermore, the daughter nuclide(s) are stable or further decay in a manner that does not interfere with or even support diagnostic and / or therapeutic medical use. Representative radionuclides that can be used in connection with the present invention are summarized in Table 7.

[0535] Table 7-1

[0536]

Table 7-2

[0537] Table 7-3

[0538]

Table 7-4

[0539] Table 7-5

[0540]

Table 7-6

[0541] Table 7-7

[0542]

Table 7-8

[0543]

Table 7-9

[0544]

Table 7-10

[0545]

Table 7-11

[0546]

Table 7-12

[0547]

Table 7-13

[0548]

Table 7-14

[0549]

Table 7-15

[0550]

Table 7-16

[0551]

Table 7-17

[0552]

Table 7-18

[0553]

Table 7-19

[0554]

Table 7-20

[0555]

Table 7-21

[0556]

Table 7-22

[0557]

Table 7-23

[0558]

Table 7-24

[0559]

Table 7-25

[0560]

Table 7-26

[0561]

Table 7-27

[0562]

Table 7-28

[0563]

Table 7-29

[0564]

Table 7-30

[0565]

Table 7-31

[0566] [Table 7-32]

[0567] [Table 7-33]

[0568] [Table 7-34]

[0569] In an embodiment of the present invention, the radionuclide is used for diagnostic purposes. Preferably, the radioisotope is, but not limited to, 43 Sc, 44 Sc, 51 Mn, 52 Mn, 64 Cu, 67 Ga, 68 Ga, 86 Y, 89 Zr, 94m Tc, 99m Tc, 111 In, 152 Tb, 155 Tb, 177 Lu, 201 Tl, 203 Pb, 18 F, 76 Br, 77 Br, 123 I, 124 I, 125 I. More preferably, the radionuclide is selected from the group comprising: 43 Sc, 44 Sc, 64 Cu, 67 Ga, 68 Ga, 86 Y, 89 Zr, 99m Tc, 111 In, 152 Tb, 155 Tb, 203 Pb, 18 F, 76Br, 77 Br, 123 I, 124 I, 125 I. Even more preferably, the radionuclide is selected from the group comprising: 64 Cu, 68 Ga, 89 Zr, 99m Tc, 111 In, 18 F, 123 I, and 124 I. However, it will also be appreciated by those skilled in the art that the use of the above radionuclides is not limited to diagnostic purposes, but also encompasses their use in therapeutic and diagnostic therapeutics when conjugated to the compounds of the present invention.

[0570] In an embodiment of the invention, a radionuclide is used in therapy. Preferably, the radioisotope is: 47 Sc, 67 Cu, 89 Sr, 90 Y, 111 In, 153 Sm, 149 Tb, 161 Tb, 177 Lu, 186 Re, 188 Re, 212 Pb, 213 Bi, 223 Ra, 225 Ac, 226 Th, 227 Th, 131 I, 211 More preferably, the radioisotope is selected from the group including At. 47 Sc, 67 Cu, 90 Y, 177 Lu, 188 Re, 212 Pb, 213 Bi, 225 Ac, 227 Th, 131 I, 211 Even more preferably, the radionuclide is selected from the group comprising: 90 Y, 177 Lu, 225 Ac,227 Th, 131 I and 211 However, it will also be appreciated by those skilled in the art that the use of the above radionuclides is not limited to therapeutic purposes, but also encompasses their use in diagnostics and diagnostic therapeutics when conjugated to the compounds of the present invention.

[0571] In certain embodiments, the compounds of the present invention are present as pharmaceutically acceptable salts. The "pharmaceutically acceptable salts" of the compounds of the present invention are preferably acid or base salts generally considered in the art to be suitable for use in contact with human or animal tissues without undue toxicity or carcinogenicity, and preferably without irritation, allergic reactions, or other problems or complications. Such salts include mineral and organic acid salts of basic residues such as amines, and alkali or organic salts of acidic residues such as carboxylic acids. The compounds of the present invention can form internal salts that are also pharmaceutically acceptable salts.

[0572] Suitable pharmaceutically acceptable salts include, but are not limited to, hydrochloric acid, phosphoric acid, bromic acid, malic acid, glycolic acid, fumaric acid, sulfuric acid, sulfamic acid, sulfanilic acid, formic acid, toluenesulfonic acid, methanesulfonic acid, benzenesulfonic acid, ethanedisulfonic acid, 2-hydroxyethylsulfonic acid, nitric acid, benzoic acid, 2-acetoxybenzoic acid, citric acid, tartaric acid, lactic acid, stearic acid, salicylic acid, glutamic acid, ascorbic acid, pamoic acid, succinic acid, fumaric acid, maleic acid, propionic acid, hydroxymaleic acid, hydroiodic acid, phenylacetic acid, alkanoic acid, such as acetic acid, HOOC-(CH2) nExamples of pharmaceutically acceptable salts include salts of acids such as -COOH (n is any integer from 0 to 4, i.e., 0, 1, 2, 3, or 4). Similarly, pharmaceutically acceptable cations include, but are not limited to, sodium, potassium, calcium, aluminum, lithium, and ammonium. Those of ordinary skill in the art will recognize additional pharmaceutically acceptable salts for the compounds provided herein. In general, pharmaceutically acceptable acid or base salts can be synthesized from parent compounds containing a basic or acidic moiety by any conventional chemical method. Briefly, such salts can be prepared by reacting the free acid or free base form of these compounds with a stoichiometric amount of the appropriate base or acid in water or an organic solvent, or in a mixture of the two. Generally, the use of nonaqueous media such as ether, ethyl acetate, ethanol, isopropanol, or acetonitrile is preferred.

[0573] A "pharmaceutically acceptable solvate" of a compound of the present invention is preferably a solvate of a compound of the present invention formed by the association of one or more solvent molecules with one or more molecules of a compound of the present invention. Preferably, the solvent is one generally considered in the art to be suitable for use in contact with human or animal tissues without undue toxicity or carcinogenicity, preferably without irritation, allergic reaction, or other problems or complications. Such solvents include organic solvents such as alcohols, ethers, esters, and amines.

[0574] The "hydrate" of the compound of the present invention is formed by the association of one or more water molecules with one or more molecules of the compound of the present invention. Such hydrates include, but are not limited to, hemihydrate, monohydrate, dihydrate, trihydrate and tetrahydrate. Regardless of the hydrate composition, all hydrates are generally considered to be pharmaceutically acceptable.

[0575] The compound of the present invention has high binding affinity to FAP and high inhibitory activity to FAP.Because of this high binding affinity, the compound of the present invention is effective, useful and / or suitable as targeting agent, and when conjugated to another part, as targeting part.Preferably herein, targeting agent is the agent that interacts with the target molecule, which is the FAP in this case.Therefore, with respect to the cells and tissues targeted by the compound of the present invention, any cells and tissues that express the FAP can be targeted or can be targeted.

[0576] In certain embodiments, the compound interacts with a fibroblast activation protein (FAP), preferably a human FAP having the amino acid sequence of SEQ ID NO: 1, or a homolog thereof, wherein the amino acid sequence of the homolog has at least 85% identity to the FAP of SEQ ID NO: 1. In preferred embodiments, the identity is 90%, preferably 95%, 96%, 97%, 98% or 99%.

[0577] The identity between two nucleic acid molecules can be determined as known to those skilled in the art.More specifically, sequence comparison algorithms can be used to calculate the percent sequence homology of test sequence(s) to reference sequence based on designated program parameters.Test sequence is preferably the sequence or protein or polypeptide that is said to be identical to different protein or peptide, or should be tested to see whether it is identical, and if so, how identical it is, and therefore this different protein or polypeptide is also called reference sequence, and is preferably wild-type protein or polypeptide, more preferably human FAP of SEQ ID NO: 1.

[0578] Optimal alignment of sequences for comparison can be carried out, for example, by the local homology algorithm of Smith & Waterman (Smith et al., Advances in Applied Mathematics, 1981, 2:482), by the homology alignment algorithm of Needleman & Wunsch (Needleman et al., J Mol Biol, 1970, 48:443), by the search for similarity method of Pearson & Lipman (Pearson et al., Proc Natl Acad Sci USA, 1988, 85:24444), or by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics software package, Genetics Computer Group, 575 Science Dr., Madison, Wis.), or by visual inspection.

[0579] An example of an algorithm suitable for determining percent sequence identity is the algorithm used in the Basic Local Alignment Search Tool (hereinafter referred to as "BLAST"). See, for example, Altschul et al., 1990 (Altschul et al., J Mol Biol, 1990, 215:403) and Altschul et al., 1997 (Altschul et al., Nucleic Acids Res, 1997, 25:3389). Software for performing BLAST analysis is publicly available through the National Center for Biotechnology Information (hereinafter referred to as "NCBI"). The default parameters used in determining sequence identity using software available from NCBI, such as BLASTN (for nucleotide sequences) and BLASTP (for amino acid sequences), are described in McGinnis et al. (McGinnis et al., Nucleic Acids Res, 2004, 32:W20).

[0580] It is within the scope of the present invention that the compounds of the present invention are used or intended for use in a method for treating the diseases disclosed herein. Such a method preferably comprises administering a therapeutically effective amount of a compound of the present invention to a subject in need thereof. Such a method includes, but is not limited to, curative or adjuvant cancer treatment. It is used as a palliative treatment when a cure is not possible and the purpose is to control the disease locally or to alleviate symptoms, or as a therapeutic treatment when the therapy has a survival benefit and may be curative.

[0581] The methods for treating diseases disclosed herein include the treatment of diseases disclosed herein, including tumors and cancers, and can be used as first therapy, or as second, third, fourth, or last therapy.It is also within the scope of the present invention to combine the compounds of the present invention with additional therapeutic approaches.Those skilled in the art will be aware that the exact treatment intent, including curative, adjuvant, neoadjuvant, therapeutic, or palliative treatment intent, depends on the type, location, and stage of the tumor, as well as the general health of the patient.

