CXCR4 targeting compounds and methods of making and using same - Patents.com

Abstract

The present disclosure relates to peptide compounds of formula A, A-II, A-III, A-III, A-IV, B, or C, or salts or solvates thereof, compositions thereof, and methods of use thereof. The compounds of the disclosure are useful for targeting CXCR4 for purposes such as imaging and / or therapy.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 63 / 332,885, filed April 20, 2022, the disclosure of which is incorporated herein by reference in its entirety.

[0002] The present invention relates to novel peptide compounds, in particular compounds that target CXCR4 for purposes such as imaging and / or therapy. [Background technology]

[0003] CXC chemokine receptor type 4 (CXCR4) is a G protein-coupled transmembrane receptor expressed in blood and immune tissues and systems. 1、2 CXCR4 has only one chemokine as a substrate, named stromal cell-derived factor-1 (SDF-1), also known as CXCL12. 3 CXCR4 is aberrantly expressed in several important pathologies involving inflammatory and immune cell trafficking, including atherosclerosis. 4 , systemic erythematosus lupus 5、6 Importantly, CXCR4 has been shown to play an important role in tumorigenesis, chemotherapy resistance and metastasis, and its expression has been detected in more than twenty different subtypes of cancers with negative prognosis. 7~12 Thus, there is a need for non-invasive in vivo molecular probes to image CXCR4-expressing tumors for better detection, staging, and monitoring of aggressive cancers. 13~16Such imaging agents would allow rapid assessment of patients for the expression of specific biomarkers without the need for invasive biopsy procedures that do not necessarily adequately capture the heterogeneity of a patient's disease. Furthermore, because the efficacy of CXCR4 inhibitors in clinical trials has been largely poor, an alternative strategy is to couple the inhibitors with radiotherapy isotopes to deliver ionized β, α, or Auger electrons to the site of disease.

[0004] LY2510924(Cyclo[Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-D-Glu]-Lys(iPr)-NH 2 ) has an IC of 79 pM 50 It is a cyclic peptide that has been reported to block the binding of SDF-1α to CXCR4 at low levels. 17 It was reported that LY2510924 was able to inhibit the growth of non-Hodgkin's lymphoma, renal cTb-ell cancer, lung cancer, colorectal cancer, and breast cancer xenograft models. LY2510924 could not improve the therapeutic efficacy of carboplatin / etoposide chemotherapy for patients with small cell lung cancer. 18 .

[0005] Many CXCR4 peptide inhibitors utilize key amino acid residues to maintain good binding affinity with CXCR4, including 1) one or more cationic charged side chain residues to contact several anionic residues present in the CXCR4 pocket, 2) a tyrosine residue, and 3) a naphthalene-based unnatural amino acid. 19 This is exemplified in the development of T140, a peptide in which each amino acid of a prototype peptide (T22) was systematically substituted based on a natural peptide that has HIV inhibitory activity through CXCR4 antagonism. 19 This has led to several potent antagonists against CXCR4, including FC131 (which was later repurposed as Pentixafor and Pentixather for imaging and radionuclide therapeutic purposes, respectively) and LY2510924 for radiotheranostics purposes.20 .

[0006] Thus, there is an unmet need in the art for improved CXCR4-targeted compounds that are imaging and therapeutic agents for the in vivo diagnosis and treatment, respectively, of diseases / disorders characterized by, for example, expression of CXCR4.

[0007] No admission is necessarily intended, nor should be construed, that any of the preceding information constitutes prior art against the present invention. Summary of the Invention

[0008] The present disclosure relates to compounds useful as imaging and / or therapeutic agents.

[0009] In some embodiments, the present invention provides a compound of formula A, formula B, or formula C, or a salt or solvate thereof: [ka] During the ceremony,

[0010] R 2a is -(CH 2 )-(R 2b )-(phenyl), where R 2b does not exist or -CH 2 -, -NH-, -S-, or -O-, where phenyl is -NH 2 , -NO 2 , -OH, -OR 2c , -SH, -SR 2c , -N 3 , -CN, or -O-phenyl, wherein the phenyl is optionally substituted at the 3-position with a halogen or -OH, wherein the phenyl is optionally substituted at the 5-position with a halogen or -OH, wherein the -O-phenyl ring is optionally substituted at the 6-position with -NH 2 , -NO 2 , -OH, -OR 2c , -SH, -SR 2c , -N 3or -CN, the -O-phenyl ring is optionally substituted at the 4-position with a halogen or -OH, the -O-phenyl ring is optionally substituted at the 3-position with a halogen or -OH, the -O-phenyl ring is optionally substituted at the 5-position with a halogen or -OH, 2c are independently 1 ~C 3 is a straight or branched alkyl group of

[0011] R 3a is C 1 ~C 5 Alkyl or R 3b R 3c where R 3b is a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 alkynylenyl, wherein C 2 ~C 5 0-2 carbons in are independently replaced with one or more N, S, and / or O heteroatoms, 3c is -N(R 3d ) 2~3 or guanidino, wherein each R 3d are independently -H or linear or branched C 1 ~C 3 is alkyl,

[0012] R 4a is R 4b R 4c where R 4b is a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 Alkynylenyl, where C 2 ~C 5 0-2 carbons in are independently replaced with one or more N, S, and / or O heteroatoms, 4cis -N(R 4d ) 2~3 or guanidino, wherein each R 4d are independently -H or linear or branched C 1 ~C 3 is alkyl,

[0013] R 5a is -(CH 2 ) 1~3 -R 5b In the formula: -(CH 2 ) 2~3 - one carbon in may be replaced with a heteroatom of N, S, or O, 5b teeth,

[0014] Phenyl,

[0015] -NH 2 , -NO 2 , -OH, -OR 5c , -SH, -SR 5c , -N 3 , -CN, or -O-phenyl, substitution at the 4-position with a halogen or -OH, and / or substitution at the 5-position with a halogen or -OH, wherein the -O-phenyl ring is -NH 2 , -NO 2 , -OH, -OR 5c , -SH, -SR 5c , -N 3 or -CN at the 4-position, wherein the -O-phenyl ring is optionally substituted at the 3-position with a halogen or -OH, wherein the -O-phenyl ring is optionally substituted at the 5-position with a halogen or -OH;

[0016] fused bicyclic or tricyclic aryl or heteroaryl rings, each of which is halogen, -OH, -OR 5c , amino, -NHR 5c , and / or N(R 5c ) 2a fused bicyclic or tricyclic aryl or heteroaryl ring, optionally substituted with one or more of

[0017] In the formula, each R 5c are independently 1 ~C 3 is a straight or branched alkyl group of

[0018] Any R 6a is H, methyl, ethyl, -C≡CH, -CH=CH 2 , -C≡C-(CH 2 ) 1-3 -OH, -C≡C-(CH 2 ) 1-3 -SH, -C≡C-(CH 2 ) 1-3 -NH 2 , -C≡C-(CH 2 ) 1-3 -COOH, -C≡C-(CH 2 ) 1-3 -CONH 2 , -C≡C-(CH 2 ) 1-3 R 6b R 6c , -CH=CH-(CH 2 ) 1-3 -OH, -CH=CH-(CH 2 ) 1-3 -SH, -CH=CH-(CH 2 ) 1-3 -NH 2 , -CH=CH-(CH 2 ) 1-3 -COOH, -CH=CH-(CH 2 ) 1-3 -CONH 2 , -CH=CH-(CH 2 ) 1-3 R 6b R 6c , -CH 2 -R 6b -OH, -CH 2 -R 6b -COOH, -CH 2 -(R 6b ) 1~3 -NH 2 , -CH 2 -R6b -CONH 2 , or -CH 2 -R 6b R 6c where each R 6b are independently absent or -CH 2 -, -NH-, -S-, or -O-; and 6c teeth,

[0019] a 5- or 6-membered aromatic ring, wherein one or more carbons are optionally independently replaced with N, S, and / or O heteroatoms and one or more groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen;

[0020] or -NH-CH(R 6a )-C(O)-NH- is replaced with [ka]

[0021] R A7a is a linear C 1 ~C 5 alkylenyl, wherein C 2 ~C 5 0-2 carbons in are independently replaced by one or more N, S, and / or O heteroatoms;

[0022] R 8a is R 8b R 8c where R 8b is a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 Alkynylenyl, where C 2 ~C 50-2 carbons in the alkylenyl, alkenylenyl, or alkynylenyl are independently replaced with one or more N, S, and / or O heteroatoms, 8c is -N(R 8d ) 2~3 or guanidino, wherein each R 8d are independently -H or linear or branched C 1 ~C 3 is alkyl,

[0023] R 9a is -C(O)NH 2 , -C(O)-OH, -CH 2 -C(O)NH 2 , -CH 2 -C(O)-OH, -CH 2 -NH 2 , -CH 2 -OH, -CH 2 -CH 2 -NH 2 , -R 9b -R 9c , or -R 9b -[Linker]-R X n1 where:

[0024] R 9b is -CH 2 -NH-C(O)-, -CH 2 -C(O)-, -CH 2 -O-, -C(O)NH-, -C(O)-N(CH 3 )-, -CH 2 -NHC(S)-, -C(S)NH-, -CH 2 -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -CH 2 -N(CH 3 )C(O)-, -C(S)N(CH 3 )-, -CH 2 -NHC(S)NH-, -CH 2 -NHC(O)NH-, -CH 2 -S-, -CH 2 -S(O)-, -CH 2 -S(O) 2-, -CH 2 -S(O) 2 -NH-, -CH 2 -S(O)-NH-, -CH 2 -Se-, -CH 2 -Se(O)-, -CH 2 -Se(O) 2 -, -CH 2 -NHNHC(O)-, -C(O)NHNH-, -CH 2 -OP(O)(O - )O-, -CH 2 -Phosphamide-, -CH 2 -Thiophosphodiester-, -CH 2 -S-tetrafluorophenyl-S-, [ka] or polyethylene glycol,

[0025] R 9c is hydrogen or a linear, branched and / or cyclic C 1 ~C 20 is an alkyl, alkenyl, or alkynyl of the formula: 2 ~C 20 wherein 0-6 carbons are independently replaced with N, S, and / or O heteroatoms, and 0-3 groups independently selected from one or a combination of oxo, hydroxyl, sulfhydryl, halogen, guanidino, carboxylic acid, sulfonic acid, sulfinic acid, and / or phosphate;

[0026] R A10 does not exist or -[linker]-R X n1 and

[0027] R A10 If does not exist, R A1a teeth,

[0028] Linear C 1 ~C 5 Alkyl, C 2 ~C 5Alkenyl, or C 2 ~C 5 alkynyl, wherein C 2 ~C 5 0-2 carbons in the alkyl, alkenyl, or alkynyl are independently replaced with one or more N, S, and / or O heteroatoms, where C is -SH, -OH, amino, carboxy, guanidino, -NH-C(O)-CH 3 , -SC(O)-CH 3 , -OC(O)-CH 3 , -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH 3 ) 1~2 , -NH 2 -CH 3 , -N(CH 3 ) 2~3 , -S-CH 3 , or -O-CH 3 and optionally substituted with one substituent selected from

[0029] Branch C 1 ~C 10 is an alkyl, alkenyl, or alkynyl of the formula: 2 ~C 10 wherein 0-3 carbons are independently replaced by one or more N, S, and / or O heteroatoms; or

[0030] R A1b R A1c where R A1b is a linear C 1 ~C 3 alkylenyl, wherein C 2 Alkylenyl or C 3 Alkylenyl may be substituted with N, S, or O heteroatoms, where R A1c teeth,

[0031] a 5- or 6-membered aromatic ring, wherein one or more carbons are optionally independently replaced with N, S, and / or O heteroatoms and one or more groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen; or

[0032] Fused bicyclic or fused tricyclic aryl groups, in which one or more carbons may be independently replaced with heteroatoms of N, S, and / or O, and may also be replaced with halogen, -OH, -OR A1d , amino, -NHR A1d , and / or N(R A1d ) 2 wherein each R A1d is independently C 1 ~C 3 a fused bicyclic or tricyclic aryl group, which is a linear or branched alkyl group of the formula:

[0033] R A10 -[Linker]-R X n1 If so, then R A1a is R A1e R A1f where R A1e is a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 Alkynylenyl, where C 2 ~C 5 0-2 carbons in the alkylenyl, alkenylenyl, and alkynylenyl are independently replaced with heteroatoms of N, S, and / or O; and R A1f -NH-C(O)-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH 3 )-, -NHC(S)-, -C(S)NH-, -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -N(CH 3)C(O)-, -C(S)N(CH 3 )-, -NHC(S)NH-, -NHC(O)NH-, -S-, -S(O)-, -S(O)-O-, -S(O) 2 -, -S(O) 2 -O-, -S(O) 2 -NH-, -S(O)-NH-, -Se-, -Se(O)-, -Se(O) 2 -, -NHNHC(O)-, -C(O)NHNH-, -OP(O)(O - )O, -phosphamide-, -thiophosphodiester-, -S-tetrafluorophenyl-S-, [ka] or polyethylene glycol,

[0034] R B1a is a linear, branched and / or cyclic C 1 ~C 10 Alkylenyl, C 2 ~C 10 Alkenylenyl, or C 2 ~C 10 alkynylenyl, wherein C 2 ~C 10 one or more carbons in the alkylenyl, alkenylenyl, or alkynylenyl may be independently replaced with heteroatoms of N, S, and / or O;

[0035] R B1-7 teeth, [ka] wherein the indole ring and the isoindole ring are each independently selected from -F, -Br, -Cl, -I, -OH, -OR B1-7b , -CO-, -COOH, -CONH 2 , -CN, -O-aryl, -NH 2 , -NHR B1-7b , N 3 , -NO 2 , -NH, -CHO, and / or -R B1-7b wherein each RB1-7b is a linear or branched C 1 ~C 3 Alkyl, C 2 ~C 3 Alkenyl, or C 2 ~C 3 is alkynyl,

[0036] R B7a is a linear C 1 ~C 5 alkylenyl, wherein C 2 ~C 5 0-2 carbons in the alkylenyl are independently replaced by one or more N, S, and / or O heteroatoms;

[0037] R B10a is an amine, -NH-(CH 3 ) 1~2 , -N(CH 3 ) 2~3 , -NH-C(O)-CH 3 , -NH-C(O)-(phenyl), or -R B10b -[Linker]-R X n1 where R B10b teeth,

[0038] -NH-C(O)-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH 3 )-, -NHC(S)-, -C(S)NH-, -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -N(CH 3 )C(O)-, -C(S)N(CH 3 )-, -NHC(S)NH-, -NHC(O)NH-, -S-, -S(O)-, -S(O)-O-, -S(O) 2 -, -S(O) 2 -O-, -S(O) 2 -NH-, -S(O)-NH-, -Se-, -Se(O)-, -Se(O) 2 -, -NHNHC(O)-, -C(O)NHNH-, -OP(O)(O -)O-, -phosphamide-, -thiophosphodiester-, -S-tetrafluorophenyl-S-, [ka] or polyethylene glycol,

[0039] R C1a teeth, [ka] wherein the indole, isoindole, and triazole rings are each independently selected from -F, -Br, -Cl, -I, -OH, -OR C1b , -CO-, -COOH, -CONH 2 , -CN, -O-aryl, -NH 2 , -NHR C1b , N 3 , -NO 2 , -NH, -CHO, and / or -R C1b wherein each R C1b is a linear or branched C 1 ~C 3 Alkyl, C 2 ~C 3 Alkenyl, or C 2 ~C 3 is alkynyl,

[0040] R C7a is a linear C 1 ~C 5 alkylenyl, wherein C 2 ~C 5 0 to 2 carbons in the alkylenyl are optionally independently replaced by one or more N, S, and / or O heteroatoms;

[0041] R C10a is R C10b -R C10c -[Linker]-R X n1 or R C10d where:

[0042] R C10bis a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 Alkynylenyl, where C 2 ~C 5 0-2 carbons in the alkylenyl, alkenylenyl, and alkynylenyl are independently replaced with heteroatoms of N, S, and / or O;

[0043] R C10c -NH-C(O)-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH 3 )-, -NHC(S)-, -C(S)NH-, -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -N(CH 3 )C(O)-, -C(S)N(CH 3 )-, -NHC(S)NH-, -NHC(O)NH-, -S-, -S(O)-, -S(O)-O-, -S(O) 2 -, -S(O) 2 -O-, -S(O) 2 -NH-, -S(O)-NH-, -Se-, -Se(O)-, -Se(O) 2 -, -NHNHC(O)-, -C(O)NHNH-, -OP(O)(O - )O-, -phosphamide-, -thiophosphodiester-, -S-tetrafluorophenyl-S-, [ka] or polyethylene glycol,

[0044] R C10d teeth,

[0045] Linear C 1 ~C 5 Alkyl, C 2 ~C 5 Alkenyl, or C 2 ~C 5 alkynyl, wherein C 2 ~C5 0-2 carbons in the alkyl, alkenyl, or alkynyl are independently replaced with heteroatoms of N, S, and / or O, where C is -SH, -OH, amino, carboxy, guanidino, -NH-C(O)-CH 3 , -SC(O)-CH 3 , -OC(O)-CH 3 , -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH 3 ) 1~2 , -NH 2 -CH 3 , -N(CH 3 ) 2~3 , -S-CH 3 , or -O-CH 3 and optionally substituted with one substituent selected from

[0046] Branch C 1 ~C 10 Alkyl, C 2 ~C 10 Alkenyl, or C 2 ~C 10 alkynyl, wherein C 2 ~C 10 wherein 0-3 carbons in the alkyl, alkenyl, or alkynyl are independently replaced with heteroatoms of N, S, and / or O; or

[0047] R C10e R C10f where R C10e is a linear C 1 ~C 3 Alkyl, C 2 Alkyl or C 3 The alkyl may be substituted with N, S, or O heteroatoms, where R C10f teeth,

[0048] a 5- or 6-membered aromatic ring, wherein one or more carbons are optionally independently replaced with N, S, and / or O heteroatoms and one or more groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen;

[0049] Fused bicyclic or fused tricyclic aryl groups, in which one or more carbons may be independently replaced with heteroatoms of N, S, and / or O, and may also be replaced with halogen, -OH, -OR C10g , amino, -NHR C10g , and / or N(R C10g ) 2 wherein R C10g is C 1 ~C 3 a fused bicyclic or fused tricyclic aryl group, which is a linear or branched alkyl group of the formula:

[0050] R y is hydrogen or R 3e R 3f where R 3e is a linear C 1 ~C 5 alkylenyl, wherein R 3f is -N(R 3g ) 2~3 where each R 3g are independently -H or linear or branched C 1 ~C 3 is alkyl,

[0051] each n1 is independently 0, 1, or 2;

[0052] Each R X is an albumin binder, a therapeutic moiety, a fluorescent label, a radiolabeled group, or a group capable of being radiolabeled, wherein 0 to 3 peptide backbone amides are independently [ka] amidine or thioamide substituted,

[0053] wherein 0 to 3 of the peptide backbone amides are N-methylated;

[0054] In the formula, the C-terminus may be amidated.

[0055] In some embodiments, the disclosure relates to a compound selected from Table 2, or a salt or solvate thereof. In some embodiments, the compound may be bound to a radiolabeled group, a group that can be radiolabeled, or an albumin binder.

[0056] In some embodiments, the disclosure relates to a compound selected from Table 4, or a salt or solvate thereof.

[0057] In some embodiments of the compounds of the present disclosure, the compounds are complexed with a radioisotope.

[0058] In some embodiments, the present disclosure relates to the use of any one of the compounds disclosed herein for imaging a CXCR4-expressing tissue in a subject.

[0059] In some embodiments, the present disclosure relates to the use of any one of the compounds disclosed herein for imaging an inflammatory condition or disease.

[0060] In some embodiments, the disclosure provides a method of treating a disease or condition characterized by expression of CXCR4 in a subject, the method comprising administering to a subject in need of treatment an effective amount of a compound, in some embodiments, the disease or condition is a cancer that expresses CXCR4.

[0061] In some embodiments, the disclosure provides a method of imaging a CXCR4-expressing tissue in a subject, the method comprising administering to a subject in need of such imaging an effective amount of a compound. [Brief description of the drawings]

[0062] The features of the present invention will become apparent from the following description taken in conjunction with the accompanying drawings.

[0063] [Figure 1] Figure 1 shows representative PET / CT images of [68Ga]Ga-BL34L11 in Z138 tumor-bearing mice at 1 and 3 hours (pi). The scale bar is in %ID / g.

[0064] [Diagram 2] Figure 2 shows representative SPECT / CT images of [177Lu]Lu-BL34L11 in Z138 tumor-bearing mice at 1 h, 4 h, 24 h, 72 h, and 120 h (post-injection). The scale bar is in %ID / g.

[0065] [Diagram 3] Figure 3 shows representative SPECT / CT images of [177Lu]Lu-BL34L20 in Z138 tumor-bearing mice at 1 h, 4 h, 24 h, 72 h, and 120 h (post-injection). The scale bar is in %ID / g.

[0066] [Figure 4] Figure 4 shows representative SPECT / CT images of [177Lu]Lu-crown-BL34 in Z138 tumor-bearing mice at 1 h, 4 h, 24 h, 72 h, and 120 h (pi). The scale bar is in %ID / g.

[0067] [Diagram 5] Figure 5 shows representative PET / CT images of [68Ga]Ga-BL34N1 in Z138 tumor-bearing mice at 1 hour (pi). The scale bar is in %ID / g.

[0068] [Figure 6]Figure 6 shows representative PET / CT images of [68Ga]Ga-BL34T1 in Z138 tumor-bearing mice at 1 and 3 hours (pi). The scale bar is in %ID / g.

[0069] [Figure 7] Figure 7 shows representative SPECT / CT images of [177Lu]Lu- BL34T1 in Z138 tumor-bearing mice at 4, 24, 72, and 120 hours (pi). The scale bar is in %ID / g.

[0070] [Figure 8] Figure 8 shows representative SPECT / CT images of [177Lu]Lu- BL34L20S in Z138 tumor-bearing mice at 4, 24, 72, and 120 hours (pi). The scale bar is in %ID / g. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0071] All publications, patents, and patent applications, including any drawings and appendices therein, are incorporated by reference in their entirety for all purposes to the same extent as if each individual publication, patent, and patent application, drawing, or appendix was specifically and individually indicated to be incorporated by reference in its entirety for all purposes.

[0072] definition As used herein, the terms "comprising," "having," "including," and "containing," as well as grammatical variations thereof, are inclusive or open ended and do not exclude additional, unrecited elements and / or method steps. When used herein in connection with a composition, use, or method, the term "consisting essentially of" indicates that additional elements and / or method steps may be present, but that these additions do not substantially affect the manner in which the recited composition, method, or use functions. When used herein in connection with a composition, use, or method, the term "consisting of" excludes the presence of additional elements and / or method steps. A composition, use, or method described herein as including certain elements and / or steps may also consist essentially of those elements and / or steps in certain embodiments, and consist of those elements and / or steps in other embodiments, whether or not those embodiments are specifically mentioned. Uses or methods described herein as including certain elements and / or steps may in certain embodiments consist essentially of those elements and / or steps and in other embodiments may consist of those elements and / or steps, whether or not those embodiments are specifically mentioned.

[0073] Reference to an element with the indefinite article "a" does not exclude the possibility that more than one element is present, unless the context clearly requires that there is one and only one. The singular forms "a," "an," and "the" include plural referents unless the content clearly dictates otherwise. When used herein in conjunction with the term "comprising," the use of the words "a" or "an" can mean "one," but is also consistent with the meaning of "one or more," "at least one," and "one or more."

[0074] Unless otherwise specified, the terms "specific embodiments," "various embodiments," "an embodiment," and similar terms include the particular features described for that embodiment, either alone or in combination with other embodiments described herein, whether other embodiments are directly or indirectly referred to and whether the features or embodiments are described in the context of a method, product, use, composition, compound, etc.

[0075] As used herein, the terms "treat," "treatment," "therapeutic," and the like include amelioration of symptoms, reduction in disease progression, improved prognosis, and reduction in recurrence (e.g., reduction in cancer recurrence).

[0076] As used herein, the term "diagnostic agent" includes "imaging agents." Thus, a "diagnostic radiometal" includes a radiometal suitable for use in an imaging agent, and a "diagnostic radioisotope" includes a radioisotope suitable for use in an imaging agent. Without limitation, diagnostic and imaging agents include compounds that include at least one fluorescent moiety and / or at least one radioisotope suitable for imaging.

[0077] The term "subject" refers to an animal (e.g., a mammal or a non-mammal). The subject may be a human or a non-human primate. The subject may be a laboratory mammal (e.g., a mouse, a rat, a rabbit, a hamster, etc.). The subject may be an agricultural animal (e.g., a horse, a sheep, a cow, a pig, a camelid, etc.) or a livestock animal (e.g., a dog, a cat, etc.). In some embodiments, the subject is a human.

[0078] The compounds disclosed herein may include their free base form, salts, or pharma- ceutically acceptable salts.Unless otherwise specified, the compounds claimed and described herein are intended to include all racemic mixtures and all individual enantiomers or combinations thereof, whether or not expressly represented herein.

[0079] The compounds disclosed herein may be shown as having one or more charged groups, may be shown with the ionizable groups in an uncharged (e.g., protonated) state, or may be shown without specifying a formal charge. As will be understood by those skilled in the art, the ionization state of a particular group in a compound (e.g., but not limited to, carboxylic acid, sulfonic acid, sulfinic acid, phosphate, etc.) depends, among other things, on the pKa of the group and the pH at its location. By way of example and not limitation, it will be understood that a carboxylic acid group (i.e., COOH) is usually deprotonated (and negatively charged) at neutral pH and at the maximum physiological pH value, unless the protonation state is stabilized. Similarly, sulfonic acid, sulfinic acid, and phosphate groups will generally be deprotonated (and negatively charged) at neutral and physiological pH values.

[0080] As used herein, the terms "salt" and "solvate" have their usual meaning in chemistry. Thus, when a compound is a salt or solvate, it is associated with a suitable counterion. Methods for preparing salts or exchanging counterions are well known in the art. Generally, such salts can be prepared by reacting the free acid forms of these compounds with a stoichiometric amount of a suitable base (e.g., but not limited to, hydroxides, carbonates, bicarbonates, etc. of Na, Ca, Mg, or K), or by reacting the free base forms of these compounds with a stoichiometric amount of a suitable acid. Such reactions are generally carried out in water, or in an organic solvent, or in a mixture of both. The counterion may be changed by ion exchange techniques, such as, for example, ion exchange chromatography. Solvates can be made by any methodology known in the art, for example, by dissolving the compound in a hot solvent (e.g., water or another solvent), followed by cooling and / or evaporation. All zwitterions, salts, solvates, and counterions are intended, unless a particular form is specifically indicated.

[0081] In certain embodiments, the salt or counterion may be pharma- ceutically acceptable for administration to a subject.More generally, for any pharmaceutical composition disclosed herein, non-limiting examples of suitable excipients include any suitable buffer, stabilizer, salt, antioxidant, complexing agent, isotonicity agent, cryoprotectant, lyoprotectant, suspending agent, emulsifying agent, antimicrobial agent, preservative, chelating agent, binder, surfactant, wetting agent, non-aqueous vehicle such as fixed oil, or sustained or controlled release polymer.See, for example, Berge et al. 1977. (J.Pharm Sci. 66:1-19), or Remington-The Science and Practice of Pharmacy, 21st edition (Gennaro et al editors. Lippincott Williams & Wilkins Philadelphia), each of which is incorporated by reference in its entirety.

[0082] As used herein, the expression "Cy-Cz" refers to a compound in which y and z are integers (e.g., C 1 ~C 15 , C 1 ~C 5 (e.g., 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-, 1 ~C 5 wherein C 2 ~C 5one or more carbons in the alkyl group may be independently replaced with a heteroatom of N, S, or O," and similar phrases are intended to include C 1 It is intended to specify that the carbon (i.e., the first carbon in the defined group, and therefore the carbon directly attached to the remainder of the compound) is not substituted. Such language is also intended to include the substitution of a single carbon, and the substitution of multiple carbons, either with the same heteroatom (e.g., one of N, S, or O) or with a combination of different heteroatoms (e.g., a combination of N, S, and / or O in a suitable configuration).

[0083] Unless expressly stated otherwise, the term "alkyl" includes any reasonable combination of the following: (1) straight-chained or branched, (2) acyclic or cyclic, the latter of which may include polycyclic (fused rings, multiple non-fused rings, or combinations thereof), and (3) unsubstituted or substituted. In the context of the expressions "alkyl, alkenyl, or alkynyl" and similar expressions, "alkyl" will be understood to be a saturated alkyl. As used herein, the term "straight-chained" is commonly understood by those of skill in the art and may generally be used to refer to a chemical entity that includes a backbone or main chain that does not split into two or more continuous chains. Non-limiting examples of straight-chained alkyls include methyl, ethyl, n-propyl, and n-butyl. As used herein, the term "branched" is commonly understood by those of skill in the art and may generally be used to refer to a chemical entity that includes a backbone or main chain that splits into two or more continuous chains. The portion of the backbone or main chain that splits in two or more directions may be straight-chained, cyclic, or any combination thereof. Non-limiting examples of branched alkyl groups include tert-butyl and isopropyl.

[0084] The term "alkylenyl" refers to the divalent analog of an alkyl group. In the context of the expressions "alkylenyl, alkenylenyl, or alkynylenyl" and similar expressions, "alkylenyl" will be understood to be a saturated alkylenyl.

[0085] As used herein, the term "saturated" when referring to a chemical entity is commonly understood by those of skill in the art and may be used generally to refer to a chemical entity that contains only single bonds and may contain linear, branched, and / or cyclic groups. 1 ~C 20 Non-limiting examples of alkyl groups include methyl, ethyl, n-propyl, i-propyl, sec-propyl, n-butyl, i-butyl, sec-butyl, t-butyl, n-pentyl, i-pentyl, sec-pentyl, t-pentyl, n-hexyl, i-hexyl, 1,2-dimethylpropyl, 2-ethylpropyl, 1-methyl-2-ethylpropyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1,2-triethylpropyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 2-ethylbutyl, 1 , 3-dimethylbutyl, 2-methylpentyl, 3-methylpentyl, sec-hexyl, t-hexyl, n-heptyl, i-heptyl, sec-heptyl, t-heptyl, n-octyl, i-octyl, sec-octyl, t-octyl, n-nonyl, i-nonyl, sec-nonyl, t-nonyl, n-decyl, i-decyl, sec-decyl, t-decyl, cyclopropanyl, cyclobutanyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, cyclooctanyl, cyclononanyl, cyclodecanyl, and the like. Thus, unless otherwise specified, C 1 ~C 20 Alkylenyl includes, but is not limited to, all divalent analogs of the above saturated alkyl groups.

[0086] As used herein, "C 3 ~C 5 The expressions "alkylenyl, alkenylenyl, or alkynylenyl of 3 ~C 5 Alkylenyl, C 3 ~C 5 Alkenylenyl, or C 3 ~C 5 It is understood to mean alkynylenyl, and also "C 1 ~C 5The expressions "alkylenyl, alkenylenyl, or alkynylenyl of 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 Similarly, as used herein, "C 5 ~C 20 The expression "alkyl, alkenyl, or alkynyl" is 5 ~C 20 Alkyl, C 5 ~C 20 Alkenyl, or C 5 ~C 20 alkynyl and "C" are understood to mean 1 ~C 20 The expressions "alkyl, alkenyl, or alkynyl of 1 ~C 20 Alkyl, C 2 ~C 20 Alkenyl, or C 2 ~C 20 is understood to mean alkynyl.

[0087] As used herein, the term "unsaturated" when referring to a chemical entity is commonly understood by those of skill in the art and may be used generally to refer to a chemical entity that contains at least one double or triple bond, and may contain linear, branched, and / or cyclic groups. 2 ~C 20 Non-limiting examples of alkenyl groups include vinyl, allyl, isopropenyl, 1-propen-2-yl, 1-buten-1-yl, 1-buten-2-yl, 1-buten-3-yl, 2-buten-1-yl, 2-buten-2-yl, octenyl, decenyl, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, cyclononanenyl, cyclodecanenyl, and the like. Thus, unless otherwise specified, C 1 ~C 20Alkenylenyl includes, but is not limited to, all divalent analogs of the above alkenyl groups. 2 ~C 20 Non-limiting examples of alkynyl groups include ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, decynyl, and the like. Thus, unless otherwise specified, C 1 ~C 20 Alkynylenyl includes, but is not limited to, all divalent analogs of the above alkynyl groups.

[0088] When one or more carbons in an alkyl, alkenyl, alkynyl, alkylenyl, alkenylenyl, alkynylenyl, etc. are specified to be independently replaced with a heteroatom, one of ordinary skill in the art will understand that various combinations of different heteroatoms may be used. Non-limiting examples of non-aromatic heterocyclic groups include aziridinyl, azetidinyl, diazetidinyl, pyrrolidinyl, pyrrolinyl, piperidinyl, piperazinyl, imidazolinyl, pyrazolidinyl, imidazolidinyl, phthalimidyl, succinimidyl, oxiranyl, tetrahydropyranyl, oxetanyl, dioxanyl, thietanyl, thiepinyl, morpholinyl, oxathiolanyl, etc. The phrase "linear, branched, and / or cyclic... alkyl, alkenyl, or alkynyl" specifically includes aryl groups. Unless further specified, "aryl" groups include both single aromatic rings as well as fused rings containing at least one aromatic ring. C 3 ~C 20 Non-limiting examples of aryl groups include phenyl (Ph), pentalenyl, indenyl, naphthyl, and azulenyl. C, which has one or more carbons replaced with a heteroatom. 3 ~C 20Non-limiting examples of aromatic rings include pyrrolyl, imidazolyl, pyrazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, quinolinyl, isoquinolinyl, acridinyl, indolyl, isoindolyl, indolizinyl, purinyl, carbazolyl, indazolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, pteridinyl, phenanthridinyl, phenazinyl, phenanthrinyl, perimidinyl, furyl, dibenzofuryl, xanthenyl, benzofuryl, thiophenyl, thianthrenyl, benzothiophenyl, phosphorinyl, phosphinolinyl, phosphindolyl, thiazolyl, oxazolyl, isoxazolyl, and the like. Similarly, the phrases "linear, branched, and / or cyclic... alkylenyl, alkenylenyl, or alkynylenyl" specifically include the divalent analogs of the linear, branched, and / or cyclic alkyl, alkenyl, or alkynyl groups defined above, including all aryl groups encompassed therein.