[0582] In an embodiment of the invention, the disease is selected from the group consisting of neoplasms not otherwise specified, benign neoplasms, neoplasms of unknown benign or malignant nature, malignant neoplasms, metastatic neoplasms, neoplasms of unknown primary or metastatic nature, benign tumor cells, tumor cells of unknown benign or malignant nature, malignant tumor cells, malignant small cell tumors, malignant giant cell tumors, malignant spindle cell tumors, epithelial neoplasms of unspecified nature, benign epithelial tumors, carcinoma in situ of unspecified nature, metastatic carcinoma of unspecified nature, carcinomatosis, benign epithelioma, malignant epithelioma, large cell carcinoma of unspecified nature, undifferentiated carcinoma of unspecified nature, atypical carcinoma of unspecified nature, pleomorphic carcinoma, giant cell and spindle cell carcinoma, giant cell carcinoma, spindle cell carcinoma, pseudosarcomatous carcinoma, pleomorphic cell carcinoma, spheroid cell carcinoma, multiple small tumors, small cell carcinoma of unspecified nature, oat cell carcinoma, small cell carcinoma, spindle cell type, papillary and squamous neoplasm, papilloma of unspecified nature, in Papillary carcinoma in situ, papillary carcinoma not otherwise specified, verrucous papilloma, verrucous carcinoma not otherwise specified, squamous cell papilloma, squamous cell carcinoma, inverted papilloma, papillomatosis not otherwise specified, squamous cell carcinoma in situ not otherwise specified, squamous cell carcinoma not otherwise specified, metastatic squamous cell carcinoma not otherwise specified, squamous cell carcinoma, keratinizing type not otherwise specified, large cell nonkeratinizing squamous cell carcinoma, small cell nonkeratinizing squamous cell carcinoma, spindle cell squamous cell carcinoma, adenoid squamous cell carcinoma, in cases where stromal invasion is suspected Squamous cell carcinoma in situ, Microinvasive squamous cell carcinoma, Queyrat's erythroplasia, Bowen's disease, Lymphoepithelial carcinoma, Basal cell neoplasm, Basal cell tumor, Basal cell carcinoma not otherwise specified, Multicentric basal cell carcinoma, Localized scleroderma basal cell carcinoma, Fibroepithelial basal cell carcinoma, Basosquamous cell carcinoma, Transforming carcinoma, Yadazoline intraepithelioma, Trichoepithelioma, Trichofolliculoma, Trichilemmomas, Calcifying epithelioma, Transitional cell papilloma and carcinoma, Transitional cell papilloma not otherwise specified, Urothelial papilloma, Transitional cell carcinoma in situ, Transitional cell carcinoma not otherwise specified, Schneiderian papilloma, Inverted transitional cell papilloma, Schneiderian carcinoma, Spindle cell transitional cell carcinoma, Basaloid carcinoma, Cloacal carcinoma, Papillary transitional cell carcinoma, Adenoma and adenocarcinoma, Adenoma not otherwise specified, Bronchial adenoma not otherwise specified, In Adenocarcinoma in situ, adenocarcinoma not otherwise specified, metastatic adenocarcinoma not otherwise specified, scirrhous adenocarcinoma, fibroplastic gastritis, superficial spreading adenocarcinoma, intestinal adenocarcinoma, diffuse carcinoma, monomorphic adenoma, basal cell adenoma, islet cell adenoma, islet cell carcinoma, insulinoma not otherwise specified, malignant insulinoma, glucagonoma not otherwise specified, malignant glucagonoma, gastrinoma not otherwise specified, malignant gastrinoma, mixed islet cell and exocrine adenocarcinoma, bile duct adenoma, cholangiocarcinoma, bile duct cystadenoma, bile duct cystadenocarcinoma,Hepatocellular adenoma, hepatocellular carcinoma not otherwise specified, benign hepatocellular cholangiomas, mixed hepatocellular carcinoma and cholangiocarcinoma, trabecular adenoma, trabecular adenocarcinoma, embryonal adenoma, eccrine cutaneous cylindroma, adenoid cystic carcinoma, cribriform carcinoma, adenomatous polyp not otherwise specified, adenocarcinoma in adenomatous polyp, tubular adenoma not otherwise specified, tubular adenocarcinoma, adenomatous polyposis colorectum, adenocarcinoma in adenomatous polyposis colorectum, multiple adenomatous polyps, solid carcinoma not otherwise specified, simple carcinoma, carcinoid tumor not otherwise specified, malignant carcinoid tumor, argyrophilic carcinoid tumor not otherwise specified, malignant argyrophilic carcinoid tumor, non-argyrophilic carcinoid tumor not otherwise specified, malignant non-argyrophilic carcinoid tumor, malignant mucinous carcinoid tumor, composite carcinoid, pulmonary adenomatosis, bronchioloalveolar adenocarcinoma, alveolar adenoma, alveolar adenocarcinoma, papillary adenoma not otherwise specified, papillary adenocarcinoma not otherwise specified, villous adenoma not otherwise specified, adenocarcinoma in villous adenoma, villous adenocarcinoma, tubulovillous adenoma, chromophobe adenoma, chromophobe carcinoma, acidophilic adenoma, acidophilic carcinoma, mixed acidophilic-basophilic adenoma, mixed acidophilic-basophilic carcinoma, acidophilic adenoma, acidophilic adenocarcinoma, basophilic adenoma, basophilic carcinoma, clear cell adenoma, clear cell adenocarcinoma not otherwise specified, adrenal-like tumor, renal cell carcinoma, clear cell adenofibroma, granular cell carcinoma, chief cell adenoma, aqueous clear cell adenoma Aqueous clear cell adenocarcinoma, mixed cell adenoma, mixed cell adenocarcinoma, lipoadenoma, follicular adenoma, follicular adenocarcinoma not otherwise specified, well-differentiated follicular adenocarcinoma, trabecular follicular adenocarcinoma, small follicular adenoma, large follicular adenoma, papillary and follicular adenocarcinoma, non-encapsulated sclerosing carcinoma, multiple endocrine adenoma, juxtaglomerular tumor, adrenocortical adenoma not otherwise specified, adrenocortical cell carcinoma, compact cell adrenocortical adenoma, severely pigmented atypical adrenocortical adenoma, clear cell adrenocortical adenoma, glomerular cell adrenocortical adenoma, mixed cell adrenocortical adenoma, endometrioid adenoma not otherwise specified, endometrioid adenoma, borderline malignant tumor, endometrioid carcinoma, endometrioid adenofibroma not otherwise specified, borderline malignant tumor Endometrial adenofibroma, malignant endometrial adenofibroma, cutaneous adnexal neoplasm, cutaneous adnexal adenoma, cutaneous adnexal carcinoma, hidradenoma, sweat gland tumor not otherwise specified, sweat gland adenocarcinoma, apocrine adenoma, apocrine adenocarcinoma, eccrine acrohidradenoma, eccrine spiradenoma, hidradenoma papillary, hidradenoma papillary, syringoma not otherwise specified, sebaceous adenoma, sebaceous adenocarcinoma, cerumen adenoma, cerumen adenocarcinoma, mucoepidermoid neoplasm, mucoepidermoid tumor, mucoepidermoid carcinoma, cystic, mucinous, and serous neoplasm, cystadenoma not otherwise specified, cystadenocarcinoma not otherwise specified, serous cystadenoma not otherwise specified, serous cystadenoma not otherwise specified, borderline malignant tumor, serous cystadenocarcinoma not otherwise specified,Papillary cystadenoma unspecified, papillary cystadenoma borderline malignant tumor, papillary cystadenocarcinoma unspecified, papillary serous cystadenoma unspecified, papillary serous cystadenoma borderline malignant tumor, papillary serous cystadenocarcinoma, serous superficial papilloma unspecified, serous humoral superficial papillary borderline malignant tumor, serous superficial papillary carcinoma, unspecified mucinous cystadenoma, mucinous cystadenoma borderline malignant tumor, unspecified mucinous cystadenocarcinoma, unspecified papillary mucinous cystadenoma, papillary mucinous cystadenoma borderline malignant tumor, papillary Mucinous cystadenocarcinoma, mucinous adenoma, mucinous adenocarcinoma, pseudomyxoma peritonei, mucin-producing adenocarcinoma, signet ring cell carcinoma, metastatic signet ring cell carcinoma, tubular, lobular, and medullary neoplasm, intraductal carcinoma in situ not otherwise specified, invasive ductal carcinoma, comedo carcinoma, comedo carcinoma in situ not otherwise specified, juvenile breast carcinoma, intraductal papilloma, intraductal papillary adenocarcinoma in situ, intracystic papillary adenoma, intracystic carcinoma in situ, intraductal papillomatosis not otherwise specified, subareolar ductal papillomatosis not otherwise specified, medullary carcinoma with amyloid stroma, medullary carcinoma with lymphocytic stroma, in lobular carcinoma in situ, lobular carcinoma not otherwise specified, invasive ductal carcinoma, inflammatory carcinoma, Paget's disease of the breast, Paget's disease and invasive ductal carcinoma, extramammary Paget's disease, acinar cell neoplasm, acinar cell adenoma, acinar cell tumor, acinar cell carcinoma, complex epithelial neoplasm, adenosquamous carcinoma, adenoid lymphoma, squamous metaplastic adenocarcinoma, chondrometaplastic and osseous metaplastic adenocarcinoma, spindle cell metaplastic adenocarcinoma, apoplastic Clin metaplastic adenocarcinoma, benign thymoma, malignant thymoma, special gonadal neoplasm, sex cord-stromal tumor, theca cell carcinoma, theca cell carcinoma, luteoma, and granulosa cell tumor not specified. , malignant granulosa cell tumor, granulosa cell-theca cell tumor, benign male germ cell tumor, male germ cell tumor not otherwise specified, malignant male germ cell tumor, Sertoli-Leydig cell tumor, ovarian male germ cell tumor tumor, tubular male germinoma not otherwise specified, Sertoli cell carcinoma, lipid-accumulating tubular male germinoma, benign Leydig cell tumor, Leydig cell tumor not otherwise specified, malignant Leydig cell tumor, hilar cell tumor, ovarian lipocytoma, adrenal rest tumor, paraganglioma and glomus tumor, paraganglioma not otherwise specified, malignant paraganglioma, sympathetic paraganglioma, parasympathetic paraganglioma, jugular body tumor, aortic body tumor, carotid bulb tumor, extra-adrenal paraganglioma not otherwise specified, malignant extra-adrenal paraganglioma, pheochromocytoma not otherwise specified, malignant pheochromocytoma, hemangiosarcoma, glomus tumor, glomus angioma, nevi and melanoma, pigmented nevi not otherwise specified, malignant melanoma not otherwise specified, nodular melanoma, balloon cell nevus, balloon cell melanoma, halo nevus,Fibrous papules of the nose, neural nevus, giant cell nevus, amelanocytic nevus, amelanotic melanoma, junctional nevus, malignant melanoma in junctional nevus, precancerous melanosis not otherwise specified, malignant melanoma in precancerous melanosis, Hutchinson's melanoma, malignant melanoma in Hutchinson's melanoma, superficial spreading melanoma, intradermal nevus, compound nevus, giant pigmented nevus, malignant melanoma in giant pigmented nevus, epithelioid nevus and spindle cell nevus, epithelioid melanoma, spindle cell melanoma not otherwise specified, spindle cell melanoma type a, spindle cell melanoma type b, mixed epithelioid and spindle cell melanoma, blue nevus not otherwise specified, malignant blue Nevus, Proliferative Blue Nevus, Soft Tissue Tumors and Sarcomas Not Otherwise Specified, Benign Soft Tissue Tumor, Sarcoma Not Otherwise Specified, Sarcomatosis Not Otherwise Specified, Spindle Cell Sarcoma, Giant Cell Sarcoma, Small Cell Sarcoma, Epithelioid Cell Sarcoma, Fibromatous Neoplasm, Fibromatous Neoplasm Not Otherwise Specified, Fibrosarcoma Not Otherwise Specified, Myxofibroma, Fibromyxoblastic Sarcoma, Periosteal Fibromatosis, Periosteal Fibrosarcoma, Fascial Fibromatosis, Fascial Fibrosarcoma, Infantile Fibrosarcoma, Elastoma, Aggressive Fibromatosis, Abdominal Fibromatosis, Tendinoid Fibromatosis, Fibrous Histiocytoma Not Otherwise Specified, Atypical Fibrous Histiocytoma, Malignant Fibrous Histiocytoma Not Otherwise Specified, Atypical Fibroxanthoma, Malignant Fibroxanthoma, Unspecified Advanced dermatofibroma, dermatofibroma protuberans, dermatofibrosarcoma not otherwise specified, myxomatous neoplasm, myxoma not otherwise specified, myxosarcoma, lipomatous neoplasm, lipoma not otherwise specified, liposarcoma not otherwise specified, fibrolipoma, well-differentiated liposarcoma, fibromyxoid lipoma, myxoid liposarcoma, round cell liposarcoma, pleomorphic liposarcoma, mixed liposarcoma, intramuscular lipoma, spindle cell lipoma, angiomyolipoma, angiomyoliposarcoma, angiolipoma not otherwise specified, invasive angiolipoma, myelolipoma, hibernation adenoma, lipoblastomatosis, myomatous neoplasm, leiomyoma not otherwise specified, intravascular leiomyomatosis, leiomyosarcoma not otherwise specified, epithelioid leiomyoma, epithelioid cutaneous leiomyosarcoma, cellular leiomyoma, deforming leiomyoma, angiomyoma, angiomyosarcoma, myoma, myoma, rhabdomyoma not otherwise specified, rhabdomyosarcoma not otherwise specified, pleomorphic rhabdomyosarcoma, mixed rhabdomyosarcoma, embryonal rhabdomyosarcoma, adult rhabdomyosarcoma, embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma, complex mixed and stromal neoplasm, endometrial stromal sarcoma, endolymphatic stromal endometriosis, adenomyoma, pleomorphic adenoma, malignant mixed tumor not otherwise specified, müllerian mixed tumor, mesodermal mixed tumor, mesodermal nephroma, nephroblastoma not otherwise specified, epithelial nephroblastoma, mesenchymal nephroblastoma, hepatoblastoma, carcinosarcoma not otherwise specified, embryonal carcinosarcoma, myoepithelioma,Benign mesenchymoma, Mesenchymoma not otherwise specified, Malignant mesenchymoma, Embryonal sarcoma, Fibroepithelial neoplasm, Brenner tumor not otherwise specified, Brenner tumor borderline malignant, Malignant Brenner tumor, Fibroadenoma not otherwise specified, Intraductal fibroadenoma not otherwise specified, Periductal fibroadenoma, Adenofibroma not otherwise specified, Serous adenofibroma, Myxoid adenofibroma, Cellular intracanalicular fibroadenoma, Cystosarcoma phyllodes not otherwise specified, Malignant cystosarcoma phyllodes not otherwise specified, Juvenile fibroadenoma, Synovial neoplasm, Benign synovial tumor, Synovial sarcoma not otherwise specified, Spindle cell synovial sarcoma, Epithelioid cell synovial sarcoma, Biphasic synovial sarcoma, Clear cell sarcoma of tendons and aponeurosis, Mesothelial neoplasm, Benign mesothelioma, Malignant mesothelioma mesothelioma, benign fibrous mesothelioma, malignant fibrous mesothelioma, benign epithelioid mesothelioma, malignant epithelioid mesothelioma, benign biphasic mesothelioma, malignant biphasic mesothelioma, adenoid tumor of unspecified type, germ cell neoplasm, dysgerminoma, seminoma of unspecified type, undifferentiated seminoma, spermatocytic seminoma, germ cell tumor, embryonal carcinoma of unspecified type, endodermal sinus tumor, polyembryoma, gonadoblastoma, benign teratoma, teratoma of unspecified type, malignant teratoma of unspecified type, teratocarcinoma, undifferentiated malignant teratoma, intermediate malignant teratoma, dermoid cyst, malignant transformed dermoid cyst, ovarial goiter of unspecified type, malignant ovarial goiter, goiter carcinoid, trophoblastic neoplasm, specified Indeterminate hydatidiform mole, invasive hydatidiform mole, choriocarcinoma, choriocarcinoma with teratoma, malignant trophoblastic teratoma, mesonephroma, benign mesonephroma, mesonephric tumor, malignant mesonephroma, endosalpingioma, vascular tumor, hemangioma not otherwise specified, angiosarcoma, cavernous hemangioma, venous hemangioma, vine hemangioma, Kupffer cell sarcoma, benign hemangioendothelioma, hemangioendothelioma not otherwise specified, malignant hemangioendothelioma, capillary hemangioma, intramuscular hemangioma, Kaposi's sarcoma, angiokeratoma, angiokeratoma verrucosa, benign hemangiopericytoma, hemangiopericytoma not otherwise specified, malignant hemangiopericytoma, angiofibroma not otherwise specified, hemangioblastoma, lymphangioma, lymphangioma not otherwise specified, lymphangiosarcoma lymphoma, capillary lymphangioma, cavernous lymphangioma, cystic lymphangioma, lymphangioleiomyomatosis, lymphangioleiomyomatosis, angiolymphangioma, osteoma and osteosarcoma, osteoma not otherwise specified, osteosarcoma not otherwise specified, chondroblastic osteosarcoma, fibroblastic osteosarcoma, angioectatic osteosarcoma, osteosarcoma in Paget's disease of bone, parosteal osteosarcoma, osteoid osteoma not otherwise specified, osteoblastoma, chondromatous neoplasm, osteochondroma, osteochondroma not otherwise specified, chondroma not otherwise specified, chondrosarcoma not otherwise specified, parosteal chondroma, parosteal chondrosarcoma, chondroblastoma not otherwise specified, malignant chondroblastoma, mesenchymal chondrosarcoma, chondromyxoid fibroma,Giant cell tumor, giant cell tumor of bone not otherwise specified, malignant giant cell tumor of bone, giant cell tumor of soft tissue not otherwise specified, malignant giant cell tumor of soft tissue, mixed bone tumor, Ewing's sarcoma, long bone adamantinoma, ossifying fibroma, odontogenic tumor, Benign odontogenic tumor, odontogenic tumor not otherwise specified, malignant odontogenic tumor, dentinoma, cementoma not otherwise specified, benign cementoblastoma, cementogenic fibroma, giant cementoma, odontoma not otherwise specified, aggregate odontoma, complex odontoma, ameloblastic fibroodontoma, ameloblastic sarcoma, adenoid odontogenic tumor, calcifying odontogenic cyst, ameloblastoma not otherwise specified, malignant ameloblastoma, odontoid ameloblastoma, flat odontogenic tumor, odontogenic myxoma, odontogenic fibroma not otherwise specified, ameloblastic fibroma, ameloblastic fibrosarcoma, odontogenic calcifying epithelioma, mixed tumor, craniopharyngioma, pinealoma, pineal cell pineoblastoma, melanotic neuroectodermal tumor, chordoma, glioma, malignant glioma, gliomatosis cerebrum, mixed glioma, subependymal glioma, subependymal giant cell astrocytoma, choroid plexus papilloma unspecified, malignant choroid plexus papilloma, ependymoma unspecified, undifferentiated ependymoma, papillary ependymoma, myxopapillary ependymoma, astrocytoma unspecified, anaplastic astrocytoma, plasmatic astrocytoma, mastocytic astrocytoma, fibrous astrocytoma, pilocytic astrocytoma, spongioblastoma unspecified, polar spongoblastoma, astroblastoma, glioblastoma unspecified, giant cell glioblastoma, glioblastoma with sarcomatous elements Blastoma, primitive polar spongioblastoma, oligodendroglioma not otherwise specified, anaplastic oligodendroglioma, oligodendroglioma, medulloblastoma not otherwise specified, desmoplastic medulloblastoma, medullomyoblastoma, cerebellar sarcoma not otherwise specified, teratocyte sarcoma, pseudoepithelioma neoplasm, ganglioneuroma, ganglioneuromatosis, neuroblastoma not otherwise specified, medulloepithelioma not otherwise specified, teratoid medulloepithelioma, neuroepithelioma not otherwise specified, cavernous neuroblastoma, ganglioglioma, neurocytoma, Pacinian tumor, retinoblastoma not otherwise specified, differentiated retinoblastoma, undifferentiated retinoblastoma, olfactory nerve tumor, sensory neurocytoma, nasal neuroblastoma, olfactory neuroepithelioma tumor, meningioma, meningioma not otherwise specified, meningiomatosis not otherwise specified, malignant meningioma, meningioma, meningioma, fibrous meningioma, psammomatous meningioma, angiomatous meningioma, hemangioblastic meningioma, hemangiopericytic meningioma, transitional meningioma, papillary meningioma, meningeal sarcomatosis, nerve sheath tumor, neurofibroma not otherwise specified, neurofibromatosis not otherwise specified, neurofibrosarcoma, melanotic neurofibroma, plexiform neurofibroma, schwannoma not otherwise specified, schwannomatosis, malignant schwannoma, neuroma not otherwise specified, granular cell tumor and alveolar soft part sarcoma, granular cell tumor not otherwise specified, malignant granular cell tumor, alveolar soft part sarcoma, lymphoma not otherwise specified or diffuse lymphoma,Benign lymphoma-like tumor, malignant lymphoma, not otherwise specified, non-Hodgkin's lymphoma, undifferentiated malignant lymphoma, not otherwise specified, stem cell malignant lymphoma, not otherwise specified, spindle cell malignant lymphoma, not otherwise specified, lymphosarcoma, not otherwise specified, lymphoplasmacytic malignant lymphoma, immunoblastic malignant lymphoma, not otherwise specified, mixed lymphocytic-histiocytic malignant lymphoma, not otherwise specified, centroblastic-centrocytic diffuse malignant lymphoma, not otherwise specified, follicular-centrocytic malignant lymphoma, not otherwise specified, well-differentiated lymphocytic malignant lymphoma, not otherwise specified, moderately differentiated lymphocytic malignant lymphoma, not otherwise specified, split-type centrocytic malignant lymphoma, not otherwise specified Malignant lymphoma, poorly differentiated lymphocytic malignant lymphoma not otherwise specified, prolymphocytic lymphosarcoma, centroblastic malignant lymphoma not otherwise specified, non-cleaved follicular-centrocyte malignant lymphoma not otherwise specified, reticulum cell sarcoma, reticulum cell sarcoma not otherwise specified, pleomorphic reticulum cell sarcoma, nodular reticulum cell sarcoma, Hodgkin's disease, Hodgkin's disease not otherwise specified, lymphocyte-predominant Hodgkin's disease, mixed cell type Hodgkin's disease, lymphocyte-depleted Hodgkin's disease not otherwise specified, lymphocyte-depleted diffuse fibromatosis-type Hodgkin's disease, lymphocyte-depleted reticular type Hodgkin's disease, nodular sclerosing Hodgkin's disease not otherwise specified, cellular phase nodular sclerosing Hodgkin's disease, Hodgkin's granuloma , Hodgkin's granuloma, Hodgkin's sarcoma, nodular lymphoma or follicular nodular lymphoma not otherwise specified, nodular mixed lymphocytic-histiocytic lymphoma, centroblastic-centrocytic follicular lymphoma, nodular well-differentiated lymphocytic lymphoma, nodular moderately differentiated lymphocytic lymphoma, follicular cleaved follicular-centrocytic lymphoma, nodular poorly differentiated lymphocytic lymphoma, follicular non-cleaved follicular-centrocytic lymphoma, mycosis fungoides, mycosis fungoides, Sézary's disease, mixed reticuloendothelial neoplasm, microglioma, malignant histiocytosis, histiocytic myeloma eosinophilic reticulosis, Letterer-Siwe disease, plasma cell neoplasm, plasma cell myeloma, benign plasma cell neoplasm, plasmacytoma not otherwise specified, malignant plasma cell neoplasm, mast cell tumor, mast cell tumor not otherwise specified, mast cell sarcoma, malignant mastocytosis, Burkitt tumor, Burkitt tumor, leukemia group, leukemia group not otherwise specified, leukemia not otherwise specified, acute leukemia not otherwise specified, subacute leukemia not otherwise specified, chronic leukemia not otherwise specified, nonleukemic leukemia not otherwise specified, combined leukemia group, combined leukemia, lymphocytic leukemia group, lymphocytic leukemia not otherwise specified, acute lymphocytic leukemia, subacute lymphocytic leukemia, chronic lymphocytic leukemia,Non-leukemic lymphocytic leukemia, prolymphocytic leukemia, plasma cell leukemia group, plasma cell leukemia, erythroleukemia group, erythroleukemia, acute erythremia, chronic erythremia, lymphosarcoma cell leukemia group, lymphosarcoma cell leukemia, myeloid leukemia group, myeloid leukemia not otherwise specified, acute myeloid leukemia, subacute myeloid leukemia, chronic myeloid leukemia, non-leukemic myeloid leukemia, neutrophilic leukemia, acute promyelocytic leukemia, basophilic leukemia group, basophilic leukemia, eosinophilic leukemia group, eosinophilic leukemia leukemia, monocytic leukemia group, monocytic leukemia not otherwise specified, acute monocytic leukemia, subacute monocytic leukemia, chronic monocytic leukemia, non-leukemic monocytic leukemia, mixed leukemia group, mast cell leukemia, megakaryocytic leukemia, megakaryocytic myelopathy, myeloid sarcoma, hairy cell leukemia, mixed myeloproliferative lymphoproliferative disorder, polycythemia vera, acute panmyelosis, chronic myeloproliferative disorder, myelosclerosis complicated by myeloid metaplasia, idiopathic thrombocythemia, chronic lymphoproliferative disorder.