[0089] As used herein, the term "substituted" is used as would be commonly understood by one of ordinary skill in the art and generally refers to a compound or chemical entity having one chemical group replaced with a different chemical group. Unless otherwise specified, a substituted alkyl is an alkyl in which one or more hydrogen atoms are each independently replaced with a non-hydrogen atom. For example, chloromethyl is a non-limiting example of a substituted alkyl, and more specifically, an example of a substituted methyl. Aminoethyl is another non-limiting example of a substituted alkyl, and more specifically, an example of a substituted ethyl. Unless otherwise specified, a substituted compound or group (e.g., alkyl, alkylenyl, aryl, etc.) may be substituted with any chemical group reasonable to one of ordinary skill in the art. For example, but not limited to, a hydrogen bonded to a carbon or heteroatom (e.g., N) may be substituted with a halide (e.g., F, I, Br, Cl), an amine, an amide, an oxo, a hydroxyl, a thiol (sulfhydryl), a phosphate ester (or phosphoric acid), a phosphonate ester, a sulfate, a SO 2 H (sulfinic acid), SO 3It may be substituted with H (sulfonic acid), alkyl, aryl, ketone, carboxaldehyde, carboxylic acid, carboxamide, nitrile, guanidino, monohalomethyl, dihalomethyl, or trihalomethyl.

[0090] As used herein, the term "guanidino" refers to -NHC(=NH)NH 2 or -NHC(=NR)NR 2 wherein each R is independently H or alkyl.

[0091] As used herein, the term "unsubstituted" is used as would be commonly understood by one of ordinary skill in the art. Non-limiting examples of unsubstituted alkyl include methyl, ethyl, tert-butyl, pentyl, etc. The phrase "optionally substituted with..." is used interchangeably with the phrase "unsubstituted or substituted."

[0092] In the structures provided herein, hydrogen may or may not be shown. In some embodiments, hydrogen (whether shown or implied) is replaced by protium (i.e., 1 H), and deuterium (i.e., 2 H), or 1 H and 2 It may be in combination with H. 1 H 2 Methods for exchanging with H are well known in the art. In the case of solvent exchangeable hydrogen, 1 H 2 Exchange with H occurs readily in the presence of a suitable deuterium source without a catalyst. The use of acids, bases, or metal catalysts, in conjunction with elevated temperature and pressure conditions, can facilitate the exchange of non-exchangeable hydrogen atoms, generally resulting in the exchange of all hydrogen atoms in the molecule. 1 From H 2 This results in an exchange for H.

[0093] The compounds disclosed herein incorporate amino acids, for example as residues in a peptide chain (linear or branched) or as amino acids that are otherwise part of the compound. Amino acids have both amino and carboxylic acid groups, either or both of which may be used for covalent attachment. Upon attachment to the remainder of the compound, the amino and / or carboxylic acid groups may be converted to an amide or another structure, for example, the carboxylic acid group of a first amino acid is converted to an amide (e.g., a peptide bond) when attached to the amino group of a second amino acid. Thus, amino acid residues can be represented by the formula -N(R a )R b C(O)—, where R a and R b is an R group. a will typically be hydrogen or methyl. The amino acid residues of a peptide may contain typical peptide (amide) bonds and may further contain bonds between a side chain functional group and a side chain or main chain functional group of another amino acid. For example, the side chain carboxylic acid of one amino acid residue (e.g., Asp, Glu, etc.) in a peptide may be bonded to the amine of another amino acid residue (e.g., Dap, Dab, Orn, Lys) in the peptide. Further details are provided below. The term "amino acid" includes proteinogenic and non-proteinogenic amino acids. Non-limiting examples of non-proteinogenic amino acids are provided in Table 1 and include: D-amino acids (including, but not limited to, the D-forms of any of the following amino acids), ornithine (Orn), 3-(1-naphthyl)alanine (Nal), 3-(2-naphthyl)alanine (2-Nal), α-aminobutyric acid, norvaline, norleucine (Nle), homonorleucine, beta-(1,2,3-triazol-4-yl)-L-alanine, 1,2,4-triazol-3-alanine, Phe(4-F), Phe(4-Cl), Phe(4-Br), Phe(4-I), Phe(4-NH 2 ), Phe(4-NO 2 ), N ε ,N ε ,N ε-Trimethyl-lysine, homoarginine (hArg), 2-amino-4-guanidinobutyric acid (Agb), 2-amino-3-guanidinopropionic acid (Agp), B-alanine, 4-aminobutyric acid, 5-aminovaleric acid, 6-aminohexanoic acid, 7-aminoheptanoic acid, 8-aminooctanoic acid, 9-aminononanoic acid, 10-aminodecanoic acid, 2-aminooctanoic acid, 2-amino-3-(anthracen-2-yl)propanoic acid, 2-amino-3-(anthracen-9-yl)propanoic acid, 2-amino-3-(pyren-1-yl)propanoic acid, Trp(5-Br), Trp(5-OCH 3 ), Trp(6-F), Trp(5-OH) or Trp(CHO), 2-aminoadipic acid (2-Aad), 3-aminoadipic acid (3-Aad), propargylglycine (Pra), homopropargylglycine (Hpg), beta-homopropargylglycine (Bpg), 2,3-diaminopropionic acid (Dap), 2,4-diaminobutyric acid (Dab), azidolysine (Lys(N 3 )), azido-ornithine (Orn(N 3 )), 2-amino-4-azidobutanoic acid Dab(N 3 ), Dap(N 3 ), 2-(5'-azidopentyl)alanine, 2-(6'-azidohexyl)alanine, 4-amino-1-carboxymethyl-piperidine (Pip), 4-(2-aminoethyl)-1-carboxymethyl-piperazine (Acp), and tranexamic acid. If not specified as an L-amino acid or a D-amino acid, the amino acid is to be understood to be an L-amino acid.

[0094] [Table 1]

[0095] As used herein, an "amide of a peptide backbone" refers to, for example, R 2a , R 3a , R 4a , R 5a , R 6a , R A7a , R B7a , and R C7a"A" refers to an amide (-C(O)-NH-) depicted within the structures of formula AI, A-II, A-III, A-III, A-IV, B, or C, including the amide bond between the carbon atoms bonded to R. One or more peptide backbone amides may be methylated or N-methylated, unless otherwise discussed herein. For example, R 2a , R 3a , R 4a , R 5a , R 6a , R A7a , R B7a , and R C7a The amide bond between the carbon atoms bonded to 3 -) can be done.

[0096] In the chemical formula (e.g., L 1 Wavy lines through or at the ends of bonds in [ka] The symbol is intended to define the R group on one side of the wavy line without altering the definition of the structure on the other side of the wavy line. 1 Any atoms shown outside the wavy lines are intended to clarify the orientation of the R group when the R group is bonded on a specific definition of the formula (e.g., -R). Thus, only the atoms between the two wavy lines constitute the definition of the R group. When atoms are not shown outside the wavy lines, or when a chemical group is shown without a wavy line but has multiple side chain bonds (e.g., -C(O)NH-, etc.), the chemical group should be read from left to right in the orientation of the formula to which the group is associated (e.g., -R a -R b -R c In the case of -, use -C(O)NH-. b The definition of -R a -NHC(O)-R c -R instead of - a -C(O)NH-R c - will be incorporated into the formula).

[0097] compound In various embodiments, a compound of formula A, B, or C, or a salt or solvate of formula A, B, or C is disclosed: [ka] The R group is defined below: wherein 0 to 3 peptide backbone amides are independently [ka] amidine or thioamide substituted, wherein 0 to 3 of the peptide backbone amides are N-methylated; In the formula, the C-terminus may be amidated.

[0098] In some embodiments, the compound has a structure of Formula A. In some embodiments, the compound is a salt of Formula A. In some embodiments, the compound is a solvate of Formula A.

[0099] In some embodiments, the compound has the structure of Formula A, or a salt or solvate thereof: [ka] During the ceremony,

[0100] R 2a is -(CH 2 )-(R 2b )-(phenyl), where R 2b does not exist or -CH 2 -, -NH-, -S-, or -O-, where phenyl is -NH 2 , -NO 2 , -OH, -OR 2c , -SH, -SR 2c , -N 3 , -CN, or -O-phenyl, wherein the phenyl is optionally substituted at the 3-position with a halogen or -OH, wherein the phenyl is optionally substituted at the 5-position with a halogen or -OH, wherein the -O-phenyl ring is optionally substituted at the 6-position with -NH 2, -NO 2 , -OH, -OR 2c , -SH, -N 3 , -CN, or -SR 2c the -O-phenyl ring is optionally substituted at the 4-position with a halogen or -OH, the -O-phenyl ring is optionally substituted at the 3-position with a halogen or -OH, the -O-phenyl ring is optionally substituted at the 5-position with a halogen or -OH, 2c are independently 1 ~C 3 is a straight or branched alkyl group of

[0101] R 3a is C 1 ~C 5 Alkyl or R 3b R 3c where R 3b is a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 alkynylenyl, wherein C 2 ~C 5 0-2 carbons in are independently replaced with one or more N, S, and / or O heteroatoms, 3c is -N(R 3d ) 2~3 or guanidino, wherein each R 3d are independently -H or linear or branched C 1 ~C 3 is alkyl,

[0102] R 4a is R 4b R 4c where R 4b is a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 Alkynylenyl, where C 2 ~C 50-2 carbons in are independently replaced with one or more N, S, and / or O heteroatoms, 4c is -N(R 4d ) 2~3 or guanidino, wherein each R 4d are independently -H or linear or branched C 1 ~C 3 is alkyl,

[0103] R 5a is -(CH 2 ) 1~3 -R 5b In the formula: -(CH 2 ) 2~3 - one carbon in may be replaced with a heteroatom of N, S, or O, 5b teeth,

[0104] Phenyl,

[0105] -NH 2 , -NO 2 , -OH, -OR 5c , -SH, -SR 5c , -N 3 , -CN, or -O-phenyl, substitution at the 4-position with a halogen or -OH, and / or substitution at the 5-position with a halogen or -OH, wherein the -O-phenyl ring is -NH 2 , -NO 2 , -OH, -OR 5c , -SH, -SR 5c , -N 3 or -CN at the 4-position, wherein the -O-phenyl ring is optionally substituted at the 3-position with a halogen or -OH, wherein the -O-phenyl ring is optionally substituted at the 5-position with a halogen or -OH;

[0106] fused bicyclic or tricyclic aryl or heteroaryl rings, each of which is halogen, -OH, -OR 5c , amino, -NHR 5c, and / or N(R 5c ) 2 a fused bicyclic or tricyclic aryl or heteroaryl ring, optionally substituted with one or more of

[0107] In the formula, each R 5c are independently 1 ~C 3 is a straight or branched alkyl group of

[0108] Any R 6a is H, methyl, ethyl, -C≡CH, -CH=CH 2 , -C≡C-(CH 2 ) 1-3 -OH, -C≡C-(CH 2 ) 1-3 -SH, -C≡C-(CH 2 ) 1-3 -NH 2 , -C≡C-(CH 2 ) 1-3 -COOH, -C≡C-(CH 2 ) 1-3 -CONH 2 , -C≡C-(CH 2 ) 1-3 R 6b R 6c , -CH=CH-(CH 2 ) 1-3 -OH, -CH=CH-(CH 2 ) 1-3 -SH, -CH=CH-(CH 2 ) 1-3 -NH 2 , -CH=CH-(CH 2 ) 1-3 -COOH, -CH=CH-(CH 2 ) 1-3 -CONH 2 , -CH=CH-(CH 2 ) 1-3 R 6b R 6c , -CH 2 -R 6b -OH, -CH 2 -R 6b -COOH, -CH 2 -(R 6b )1~3 -NH 2 , -CH 2 -R 6b -CONH 2 , or -CH 2 -R 6b R 6c where each R 6b are independently absent or -CH 2 -, -NH-, -S-, or -O-; and 6c teeth,

[0109] a 5- or 6-membered aromatic ring, wherein one or more carbons are optionally independently replaced with N, S, and / or O heteroatoms and one or more groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen;

[0110] or -NH-CH(R 6a )-C(O)-NH-, [ka] is replaced by

[0111] R A7a is a linear C 1 ~C 5 alkylenyl, wherein C 2 ~C 5 0-2 carbons in are independently replaced by one or more N, S, and / or O heteroatoms;

[0112] R 8a is R 8b R 8c where R 8b is a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 Alkynylenyl, where C 2 ~C 50-2 carbons in the alkylenyl, alkenylenyl, or alkynylenyl are independently replaced with one or more N, S, and / or O heteroatoms, 8c is -N(R 8d ) 2~3 or guanidino, wherein each R 8d are independently -H or linear or branched C 1 ~C 3 is alkyl,

[0113] R 9a is -C(O)NH 2 , -C(O)-OH, -CH 2 -C(O)NH 2 , -CH 2 -C(O)-OH, -CH 2 -NH 2 , -CH 2 -OH, -CH 2 -CH 2 -NH 2 , -R 9b -R 9c , or -R 9b -[Linker]-R X n1 where:

[0114] R 9b is -CH 2 -NH-C(O)-, -CH 2 -C(O)-, -CH 2 -O-, -C(O)NH-, -C(O)-N(CH 3 )-, -CH 2 -NHC(S)-, -C(S)NH-, -CH 2 -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -CH 2 -N(CH 3 )C(O)-, -C(S)N(CH 3 )-, -CH 2 -NHC(S)NH-, -CH 2 -NHC(O)NH-, -CH 2 -S-, -CH 2 -S(O)-, -CH 2 -S(O) 2-, -CH 2 -S(O) 2 -NH-, -CH 2 -S(O)-NH-, -CH 2 -Se-, -CH 2 -Se(O)-, -CH 2 -Se(O) 2 -, -CH 2 -NHNHC(O)-, -C(O)NHNH-, -CH 2 -OP(O)(O - )O-, -CH 2 -Phosphamide-, -CH 2 -Thiophosphodiester-, -CH 2 -S-tetrafluorophenyl-S-, [ka] or polyethylene glycol,

[0115] R 9c is hydrogen or a linear, branched and / or cyclic C 1 ~C 20 is an alkyl, alkenyl, or alkynyl of the formula: 2 ~C 20 wherein 0-6 carbons are independently replaced with N, S, and / or O heteroatoms, and 0-3 groups independently selected from one or a combination of oxo, hydroxyl, sulfhydryl, halogen, guanidino, carboxylic acid, sulfonic acid, sulfinic acid, and / or phosphate;

[0116] R A10 does not exist or -[linker]-R X n1 and

[0117] R A10 If does not exist, R A1a teeth,

[0118] Linear C 1 ~C 5 Alkyl, C 2 ~C 5Alkenyl, or C 2 ~C 5 alkynyl, wherein C 2 ~C 5 0-2 carbons in the alkyl, alkenyl, or alkynyl are independently replaced with one or more N, S, and / or O heteroatoms, where C is -SH, -OH, amino, carboxy, guanidino, -NH-C(O)-CH 3 , -SC(O)-CH 3 , -OC(O)-CH 3 , -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH 3 ) 1~2 , -NH 2 -CH 3 , -N(CH 3 ) 2~3 , -S-CH 3 , or -O-CH 3 and optionally substituted with one substituent selected from

[0119] Branch C 1 ~C 10 is an alkyl, alkenyl, or alkynyl of the formula: 2 ~C 10 wherein 0-3 carbons are independently replaced by one or more N, S, and / or O heteroatoms; or

[0120] R A1b R A1c where R A1b is a linear C 1 ~C 3 alkylenyl, wherein C 2 Alkylenyl or C 3 Alkylenyl may be substituted with N, S, or O heteroatoms, where R A1c teeth,

[0121] a 5- or 6-membered aromatic ring, wherein one or more carbons are optionally independently replaced with N, S, and / or O heteroatoms and one or more groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen; or

[0122] Fused bicyclic or fused tricyclic aryl groups, in which one or more carbons may be independently replaced with heteroatoms of N, S, and / or O, and may also be replaced with halogen, -OH, -OR A1d , amino, -NHR A1d , and / or N(R A1d ) 2 wherein each R A1d is independently C 1 ~C 3 a fused bicyclic or tricyclic aryl group, which is a linear or branched alkyl group of the formula:

[0123] R A10 -[Linker]-R X n1 If so, then R A1a is R A1e R A1f where R A1e is a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 Alkynylenyl, where C 2 ~C 5 0-2 carbons in the alkylenyl, alkenylenyl, and alkynylenyl are independently replaced with heteroatoms of N, S, and / or O; and R A1f -NH-C(O)-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH 3 )-, -NHC(S)-, -C(S)NH-, -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -N(CH 3)C(O)-, -C(S)N(CH 3 )-, -NHC(S)NH-, -NHC(O)NH-, -S-, -S(O)-, -S(O)-O-, -S(O) 2 -, -S(O) 2 -O-, -S(O) 2 -NH-, -S(O)-NH-, -Se-, -Se(O)-, -Se(O) 2 -, -NHNHC(O)-, -C(O)NHNH-, -OP(O)(O - )O-, -phosphamide-, -thiophosphodiester-, -S-tetrafluorophenyl-S-, [ka] or polyethylene glycol,

[0124] R y is hydrogen or R 3e R 3f where R 3e is a linear C 1 ~C 5 alkylenyl, wherein R 3f is -N(R 3g ) 2~3 where each R 3g are independently -H or linear or branched C 1 ~C 3 is alkyl,

[0125] each n1 is independently 0, 1, or 2;

[0126] Each R X is an albumin binder, a therapeutic moiety, a fluorescent label, a radiolabeled group, or a group that can be radiolabeled;

[0127] wherein 0 to 3 peptide backbone amides are independently [ka] amidine or thioamide substituted,

[0128] wherein 0 to 3 of the peptide backbone amides are N-methylated;

[0129] In the formula, the C-terminus may be amidated.

[0130] In some embodiments of the compound of formula A, the compound does not have the following combination: -NH-CH(R 2a )-C(O)- to form a Tyr residue; -NH-CH(R 4a )-C(O)- to form a D-Arg residue, -NH-CH(R 5a )-C(O)- forms a 2-Nal residue, and R 6a is H.

[0131] In some embodiments of the compound of formula A,

[0132] R A10 -[Linker]-R X n1 and

[0133] The linker is X 1 L 1 , X 1 L 1 X 1 L 1 , or X 1 L 1 X 1 L 1 X 1 L 1 and

[0134] X 1 Each independently represents -CH 2 -, [ka] and

[0135] L 1 each independently represents -NH-, -C(O)-, -NHC(O)-, -C(O)NH-, -N(CH 3 )C(O)-, or -C(O)N(CH 3 )-and

[0136] R 11 are each independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid; and

[0137] R Z are each independently an albumin binder.

[0138] In some embodiments of the compound of formula A, R y is R 3e R 3f It is.

[0139] In some embodiments of the compound of formula A, the compound comprises an albumin binder.

[0140] In some embodiments, the compound has a structure of Formula B. In some embodiments, the compound is a salt of Formula B. In some embodiments, the compound is a solvate of Formula B.

[0141] In some embodiments, the compound has the structure of formula B, or a salt or solvate thereof: [ka] During the ceremony,

[0142] R 2a is -(CH 2 )-(R 2b )-(phenyl), where R 2b does not exist or -CH 2 -, -NH-, -S-, or -O-, where phenyl is -NH 2 , -NO 2 , -OH, -OR 2c , -SH, -SR 2c , -N 3 , -CN, or -O-phenyl, wherein the phenyl is optionally substituted at the 3-position with a halogen or -OH, wherein the phenyl is optionally substituted at the 5-position with a halogen or -OH, wherein the -O-phenyl ring is optionally substituted at the 6-position with -NH2 , -NO 2 , -OH, -OR 2c , -SH, -SR 2c , -N 3 or -CN, the -O-phenyl ring is optionally substituted at the 4-position with a halogen or -OH, the -O-phenyl ring is optionally substituted at the 3-position with a halogen or -OH, the -O-phenyl ring is optionally substituted at the 5-position with a halogen or -OH, 2c are independently 1 ~C 3 is a straight or branched alkyl group of

[0143] R 3a is C 1 ~C 5 Alkyl or R 3b R 3c where R 3b is a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 alkynylenyl, wherein C 2 ~C 5 0-2 carbons in are independently replaced with one or more N, S, and / or O heteroatoms, 3c is -N(R 3d ) 2~3 or guanidino, wherein each R 3d are independently -H or linear or branched C 1 ~C 3 is alkyl,

[0144] R 4a is R 4b R 4c where R 4b is a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 Alkynylenyl, where C 2 ~C 50-2 carbons in are independently replaced with one or more N, S, and / or O heteroatoms, 4c is -N(R 4d ) 2~3 or guanidino, wherein each R 4d are independently -H or linear or branched C 1 ~C 3 is alkyl,

[0145] R 5a is -(CH 2 ) 1~3 -R 5b In the formula: -(CH 2 ) 2~3 - one carbon in may be replaced with a heteroatom of N, S, or O, 5b teeth,

[0146] Phenyl,

[0147] -NH 2 , -NO 2 , -OH, -OR 5c , -SH, -SR 5c , -N 3 , -CN, or -O-phenyl, substitution at the 4-position with a halogen or -OH, and / or substitution at the 5-position with a halogen or -OH, wherein the -O-phenyl ring is -NH 2 , -NO 2 , -OH, -OR 5c , -SH, -SR 5c , -N 3 or -CN at the 4-position, wherein the -O-phenyl ring is optionally substituted at the 3-position with a halogen or -OH, wherein the -O-phenyl ring is optionally substituted at the 5-position with a halogen or -OH;

[0148] fused bicyclic or tricyclic aryl or heteroaryl rings, each of which is halogen, -OH, -OR 5c , amino, -NHR 5c, and / or N(R 5c ) 2 a fused bicyclic or tricyclic aryl or heteroaryl ring, optionally substituted with one or more of

[0149] In the formula, each R 5c are independently 1 ~C 3 is a straight or branched alkyl group of

[0150] Any R 6a is H, methyl, ethyl, -C≡CH, -CH=CH 2 , -C≡C-(CH 2 ) 1-3 -OH, -C≡C-(CH 2 ) 1-3 -SH, -C≡C-(CH 2 ) 1-3 -NH 2 , -C≡C-(CH 2 ) 1-3 -COOH, -C≡C-(CH 2 ) 1-3 -CONH 2 , -C≡C-(CH 2 ) 1-3 R 6b R 6c , -CH=CH-(CH 2 ) 1-3 -OH, -CH=CH-(CH 2 ) 1-3 -SH, -CH=CH-(CH 2 ) 1-3 -NH 2 , -CH=CH-(CH 2 ) 1-3 -COOH, -CH=CH-(CH 2 ) 1-3 -CONH 2 , -CH=CH-(CH 2 ) 1-3 R 6b R 6c , -CH 2 -R 6b -OH, -CH 2 -R 6b -COOH, -CH 2 -(R 6b )1-3 -NH 2 , -CH 2 -R 6b -CONH 2 , or -CH 2 -R 6b R 6c where each R 6b are independently absent or -CH 2 -, -NH-, -S-, or -O-; and 6c teeth,

[0151] a 5- or 6-membered aromatic ring, wherein one or more carbons are optionally independently replaced with N, S, and / or O heteroatoms and one or more groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen;

[0152] or -NH-CH(R 6a )-C(O)-NH-, [ka] is replaced by

[0153] R 8a is R 8b R 8c where R 8b is a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 Alkynylenyl, where C 2 ~C 5 0-2 carbons in the alkylenyl, alkenylenyl, or alkynylenyl are independently replaced with one or more N, S, and / or O heteroatoms, 8c is -N(R 8d ) 2~3 or guanidino, wherein each R 8d are independently -H or linear or branched C 1 ~C3 is alkyl,

[0154] R 9a is -C(O)NH 2 , -C(O)-OH, -CH 2 -C(O)NH 2 , -CH 2 -C(O)-OH, -CH 2 -NH 2 , -CH 2 -OH, -CH 2 -CH 2 -NH 2 , -R 9b -R 9c , or -R 9b -[Linker]-R X n1 where:

[0155] R 9b is -CH 2 -NH-C(O)-, -CH 2 -C(O)-, -CH 2 -O-, -C(O)NH-, -C(O)-N(CH 3 )-, -CH 2 -NHC(S)-, -C(S)NH-, -CH 2 -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -CH 2 -N(CH 3 )C(O)-, -C(S)N(CH 3 )-, -CH 2 -NHC(S)NH-, -CH 2 -NHC(O)NH-, -CH 2 -S-, -CH 2 -S(O)-, -CH 2 -S(O) 2 -, -CH 2 -S(O) 2 -NH-, -CH 2 -S(O)-NH-, -CH 2 -Se-, -CH 2 -Se(O)-, -CH 2 -Se(O) 2 -, -CH 2-NHNHC(O)-, -C(O)NHNH-, -CH 2 -OP(O)(O - )O-, -CH 2 -Phosphamide-, -CH 2 -Thiophosphodiester-, -CH 2 -S-tetrafluorophenyl-S-, [ka] or polyethylene glycol,

[0156] R 9c is hydrogen or a linear, branched and / or cyclic C 1 ~C 20 is an alkyl, alkenyl, or alkynyl of the formula: 2 ~C 20 wherein 0-6 carbons are independently replaced with N, S, and / or O heteroatoms, and 0-3 groups independently selected from one or a combination of oxo, hydroxyl, sulfhydryl, halogen, guanidino, carboxylic acid, sulfonic acid, sulfinic acid, and / or phosphate;

[0157] R B1a is a linear, branched and / or cyclic C 1 ~C 10 Alkylenyl, C 2 ~C 10 Alkenylenyl, or C 2 ~C 10 alkynylenyl, wherein C 2 ~C 10 one or more carbons in the alkylenyl, alkenylenyl, or alkynylenyl may be independently replaced with heteroatoms of N, S, and / or O;

[0158] R B1-7 teeth, [ka] wherein the indole ring and the isoindole ring are each independently selected from -F, -Br, -Cl, -I, -OH, -ORB1-7b , -CO-, -COOH, -CONH 2 , -CN, -O-aryl, -NH 2 , -NHR B1-7b , N 3 , -NO 2 , -NH, -CHO, and / or -R B1-7b wherein each R B1-7b is a linear or branched C 1 ~C 3 Alkyl, C 2 ~C 3 Alkenyl, or C 2 ~C 3 is alkynyl,

[0159] R B7a is a linear C 1 ~C 5 alkylenyl, wherein C 2 ~C 5 0-2 carbons in the alkylenyl are independently replaced by one or more N, S, and / or O heteroatoms;

[0160] R B10a is an amine, -NH-(CH 3 ) 1~2 , -N(CH 3 ) 2~3 , -NH-C(O)-CH 3 , -NH-C(O)-(phenyl), or -R B10b -[Linker]-R X n1 where R B10b teeth,

[0161] -NH-C(O)-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH 3 )-, -NHC(S)-, -C(S)NH-, -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -N(CH 3 )C(O)-, -C(S)N(CH 3 )-, -NHC(S)NH-, -NHC(O)NH-, -S-, -S(O)-, -S(O)-O-, -S(O) 2-, -S(O) 2 -O-, -S(O) 2 -NH-, -S(O)-NH-, -Se-, -Se(O)-, -Se(O) 2 -, -NHNHC(O)-, -C(O)NHNH-, -OP(O)(O - )O-, -phosphamide-, -thiophosphodiester-, -S-tetrafluorophenyl-S-, [ka] or polyethylene glycol,

[0162] each n1 is independently 0, 1, or 2;

[0163] Each R X is an albumin binder, a therapeutic moiety, a fluorescent label, a radiolabeled group, or a group that can be radiolabeled;

[0164] wherein 0 to 3 peptide backbone amides are independently [ka] amidine or thioamide substituted,

[0165] wherein 0 to 3 of the peptide backbone amides are N-methylated;

[0166] In the formula, the C-terminus may be amidated.

[0167] In some embodiments, the compound has a structure of formula C. In some embodiments, the compound is a salt of formula C. In some embodiments, the compound is a solvate of formula C.

[0168] In some embodiments, the compound has the structure of Formula C, or a salt or solvate thereof: [ka] During the ceremony,

[0169] R 2a is -(CH 2 )-(R 2b )-(phenyl), where R 2b does not exist or -CH 2 -, -NH-, -S-, or -O-, where phenyl is -NH 2 , -NO 2 , -OH, -OR 2c , -SH, -SR 2c , -N 3 , -CN, or -O-phenyl, wherein the phenyl is optionally substituted at the 3-position with a halogen or -OH, wherein the phenyl is optionally substituted at the 5-position with a halogen or -OH, wherein the -O-phenyl ring is optionally substituted at the 6-position with -NH 2 , -NO 2 , -OH, -OR 2c , -SH, -SR 2c , -N 3 or -CN, the -O-phenyl ring is optionally substituted at the 4-position with a halogen or -OH, the -O-phenyl ring is optionally substituted at the 3-position with a halogen or -OH, the -O-phenyl ring is optionally substituted at the 5-position with a halogen or -OH, 2c are independently 1 ~C 3 is a straight or branched alkyl group of

[0170] R 3a is C 1 ~C 5 Alkyl or R 3b R 3c where R 3b is a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 alkynylenyl, wherein C 2 ~C 5 0-2 carbons in are independently replaced with one or more N, S, and / or O heteroatoms, 3c is -N(R 3d )2~3 or guanidino, wherein each R 3d are independently -H or linear or branched C 1 ~C 3 is alkyl,

[0171] R 4a is R 4b R 4c where R 4b is a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 Alkynylenyl, where C 2 ~C 5 0-2 carbons in are independently replaced with one or more N, S, and / or O heteroatoms, 4c is -N(R 4d ) 2~3 or guanidino, wherein each R 4d are independently -H or linear or branched C 1 ~C 3 is alkyl,

[0172] R 5a is -(CH 2 ) 1~3 -R 5b In the formula: -(CH 2 ) 2~3 - one carbon in may be replaced with a heteroatom of N, S, or O, 5b teeth,

[0173] Phenyl,

[0174] -NH 2 , -NO 2 , -OH, -OR 5c , -SH, -SR 5c , -N 3 , -CN, or -O-phenyl, substitution at the 4-position with a halogen or -OH, and / or substitution at the 5-position with a halogen or -OH, wherein the -O-phenyl ring is -NH2 , -NO 2 , -OH, -OR 5c , -SH, -SR 5c , -N 3 or -CN at the 4-position, wherein the -O-phenyl ring is optionally substituted at the 3-position with a halogen or -OH, wherein the -O-phenyl ring is optionally substituted at the 5-position with a halogen or -OH;

[0175] fused bicyclic or tricyclic aryl or heteroaryl rings, each of which is halogen, -OH, -OR 5c , amino, -NHR 5c , and / or N(R 5c ) 2 a fused bicyclic or tricyclic aryl or heteroaryl ring, optionally substituted with one or more of

[0176] In the formula, each R 5c are independently 1 ~C 3 is a straight or branched alkyl group of

[0177] Any R 6a is H, methyl, ethyl, -C≡CH, -CH=CH 2 , -C≡C-(CH 2 ) 1-3 -OH, -C≡C-(CH 2 ) 1-3 -SH, -C≡C-(CH 2 ) 1-3 -NH 2 , -C≡C-(CH 2 ) 1-3 -COOH, -C≡C-(CH 2 ) 1-3 -CONH 2 , -C≡C-(CH 2 ) 1-3 R 6b R 6c , -CH=CH-(CH 2 ) 1-3 -OH, -CH=CH-(CH 2) 1-3 -SH, -CH=CH-(CH 2 ) 1-3 -NH 2 , -CH=CH-(CH 2 ) 1-3 -COOH, -CH=CH-(CH 2 ) 1-3 -CONH 2 , -CH=CH-(CH 2 ) 1-3 R 6b R 6c , -CH 2 -R 6b -OH, -CH 2 -R 6b -COOH, -CH 2 -(R 6b ) 1-3 -NH 2 , -CH 2 -R 6b -CONH 2 , or -CH 2 -R 6b R 6c where each R 6b are independently absent or -CH 2 -, -NH-, -S-, or -O-; and 6c teeth,

[0178] a 5- or 6-membered aromatic ring, wherein one or more carbons are optionally independently replaced with N, S, and / or O heteroatoms and one or more groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen;

[0179] or -NH-CH(R 6a )-C(O)-NH-, [ka] is replaced by

[0180] R A7a is a linear C 1 ~C 5 alkylenyl, wherein C2 ~C 5 0-2 carbons in are independently replaced by one or more N, S, and / or O heteroatoms;

[0181] R 8a is R 8b R 8c where R 8b is a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 Alkynylenyl, where C 2 ~C 5 0-2 carbons in the alkylenyl, alkenylenyl, or alkynylenyl are independently replaced with one or more N, S, and / or O heteroatoms, 8c is -N(R 8d ) 2~3 or guanidino, wherein each R 8d are independently -H or linear or branched C 1 ~C 3 is alkyl,

[0182] R 9a is -C(O)NH 2 , -C(O)-OH, -CH 2 -C(O)NH 2 , -CH 2 -C(O)-OH, -CH 2 -NH 2 , -CH 2 -OH, -CH 2 -CH 2 -NH 2 , -R 9b -R 9c , or -R 9b -[Linker]-R X n1 where:

[0183] R 9b is -CH 2 -NH-C(O)-, -CH 2 -C(O)-, -CH 2-O-, -C(O)NH-, -C(O)-N(CH 3 )-, -CH 2 -NHC(S)-, -C(S)NH-, -CH 2 -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -CH 2 -N(CH 3 )C(O)-, -C(S)N(CH 3 )-, -CH 2 -NHC(S)NH-, -CH 2 -NHC(O)NH-, -CH 2 -S-, -CH 2 -S(O)-, -CH 2 -S(O) 2 -, -CH 2 -S(O) 2 -NH-, -CH 2 -S(O)-NH-, -CH 2 -Se-, -CH 2 -Se(O)-, -CH 2 -Se(O) 2 -, -CH 2 -NHNHC(O)-, -C(O)NHNH-, -CH 2 -OP(O)(O - )O-, -CH 2 -Phosphamide-, -CH 2 -Thiophosphodiester-, -CH 2 -S-tetrafluorophenyl-S-, [ka] or polyethylene glycol,

[0184] R 9c is hydrogen or a linear, branched and / or cyclic C 1 ~C 20 is an alkyl, alkenyl, or alkynyl of the formula: 2 ~C 20wherein 0-6 carbons are independently replaced with N, S, and / or O heteroatoms, and 0-3 groups independently selected from one or a combination of oxo, hydroxyl, sulfhydryl, halogen, guanidino, carboxylic acid, sulfonic acid, sulfinic acid, and / or phosphate;

[0185] R C1a teeth, [ka] wherein the indole, isoindole, and triazole rings are each independently selected from -F, -Br, -Cl, -I, -OH, -OR C1b , -CO-, -COOH, -CONH 2 , -CN, -O-aryl, -NH 2 , -NHR C1b , N 3 , -NO 2 , -NH, -CHO, and / or -R C1b wherein each R C1b is a linear or branched C 1 ~C 3 Alkyl, C 2 ~C 3 Alkenyl, or C 2 ~C 3 is alkynyl,

[0186] R C7a is a linear C 1 ~C 5 alkylenyl, wherein C 2 ~C 5 0 to 2 carbons in the alkylenyl are optionally independently replaced by one or more N, S, and / or O heteroatoms;

[0187] R C10a is R C10b -R C10c -[Linker]-R X n1 or R C10d where:

[0188] RC10b is a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 Alkynylenyl, where C 2 ~C 5 0-2 carbons in the alkylenyl, alkenylenyl, and alkynylenyl are independently replaced with heteroatoms of N, S, and / or O;

[0189] R C10c -NH-C(O)-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH 3 )-, -NHC(S)-, -C(S)NH-, -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -N(CH 3 )C(O)-, -C(S)N(CH 3 )-, -NHC(S)NH-, -NHC(O)NH-, -S-, -S(O)-, -S(O)-O-, -S(O) 2 -, -S(O) 2 -O-, -S(O) 2 -NH-, -S(O)-NH-, -Se-, -Se(O)-, -Se(O) 2 -, -NHNHC(O)-, -C(O)NHNH-, -OP(O)(O - )O-, -phosphamide-, -thiophosphodiester-, -S-tetrafluorophenyl-S-, [ka] or polyethylene glycol,

[0190] R C10d teeth,

[0191] Linear C 1 ~C 5 Alkyl, C 2 ~C 5 Alkenyl, or C 2 ~C 5 alkynyl, wherein C2 ~C 5 0-2 carbons in the alkyl, alkenyl, or alkynyl are independently replaced with heteroatoms of N, S, and / or O, where C is -SH, -OH, amino, carboxy, guanidino, -NH-C(O)-CH 3 , -SC(O)-CH 3 , -OC(O)-CH 3 , -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH 3 ) 1~2 , -NH 2 -CH 3 , -N(CH 3 ) 2~3 , -S-CH 3 , or -O-CH 3 and optionally substituted with one substituent selected from

[0192] Branch C 1 ~C 10 Alkyl, C 2 ~C 10 Alkenyl, or C 2 ~C 10 alkynyl, wherein C 2 ~C 10 wherein 0-3 carbons in the alkyl, alkenyl, or alkynyl are independently replaced with heteroatoms of N, S, and / or O; or

[0193] R C10e R C10f where R C10e is a linear C 1 ~C 3 Alkyl, C 2 Alkyl or C 3 The alkyl may be substituted with N, S, or O heteroatoms, where R C10f teeth,

[0194] a 5- or 6-membered aromatic ring, wherein one or more carbons are optionally independently replaced with N, S, and / or O heteroatoms and one or more groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen;

[0195] Fused bicyclic or fused tricyclic aryl groups, in which one or more carbons may be independently replaced with heteroatoms of N, S, and / or O, and may also be replaced with halogen, -OH, -OR C10g , amino, -NHR C10g , and / or N(R C10g ) 2 wherein R C10g is C 1 ~C 3 a fused bicyclic or fused tricyclic aryl group, which is a linear or branched alkyl group of the formula:

[0196] each n1 is independently 0, 1, or 2;

[0197] Each R X is an albumin binder, a therapeutic moiety, a fluorescent label, a radiolabeled group, or a group that can be radiolabeled;

[0198] wherein 0 to 3 peptide backbone amides are independently [ka] amidine or thioamide substituted,

[0199] wherein 0 to 3 of the peptide backbone amides are N-methylated;

[0200] In the formula, the C-terminus may be amidated.