[0583] In an embodiment of the invention, the disease is selected from the group consisting of pancreatic tumors, pancreatic adenocarcinoma, tumors of the head of the pancreas, body of the pancreas, tail of the pancreas, pancreatic duct, islets of Langerhans, tumors of the neck of the pancreas, prostate tumors, prostate cancer, prostate, neuroendocrine tumors, breast cancer, tumors of the central breast, upper inner quadrant of the breast, lower inner quadrant of the breast, upper outer quadrant of the breast, lower outer quadrant of the breast, axillary process of the breast, tumors of double lesions of the breast, early-onset breast cancer, parathyroid tumors, myeloma, lung cancer, small cell lung cancer, non-small cell lung cancer, tumors of the main bronchus, tumors of the upper lobe of the lung, tumors of the middle lobe of the lung, tumors of the lower lobe of the lung, colorectal cancer, ascending colon, colon Hepatic flexure, transverse colon, splenic flexure, descending colon, sigmoid colon, colonic overlap, small intestinal tumors, liver tumors, hepatocellular adenoma, hepatocellular carcinoma, hepatocellular cholangiocarcinoma, mixed hepatocellular carcinoma and cholangiocarcinoma (ombined), hepatoblastoma, ovarian cancer, sarcoma, osteosarcoma, fibrosarcoma, gastrointestinal stromal tumors, gastrointestinal tract, gastric cancer, thyroid cancer, medullary thyroid carcinoma, thyroid gland, renal cell carcinoma, renal pelvis, bladder tumors, bladder cancer, bladder trigone, bladder dome, bladder lateral wall, bladder posterior wall, ureteral orifice, urachal tumors, overlapping bladder lesions, basal cell carcinoma, basal cell neoplasms, basal cell tumors, basal cell carcinoma, multicentric basal cell carcinoma Basal cell carcinoma, basaloid carcinoma, basal cell adenoma, squamous cell carcinoma, oral squamous cell carcinoma, laryngeal squamous cell carcinoma, cervical cancer, extracervical, cervical overlap, tumors of the uterine cervix, uterine isthmus, uterine tumor, ovarian tumor, cervical esophagus, thoracic esophagus, abdominal esophagus, upper third of the esophagus, middle third of the esophagus, lower third of the esophagus, tumors of overlapping esophageal lesions, endometrial cancer, head and neck cancer, lymphoma, malignant mesothelioma, mesothelial neoplasm, mesothelioma, fibrous mesothelioma, epithelioid mesothelioma, epithelioid mesothelioma, duodenal cancer, neuroendocrine tumor, neuroendocrine tumor of the lung, pancreas neuroendocrine tumors of the stomach, neuroendocrine tumors of the foregut, neuroendocrine tumors of the midgut, neuroendocrine tumors of the hindgut, gastroenteropancreatic neuroendocrine tumors, neuroendocrine carcinoma, neuroendocrine tumors of the breast, neuroendocrine tumors of the ovary, testicular cancer, thymic carcinoma, tumors of the stomach, fundus, body, antrum, pylorus, lesser curvature, greater curvature, overlapping lesions of the stomach, paraganglioma, ganglioneuroma, melanoma, malignant melanoma, nodular melanoma, amelanotic melanoma, superficial spreading melanoma, epithelioid cell melanoma, spindle cell melanoma, mixed epithelioid cell and spindle cell melanoma.