[0201] In some embodiments of the compounds of Formula A, B, and / or C, the compound comprises an albumin binder.

[0202] In some embodiments of the compounds of formula A, B, and / or C, R 9a is R 9b -[Linker]R x n1 In some embodiments of the compounds of formula A, B, and / or C, R 3a is C 1 ~C 5 In some embodiments of the compounds of Formula A, B, and / or C, at least one peptide backbone amide is N-methylated. In some embodiments of the compounds of Formula A, B, and / or C, at least one peptide backbone amide is substituted with an amidine.

[0203] In some embodiments of the compounds of formula A, B, and / or C, the amide of one peptide backbone is [ka] amidine, or thioamide. In some embodiments, two peptide backbone amides are replaced. In some embodiments, three peptide backbone amides are replaced. In some embodiments, zero peptide backbone amides are replaced.

[0204] In some embodiments of compounds of Formula A, B, and / or C, at least one peptide backbone amide is N-methylated. In some embodiments, one peptide backbone amide is N-methylated. In some embodiments, two peptide backbone amides are N-methylated. In some embodiments, three peptide backbone amides are N-methylated. In some embodiments, zero peptide backbone amides are N-methylated.

[0205] In some embodiments of compounds of Formula A, B, and / or C, at least one peptide backbone amide is substituted with an amidine. In some embodiments, one peptide backbone amide is substituted with an amidine. In some embodiments, two peptide backbone amides are each substituted with an amidine. In some embodiments, three peptide backbone amides are each substituted with an amidine. In some embodiments, zero peptide backbone amides are each substituted with an amidine.

[0206] In some embodiments, R 3a and R 4a Between 4a and R 5a Between or R 5a and R 6a The carbonyl of the peptide backbone between 3a )-C(=N)-NH-CH(R 4a )-, -CH(R 4a )-C(=N)-NH-CH(R 5a )- or -CH(R 5a )-C(=N)-NH-CH(R 6a In some embodiments, R 3a and R 4a The carbonyl of the peptide backbone between 3a )-C(=N)-NH-CH(R 4a In some embodiments, R 4a and R 5a The carbonyl of the peptide backbone between 4a )-C(=N)-NH-CH(R 5a )-) is replaced by R 5a and R 6a The carbonyl of the peptide backbone between 5a )-C(=N)-NH-CH(R 6a )-) is substituted.

[0207] In some embodiments of the compounds of formula A, B, and / or C, R 2a is -(CH2 )-(R 2b )-(phenyl), where R 2b does not exist or -CH 2 -, -NH-, -S-, or -O-, where phenyl is -NH 2 , -NO 2 , -OH, -OR 2c , -SH, -SR 2c , -N 3 , -CN, or -O-phenyl, wherein the phenyl is optionally substituted at the 3-position with a halogen or -OH, wherein the phenyl is optionally substituted at the 5-position with a halogen or -OH, wherein the -O-phenyl ring is optionally substituted at the 6-position with -NH 2 , -NO 2 , -OH, -OR 2c , -SH, -SR 2c , -N 3 or -CN, the -O-phenyl ring is optionally substituted at the 4-position with a halogen or -OH, the -O-phenyl ring is optionally substituted at the 3-position with a halogen or -OH, the -O-phenyl ring is optionally substituted at the 5-position with a halogen or -OH, 2c are independently 1 ~C 3 is a straight or branched alkyl group.

[0208] In some embodiments of the compounds of formula A, B, and / or C, R 2b is absent. In some embodiments, R 2b is -CH 2 In some embodiments, R 2b In some embodiments, R 2b is -S-. In some embodiments, R 2b is -O-.

[0209] In some embodiments of the compounds of formula A, B, and / or C, R 2a is -(CH 2 )-(R 2b )-(phenyl), where R 2b is absent or -CH 2- and phenyl is -NH 2 , -NO 2 , -OH, -OR 2c , -SH, -SR 2c , -N 3 , -CN, or -O-phenyl. In some embodiments, the phenyl is substituted at the 4 position with -NH 2 In some embodiments, the phenyl is substituted at the 4 position with -NO 2 In some embodiments, the phenyl is substituted at the 4 position with -OH. In some embodiments, the phenyl is substituted at the 4 position with -SH. In some embodiments, the phenyl is substituted at the 4 position with -O-phenyl. In some embodiments, the phenyl is unsubstituted at the 3 and 5 positions. In some embodiments, the phenyl is substituted at the 3 position. In some embodiments, the phenyl is substituted at the 5 position. In some embodiments, the phenyl is substituted at the 3 and 5 positions. In some embodiments, the halogen substituent is iodine. The substituents at the 3 and 5 positions can be the same or different (e.g., different halogens, or a combination of halogen and -OH).

[0210] In some embodiments of the compounds of formula A, B, and / or C, -NH-CH(R 2a )-C(O)- forms an L-amino acid residue. In some embodiments, -NH-CH(R 2a )-C(O)- forms a D-amino acid residue. In some embodiments, -NH-CH(R 2a )-C(O)- forms a Tyr residue. In some embodiments, -NH-CH(R 2a )-C(O)- forms a Phe residue. In some embodiments, -NH-CH(R 2a )-C(O)- is (4-NO 2 In some embodiments, a -NH-CH(R 2a )-C(O)- is (4-NH 2 In some embodiments, a -NH-CH(R 2a)-C(O)- forms a hTyr residue. In some embodiments, -NH-CH(R 2a )-C(O)- forms a (3-I)Tyr residue. In some embodiments, -NH-CH(R 2a )-C(O)- forms a Glu residue. In some embodiments, -NH-CH(R 2a )-C(O)- forms a Gln residue. In some embodiments, -NH-CH(R 2a )-C(O)- forms a D-Tyr residue.

[0211] In some embodiments of the compounds of formula A, B, and / or C, R 3a is C 1 ~C 5 Alkyl or R 3b R 3c where R 3b is a linear C 1 ~C 5 is an alkylenyl, alkenylenyl, or alkynylenyl of the formula: 2 ~C 5 0-2 carbons in the alkylenyl, alkenylenyl, or alkynylenyl are independently replaced with one or more N, S, and / or O heteroatoms, 3c is -N(R 3d ) 2~3 or guanidino, wherein each R 3d are independently -H or linear or branched C 1 ~C 3 It is an alkyl.

[0212] In some embodiments of the compounds of formula A, B, and / or C, R 3a is R 3b R 3c where R 3b is a linear C 1 ~C 5 is an alkylenyl, alkenylenyl, or alkynylenyl of the formula: 2 ~C 50-2 carbons in the alkylenyl, alkenylenyl, or alkynylenyl are independently replaced with one or more N, S, and / or O heteroatoms, 3c is -N(R 3d ) 2~3 or guanidino, wherein each R 3d are independently -H or linear or branched C 1 ~C 3 It is an alkyl.

[0213] In some embodiments of the compounds of formula A, B, and / or C, R 3b is a linear C 1 ~C 5 In some embodiments, R is an alkylenyl, alkenylenyl, or alkynylenyl (i.e., without heteroatoms). 3b is C 2 ~C 5 In some embodiments, R 3b is a linear C 1 ~C 5 It is alkylenyl.

[0214] In some embodiments of the compounds of formula A, B, and / or C, R 3c is guanidino. In some embodiments, R 3c is -N(R 3d ) 2~3 In some embodiments, R 3c is -N(R 3d ) 2~3 where each R 3d is a linear or branched C 1 ~C 3 In some embodiments, R 3c is -N(R 3d ) 2~3 where each R 3d is methyl. In some embodiments, R 3c is -N(R 3d ) 2~3 where each R3d is independently -H or methyl. In some embodiments, R 3c is -NH 2 or -NH 3 It is.

[0215] In some embodiments of the compounds of formula A, B, and / or C, R 3a is C 1 ~C 5 In some embodiments, R 3a is methyl. In some embodiments, R 3a is ethyl. In some embodiments, R 3a is propyl. In some embodiments, R 3a is butyl. In some embodiments, R 3a is pentyl.

[0216] In some embodiments of the compound of formula A, -NR y -CH(R 3a )-C(O)- forms an L-amino acid residue. In some embodiments, -NR y -CH(R 3a )-C(O)- forms a D-amino acid residue. In some embodiments, -NR y -CH(R 3a )-C(O)- forms a Lys(iPr) residue. In some embodiments, -NR y -CH(R 3a )-C(O)- is Arg(Me) 2 In some embodiments, the -NR y -CH(R 3a )-C(O)- forms an Arg(Me) residue.

[0217] In some embodiments of the compound of formula A, NR y -CH(R 3a )-C(O)- is -NH-CH(R 3a )—C(O)—. In some embodiments, —NH—CH(R 3a)-C(O)- forms an L-amino acid residue. In some embodiments, -NH-CH(R 3a )-C(O)- forms a D-amino acid residue. In some embodiments, -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue. In some embodiments, -NH-CH(R 3a )-C(O)- is Arg(Me) 2 In some embodiments, the -NH-CH(R 3a )-C(O)- forms an Arg(Me) residue.

[0218] In some embodiments of the compound of formula A, NR y -CH(R 3a )-C(O)- is -NCH 3 -CH(R 3a )-C(O)-. In some embodiments, -NCH 3 -CH(R 3a )-C(O)- forms an L-amino acid residue. In some embodiments, -NCH 3 -CH(R 3a )-C(O)- forms a D-amino acid residue. In some embodiments, -NCH 3 -CH(R 3a )-C(O)- forms a Lys(iPr) residue. In some embodiments, -NCH 3 -CH(R 3a )-C(O)- is Arg(Me) 2 (asymmetric) residue. In some embodiments, -NCH 3 -CH(R 3a )-C(O)- forms an Arg(Me) residue.

[0219] In some embodiments of Formula A, R y is hydrogen, C 1 ~C 5 Alkyl, or R 3e R 3f where R 3e is a linear C 1 ~C 5 alkylenyl, wherein R3f is -N(R 3g ) 2~3 where each R 3g are independently -H or linear or branched C 1 ~C 3 It is an alkyl.

[0220] In some embodiments of Formula A, R y is hydrogen. In some embodiments of Formula A, R y is C 1 ~C 5 In some embodiments, R y is methyl.

[0221] In some embodiments of Formula A, R y is R 3e R 3f where R 3e is a linear C 1 ~C 5 alkylenyl, wherein R 3f is -N(R 3g ) 2~3 where each R 3g are independently -H or linear or branched C 1 ~C 3 In some embodiments, R y is (C 1~5 Alkylenyl)-NH(C 2~3 In some embodiments, R y is (C 4 alkylenyl)-NH(isopropyl).

[0222] In some embodiments of the compounds of formula B and / or C, -NH-CH(R 3a )-C(O)- forms an L-amino acid residue. In some embodiments, -NH-CH(R 3a )-C(O)- forms a D-amino acid residue. In some embodiments, -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue. In some embodiments, -NH-CH(R 3a)-C(O)- is Arg(Me) 2 In some embodiments, the -NH-CH(R 3a )-C(O)- forms an Arg(Me) residue.

[0223] In some embodiments of the compounds of formula A, B, and / or C, R 4a is R 4b R 4c where R 4b is a linear C 1 ~C 5 is an alkylenyl, alkenylenyl, or alkynylenyl of the formula C 2 ~C 5 0-2 carbons in are independently replaced with one or more N, S, and / or O heteroatoms, 4c is -N(R 4d ) 2~3 or guanidino, wherein each R 4d are independently -H or linear or branched C 1 ~C 3 It is an alkyl.

[0224] In some embodiments of the compounds of formula A, B, and / or C, R 4b is a linear C 1 ~C 5 In some embodiments, R is an alkylenyl, alkenylenyl, or alkynylenyl (i.e., without heteroatoms). 4b is C 2 ~C 5 In some embodiments, R 4b is a linear C 1 ~C 5 It is alkylenyl.

[0225] In some embodiments of the compounds of formula A, B, and / or C, R 4c is guanidino. In some embodiments, R 4c is -N(R 4d ) 2~3In some embodiments, R 4c is -N(R 4d ) 2~3 where each R 4d is a linear or branched C 1 ~C 3 In some embodiments, R 4c is -N(R 4d ) 2~3 where each R 4d is methyl. In some embodiments, R 4c is -N(R 4d ) 2~3 where each R 4d is independently -H or methyl. In some embodiments, R 4c is -NH 2 or -NH 3 It is.

[0226] In some embodiments of the compounds of formula A, B, and / or C, -NH-CH(R 4a )-C(O)- forms a D-amino acid residue. In some embodiments, -NH-CH(R 4a )-C(O)- forms an L-amino acid residue. In some embodiments, -NH-CH(R 4a )-C(O)- forms a D-Arg residue. In some embodiments, -NH-CH(R 4a )-C(O)- forms a D-hArg residue.

[0227] In some embodiments of formula A, B, and / or C, -NH-CH(R 4a The carbonyl of -C(O)- is replaced with an imino to form -NH-CH(R 4a )-C(=NH)-. In some embodiments, -NH-CH(R 4a )-C(=NH)- forms a D-amino acid residue. In some embodiments, -NH-CH(R 4a )-C(=NH)- forms an L-amino acid residue. In some embodiments, -NH-CH(R 4a)-C(O)- forms a D-Arg residue. In some embodiments, -NH-CH(R 4a )-C(=NH)- forms a D-hArg residue.

[0228] In some embodiments of the compounds of formula A, B, and / or C, R 5a is -(CH 2 ) 1~3 -R 5b In the formula: -(CH 2 ) 2~3 - one carbon in may be replaced with a heteroatom of N, S, or O, 5b teeth, Phenyl, -NH 2 , -NO 2 , -OH, -OR 5c , -SH, -SR 5c , -N 3 , -CN, or -O-phenyl, substitution at the 4-position with a halogen or -OH, and / or substitution at the 5-position with a halogen or -OH, wherein the -O-phenyl ring is -NH 2 , -NO 2 , -OH, -OR 5c , -SH, -SR 5c , -N 3 or -CN at the 4-position, wherein the -O-phenyl ring is optionally substituted at the 3-position with a halogen or -OH, wherein the -O-phenyl ring is optionally substituted at the 5-position with a halogen or -OH; Fused bicyclic or fused tricyclic aryl groups, in which one or more carbons may be independently replaced with heteroatoms of N, S, and / or O, and may also be replaced with halogen, -OH, -OR 5c , amino, -NHR 5c , and / or N(R 5c ) 2 a fused bicyclic or fused tricyclic aryl group, optionally independently substituted with one or a combination of In the formula, each R 5c are independently1 ~C 3 is a straight or branched alkyl group.

[0229] In some embodiments of the compounds of formula A, B, and / or C, R 5a is -CH 2 -R 5b In some embodiments, R 5a is -CH 2 -CH 2 -R 5b In some embodiments, R 5a is -CH 2 -CH 2 -CH 2 -R 5b It is.

[0230] In some embodiments of the compounds of formula A, B, and / or C, R 5b is phenyl, -NH 2 , -NO 2 , -OH, -OR 5c , -SH, -SR 5c , -N 3 , -CN, or -O-phenyl, substitution at the 4-position with a halogen or -OH, and / or substitution at the 5-position with a halogen or -OH, wherein the -O-phenyl ring is -NH 2 , -NO 2 , -OH, -OR 5c , -SH, -SR 5c , -N 3 or -CN, where the -O-phenyl ring is optionally substituted at the 3-position with a halogen or -OH, and where the -O-phenyl ring is optionally substituted at the 5-position with a halogen or -OH. 5b is phenyl, -NH 2 , -NO 2 , -OH, -SH, -N 3, -CN, or -O-phenyl, at the 4 position with a halogen or -OH, and / or at the 5 position with a halogen or -OH. In some embodiments, the phenyl is unsubstituted at the 4 position. In some embodiments, the phenyl is unsubstituted at the -NH 2 In some embodiments, the phenyl is substituted at the 4 position with -NO 2 In some embodiments, the phenyl is substituted at the 4 position with -OH. In some embodiments, the phenyl is substituted at the 4 position with -OR 5c In some embodiments, the phenyl is substituted at the 4 position with -SH. In some embodiments, the phenyl is substituted at the 4 position with -SR 5c In some embodiments, the phenyl is substituted at the 4 position with -N 3 In some embodiments, the phenyl is substituted at the 4 position with -CN. In some embodiments, the phenyl is substituted at the 4 position with -O-phenyl. In some embodiments, each R 5c are independently 1 ~C 3 In some embodiments, each R 5c is methyl. In some embodiments, the phenyl is unsubstituted at the 3-position. In some embodiments, the phenyl is substituted at the 3-position with a halogen. In some embodiments, the phenyl is substituted at the 3-position with -OH. In some embodiments, the phenyl is substituted at the 5-position with a halogen. In some embodiments, the phenyl is substituted at the 5-position with -OH. In some embodiments, the halogen is iodine. In some embodiments, the -O-phenyl ring is unsubstituted. In some embodiments, the -O-phenyl ring is substituted at the 4-position. In some embodiments, the -O-phenyl ring is substituted at the 3-position. In some embodiments, the -O-phenyl ring is substituted at the 5-position.

[0231] In some embodiments of the compounds of formula A, B, and / or C, R 5bis a fused bicyclic or fused tricyclic aryl group, wherein one or more carbons may be independently replaced with N, S, and / or O heteroatoms and independently replaced with halogen, -OH, -OR 5c , amino, -NHR 5c , and / or N(R 5c ) 2 In some embodiments, each R 5c are independently 1 ~C 3 In some embodiments, each R 5c is methyl. In some embodiments, R 5b is a fused bicyclic or fused tricyclic aryl group, where 0-3 carbons are independently replaced with N, S, and / or O heteroatoms, and may also be independently replaced with one or a combination of halogen, -OH, and / or amino. 5b is a fused bicyclic or fused tricyclic aryl group, optionally independently substituted with one or a combination of halogen, -OH, and / or amino. In some embodiments, R 5b is a fused bicyclic or tricyclic aryl group, optionally substituted with 0-3 groups selected from halogen, -OH, and / or amino. In some embodiments, R 5b is a fused bicyclic or fused tricyclic aryl group. In some embodiments, R 5b excludes 9-linked anthracenyl. In some embodiments, each ring of a fused bicyclic or fused tricyclic aryl group independently has 4, 5, or 6 ring carbons, wherein 0-3 carbons are independently replaced with N, S, and / or O heteroatoms, and such embodiments may be substituted or unsubstituted as defined above.

[0232] In some embodiments of the compounds of formula A, B, and / or C, -NH-CH(R 5a)-C(O)- forms an L-amino acid residue. In some embodiments, -NH-CH(R 5a )-C(O)- forms a D-amino acid residue. In some embodiments, -NH-CH(R 5a )-C(O)- forms a 2-(Ant)Ala residue. In some embodiments, -NH-CH(R 5a )-C(O)- forms a 2-Nal residue. In some embodiments, -NH-CH(R 5a )-C(O)- forms a Trp residue. In some embodiments, -NH-CH(R 5a )-C(O)- is (4-NH 2 )Phe residue. In some embodiments, -NH-CH(R 5a )-C(O)- forms a hTyr residue. In some embodiments, -NH-CH(R 5a )-C(O)- forms a Tyr residue.

[0233] In some embodiments of formula A, B, and / or C, -NH-CH(R 5a The carbonyl of -C(O)- is replaced with an imino to form -NH-CH(R 5a In some embodiments of Formula A, B, and / or C, -NH-CH(R 5a The amide of the backbone of -C(O)- is replaced with an amidine to give -NH-CH(R 5a )-C(=NH)-. In some embodiments, -NH-CH(R 5a )-C(O)- forms an L-amino acid residue, and the backbone amide is replaced with an amidine. In some embodiments, -NH-CH(R 5a )-C(O)- forms a D-amino acid residue, and the backbone amide is replaced with an amidine. In some embodiments, -NH-CH(R 5a )-C(O)- forms a 2-(Ant)Ala residue, and the backbone amide is replaced with an amidine. In some embodiments, -NH-CH(R 5a)-C(O)- forms a 2-Nal residue, and the backbone amide is replaced with an amidine. In some embodiments, -NH-CH(R 5a In some embodiments, -NH-CH(R 5a )-C(O)- is (4-NH 2 )Phe residue, and the backbone amide is replaced with an amidine. 5a In some embodiments, -NH-CH(R 5a )-C(O)- forms a Tyr residue and the backbone amide is replaced with an amidine.

[0234] In some embodiments of the compounds of formula A, B, and / or C, any of the following: (a)R 6a is H, methyl, ethyl, -C≡CH, -CH=CH 2 , -C≡C-(CH 2 ) 1-3 -OH, -C≡C-(CH 2 ) 1-3 -SH, -C≡C-(CH 2 ) 1-3 -NH 2 , -C≡C-(CH 2 ) 1-3 -COOH, -C≡C-(CH 2 ) 1-3 -CONH 2 , -C≡C-(CH 2 ) 1-3 R 6b R 6c , -CH=CH-(CH 2 ) 1-3 -OH, -CH=CH-(CH 2 ) 1-3 -SH, -CH=CH-(CH 2 ) 1-3 -NH 2 , -CH=CH-(CH 2 ) 1-3 -COOH, -CH=CH-(CH 2 ) 1-3-CONH 2 , -CH=CH-(CH 2 ) 1-3 R 6b R 6c , -CH 2 -R 6b -OH, -CH 2 -R 6b -COOH, -CH 2 -(R 6b ) 1-3 -NH 2 , -CH 2 -R 6b -CONH 2 , or -CH 2 -R 6b R 6c where each R 6b are independently absent or -CH 2 -, -NH-, -S-, or -O-, wherein R 6c teeth, a 5- or 6-membered aromatic ring, wherein one or more carbons are optionally independently replaced with N, S, and / or O heteroatoms and one or more groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen; or (b) -NH-CH(R 6a )-C(O)-NH-, [ka] is replaced by.

[0235] In some embodiments of the compounds of formula A, B, and / or C, R 6a is H. In some embodiments, R 6a is methyl. In some embodiments, R 6a is ethyl. In some embodiments, R 6a is -C≡CH. In some embodiments, R 6a is -CH=CH 2 In some embodiments, R 6a is -CH 2 -R 6b-In some embodiments, R 6a is -CH 2 -R 6b- In some embodiments, R 6a is -CH 2 -(R 6b ) 1~3 -NH 2 In some embodiments, R 6a is -CH 2 -R 6b- CONH 2 In some embodiments, R 6a is -C≡C-(CH 2 ) 1~3 In some embodiments, R 6a is -C≡C-(CH 2 ) 1~3 In some embodiments, R 6a is -C≡C-(CH 2 ) 1~3 -NH 2 In some embodiments, R 6a is -C≡C-(CH 2 ) 1~3 In some embodiments, R 6a is -C≡C-(CH 2 ) 1~3 -CONH 2 In some embodiments, R 6a is -C≡C-(CH 2 ) 1~3 R 6b R 6c In some embodiments, R 6a is -CH=CH-(CH 2 ) 1~3 In some embodiments, R 6a is -CH=CH-(CH 2 ) 1~3 In some embodiments, R 6a is -CH=CH-(CH 2 ) 1~3 -NH 2 In some embodiments, R 6a is -CH=CH-(CH 2) 1~3 In some embodiments, R 6a is -CH=CH-(CH 2 ) 1~3 -CONH 2 In some embodiments, R 6a is -CH=CH-(CH 2 ) 1~3 R 6b R 6c Each R 6b are independently absent or -CH 2 In some embodiments, R 6b is absent. In some embodiments, R 6b is -CH 2 -It is.

[0236] In some embodiments of the compounds of formula A, B, and / or C, R 6a is H, methyl, ethyl, -C≡CH, -CH=CH 2 , -CH 2 -R 6b -OH, -CH 2 -R 6b -COOH, -CH 2 -(R 6b ) 1-3 -NH 2 , -CH 2 -R 6b -CONH 2 , or -CH 2 -R 6b R 6c In some embodiments, R 6a is -CH 2 -R 6b R 6c Each R 6b are independently absent or -CH 2 In some embodiments, R 6b is absent. In some embodiments, R 6b is -CH 2 In some embodiments, R 6cis a 5- or 6-membered aromatic ring, in which 0-3 carbons are independently replaced with N, S, and / or O heteroatoms, and optionally substituted with 0-3 groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen, and in some embodiments the ring is unsubstituted. 6c is a 5- or 6-membered aryl, optionally substituted with 0-3 groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen; in some embodiments, the aryl is unsubstituted.

[0237] In some embodiments of the compounds of formula A, B, and / or C, -NH-CH(R 6a )-C(O)-NH- is [ka] In some embodiments, the group is substituted with -NH-CH(R 6a )-C(O)-NH- is [ka] is replaced by.

[0238] In some embodiments of the compounds of formula A, B, and / or C, -NH-CH(R 6a )-C(O)- forms a D-amino acid residue. In some embodiments, -NH-CH(R 6a )-C(O)- forms an L-amino acid residue. In some embodiments, -NH-CH(R 6a )-C(O)- forms a His residue. In some embodiments, -NH-CH(R 6a )-C(O)- forms a D-His residue. In some embodiments, -NH-CH(R 6a )-C(O)- forms a D-Glu residue. In some embodiments, -NH-CH(R 6a )-C(O)- forms a D-Gln residue. In some embodiments, -NH-CH(R 6a)-C(O)- forms a D-Ala residue. In some embodiments, -NH-CH(R 6a )-C(O)- forms a D-Phe residue. In some embodiments, -NH-CH(R 6a )-C(O)- forms a D-Ser residue. In some embodiments, -NH-CH(R 6a )-C(O)- forms a D-Dab residue. In some embodiments, -NH-CH(R 6a )-C(O)- forms a D-Dap residue.

[0239] In some embodiments of the compounds of formula A, B, and / or C, R 8a is R 8b R 8c where R 8b is a linear C 1 ~C 5 alkylenyl, alkenylenyl, or alkynylenyl of the formula: 2 ~C 5 0-2 carbons in are independently replaced with one or more N, S, and / or O heteroatoms, 8c is -N(R 8d ) 2~3 or guanidino, wherein each R 8d are independently -H or linear or branched C 1 ~C 3 It is an alkyl.

[0240] In some embodiments of the compounds of formula A, B, and / or C, R 8b is a linear C 1 ~C 5 In some embodiments, R is an alkylenyl, alkenylenyl, or alkynylenyl (i.e., without heteroatoms). 8b is C 2 ~C 5 In some embodiments, R 8b is a linear C 1 ~C 5 It is alkylenyl.

[0241] In some embodiments of the compounds of formula A, B, and / or C, R 8c is guanidino. In some embodiments, R 8c is -N(R 8d ) 2~3 In some embodiments, R 8c is -N(R 8d ) 2~3 where each R 8d is a linear or branched C 1 ~C 3 In some embodiments, R 8c is -N(R 8d ) 2~3 where each R 8d is methyl. In some embodiments, R 8c is -N(R 8d ) 2~3 where each R 8d is independently -H or methyl. In some embodiments, R 8c is -NH 2 or -NH 3 It is.

[0242] In some embodiments of the compounds of formula A, B, and / or C, -NH-CH(R 8a )-C(O)- forms an L-amino acid residue. In some embodiments, -NH-CH(R 8a )-C(O)- forms a D-amino acid residue. In some embodiments, -NH-CH(R 8a As used herein, the term "-NH-CH(R)" as used with respect to Formula A, AI, A-II, A-III, A-IV, B, and / or C, 8a In the expression "-C(O)-", the -C(O)- portion is R 9a For example, in some embodiments, -NH-CH(R 8a )- is R 9a Together with the additional -C(O)-, it forms an L-amino acid residue, a D-amino acid residue, or a Lys(iPr) residue.

[0243] In some embodiments of the compounds of formula A, B, and / or C, -NH-CH(R 8a )- is R 9a Together with the additional -C(O)-, they form an amino acid residue. 9a -C(O)- combined with -NH-CH(R 8a In some embodiments, the amino acid residue formed by -NH-CH(R 8a )- is R 9a Together with the additional -C(O)- to form a Lys(iPr) residue. 8a )- is R 9a Together with the additional -C(O)-, they form an amidated Lys(iPr) residue. In some embodiments, -NH-CH(R 8a )- is R 9a Together with the -C(O)-, Lys(iPr)-NH 2 Form.

[0244] In some embodiments of the compounds of formula A, B, and / or C, R 9a is -C(O)NH 2 , -C(O)-OH, -CH 2 -C(O)NH 2 , -CH 2 -C(O)-OH, -CH 2 -NH 2 , -CH 2 -OH, -CH 2 -CH 2 -NH 2 , -R 9b -R 9c , or -R 9b -[Linker]-R X n1 where: R 9b is -CH 2 -NH-C(O)-, -CH 2 -C(O)-, -CH 2 -O-, -C(O)NH-, -C(O)-N(CH 3 )-, -CH2 -NHC(S)-, -C(S)NH-, -CH 2 -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -CH 2 -N(CH 3 )C(O)-, -C(S)N(CH 3 )-, -CH 2 -NHC(S)NH-, -CH 2 -NHC(O)NH-, -CH 2 -S-, -CH 2 -S(O)-, -CH 2 -S(O) 2 -, -CH 2 -S(O) 2 -NH-, -CH 2 -S(O)-NH-, -CH 2 -Se-, -CH 2 -Se(O)-, -CH 2 -Se(O) 2 -, -CH 2 -NHNHC(O)-, -C(O)NHNH-, -CH 2 -OP(O)(O - )O-, -CH 2 -Phosphamide-, -CH 2 -Thiophosphodiester-, -CH 2 -S-tetrafluorophenyl-S-, [ka] or polyethylene glycol, R 9c is hydrogen or a linear, branched and / or cyclic C 1 ~C 20 is an alkyl, alkenyl, or alkynyl of the formula: 2 ~C 20 wherein 0-6 carbons are independently substituted with N, S, and / or O heteroatoms, and 0-3 groups independently selected from one or a combination of oxo, hydroxyl, sulfhydryl, halogen, guanidino, carboxylic acid, sulfonic acid, sulfinic acid, and / or phosphate.

[0245] In some embodiments of the compounds of formula A, B, and / or C, R 9a is -C(O)NH 2 , -C(O)-OH, -CH 2 -C(O)NH 2 , -CH 2 In some embodiments, R 9a -R 9b -R 9c where R 9b is -C(O)NH-.

[0246] In some embodiments of the compounds of formula A, B and / or C, R 9c teeth, [ka] where R 9d is a linear or branched C 1 ~C 5 is an alkylenyl, alkenylenyl, or alkynylenyl of the formula C 2 ~C 5 0-2 carbons in are independently replaced with heteroatoms of N, S, and / or O, 9e are carboxylic acid, sulfonic acid, sulfinic acid, phosphoric acid, amino, guanidino, -SH, -OH, -NH-C(O)-CH 3 , -SC(O)-CH 3 , -OC(O)-CH 3 , -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-CH 3 , -N(CH 3 ) 2 , -S-CH 3 , -O-CH 3 and phenyl, wherein R 9f is amino or -OH. In some embodiments, R 9d is a linear or branched C 1 ~C 5 In some embodiments, R is an alkylenyl, alkenylenyl, or alkynylenyl (i.e., without heteroatoms).9d is a linear or branched C 1 ~C 5 It is alkylenyl.

[0247] In some embodiments of the compounds of formula A, B, and / or C, R 9a -R 9b -[Linker]-R X n1 In some of these embodiments, R 9b is -C(O)NH-.