[0584] In further embodiments, the condition is lateral upper lip, lateral lower lip, lateral lip unspecified, upper lip mucosa, lower lip mucosa, labial mucosa unspecified, labial commissure, overlapping lesions of lip, base of tongue unspecified, dorsal surface of tongue unspecified, tongue border, ventral surface of tongue unspecified, anterior two-thirds of tongue unspecified, lingual tonsil, overlapping lesions of tongue, tongue unspecified, upper gingiva, lower gingiva, gingiva unspecified, anterior floor of mouth, lateral floor of mouth, overlapping lesions of floor of mouth, floor of mouth unspecified, hard palate, soft palate unspecified, uvula, overlapping lesions of palate, palate unspecified, buccal mucosa, oral vestibule, retromolar area, overlapping lesions of other and unspecified parts of oral cavity, oral cavity unspecified, ear Submandibular gland, sublingual gland, major salivary gland overlap lesion, major salivary gland unspecified, tonsil fossa, tonsil pillar, tonsil overlap lesion, tonsil unspecified, fossa, anterior surface of epiglottis, lateral oropharyngeal wall, posterior oropharyngeal wall, branchial clefts, oropharynx overlap lesion, oropharynx unspecified, superior nasopharynx wall, posterior nasopharynx wall, lateral nasopharynx wall, anterior nasopharynx wall, nasopharynx unspecified, pyriform sinus, postcricoid surface, hypopharyngeal surface of aryepiglottic fold, posterior hypopharyngeal wall, hypopharyngeal overlap lesion, hypopharynx unspecified, pharynx unspecified, laryngopharynx, Waldeyer's ring, lip, oral and pharyngeal overlap lesion, cervical esophagus, thoracic esophagus, abdominal esophagus, esophagus upper third of the esophagus, middle third of the esophagus, lower third of the esophagus, esophageal duplication, esophagus not otherwise specified, cardia not otherwise specified, fundus, body, antrum, pylorus, lesser curvature of the stomach not otherwise specified, greater curvature of the stomach not otherwise specified, gastric duplication, stomach not otherwise specified, duodenum, jejunum, ileum, Meckel's diverticulum, small intestinal duplication, small intestine not otherwise specified, cecum, appendix, ascending colon, hepatic flexure of the colon, transverse colon, splenic flexure of the colon, descending colon, sigmoid colon, colonic duplication, colon not otherwise specified, rectosigmoid junction, rectum not otherwise specified, anus not otherwise specified, anal canal, cloacal layer, anorectal and anal canal duplication, liver , intrahepatic bile duct, gallbladder, extrahepatic bile duct, ampulla of Vater, biliary duplication, biliary tract unspecified, head of pancreas, body of pancreas, tail of pancreas, pancreatic duct, islets of Langerhans, pancreatic neck, pancreatic duplication, pancreas unspecified, intestinal tract unspecified, digestive system duplication, gastrointestinal tract unspecified, nasal cavity, middle ear, maxillary sinus, ethmoid sinus, frontal sinus, sphenoid sinus, accessory sinus duplication, accessory sinus unspecified, glottis, supraglottis, subglottis, laryngeal cartilage, laryngeal duplication, larynx unspecified, trachea, main bronchus, upper lobe of lung, middle lobe of lung, lower lobe of lung, lung duplication, lung unspecified, thymus, heart, anterior mediastinum, posterior mediastinum, mediastinum unspecified, pleura unspecified,Overlapping lesions of the heart, mediastinum and pleura, upper respiratory tract unspecified, respiratory system and intrathoracic organs unspecified, airway unspecified, upper limb long bone joints, upper limb short bone joints, lower limb long bone joints, lower limb short bone joints, limb bone joints and articular cartilage overlapping lesions, limb bones unspecified, skull and facial bones, mandible, vertebral column, ribs, sternum, clavicle, pelvic bone, bone joints and articular cartilage overlapping lesions, bones unspecified, blood, bone marrow, spleen, reticuloendothelial system unspecified, hematopoietic system unspecified, skin unspecified lips, eyelids unspecified, external ear, facial skin, scalp and neck skin, trunk skin, upper limb skin, lower limb skin, head and neck peripheral nerves, shoulder and arm peripheral Peripheral nerves, peripheral nerves of legs, peripheral nerves of chest, peripheral nerves of abdomen, peripheral nerves of pelvis, peripheral nerves of trunk, peripheral nerve and autonomic nervous system overlap, autonomic nervous system unspecified, retroperitoneum, peritoneum, peritoneum unspecified, retroperitoneal and peritoneal overlap, connective tissue of head, connective tissue of arms, connective tissue of legs, connective tissue of chest, connective tissue of abdomen, connective tissue of pelvis, trunk connective tissue unspecified, subcutaneous connective tissue and other soft tissue overlap, connective tissue unspecified, nipple, central breast, upper inner quadrant of breast, lower inner quadrant of breast, upper outer quadrant of breast, lower outer quadrant of breast, Axillary process of breast, overlapping lesion of breast, breast unspecified, labia majora, labia minora, clitoris, overlapping lesion of vulva, unspecified vulva, unspecified vagina, cervix, ectocervix, overlapping lesion of cervix, uterine isthmus, endometrium, myometrium, fundus, overlapping lesion of uterine body, corpus uteri, unspecified uterus, ovary, fallopian tube, broad ligament of uterus, round ligament, parametrium, uterine adnexa, Wolffian body, overlapping lesion of female genital tract, unspecified female genital tract, foreskin, glans penis, body of penis, overlapping lesion of penis, penis unspecified, prostate, cryptorchidism, descended testis, testis unspecified, epididymis, sperm Cord, scrotum unspecified, tunica vaginalis testis, overlapping lesions of male genitalia, male genitalia unspecified, kidney unspecified, renal pelvis, ureter, trigone, bladder dome, lateral bladder wall, posterior bladder wall, ureteral orifice, urachus, overlapping lesions of bladder, bladder unspecified, urethra, accessory urinary gland, overlapping lesions of urinary tract, urinary system unspecified, conjunctiva, cornea unspecified, retina, choroid, ciliary body, lacrimal gland, orbit unspecified, overlapping lesions of eye and adnexa, eye unspecified, meninges, spinal meninges, meninges unspecified, cerebrum, frontal lobe, temporal lobe, parietal lobe, occipital lobe, ventricle unspecified, cerebellum unspecified, brainstem, overlapping lesions of brain, brain unspecified, spinal cord, cauda equina,The tumor may occur in organs and tissues selected from the group including olfactory nerve, optic nerve, auditory nerve, unspecified cranial nerve, overlapping lesions of brain and central nervous system, unspecified nervous system, thyroid, adrenal cortex, adrenal medulla, unspecified adrenal gland, parathyroid gland, pituitary gland, craniopharyngeal duct, pineal gland, carotid body, aortic body, overlapping lesions of endocrine glands and related structures, unspecified endocrine gland, unspecified face or neck, unspecified chest, unspecified abdomen, unspecified pelvis, unspecified upper extremity, unspecified lower extremity, other unspecified location, overlapping lesions of unspecified location, facial, head and neck lymph nodes, intrathoracic lymph nodes, intraperitoneal lymph nodes, axillary arm lymph nodes, inguinal leg lymph nodes, pelvic lymph nodes, lymph nodes in multiple regions, unspecified lymph nodes, and unknown primary site.

[0585] Subjects treated with the compounds disclosed and claimed herein can be treated in combination with other non-surgical anti-proliferative (e.g., anti-cancer) drug therapies. In one embodiment, the compounds may be administered in combination with an anti-cancer compound, such as a cytostatic compound. A cytostatic compound is a compound (e.g., a small molecule, nucleic acid, or protein) that inhibits cell growth and / or proliferation. In some embodiments, the cytostatic compound is directed against malignant cells of a tumor. In yet other embodiments, the cytostatic compound inhibits the growth and / or proliferation of vascular smooth muscle cells or fibroblasts.

[0586] Suitable antiproliferative or cytostatic compounds for use with the compounds disclosed and claimed herein include anti-cancer drugs.Some anti-cancer drugs that can be used are well known and include, but are not limited to, acivicin; aclarubicin; acodazole hydrochloride; acronine; adozelesin; aldesleukin; altretamine; ambomycin; amethanthrone acetate; aminoglutethimide; amsacrine; anastrozole; anthramycin; asparaginase; asperlin; azacytidine; azetepa; azotomycin; batimastat; benzodepa; bicalutamide; bisantrene hydrochloride; bisnafide dimesylate; bizelesin; Bleomycin sulfate;Brequinar sodium;Bropirimine;Busulfan;Cactinomycin;Calsterone;Caracemide;Carbetimer;Carboplatin;Carmustine;Carubicin hydrochloride;Carzelesin;Cedefingol;Chlorambucil;Ciloremycin;Cisplatin;Cladribine;Crisnatol mesylate;Cyclophosphamide;Cytarabine;Dacarbazine;Dactinomycin;Daunorubicin hydrochloride;Decitabine;Dexormaplatin;Dezaguanine;Dezaguanine mesylate;Diaziquone;Doceta Doxorubicin; Doxorubicin hydrochloride; Droloxifene; Droloxifene citrate; Dromostanolone propionate; Duazomycin; Edatrexate; Eflornithine hydrochloride; Elsamitrucin; Enloplatin; Enpromate; Epipropizine; Epirubicin hydrochloride; Elbrozole; Esorubicin hydrochloride; Estramustine; Estramustine phosphate sodium; Etanidazole; Etoposide; Etoposide phosphate; Etoprine; Fadrozole hydrochloride; Fazarabine; Fenretinide; Flocc Uridine; Fludarabine phosphate; Fluorouracil; Flurocitabine; Fosquidone; Fostriecin sodium; Gemcitabine; Gemcitabine hydrochloride; Hydroxyurea; Idarubicin hydrochloride; Ifosfamide; Irmofosine; Interferon alfa-2a; Interferon alfa-2b; Interferon alfa-n1; Interferon alfa-n3; Interferon beta-1a; Interferon gamma-1b; Iproplatin; Irinotecan hydrochloride; Lanreotide acetate; Letrozole;Leuprolide acetate; Liarozole hydrochloride; Lometrexol sodium; Lomustine; Losoxantrone hydrochloride; Masoprocol; Maytansine; Mechlorethamine hydrochloride; Megestrol acetate; Melengestrol acetate; Melphalan; Menogaril; Mercaptopurine; Methotrexate; Methotrexate sodium; Metoprine; Meturedepa; Mitindomide; Mitocalcin; Mitochromin; Mitogillin; Mitomarcin; Mitomycin; Mitospar; Mitotane; Mitoxantrone hydrochloride; Mycophenolic acid; Ni Raparib; Nocodazole; Nogalamycin; Olparib; Ormaplatin; Oxisuran; Paclitaxel; Pegaspargase; Periomycin; Pentamustine; Peplomycin sulfate; Perfosfamide; Pipobroman; Piposulfan; Piroxantrone hydrochloride; Plicamycin; Promestane; Porfimer sodium; Porfiromycin; Prednimustine; Procarbazine hydrochloride; Puromycin; Puromycin hydrochloride; Pirazofurin; Ribopurin; Rogletimide; Rucaparib; Safingo ru; safingol hydrochloride; semustine; simtrazene; sparfosate sodium; sparsomycin; spirogermanium hydrochloride; spiromustine; spiroplatin; streptonigrin; streptozocin; sulofenur; talazoparib; tallysomycin; taxol; taxotere; tecogalan sodium; tegafur; teloxantrone hydrochloride; temoporfin; teniposide; teroxylon; testolactone; thiamiprine; thioguanine; thiotepa; tiazofurin; tirapazamine; topotecan hydrochloride; Toremifene citrate; trestron acetate; triciribine phosphate; trimetrexate; trimetrexate glucuronate; tuburozole hydrochloride; uracil mustard; uredepa; vapreotide; veraparib; verteporfin; vinblastine sulfate; vincristine sulfate; vindesine; vindesine sulfate; vinepidine sulfate; vinglisinate sulfate; vinleurosine sulfate; vinorelbine tartrate; vinrocidine sulfate; vinzolidine sulfate; vorozole; zeniplatin; zinostatin; and zorubicin hydrochloride.

[0587] Other anti-cancer drugs include, but are not limited to, 20-epi-1,25-dihydroxyvitamin D3; 5-ethynyluracil; abiraterone; acylfulvene; adecipenol; adozelesin; ALL-TK antagonists; ambamustine; amidox; amifostine; aminolevulinic acid; amrubicin; anagrelide; andrographolide; angiogenesis inhibitors; antagonist D; antagonist G; antarelix; anti-dorsalizing morphogenetic protein-1 (anti-dorsalizing morphogenetic protein-1) protein-1); antiestrogens; antineoplastons; antisense oligonucleotides; aphidicolin glycinate; apoptosis gene modulators; apoptosis regulators; apurinic acid; ara-CDP-DL-PTBA; arginine deaminase; asulaculin; atamestane; atlimustine; axinastatin 1; axinastatin 2; axinastatin 3; azasetron; azatoxins; azatyrosine; baccatin III derivatives; balanol; batimastat; BCR / ABL antagonists; benzochlorins; benzoylstaurosporines; beta-lactam derivatives; beta-arretin; betaclamycin B; betulinic acid; bFGF inhibitors; bisaziridinylspermine; bisnafide; bisstraten A; brefullate; budotitanium; buthionine sulfoximine; calcipotriol; calphostin C; camptothecin derivatives; canarypox IL-2; capecitabine; carboxamido-amino-triazoles; carboxyamidotriazoles; CaRest M3; CARN 700; cartilage-derived inhibitor; casein kinase inhibitor (ICOS); castanospermine; cecropin B; cetrorelix; chlorin; chloroquinoxaline sulfonamide; cicaprost; cis-porphyrin; clomiphene analog; clotrimazole; colismycin A; colismycin B; combretastatin A4; combretastatin analog; conagenin; crambecidin 816; crisnatol; cryptophycin 8; cryptophycin A derivative; curacin A; cyclopentaanthraquinone; cycloplatam; sipemycin; cytarabine ocphosphate; cytolytic factors; cytostatin; dacliximab; dehydrodidemnin B; deslorelin;Dexphosphamide; dexrazoxane; dexverapamil; didemnin B; didox; diethylnorspermine; dihydro-5-azacytidine; 9-dihydrotaxol; dioxamycin; diphenylspiromustine; docosanol; dolasetron; doxifluridine; dronabinol; duocarmycin SA; ebselen; ecomustine; edelfosine; edrecolomab; eflomitin; elemene; emiteflu; epirubicin; epristeride; estramustine analogs; estrogen agonists; Estrogen antagonists; etanidazole; etoposide phosphate; exemestane; filgrastim; finasteride; flavopiridol; flezelastine; fluasterone; fludarabine; fluorodaunornithine hydrochloride; forfenimex; formestane; fotemustine; gadolinium texaphyrin; gallium nitrate; gallocitabine; ganirelix; gelatinase inhibitors; glutathione inhibitors; hepsulfam; heregulin; hexamethylene bisacetamide; hypericin; ibandronate; idoxifene; idramantone; ilmofo Cinnam; Ilomastat; Imidazoacridone; Imiquimod; Immunostimulatory peptides; Insulin-like growth factor-I receptor inhibitors; Interferon agonists; Interferons; Interleukins; Iobengan; Iododoxorubicin; 4-ipomeanol; Irinotecan; Ilopract; Irsogladine; Isobengazole; Isohomohalichondrin B; Itasetron; Jasplakinolide; Kahalalide F; Lamellarin-N triacetate; Lanreotide; Leinamycin; Lenograstim; Lentinan sulfate; Leptolus Statins; leukemia inhibitory factor; leukocyte alpha interferon; leuprolide + estrogen + progesterone; leuprorelin; levamisole; liarozole; linear polyamine analogs; lipophilic disaccharide peptides; lipophilic platinum compounds; lisoclinamide 7; lobaplatin; lombricin; lometrexol; lonidamine; losoxantrone; lovastatin; loxoribine; lutotecan; lutetium texaphyrin; lisofylline; lytic peptides; maytansine; mannostatin A; marimastat; massoprocol; maspin; matrilysin inhibitors;Matrix metalloproteinase inhibitors; mervalone; meterelin; methioninase; metoclopramide; MIF inhibitors; mifepristone; miltefosine; millimostim; mismatched double-stranded RNA; mitoguazone; mitolactol; mitomycin analogs; mitonafide; mitotoxin fibroblast growth factor-saporin; mofalotene; monoclonal antibodies, human chorionic gonadotropin; monophosphoryl lipid A + mycobacterium cell wall sk; mopidamol; multidrug resistance gene inhibitors; multiple tumor suppressor 1-based Anticancer therapy; Mustard anticancer compounds; Mycaperoxide B; Mycobacterial cell wall extract; Myriaporone; N-acetyldinaline; N-substituted benzamides; Nafarelin; Nagrestip; Naloxone + pentazocine; Napavine; Naphterpine; Nartograstim; Nedaplatin; Nemorubicin; Neridronic acid; Neutral endopeptidase; Nilutamide; Nisamycin; Nitric oxide modulators; Nitroxide antioxidants; Nitrulline; O6-benzylguanine; Octreotide; Oxenone; Oligonucleotides; Onapristone; Ondanse Tron; Ondansetron; Oracin; Oral cytokine inducers; Osateron; Oxaliplatin; Oxaunomycin; Paclitaxel analogs; Paclitaxel derivatives; Palauamine; Palmitoylrhizoxin; Pamidronate; Panaxytriol; Panomyphen; Parabactin; Pazeliptin; Pegaspargase; Perdecin; Pentosan polysulfate sodium; Pentostatin; Pentrozole; Perflubron; Perfosfamide; Perillyl alcohol; Phenazinomycin; Phenylacetate; Phosphatase inhibitors; Picibanil; Pi Rocarpine hydrochloride; Pirarubicin; Piritrexim; Prasetin A; Prasetin B; Plasminogen activator inhibitors; Platinum complexes; Platinum compounds; Platinum-triamine complexes; Porfimer sodium; Porfiromycin; Propylbis-acridone; Prostaglandin J2; Proteasome inhibitors; Protein A-based immunomodulators; Protein kinase C inhibitors; Protein kinase C inhibitor(s); Microalgae; Protein tyrosine phosphatase inhibitors; Purine nucleoside phosphorylase inhibitors; Purpurin; Pyrazoloacridines;Pyridoxylated hemoglobin polyoxyethylene conjugate; raf antagonist; raltitrexed; ramosetron; ras farnesyl protein transferase inhibitor; ras inhibitor; ras-GAP inhibitor; demethylated leteriptin; rhenium etidronate (Re186); rhizoxin; ribozyme; RII retinamide; rohitukin; romurtide; roquinimex; rubiginone B1; ruboxil; saintopine; SarCNU; saclophytol A; sargramostim; Sdi1 mimetic; aging Origin inhibitor 1; Sense oligonucleotide; Signal transduction inhibitor; Signal transduction modulator; Single-chain antigen-binding protein; Schizofuran; Sobuzoxane; Sodium borocaptate; Sodium phenylacetate; Sorbrol; Somatomedin-binding protein; Sonermin; Sparfosic acid; Spicamycin D; Spiromustine; Splenopentin; Spongistatin 1; Squalamine; Stem cell inhibitor; Stem cell division inhibitor; Stipiamide; Stromelysin inhibitor; Sulfinosine; Superactive vasoactive intestinal peptide antagonist To; Sladista; Suramin; Swainsonine; Synthetic glycosaminoglycans; Talimustine; Tamoxifen methiodide; Tauromustine; Tazarotene; Tecogalan sodium; Tegafur; Terlapyrylium; Telomerase inhibitors; Temozolomide; Tetrachlorodecaoxide; Tetrazomine; Taliblastine; Thalidomide; Thiocoraline; Thrombopoietin; Thrombopoietin mimetics; Thymalfasin; Thymopoietin receptor agonists; Thymotrin; Thyroid-stimulating hormone; Ethyl etiopluprins; Ni Titanocene chloride; topsentin; toremifene; totipotent stem cell factor; translation inhibitors; tretinoin; triacetyluridine; triciribine; tropisetron; turosteride; tyrosine kinase inhibitors; tyrphostins; UBC inhibitors; ubenimex; urogenital sinus-derived growth inhibitory factor; urokinase receptor antagonists; variolin B; vector systems, erythrocyte gene therapy; veraresol; veramine; verudin; vinorelbine; vinxartin; vitaxin; zanoterone; zilascorub; and zinostatin stimalamer.

[0588] The compounds disclosed and claimed herein may also be used in combination with any of the following treatments: Therapy in combination with inhibitors of poly(ADP-ribose) polymerase (PARP), a class of chemotherapy drugs that target cancers with defective DNA damage repair (Yuan et al., Expert Opin Ther Pat, 2017, 27:363). Such PARP inhibitors include, but are not limited to, olaparib, rupacarib, velaparib, niraparib, talazoparib, pamiparib, iniparib, E7449, and A-966492.

[0589] For example, nuclear factor-kappa B signal transduction therapy is combined with inhibitors of signal transduction pathways and mechanisms that lead to the repair of DNA single-strand and double-strand breaks (Pilie et al., Nat Rev Clin Oncol, 2019, 16:81; Zhang et al., Chin J Cancer, 2012, 31:359). Such inhibitors include, but are not limited to, inhibitors of ATM and ATR kinase, checkpoint kinase 1 and 2, DNA-dependent protein kinase, and WEE1 kinase (Pilie et al., Nat Rev Clin Oncol, 2019, 16:81).

[0590] Immunomodulators (Khalil et al., Nat Rev Clin Oncol, 2016, 13:394), cancer vaccines (Hollingsworth et al., NPJ Vaccines, 2019, 4:7), immune checkpoint inhibitors (e.g., PD-1, PD-L1, CTLA-4 inhibitors) (Wei et al., Cancer Discov, 2018, 8:1069), cyclin D kinase 4 / 6 inhibitors (Goel et al., Trends Cell Biol, 2018, 28:911), antibodies that can bind to tumor cells and / or metastases and induce antibody-dependent cellular cytotoxicity (ADCC) (Kellner et al., Transfus Med Hemother, 2017, 44:327), T cell or NK cell engagers (e.g., bispecific antibodies) (Yu et al., J Cancer Res Clin Oncol, 2019, 145:941), in combination with cell therapy using expanded autologous or allogeneic immune cells (e.g., chimeric antigen receptor T (CAR-T) cells) (Khalil et al., Nat Rev Clin Oncol, 2016, 13:394). Immune checkpoint inhibitors include, but are not limited to, nivolumab, ipilimumab, pembrolizumab, atezolizumab, avelumab, durvalumab, and cemiplimab.

[0591] According to the present invention, the compound can be administered before, simultaneously with, or after other anti-cancer compounds. The administration schedule can include administering different agents in an alternating manner. In other embodiments, the compound can be delivered before and during, during and after, or before and after treatment with other therapies. In some cases, the compound is administered more than 24 hours before the administration of other anti-proliferative treatments. In other embodiments, more than one anti-proliferative therapy can be administered to the subject. For example, the subject can receive the compound of the present invention in combination with both surgery and at least one other anti-proliferative compound. Alternatively, the compound can be administered in combination with more than one anti-cancer drug.

[0592] In some embodiments, the compounds of the present invention are used to detect cells and tissues that overexpress FAP, and such detection is achieved by conjugating a detectable label, preferably a detectable radionuclide, to the compounds of the present invention.In preferred embodiments, the cells and tissues to be detected are diseased cells and tissues, and / or are the sole cause of disease and / or disease symptoms, or are part of the underlying pathology of disease.In more preferred embodiments, the diseased cells and tissues cause and / or are part of oncological conditions (e.g., neoplasia, tumor, and cancer) or non-oncological conditions (e.g., inflammatory disease, cardiovascular disease, autoimmune disease, and fibrotic disease).

[0593] In another embodiment, the compounds of the present invention are used to treat cells and tissues that overexpress FAP. In a preferred embodiment, the treated cells and tissues are diseased cells and tissues, and / or are one or the only cause of disease and / or disease symptoms, or are part of the underlying pathology of disease. In a more preferred embodiment, the diseased cells and tissues cause and / or are part of oncological adaptations (e.g., neoplasia, tumor, and cancer), and therapeutic activity is achieved by conjugating a therapeutically active effector, preferably a therapeutically active radionuclide, to the compounds of the present invention. In a more preferred embodiment, the diseased cells and tissues cause and / or are part of non-oncological adaptations (e.g., inflammatory diseases, cardiovascular diseases, autoimmune diseases, and fibrotic diseases), and therapeutic activity is achieved by inhibiting the enzymatic activity of FAP.

[0594] In further embodiments, particularly when the disease is a non-tumor disease or non-tumor indication (e.g., inflammatory disease, cardiovascular disease, autoimmune disease, and fibrotic disease), the compounds of the present invention are administered in a therapeutically effective amount; preferably, the compounds of the present invention do not contain therapeutically active nuclides. An effective amount is the amount of compound administered that is sufficient to produce a therapeutically or medically desired result or effect in the subject to which the compound is administered. The effective amount will vary depending on the particular condition being treated, the age and physical condition of the subject being treated, the severity of the condition, the duration of treatment, the nature of concurrent or concomitant therapy (if any), the particular route of administration, and factors within the knowledge and expertise of the medical professional. For example, in the context of a method for treating a subject with a condition characterized by abnormal cell proliferation, an effective amount for inhibiting proliferation would be an amount sufficient to reduce or completely stop abnormal cell proliferation, for example, to slow or stop the development or progression of a cell mass such as a tumor. As used in this embodiment, "inhibit" encompasses all of the above.

[0595] In other embodiments, a therapeutically effective amount will be the amount necessary to prolong the dormancy of micrometastases or stabilize remaining primary tumor cells following surgery or drug therapy. Generally, when using unconjugated compounds that do not contain a therapeutically active radionuclide, the therapeutically effective amount will vary depending on the age, condition, and sex of the subject, as well as the nature and extent of the disease in the subject, all of which can be determined by one of ordinary skill in the art. Dosages can be adjusted by the individual physician or veterinarian, particularly in the event of complications. A therapeutically effective amount typically ranges from 0.1 μg / kg to about 2000 mg / kg, or 1.0 μg / kg to about 1000 mg / kg, or about 0.1 mg / kg to about 500 mg / kg, or about 1.0 mg / kg to about 100 mg / kg, administered in one or more doses per day for one or more days. If desired, the effective daily dose of the active compound may be administered as two, three, four, five, six, or more subdoses, for example, administered separately at appropriate intervals throughout the day, in unit dosage forms, as needed. In some embodiments, the compound is administered for more than 7 days, more than 10 days, more than 14 days, and more than 20 days. In still other embodiments, the compound is administered for several weeks or several months. In still other embodiments, the compound is delivered every other day. For example, the agent is delivered every 2 days, or every 3 days, or every 4 days, or every 5 days, or every 6 days, or every week, or every month.

[0596] In a preferred embodiment, the compounds of the invention are for use in the treatment and / or prevention of disease, whereby such treatment is radionuclide therapy. Preferably, radionuclide therapy utilizes or is based on different forms of radiation emitted by radionuclides. Such radiation includes, for example, photon radiation, but is not limited to, β -The radiation may be any one of electron radiation, including particle and Auger electron radiation, proton radiation, neutron radiation, positron radiation, alpha particle radiation or ion beam radiation.Depending on the type of particle or radiation emitted by the radionuclide, radionuclide therapy can be distinguished, for example, as photon-emitting radionuclide therapy, electron-emitting radionuclide therapy, proton-emitting radionuclide therapy, neutron-emitting radionuclide therapy, positron-emitting radionuclide therapy, alpha particle-emitting radionuclide therapy or ion beam radionuclide therapy.All these forms of radionuclide therapy are encompassed by the present invention, and all these forms of radionuclide therapy can be realized by the compound of the present invention, preferably under the condition that the radionuclide bound to the compound of the present invention, more preferably as an effector, provides this type of radiation.

[0597] Radionuclide therapy preferably works by damaging the DNA of cells. Damage is caused by photons, electrons, protons, neutrons, positrons, alpha particles, or ion beams, which directly or indirectly ionize the atoms that make up the DNA chain. Indirect ionization occurs as a result of the ionization of water, forming free radicals, particularly hydroxyl radicals, which then damage DNA.

[0598] In the most common forms of radionuclide therapy, many of the effects of radiation are due to free radicals. Because cells have mechanisms for repairing DNA damage, breaking DNA on both strands proves to be the most significant technique for altering cellular characteristics. Because cancer cells are generally undifferentiated and stem cell-like, they replicate more and have a reduced ability to repair sublethal damage compared to many healthy, differentiated cells. DNA damage is inherited through cell division, causing cancer cells to accumulate damage and die or replicate more slowly.

[0599] Oxygen is a potent radiosensitizer, increasing the effectiveness of a given dose of radiation by forming DNA-damaging free radicals. Therefore, the use of hyperbaric oxygen tanks, blood substitutes that deliver large amounts of oxygen, hypoxic cell radiosensitizers such as misonidazole and metronidazole, and hypoxic cell toxins such as tirapazamine can be applied.

[0600] Other factors to consider when selecting the radioactive dose include whether the patient is receiving chemotherapy, whether the radiation therapy is administered before or after surgery, and the degree of success of the surgery.

[0601] The total radioactive dose can be fractionated, i.e., spread over time as one or more treatments, for several important reasons. Fractionation allows normal cells time to recover, while tumor cells generally repair less efficiently between fractionated doses. Fractionation also allows tumor cells that were in a relatively radioresistant phase of the cell cycle during one treatment to cycle back to a sensitive phase before the next fractionated dose is administered. Similarly, tumor cells that were chronically or acutely hypoxic and therefore more radioresistant can reoxidize between fractions, improving tumor cell killing.

[0602] It is generally known that different cancers respond differently to radiation therapy. The response of a cancer to radiation is described by its radiosensitivity. Cancer cells that are highly radiosensitive are rapidly killed by moderate doses of radiation. These include leukemia, many lymphomas, and germ cell tumors.

[0603] To some extent, it is important to distinguish the radiosensitivity of a particular tumor, a laboratory measurement, from the "cure potential" of the cancer with an internally delivered dose of radioactivity in actual clinical practice. For example, leukemia is generally not curable with radiation therapy because it is disseminated throughout the body. Lymphoma may be curable with radiation if localized to one area of ​​the body. Similarly, many common, moderately radioresponsive tumors can be treated with curative doses of radioactivity if they are in their early stages. This is true, for example, for non-melanoma skin cancer, head and neck cancer, non-small cell lung cancer, cervical cancer, anal cancer, and prostate cancer.