[0248] In some embodiments of the compounds of formula A, B, and / or C, R 9a is -C(O)NH 2 , -C(O)-OH, -R 9b -R 9c , or -R 9b -[Linker]-R X n1 and R 9b -C(O)NH-, -C(O)-N(CH 3 )-, -C(O)N(CH 3 )-, or -C(O)NHNH-.

[0249] In some embodiments of the compound of formula A, R A7a is a linear C 1 ~C 5 alkylenyl, wherein C 2 ~C 5 0-2 carbons in R are independently replaced with one or more N, S, and / or O heteroatoms. A7a is a linear C 1 ~C 5 In some embodiments, R is an alkylenyl (i.e., no heteroatoms). A7a is a linear C 1 ~C 5 Alkylenyl, where C 2 ~C 5 In some embodiments, one carbon in R is a heteroatom selected from N, S, or O. A7a is -CH 2In some embodiments, R A7a is -CH 2 -CH 2 -It is.

[0250] In some embodiments, —NH—CH(R A7a )-C(O)- forms a D-amino acid residue. In some embodiments, -NH-CH(R A7a )-C(O)- forms an L-amino acid residue.

[0251] In some embodiments, —NH—CH(R A7a )-C(O)- forms a D-amino acid residue, and R A7a is C 1 ~C 3 In some embodiments, -NH-CH(R A7a )-C(O)- forms an L-amino acid residue, and R A7a is C 1 -C 3 It is an alkynyl.

[0252] In some embodiments of the compound of formula A, R A10 does not exist or -[linker]-R X n1 It is.

[0253] In some embodiments of the compound of formula A, R A10 If does not exist, R A1a teeth, Linear C 1 ~C 5 is an alkyl, alkenyl, or alkynyl of the formula: 2 ~C 5 0-2 carbons in are independently replaced by one or more N, S, and / or O heteroatoms, where C is -SH, -OH, amino, carboxy, guanidino, -NH-C(O)-CH 3 , -SC(O)-CH 3 , -OC(O)-CH 3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH 3 ) 1~2 , -NH 2 -CH 3 , -N(CH 3 ) 2~3 , -S-CH 3 , or -O-CH 3 and optionally substituted with one substituent selected from Branch C 1 ~C 10 is an alkyl, alkenyl, or alkynyl of the formula: 2 ~C 10 wherein 0-3 carbons are independently replaced by one or more N, S, and / or O heteroatoms; or R A1b R A1c where R A1b is a linear C 1 ~C 3 alkylenyl, wherein C 2 Alkylenyl or C 3 Alkylenyl may be substituted with N, S, or O heteroatoms, where R A1c teeth, a 5- or 6-membered aromatic ring, wherein one or more carbons are optionally independently replaced with N, S, and / or O heteroatoms and one or more groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen; or Fused bicyclic or fused tricyclic aryl groups, in which one or more carbons may be independently replaced with heteroatoms of N, S, and / or O, and may also be replaced with halogen, -OH, -OR A1d , amino, -NHR A1d , and / or N(R A1d ) 2 wherein each R A1d is independently C 1 ~C 3a linear or branched alkyl group of the formula:

[0254] In some embodiments of the compound of formula A, R A10 -[Linker]-R X n1 If so, then R A1a is R A1e R A1f where R A1e is a linear C 1 ~C 5 is an alkylenyl, alkenylenyl, or alkynylenyl of the formula C 2 ~C 5 0-2 carbons in are independently replaced with heteroatoms of N, S, and / or O, and R A1f -NH-C(O)-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH 3 )-, -NHC(S)-, -C(S)NH-, -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -N(CH 3 )C(O)-, -C(S)N(CH 3 )-, -NHC(S)NH-, -NHC(O)NH-, -S-, -S(O)-, -S(O)-O-, -S(O) 2 -, -S(O) 2 -O-, -S(O) 2 -NH-, -S(O)-NH-, -Se-, -Se(O)-, -Se(O) 2 -, -NHNHC(O)-, -C(O)NHNH-, -OP(O)(O - )O-, -phosphamide-, -thiophosphodiester-, -S-tetrafluorophenyl-S-, polyethylene glycol [ka] It is.

[0255] In some embodiments of the compound of formula A, -NH-CH(R A1a )-C(O)- forms an L-amino acid residue. In some embodiments, -NH-CH(RA1a )-C(O)- forms a D-amino acid residue.

[0256] In some embodiments of the compound of formula A, R A10 does not exist.

[0257] In some embodiments of the compound of formula A, R A10 If does not exist, R A1a is a linear C 1 ~C 5 is an alkyl, alkenyl, or alkynyl group, which is -SH, -OH, amino, carboxy, guanidino, -NH-C(O)-CH 3 , -SC(O)-CH 3 , -OC(O)-CH 3 , -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH 3 ) 1~2 , -NH 2 -CH 3 , -N(CH 3 ) 2~3 , -S-CH 3 , or -O-CH 3 In some embodiments, R A10 If does not exist, R A1a is a linear C 1 ~C 5 Alkyl, which is -SH, -OH, amino, carboxy, guanidino, -NH-C(O)-CH 3 , -SC(O)-CH 3 , -OC(O)-CH 3 , -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH 3 ) 1~2 , -NH 2 -CH 3 , -N(CH 3 ) 2~3 , -S-CH 3 , or -O-CH 3 may be substituted with one substituent selected from the group consisting of

[0258] In some embodiments of the compound of formula A, R A10 If does not exist, R A1a is the C of the branch 1 ~C 10 In some embodiments, R A10 If does not exist, R A1a is branch C 1 ~C 10 It is an alkyl.

[0259] In some embodiments of the compound of formula A, R A10 If does not exist, R A1a is R A1b R A1c In some embodiments, R A1b is a linear C 1 ~C 3 In some embodiments, R A1c is a 5- or 6-membered aromatic ring, where 0-4 carbons are independently replaced with N, S, and / or O heteroatoms, and 0-4 groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen. A1c is a fused bicyclic or fused tricyclic aryl group, where 0-6 carbons are independently replaced with heteroatoms of N, S, and / or O, and are also independently selected from halogen, -OH, -OR A1d , amino, -NHR A1d , and / or N(R A1d ) 2 In some embodiments, R A1d is methyl. In some embodiments, each ring of a fused bicyclic or fused tricyclic aryl group independently has 4, 5, or 6 ring carbons, where 0-3 carbons are independently replaced with N, S, and / or O heteroatoms, and such embodiments may be substituted or unsubstituted as defined above.

[0260] In some embodiments of the compound of formula A, -NH-CH(R A1a )-C(O)- forms a Phe residue, a 1-Nal residue, a 2-Nal residue, a Tyr residue, a Trp residue, a Lys residue, a hLys residue, a Lys(Ac) residue, a Dap residue, a Dab residue, or an Orn residue. In some embodiments of the compound of formula A, -NH-CH(R A1a )-C(O)- forms an L-Phe residue, an L-1-Nal residue, an L-2-Nal residue, an L-Tyr residue, an L-Trp residue, an L-Lys residue, an L-hLys residue, an L-Lys(Ac) residue, an L-Dap residue, an L-Dab residue, or an L-Orn residue. In some embodiments of the compound of formula A, -NH-CH(R A1a )-C(O)- forms a Phe residue. In some embodiments, -NH-CH(R A1a )-C(O)- forms a 1-Nal residue. In some embodiments, -NH-CH(R A1a )-C(O)- forms a 2-Nal residue. In some embodiments, -NH-CH(R A1a )-C(O)- forms a Tyr residue. In some embodiments, -NH-CH(R A1a )-C(O)- forms a Trp residue. In some embodiments, -NH-CH(R A1a )-C(O)- forms a Lys residue. In some embodiments, -NH-CH(R A1a )-C(O)- forms a hLys residue. In some embodiments, -NH-CH(R A1a )-C(O)- forms a Lys(Ac) residue. In some embodiments, -NH-CH(R A1a )-C(O)- forms a Dap residue. In some embodiments, -NH-CH(R A1a )-C(O)- forms a Dab residue. In some embodiments, -NH-CH(R A1a )-C(O)- forms an Orn residue.

[0261] In some embodiments of the compound of formula A, R A10 -[Linker]-R X n1 and RA1a is R A1e R A1f In some embodiments, R A1e is a linear C 1 ~C 5 In some embodiments, R A1e is a linear C 1 ~C 5 In some embodiments, R A1f -NH-C(O)-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH 3 )-, -NHC(S)-, -C(S)NH-, -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -N(CH 3 )C(O)-, -C(S)N(CH 3 )-, -NHC(S)NH-, -NHC(O)NH-, -S-, -S(O)-, -S(O)-O-, -S(O) 2 -, -S(O) 2 -NH-, -S(O)-NH-, -NHNHC(O)-, -C(O)NHNH-, polyethylene glycol, [ka] It is.

[0262] All embodiments described herein for Formula A may be embodiments of Formula AI, Formula A-II, Formula III, and / or Formula A-IV to the extent that the definition is encompassed by Formula AI, Formula A-II, Formula III, and / or Formula IV.

[0263] In some embodiments of the compound of formula B, R B1a is a linear, branched and / or cyclic C 1 ~C 10 is an alkylenyl, alkenylenyl, or alkynylenyl of the formula: 2 ~C 10 One or more carbons therein may be independently replaced with N, S, and / or O heteroatoms.

[0264] In some embodiments of the compound of formula B, R B1-7 teeth, [ka] wherein indole and isoindole are -F, -Br, -Cl, -I, -OH, -OR B1-7b , -CO-, -COOH, -CONH 2 , -CN, -O-aryl, -NH 2 , -NHR B1-7b , N 3 , -NO 2 , -NH, -CHO, and / or -R B1-7b wherein each R B1-7b is a linear or branched C 1 ~C 3 In some embodiments, the indoles and isoindoles are unsubstituted. In some embodiments, the indoles and isoindoles are -F, -Br, -Cl, -I, -OH, -OR C1b , -CO-, -COOH, -CONH 2 , -CN, -O-aryl, -NH 2 , -NHR C1b , N 3 , -NO 2 , -NH, -CHO, and / or -R C1b In some embodiments, each R C1b is methyl. In some embodiments, the aryl is a 5- or 6-membered aromatic ring.

[0265] In some embodiments of the compound of formula B, R B7a is a linear C 1 ~C 5 alkylenyl, wherein C 2 ~C 5 0-2 carbons in R may be independently replaced with one or more N, S, and / or O heteroatoms. B7a is a linear C 1 ~C5 In some embodiments, R is an alkylenyl (i.e., no heteroatoms). B7a is a linear C 1 ~C 5 Alkylenyl, where C 2 ~C 5 In some embodiments, one carbon in R is a heteroatom selected from N, S, or O. B7a is -CH 2 In some embodiments, R B7a is -CH 2 -CH 2 In some embodiments, -NH-CH(R C7a )-C(O)- forms a D-amino acid residue. In some embodiments, -NH-CH(R C7a )-C(O)- forms an L-amino acid residue.

[0266] In some embodiments of the compound of formula B, R B1-7 teeth, [ka] wherein indole and isoindole are -F, -Br, -Cl, -I, -OH, -OR B1-7b , -CO-, -COOH, -CONH 2 , -CN, -O-aryl, -NH 2 , -NHR B1-7b , N 3 , -NO 2 , -NH, -CHO, and / or -R B1-7b wherein each R B1-7b is a linear or branched C 1 ~C 3 In some embodiments, the indoles and isoindoles are -F, -Br, -Cl, -I, -OH, -OR C1b , -CO-, -COOH, -CONH 2 , -CN, -O-aryl, -NH 2 , -NHR C1b , N 3 , -NO2 , -NH, -CHO, and / or -R C1b In some embodiments, each R C1b is methyl. In some embodiments, aryl is a 5 or 6 membered aromatic ring. In some embodiments, R B1-7 teeth, [ka] It is.

[0267] In some embodiments of the compound of formula B, R B1a is -(CH 2 ) 1~2 - and R B1-7 teeth, [ka] and R B7a is -(CH 2 ) 1~2 -It is.

[0268] In some embodiments of the compound of formula B, R B1a -R B1-7 -R B7a teeth, [ka] It is.

[0269] In some embodiments of the compound of formula B, -NH-CH(R B7a )-C(O)- forms a D-amino acid residue. In some embodiments, -NH-CH(R B7a )-C(O)- forms an L-amino acid residue.

[0270] In some embodiments of the compound of formula B, R B10a is an amine, -NH-(CH 3 ) 1~2 , -N(CH 3 ) 2~3 , -NH-C(O)-CH 3, -NH-C(O)-(phenyl), or -R B10b -[Linker]-R X n1 where R B10b teeth, -NH-C(O)-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH 3 )-, -NHC(S)-, -C(S)NH-, -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -N(CH 3 )C(O)-, -C(S)N(CH 3 )-, -NHC(S)NH-, -NHC(O)NH-, -S-, -S(O)-, -S(O)-O-, -S(O) 2 -, -S(O) 2 -O-, -S(O) 2 -NH-, -S(O)-NH-, -Se-, -Se(O)-, -Se(O) 2 -, -NHNHC(O)-, -C(O)NHNH-, -OP(O)(O - )O-, -phosphamide-, -thiophosphodiester-, -S-tetrafluorophenyl-S-, [ka] Or polyethylene glycol.

[0271] In some embodiments of the compound of formula B, R B10a is an amine, -NH-(CH 3 ) 1~2 , -N(CH 3 ) 2~3 , -NH-C(O)-CH 3 or -NH-C(O)-(phenyl).

[0272] In some embodiments of the compound of formula B, R B10a -R B10b -[Linker]-R X n1 In some of these embodiments, R B10b -NH-C(O)-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH3 )-, -NHC(S)-, -C(S)NH-, -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -N(CH 3 )C(O)-, -C(S)N(CH 3 )-, -NHC(S)NH-, -NHC(O)NH-, -NHNHC(O)-, -C(O)NHNH-, [ka] or polyethylene glycol. In some embodiments, R B10a is -NHC(O)-[linker]-R X n1 or -N(CH 3 )C(O)-[Linker]-R X n1 It is.

[0273] In some embodiments, the linker is X 1 L 1 , X 1 L 1 X 1 L 1 , or X 1 L 1 X 1 L 1 X 1 L 1 and

[0274] X 1 Each independently represents -CH 2 -, [ka] and

[0275] L 1 each independently represents -NH-, -C(O)-, -NHC(O)-, -C(O)NH-, -N(CH 3 )C(O)-, or -C(O)N(CH 3 )-and

[0276] R 11are each independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid; and

[0277] R Z are each independently an albumin binder.

[0278] In some embodiments, the linker is X 1a L 1a X 1b L 1b and

[0279] X 1a teeth, [ka] and

[0280] L 1a is -NH- or -NHC(O)-,

[0281] X 1b teeth, [ka] and

[0282] L 1b is -NH-, or -NHC(O)-.

[0283] In some embodiments, the linker is X 1a L 1a X 1b L 1b and

[0284] X 1a teeth, [ka] and

[0285] L 1a is -NH- or -NHC(O)-,

[0286] X1b teeth, [ka] and

[0287] L 1b is -NH-, or -NHC(O)-.

[0288] In some embodiments, R B10a is -NHC(O)-[linker]-R X n1 and the linker is X 1a L 1a X 1b L 1b and

[0289] X 1a is C 1 ~C 2 alkenyl, L 1a is -NH-C(O), and X 1b teeth, [ka] And L 1b is -NH- and R 11 is independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid. 11 is sulfonic acid (-SO 3 H).

[0290] In some embodiments of the compound of formula C, R C1a teeth, [ka] wherein the indole, isoindole, and triazole rings are each independently selected from the group consisting of -F, -Br, -Cl, -I, -OH, -OR C1b , -CO-, -COOH, -CONH 2 , -CN, -O-aryl, -NH 2 , -NHR C1b , N 3 , -NO 2, -NH, -CHO, and / or -R C1b wherein each R C1b is a linear or branched C 1 ~C 3 with the proviso that the compound of formula C is cyclo(isoindole)[Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-D-Cys]-Lys(iPr)-NH 2 , cyclo(isoindole) [Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-Cys]-Lys(iPr)-NH 2 , cyclo(isoindole N a -S)[Lys(Cys(Acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH 2 , Cyclo(Me-isoindole N a -S)[Lys(Cys(Acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH 2 , Cyclo(NO 2 -Isoindole N a -S)[Lys(Cys(Acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH 2 , and cyclo(NO 2 -Isoindole N a -S)[Lys(Cys(Acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-hCys]-Lys(iPr)-NH 2 In some embodiments, the indoles and isoindoles are not substituted. In some embodiments, the indoles and isoindoles are not substituted. In some embodiments, the indoles and isoindoles are not substituted. C1b , -CO-, -COOH, -CONH 2 , -CN, -O-aryl, -NH 2 , -NHR C1b , N 3 , -NO2 , -NH, -CHO, and / or -R C1b In some embodiments, each R C1b is methyl. In some embodiments, the aryl is a 5- or 6-membered aromatic ring.

[0291] In some embodiments of the compound of formula C, R C1a teeth, [ka] wherein indole and isoindole are -F, -Br, -Cl, -I, -OH, -OR C1b , -CO-, -COOH, -CONH 2 , -CN, -O-aryl, -NH 2 , -NHR C1b , N 3 , -NO 2 , -NH, -CHO, and / or -R C1b wherein each R C1b is a linear or branched C 1 ~C 3 with the proviso that the compound of formula C is cyclo(isoindole)[Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-D-Cys]-Lys(iPr)-NH 2 , cyclo(isoindole) [Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-Cys]-Lys(iPr)-NH 2 , cyclo(isoindole N a -S)[Lys(Cys(Acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH 2 , Cyclo(Me-isoindole N a -S)[Lys(Cys(Acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH 2 , Cyclo(NO 2 -Isoindole Na -S)[Lys(Cys(Acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH 2 , and cyclo(NO 2 -Isoindole N a -S)[Lys(Cys(Acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-hCys]-Lys(iPr)-NH 2 In some embodiments, the indoles and isoindoles are not substituted. In some embodiments, the indoles and isoindoles are not substituted. In some embodiments, the indoles and isoindoles are not substituted. C1b , -CO-, -COOH, -CONH 2 , -CN, -O-aryl, -NH 2 , -NHR C1b , N 3 , -NO 2 , -NH, -CHO, and / or -R C1b In some embodiments, each R C1b is methyl. In some embodiments, the aryl is a 5- or 6-membered aromatic ring.

[0292] In some embodiments of the compound of formula C, R C1a teeth, [ka] It is.

[0293] In some embodiments of the compound of formula C, R C1a teeth, [ka] with the proviso that the compound of formula C is cyclo(isoindole) [Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-D-Cys]-Lys(iPr)-NH 2, cyclo(isoindole) [Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-Cys]-Lys(iPr)-NH 2 , cyclo(isoindole N a -S)[Lys(Cys(Acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH 2 , Cyclo(Me-isoindole N a -S)[Lys(Cys(Acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH 2 , Cyclo(NO 2 -Isoindole N a -S)[Lys(Cys(Acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH 2 , and cyclo(NO 2 -Isoindole N a -S)[Lys(Cys(Acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-hCys]-Lys(iPr)-NH 2 No.

[0294] In some embodiments of the compound of formula C, R C7a is a linear C 1 ~C 5 alkylenyl, wherein C 2 ~C 5 0-2 carbons in R may be independently replaced with one or more N, S, and / or O heteroatoms. C7a is a linear C 1 ~C 5 In some embodiments, R is an alkylenyl (i.e., no heteroatoms). C7a is a linear C 1 ~C 2 In some embodiments, R C7a is a linear C 1 ~C 5 Alkylenyl, where C2 ~C 5 In some embodiments, one carbon in R is a heteroatom selected from N, S, or O. C7a is -(CH 2 ) 1~2 In some embodiments, -NH-CH(R C7a )-C(O)- forms a D-amino acid residue. In some embodiments, -NH-CH(R C7a )-C(O)- forms an L-amino acid residue.

[0295] In some embodiments of the compound of formula C, R C1a teeth, [ka] and R C7a is a linear C 1 ~C 2 It is alkylenyl.

[0296] In some embodiments of the compound of formula C, R C1a teeth, [ka] and R C7a is a linear C 1 ~C 2 alkylenyl, with the proviso that the compound of formula C is cyclo(isoindole) [Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-D-Cys]-Lys(iPr)-NH 2 , cyclo(isoindole) [Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-Cys]-Lys(iPr)-NH 2 , cyclo(isoindole N a -S)[Lys(Cys(Acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH 2 , Cyclo(Me-isoindole N a-S)[Lys(Cys(Acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH 2 , Cyclo(NO 2 -Isoindole N a -S)[Lys(Cys(Acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH 2 , and cyclo(NO 2 -Isoindole N a -S)[Lys(Cys(Acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-hCys]-Lys(iPr)-NH 2 No.

[0297] In some embodiments of the compound of formula C, R C10a is R C10b -R C10c -[Linker]-R X n1 or R C10d where: R C10b is a linear C 1 ~C 5 is an alkylenyl, alkenylenyl, or alkynylenyl of the formula C 2 ~C 5 0-2 carbons in are independently replaced by N, S, and / or O heteroatoms; R C10c -NH-C(O)-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH 3 )-, -NHC(S)-, -C(S)NH-, -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -N(CH 3 )C(O)-, -C(S)N(CH 3 )-, -NHC(S)NH-, -NHC(O)NH-, -S-, -S(O)-, -S(O)-O-, -S(O) 2 -, -S(O) 2 -O-, -S(O) 2-NH-, -S(O)-NH-, -Se-, -Se(O)-, -Se(O) 2 -, -NHNHC(O)-, -C(O)NHNH-, -OP(O)(O - )O-, -phosphamide-, -thiophosphodiester-, -S-tetrafluorophenyl-S-, [ka] or polyethylene glycol, R C10d teeth, Linear C 1 ~C 5 is an alkyl, alkenyl, or alkynyl of the formula: 2 ~C 5 0-2 carbons in are independently replaced with heteroatoms of N, S, and / or O, where C is -SH, -OH, amino, carboxy, guanidino, -NH-C(O)-CH 3 , -SC(O)-CH 3 , -OC(O)-CH 3 , -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH 3 ) 1~2 , -NH 2 -CH 3 , -N(CH 3 ) 2~3 , -S-CH 3 , or -O-CH 3 and optionally substituted with one substituent selected from Branch C 1 ~C 10 is an alkyl, alkenyl, or alkynyl of the formula: 2 ~C 10 0-3 carbons in are independently replaced with heteroatoms of N, S, and / or O; or R C10e R C10f where R C10e is a linear C 1 ~C 3 Alkyl, C 2 Alkyl or C 3The alkyl may be substituted with N, S, or O heteroatoms, where R C10f teeth, a 5- or 6-membered aromatic ring, wherein one or more carbons are optionally independently replaced with N, S, and / or O heteroatoms and one or more groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen; or Fused bicyclic or fused tricyclic aryl groups, in which one or more carbons may be independently replaced with heteroatoms of N, S, and / or O, and may also be replaced with halogen, -OH, -OR C10g , amino, -NHR C10g , and / or N(R C10g ) 2 wherein R C10g is C 1 ~C 3 a linear or branched alkyl, a fused bicyclic or a fused tricyclic aryl group.

[0298] In some embodiments of the compound of formula C, R C10a is R C10b -R C10c -[Linker]-R X n1 In some embodiments, R C10b is a linear C 1 ~C 5 In some embodiments, R C10b is a linear C 1 ~C 5 In some embodiments, R C10c -NH-C(O)-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH 3 )-, -NHC(S)-, -C(S)NH-, -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -N(CH 3 )C(O)-, -C(S)N(CH 3)-, -NHC(S)NH-, -NHC(O)NH-, -NHNHC(O)-, -C(O)NHNH-, [ka] or polyethylene glycol. In some embodiments, R C10c is -NHC(O)- or -N(CH 3 )C(O)-.

[0299] In some embodiments, the linker is X 1 L 1 , X 1 L 1 X 1 L 1 , or X 1 L 1 X 1 L 1 X 1 L 1 and

[0300] X 1 Each independently represents -CH 2 -, [ka] and

[0301] L 1 each independently represents -NH-, -C(O)-, -NHC(O)-, -C(O)NH-, -N(CH 3 )C(O)-, or -C(O)N(CH 3 )-and

[0302] R 11 are each independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid; and

[0303] R Z are each independently an albumin binder.

[0304] In some embodiments, the linker is X 1a L 1a X 1b L1b and

[0305] X 1a teeth, [ka] and

[0306] L 1a is -NH- or -NHC(O)-,

[0307] X 1b teeth, [ka] and

[0308] L 1b is -NH-, or -NHC(O)-.

[0309] In some embodiments, the linker is X 1a L 1a X 1b L 1b and

[0310] X 1a teeth, [ka] and

[0311] L 1a is -NH- or -NHC(O)-,

[0312] X 1b teeth, [ka] and

[0313] L 1b is -NH-, or -NHC(O)-.

[0314] In some embodiments, the linker is X 1a L 1a X 1b L 1b and

[0315] X 1a teeth, [ka] and

[0316] L 1a is -NH- or -NHC(O)-,

[0317] X 1b teeth, [ka] and

[0318] L 1b is -NH-, or -NHC(O)-.

[0319] In some embodiments, the linker is X 1a L 1a X 1b L 1b X 1c L 1c and

[0320] X 1a teeth, [ka] and

[0321] L 1a is -NH- or -NHC(O)-,

[0322] X 1b teeth, [ka] and

[0323] L1b is -NH- or -NHC(O)-,

[0324] X 1c is -CH 2 - and

[0325] L 1c is -NH-, or -NHC(O)-.

[0326] In some embodiments, the linker is X 1a L 1a X 1b L 1b X 1c L 1c and

[0327] X 1a teeth, [ka] and

[0328] L 1a is -NH- or -NHC(O)-,

[0329] X 1b is -CH 2 - and

[0330] L 1b is -NH- or -NHC(O)-,

[0331] X 1c teeth, [ka] and

[0332] L 1c is -NH-, or -NHC(O)-.

[0333] In some embodiments, R C10a is -NHC(O)-[linker]-R X n1and the linker is X 1a L 1a X 1b L 1b and

[0334] X 1a is C 1 ~C 2 alkenyl, L 1a is -NH-C(O), and X 1b teeth, [ka] And L 1b is -NH- and R 11 is independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid.

[0335] In some embodiments, R 11 is sulfonic acid (-SO 3 H).

[0336] In some embodiments of the compound of formula C, R C10a is R C10d It is.

[0337] In some embodiments of the compound of formula C, R C10d is a linear C 1 ~C 5 is an alkyl, alkenyl, or alkynyl of the formula: 2 ~C 5 0-2 carbons in are independently replaced with heteroatoms of N, S, and / or O, where C is -SH, -OH, amino, carboxy, guanidino, -NH-C(O)-CH 3 , -SC(O)-CH 3 , -OC(O)-CH 3 , -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH 3 ) 1~2 , -NH 2 -CH 3 , -N(CH 3 ) 2~3 , -S-CH3 , and -O-CH 3 may be substituted with one substituent selected from the group consisting of:

[0338] In some embodiments of the compound of formula C, R C10d is a linear C 1 ~C 5 is an alkyl, alkenyl, or alkynyl group, where C is -SH, -OH, amino, carboxy, guanidino, -NH-C(O)-CH 3 , -SC(O)-CH 3 , -OC(O)-CH 3 , -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH 3 ) 1~2 , -NH 2 -CH 3 , -N(CH 3 ) 2~3 , -S-CH 3 , and -O-CH 3 In some embodiments, R C10d is a linear C 1 ~C 5 alkyl, where C is -SH, -OH, amino, carboxy, guanidino, -NH-C(O)-CH 3 , -SC(O)-CH 3 , -OC(O)-CH 3 , -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH 3 ) 1~2 , -NH 2 -CH 3 , -N(CH 3 ) 2~3 , -S-CH 3 , and -O-CH 3 may be substituted with one substituent selected from the group consisting of:

[0339] In some embodiments of the compound of formula C, R C10d is the C of the branch 1 ~C10 is an alkyl, alkenyl, or alkynyl of the formula: 2 ~C 10 0-3 carbons in are independently replaced with heteroatoms of N, S, and / or O. In some embodiments, R C10d is the C of the branch 1 ~C 10 In some embodiments, R C10d is branch C 1 ~C 10 It is an alkyl.

[0340] In some embodiments of the compound of formula C, R C10d is R C10e R C10f In some embodiments, R C10e is a linear C 1 ~C 3 In some embodiments, R C10f is a 5- or 6-membered aromatic ring, where 0-4 carbons are independently replaced with N, S, and / or O heteroatoms, and 0-4 groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen. C10f is a fused bicyclic or fused tricyclic aryl group, where 0-6 carbons are independently replaced with heteroatoms of N, S, and / or O, and are also independently selected from halogen, -OH, -OR C10g , amino, -NHR C10g , and / or N(R C10g ) 2 wherein R C10g is C 1 ~C 3 In some embodiments, R C10gis methyl. In some embodiments, each ring of a fused bicyclic or fused tricyclic aryl group independently has 4, 5, or 6 ring carbons, where 0-3 carbons are independently replaced with N, S, and / or O heteroatoms, and such embodiments may be substituted or unsubstituted as defined above.

[0341] In some embodiments of the compound of formula A, -NH-CH(R 2a )-C(O)- forms (3-I) Tyr residue, -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R 5a )-C(O)- is 2-Nal or (4-NH 2 )Phe residue, -NH-CH(R 6a )-C(O)- forms a Gly residue, and -NH-CH(R A7a )-C(O)- forms a D-amino acid, where R A7a is C 1 ~C 3 Alkyenyl, and -NH-CH(R 8a )-C(O)- forms a Lys(iPr) residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- forms a 2-Nal residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- is (4-NH 2 ) Phe residue.

[0342] In some embodiments of the compound of formula A, -NH-CH(R 2a )-C(O)- forms a Tyr residue, and -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R 5a )-C(O)- is a 2-Nal residue or (4-NH 2 )Phe residue, -NH-CH(R6a )-C(O)- forms a D-Ala residue, and -NH-CH(R A7a )-C(O)- forms a D-amino acid residue, where R A7a is C 1 ~C 3 Alkyenyl, and -NH-CH(R 8a )-C(O)- forms a Lys(iPr) residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- forms a 2-Nal residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- is (4-NH 2 ) Phe residue.

[0343] In some embodiments of the compound of formula A, -NH-CH(R 2a )-C(O)- is (4-NH 2 )Phe residue, -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R 5a )-C(O)- is a 2-Nal residue or (4-NH 2 )Phe residue, -NH-CH(R 6a )-C(O)- forms a Gly residue, and -NH-CH(R A7a )-C(O)- forms a D-amino acid residue, where R A7a is C 1 ~C 3 Alkyenyl, and -NH-CH(R 8a )-C(O)- forms a Lys(iPr) residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- forms a 2-Nal residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- is (4-NH 2 ) Phe residue.

[0344] In some embodiments of the compound of formula A, -NH-CH(R2a )-C(O)- is (4-NO 2 )Phe residue, -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R 5a )-C(O)- is a 2-Nal residue or (4-NH 2 )Phe residue, -NH-CH(R 6a )-C(O)- forms a Gly residue, and -NH-CH(R A7a )-C(O)- forms a D-amino acid residue, where R A7a is C 1 ~C 3 Alkyenyl, and -NH-CH(R 8a )-C(O)- forms a Lys(iPr) residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- forms a 2-Nal residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- is (4-NH 2 ) Phe residue.

[0345] In some embodiments of the compound of formula A, -NH-CH(R 2a )-C(O)- forms a hTyr residue, and -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R 5a )-C(O)- is a 2-Nal residue or (4-NH 2 )Phe residue, -NH-CH(R 6a )-C(O)- forms a Gly residue, and -NH-CH(R A7a )-C(O)- forms a D-amino acid residue, where R A7a is C 1 ~C 3 Alkyenyl, and -NH-CH(R 8a)-C(O)- forms a Lys(iPr) residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- forms a 2-Nal residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- is (4-NH 2 ) Phe residue.

[0346] In some embodiments of the compound of formula A, -NH-CH(R 2a )-C(O)- forms a Tyr residue, and -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R 5a )-C(O)- is a 2-Nal residue or (4-NH 2 )Phe residue, -NH-CH(R 6a )-C(O)- forms a D-His residue, and -NH-CH(R A7a )-C(O)- forms a D-amino acid residue, where R A7a is C 1 ~C 3 Alkyenyl, and -NH-CH(R 8a )-C(O)- forms a Lys(iPr) residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- forms a 2-Nal residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- is (4-NH 2 ) Phe residue.

[0347] In some embodiments of the compound of formula A, -NH-CH(R 2a )-C(O)- forms a Tyr residue, and -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R 5a )-C(O)- is a 2-Nal residue or (4-NH 2)Phe residue, -NH-CH(R 6a )-C(O)- forms a His residue, and -NH-CH(R A7a )-C(O)- forms a D-amino acid residue, where R A7a is C 1 ~C 3 Alkyenyl, and -NH-CH(R 8a )-C(O)- forms a Lys(iPr) residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- forms a 2-Nal residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- is (4-NH 2 ) Phe residue.

[0348] In some embodiments of the compound of formula A, -NH-CH(R 2a )-C(O)- forms a Tyr residue, and -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R 5a )-C(O)- is a 2-Nal residue or (4-NH 2 )Phe residue, -NH-CH(R 6a )-C(O)- forms a D-Ser residue, and -NH-CH(R A7a )-C(O)- forms a D-amino acid residue, where R A7a is C 1 ~C 3 Alkyenyl, and -NH-CH(R 8a )-C(O)- forms a Lys(iPr) residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- forms a 2-Nal residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- is (4-NH 2 ) Phe residue.

[0349] In some embodiments of the compound of formula A, -NH-CH(R2a )-C(O)- forms a Tyr residue, and -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R 5a )-C(O)- is a 2-Nal residue or (4-NH 2 )Phe residue, -NH-CH(R 6a )-C(O)- forms a D-Glu residue, and -NH-CH(R A7a )-C(O)- forms a D-amino acid residue, where R A7a is C 1 ~C 3 Alkyenyl, and -NH-CH(R 8a )-C(O)- forms a Lys(iPr) residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- forms a 2-Nal residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- is (4-NH 2 ) Phe residue.

[0350] In some embodiments of the compound of formula A, -NH-CH(R 2a )-C(O)- forms a Tyr residue, and -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R 5a )-C(O)- is a 2-Nal residue or (4-NH 2 )Phe residue, -NH-CH(R 6a )-C(O)- forms a D-His residue, and -NH-CH(R A7a )-C(O)- forms a D-amino acid residue, where R A7a is C 1 ~C 3 Alkyenyl, and -NH-CH(R 8a )-C(O)- forms a Lys(iPr) residue. In some of these embodiments, -NH-CH(R 5a)-C(O)- forms a 2-Nal residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- is (4-NH 2 ) Phe residue.