[0604] A tumor's response to radiation therapy is also related to its size. For complex reasons, very large tumors are less responsive to radiation than small tumors or microscopic disease. Various strategies are used to overcome this effect. The most common technique is surgical resection before radiation therapy. This is most commonly seen in the treatment of breast cancer with wide local excision or mastectomy, followed by adjuvant radiation therapy. Another method is to shrink the tumor using neoadjuvant chemotherapy before radionuclide therapy. A third technique is to enhance the cancer's radiosensitivity by administering certain drugs during the course of radiation therapy. Examples of radiosensitizing drugs include, but are not limited to, cisplatin, nimorazole, and cetuximab.

[0605] Intraoperative radiation therapy is a special type of radiation therapy delivered immediately after the surgical removal of the cancer. This method has been used in breast cancer (targeted intraoperative radiation therapy), brain tumors, and rectal cancer.

[0606] Radionuclide therapy itself is painless. Many low-dose palliative treatments are minimally or ineffective. Higher-dose treatments can cause side effects that vary during treatment (acute side effects), within months or years after treatment (long-term side effects), or even after further treatment (cumulative side effects). The nature, severity, and persistence of side effects depend on the organ receiving the radiation, the treatment itself (type of radionuclide, dose, fractionation, concurrent chemotherapy), and the patient.

[0607] It is within the scope of the present invention that each and any of the above strategies may be implemented insofar as the methods for treating the diseases of the present invention are known as such in the art and constitute further embodiments of the present invention.

[0608] It is also within the scope of the present invention that the compounds of the present invention be used in methods for the diagnosis of the diseases disclosed herein, preferably comprising the step of administering a diagnostically effective amount of a compound of the present invention to a subject in need thereof.

[0609] According to the present invention, the imaging method is selected from the group consisting of scintigraphy, single photon emission computed tomography (SPECT) and positron emission tomography (PET). In a preferred embodiment of the present invention, the compounds according to the present invention comprising a chelator from the N4 chelator family, more preferably a chelator that chelates a Tc radionuclide, are particularly suitable for use in methods and procedures using SPECT. In this embodiment, the chelator from the N4 chelator family is N4Ac.

[0610] In a preferred embodiment of the invention, compounds according to the invention that comprise a NODAGA chelator, more preferably that chelate a Ga radionuclide, are particularly suitable for use in methods and procedures that employ PET.

[0611] Scintigraphy is a form of diagnostic examination or method used in nuclear medicine, in which a radiopharmaceutical is internalized by cells, tissues and / or organs, preferably in vivo, and the radiation emitted by the internalized radiopharmaceutical is captured by an external detector (gamma camera) to form and display a two-dimensional image.In contrast, SPECT and PET form and display a three-dimensional image.For this reason, SPECT and PET are classified as separate technologies from scintigraphy, but they also use a gamma camera to detect internal radiation.Scintigraphy is different from diagnostic X-ray, in which external radiation passes through the body to form an image.

[0612] Single-photon emission computed tomography (SPECT) scans are a type of nuclear imaging technique that uses gamma rays. They are very similar to traditional nuclear medicine 2D imaging using a gamma camera. Before a SPECT scan, the patient is injected with a radiolabeled chemical that emits gamma rays that can be detected by the scanner. A computer collects information from the gamma camera and converts it into 2D cross-sectional images. These cross-sectional images can be reconstructed to form a 3D image of the organ or tissue. SPECT involves the detection of gamma rays emitted by radionuclides provided by radiolabeled chemicals, both singly and sequentially. To acquire a SPECT image, the gamma camera rotates around the patient. Projection images are acquired at specified points during the rotation, typically every 3–6°. A full 360° rotation is often used to obtain an optimal reconstruction. The time required to acquire each projection image also varies, but 15–20 seconds is typical. This gives a total scan time of 15–20 minutes. Multi-headed gamma cameras are faster. SPECT acquisition is very similar to 2D gamma camera imaging, so the same radiopharmaceuticals can be used.

[0613] Positron emission tomography (PET) is a noninvasive diagnostic imaging technique for measuring the biochemical state or metabolic activity of cells in the human body. PET is unique because it produces images of basic biochemistry or function within the body. Traditional diagnostic techniques, such as X-rays, CT scans, or MRIs, produce images of the body's anatomy or structure. The premise of these techniques is that they can visualize changes in the structure or structure associated with disease. Biochemical processes are also altered by disease and may occur before overall changes in the anatomy. PET is an imaging technique that can visualize some of these early biochemical changes. PET scanners rely on radiation emitted by the patient to create images. Each patient is given a minute amount of a radiopharmaceutical that closely resembles a natural substance used by the body or that specifically binds to a receptor or molecular structure. As a radioisotope undergoes positron-emitting decay (also known as beta-plus decay), it emits a positron, the antiparticle counterpart of the electron. After traveling up to a few millimeters, the positron encounters an electron, annihilates, and generates a pair of counter-moving (gamma) photons. These are detected when they reach the scintillation material in the scanning device, producing a flash of light that is detected by a photomultiplier tube or silicon avalanche photodiode. The technique relies on the simultaneous or coincident detection of photon pairs. Photons that do not arrive as a pair, i.e., within a few nanoseconds of e...

Claims

1. Formula (I) 【Chemistry 1】 Cyclic peptides and an N-terminal modifying group A attached to Xaa1, the peptide sequence is drawn from left to right in the N-terminal to C-terminal direction; Xaa1 is a group represented by formula (II) 【Chemistry 2】 is a residue of an amino acid R １ａ is —NH—, R １ｂ is H or CH ３ and n=0 or 1; the N-terminal modification group A is covalently bonded to the nitrogen atom of Xaa1; the carbonyl group of Xaa1 is covalently bonded to the nitrogen of Xaa2, and the sulfur atom of Xaa1 is covalently bonded to Yc as a thioether; Xaa2 is a group represented by formula (III), (IV), or (XX) 【Transformation 3】 is a residue of an amino acid R ２ａ , R ２ｂ , R ２ｃ are each independently (C １ ~C ２ ) alkyl and H, wherein (C １ ~C ２ ) alkyl is OH, NH ２ , halogen, (C ５ ~C ７ ) cycloalkyl; p=0, 1, or 2; v=1 or 2, w=1, 2, or 3, and The amino acid of formula (IV) may contain methyl, OH, NH at positions 3 and 4 of the indicated ring. ２ and F, Xaa3 is represented by formula (V) or (XX) 【Chemistry 4】 is a residue of an amino acid X ３ is CH ２ , C.F. ２ , CH-R ３ｂ , S, O, and NH; p=1 or 2; v=1 or 2, w=1, 2, or 3; R ３ａ H, methyl, OH, NH ２ , or F, R ３ｂ is methyl, OH, NH ２ , or F, Xaa4 is a group represented by formula (VI) 【Transformation 5】 is a residue of an amino acid R ４ａ H, OH, COOH, CONH ２ , X ４ and —NH—CO—X ４ and X is selected from the group consisting of ４ But (C １ ~C ６ ) alkyl, (C ５ ~C ６ ) aryl, and (C ５ ~C ６ ) heteroaryl; and X ４ is methyl, CONH ２ , halogen, NH ２ and OH, q=1, 2, or 3, and the one, two, or three CH ２ -group, one or two hydrogen atoms of which are independently methyl, ethyl, (C ５ ~C ６ ) aryl, or (C ５ ~C ６ ) optionally substituted by heteroaryl; R ４ｂ is methyl or H, Xaa5 is structure (VII) 【Transformation 6】 is a residue of an amino acid R ５ is OH and NH ２ is selected from the group r=1, 2, or 3; Xaa6 is an amino acid selected from the group consisting of aromatic L-α-amino acids and heteroaromatic L-α-amino acids; Xaa7 is a group represented by formula (IX) 【Transformation 7】 is an aminothiol or amino acid residue of R ７ａ -CO-, -COOH, -CONH ２ , -CH ２ -OH, -(CO)-NH-R ７ｂ , -(CO)-(NR ７ｃ )-R ７ｂ , or H, and R ７ｂ and R ７ｃ are each independently (C １ ~C ４ ) alkyl, t is 1 or 2, Yc is a group represented by the formula (X) 【Transformation 8】 and connecting the S atom of Xaa1 with the S atom of Xaa7 under the formation of two thioether linkages, thereby forming a compound of formula (XXI) 【Chemistry 9】 forming a ring structure of the substitution pattern of the aromatic group of formula (X) is ortho, meta, or para; n=0 or 1; t=1 or 2, Y １ is C—H or N, Y ２ is N or C-R ｃ１ and R ｃ１ is H or CH ２ -R ｃ２ and R ｃ２ is of formula (XI), (XII), or (XXII) 【Chemistry 10】 The structure is R ｃ３ and R ｃ４ are each independently H and (C １ ~C ４ ) alkyl; and u=1, 2, 3, 4, 5, or 6; x and y are each independently 1, 2, or 3; and X=O or S; In formulas (XI) and (XXII), one of the nitrogen atoms is R ｃ１ No-CH ２ -, and in formula (XII), -X- is R ｃ１ No-CH ２ - and The N-terminal modifying group A is a blocking group Ab1, and the blocking group Ab1 is R ａ１ -NH-C(O)-, and R ａ１ OH, F, COOH, (C ３ ~C ８ ) cycloalkyl, aryl, heteroaryl, and (C ３ ~C ８ ) C, each of which may be independently substituted with up to two substituents independently selected from the group consisting of heterocycles; ３ Alkyl, C ４ Alkyl, or C ５ alkyl, (C １ ~C ８ ) In alkyl, -CH ２ A compound, or a pharmaceutically acceptable salt, hydrate or pharmaceutically acceptable solvate thereof, wherein one of the - groups may be replaced by -S- or -O-.

2. R ａ１ The compound of claim 1, or a pharmaceutically acceptable salt, hydrate or solvate thereof, wherein is n-butyl.

3. Yc 【Chemistry 11】 The structure is R ｃ１ is CH ２ -R ｃ２ or H, R ｃ２ is represented by formula (XIId) or formula (XXIIb) 【Chemistry 12】 The structure is Z is a chelator which may include a linker; R ｃ４ is H or methyl, and 3. The compound of claim 1 or 2, or a pharmaceutically acceptable salt, hydrate or solvate thereof, wherein u=1, 2, 3, 4, or 5.

4. R ｃ２ is represented by formula (XIId) 【Chemistry 13】 The structure is u=1, R ｃ４ 4. The compound of claim 3, or a pharmaceutically acceptable salt, hydrate or solvate thereof, wherein

5. 5. The compound of claim 3 or 4, or a pharmaceutically acceptable salt, hydrate or solvate thereof, wherein the linker is selected from the group consisting of Ttds and O2Oc.

6. The compound of claim 1, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, The compound is 【Chemistry 14-1】 【Chemistry 14-2】 【Chemistry 14-3】 【Chemistry 14-4】 【Chemistry 14-5】 【Chemistry 14-6】 【Chemistry 14-7】 【Chemistry 14-8】 【Chemistry 14-9】 【Chemistry 14-10】 【Chemistry 14-11】 【Chemistry 14-12】 [Chemistry 14-13] 【Chemistry 14-14】 selected from the group consisting of The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

7. Formula (I) 【Chemistry 15】 Cyclic peptides and an N-terminal modifying group A attached to Xaa1, the peptide sequence is drawn from left to right in the N-terminal to C-terminal direction; Xaa1 is a group represented by formula (II) 【Chemistry 16】 is a residue of an amino acid R １ａ is —NH—, R １ｂ is H or CH ３ and n=0 or 1; the N-terminal modification group A is covalently bonded to the nitrogen atom of Xaa1; the carbonyl group of Xaa1 is covalently bonded to the nitrogen of Xaa2; the sulfur atom of Xaa1 is covalently bonded to Yc as a thioether; Xaa2 is a group represented by formula (III), (IV), or (XX) 【Chemistry 17】 is a residue of an amino acid R ２ａ , R ２ｂ , R ２ｃ are each independently (C １ ~C ２ ) alkyl and H, wherein (C １ ~C ２ ) alkyl is OH, NH ２ , halogen, (C ５ ~C ７ ) cycloalkyl; p=0, 1, or 2; v=1 or 2, w=1, 2, or 3, and The amino acid of formula (IV) may contain methyl, OH, NH at positions 3 and 4 of the indicated ring. ２ and F, Xaa3 is represented by formula (V) or (XX) [Chemistry 18] is a residue of an amino acid X ３ is CH ２ , C.F. ２ , CH-R ３ｂ , S, O, and NH; p=1 or 2; v=1 or 2, w=1, 2, or 3; R ３ａ H, methyl, OH, NH ２ , or F, R ３ｂ Methyl, OH, NH ２ , or F, Xaa4 is a group represented by formula (VI) 【Chemistry 19】 is a residue of an amino acid R ４ａ H, OH, COOH, CONH ２ , X ４ and —NH—CO—X ４ and X is selected from the group consisting of ４ But (C １ ~C ６ ) alkyl, (C ５ ~C ６ ) aryl, and (C ５ ~C ６ ) heteroaryl; and X ４ is methyl, CONH ２ , halogen, NH ２ and OH, q=1, 2, or 3, and the one, two, or three CH ２ -group, one or two hydrogen atoms of which are independently methyl, ethyl, (C ５ ~C ６ ) aryl, or (C ５ ~C ６ ) optionally substituted by heteroaryl; R ４ｂ is methyl or H, Xaa5 is structure (VII) 【Chemistry 20】 is a residue of an amino acid R ５ is OH and NH ２ is selected from the group r=1, 2, or 3; Xaa6 is an amino acid selected from the group consisting of aromatic L-α-amino acids and heteroaromatic L-α-amino acids; Xaa7 is a group represented by formula (IX) 【Chemistry 21】 is an aminothiol or amino acid residue of R ７ａ -CO-, -COOH, -CONH ２ , -CH ２ -OH, -(CO)-NH-R ７ｂ , -(CO)-(NR ７ｃ )-R ７ｂ , or H, R ７ｂ and R ７ｃ are each independently (C １ ~C ４ ) alkyl, t is 1 or 2, Yc is a group represented by the formula (X) 【Chemistry 22】 and connecting the S atom of Xaa1 with the S atom of Xaa7 under the formation of two thioether linkages, thereby forming a compound of formula (XXI) 【Chemistry 23】 forming a ring structure of the substitution pattern of the aromatic group of formula (X) is ortho, meta, or para; n=0 or 1; t=1 or 2, Y １ is C—H, Y ２ is C-R ｃ１ and R ｃ１ is CH ２ -R ｃ２ or H, R ｃ２ is of formula (XIId) or (XXIIc) 【Chemistry 24】 The structure is u=1, R ｃ４ is H, Z is a chelator which may include a linker; The N-terminal modifying group A is a blocking group Ab1, and the blocking group Ab1 is R ａ１ -NH-C(O)-, and R ａ１ OH, F, COOH, (C ３ ~C ８ ) cycloalkyl, aryl, heteroaryl, and (C ３ ~C ８ ) optionally substituted with up to two substituents independently selected from the group consisting of heterocycles (C １ ~C ８ ) alkyl, and (C １ ~C ８ ) In alkyl, -CH ２ A compound, or a pharmaceutically acceptable salt, hydrate or pharmaceutically acceptable solvate thereof, wherein one of the - groups may be replaced by -S- or -O-.