[0351] In some embodiments of the compound of formula A, -NH-CH(R 2a )-C(O)- forms a Tyr residue, and -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R 5a )-C(O)- forms a (2-Ant)Ala residue, and -NH-CH(R 6a )-C(O)- forms a Gly residue, and -NH-CH(R A7a )-C(O)- forms a D-amino acid residue, where R A7a is C 1 ~C 3 Alkyenyl, and -NH-CH(R 8a )-C(O)- forms a Lys(iPr) residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- forms a 2-Nal residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- is (4-NH 2 ) Phe residue.

[0352] In some embodiments of the compound of formula A, -NH-CH(R 2a )-C(O)- forms a Tyr residue, and -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R 5a )-C(O)- is a 2-Nal residue or (4-NH 2 )Phe residue, -NH-CH(R 6a )-C(O)- forms a D-Ala residue, and -NH-CH(R A7a)-C(O)- forms a D-amino acid residue, where R A7a is C 1 ~C 3 Alkyenyl, and -NH-CH(R 8a )-C(O)- forms a Lys(iPr) residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- forms a 2-Nal residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- is (4-NH 2 ) Phe residue.

[0353] In some embodiments of the compound of formula A, -NH-CH(R 2a )-C(O)- forms a Tyr residue, and -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R A7a )-C(O)- forms a D-amino acid residue, where R A7a is C 1 ~C 3 Alkyenyl, and -NH-CH(R 8a )-C(O)- forms a Lys(iPr) residue. In some of these embodiments, -NH-CH(R 6a )-C(O)- forms a Gly residue. In some of these embodiments, -NH-CH(R 6a )-C(O)- forms a D-Ala residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- forms a 2-Nal residue. In some of these embodiments, -NH-CH(R 5a )-C(O)- is (4-NH 2 In some of these embodiments, -NH-CH(R A1a )-C(O)- forms a Phe residue, and R A10 is absent. In some embodiments, R A10 -[Linker]-R Xn1 and R.A. 1e is a linear C 1 ~C 5 alkylenyl, and R A1f is -NHC(O).

[0354] In some embodiments of the compounds of formula A, one or more of the following conditions are met: a) -NH-CH(R 2a )-C(O)- forms a Tyr residue; b) -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue; c) -NH-CH(R 4a )-C(O)- forms a D-Arg residue; d) -NH-CH(R 5a )-C(O)- forms a 2-Nal residue, and / or e) -NH-CH(R 6a )-C(O)- forms a D-Ala residue.

[0355] In some embodiments of the compound of formula A, -NH-CH(R 2a )-C(O)- forms a Tyr residue, and -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R 5a )-C(O)- forms a 2-Nal residue, and -NH-CH(R 6a )-C(O)- forms a D-Ala residue.

[0356] In some embodiments of the compound of formula A, -NH-CH(R 2a )-C(O)- forms a Tyr residue, and -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R A7a )-C(O)- forms a D-amino acid residue, where R A7a is C1 ~C 3 Alkyenyl, and -NH-CH(R 8a )- is R 9a Together with the additional -C(O)- to form a Lys(iPr) residue. 6a )-C(O)- forms a Gly, D-Ala, D-Gln, or D-Asn residue. In some embodiments, -NH-CH(R A1a )-C(O)- forms a Phe residue, and R 10A is absent. In some embodiments, R A10 -[Linker]-R X n1 and R A1e is a linear C 1 ~C 5 alkylenyl, and R A1f is -NH-C(O)-.

[0357] In some embodiments of the compound of formula A, -NH-CH(R 2a )-C(O)- forms a Tyr residue, -NCH 3 -CH(R 3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R 5a )-C(O)- forms a 2-Nal residue, -NH-CH(R 6a )-C(O)- forms D-Ala, and -NH-CH(R A7a )-C(O)- forms a D-amino acid residue, where R A7a is C 1 ~C 3 Alkyenyl, and -NH-CH(R 8a )- is R 9a Together with the additional -C(O)- to form a Lys(iPr) residue. 8a )- is R 9a Together with the additional -C(O)-, they form an amidated Lys(iPr) residue. In some embodiments, -NH-CH(R 8a)- is R 9a Together with the -C(O)-, Lys(iPr)-NH 2 Form.

[0358] In some embodiments of the compound of formula A, -NH-CH(R 2a )-C(O)- forms a Tyr residue, and -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R 5a )-C(=NH)- forms a 2-Nal residue, -NH-CH(R 6a )-C(O)- forms D-Ala, and -NH-CH(R A7a )-C(O)- forms a D-amino acid residue, where R A7a is C 1 ~C 3 Alkyenyl, and -NH-CH(R 8a )- is R 9a Together with the additional -C(O)- to form a Lys(iPr) residue. In some embodiments of the compound of formula A, -NH-CH(R 2a )-C(O)- forms a Tyr residue, and -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R 5a )-C(O)- forms a 2-Nal residue, and the backbone amide is replaced with an amidine, -NH-CH(R 6a )-C(O)- forms D-Ala, and -NH-CH(R A7a )-C(O)- forms a D-amino acid residue, where R A7a is C 1 ~C 3 Alkyenyl, and -NH-CH(R 8a )- is R 9a Together with the additional -C(O)- to form a Lys(iPr) residue. In some embodiments of the compound of formula A, -NH-CH(R 2a )-C(O)- forms a Tyr residue, and -NH-CH(R3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R 5a )-C(=NH)-, where R 5a is -CH 2 (2-naphthyl) and -NH-CH(R 6a )-C(O)- forms D-Ala, and -NH-CH(R A7a )-C(O)- forms a D-amino acid residue, where R A7a is C 1 ~C 3 Alkyenyl, and -NH-CH(R 8a )- is R 9a Together with the additional -C(O)- to form a Lys(iPr) residue. 8a )- is R 9a Together with the additional -C(O)-, they form an amidated Lys(iPr) residue. In some embodiments, -NH-CH(R 8a )- is R 9a Together with the -C(O)-, Lys(iPr)-NH 2 Form.

[0359] In some embodiments of the compound of formula A, -NH-CH(R 2a )-C(O)- forms a Tyr residue, and -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(=NH)- forms a D-Arg residue, -NH-CH(R 5a )-C(O)- forms a 2-Nal residue, -NH-CH(R 6a )-C(O)- forms D-Ala, and -NH-CH(R A7a )-C(O)- forms a D-amino acid residue, where R A7a is C 1 ~C 3 Alkyenyl, and -NH-CH(R 8a )- is R 9aTogether with the additional -C(O)- to form a Lys(iPr) residue. In some embodiments of the compound of formula A, -NH-CH(R 2a )-C(O)- forms a Tyr residue, and -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and the backbone amide is replaced by an amidine, -NH-CH(R 5a )-C(O)- forms a 2-Nal residue, -NH-CH(R 6a )-C(O)- forms D-Ala, and -NH-CH(R A7a )-C(O)- forms a D-amino acid residue, where R A7a is C 1 ~C 3 Alkyenyl, and -NH-CH(R 8a )- is R 9a Together with the additional -C(O)- to form a Lys(iPr) residue. In some embodiments of the compound of formula A, -NH-CH(R 2a )-C(O)- forms a Tyr residue, and -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(=NH)-, where R 4a is -(CH 2 ) 3 NHC(=NH)NH 2 and -NH-CH(R 5a )-C(O)- forms a 2-Nal residue, -NH-CH(R 6a )-C(O)- forms D-Ala, and -NH-CH(R A7a )-C(O)- forms a D-amino acid residue, where R A7a is C 1 ~C 3 Alkyenyl, and -NH-CH(R 8a )- is R 9a Together with the additional -C(O)- to form a Lys(iPr) residue. 8a )- is R 9aTogether with the additional -C(O)-, they form an amidated Lys(iPr) residue. In some embodiments, -NH-CH(R 8a )- is R 9a Together with the -C(O)-, Lys(iPr)-NH 2 Form.

[0360] In some embodiments of the compound of formula A, -NH-CH(R 2a )-C(O)- forms a Tyr residue, and -NH-CH(R 3a )-C(=NH)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R 5a )-C(O)- forms a 2-Nal residue, -NH-CH(R 6a )-C(O)- forms D-Ala, and -NH-CH(R A7a )-C(O)- forms a D-amino acid residue, where R A7a is C 1 ~C 3 Alkyenyl, and -NH-CH(R 8a )- is R 9a Together with the additional -C(O)- to form a Lys(iPr) residue. In some embodiments of the compound of formula A, -NH-CH(R 2a )-C(O)- forms a Tyr residue, and -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, and the backbone amide is replaced by an amidine, -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R 5a )-C(O)- forms a 2-Nal residue, -NH-CH(R 6a )-C(O)- forms D-Ala, and -NH-CH(R A7a )-C(O)- forms a D-amino acid residue, where R A7a is C 1 ~C 3 Alkyenyl, and -NH-CH(R 8a )- is R 9aTogether with the additional -C(O)- to form a Lys(iPr) residue. In some embodiments of the compound of formula A, -NH-CH(R 2a )-C(O)- forms a Tyr residue, and -NH-CH(R 3a )-C(=NH)-, where R 3a is -(CH 2 ) 4 NH(iPr) and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R 5a )-C(O)- forms a 2-Nal residue, -NH-CH(R 6a )-C(O)- forms D-Ala, and -NH-CH(R A7a )-C(O)- forms a D-amino acid residue, where R A7a is C 1 ~C 3 Alkyenyl, and -NH-CH(R 8a )- is R 9a Together with the additional -C(O)- to form a Lys(iPr) residue. 8a )- is R 9a Together with the additional -C(O)-, they form an amidated Lys(iPr) residue. In some embodiments, -NH-CH(R 8a )- is R 9a Together with the -C(O)-, Lys(iPr)-NH 2 Form.

[0361] In some embodiments of the compound of formula B, -NH-CH(R 2a )-C(O)- forms a Tyr residue, and -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R 8a )-C(O)- forms a Lys(iPr) residue. In some of these embodiments, -NH-CH(R 6a)-C(O)- forms a Gly, D-Ala, D-Gln, or D-Asn residue, and -NH-CH(R 5a )-C(O)- is a 2-Nal residue, (2-Ant)Ala residue, or (4-NH 2 ) Phe residue.

[0362] In some embodiments of the compound of formula B, -NH-CH(R 2a )-C(O)- forms a Tyr residue, and -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R 5a )-C(O)- forms a 2-Nal residue, and -NH-CH(R 6a )-C(O)- forms D-Ala.

[0363] In some embodiments of the compound of formula C, -NH-CH(R 2a )-C(O)- forms a Tyr residue, and -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R 5a )-C(O)- forms a 2-Nal residue, and -NH-CH(R 6a )-C(O)- forms D-Ala.

[0364] In some embodiments of the compound of formula A, the compound has the structure of formula AI: [ka]

[0365] During the ceremony,

[0366] R 2a is -(CH 2 )-(R 2b )-(phenyl), where R 2bdoes not exist or -CH 2 -, -NH-, -S-, or -O-, where phenyl is -NH 2 , -NO 2 , -OH, -OR 2c , -SH, -SR 2c , -N 3 , -CN, or -O-phenyl at the 4-position, or halogen or -OH at the 3-position, 2c are independently 1 ~C 3 is a straight or branched alkyl group of

[0367] R 3a is R 3b R 3c where R 3b is a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 alkynylenyl, where R 3c is -N(R 3d ) 2~3 or guanidino, wherein each R 3d are independently -H or linear or branched C 1 ~C 3 is alkyl,

[0368] R 4a is R 4b R 4c where R 4b is a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 alkynylenyl, where R 4c is -N(R 4d ) 2~3 or guanidino, wherein each R 4d are independently -H or linear or branched C 1 ~C 3 is alkyl,

[0369] R 5a is -(CH 2 ) 1~3 -R 5b where R 5b teeth,

[0370] Phenyl, -NH 2 , -NO 2 , -OH, -SH, -N 3 , -CN, or -O-phenyl at the 4-position, a halogen or -OH at the 3-position, and / or a halogen or -OH at the 5-position;

[0371] A fused bicyclic or tricyclic aryl or heteroaryl ring, which may be halogen, -OH, -OR 5c , amino, -NHR 5c , and / or N(R 5c ) 2 and

[0372] In the formula, R 5c are each independently: C 1 ~C 3 is a straight or branched alkyl group of

[0373] R 6a is methyl, ethyl, -C≡CH, -CH=CH 2 , -CH 2 -R 6b -OH, -CH 2 -R 6b -COOH, -CH 2 -(R 6b ) 1-3 -NH 2 , -CH 2 -R 6b -CONH 2 , or -CH 2 -R 6b R 6c where each R 6bare independently absent or -CH 2 -, -NH-, -S-, or -O-, wherein R 6c is a 5- or 6-membered aromatic ring, wherein 0-3 carbons are independently replaced with N, S, and / or O heteroatoms, and optionally substituted with 0-3 groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen;

[0374] R 8a is R 8b R 8c where R 8b is a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 alkynylenyl, where R 8c is -N(R 8d ) 2~3 or guanidino, wherein each R 8d are independently -H or linear or branched C 1 ~C 3 is alkyl,

[0375] R 9a is -C(O)NH 2 , -C(O)-OH, -CH 2 -C(O)NH 2 , -CH 2 -C(O)-OH, -R 9b -R 9c , or -R 9b -[Linker]-R X n1 where R 9b is -C(O)NH-, and R 9c teeth, [ka] where R 9d is a linear or branched C 1 ~C 5 alkylenyl, R 9eare carboxylic acid, sulfonic acid, sulfinic acid, phosphoric acid, amino, guanidino, -SH, -OH, -NH-C(O)-CH 3 , -SC(O)-CH 3 , -OC(O)-CH 3 , NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-CH 3 , -N(CH 3 ) 2 , -S-CH 3 , -O-CH 3 , or phenyl, and R 9f is amino or -OH,

[0376] R A7a is C 1 ~C 3 is alkylenyl,

[0377] R A10 does not exist or -[linker]-R X n1 and

[0378] R A10 If does not exist, R A1a teeth,

[0379] Linear C 1 ~C 5 is an alkyl, alkenyl, or alkynyl of the formula: 2 ~C 5 0-2 carbons in are independently replaced by one or more N, S, and / or O heteroatoms, where C is -SH, -OH, amino, carboxy, guanidino, -NH-C(O)-CH 3 , -SC(O)-CH 3 , -OC(O)-CH 3 , -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH 3 ) 1~2 , -NH 2 -CH 3 , -N(CH 3 ) 2~3 , -S-CH3 , or -O-CH 3 and optionally substituted with one substituent selected from

[0380] Branch C 1 ~C 10 is an alkyl, alkenyl, or alkynyl of the formula: 2 ~C 10 wherein 0-3 carbons are independently replaced by one or more N, S, and / or O heteroatoms; or

[0381] R A1b R A1c where R A1b is a linear C 1 ~C 3 alkylenyl, wherein C 2 Alkylenyl or C 3 Alkylenyl may be substituted with N, S, or O heteroatoms, where R A1c teeth,

[0382] a 5- or 6-membered aromatic ring, wherein one or more carbons are optionally independently replaced with N, S, and / or O heteroatoms and one or more groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen; or

[0383] Fused bicyclic or fused tricyclic aryl groups, in which one or more carbons may be independently replaced with heteroatoms of N, S, and / or O, and may also be replaced with halogen, -OH, -OR A1d , amino, -NHR A1d , and / or N(R A1d ) 2 wherein each R A1d is independently C 1 ~C 3 a fused bicyclic or tricyclic aryl group, which is a linear or branched alkyl group of the formula:

[0384] R A10 -[Linker]-R X n1 If so, then R A1a is R A1e R A1f where R A1e is a linear C 1 ~C 5 is an alkylenyl, alkenylenyl, or alkynylenyl of the formula C 2 ~C 5 0-2 carbons in are independently replaced with heteroatoms of N, S, and / or O, and R A1f -NH-C(O)-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH 3 )-, -NHC(S)-, -C(S)NH-, -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -N(CH 3 )C(O)-, -C(S)N(CH 3 )-, -NHC(S)NH-, -NHC(O)NH-, -S-, -S(O)-, -S(O)-O-, -S(O) 2 -, -S(O) 2 -O-, -S(O) 2 -NH-, -S(O)-NH-, -Se-, -Se(O)-, -Se(O) 2 -, -NHNHC(O)-, -C(O)NHNH-, -OP(O)(O - )O-, -phosphamide-, -thiophosphodiester-, -S-tetrafluorophenyl-S-, [ka] or polyethylene glycol,

[0385] The linker is X 1 L 1 , X 1 L 1 X 1 L 1 , or X 1 L 1 X 1 L 1 X 1 L1 and

[0386] X 1 Each independently represents -CH 2 -, [ka] and

[0387] L 1 each independently represents -NH-, -C(O)-, -NHC(O)-, -C(O)NH-, -N(CH 3 )C(O)-, or -C(O)N(CH 3 )-and

[0388] R 11 are each independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid; and

[0389] R Z are each independently an albumin binder;

[0390] each n1 is independently 0, 1, or 2;

[0391] Each R X is an albumin binder, a therapeutic moiety, a fluorescent label, a radiolabeled group, or a group that can be radiolabeled;

[0392] wherein 0 to 3 peptide backbone amides are independently [ka] amidine or thioamide substituted,

[0393] wherein 0 to 3 of the peptide backbone amides are N-methylated;

[0394] In the formula, the C-terminus may be amidated.

[0395] In some embodiments of the compound of formula A or AI, -NH-CH(RA1a )-C(O)- forms an L amino acid residue.

[0396] In some embodiments of the compound of formula A or AI, -NH-CH(R A1a )-C(O)- forms a Phe residue, a 1-Nal residue, a 2-Nal residue, a Tyr residue, a Trp residue, a Lys residue, a hLys residue, a Lys(Ac) residue, a Dap residue, a Dab residue, or an Orn residue. In some embodiments of the compound of formula A, -NH-CH(R A1a )-C(O)- forms an L-Phe residue, an L-1-Nal residue, an L-2-Nal residue, an L-Tyr residue, an L-Trp residue, an L-Lys residue, an L-hLys residue, an L-Lys(Ac) residue, an L-Dap residue, an L-Dab residue, or an L-Orn residue.

[0397] In some embodiments of the compounds of formula A or AI, R A10 -[Linker]-R X n1 and R 9a is -C(O)NH 2 , -C(O)-OH, -CH 2 -C(O)NH 2 , or -CH 2 -C(O)-OH.

[0398] In some embodiments of the compound of formula A, the compound has the structure of formula A-II: [ka]

[0399] During the ceremony,

[0400] -NH-CH(R 2a )-C(O)- is a Tyr residue, a Phe residue, or (4-NO 2 )-Phe residue, (4-NH 2 )-Phe residue, hTyr residue, (3-I)Tyr residue, Glu residue, Gln residue, or D-Tyr residue;

[0401] -NH-CH(R 3a )-C(O)- is a Lys(iPr) residue, Arg(Me) 2 (asymmetric) residue, or Arg(Me) residue,

[0402] -NH-CH(R 4a )-C(O)- forms a D-Arg or D-hArg residue;

[0403] -NH-CH(R 5a )-C(O)- is a 2-(Ant)Ala residue, a 2-Nal residue, a Trp residue, a (4-NH 2 ) forming a Phe residue, an hTyr residue, or a Tyr residue;

[0404] -NH-CH(R 6a )-C(O)- forms His, D-His, D-Glu, D-Gln, D-Ala, D-Phe, D-Ser, D-Dab, and D-Dap residues;

[0405] R 8a is R 8b R 8c where R 8b is a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 alkynylenyl, where R 8c is -N(R 8d ) 2~3 or guanidino, wherein each R 8d are independently -H or linear or branched C 1 ~C 3 is alkyl,

[0406] R 9a is -C(O)NH 2 , -C(O)-OH, -CH 2 -C(O)NH 2 , -CH2 -C(O)-OH, or -R 9b -[Linker]-R X n1 and

[0407] R 9b is -C(O)NH-,

[0408] R A7a is C 1 ~C 3 is alkylenyl,

[0409] R A10 does not exist or -[linker]-R X n1 and

[0410] R A10 If does not exist, R A1a is a linear C 1 ~C 5 Alkyl, -SH, -OH, amino, carboxy, guanidino, -NH-C(O)-CH 3 , -SC(O)-CH 3 , -OC(O)-CH 3 , -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH 3 ) 1~2 , -NH 2 -CH 3 , -N(CH 3 ) 2~3 , -S-CH 3 , or -O-CH 3 , or branch C 1 ~C 10 A straight-chain C optionally substituted with one substituent selected from alkyl, alkenyl, or alkynyl 1 ~C 5 is alkyl,

[0411] R A10 -[Linker]-R X n1 If so, then R A1a is R A1e RA1f where R A1e is a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 alkynylenyl, and R A1f -NH-C(O)-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH 3 )-, -NHC(S)-, -C(S)NH-, -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -N(CH 3 )C(O)-, -C(S)N(CH 3 )-, -NHC(S)NH-, -NHC(O)NH-, -S-, -S(O)-, -S(O)-O-, -S(O) 2 -, -S(O) 2 -NH-, -S(O)-NH-, -NHNHC(O)-, -C(O)NHNH-, [ka] or polyethylene glycol, each linker independently being a linear or branched chain of 1 to 10 units of X 1 L 1 and / or X 1 (L 1 ) 2 where:

[0412] each X 1 are independently linear, branched, and / or cyclic C 1 ~C 15 Alkylenyl, C 2 ~C 15 Alkenylenyl, or C 2 ~C 15 alkynylenyl, wherein 0-6 carbons are independently replaced with N, S, and / or O heteroatoms, and 0-3 groups independently selected from one or a combination of oxo, hydroxyl, sulfhydryl, halogen, guanidino, carboxylic acid, sulfonic acid, sulfinic acid, and / or phosphate;

[0413] Each L 1 are independently -NH-C(O)-, -NH-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH 3 )-, -NHC(S)-, -C(S)NH-, -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -N(CH 3 )C(O)-, -C(S)N(CH 3 )-, -NHC(S)NH-, -NHC(O)NH-, -S-, -S(O)-, -S(O)-O-, -S(O) 2 -, -S(O) 2 -O-, -S(O) 2 -NH-, -S(O)-NH-, -Se-, -Se(O)-, -Se(O) 2 -, -NHNHC(O)-, -C(O)NHNH-, -OP(O)(O - )O-, -phosphamide-, -thiophosphodiester-, -S-tetrafluorophenyl-S-, [ka] or polyethylene glycol,

[0414] The linker is X 1 L 1 , X 1 L 1 X 1 L 1 , or X 1 L 1 X 1 L 1 X 1 L 1 and

[0415] X 1 Each independently represents -CH 2 -, [ka] and

[0416] L 1each independently represents -NH-, -C(O)-, -NHC(O)-, -C(O)NH-, -N(CH 3 )C(O)-, or -C(O)N(CH 3 )-and

[0417] R 11 are each independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid; and

[0418] R Z are each independently an albumin binder;

[0419] each n1 is independently 0, 1, or 2;

[0420] Each R X is an albumin binder, a therapeutic moiety, a fluorescent label, a radiolabeled group, or a group that can be radiolabeled;

[0421] wherein 0 to 3 peptide backbone amides are independently

[0422] [ka] amidine or thioamide substituted,

[0423] wherein 0 to 3 of the peptide backbone amides are N-methylated;

[0424] In the formula, the C-terminus may be amidated.

[0425] In some embodiments of the compound of formula A, the compound has the structure of formula A-III: [ka]

[0426] During the ceremony,

[0427] R 2a is -(CH2 )-(R 2b )-(phenyl), where R 2b does not exist or -CH 2 -, -NH-, -S-, or -O-, where phenyl is -NH 2 , -NO 2 , -OH, -OR 2c , -SH, -SR 2c , -N 3 , -CN, or -O-phenyl at the 4-position, or halogen or -OH at the 3-position, 2c are independently 1 ~C 3 is a straight or branched alkyl group of

[0428] R 3a is C 1 ~C 5 is alkyl,

[0429] R y is hydrogen or R 3e R 3f where R 3e is a linear C 1 ~C 5 alkylenyl, wherein R 3f is -N(R 3g ) 2~3 where each R 3g are independently -H or linear or branched C 1 ~C 3 is alkyl,

[0430] R 4a is R 4b R 4c where R 4b is a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 alkynylenyl, where R 4c is -N(R 4d ) 2~3 or guanidino, wherein each R4d are independently -H or linear or branched C 1 ~C 3 is alkyl,

[0431] R 5a is -(CH 2 ) 1~3 -R 5b where R 5b teeth,

[0432] Phenyl, -NH 2 , -NO 2 , -OH, -SH, -N 3 , -CN, or -O-phenyl at the 4-position, a halogen or -OH at the 3-position, and / or a halogen or -OH at the 5-position;

[0433] A fused bicyclic or tricyclic aryl or heteroaryl ring, which may be halogen, -OH, -OR 5c , amino, -NHR 5c , and / or N(R 5c ) 2 and

[0434] In the formula, R 5c are each independently: C 1 ~C 3 is a straight or branched alkyl group of

[0435] R 6a is H, methyl, ethyl, -C≡CH, -CH=CH 2 , -CH 2 -R 6b -OH, -CH 2 -R 6b -COOH, -CH 2 -(R 6b ) 1~3 -NH 2 , -CH 2 -R 6b -CONH 2 , or -CH2 -R 6b R 6c where each R 6b are independently absent or -CH 2 -, -NH-, -S-, or -O-; and 6c is a 5- or 6-membered aromatic ring, wherein 0-3 carbons are independently replaced with N, S, and / or O heteroatoms, and optionally substituted with 0-3 groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen;

[0436] R 8a is R 8b R 8c where R 8b is a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 alkynylenyl, where R 8c is -N(R 8d ) 2~3 or guanidino, wherein each R 8d are independently -H or linear or branched C 1 ~C 3 is alkyl,

[0437] R 9a is -C(O)NH 2 , -C(O)-OH, -CH 2 -C(O)NH 2 , -CH 2 -C(O)-OH, -R 9b -R 9c , or -R 9b -[Linker]-R X n1 where R 9b is -C(O)NH-, and R 9c teeth, [ka] where R 9d is a linear or branched C1 ~C 5 alkylenyl, R 9e are carboxylic acid, sulfonic acid, sulfinic acid, phosphoric acid, amino, guanidino, -SH, -OH, -NH-C(O)-CH 3 , -SC(O)-CH 3 , -OC(O)-CH 3 , -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-CH 3 , -N(CH 3 ) 2 , -S-CH 3 , -O-CH 3 , or phenyl, and R 9f is amino or -OH,

[0438] R A7a is C 1 ~C 3 is alkylenyl,

[0439] R A10 does not exist or -[linker]-R X n1 and

[0440] R A10 If does not exist, R A1a teeth,

[0441] Linear C 1 ~C 5 Alkyl, C 2 ~C 5 Alkenyl, or C 2 ~C 5 alkynyl, wherein C 2 ~C 5 0-2 carbons in the alkyl, alkenyl, or alkynyl are independently replaced with one or more N, S, and / or O heteroatoms, where C is -SH, -OH, amino, carboxy, guanidino, -NH-C(O)-CH 3 , -SC(O)-CH 3 , -OC(O)-CH 3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH 3 ) 1~2 , -NH 2 -CH 3 , -N(CH 3 ) 2~3 , -S-CH 3 , or -O-CH 3 and optionally substituted with one substituent selected from

[0442] Branch C 1 ~C 10 is an alkyl, alkenyl, or alkynyl of the formula: 2 ~C 10 0-3 carbons in are independently replaced by one or more N, S, and / or O heteroatoms, or R A1b R A1c where R A1b is a linear C 1 ~C 3 alkylenyl, wherein C 2 Alkylenyl or C 3 Alkylenyl may be substituted with N, S, or O heteroatoms, where R A1c teeth,

[0443] a 5- or 6-membered aromatic ring, wherein one or more carbons are optionally independently replaced with N, S, and / or O heteroatoms and one or more groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen; or

[0444] Fused bicyclic or fused tricyclic aryl groups, in which one or more carbons may be independently replaced with heteroatoms of N, S, and / or O, and may also be replaced with halogen, -OH, -OR A1d , amino, -NHR A1d , and / or N(R A1d ) 2 wherein each RA1d is independently C 1 ~C 3 a fused bicyclic or tricyclic aryl group, which is a linear or branched alkyl group of the formula:

[0445] R A10 But -[Linker]-R X n1 If so, then R A1a is R A1e R A1f where:

[0446] R A1e is a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 Alkynylenyl, where C 2 ~C 5 0-2 carbons in the alkylenyl, alkenylenyl, or alkynylenyl are independently replaced with heteroatoms of N, S, and / or O;

[0447] R A1f -NH-C(O)-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH 3 )-, -NHC(S)-, -C(S)NH-, -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -N(CH 3 )C(O)-, -C(S)N(CH 3 )-, -NHC(S)NH-, -NHC(O)NH-, -S-, -S(O)-, -S(O)-O-, -S(O) 2 -, -S(O) 2 -O-, -S(O) 2 -NH-, -S(O)-NH-, -Se-, -Se(O)-, -Se(O) 2 -, -NHNHC(O)-, -C(O)NHNH-, -OP(O)(O - )O-, -phosphamide-, -thiophosphodiester-, -S-tetrafluorophenyl-S-, [ka] or polyethylene glycol,

[0448] The linker is X 1 L 1 , X 1 L 1 X 1 L 1 , or X 1 L 1 X 1 L 1 X 1 L 1 and

[0449] X 1 Each independently represents -CH 2 -, [ka] and

[0450] L 1 each independently represents -NH-, -C(O)-, -NHC(O)-, -C(O)NH-, -N(CH 3 )C(O)-, or -C(O)N(CH 3 )-and

[0451] R 11 are each independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid; and

[0452] R Z are each independently an albumin binder;

[0453] each n1 is independently 0, 1, or 2;

[0454] Each R X is an albumin binder, a therapeutic moiety, a fluorescent label, a radiolabeled group, or a group that can be radiolabeled;

[0455] wherein 0 to 3 peptide backbone amides are independently

[0456] [ka] amidine or thioamide substituted,

[0457] wherein 0 to 3 of the peptide backbone amides are N-methylated;

[0458] In the formula, the C-terminus may be amidated.

[0459] In some embodiments of the compound of formula A, the compound has the structure of formula A-IV: [ka]

[0460] During the ceremony,

[0461] -NH-CH(R 2a )-C(O)- is a Tyr residue, a Phe residue, or (4-NO 2 )-Phe residue, (4-NH 2 )-Phe residue, hTyr residue, (3-I)Tyr residue, Glu residue, Gln residue, or D-Tyr residue;

[0462] -NH-CH(R 4a )-C(O)- forms a D-Arg or D-hArg residue;

[0463] -NH-CH(R 5a )-C(O)- is a 2-(Ant)Ala residue, a 2-Nal residue, a Trp residue, a (4-NH 2 ) forming a Phe residue, an hTyr residue, or a Tyr residue;

[0464] -NH-CH(R 6a )-C(O)- forms His, D-His, D-Glu, D-Gln, D-Ala, D-Phe, D-Ser, D-Dab, and D-Dap residues;

[0465] R 3a is C 1 ~C 5 is alkyl,

[0466] R y is hydrogen or R 3e R 3f where R 3e is a linear C 1 ~C 5 alkylenyl, wherein R 3f is -N(R 3g ) 2~3 where each R 3g are independently -H or linear or branched C 1 ~C 3 is alkyl,

[0467] R 8a is R 8b R 8c where R 8b is a linear C 1 ~C 5 Alkylenyl, C 2 ~C 5 Alkenylenyl, or C 2 ~C 5 alkynylenyl, where R 8c is -N(R 8d ) 2~3 or guanidino, wherein each R 8d are independently -H or linear or branched C 1 ~C 3 is alkyl,

[0468] R 9a is -C(O)NH 2 , -C(O)-OH, -CH 2 -C(O)NH 2 , -CH 2 -C(O)-OH, or -R 9b -[Linker]-R X n1 and

[0469] R 9bis -C(O)NH-,

[0470] R A7a is C 1 ~C 3 is alkylenyl,

[0471] R A10 does not exist or -[linker]-R X n1 and

[0472] R A10 If does not exist, R A1a is a linear C 1 ~C 5 Alkyl, -SH, -OH, amino, carboxy, guanidino, -NH-C(O)-CH 3 , -SC(O)-CH 3 , -OC(O)-CH 3 , -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH 3 ) 1~2 , -NH 2 -CH 3 , -N(CH 3 ) 2~3 , -S-CH 3 , -O-CH 3 , or branch C 1 ~C 10 A straight chain C optionally substituted with one substituent selected from the group consisting of alkyl, alkenyl, and alkynyl 1 ~C 5 is alkyl,

[0473] R A10 But -[Linker]-R X n1 If so, then R A1a is R A1e R A1f where:

[0474] R A1e is a linear C 1 ~C 5 Alkylenyl, C 2 ~C5 Alkenylenyl, or C 2 ~C 5 Alkynylenyl, where C 2 ~C 5 0-2 carbons in the alkylenyl, alkenylenyl, or alkynylenyl are independently replaced with heteroatoms of N, S, and / or O;

[0475] R A1f -NH-C(O)-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH 3 )-, -NHC(S)-, -C(S)NH-, -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -N(CH 3 )C(O)-, -C(S)N(CH 3 )-, -NHC(S)NH-, -NHC(O)NH-, -S-, -S(O)-, -S(O)-O-, -S(O) 2 -, -S(O) 2 -O-, -S(O) 2 -NH-, -S(O)-NH-, -Se-, -Se(O)-, -Se(O) 2 -, -NHNHC(O)-, -C(O)NHNH-, -OP(O)(O - )O-, -phosphamide-, -thiophosphodiester-, -S-tetrafluorophenyl-S-, [ka] or polyethylene glycol,

[0476] The linker is X 1 L 1 , X 1 L 1 X 1 L 1 , or X 1 L 1 X 1 L 1 X 1 L 1 and X 1 Each independently represents -CH 2 -, [ka] and L 1 each independently represents -NH-, -C(O)-, -NHC(O)-, -C(O)NH-, -N(CH 3 )C(O)-, or -C(O)N(CH 3 )-and

[0477] R 11 are each independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid; and

[0478] R Z are each independently an albumin binder;

[0479] each n1 is independently 0, 1, or 2;

[0480] Each R X is an albumin binder, a therapeutic moiety, a fluorescent label, a radiolabeled group, or a group that can be radiolabeled;

[0481] wherein 0 to 3 peptide backbone amides are independently

[0482] [ka] amidine or thioamide substituted,

[0483] wherein 0 to 3 of the peptide backbone amides are N-methylated;

[0484] In the formula, the C-terminus may be amidated.

[0485] In some embodiments of the compounds of formula A, A-III, or A-IV, -NH-CH(R 2a )-C(O)- forms a Tyr residue, and -NH-CH(R 4a )-C(O)- forms a D-Arg residue, and -NH-CH(R 5a)-C(O)- forms a 2-Nal residue, -NH-CH(R 6a )-C(O)- forms D-Ala, and -NH-CH(R A7a )-C(O)- forms a D-amino acid residue, where R A7a is C 1 ~C 3 Alkyenyl, and -NH-CH(R 8a )- is R 9a Together with the additional -C(O)- to form a Lys(iPr) residue, y is -(CH 2 ) 4 -NH-(iPr) and R 3a is -CH 3 It is.

[0486] The various embodiments discussed herein for formula A can also be applied to compounds of formula AI, A-II, A-III, and / or A-IV.

[0487] In some embodiments of the compounds of formula A, AI, A-II, A-III, A-IV, B, or C, -NH-CH(R 6a )-C(O)- forms a Gly, D-Ala, D-Gln, or D-Asn residue.

[0488] In some embodiments of the compounds of formula A, AI, A-II, A-III, A-IV, B, or C, -NH-CH(R A1a )-C(O)- forms a Phe residue, and R A10 is absent. In some embodiments, R A10 -[Linker]-R X n1 and R A1e is a linear C 1 ~C 5 alkylenyl, and R A1f is -NH-C(O)-.

[0489] The term "[linker]" refers to a linker, which can be any linker. Non-limiting examples include peptide and polyethylene glycol based linkers.

[0490] In some embodiments of the compounds of formula A, AI, A-II, A-III, A-IV, B, or C, R X n1 wherein each n1 is independently 0, 1, or 2. In some embodiments, each n1 is 0. In some embodiments, each n1 is 1. In some embodiments, each n1 is 2. In some embodiments, each n1 is the same. In some embodiments, each n1 is different.

[0491] In some embodiments of the compound of formula A, AI, A-II, A-III, A-IV, B, or C, each R X is an albumin binder, a therapeutic moiety, a fluorescent label, a radiolabeled group, or a group that can be radiolabeled. X is a therapeutic moiety, a fluorescent label, a radiolabeled group, or a group that can be radiolabeled.

[0492] The present disclosure also relates to one or more compounds comprising a compound selected from Table 2, or a salt or solvate thereof, which may be coupled, optionally via a linker, to a radiolabeled group, a group capable of being radiolabeled, or an albumin binding group. In one embodiment, the compound of the present disclosure is coupled, optionally via one or more linkers, to a metal chelator and / or an albumin binder. In one embodiment, the compound of the present disclosure is coupled, optionally via one or more linkers, to a metal chelator and an albumin binder.

[0493] The present disclosure also relates to one or more of the compounds selected from Table 2, or salts or solvates thereof, which may be attached, optionally via a linker, to a radiolabeled group, a group that can be radiolabeled, or an albumin binding group. In one embodiment, the compounds of the present disclosure are attached, optionally via one or more linkers, to a metal chelator and / or an albumin binder. In one embodiment, the compounds of the present disclosure are attached, optionally via one or more linkers, to a metal chelator and an albumin binder.

[0494] [Table 2]

[0495] In some embodiments of the compounds of Formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2, each linker, if present, is independently a linear or branched chain of 1 to 10 units of X 1 L 1 , X 1 L 1 X 1 L 1 , X 1 L 1 X 1 L 1 X 1 L 1 , and / or X 1 (L 1 ) 2 where: each X 1 are independently linear, branched, and / or cyclic C 1 ~C 15 wherein 0-6 carbons are independently replaced with N, S, and / or O heteroatoms, and 0-3 groups independently selected from one or a combination of oxo, hydroxyl, sulfhydryl, halogen, guanidino, carboxylic acid, sulfonic acid, sulfinic acid, and / or phosphate; Each L 1are independently -NH-, -NH-C(O)-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH 3 )-, -NHC(S)-, -C(S)NH-, -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -N(CH 3 )C(O)-, -C(S)N(CH 3 )-, -NHC(S)NH-, -NHC(O)NH-, -S-, -S(O)-, -S(O)-O-, -S(O) 2 -, -S(O) 2 -O-, -S(O) 2 -NH-, -S(O)-NH-, -Se-, -Se(O)-, -Se(O) 2 -, -NHNHC(O)-, -C(O)NHNH-, -OP(O)(O - )O-, -phosphamide-, -thiophosphodiester-, -S-tetrafluorophenyl-S-, [ka] Or polyethylene glycol.

[0496] In some embodiments, each L 1 are independently -S-, -NHC(O)-, -C(O)NH-, -N(CH 3 )C(O)-, -C(O)N(CH 3 )-, -NHC(S)-, -C(S)NH-, -N(CH 3 )C(S)-, -C(S)N(CH 3 )-, NHC(S)NH-, -S-, -O-, -S(O)-, -S(O) 2 -, -Se-, -Se(O)-, -Se(O) 2 -, -NHNHC(O)-, -C(O)NHNH-, -OP(O)(O - )O-, -OP(O)(S - )O-, [ka] It is.

[0497] In some embodiments, each L1 are independently -S-, -NHC(O)-, -C(O)NH-, -N(CH 3 )C(O)-, -C(O)N(CH 3 )-, [ka] It is.

[0498] In some embodiments, each L 1 are independently -NH-, -C(O)-, -NHC(O)-, -C(O)NH-, -N(CH 3 )C(O)-, or -C(O)N(CH 3 )-.

[0499] In some embodiments, the linker is X 1 L 1 Wherein X 1 is -(CH 2 ) 1~5 -, -CH(COOH)-(CH 2 ) 0~4 - or -CH(CONH 2 )-(CH 2 ) 0~4 - and L 1 -NH-, -C(O)-, -NHC(O)-, -C(O)NH-, -N(CH 3 )C(O)-, or -C(O)N(CH 3 )-.

[0500] In some embodiments of the compounds of Formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2, at least one linker contains at least one carboxylic acid, sulfonic acid, sulfinic acid, or phosphate group and has a net negative charge at physiological pH.

[0501] In some embodiments of the compounds of Formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2, at least one linker contains at least one chemical group, such as a guanidino, or an amino group, that has a net positive charge at physiological pH.

[0502] In some embodiments of the compounds of Formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2, at least one linker comprises 1 to 8 units of X 1 L 1 and 0-2 units of X 1 (L 1 ) 2 It consists of:

[0503] In some embodiments, each X 1 are independently linear, branched, and / or cyclic C 1 ~C 15 It is alkylenyl.

[0504] In some embodiments, each X 1 are independently -CH 2 - or where each R 11 are independently carboxylic acids, sulfonic acids, sulfinic acids, or phosphoric acids [ka] or [ka] or [ka] or [ka] It is.

[0505] In some embodiments, two X 1 Each L between groups 1 are independently -NHC(O)-, -C(O)NH-, -N(CH 3 )C(O)-, or -C(O)N(CH 3 )- and R X Each L that is connected 1 are independently -S-, -NHC(O)-, -C(O)NH-, -N(CH 3)C(O)-, -C(O)N(CH 3 )-, [ka] It is.

[0506] In some embodiments of the compounds of Formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2, the linker is X 1 L 1 , X 1 L 1 X 1 L 1 , or X 1 L 1 X 1 L 1 X 1 L 1 where each X 1 are the same or different, and each L 1 are the same or different.

[0507] In one embodiment, X 1 teeth, [ka] where each R 11 is independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid. 1 teeth, [ka] where each R 11 is independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid.

[0508] In one embodiment, X 1 teeth, [ka] where each R 11 is independently a guanidino or amino group. 1 teeth, [ka] where each R 11 is independently a guanidino or amino group.

[0509] In one embodiment, X 1 teeth, [ka] where each R Z is independently an albumin binder. In some embodiments, L 1 is -NH-, -NHC(O)-, or -C(O)NH-.

[0510] In one embodiment, X 1 teeth, [ka] where each R Z is independently an albumin binder. In some embodiments, L 1 is -NH-, -NHC(O)-, or -C(O)NH-.

[0511] In one embodiment, the linker is X 1 L 1 Wherein X 1 teeth, [ka] where each R 11 is independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid, and L 1 is -NH- or -NHC(O)-.

[0512] In one embodiment, the linker is X 1a L 1a X 1b L 1b Wherein X 1a teeth, [ka] where each R 11 are independently carboxylic acids, sulfonic acids, sulfinic acids, or phosphoric acids; L 1a is -NH- or -NHC(O)-, and X 1b teeth, [ka] where each R Z are independently albumin binders, and L 1b is -NH- or -NHC(O)-. In some embodiments, L 1 is -NH-, -NHC(O)-, or -C(O)NH-.

[0513] In one embodiment, the linker is X 1a L 1a X 1b L 1b Wherein X 1a teeth, [ka] where each R Z are independently albumin binders, and L 1a is -NH- or -NHC(O)-, and X 1b teeth, [ka] where each R 11 is independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid, and L 1b is -NH- or -NHC(O)-. In some embodiments, L 1 is -NH-, -NHC(O)-, or -C(O)NH-.

[0514] In one embodiment, the linker is X 1a L 1a X 1b L 1b Wherein X 1a teeth, [ka] where each R 11 are independently carboxylic acids, sulfonic acids, sulfinic acids, or phosphoric acids; L 1a is -NH- or -NHC(O)-, and X 1b teeth, [ka] where each R Z are independently albumin binders, and L 1 is -NH-, -NHC(O)-, or -C(O)NH-, and L 1b is -NH- or -NHC(O)-.

[0515] In one embodiment, the linker is X 1a L 1a X 1b L 1b Wherein X 1a teeth, [ka] where each R Z are independently albumin binders, and L 1 is -NH-, -NHC(O)-, or -C(O)NH-, and L 1a is -NH- or -NHC(O)-, and X 1b teeth, [ka] where each R 11 is independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid, and L 1b is -NH- or -NHC(O)-.

[0516] In one embodiment, the linker is X 1a L 1a X 1b L 1b X 1c L 1c Wherein X 1ateeth, [ka] And each R Z are independently albumin binders, and L 1 is -NH-, -NHC(O)-, or -C(O)NH-, and L 1a is -NH- or -NHC(O)-, and X 1b is -CH 2 - and L 1b is -NH- or -NHC(O)-, and X 1c teeth, [ka] where each R 11 is independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid, and L 1c is -NH- or -NHC(O)-.

[0517] In one embodiment, the linker is X 1a L 1a X 1b L 1b X 1c L 1c Wherein X 1a teeth, [ka] And each R Z are independently albumin binders, and L 1 is -NH-, -NHC(O)-, or -C(O)NH-, and L 1a is -NH- or -NHC(O)-, and X 1b teeth, [ka] where each R 11 are independently carboxylic acids, sulfonic acids, sulfinic acids, or phosphoric acids; L 1b is -NH- or -NHC(O)-, and X 1c is -CH 2- and L 1c is -NH- or -NHC(O)-.

[0518] In some embodiments of the compounds of Formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2, the linker is R A1f together with a linear or branched peptide linker (Xaa) 1~5 wherein each Xaa is independently selected from a residue of a proteinogenic or non-proteinogenic amino acid, and wherein the amino group within each Xaa is optionally methylated. In one embodiment, the amino group within each Xaa is optionally N-methylated.

[0519] In some embodiments of the compounds of Formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2, the linker is R A1f together with a linear or branched peptide linker (Xaa) 1~5 wherein at least one Xaa is selected from cysteic acid, Glu, Asp, or 2-aminoadipic acid (2-Aad), and wherein the amino group within each Xaa is optionally methylated. In one embodiment, the amino group within each Xaa is optionally N-methylated.

[0520] In some embodiments of the compounds of Formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2, the linker is R A1f together form an amino acid residue selected from cysteic acid, Glu, Asp, or 2-aminoadipic acid (2-Aad), and wherein the amino group in Xaa is optionally methylated. In one embodiment, the amino group in each Xaa is optionally N-methylated.

[0521] In some embodiments of the compounds of Formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2, the linker is R A1f together with a linear or branched peptide linker (Xaa) 1~5wherein at least one Xaa is Dap, Dab, Orn, Arg, hArg, Agb, Agp, Acp, Pip, or N ε ,N ε ,N ε -trimethyl-lysine, and wherein the amino group within each Xaa is optionally methylated. In one embodiment, the amino group within each Xaa is optionally N-methylated.

[0522] In some embodiments of the compounds of Formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2, the linker is R A1f together form an amino acid residue selected from D-Arg, L-Arg, D-hArg, L-hArg, or Pip, and wherein the amino group in Xaa is optionally methylated. In one embodiment, the amino group in each Xaa is optionally N-methylated.

[0523] In some embodiments of the compounds of Formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2, at least one linker is a linear or branched peptide of amino acid residues selected from the proteinogenic and / or non-proteinogenic amino acid residues listed in Table 1.

[0524] In some embodiments of the compound of formula A, AI, A-II, A-III, A-IV, B, or C, two X 1 Each L between groups 1 is methylated or unmethylated, and wherein R X Each L that is connected 1 are independently -S-, -NHC(O)-, -C(O)NH-, -N(CH 3 )C(O)-, -C(O)N(CH 3 )-, [ka] It is.

[0525] In some embodiments, two X1 Each L between groups 1 is the unmethylated amide.

[0526] In some embodiments of the compounds of Formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2, the linker forms a peptide linker of one to three amino acids selected from one or a combination of cysteic acid, Glu, Asp, and / or 2-aminoadipic acid (2-Aad) connected via an amide bond. In some embodiments, the linker forms one amino acid residue selected from cysteic acid, Glu, Asp, or 2-aminoadipic acid (2-Aad). In some embodiments, the linker is a cysteic acid residue.

[0527] In some embodiments, R X Each L that is connected 1 are independently -NHC(O)-, -C(O)NH-, [ka] In some embodiments, R X Each L1 linking is independently -NHC(O)- or -C(O)NH-.

[0528] In some embodiments of the compound of formula A, AI, A-II, A-III, A-IV, B, or C, at least one R X is an albumin binder. In some embodiments, the albumin binder is an albumin binder comprising the linker L 1 and the albumin binder is -(CH 2 ) n2 -CH 3 In the formula, n2 is 8 to 20 or -(CH 2 ) n3 -C(O)OH, where n3 is 8 to 20; or [ka] In the formula, n4=1 to 4, and R 12I, Br, F, Cl, H, OH, OCH 3 , N.H. 2 , NO 2 , or C.H. 3 It is.

[0529] In some embodiments of the compound of formula A, AI, A-II, A-III, A-IV, B, or C, at least one R X is an albumin binder, and the albumin binder is a linker L 1 and the albumin binder is -(CH 2 ) 8~20 -CH 3 , -(CH 2 ) 8~20 -C(O)OH, or [ka] where R 12 I, Br, F, Cl, H, OH, OCH 3 , N.H. 2 , NO 2 , or C.H. 3 In some embodiments, the albumin binder is [ka] where R 12 I, Br, F, Cl, H, OH, OCH 3 , N.H. 2 , NO 2 , or C.H. 3 In some embodiments, the albumin binder is [ka] where R 12 I, Br, Cl, H, OCH 3 , NO 2 , or C.H. 3 It is.

[0530] In some embodiments of a compound of Formula A, AI, A-II, A-III, A-IV, B, or C, the albumin binder is [ka] It is.

[0531] In some embodiments of a compound of Formula A, AI, A-II, A-III, A-IV, B, or C, the albumin binder is [ka] It is.

[0532] In some embodiments of the compound of formula A, AI, A-II, A-III, A-IV, B, or C, at least one R X is a radiolabeled group, or a group that can be radiolabeled (e.g., via a conjugate of a radiometal group or a radiolabeled prosthetic group, or via an isotope-radioisotope exchange reaction).

[0533] In some embodiments of the compounds of Formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2, the compound comprises a first linker that is attached to a radiolabeling group or to a group that can be radiolabeled, and further comprises a second linker that is attached to an albumin binder.

[0534] In some embodiments of compounds of Formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2, the compound comprises a first linker coupled to a first radiolabeled group or a first group that can be radiolabeled and further comprises a second linker coupled to a second radiolabeled group or a second group that can be radiolabeled, and the compound may further comprise an albumin binder coupled to either or both of the first linker and the second linker.

[0535] In some embodiments of the compounds of Formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2, the compounds include only one linker attached to one or two groups that consist of a radiolabeled group and / or a group that can be radiolabeled, and the linker is optionally further attached to an albumin binder.

[0536] In some embodiments of the compounds of Formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2, each group that can be radiolabeled can be independently selected from the group consisting of a metal chelator, trifluoroborate (BF), which can be complexed with a radiometal or a radioisotope-bound metal. 3 )-containing conjugation groups, or conjugation groups containing silicon-fluorine-acceptor moieties, sulfonyl fluorides, or phosphoryl fluorides.

[0537] In some embodiments of the compounds of Formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2, R X is a radioactive metal (e.g. 68 Ga or 177 Lu) or to form complexes with radioisotopes (e.g., Al 18 In some embodiments of the compounds of Formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2, R X is a radioactive metal (e.g. 68 Ga or 177 Lu) or to form complexes with radioisotopes (e.g., Al 18F) is a metal chelator that may be complexed with the metal chelator. The chelator may be any metal chelator suitable for binding to a radiometal or to a metal-containing prosthetic group bound to a radioisotope (e.g., polyaminocarboxylates, etc.). Many suitable chelators are known, for example, as reviewed in Price and Orvig, Chem. Soc. Rev., 2014, 43, 260-290, which is incorporated by reference in its entirety. Non-limiting examples of suitable chelating agents include those selected from the group consisting of DOTA and derivatives, DOTAGA, NOTA, NODAGA, NODASA, CB-DO2A, 3p-C-DEPA, TCMC, DO3A, DTPA and DTPA analogs optionally selected from CHX-A″-DTPA and 1B4M-DTPA, TETA, NOPO, Me-3,2-HOPO, CB-TE1A1P, CB-TE2P, MM-TE2A, DM-TE2A, sarcofagin and SarAr, SarAr-NCS, diamSar, AmBaSar, and BaBaSar, TRAP, AAZTA, DATA and DATA derivatives, H 2 -macropa or its derivatives, H 2 dedpa, H 4 octapa, H 4 py4pa, H 4 Pypa, H 2 azapa, H 5 decapa, and other picolinic acid derivatives, CP256, PCTA, C-NETA, C-NE3TA, HBED, SHBED, BCPA, CP256, YM103, desferoxamine (DFO) and DFO derivatives, and H 6 Illustrative non-limiting examples of suitable chelating agents and exemplary radioisotopes (radiometals) chelated by these chelating agents are shown in Table 3. In an alternative embodiment, R X includes a chelating agent selected from those listed above or in Table 3, or any other suitable chelating agent. One of skill in the art can substitute another chelating agent for any of the chelating agents listed herein.

[0538] [Table 3-1] [Table 3-2] [Table 3-3] [Table 3-4] [Table 3-5] [Table 3-6]

[0539] It will be understood by those of skill in the art how metal chelators, such as those listed in Table 3, can be attached to the linkers or peptides of the present disclosure by replacing one or more atoms or chemical groups of the metal chelator to form a connection. For example, one of the carboxylic acids present in the metal chelator structure can form an amide or ester bond with the linker or peptide. In one embodiment, the bond formed between the linker and the metal chelator is L 1 and the like (for example, if an amide bond attaches the metal chelator to the linker, the definition of L1(-NH-C(O)-) can encompass amides under formula A, AI, A-II, A-III, A-IV, B, or C, even though the carbonyl group can be derived from a metal chelator depicted in Table 3).

[0540] In some embodiments of the compound of Formula A, AI, A-II, A-III, A-IV, B, or C, the compound excludes compounds disclosed in International Patent Application No. PCT / CA2021 / 051486, which is incorporated by reference in its entirety for all purposes. In some embodiments, the compound is cyclo[Phe-(4-NH 2)Phe-Lys(iPr)-D-Arg-2-Nal-Gly-D-Glu]-Lys(iPr)、シクロ[Phe-(4-NO 2 )Phe-Lys(iPr)-D-Arg-2-Nal-Gly-D-Glu]-Lys(iPr)、シクロ[Phe-hTyr-Lys(iPr)-D-Arg-2-Nal-Gly-D-Gl u]-Lys(iPr)、シクロ[Phe-(3-I)Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-D-Glu]-Lys(iPr)、シクロ[Phe-Tyr-Arg(Me) 2(Asymmetry)-D-Arg-2-Nal-Gly-D-Glu]-Lys(iPr), cyclo[Phe-Tyr-Lys(iPr)-D-Arg-(2-Ant)Ala-Gly-D-Glu]-Lys(iPr), cyclo[Phe-Tyr-Lys(iPr)-D-Arg-(9-Ant)Ala-Gly-D-Glu]-Lys(iPr), cyclo[Phe-Tyr-Lys(iPr)-D-Arg-(adamantyl)Ala-Gly-D-Glu]-Lys(iPr), cyclo[Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr), cyclo[Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-His-D-Glu]-Lys(iPr), cyclo[Phe-Tyr-Lys(iPr)-D-Arg-2Nal-His-D-Glu]-Lys(iPr), cyclo[Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Phe-D-Glu]-Lys(iPr), cyclo[Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Leu-D-Glu]-Lys(iPr), cyclo[Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Glu-D-Glu]-Lys(iPr), cyclo[Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Dab-D-Glu]-Lys(iPr), cyclo[Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Dap-D-Glu]-Lys(iPr), cyclo[Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ser-D-Glu]-Lys(iPr), cyclo[Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Gln-D-Glu]-Lys(iPr), cyclo[Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Asn-D-Glu]-Lys(iPr), cyclo[1Nal-Tyr-Lys(iPr)-D-Arg-2Nal-Gly-D-Glu]-Lys(iPr), cyclo[Tyr-Tyr-Lys(iPr)-D-Arg-2Nal-Gly-D-Glu]-Lys(iPr), cyclo[Trp-Tyr-Lys(iPr)-D-Arg-2Nal-Gly-D-Glu]-Lys(iPr),シクロ(イソインドール)[Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-D-Cys]-Lys(iPr) -Lys(iPr)-D-Arg-2-Nal-Gly-Cys]-Lys(iPr)、シクロ[Phe-Tyr-Lys(iPr)-D-Arg-(カルボキシ-m-カルボラララD ap-Gly-D-Glu]-Lys(iPr)、シクロ[Lys(Ac)-Tyr-Lys(iPr)-D-Arg-2Nal-Gly-D-Glu]-Lys(iPr)、シクロ[ Phe-D-Tyr-Lys(iPr)-DArg-2Nal-D-Ala-D-Glu]-Lys(iPr)、シクロ[Phe-Tyr-Lys(iPr)-DArg-(4-NH、 2 )Phe-D-Ala-D-Glu]-Lys(iPr)、シクロ[Phe-Tyr-Lys(iPr)-DArg-hTyr-D-Ala-D-Glu]-Lys(iPr)、シクロ[Phe-Tyr-L ys(iPr)-DArg-(COOH)Phe-D-Ala-D-Glu]-Lys(iPr)、シクロ[Phe-Tyr-Lys(iPr)-DArg-チロニン-D-Ala-D-Glu]-Lys( iPr)、シクロ[Phe-Tyr-Arg(Me)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr)、シクロ[Lys(Ac)-Gln-Lys(iPr)-D-Arg-2Nal -D-Ala-D-Glu]-Lys(iPr)、シクロ[Lys(Ac)-Glu-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr)、シクロ[Phe-(4-NH 2)Phe-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Glu]-Lys(iPr)、シクロ[Lys(Ac)-Tyr-Lys(iPr)-D-Arg-Trp -D-Ala-D-Glu]-Lys(iPr)、シクロ[Lys(D-Glu-Ac)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys( iPr)、シクロ[Lys(Ac-D-Arg)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr)、シクロ[Lys(Ac-D- Arg)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr)、シクロ[Lys(Ac-D-Phe)-Tyr-Lys(iPr)-D -Arg-2Nal-D-Ala-D-Glu]-Lys(iPr)、シクロ[Lys(CysAcid-CysAcid-CysAcid-DOTA-Ga)-Tyr-Lys(i Pr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr)、シクロ[Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]- Lys(iPr)-Lys(Glu-Ac)、シクロ[Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr)-Lys(Ac) 、シクロ[Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr)-Lys(Glu-Glu-Ac)、、クロ[Phe-(4NH 2 )Phe-Lys(iPr)-D-Arg-2Nal-Gly-D-Glu]-Lys(iPr)-Lys(Glu-Glu-Glu-DOTA-Ga)、シクロ[Phe-(4-NH 2)Phe-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr)-Lys(Glu-Glu-Glu-DOTA-Ga). [Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr)-Lys(Glu-Glu-Glu-DOTA-Ga)、 [Phe-hTyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr)-Lys(Glu-Glu-Glu-DOTA- Ga) and silver(synthetic) [Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Cys]-Lys(iPr) and silver(synthetic N.). a -S)[Lys(Cys(Acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr) a -S)[Lys(Cys(Acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)、シクロ(NO 2 -イインールN a -S)[Lys(Cys(Acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)、シクロ(NO 2 -isoindole N a -S)[Lys(Cys(Acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-hCys]-Lys(iPr)、シクロ[Lys(CysAcid 2-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr)、シクロ[Lys(CysAcid-D OTA)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr)、シクロ[Lys(CysAcid-DOTA-G a)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr)、シクロ[Lys(CysAcid-DOTA-Lu) -Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr)、シクロ[Lys(CysAcid-DOTA)-(4-NH 2 )Phe-Lys(iPr)-D-Arg-2Nal-Gly-D-Glu]-Lys(iPr)、シクロ[Lys(CysAcid-DOTA)-(4-NH 2 )Phe-Lys(iPr)-D-Arg-2Nal-Gly-D-Glu]-Lys(iPr)、シクロ[Lys(CysAcid-DOTA)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Asn- D-Glu]-Lys(iPr)、シクロ[Lys(CysAcid-DOTA)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Asn-D-Glu]-Lys(iPr)、シクロ-[Phe-Tyr s(iPr)-D-Arg-2Nal-D-Asn-D-Glu]-Lys(iPr)-Lys(CysAcid-DOTA)、シクロ[Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Asn-D -Glu]-Lys(iPr)-Lys(CysAcid-DOTA)、シクロ[Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Asn-D-Glu]-Lys(iPr)-Lys(CysAcid 2 -DOTA)、シクロ[Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Asn-D-Glu]-Lys(iPr)-Lys(CysAcid 2-DOTA-Ga), cyclo[Lys(CysAcid-amide-N,N-dimethyl-ammoniomethyl-trifluoroborate)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr), cyclo[Lys(CysAcid-triazole-N,N-dimethyl-ammoniomethyl-trifluoroborate)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr), cyclo[Lys(D-Arg-DOTA)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr), cyclo[Lys(D-Arg-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2N al-D-Ala-D-Glu]-Lys(iPr), cyclo[Lys(CysAcid-DOTA)-(3-I)Tyr-Lys(iPr)-D-Arg-2Nal-D-A la-D-Glu]-Lys(iPr), cyclo[Lys(CysAcid-DOTA-Ga)-(3-I)Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala- [Orn(CysAcid-DOTA)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr), cyclo[Orn(CysAcid-DOTA)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr), or cyclo[Dap(CysAcid-DOTA)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr). In some embodiments of the disclosure, the compound comprises a compound of Table 4, or a salt or solvate thereof. In some embodiments, the compound is a complex with a radioisotope.

[0541] In some embodiments of the disclosure, the compound is selected from Table 4, or a salt or solvate thereof. In some embodiments, the compound is a complex with a radioisotope.

[0542] In some embodiments, the compound is selected from BL34L6, BL34L7, BL34L8, BL34L11, BL34N1, BL34P1, BL34L16, BL34L20, Crown-BL34, 3NOPA-BL34L2, BL34T1, BL34L20S, Compound A, Compound B, Compound C, or Compound D, or a salt or solvate thereof. In some embodiments, the compound is a complex with a radioisotope.

[0543] In some embodiments, the compound is 68 Ga]Ga-BL34L6, [ 68 Ga]Ga-BL34L7,[ 177 Lu]Lu-BL34L11, [ 68 Ga]Ga-BL34L16, [ 177 Lu]Lu-BL34L20, [ 68 Ga]Ga-3NOPA-BL34L2, [ 177 Lu]Lu-crown-BL34,[ 68 Ga]Ga-BL34N1, or [ 68 Ga]Ga-BL34T1.

[0544] [Table 4]

[0545] In some embodiments, compounds of the present disclosure include a group that can be radiolabeled. In some embodiments, compounds of the present disclosure include a metal chelator.

[0546] In some embodiments, the compounds of the present disclosure include DOTA as a metal chelator. In some embodiments, the compounds of the present disclosure include DOTA as a metal chelator in a complex with a radioisotope. In one embodiment, the radioisotope is 64 Cu, 67 Cu, 90 Y, 153 Sm, 149 Tb, 152 Tb, 155 Tb, 161 Tb, 177Lu, 225 Ac, 213 Bi, 224 Ra, 212 Bi, 227 Th, 223 Ra, 186 Re, 188 Re, 94m Tc, 68 Ga, 61 Cu, 67 Ga, 99m Tc, 111 In, 44 Sc, 86 Y, 89 Zr, 90 Nb, 117m Sn, 165 Er, 211 At, 203 Pb, 212 Pb, 47 Sc, 166 Ho, 149 Pm, 159 Gd, 105 Rh, 109 Pd, 198 Au, 199 Au, 175 Yb, 142 Pr, or 114m In one embodiment, the radioisotope is 177 Lu, 111 In, 213 Bi, 68 Ga, 67 Ga, 203 Pb, 212 Pb, 44 Sc, 47 Sc, 90 Y, 86 Y, 225 Ac, 117m Sn, 153 Sm, 149 Tb, 152 Tb, 155 Tb, 161 Tb, 165 Er, 224 Ra, 212 Bi, 227 Th, 223 Ra, 64 Cu, or 67 In one embodiment, the radioisotope in the complex with DOTA is68 Ga or 67 It's Ga.

[0547] In some embodiments of the compound of formula A, AI, A-II, A-III, A-IV, B, or C, R of the compound X is a polyaminocarboxylate chelator. In some such embodiments, the chelator is attached via an amide bond. In some embodiments, R X is DOTA or a derivative thereof, TETA or a derivative thereof, SarAr or a derivative thereof, NOTA or a derivative thereof, TRAP or a derivative thereof, HBED or a derivative thereof, 2,3-HOPO or a derivative thereof, PCTA (3,6,9,15-tetraazabicyclo[9.3.1]-pentadeca-1(15),11,13-triene-3,6,9,-triacetic acid) or a derivative thereof, DFO or a derivative thereof, DTPA or a derivative thereof, OCTAPA (N,N'-bis(6-carboxy-2-pyridylmethyl)-ethylenediamine-N,N'-diacetic acid) or a derivative thereof, or H2-MACROPA or a derivative thereof. In some embodiments, R X is DOTA. In some embodiments, R X is a chelator moiety in a complex with a radioisotope X, where X is 64 Cu, 67 Cu, 90 Y, 111 In, 114m In, 117m Sn, 153 Sm, 149 Tb, 152 Tb, 155 Tb, 161 Tb, 177 Lu, 225 Ac, 213 Bi, 224 Ra, 212 Bi, 212 Pb, 227 Th, 223 Ra, 47 Sc, 186 Re, or 188 In some embodiments, X is 177In some embodiments, R X is a chelator moiety in a complex with a radioisotope X, where X is 64 Cu, 68 Ga, 86 Y, 111 In, 94m Tc, 44 Sc, 89 Zr, or 99m In some embodiments, X is 68 It's Ga.

[0548] In some embodiments, the chelator is conjugated to a radioisotope. The conjugated radioisotope is 68 Ga, 61 Cu, 64 Cu, 67 Ga, 99m Tc, 111 In, 44 Sc, 86 Y, 89 Zr, 90 Nb, 177 Lu, 117m Sn, 165 Er, 90 Y, 227 Th, 225 Ac, 213 Bi, 212 Bi, 211 At, 203 Pb, 212 Pb, 47 Sc, 166 Ho, 188 Re, 186 Re, 149 Pm, 159 Gd, 105 Rh, 109 Pd, 198 Au, 199 Au, 175 Yb, 142 Pr, 114m In some embodiments, the chelator is a chelator of Table 3 and the conjugated radioisotope is a radioisotope shown in Table 3 as the binder of the chelator.

[0549] In some embodiments, the chelator is not conjugated to a radioisotope.

[0550] In some embodiments, the chelator is 177 Lu, 111 In, 213 Bi, 68 Ga, 67 Ga, 203 Pb, 212 Pb, 44 Sc, 47 Sc, 90 Y, 86 Y, 225 Ac, 117m Sn, 153 Sm, 149 Tb, 152 Tb, 155 Tb, 161 Tb, 165 Er, 224 Ra, 212 Bi, 227 Th, 223 Ra, 64 Cu or 67 DOTA conjugated with Cu or its derivatives; 225 H2-MACROPA conjugated with Ac, 227 Me-3,2-HOPO conjugated with Th, 225 Ac, 227 Th, or 177 H conjugated with Lu 4 py4pa, 177 H conjugated with Lu 4 pypa, 68 NODAGA conjugated with Ga, 111 DTPA conjugated with In, or 89 This is DFO conjugated with Zr.

[0551] In some embodiments, the chelator is TETA, SarAr, NOTA, TRAP, HBED, 2,3-HOPO, PCTA, DFO, DTPA, OCTAPA, or another picolinic acid derivative.

[0552] In some embodiments, the compounds of the present disclosure include CROWN as a metal chelator. In some embodiments, the compounds of the present disclosure include CROWN as a metal chelator in a complex with a radioisotope. In some embodiments, the radioisotope is 225 In some embodiments, the radioisotope is 227 In some embodiments, the radioisotope is 152 Tb, 155 Tb, 149 Tb, or 161 Tb.

[0553] In some embodiments of the compounds of formula A, AI, A-II, A-III, A-IV, B, or C, R X Examples include mercaptoacetyl, hydrazinonicotinamide, dimercaptosuccinic acid, 1,2-ethylenediylbis-L-cysteine ​​diethyl ester, methylene diphosphonate, hexamethylpropyleneamine oxime, and hexakis(methoxyisobutylisonitrile). 99m Tc, 94m Tc, 186 Re, or 188 In some embodiments, R X is a chelating agent, the chelating agent being mercaptoacetyl, hydrazinonicotinamide, dimercaptosuccinic acid, 1,2-ethylenediylbis-L-cysteine ​​diethyl ester, methylene diphosphonate, hexamethylpropyleneamine oxime, or hexakis(methoxyisobutylisonitrile). In some of these embodiments, the chelating agent is conjugated with a radioisotope. In some such embodiments, the radioisotope is 99m Tc, 94m Tc, 186 Re, or 188 Re.