8. R ｃ２ is represented by formula (XIId) 【Chemistry 25】 The structure is u=1, R ｃ４ is H, 8. The compound of claim 7, or a pharmaceutically acceptable salt, hydrate or solvate thereof, wherein Z is a chelator which may include a linker.

9. 9. The compound of claim 8, or a pharmaceutically acceptable salt, hydrate or solvate thereof, wherein the linker is selected from the group consisting of Ttds, O2Oc, and PEG6.

10. R ａ１ OH, F, COOH, (C ３ ~C ８ ) cycloalkyl, aryl, heteroaryl, and (C ３ ~C ８ ) C, each of which may be independently substituted with up to two substituents independently selected from the group consisting of heterocycles; ３ Alkyl, C ４ Alkyl, or C ５ alkyl, (C １ ~C ８ ) In alkyl, —CH ２ 10. The compound according to any one of claims 7 to 9, or a pharmaceutically acceptable salt, hydrate or solvate thereof, wherein one of the - groups is optionally replaced by -S- or -O-.

11. R ａ１ is C ３ Alkyl, C ４ Alkyl, and C ５ 11. The compound of claim 10, or a pharmaceutically acceptable salt, hydrate or pharmaceutically acceptable solvate thereof, wherein the compound is selected from the group consisting of alkyl.

12. R ａ１ The compound of claim 10 or 11, or a pharmaceutically acceptable salt, hydrate or solvate thereof, wherein is n-butyl.

13. The compound of claim 7, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, The compound 【Chemistry 26-1】 【Chemistry 26-2】 【Chemistry 26-3】 【Chemistry 26-4】 【Chemistry 26-5】 【Chemistry 26-6】 【Chemistry 26-7】 【Chemistry 26-8】 【Chemistry 26-9】 【Chemistry 26-10】 【Chemistry 26-11】 【Chemistry 26-12】 【Chemistry 26-13】 [Chemistry 26-14] selected from the group consisting of The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

14. Formula (I) 【Chemistry 27】 Cyclic peptides and an N-terminal modifying group A attached to Xaa1, the peptide sequence is drawn from left to right in the N-terminal to C-terminal direction; Xaa1 is a group represented by formula (II) 【Chemistry 28】 is a residue of an amino acid R １ａ is —NH—, R １ｂ is H or CH ３ and n=0 or 1; the N-terminal modification group A is covalently bonded to the nitrogen atom of Xaa1; the carbonyl group of Xaa1 is covalently bonded to the nitrogen of Xaa2, and the sulfur atom of Xaa1 is covalently bonded to Yc as a thioether; Xaa2 is a group represented by formula (III), (IV), or (XX) 【Chemistry 29】 is a residue of an amino acid R ２ａ , R ２ｂ , R ２ｃ are each independently (C １ ~C ２ ) alkyl and H, wherein (C １ ~C ２ ) alkyl is OH, NH ２ , halogen, (C ５ ~C ７ ) optionally substituted by a substituent selected from the group consisting of cycloalkyl; p=0, 1, or 2; v=1 or 2, w=1, 2, or 3; The amino acid of formula (IV) may contain methyl, OH, NH at positions 3 and 4 of the indicated ring. ２ and F, Xaa3 is represented by formula (V) or (XX) 【Transformation 30】 is a residue of an amino acid X ３ is CH ２ , C.F. ２ , CH-R ３ｂ , S, O, and NH; p=1 or 2; v=1 or 2, w=1, 2, or 3; R ３ａ H, methyl, OH, NH ２ , or F, R ３ｂ Methyl, OH, NH ２ , or F, Xaa4 is a group represented by formula (VI) 【Chemistry 31】 is a residue of an amino acid R ４ａ H, OH, COOH, CONH ２ , X ４ and —NH—CO—X ４ and X is selected from the group consisting of ４ But (C １ ~C ６ ) alkyl, (C ５ ~C ６ ) aryl, and (C ５ ~C ６ ) heteroaryl; and X ４ is methyl, CONH ２ , halogen, NH ２ and OH, q=1, 2, or 3, and the one, two, or three CH ２ -group, one or two hydrogen atoms of which are independently methyl, ethyl, (C ５ ~C ６ ) aryl, or (C ５ ~C ６ ) optionally substituted by heteroaryl; R ４ｂ is methyl or H, Xaa5 is structure (VII) 【Chemistry 32】 is a residue of an amino acid R ５ is OH and NH ２ and r=1, 2, or 3; Xaa6 is an amino acid selected from the group consisting of aromatic L-α-amino acids and heteroaromatic L-α-amino acids; Xaa7 is a group represented by formula (IX) 【Transformation 33】 is an aminothiol or amino acid residue of R ７ａ -CO-, -COOH, -CONH ２ , -CH ２ -OH, -(CO)-NH-R ７ｂ , -(CO)-(NR ７ｃ )-R ７ｂ , or H, R ７ｂ and R ７ｃ are each independently (C １ ~C ４ ) alkyl, and t is 1 or 2, Yc is a group represented by the formula (X) 【Transformation 34】 and connecting the S atom of Xaa1 with the S atom of Xaa7 under the formation of two thioether linkages, thereby forming a compound of formula (XXI) 【Chemistry 35】 forming a ring structure of the substitution pattern of the aromatic group of formula (X) is meta; n=0 or 1; t=1 or 2, Y １ is C—H or N, Y ２ is C-R ｃ１ and R ｃ１ is H, the N-terminal modification group A is the amino acid Aaa; The amino acid Aaa has the structure (XIV) 【Transformation 36】 is an L-amino acid residue of R ａ２ But (C １ ~C ６ ) alkyl and modified (C １ ~C ６ ) alkyl, modified (C １ ~C ６ ) alkyl with one —CH ２ - group is replaced by -S- or -O-, the amino acid Aaa is covalently attached to a linker, the linker is covalently attached to a chelator Z, the linker consisting of (a) a first linker or (b) a first linker and a second linker; if the linker consists of the first linker, the first linker is covalently attached to the chelator and the amino acid Aaa; and when the first linker consists of a first linker and a second linker, the first linker is covalently bonded to the amino acid Aaa and the second linker, and the second linker is covalently bonded to the chelator; the first linker is selected from the group consisting of Ttds and PEG6; A compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, wherein the second linker is selected from the group consisting of PPAc and PEG6.

15. R ａ２ is C ４ 15. The compound of claim 14, or a pharmaceutically acceptable salt, hydrate or pharmaceutically acceptable solvate thereof, wherein R is alkyl.

16. R ａ２ 16. The compound of claim 14 or 15, or a pharmaceutically acceptable salt, hydrate or solvate thereof, wherein is n-butyl.

17. 17. The compound of any one of claims 14 to 16, or a pharmaceutically acceptable salt, hydrate or pharmaceutically acceptable solvate thereof, wherein the amino acid Aaa is a residue of Nle.

18. Y １ 18. The compound of any one of claims 14 to 17, or a pharmaceutically acceptable salt, hydrate or pharmaceutically acceptable solvate thereof, wherein is C-H.

19. the linker comprises a first linker, the first linker being selected from the group consisting of 1,13-diamino-4,7,10-trioxatridecane-succinic acid (Ttds) and PEG6; or 18. The compound of any one of claims 14 to 17, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, wherein the linker consists of a first linker and a second linker, the first linker being selected from the group consisting of 1,13-diamino-4,7,10-trioxatridecane-succinic acid (Ttds) and PEG6, and the second linker being selected from the group consisting of 4-carboxymethylpiperazine (PPAc) and PEG6.

20. 20. The compound of claim 19, or a pharmaceutically acceptable salt, hydrate or solvate thereof, wherein the first linker is Ttds and the second linker is PPAc.

21. 21. The compound of any one of claims 14 to 20, or a pharmaceutically acceptable salt, hydrate or pharmaceutically acceptable solvate thereof, wherein the amino acid is attached to Xaa7.

22. 22. The compound of claim 21, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, wherein the amino acid attached to Xaa7 is selected from the group consisting of β-alanine (Bal), Asp, asp, Gly, γ-aminobutyric acid (Gab), Ser, N-methyl-glycine (Nmg), (S)-β-homophenylalanine (Bhf), Lys, 1,5-diaminopentane (Ape), 1,13-diamino-4,7,10-trioxatridecane-succinic acid (Ttds), and (S)-β-homolisine (Bhk).

23. The compound of claim 14, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, The compound is 【Chemistry 37-1】 【Chemistry 37-2】 【Chemistry 37-3】 【Chemistry 37-4】 【Chemistry 37-5】 【Chemistry 37-6】 【Chemistry 37-7】 【Chemistry 37-8】 【Chemistry 37-9】 【Chemistry 37-10】 【Chemistry 37-11】 【Chemistry 37-12】 【Chemistry 37-13】 【Chemistry 37-14】 【Chemistry 37-15】 【Chemistry 37-16】 【Chemistry 37-17】 [Chemistry 37-18] 【Chemistry 37-19】 N4Ac-Ttds-Nle-[Cys-(3MeBn)-Pro-Pro-Thr-Gln-Phe-Cys]-OH, and N4Ac-PEG6-Nle-[Cys-(3MeBn)-Pro-Pro-Thr-Glu-Phe-Cys]-OH (In the formula, N4Ac is 6-carboxy-1,4,8,11-tetraazaundecane, Ttds is 1,13-diamino-4,7,10-trioxatridecane-succinic acid; Nle is (S)-norleucine; 3MeBn is 3-methylbenzylidene selected from the group consisting of The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

24. Formula (I) 【Transformation 38】 Cyclic peptides and an N-terminal modifying group A attached to Xaa1, the peptide sequence is drawn from left to right in the N-terminal to C-terminal direction; Xaa1 is a group represented by formula (II) 【Chemistry 39】 is a residue of an amino acid R １ａ is —NH—, R １ｂ is H or CH ３ and n=0 or 1; the N-terminal modification group A is covalently bonded to the nitrogen atom of Xaa1; the carbonyl group of Xaa1 is covalently bonded to the nitrogen of Xaa2, and the sulfur atom of Xaa1 is covalently bonded to Yc as a thioether; Xaa2 is a group represented by formula (III), (IV), or (XX) 【Chemistry 40】 is a residue of an amino acid R ２ａ , R ２ｂ , R ２ｃ are each independently (C １ ~C ２ ) alkyl and H, wherein (C １ ~C ２ ) alkyl is OH, NH ２ , halogen, (C ５ ~C ７ ) cycloalkyl; p=0, 1, or 2; v=1 or 2, w=1, 2, or 3, and The amino acid of formula (IV) may contain methyl, OH, NH at positions 3 and 4 of the indicated ring. ２ and F, Xaa3 is represented by formula (V) or (XX) 【Chemistry 41】 is a residue of an amino acid X ３ is CH ２ , C.F. ２ , CH-R ３ｂ , S, O, and NH; p=1 or 2; v=1 or 2, w=1, 2, or 3; R ３ａ H, methyl, OH, NH ２ , or F, R ３ｂ Methyl, OH, NH ２ , or F, Xaa4 is a group represented by formula (VI) 【Chemistry 42】 is a residue of an amino acid R ４ａ H, OH, COOH, CONH ２ , X ４ and —NH—CO—X ４ and X is selected from the group consisting of ４ But (C １ ~C ６ ) alkyl, (C ５ ~C ６ ) aryl, and (C ５ ~C ６ ) heteroaryl; and X ４ is methyl, CONH ２ , halogen, NH ２ and OH, q=1, 2, or 3, and the one, two, or three CH ２ -group, one or two hydrogen atoms of which are independently methyl, ethyl, (C ５ ~C ６ ) aryl, or (C ５ ~C ６ ) optionally substituted by heteroaryl; R ４ｂ is methyl or H, Xaa5 is structure (VII) 【Chemistry 43】 is a residue of an amino acid R ５ is OH and NH ２ and r=1, 2, or 3; Xaa6 is an amino acid selected from the group consisting of aromatic L-α-amino acids and heteroaromatic L-α-amino acids; Xaa7 is a group represented by formula (IX) 【Chemistry 44】 is an aminothiol or amino acid residue of R ７ａ -CO-, -COOH, -CONH ２ , -CH ２ -OH, -(CO)-NH-R ７ｂ , -(CO)-(NR ７ｃ )-R ７ｂ , or H, R ７ｂ and R ７ｃ are each independently (C １ ~C ４ ) alkyl, t is 1 or 2, Yc is a group represented by the formula (X) 【Chemistry 45】 and connecting the S atom of Xaa1 with the S atom of Xaa7 under the formation of two thioether linkages, thereby forming a compound of formula (XXI) 【Chemistry 46】 forming a ring structure of the substitution pattern of the aromatic group of formula (X) is meta; n=0 or 1; t=1 or 2, Y １ is C—H, Y ２ is C-R ｃ１ and R ｃ１ is CH ２ -R ｃ２ and R ｃ２ is represented by formula (XIId) 【Chemistry 47】 The structure is u=1, 2, 3, 4, 5, or 6; R ｃ４ is H or methyl, Z is a chelator which may include a linker; and The N-terminal modifying group A is a blocking group Ab1, and the blocking group Ab1 is R ａ１１ —C(O)—; R ａ１１ is C ４ Alkyl or C ５ alkyl, C ４ Alkyl and C ５ In each and any one of the alkyls, the —CH ２ - a compound, or a pharmaceutically acceptable salt, hydrate or pharmaceutically acceptable solvate thereof, wherein one of the groups may be replaced by -O- or -S-.