[0554] In one embodiment of a compound of formula A, AI, A-II, A-III, A-IV, B, or C, Table 2, or a derivative thereof (e.g., when a compound of Table 2 is linked, optionally via a linker, to a radiolabeled group or a group that can be radiolabeled), or Table 4, the radioisotope is 64 Cu, 67 Cu, 90 Y, 153 Sm, 152 Tb, 155 Tb, 149 Tb, 161 Tb, 177 Lu, 225 Ac, 213 Bi, 224 Ra, 212 Bi, 227 Th, 223 Ra, 186 Re, 188 Re, 94m Tc, 68 Ga, 61 Cu, 67 Ga, 99m Tc, 111 In, 44 Sc, 86 Y, 89 Zr, 90 Nb, 117m Sn, 165 Er, 211 At, 203 Pb, 212 Pb, 47 Sc, 166 Ho, 149 Pm, 159 Gd, 105 Rh, 109 Pd, 198 Au, 199 Au, 175 Yb, 142 Pr, or 114m In one embodiment, the radioisotope is 177 Lu, 111 In, 213 Bi, 68 Ga, 67 Ga, 203 Pb, 212 Pb, 44 Sc, 47 Sc, 90 Y, 86Y, 225 Ac, 117m Sn, 153 Sm, 149 Tb, 152 Tb, 155 Tb, 161 Tb, 165 Er, 224 Ra, 212 Bi, 227 Th, 223 Ra, 64 Cu, or 67 It is Cu.

[0555] In one embodiment of the compound of formula A, AI, A-II, A-III, A-IV, B, or C, or of Table 2, or a derivative thereof, or of the compound of Table 4, at least one R X comprises or is complexed with an imaging radioisotope, the compound is bound to a metal chelator which complexes with the imaging radioisotope, or the compound is BF comprising the imaging radioisotope. 3 is attached to a prosthetic group containing

[0556] In one embodiment of the compound of formula A, AI, A-II, A-III, A-IV, B, or C, or of Table 2 or a derivative thereof, or of the compound of Table 4, the imaging radioisotope is 68 Ga, 67 Ga, 61 Cu, 64 Cu, 99m Tc, 114m In, 111 In, 44 Sc, 86 Y, 89 Zr, 90 Nb, 18 F, 131 I, 123 I, 124 I, 152 Tb, 155 Tb, or 72 In one embodiment, the imaging radioisotope is 68 Ga, 67 Ga, 61 Cu, 64 Cu, 99m Tc, 114m In,111 In, 44 Sc, 86 Y, 89 Zr, 90 Nb, 131 I, 123 I, 124 I, or 72 As.

[0557] In one embodiment of the compound of formula A, AI, A-II, A-III, A-IV, B, or C, or a compound of Table 2 or a derivative thereof, or a compound of Table 4, at least one R X The compound contains an imaging radioisotope or is complexed with a therapeutic radioisotope, or the compound is bound to a metal chelator which complexes with a therapeutic radioisotope.

[0558] A compound of formula A, AI, A-II, A-III, A-IV, B, or C, or of Table 2, or a derivative thereof, or a compound of Table 4. In one embodiment, the therapeutic radioisotope is 165 Er, 212 Bi, 211 At, 166 Ho, 149 Pm, 159 Gd, 105 Rh, 109 Pd, 198 Au, 199 Au, 175 Yb, 142 Pr, 177 Lu, 111 In, 213 Bi, 212 Pb, 47 Sc, 90 Y, 117m Sn, 153 Sm, 149 Tb, 161 Tb, 224 Ra, 225 Ac, 227 Th, 223 Ra, 77 As, 131 I, 64 Cu, or 67 It is Cu.

[0559] In some embodiments of the compounds of formula A, AI, A-II, A-III, A-IV, B, or C, R X is, for example, 1,4,7-triazacyclononane-1,4-diacetate (NODA). 18 F-Aluminum fluoride ([ 18 In some embodiments, the chelator is NODA. In some embodiments, the chelator is a chelator capable of binding to [F]AlF). In some embodiments, the chelator is NODA. 18 F]AlF.

[0560] In some embodiments of the compounds of formula A, AI, A-II, A-III, A-IV, B, or C, R X teeth, 72 As or 77 A chelator capable of binding As, such as a trithiol chelate. In some embodiments, the chelator is a trithiol chelate. In some embodiments, the chelator is 72 In some embodiments, the chelator is 77 It is conjugated to As.

[0561] In some embodiments of the compounds of formula A, AI, A-II, A-III, A-IV, B, or C, R X teeth, 18 F / 19 F-exchangeable radiolabeling trifluoroborate (BF 3 ) is a linking group containing such R X The group is the only R X (n1=1), or the first R X An additional R, which may be the same as or different from X The linking group may be added to the -R 13 R 14 BF 3 where R 13 are independently -(CH 2 ) 1~5 - and -R 14 BF 3The groups may be independently selected from one or a combination of those listed in Table 5 (below), Table 6 (below), or [ka] where each R 15 and each R 16 are independently 1 ~C 5 For Tables 5 and 6, -OR, -SR, -NR-, -NHR, or -NR 2 In pyridine substituted with a group, R is C 1 ~C 5 is a branched or straight chain alkyl.

[0562] In some embodiments of the compounds of formula A, AI, A-II, A-III, A-IV, B, or C, or of Table 2 or derivatives thereof, or of the compounds of Table 4, -R 14 BF 3 is selected from those listed in Table 5. In some embodiments, -R 14 BF 3 is independently selected from one or a combination of those listed in Table 6. In some embodiments, at least one fluorine is 18 F. In some embodiments, all three fluorines are 19 It's F.

[0563] [Table 5-1] [Table 5-2]

[0564] [Table 6-1] [Table 6-2]

[0565] In some embodiments, R 14 BF 3 teeth, [ka] [ka] where -OR, -SR, -NR-, -NHR, or -NR 2 In pyridines substituted with R (if present) is a branched or straight chain C 1 ~C 5 In some embodiments, R is a branched or straight chain C alkyl. 1 ~C 5 In some embodiments, R is a saturated alkyl. In some embodiments, R is methyl. In some embodiments, R is ethyl. In some embodiments, R is propyl. In some embodiments, R is isopropyl. In some embodiments, R is n-butyl. In some embodiments, one fluorine is 18 F. In some embodiments, all three fluorines are 19 It's F.

[0566] In some embodiments, R 14 BF 3 teeth, [ka] [ka] where -OR, -SR, -NR-, or -NR 2 In pyridines substituted with R (if present) is a branched or straight chain C 1 ~C 5 In some embodiments, R is a branched or straight chain C alkyl. 1 ~C 5In some embodiments, R is a saturated alkyl. In some embodiments, R is methyl. In some embodiments, R is ethyl. In some embodiments, R is propyl. In some embodiments, R is isopropyl. In some embodiments, R is n-butyl. In some embodiments, -R 14 BF 3 teeth, [ka] In some embodiments, one fluorine is 18 F. In some embodiments, all three fluorines are 19 It's F.

[0567] In some embodiments, -R 14 BF 3 teeth, [ka] In some embodiments, R 15 is methyl. In some embodiments, R 15 is ethyl. In some embodiments, R 15 is propyl. In some embodiments, R 15 is isopropyl. In some embodiments, R 15 is butyl. In some embodiments, R 15 is n-butyl. In some embodiments, R 15 is pentyl. In some embodiments, R 16 is methyl. In some embodiments, R 16 is ethyl. In some embodiments, R 16 is propyl. In some embodiments, R 16 is isopropyl. In some embodiments, R 16 is butyl. In some embodiments, R 16 is n-butyl. In some embodiments, R 16 is pentyl. In some embodiments, R15 and R 16 In some embodiments, at least one fluorine is 18 F. In some embodiments, all three fluorines are 19 It's F.

[0568] In some embodiments of the compounds of formula A, AI, A-II, A-III, A-IV, B, or C, R X is a prosthetic group containing a silicon-fluorine-acceptor moiety. In some embodiments, the fluorine of the silicon-fluorine acceptor moiety is 18 F. The conjugated group containing the silicon-fluorine-acceptor moiety is [ka] wherein R 17 and R 18 are independently linear or branched, cyclic or acyclic, and / or aromatic or non-aromatic C 1 ~C 10 In some embodiments, R 17 and R 18 is independently selected from the group consisting of phenyl, tert-butyl, sec-propyl, isopropyl, methyl, pyridyl, 2-indolyl, and 3-indolyl. [ka] In some embodiments, the prosthetic group is [ka] In some embodiments, the prosthetic group is [ka] In some embodiments, the prosthetic group is [ka] In some embodiments, the conjugating group is a heteroarylated group, exemplified, but not limited to, by the following: [ka] In this formula, R is hydrogen, alkyl, or aryl.

[0569] In some embodiments of the compounds of formula A, AI, A-II, A-III, A-IV, B, or C, R X is a therapeutic moiety, including any chemical moiety capable of producing a therapeutic effect, such as a small molecule drug.

[0570] In some embodiments of the compounds of formula A, AI, A-II, A-III, A-IV, B, or C, R X is a fluorescent label.

[0571] The present disclosure also relates to compositions comprising any one of the compounds of formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2 or derivatives thereof, or the compounds of Table 4 described herein.

[0572] In some embodiments of the compound of formula A, the compound is [ka] [ka] [ka] [ka] [ka] or a salt or solvate thereof. In some embodiments, the compound is complexed with a radioisotope.

[0573] In some embodiments of the compound of formula A, the compound is [ka] or a salt or solvate thereof. In some embodiments, the compound is complexed with a radioisotope.

[0574] In some embodiments of the compound of formula B, the compound is [ka] or a salt or solvate thereof. In some embodiments, the compound is complexed with a radioisotope.

[0575] In some embodiments of the compound of formula C, the compound is [ka] [ka] [ka] or a salt or solvate thereof. In some embodiments, the compound is complexed with a radioisotope.

[0576] How to use The present disclosure also relates to a compound of formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2, or a derivative thereof, or any one of the compounds of Table 4, as described herein, for use in imaging CXCR4 expressing tissue in a subject, or for use in imaging an inflammatory condition or disease. In one embodiment, the compound comprises at least one R X which includes or is complexed with an imaging radioisotope, the compound being bound to a metal chelator which complexes with the imaging radioisotope, or the compound being BF which includes an imaging radioisotope. 3In one embodiment, the imaging radioisotope is attached to a prosthetic group containing 68 Ga, 67 Ga, 61 Cu, 64 Cu, 99m Tc, 114m In, 111 In, 44 Sc, 86 Y, 89 Zr, 90 Nb, 18 F, 131 I, 123 I, 124 I, 152 Tb, 155 Tb, or 72 In one embodiment, the imaging radioisotope is 68 Ga, 67 Ga, 61 Cu, 64 Cu, 99m Tc, 114m In, 111 In, 44 Sc, 86 Y, 89 Zr, 90 Nb, 131 I, 123 I, 124 I, or 72 As.

[0577] The present disclosure also relates to a method of imaging CXCR4 expressing tissue, the method comprising administering to a subject in need of such imaging an effective amount of any one of the compounds of formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2 or derivatives thereof, or the compounds of Table 4, as described herein. In one embodiment, the compound comprises at least one R X which includes or is complexed with an imaging radioisotope, the compound being bound to a metal chelator which complexes with the imaging radioisotope, or the compound being BF which includes an imaging radioisotope. 3 In one embodiment, the imaging radioisotope is attached to a prosthetic group containing 68 Ga, 67 Ga, 61 Cu,64 Cu, 99m Tc, 114m In, 111 In, 44 Sc, 86 Y, 89 Zr, 90 Nb, 18 F, 131 I, 123 I, 124 I, 152 Tb, 155 Tb, or 72 In one embodiment, the imaging radioisotope is 68 Ga, 67 Ga, 61 Cu, 64 Cu, 99m Tc, 114m In, 111 In, 44 Sc, 86 Y, 89 Zr, 90 Nb, 131 I, 123 I, 124 I, or 72 As.

[0578] The present disclosure also relates to any one of the compounds of formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2 or derivatives thereof, or the compounds of Table 4 described herein, for use in treating a disease or condition characterized by expression of CXCR4 in a subject. In one embodiment, the disease or condition is a cancer that expresses CXCR4. In one embodiment, the compound comprises at least one R X which comprises an imaging radioisotope, or the compound is complexed with a therapeutic radioisotope, or the compound is bound to a metal chelator to which the therapeutic radioisotope is complexed. In one embodiment, the therapeutic radioisotope is 165 Er, 212 Bi, 211 At, 166 Ho, 149 Pm, 159 Gd, 105 Rh, 109 Pd, 198 Au, 199 Au,175 Yb, 142 Pr, 177 Lu, 111 In, 213 Bi, 212 Pb, 47 Sc, 90 Y, 117m Sn, 153 Sm, 149 Tb, 161 Tb, 224 Ra, 225 Ac, 227 Th, 223 Ra, 77 As, 131 I, 64 Cu, or 67 It is Cu.

[0579] The present disclosure also relates to a method of treating a disease or condition characterized by expression of CXCR4, comprising administering to a subject in need of treatment an effective amount of any one of the compounds of formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2 or derivatives thereof, or the compounds of Table 4, as described herein. In one embodiment, the disease or condition is a cancer that expresses CXCR4. In one embodiment, the compound comprises at least one R X which comprises an imaging radioisotope, or the compound is complexed with a therapeutic radioisotope, or the compound is bound to a metal chelator to which the therapeutic radioisotope is complexed. In one embodiment, the therapeutic radioisotope is 165 Er, 212 Bi, 211 At, 166 Ho, 149 Pm, 159 Gd, 105 Rh, 109 Pd, 198 Au, 199 Au, 175 Yb, 142 Pr, 177 Lu, 111 In, 213 Bi, 212 Pb, 47 Sc, 90 Y, 117m Sn, 153 Sm,149 Tb, 161 Tb, 224 Ra, 225 Ac, 227 Th, 223 Ra, 77 As, 131 I, 64 Cu, or 67 It is Cu.

[0580] In some embodiments, a compound of Formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2, or a derivative thereof, or a compound of Table 4, has an IC of 50 nM or less. 50 In some embodiments, the compound inhibits SDF-1α binding to CXCR4 in vitro with an IC of 25 nM or less. 50 In some embodiments, the compound inhibits SDF-1α binding to CXCR4 in vitro with an IC of 10 nM or less. 50 and inhibits SDF-1α binding to CXCR4 in vitro.

[0581] Overexpression of CXCR4 has been observed in more than 23 types of malignancies, including brain, breast, and prostate cancer. In addition, leukemia, lymphoma, and myeloma have significant CXCR4 expression. Retrospective studies have shown that CXCR4 expression correlates with decreased survival in prostate and melanoma patients. In addition, CXCR4 expression is a prognostic factor for disease recurrence in acute and chronic myeloid leukemia, acute myeloid leukemia, and multiple myeloma. The SDF-1 / CXCR4 axis mediates cancer growth, enhances metastasis, recruits stromal and immune cells to support malignant growth, and confers chemoresistance. Radiolabeled CXCR4 probes can be used for early diagnosis of solid and hematological malignancies that express CXCR4. These imaging agents can be used to confirm the diagnosis of malignancies or to guide local ablative treatment if the disease is localized. Such ligands may also be used to monitor response to therapy by providing an independent assessment of the residual cellular content of tumors known to overexpress CXCR4. 68Ga]Ga-Pentixafor has been used by Wester's group for cancer imaging to identify potential responders to internal radiation therapy.

[0582] Dysregulation of the SDF-1 / CXCR4 axis also mediates several inflammatory conditions. In rheumatoid arthritis (RA), SDF-1 / CXCR4 signaling is involved in the proinflammatory migration of activated T cells to sites of inflammation, and specifically, the synovium of RA patients showed the presence of T cells with increased expression of CXCR4. Given the burden of RA on the population in terms of morbidity and mortality, there has been a significant amount of research into the development of therapeutic agents that mediate the inflammatory response, and in particular, novel biologics have been approved by the FDA in the past few years. Radiolabeled CXCR4 probes for positron emission tomography imaging will enable the diagnosis and prediction of rheumatoid arthritis and will also be used to monitor the therapy of new disease-modifying antirheumatic drugs in clinical trials. CXCR4 expression is associated with a high incidence of inflammatory disease in diseases with inflammatory components, including infectious bone disease, urinary tract infections as a complication after kidney transplantation, myocardial infarction, and ischemic stroke. 68 It has been detected by PET imaging using [Ga]Ga-Pentixafor. Imaging of CXCR4 may play an important role in the diagnosis and monitoring of other inflammatory diseases in the future.

[0583] In the context of cardiac pathology, inflammatory disease of the cardiovascular wall is mediated in part by dysregulation of the SDF-1 / CXCR4 axis. In early atherosclerosis, the SDF-1 / CXCR4 axis recruits endothelial progenitor cells towards sites of peripheral vascular injury, thereby initiating plaque formation, although there is some evidence for an antiatherogenic effect. Atherosclerotic plaques are characterized by the presence of hypoxia, which has been shown to upregulate CXCR4 expression and affect cell trafficking. Finally, in a rabbit model of atherosclerosis, [ 68 In this study, [Ga]Ga-Pentixafor enabled visualization of atherosclerotic plaques by PET. 68Using [Ga]Ga-Pentixafor, atherosclerotic plaques were identified in patients with a history of atherosclerosis. Thus, PET diagnostic agents targeting CXCR4 are potentially viable as an alternative method to diagnose and obtain prognostic information regarding atherosclerosis.

[0584] In some embodiments, the disease or condition characterized by the expression of CXCR4 is leukemia, lymphoma, and myeloma.In some embodiments, the disease or condition characterized by the expression of CXCR4 is hematological malignancy.In some embodiments, the disease or condition characterized by the expression of CXCR4 is inflammatory disease.In some embodiments, the inflammatory disease is atherosclerosis.

[0585] In some embodiments, the disease or condition characterized by expression of CXCR4 is a cardiovascular disease.

[0586] In some embodiments, the disease or condition characterized by expression of CXCR4 is a disease or condition characterized by overexpression of CXCR4 or aberrant expression of CXCR4.

[0587] In some embodiments, the CXCR4-expressing cancer is a hematological malignancy. In some embodiments, the CXCR4-expressing cancer is a leukemia, lymphoma, or myeloma.

[0588] In certain embodiments, the compound of formula A, AI, A-II, A-III, A-IV, B, or C is conjugated to a radioisotope for positron emission tomography (PET) or single photon emission computed tomography (SPECT) imaging of tissues expressing CXCR4, or for imaging of inflammatory conditions or diseases (e.g., rheumatoid arthritis or cardiovascular disease), and the compound is conjugated to a radioisotope that is a positron emitter or a gamma emitter. Without limitation, the positron or gamma emitting radioisotope is 68 Ga, 67Ga, 61 Cu, 64 Cu, 99m Tc, 110m In, 111 In, 44 Sc, 86 Y, 89 Zr, 90 Nb, 18 F, 131 I, 123 I, 124 I or 72 It can be As.

[0589] When the radioisotope (e.g., X) is a diagnostic radioisotope, the use of certain embodiments of the compounds for the preparation of radiolabeled tracers for imaging is disclosed. Also disclosed is a method of imaging a tissue expressing CXCR4 or an inflammatory condition or disease in a subject, comprising administering to the subject a composition comprising a compound of certain embodiments and a pharma- ceutically acceptable excipient, and imaging the subject, for example, using positron emission tomography (PET). When the tissue is a diseased tissue (e.g., a CXCR4-expressing cancer), then a CXCR4-targeted therapy can be selected to treat the subject. Thus, the use of certain compounds of the present invention in imaging a CXCR4-expressing cancer in a subject is disclosed, and R X contains or is complexed with a diagnostic or imaging radioisotope. In some embodiments, the subject is a human.

[0590] Considering the widespread expression of CXCR4 in cancer, there has been great progress in the development of CXCR4-targeted therapeutics. CXCR4 inhibitors have shown efficacy in mouse tumor models, but very few drugs have shown efficacy in clinical trials, either in treating tumors or preventing metastasis. Plerixafor, also known as AMD3100, originally developed for the treatment of HIV, is the only CXCR4 antagonist approved by the FDA to date. AMD3100 is administered to lymphoma and multiple myeloma patients to mobilize hematopoietic stem cells into the peripheral blood for collection and autologous transplantation rather than as a direct method of treatment. There is an unmet clinical need to treat cancers that express CXCR4, many of which are resistant to currently available standard therapies.

[0591] Cancers that are CXCR4 positive may be sensitive to internal radiotherapy. In this application, peptides targeting CXCR4 are radiolabeled with radioisotopes, usually beta or alpha particle emitters, to deliver high localized doses of radiation to the lesion. These radioactive emissions usually cause DNA damage, thereby inducing cell death. This therapy is utilized in oncology, where somatostatin receptors (for neuroendocrine tumors) and prostate-specific membrane antigen (for metastatic castration-resistant prostate cancer) are two examples. Unlike external beam radiotherapy, this systemic treatment can also be effective in the metastatic setting. Therapeutic radioisotopes include: 177 Lu, 90 Y, 225 Ac, and 64 These include, but are not limited to, Cu.

[0592] Regarding cardiac pathology, 90 Y]Y-Pentixather or [ 177 A small retrospective study using internal radiotherapy with [Lu]Lu-Pentixather demonstrated regression of CXCR4 expression and activity in patients with previously identified atherosclerotic plaques. Thus, radionuclide therapy may present a novel therapeutic pathway for inflammatory diseases such as atherosclerosis.

[0593] In certain embodiments, the compound of formula A, AI, A-II, A-III, A-IV, B, or C is conjugated to a radioisotope for use in therapy (e.g., cancer therapy). 165 Er, 212 Bi, 211 At, 166 Ho, 149 Pm, 159 Gd, 105 Rh, 109 Pd, 198 Au, 199 Au, 175 Yb, 142 Pr, 177 Lu(β-emitter, t 2 / 1 =6.65d), 111 In, 213 Bi, 212 Pb, 47 Sc, 90 Y(β-emitter, t 2 / 1 =2.66d), 117m Sn, 153 Sm, 149 Tb, 161 Tb, 224 Ra, 225 Ac(α-emitter, t 2 / 1 =9.95d), 227 Th, 223 Ra, 77 As, 131 I, 64 Cu, or 67 These include radioactive isotopes such as Cu.

[0594] When the radioisotope (e.g., X) is a therapeutic radioisotope, the use of certain embodiments of the compound (or pharmaceutical composition thereof) for the treatment of a disease or condition characterized by the expression of CXCR4 in a subject is disclosed. Accordingly, the use of the compound in the preparation of a medicament for treating a disease or condition characterized by the expression of CXCR4 in a subject is provided. Also provided is a method of treating a disease or condition characterized by the expression of CXCR4 in a subject, comprising administering to the subject a composition comprising a compound of formula A, AI, A-II, A-III, A-IV, B, or C, or a salt or solvate thereof, and a pharma- ceutically acceptable excipient. For example, but not limited to, the disease can be a CXCR4-expressing cancer (e.g., non-Hodgkin's lymphoma, lymphoma, multiple myeloma, leukemia, adrenocortical carcinoma, lung cancer, breast cancer, renal cell carcinoma, colorectal cancer). Accordingly, the use of certain compounds of the present invention for the treatment of a CXCR4-expressing cancer in a subject is disclosed, and R X comprises or is complexed with a therapeutic radioisotope. In some embodiments, the subject is a human. Manufacturing method

[0595] The compounds presented herein incorporate peptides, which may be synthesized by any of a variety of methods established in the art, including, but not limited to, solution and solid phase peptide synthesis using 9-fluorenylmethoxycarbonyl (Fmoc) and / or t-butyloxycarbonyl (Boc) chemistries, and / or other synthetic approaches.

[0596] Solid phase peptide synthesis methods and techniques are well established in the art. For example, a peptide can be synthesized by sequentially incorporating the desired amino acid residues one at a time. In such methods, peptide synthesis typically begins with coupling the C-terminal amino acid of the peptide of interest to a suitable resin. Prior to this, the reactive side chain and alpha amino group of the amino acid are protected from reaction by suitable protecting groups, allowing only the alpha carboxyl group to react with functional groups such as amine, hydroxyl, or alkyl halide groups on the solid support. After coupling the C-terminal amino acid to the support, the protecting groups on the side chain and / or alpha amino group of the amino acid are selectively removed to allow coupling of the next amino acid of interest. This process is repeated until the desired peptide is fully synthesized, at which point the peptide can be deprotected, cleaved from the support, and purified. A non-limiting example of an instrument for solid phase peptide synthesis is the Aapptec Endeavor 90 peptide synthesizer.

[0597] To allow the coupling of further amino acids, the Fmoc protecting group can be removed from the amino acid on the solid support under mildly basic conditions, such as piperidine (20-50% v / v) in DMF. The amino acid to be added must also be activated for coupling (e.g., at the alpha carboxylate). Non-limiting examples of activators include, but are not limited to, 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU), 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU), 2-(7-aza-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU), benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP), benzotriazol-1-yl-oxy-tris(pyrrolidino)phosphonium hexafluorophosphate (PyBOP). Racemization is minimized by using triazoles such as 1-hydroxy-benzotriazole (HOBt) and 1-hydroxy-7-aza-benzotriazole (HOAt). Coupling may be carried out in the presence of a suitable base such as N,N-diisopropylethylamine (DIPEA / DIEA). For long peptides or if desired, peptide synthesis and ligation may be used.

[0598] Apart from the formation of a typical peptide bond to extend a peptide, the peptide can be extended in a branched manner by coupling to a side chain functional group (e.g., a carboxylic acid group or an amino group), either side chain to side chain or side chain to amino or carboxylate of the backbone. Coupling to amino acid side chains can be performed by any known method and can be performed on resin or without resin. Non-limiting examples include forming amides between an amino acid side chain containing a carboxyl group (e.g., Asp, D-Asp, Glu, D-Glu, Aad, etc.) and an amino acid side chain containing an amino group (e.g., Lys, D-Lys, Orn, D-Orn, Dab, D-Dab, Dap, D-Dap, etc.) or the peptide N-terminus, forming amides between an amino acid side chain containing an amino group (e.g., Lys, D-Lys, Orn, D-Orn, Dab, D-Dab, Dap, D-Dap, etc.) and either an amino acid side chain containing a carboxyl group (e.g., Asp, D-Asp, Glu, D-Glu, etc.) or the peptide C-terminus, and ... azide group (e.g., Lys(N 3 ), D-Lys(N 3) and the formation of 1,2,3-triazoles via click chemistry between amino acid side chains containing aryl groups (e.g., Pra, D-Pra, etc.) and alkyne groups (e.g., Pra, D-Pra, etc.). While protecting groups on the appropriate functional groups must be selectively removed prior to amide bond formation, the reaction between alkyne groups and azide groups via click reaction to form 1,2,3-triazoles does not require selective deprotection. Non-limiting examples of selectively removable protecting groups include 2-phenylisopropyl ester (O-2-PhiPr) (e.g., on Asp / Glu), as well as 4-methyltrityl (Mtt), allyloxycarbonyl (alloc), 1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene))ethyl (Dde), and 1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-3-methylbutyl (ivDde) ​​(e.g., on Lys / Orn / Dab / Dap). The O-2-PhiPr and Mtt protecting groups can be selectively deprotected under mildly acidic conditions, such as 2.5% trifluoroacetic acid (TFA) in DCM. The Alloc protecting group can be selectively deprotected using tetrakis(triphenylphosphine)palladium(0) and phenylsilane in DCM. The Dde and ivDde protecting groups can be selectively deprotected using 2-5% hydrazine in DMF. The deprotected side chains of Asp / Glu (L or D) and Lys / Orn / Dab / Dap (L or D) can then be coupled, for example, by using the coupling reaction conditions described above.

[0599] Compounds of formula A, AI, A-II, A-III, and A-IV can be cyclized by linking the peptide N-terminus to the side chain carboxylate (at residue 7 of the peptide) using the techniques described above (exemplary reaction conditions are described in the Examples). Compounds of formula B can be cyclized using an intracyclic tryptathionine stapling reaction or an isoindole stapling reaction, termed FICk. 21The side chains of residues at positions 1 and 7 in the peptide can be linked (exemplary reaction conditions are described in the Examples) and the resulting isoindole will image with unique fluorescent properties. Compounds of formula C can be similarly cyclized using, for example, a thiolactic amino acid at residue 1 in the peptide, as shown in the following scheme: [ka]

[0600] The amide of the peptide backbone may be N-methylated (i.e., alpha aminomethylation). This may be accomplished by directly using Fmoc-N-methylated amino acids during peptide synthesis. Alternatively, N-methylation under Mitsunobu conditions may be performed. First, the free primary amine group is protected using 4-nitrobenzenesulfonyl chloride (Ns-Cl) and 2,4,6-trimethylpyridine (collidine) in NMP. N-methylation may then be achieved in the presence of triphenylphosphine, diisopropyl azodicarboxylate (DIAD), and methanol. N-deprotection may then be performed using mercaptoethanol and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in NMP. HATU, HOAt, and DIEA may be used to couple the protected amino acid to the N-methylated alpha amino group.

[0601] Thioether (-S-) bond formation (e.g., L 1(vs. ) can be accomplished either on the solid phase or in solution phase. For example, the formation of a thioether (-S-) bond can be achieved by coupling a thiol-containing compound (such as a thiol group on a cysteine ​​side chain) with an alkyl halide (such as 3-(Fmoc-amino)propyl bromide) in a suitable solvent (such as N,N-dimethylformamide) in the presence of a base (such as N,N-diisopropylethylamine). When the reaction is carried out in solution phase, the reactants used are preferably in equivalent molar ratios (1:1), and the desired product can be purified by flash column chromatography or high performance liquid chromatography (HPLC). When the reaction is carried out on the solid phase, i.e., one reactant is bound to the solid phase, the other reactant is usually used in excess (3 or more equivalents of the reactant bound to the solid phase). After the reaction, excess unreacted reactants and reagents can be removed by sequentially washing the solid phase (resin) using a combination of solvents such as, for example, N,N-dimethylformamide, methanol, and dichloromethane.

[0602] Formation of a bond between a thiol group and a maleimide group (e.g., L 1 (vs. ) can be carried out using the conditions described above for the formation of thioether (-S-) bonds, simply by replacing the alkyl halide with a maleimide-containing compound. Similarly, this reaction can be carried out on the solid phase or in solution phase. When the reaction is carried out in solution phase, the reactants used are preferably in equivalent molar ratios (1:1), and the desired product can be purified by flash column chromatography or high performance liquid chromatography (HPLC). When the reaction is carried out on the solid phase, i.e., one reactant is bound to the solid phase, the other reactant is usually used in excess (3 or more equivalents of the reactant bound to the solid phase). After the reaction, excess unreacted reactants and reagents can be removed by sequentially washing the solid phase (resin) using a combination of solvents such as, for example, N,N-dimethylformamide, methanol, and dichloromethane.

[0603] A non-peptide moiety (e.g., a radiolabel group, an albumin binding group, and / or a linker) can be coupled to the peptide N-terminus while the peptide is attached to a solid support. This is facilitated when the non-peptide moiety contains an activated carboxylate (and optionally a protecting group), allowing the coupling to be performed on the resin. By way of example and not limitation, a bifunctional chelator such as 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) tris(tert-butyl ester) can be activated in the presence of N-hydroxysuccinimide (NHS) and N,N'-dicyclohexylcarbodiimide (DCC) and coupled to the peptide. Alternatively, the non-peptide moiety may be incorporated into the compound via a copper-catalyzed click reaction under either solution-phase or solid-phase conditions. The copper-catalyzed click reaction is well established in the art. For example, 2-azidoacetic acid is first activated by NHS and DCC and coupled to the peptide. The alkyne-containing non-peptide moiety is then reacted with Cu in water and organic solvents such as acetonitrile (ACN) and DMF. 2+ and sodium ascorbate. Non-peptide moieties may also be added in the solution phase, which is quite commonly done.

[0604] The synthesis of chelating agents is well known, and many chelating agents are commercially available (e.g., from Sigma-Aldrich™ / Milipore Sigma™, etc.). Protocols for conjugating radiometals to chelating agents are also well known (e.g., see Example 1 below). The synthesis of silicon-fluorine-acceptor moieties can be achieved according to previously reported procedures (e.g., Bernard-Gauthier et al. Biomed Res Int. 2014 2014:454503; Kostikov et al. Nature Protocols 2012 7:1956-1963; Kostikov et al. Bioconjug Chem. 2012 18:23:106-114, each of which is incorporated by reference in its entirety). The synthesis or acquisition of radioisotope-substituted aryl groups is similarly easy.

[0605] R on the compound 13 R 14 BF 3 Synthesis of the elements can be accomplished according to previously reported procedures (e.g., Liu et al. Angew Chem Int Ed 2014 53:11876-11880; Liu et al. J Nucl Med 2015 55:1499-1505; Liu et al. Nat Protoc 2015 10:1423-1432; Kuo et al., J Nucl Med 2019 60:1160-1166, each of which is incorporated by reference in its entirety). Generally, this BF 3 The containing motif is BF on the linker. 3 By forming a 1,2,3-triazole ring between the containing azide (or alkynyl) group and the alkynyl (or azide) group, or by forming a BF 3 It can be coupled to a linker via click chemistry by forming an amide bond between the containing carboxylate and amino groups. 3To generate the boronic ester-containing azide, alkyne, or carboxylate, first, the boronic ester-containing azide, alkyne, or carboxylate was reacted with HCl, DMF, and KHF. 2 The boronic acid ester BF in a mixture of 3 It is prepared by conversion of alkyl to BF 3 For aryl BF, a boronic ester-containing azide, alkyne, or carboxylate can be prepared by coupling a boronic ester-containing alkyl halide (such as iodomethylboronic acid pinacol ester) with an amine-containing azide, alkyne, or carboxylate (such as N,N-dimethylpropargylamine). 3 For , the boronic ester can be prepared via Suzuki coupling using an aryl halide (iodine or bromide) and bis(pinacolato)diboron.

[0606] 18 F- 19 BF by F isotope exchange reaction 3 Compounds contained 18 F-fluorination can be achieved according to previously published procedures (Liu et al. Nat Protoc 2015 10:1423-1432, incorporated by reference in its entirety). Generally, about 100 nmol of BF 3 The compound was dissolved in 15 μl of pyridazine-HCl buffer (pH = 2.0-2.5, 1 M), 15 μl of DMF, and 1 μl of 7.5 mM KHF. 2 Dissolves in the aqueous mixture. 18 F-fluoride solution (60 μl in saline) is added and the resulting solution is heated for 20 min at 80° C. At the end of the reaction, the desired product can be purified by solid phase extraction or by reversed-phase high performance liquid chromatography (HPLC) using a mixture of water and acetonitrile as the mobile phase.