25. (a) R ａ１１ is C ５ Is it alkyl? (b) R ａ１１ is C ４ Is it alkyl? (c) R ａ１１ Structure (XXXI) 【Chemistry 48】 Or (d) R ａ１１ is structure (XXXII) 【Chemistry 49】 or (e) R ａ１１ is structure (XXXIII) [Transformation 50] 25. The compound of claim 24, which is: or a pharmaceutically acceptable salt, hydrate or pharmaceutically acceptable solvate thereof.

26. R ａ１１ is n-pentyl or structure (XXX) 【Chemistry 51】 26. The compound of claim 25, wherein:

27. R ａ１１ 26. The compound of claim 25, or a pharmaceutically acceptable salt, hydrate or solvate thereof, wherein is n-butyl.

28. The chelator Z is represented by the formula (XIId) 【Chemistry 52】 is covalently bonded to the N atom of the structure ｃ４ 28. The compound of any one of claims 24 to 27, or a pharmaceutically acceptable salt, hydrate or pharmaceutically acceptable solvate thereof, wherein

29. the chelator Z comprises a linker, the linker is covalently bonded to the chelator, and has the formula (XIId) 【Chemistry 53】 29. The compound of any one of claims 24 to 28, wherein:

30. 30. The compound of claim 29, or a pharmaceutically acceptable salt, hydrate or solvate thereof, wherein the linker is selected from the group consisting of Ttds and O2Oc.

31. The compound of any one of claims 24 to 30, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, The compound 【Chemistry 54-1】 【Chemistry 54-2】 【Chemistry 54-3】 【Chemistry 54-4】 【Chemistry 54-5】 【Chemistry 54-6】 【Chemistry 54-7】 【Chemistry 54-8】 【Chemistry 54-9】 【Chemistry 54-10】 【Chemistry 54-11】 【Chemistry 54-12】 【Chemistry 54-13】 【Chemistry 54-14】 Hex-[Cys-(tMeBn(NODAGA-O2Oc-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH, Hex-[Cys(tMeBn(PCTA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH, Hex-[Cys(tMeBn(NOPO-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH], Hex-[Cys(tMeBn(DATA-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH, and Hex-[Cys(tMeBn(NOPO-Ttds-AET))-Pro-Pro-Thr-Gln-Phe-Cys]-OH (In the formula, Hex is hexanoic acid; tMeBn is 1,3,5-trimethylbenzylidene; NODAGA is 1,4,7-triazacyclononane, 1-glutaric acid-4,7-acetic acid; PCTA is 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid; NOPO is 3-(((4,7-bis((hydroxy(hydroxymethyl)phosphoryl)methyl)-1,4,7-triazonan-1-yl)methyl)(hydroxy)phosphoryl)propanoic acid; DATA is (6-pentanoic acid)-6-(amino)methyl-1,4-diazepinetriacetic acid, O2Oc is 3,6-dioxaoctanoic acid, Ttds is 1,13-diamino-4,7,10-trioxatridecane-succinic acid; AET is 2-aminoethanethiol selected from the group consisting of The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

32. The compound of any one of claims 1 to 5, 7 to 12, 14 to 22, and 24 to 30, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, wherein Xaa1 is a D-amino acid residue selected from the group consisting of cys, (R)-homocysteine ​​(hcy), and (S)-penicillamine (pen), or Xaa1 is an L-amino acid residue selected from the group consisting of Cys, (S)-homocysteine ​​(Hcy), and (R)-penicillamine (Pen).

33. 33. The compound of claim 32, or a pharmaceutically acceptable salt, hydrate or solvate thereof, wherein Xaa1 is Cys.

34. 34. The compound of any one of claims 1 to 5, 7 to 12, 14 to 22, 24 to 30, and 32 to 33, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, wherein Xaa2 is an amino acid residue selected from the group consisting of Pro, N-methyl-glycine (Nmg), Gly, and derivatives thereof.

35. 35. The compound of any one of claims 1 to 5, 7 to 12, 14 to 22, 24 to 30, and 32 to 34, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, wherein Xaa3 is an amino acid residue selected from the group consisting of Pro, (2S,4R)-4-hydroxy-pyrrolidine-2-carboxylic acid (Hyp), (2S,4R)-4-fluoro-pyrrolidine-2-carboxylic acid (Tfp), 4-cis-fluoroproline (Cfp), (S)-5,5-dimethyl-proline (Dmp), (S)-azetidine-2-carboxylic acid (Aze), and (S)-piperidine-2-carboxylic acid (Pip), and derivatives thereof.

36. 36. The compound of any one of claims 1 to 5, 7 to 12, 14 to 22, 24 to 30, and 32 to 35, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, wherein Xaa4 is an amino acid residue selected from the group consisting of Thr, (S)-homoserine (Hse), Asn, Gln, and Ser, and derivatives thereof.

37. 37. The compound of any one of claims 1 to 5, 7 to 12, 14 to 22, 24 to 30 and 32 to 36, or a pharmaceutically acceptable salt, hydrate or solvate thereof, wherein Xaa5 is an amino acid residue selected from the group consisting of Gln and Glu, and derivatives thereof.

38. Xaa6 is represented by the formula (VIIIa), (VIIIb), (VIIIc), and (VIIId) 【Transformation 55】 and R ６ａ and R ６ｂ are each independently selected from the group consisting of H, methyl, ethyl, propyl, and isopropyl; R ６ｃ represents 0 to 3 substituents, each of which is independently Cl, F, Br, or NO ２ , N.H. ２ , C.N., C.F. ３ , OH, OR ６ｄ , and C １ ~C ４ is selected from the group consisting of alkyl, R ６ｄ is selected from the group consisting of methyl, ethyl, propyl, and isopropyl; and 38. The compound of any one of claims 1 to 5, 7 to 12, 14 to 22, 24 to 30 and 32 to 37, or a pharmaceutically acceptable salt, hydrate or pharmaceutically acceptable solvate thereof, wherein s is 0 or 1.

39. 39. The compound of claim 38, or a pharmaceutically acceptable salt, hydrate or solvate thereof, wherein Xaa6 is an amino acid residue selected from the group consisting of Phe, (S)-2-chloro-phenylalanine (Ocf), (S)-4-pyridyl-alanine (Ppa), (S)-β-(2-thienyl)-alanine (Thi), 3-(1-naphthyl)alanine (1Ni), (S)-2-trifluoromethyl-phenylalanine (Otf), and 3-pyridyl-alanine (Mpa), and derivatives thereof.

40. Xaa7 is Cys-OH, Cys, Cys-NH ２ , (R)-cysteinol (Cysol), 2-aminoethanethiol (AET), (S)-homocysteine ​​(Hcy), cys, cys-OH, cys-NH ２ 40. The compound of any one of claims 1 to 5, 7 to 12, 14 to 22, 24 to 30 and 32 to 39, or a pharmaceutically acceptable salt, hydrate or solvate thereof, wherein the aminothiol residue is selected from the group consisting of (R)-homocysteine ​​(hcy).

41. The chelator is ９９ｍ Tc(CO) ３ -Chelators, CB-TE2A, CHX-A''-DTPA, DTPA, DATA, DFO, HBED, Crown, DOTAGA, DOTAM (also referred to as TCMC), FSC, H4octapa, Macropa, HEHA, HOPO, Hynic, PCTA, PSC, NETA, DOTA, NODA-MPAA, NODAGA, NOTP, N ｘ S ４－ｘ (N ４ , N ２ S ２ , N ３ 50. The compound of any one of claims 1 to 5, 7 to 12, 14 to 22, 24 to 30 and 32 to 40, or a pharmaceutically acceptable salt, hydrate or pharmaceutically acceptable solvate thereof, selected from the group consisting of NOPO, NOTA, Pycup, RESCA, sarcofagin, TETA, THP, and TRAP.

42. 42. A compound according to any one of claims 1 to 41, or a pharmaceutically acceptable salt, hydrate or pharmaceutically acceptable solvate thereof, comprising a diagnostically active nuclide or a therapeutically active nuclide.

43. said therapeutically active nuclide a) ４７ Sc, ６７ Cu, ８９ Sr, ９０ Y. １３１ I, １１１ In, １５３ Sm, １４９ Tb, １６１ Tb, １７７ Lu, １８６ Re, １８８ Re, ２１１ At, ２１２ Pb, ２１３ Bi, ２２３ Ra, ２２４ Ra, ２２５ Ac, ２２６ Th, and ２２７ Th, or b) particle-emitting isotopes for therapeutic use, having decay energies between 0.039 and 10 MeV; or said diagnostically active nuclide a) １８ F. ４３ Sc, ４４ Sc, ５１ Mn, ５２ Mn, ６４ Cu, ６７ Ga, ６８ Ga, ７６ Br, ７７ Br, ８６ Y. ８９ Zr, ９４ｍ Tc, ９９ｍ Tc, １１１ In, １２３ I, １２４ I, １２５ I, １５２ Tb, １５５ Tb, １７７ Lu, ２０１ Tl, and ２０３ Pb; or b) gamma-emitting isotopes for diagnostic use, with decay energies between 0.004 and 10 MeV; 43. The compound of claim 42, or a pharmaceutically acceptable salt, hydrate or pharmaceutically acceptable solvate thereof.

44. 44. A compound according to any one of claims 1 to 43, or a pharmaceutically acceptable salt, hydrate or solvate thereof, which interacts with human fibroblast activation protein (FAP) having the amino acid sequence of SEQ ID NO: 1 or a homolog thereof, wherein the amino acid sequence of the homolog has at least 85% identity with the amino acid sequence of SEQ ID NO:

1.

45. 45. The compound of claim 44, or a pharmaceutically acceptable salt, hydrate or solvate thereof, which is an inhibitor of fibroblast activation protein (FAP).

46. 46. ​​A radionuclide chelate complex comprising a compound of any one of claims 1 to 41, and 44 to 45, or a pharmaceutically acceptable salt, hydrate, or pharmaceutically acceptable solvate thereof, and a radionuclide, wherein the radionuclide is complexed by a chelator.

47. The radionuclide chelate complex of claim 46, the radionuclide is a therapeutically active radionuclide; a) said therapeutically active radionuclide is selected from the group consisting of 47 Sc, 67 Cu, 89 Sr, 90 Y, 131 I, 111 In, 153 Sm, 149 Tb, 161 Tb, 177 Lu, 186 Re, 188 Re, 211 At, 212 Pb, 213 Bi, 223 Ra, 224 Ra, 225 Ac, 226 Th, and 227 Th; or b) particle-emitting isotopes for therapeutic use, the decay energy of which is between 0.039 and 10 MeV; or the radionuclide is a diagnostically active radionuclide; a) the diagnostically active nuclide is selected from the group consisting of 18F, 43Sc, 44Sc, 51Mn, 52Mn, 64Cu, 67Ga, 68Ga, 76Br, 77Br, 86Y, 89Zr, 94mTc, 99mTc, 111In, 123I, 124I, 125I, 152Tb, 155Tb, 177Lu, 201Tl, and 203Pb; or b) Radionuclide chelate complexes of gamma-emitting isotopes for diagnostic use, with decay energies between 0.004 and 10 MeV.

48. 48. A compound according to claim 1 to 45, or a pharmaceutically acceptable salt, solvate or hydrate thereof, or a radionuclide chelate complex according to any of claims 46 to 47, and At least one additional anti-cancer compound Including, combinations.

49. 48. A compound according to any one of claims 1 to 45, or a pharmaceutically acceptable salt, hydrate or pharmaceutically acceptable solvate thereof, or a radionuclide chelate complex according to any one of claims 46 to 47, or a combination according to claim 48, and pharmaceutically acceptable excipients A pharmaceutical composition comprising:

50. 50. The pharmaceutical composition of claim 49 for use in a method for the diagnosis of a disease.

51. 50. The pharmaceutical composition of claim 49 for use in a method for the treatment of a disease.

52. 52. The pharmaceutical composition of claim 50 or 51, wherein the disease is a disease involving fibroblast activation protein (FAP).

53. 53. The pharmaceutical composition of claim 52, wherein the disease is a disease associated with upregulated expression of fibroblast activation protein (FAP).

54. 54. The pharmaceutical composition of any one of claims 50 to 53, wherein the disease is a neoplasm.

55. 55. The pharmaceutical composition of claim 54, wherein the disease is cancer or a tumor.

56. 56. The pharmaceutical composition of any one of claims 50 to 55, wherein the disease is selected from the group comprising solid tumors, epithelial tumors, bladder cancer, breast cancer, cervical cancer, colorectal cancer, cholangiocarcinoma, endometrial cancer, esophageal cancer, gastric cancer, gastrointestinal stromal tumors, head and neck cancer, liver cancer, lung cancer, melanoma, mesothelioma, neuroendocrine tumors and carcinomas, ovarian cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, salivary gland cancer, sarcoma, squamous cell carcinoma, and thyroid cancer.

57. 54. The pharmaceutical composition of any one of claims 50 to 53, wherein the disease is selected from the group comprising inflammatory diseases, cardiovascular diseases, autoimmune diseases, and fibrotic diseases.

58. 48. A kit comprising a compound of any one of claims 1 to 45, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a radionuclide chelate complex of any one of claims 46 to 47, wherein the kit may comprise one or more excipients or one or more devices, said devices being selected from the group comprising a labeling device, a purification device, a handling device, a radiation protection device, an analytical device, or an administration device.

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