[0607] Once the peptide is fully synthesized on the solid support, the desired peptide can be cleaved from the solid support using a suitable reagent such as TFA, triisopropylsilane (TIS), and water. At the same time, side chain protecting groups such as Boc, pentamethyldihydrobenzofuran-5-sulfonyl (Pbf), trityl (Trt), and tert-butyl (tBu) are removed (i.e., deprotected). The crude peptide can be precipitated and recovered from the solution by adding cold ether followed by centrifugation. Purification and characterization of the peptide can be performed by standard separation techniques such as high performance liquid chromatography (HPLC) based on the size, charge, and polarity of the peptide. The characteristics of the purified peptide can be confirmed by mass spectrometry or other similar approaches.

[0608] The invention is further illustrated in the following examples for the synthesis and evaluation of specific compounds. EXAMPLES

[0609] chemical synthesis experiment :

[0610] Reagents and solvents were purchased from commercial sources and used without further purification unless otherwise stated. Peptides were synthesized on a Liberty Blue automated microwave peptide synthesizer (CEM Corporations) or a PurePep Chorus GT (Gyros Protein Technologies). High performance liquid chromatography (HPLC) was performed on (1) an Agilent 1260 Infinity system equipped with a Model 1200 quaternary pump, a Model 1200 UV absorbance detector, and a Bioscan NaI scintillation detector, (2) an Agilent 1100 HPLC system, or (3) an Agilent 1260 Infinity II preparative system equipped with a Model 1260 Infinity II preparative binary pump, a Model 1260 Infinity variable wavelength detector (set at 220 nm), and a 1290 Infinity II preparative Open-Bed fraction collector. The HPLC columns used for the synthesis were semi-preparative (Agilent Eclipse XDB-C18, 5 μm, 9.4×250 mm) or preparative (Gemini, NX-C18, 5 μm, 110 Å, 50×30 mm) columns purchased from Phenomenex. Mass spectrometry was performed using an AB SCIEX 4000 QTRAP mass spectrometer system equipped with an ESI ion source or a Waters 2695 separation module and a Waters Micromass ZQ mass spectrometer system.

[0611] Synthesis of BL34L6 [ka]

[0612] On a 0.1 mmol scale, Rink Amide Protide resin was deprotected with 20% piperidine-DMF (3 mL) at 90° C. (1 min) and then washed with DMF (3 mL×3). Fmoc-Lys(iPr,Boc)-OH (5 eq, 0.5 mmol, 0.2 M in DMF) was then coupled at 90° C. (4 min) using 1 M DIC / 1 M Oxyma (1 mL / 0.5 mL) in DMF, followed by Fmoc deprotection as described above. Fmoc-D-Glu(OAll)-OH, Fmoc-D-Ala-OH (x2), Fmoc-2-Nal-OH (x2), Fmoc-D-Arg(Pbf)-OH (x2), Fmoc-Lys(iPr,Boc)-OH, Fmoc-Tyr(tBu)-OH (x2), and Fmoc-Lys(ivDde)-OH were sequentially coupled in a similar manner. The -OAll (allyloxy) group was converted to phenylalanine by the addition of Pd(PPh 3 ) 4 / phenylsilane (0.25 / 15 equiv.) (35 °C, 6 min, ×2), followed by Fmoc deprotection. Cyclization was performed with HATU / HOAt / DIPEA (1 / 1 / 2 equiv.) at 75 °C (12 min, ×3). The ivDde group was removed with 2% hydrazine in DMF (3 mL, room temperature, 5 min, ×5). Fmoc-cysteic acid and Fmoc-Lys(ivDde)-OH were coupled as described above. The synthesis continued with the coupling of DOTA (4 equiv.) using HATU / HOAt / DIPEA (4 / 4 / 8 equiv.), followed by deprotection of ivDde, and coupling of 4-(4-methoxyphenyl)butanoic acid using HATU / HOAt / DIPEA (4 / 4 / 8 equiv.). The peptide was chromatographed in TFA / TIP / H2O at 35 °C for 3 h. 2 The crude peptide was cleaved from the resin with HO / phenol (90 / 2.5 / 2.5 / 5%). The crude peptide was precipitated in cold diethyl ether, washed with ether (x2), and purified with HO / phenol (90 / 2.5 / 2.5 / 5%). 2 The crude peptide was lyophilized in a mixture of solvent A:H2O / MeCN. 2 O / 0.1% TFA, and B:MeCN / 0.1% TFA at 4.5 mL / min (31% B over 20 min, t R= 7.189 min) and purified on a semi-preparative HPLC column. The sample was lyophilized to a white solid. Mass calculated (M+H + ): 2026.08 m / z; Measured value (M+3H + ) / 3:676.21 m / z.

[0613] Synthesis of BL34L7 [ka]

[0614] On a 0.1 mmol scale, Rink Amide Protide resin was deprotected with 20% piperidine-DMF (3 mL) at 90° C. (1 min) and then washed with DMF (3 mL×3). Fmoc-Lys(iPr,Boc)-OH (5 eq, 0.5 mmol, 0.2 M in DMF) was then coupled at 90° C. (4 min) using 1 M DIC / 1 M Oxyma (1 mL / 0.5 mL) in DMF, followed by Fmoc deprotection as described above. Fmoc-D-Glu(OAll)-OH, Fmoc-D-Ala-OH (x2), Fmoc-2-Nal-OH (x2), Fmoc-D-Arg(Pbf)-OH (x2), Fmoc-Lys(iPr,Boc)-OH, Fmoc-Tyr(tBu)-OH (x2), and Fmoc-Lys(ivDde)-OH were sequentially coupled in a similar manner. The -OAll group was converted to phenylalanine by the addition of Pd(PPh 3 ) 4 / phenylsilane (0.25 / 15 equiv.) (35 °C, 6 min, ×2), followed by Fmoc deprotection. Cyclization was performed with HATU / HOAt / DIPEA (1 / 1 / 2 equiv.) at 75 °C (12 min, ×3). The ivDde group was removed with 2% hydrazine in DMF (3 mL, room temperature, 5 min, ×5). Fmoc-Lys(ivDde)-OH and Fmoc-cysteic acid were coupled as described above. The synthesis continued with the coupling of DOTA (4 equiv.) using HATU / HOAt / DIPEA (4 / 4 / 8 equiv.), followed by deprotection of ivDde, and coupling of 4-(4-methoxyphenyl)butanoic acid with HATU / HOAt / DIPEA (4 / 4 / 8 equiv.). The peptide was chromatographed in TFA / TIP / H at 35 °C for 3 h. 2 The crude peptide was cleaved from the resin with HO / phenol (90 / 2.5 / 2.5 / 5%). The crude peptide was precipitated in cold diethyl ether, washed with ether (x2), and purified with HO / phenol (90 / 2.5 / 2.5 / 5%). 2 The crude peptide was lyophilized in a mixture of solvent A:H2O / ACN. 2 O / 0.1% TFA, and B:MeCN / 0.1% TFA at 4.5 mL / min (31% B over 20 min, t R = 6.796 min) and purified on a semi-preparative HPLC column. The sample was lyophilized to a white solid. Calculated mass (M+H + ): 2026.08 m / z; Measured value (M+3H) 3+ / 3:676.21m / z.

[0615] Synthesis of BL34L8 [ka]

[0616] On a 0.1 mmol scale, Rink Amide Protide resin was deprotected with 20% piperidine-DMF (3 mL) at 90° C. (1 min) and then washed with DMF (3 mL×3). Fmoc-Lys(Mtt)-OH (5 eq, 0.5 mmol, 0.2 M in DMF) was then coupled twice at 75° C. (12 min) using HATU / HOAt / DIPEA (5 / 5 / 10 eq). The resin was deprotected with 20% piperidine-DMF (3 mL) at 90° C. (1 min) and then washed with DMF (3 mL×3). Fmoc-Lys(iPr,Boc)-OH (5 equiv., 0.5 mmol, 0.2 M in DMF) was then coupled at 90° C. (4 min) using 1 M DIC / 1 M Oxyma in DMF (1 mL / 0.5 mL) followed by Fmoc deprotection as described above. Fmoc-D-Glu(OAll)-OH, Fmoc-D-Ala-OH (×2), Fmoc-2-Nal-OH (×2), Fmoc-D-Arg(Pbf)-OH (×2), Fmoc-Lys(iPr,Boc)-OH, Fmoc-Tyr(tBu)-OH (×2), and Fmoc-Lys(ivDde)-OH were sequentially coupled in a similar manner. The -OAll group was converted to phenylalanine using Pd(PPh 3 ) 4 / phenylsilane (0.25 / 15 equiv.) (35°C, 6 min, x2), followed by Fmoc deprotection. Cyclization was carried out with HATU / HOAt / DIPEA (1 / 1 / 2 equiv.) at 75°C (12 min, x3). The ivDde group was removed with 2% hydrazine in DMF (3 mL, room temperature, 5 min, x5). Fmoc-cysteic acid was coupled as described above. After Fmoc deprotection, DOTA (4 equiv.) was coupled using HATU / HOAt / DIPEA (4 / 4 / 8 equiv.). The Mtt protecting group was then removed with 2% TFA in DCM (4 mL, room temperature, 2 min, x8) and washed with DCM (3 mL x5) and DMF (4 mL x5). The resin was neutralized with 10% DIPEA in DMF (5 mL, 5 min, twice) before coupling of 4-(4-methoxyphenyl)butanoic acid. The peptide was chromatographed in TFA / TIP / H at 35° C. for 3 h. 2The crude peptide was cleaved from the resin with HO / phenol (90 / 2.5 / 2.5 / 5%). The crude peptide was precipitated in cold diethyl ether, washed with ether (x2), and purified with HO / phenol (90 / 2.5 / 2.5 / 5%). 2 The crude peptide was lyophilized in a mixture of solvent A:H2O / MeCN. 2 O / 0.1% TFA, and B:MeCN / 0.1% TFA at 4.5 mL / min (31% B over 20 min, t R = 5.827 min) and purified on a semi-preparative HPLC column. Calculated mass (M+H + ): 2026.08 m / z; Measured value (M+3H) 3+ / 3:676.41m / z.

[0617] Synthesis of BL34L11 [ka]

[0618] On a 0.1 mmol scale, Rink Amide Protide resin was deprotected with 20% piperidine-DMF (3 mL) at 90° C. (1 min) and then washed with DMF (3 mL×3). Fmoc-Lys(iPr,Boc)-OH (5 eq, 0.5 mmol, 0.2 M in DMF) was then coupled at 90° C. (4 min) using 1 M DIC / 1 M Oxyma (1 mL / 0.5 mL) in DMF, followed by Fmoc deprotection as described above. Fmoc-D-Glu(OAll)-OH, Fmoc-D-Ala-OH (x2), Fmoc-2-Nal-OH (x2), Fmoc-D-Arg(Pbf)-OH (x2), Fmoc-Lys(iPr,Boc)-OH, Fmoc-Tyr(tBu)-OH (x2), and Fmoc-Lys(ivDde)-OH were sequentially coupled in a similar manner. The -OAll group was converted to phenylalanine by the addition of Pd(PPh 3 ) 4 / phenylsilane (0.25 / 15 equiv.) (35 °C, 6 min, ×2), followed by Fmoc deprotection. Cyclization was performed with HATU / HOAt / DIPEA (1 / 1 / 2 equiv.) at 75 °C (12 min, ×3). The ivDde group was removed with 2% hydrazine in DMF (3 mL, room temperature, 5 min, ×5). Fmoc-Lys(ivDde)-OH and Fmoc-cysteic acid were coupled as described above. The synthesis continued with the coupling of DOTA (4 equiv.) using HATU / HOAt / DIPEA (4 / 4 / 8 equiv.), followed by ivDde deprotection and coupling of 4-(4-iodophenyl)butanoic acid with HATU / HOAt / DIPEA (4 / 4 / 8 equiv.). The peptide was chromatographed in TFA / TIP / H2O at 35 °C for 3 h. 2 The crude peptide was cleaved from the resin with HO / phenol (90 / 2.5 / 2.5 / 5%). The crude peptide was precipitated in cold diethyl ether, washed with ether (x2), and purified with HO / phenol (90 / 2.5 / 2.5 / 5%). 2 The crude peptide was lyophilized in a mixture of solvent A:H2O / MeCN. 2 O / 0.1% TFA, and B: MeCN / 0.1% TFA at 30 mL / min (31% B over 15 min, t R = 8.617 min) and purified by preparative HPLC. The sample was lyophilized to a white solid. Calculated mass (M+H + ): 2121.96 m / z; Measured value (M+2H) 2+ / 2:1061.98m / z.

[0619] Synthesis of Compound A [ka] MT16-145-L-Hpi Compound A

[0620] Synthesis of MT16-145-L-Hpi : MBHA Rink Amide (0.04 mmol) resin was solvated in 3 mL of DMF and N 2 The resin was mixed by bubbling for 20 min and then drained. The resin was resuspended in 3 mL of 20% piperidine-DMF and N 2The resin was mixed by bubbling at 50° C. for 1 min, the solution was drained, and the process was repeated with a fresh 3 mL portion of DMF. The resin was washed three times with 3 mL portions of DMF (N 2 The resin was initially loaded by bubbling with 500 ml of DMF containing Fmoc-Xaa-OH (100 mM), HCTU (100 mM), N-methyl-morpholine (200 mM) along with at least 7.5 equivalents of amino acid and coupling agent. The resin suspended in the coupling solution was then heated at 50° C. for 5 min with N 2 The mixture was mixed by bubbling with N at 50 °C for 50 min with the exception of the Fmoc-Aza-Xaa-OH dipeptide, which was mixed with N 2 The Fmoc-Hpi-OH was mixed by bubbling with N at room temperature for 1 h. 2 The resin was washed with 3 mL portions of DMF (×3) (N 2 After the last coupling, the resin was then washed with 3 mL portions of DCM (×4) (N 2 The resin was then mixed by bubbling with N 2 The resin was dried by running DMF over it for 20 min. The resin was manually suspended in 5 mL of DMF in the synthesizer and dried over N 2 The resin was mixed and Fmoc deprotected on the synthesizer by bubbling with 500 ml of DCM for 20 min, then washed with DMF (×3). A solution of 74.1 mg of Fmoc-β-Ala-OH, 102.2 mg of COMU, and 0.12 mL of DIEA in 1 mL of DMF was added to the reaction vessel and bubbled for approximately 1-1.5 h. A fresh coupling solution was prepared every hour. This process was repeated three times, resulting in a total reaction time of 5.5 h. After the final round of coupling, the resin was washed with DCM (×4) and dried on the peptide synthesizer for 20 min. The resin-bound linear peptide was manually suspended in 5 mL of DMF on the synthesizer and bubbled with N for 20 min. 2 The mixture was mixed by bubbling with 500 ml of water. Fmoc was deprotected by treatment with 20% piperidine-DMF (3 mL) and N 2The resin was washed with DMF (x3). The resin was mixed in the synthesizer with 1:2:2 Ac for 30 min. 2 The resin was incubated with 5 mL of 200 / EtOAc / collidine, then washed with DMF (x3), then with DCM (x4), and then dried for 20 min. The dried resin was stirred overnight in a round bottom flask with 2 mL of TFA. The next morning, the resin was stirred with 50 μL of TIS and 50 μL of HO until the bright yellow color disappeared. 2 The TFA was filtered into a 15 mL Falcon tube and Et 2 Triturate in 2024 (x3), dry the pellet under air, and then centrifuge in 2024 with 0.1% FA. 2 Dissolved in O / MeCN and eluted in H2O containing 0.1% FA on a 50 x 21 mm column. 2 Purification was performed by HPLC on a C18 with gradient elution using O / MeCN. Pure fractions were collected, frozen and lyophilized. The pure peptide was purified by HPLC using solvent A:H 2 The reinjections were performed using A: MeCN / 0.1% FA, and B: MeCN / 0.1% FA, which were performed on an Agilent Eclipse XDDC18 C18 column (9.4 × 250 mm) with 95% H2O containing 0.1% FA for 0–32 min. 2 O to 65%H 2 in 25% H2O, then in 65% H2O containing 0.1% FA for 32–35 min. 2 The elution was performed with 2 mL / min of 0 (t R = 23.362 min). LRMS-ESI (m / z): C 68 H 98 N 16 O 11 S(M+2H) 2+ / 2 Calculated value 673.4 m / z, measured value 673.7 m / z.

[0621] Synthesis of Compound A From the synthesis of MT16-145-L-Hpi, after addition of Fmoc-β-Ala-OH, Fmoc was deprotected by treatment with 20% piperidine-DMF (3 mL) to give N 2Mix by bubbling with 50 μL TIS and 50 μL H2O until the bright yellow color disappears. The resin is washed with DMF (×3). Fmoc-cysteic acid and then DOTA are coupled at 4 / 4 / 8 equiv. using HATU and DIEA in DMF at room temperature. The dry resin is stirred overnight in a round bottom flask with 2 mL TFA. The next morning, add 50 μL TIS and 50 μL H2O until the bright yellow color disappears. 2 Add EtO. Filter the TFA into a 15 mL Falcon tube and add 2 Triturate with O (×3) and allow the pellet to dry in air.

[0622] Synthesis of Compound B [ka] MT16-133-D-Hpi Compound B

[0623] Synthesis of MT16-145-D-Hpi From the synthesis of MT16-145-L-Hpi, instead of Fmoc-L-Hpi, Fmoc-D-Hpi-OH was used, 2 The mixture was mixed at room temperature for 1 hour by bubbling with 1 mL of DMF. The resin was washed with 3 mL of DMF (×3) (N 2 After the last coupling, the resin was then washed with 3 mL portions of DCM (×4) (N 2 The resin was mixed by bubbling with N 2 The resin was manually suspended in 5 mL of DMF on the synthesizer and dried by flushing with N 2 The mixture was mixed for 20 min with bubbling at 25°C. Fmoc was deprotected on the synthesizer and then washed with DMF (×3). 74.1 mg Fmoc-β-Ala-OH, 102.2 mg COMU in 1 mL DMF, and 0.12 mL DIEA were added to the reaction vessel and bubbled for approximately 1-1.5 h. A fresh coupling solution was made every hour. This was repeated three times, resulting in a total reaction time of 5.5 h. After the final round of coupling, the resin was washed with DCM (×4) and dried on the peptide synthesizer for 20 min. The resin-bound linear peptide was manually suspended in 5 mL DMF on the synthesizer and bubbled with N for 20 min.2 The mixture was mixed by bubbling with 500 ml of water. Fmoc was deprotected by treatment with 20% piperidine-DMF (3 mL) and N 2 The resin was washed with DMF (x3). The resin was mixed in the synthesizer with 1:2:2 Ac for 30 min. 2 The resin was incubated with 5 mL of 200 / EtOAc / collidine, then washed with DMF (x3), then with DCM (x4), and then dried for 20 min. The dried resin was stirred overnight in a round bottom flask with 2 mL of TFA. The next morning, the resin was stirred with 50 μL of TIS and 50 μL of HO until the bright yellow color disappeared. 2 The TFA was filtered into a 15 mL Falcon tube and Et 2 Triturate in 2024 (x3), dry the pellet under air, and then centrifuge in 2024 with 0.1% FA. 2 Dissolved in O / MeCN and eluted in H2O containing 0.1% FA on a 50 x 21 mm column. 2 Purification was performed by HPLC on a C18 with gradient elution using O / MeCN. Pure fractions were collected, frozen and lyophilized. The pure peptide was purified by HPLC using solvent A:H 2 The reinjections were performed using A: MeCN / 0.1% FA, and B: MeCN / 0.1% FA, which were run on an Agilent Eclipse XDDC18 C18 column (9.4 × 250 mm) with 95% H2O containing 0.1% FA for 0–32 min. 2 O to 65%H 2 2H2O, then 65–0% HO containing 0.1% FA for 32–35 min. 2 The elution was performed with 2 mL / min of 0 (t R = 24.171 min). LRMS-ESI (m / z): C 68 H 98 N 16 O 11 S(M+2H) 2+ / 2 Calculated value 673.4 m / z, measured value 673.6 m / z.

[0624] Synthesis of Compound B From the synthesis of MT16-145-D-Hpi, after addition of Fmoc-β-Ala-OH, Fmoc was deprotected by treatment with 20% piperidine-DMF (3 mL), and N 2The resin is washed with DMF (x3). Fmoc-cysteic acid and then DOTA are coupled at room temperature using HATU and DIEA in DMF at 4 / 4 / 8 equiv. The dry resin is stirred overnight in a round bottom flask with 2 mL of TFA. The next morning, 50 μL of TIS and 50 μL of HO are added until the bright yellow color disappears. 2 Add EtO. Filter the TFA into a 15 mL Falcon tube. 2 The mixture was triturated with O (×3) and the pellet was dried under air.

[0625] Synthesis of BL34N1 [ka]

[0626] On a 0.2 mmol scale, Fmoc-Rink Amide MBHA resin (Iris GMBH, 0.08 mmol / g) was deprotected twice with 20% v / v piperidine in DMF for 30 min at room temperature and washed 7 times with 3 mL of DMF. Fmoc-Lys(iPr,Boc)-OH was then conjugated to the resin using 4 / 8 / 4 equivalents of Fmoc-AA-OH / DIC / Oxyma in DMF for 1 h. The resin was washed 7 times with 3 mL of DMF after each deprotection. The Fmoc group was removed with 20% v / v piperidine in DMF for 25 min. Fmoc-D-Glu(OAll)-OH, Fmoc-D-Ala (x2), Fmoc-2-NaI-OH (x2), Fmoc-D-Arg(Pbf)-OH (x2), and Fmoc-Lys(iPr,Boc)-OH were sequentially coupled to the peptidyl resin following a similar procedure.

[0627] Resin (0.15 mmol) was dissolved in CH 2 Cl 2 The resin was treated with o-nitrobenzenesulfonyl chloride (3 equiv.) and 2,4,6-collidine (5 equiv.) in 0.1 M at room temperature for 2 h. After washing the resin (CH 2 Cl 2x 3, DMF x 3, and THF x 3), a suspension of N-Ns protected resin in anhydrous THF (0.1 M) was added with MeOH (5 equiv.), PPh 3 (5 equiv.), and diethyl diazodicarboxylate (5 equiv.) were added at 0° C. The mixture was shaken at room temperature for 2 h, and then the resin was washed (THF×3 and CHCl 3 ×3). The N-methylated resin was treated with DBU (5 eq.) and 2-mercaptoethanol (10 eq.) at room temperature for 1.5 h to give a protected peptide resin with an N-methyl amino acid at the N-terminus. HATU and 1-hydroxy-7-azabenzotriazole (HOAt) were used for coupling of Fmoc amino acids to N-methyl amino acids. The Fmoc group was deprotected by treatment with 20% (v / v) piperidine-DMF for 20 min. In this case, it was Fmoc-Tyr(tBu)-OH. Fmoc-Lys(ivDde)-OH (×2) was sequentially coupled to the peptidyl resin using 4 / 8 / 4 eq. of Fmoc-AA-OH / DIC / Oxyma in DMF and shaken for 1 h. The -OAll protecting group on D-Glu was deprotected with Pd(PPh 3 ) 4 (30 mg) / phenylsilane (450 μL) was used (4 × 25 min, room temperature). The N on Lys(ivDde) ​​was then removed. a -Fmoc was removed and cyclization was carried out using DIC / HOBt in DMF (2 x 2 h at room temperature). After cyclization, 3 mL of 2% N in DMF was added for 10 min for 4 cycles. 2 H 4 The ivDde group was removed by adding Fmoc-cysteic acid followed by DOTA(tBu) 3 was coupled at room temperature using HATU and DIEA in DMF at 4 / 4 / 8 equivalents. The peptide was then eluted in TFA / TIS / H 92.5 / 2.5 / 2.5 for 5 hours at room temperature. 2The peptides were simultaneously deprotected and cleaved from the resin by treatment with a cocktail of 0.25% TFA. After filtration, the TFA was removed in vacuo and the peptides were precipitated by the addition of cold diethyl ether. The crude peptides were first washed with 0.1% TFA in 0.25% H2O for 0–7 min. 2 The mixture was eluted with 5% MeCN in O, then 5 to 35% MeCN for 7-8 min, then 35 to 100% MeCN for 8-9 min at a flow rate of 15 mL / min (t R = 5.167 min) and purified by semi-preparative HPLC using a semi-preparative column. 80 H 126 N 20 O 21 S calculated mass: [M+2H] 2+ / 2: 868.5 m / z; Measured value [M+2H] 2+ / 2:869.0m / z.

[0628] Synthesis of BL34P1 [ka]

[0629] After removal of the Fmoc group of Fmoc-D-Arg-OH on a 0.05 mmol scale from the synthesis of BL34N1, the resin was coupled twice with 4 / 8 / 4 equivalents of Fmoc-D-Ala-OH / DIC / Oxyma in DMF for 1 h at room temperature. After coupling of Fmoc-D-Ala-OH, the Fmoc group was removed with 20% v / v piperidine in DMF for 25 min and the resin was washed seven times before being eluted with CH 2 Cl 2 The resin was treated with o-nitrobenzenesulfonyl chloride (3 equiv.) and 2,4,6-collidine (5 equiv.) in 0.1 M at room temperature for 2 h. After washing the resin (CH 2 Cl 2 x 3, DMF x 3, and THF x 3), a suspension of N-Ns protected resin in anhydrous THF (0.1 M) was treated with tBu-(4-hydroxybutyl)(isopropyl)carbamate (5 equiv.), PPh 3(5 equiv.), and diethyl diazodicarboxylate (5 equiv.) were added at 0° C. The mixture was shaken at room temperature for 2 h, and then the resin was washed (THF×3 and CHCl 3 ×3). This cycle was repeated three times for complete alkylation. The N-alkylated resin was treated with DBU (5 eq.) and 2-mercaptoethanol (10 eq.) at room temperature for 1.5 h to give a protected peptide resin with an N-methyl amino acid at the N-terminus. HATU and HOAt were used for coupling of Fmoc amino acids to N-methyl amino acids. The Fmoc group was deprotected by treatment with 20% (v / v) piperidine-DMF for 20 min. In this case it was Fmoc-Tyr(tBu)-OH. Fmoc-Lys(ivDde)-OH (×2) was sequentially coupled to the peptidyl resin using 4 / 8 / 4 eq. of Fmoc-AA-OH / DIC / Oxyma in DMF and shaken for 1 h. The -OAll protecting group on D-Glu was deprotected with Pd(PPh) in DCM (5 mL). 3 ) 4 (10 mg) / phenylsilane (150 μL) was used (4 × 25 min, room temperature). The N on Lys(ivDde) ​​was then removed. a -Fmoc was removed and cyclization was carried out using DIC / HOBt in DMF (2 x 2 h at room temperature). After cyclization, 3 mL of 2% N in DMF was added for 10 min for 4 cycles. 2 H 4 The ivDde group was removed by adding Fmoc-cysteic acid-OH, followed by DOTA(tBu) 3 was coupled at room temperature using HATU and DIEA in DMF at 4 / 4 / 8 equivalents. The peptide was then eluted in TFA / TIS / H 92.5 / 2.5 / 2.5 for 5 hours at room temperature. 2 The peptide was simultaneously deprotected and cleaved from the resin by treatment with a cocktail solution of O. After filtration, the TFA was removed in vacuo and the peptide was precipitated by the addition of cold diethyl ether.

[0630] The crude peptides were eluted with 5% acetonitrile in water containing 0.1% TFA for 0–7 min, then with 5 to 35% acetonitrile for 7–8 min, then with 35–100% acetonitrile for 8–9 min at a flow rate of 15 mL / min (t R =5.478 min) and purified by semi-preparative HPLC using a semi-preparative column. ESI-MS: BL34P1, C 81 H 128 N 20 O 21 Calculated value of SNaK [M+Na+K] 2+ / 2 906.1m / z; Measured value [M+Na+K] 2+ / 2 906.6m / z.

[0631] Synthesis of BL34L16 [ka]

[0632] On a 0.1 mmol scale, Rink Amide Protide resin was deprotected with 20% piperidine-DMF (3 mL) at 90° C. (1 min) and then washed with DMF (3 mL×3). Fmoc-Lys(iPr,Boc)-OH (5 eq, 0.5 mmol, 0.2 M in DMF) was then coupled at 90° C. (4 min) using 1 M DIC / 1 M Oxyma (1 mL / 0.5 mL) in DMF, followed by Fmoc deprotection as described above. Fmoc-D-Glu(OAll)-OH, Fmoc-D-Ala-OH (x2), Fmoc-2-Nal-OH (x2), Fmoc-D-Arg(Pbf)-OH (x2), Fmoc-Lys(iPr,Boc)-OH, Fmoc-Tyr(tBu)-OH (x2), and Fmoc-Lys(ivDde)-OH were sequentially coupled in a similar manner. The -OAll group was removed with Pd(PPh3)4 / phenylsilane (0.25 / 15 equiv.) (35°C, 6 min, x2), followed by Fmoc deprotection. Cyclization was carried out with HATU / HOAt / DIPEA (1 / 1 / 2 equiv.) at 75°C (12 min, x3). The ivDde group was removed with 2% hydrazine in DMF (3 mL, room temperature, 5 min, x5). Fmoc-Lys(ivDde)-OH and Fmoc-cysteic acid were coupled as described above. The synthesis continued with the coupling of DOTA (4 equiv.) using HATU / HOAt / DIPEA (4 / 4 / 8 equiv.), followed by ivDde deprotection and coupling of 4-(4-chlorophenyl)butanoic acid using HATU / HOAt / DIPEA (4 / 4 / 8 equiv.). The peptide was incubated for 3 h at 35° C. with TFA / TIP / H. 2 The crude peptide was cleaved from the resin with HO / phenol (90 / 2.5 / 2.5 / 5%). The crude peptide was precipitated in cold diethyl ether, washed with ether (x2), and purified with HO / phenol (90 / 2.5 / 2.5 / 5%). 2 The crude peptide was lyophilized in a mixture of solvent A:H2O / MeCN. 2Purified by preparative HPLC using B: MeCN / 0.1%TFA and C: O / 0.1%TFA at 30 mL / min (20% to 40% B over 15 min, tR=7.82 min). The sample was lyophilized to a white solid. Calculated mass (M+H+): 2030.03 m / z; Found (M+3H)3+ / 3: 677.81 m / z.

[0633] Synthesis of compounds C and D [ka]

[0634] Compounds C and D can be made following the exemplary synthetic route outlined above for BL34L16.

[0635] Synthesis of BL34L20 [ka]

[0636] On a 0.1 mmol scale, Rink Amide Protide resin was deprotected with 20% piperidine-DMF (3 mL) at 90° C. (1 min) and then washed with DMF (3 mL×3). Fmoc-Lys(iPr,Boc)-OH (5 eq, 0.5 mmol, 0.2 M in DMF) was then coupled at 90° C. (4 min) using 1 M DIC / 1 M Oxyma (1 mL / 0.5 mL) in DMF, followed by Fmoc deprotection as described above. Fmoc-D-Glu(OAll)-OH, Fmoc-D-Ala-OH (x2), Fmoc-2-Nal-OH (x2), Fmoc-D-Arg(Pbf)-OH (x2), Fmoc-Lys(iPr,Boc)-OH, Fmoc-Tyr(tBu)-OH (x2), and Fmoc-Lys(ivDde)-OH were sequentially coupled in a similar manner. The -OAll group was removed with Pd(PPh3)4 / phenylsilane (0.25 / 15 equiv.) (35°C, 6 min, x2), followed by Fmoc deprotection. Cyclization was carried out with HATU / HOAt / DIPEA (1 / 1 / 2 equiv.) at 75°C (12 min, x3). The ivDde group was removed with 2% hydrazine in DMF (3 mL, room temperature, 5 min, x5). Fmoc-Lys(ivDde)-OH and Fmoc-cysteic acid were coupled as described above. The synthesis continued with attachment of DOTA (4 equiv.) using HATU / HOAt / DIPEA (4 / 4 / 8 equiv.), followed by ivDde deprotection and coupling of 4-(4-bromophenyl)butanoic acid with HATU / HOAt / DIPEA (4 / 4 / 8 equiv.). The peptide was incubated for 3 h at 35° C. with TFA / TIP / H. 2 The crude peptide was cleaved from the resin with HO / phenol (90 / 2.5 / 2.5 / 5%). The crude peptide was precipitated in cold diethyl ether, washed with ether (x2), and purified with HO / phenol (90 / 2.5 / 2.5 / 5%). 2 The crude peptide was lyophilized in a mixture of solvent A:H2O / MeCN. 2Purified by preparative HPLC using O / 0.1% TFA, and B: MeCN / 0.1% TFA, 30 mL / min (25% to 35% B over 15 min, tR=6.00 min). The sample was lyophilized to a white solid. Calculated mass (M+H+): 2073.98 m / z; Found (M+2H)2+ / 2: 1038.29 m / z.

[0637] Synthesis of Crown-BL34 [ka]

[0638] On a 0.05 mmol scale, Rink Amide Protide resin was deprotected by treating the resin with 20% piperidine in DMF (3 x 8 min). Fmoc-Lys(iPr,Boc)-OH was then attached to the resin, followed by coupling of Fmoc-D-Glu(OAll)-OH, Fmoc-D-Ala-OH, Fmoc-2-Nal-OH, Fmoc-D-Arg(Pbf)-OH, Fmoc-Lys(iPr,Boc)-OH, Fmoc-Tyr(tBu)-OH, and Fmoc-Lys(ivDde)-OH via solid-phase peptide synthesis using Fmoc-based chemistry. All couplings were performed in DMF using Fmoc-protected amino acids (4 equiv.), HATU (4 equiv.), and DIEA (7 equiv.). The -OAll group was removed with Pd(PPh3)4 / phenylsilane (0.25 / 24 equiv.) (30 min, ×2) followed by Fmoc deprotection. Cyclization was performed with HATU / HOAt / DIPEA (3 / 3 / 6 equiv.) and coupled for 12 h. The ivDde group was removed with 2% hydrazine in DMF (5 × 5 min). Fmoc-cysteic acid was coupled as described above. The synthesis continued with the coupling of crown(tBu)3 (4 equiv.) using HATU / DIPEA (4 / 7 equiv.). The peptide was then deprotected and simultaneously cleaved from the resin by treatment with 95 / 5 trifluoroacetic acid (TFA) / triisopropylsilane (TIS) for 2 h at room temperature. After filtration, the peptide was precipitated by adding cold diethyl ether to the TFA solution. The crude peptide was purified by HPLC using a semi-preparative column. HPLC conditions were 13% acetonitrile in trace metals water with 0.1% formic acid at a flow rate of 4.5 mL / min. Retention time was 9.7 min. The eluate containing the desired peptide was collected, pooled and lyophilized. Calculated mass (M+H+): 1809.96 m / z; Found (M+2H). 2+ / 2:905.72m / z.

[0639] Synthesis of 3NOPA-BL34L2 [ka] [ka] Scheme: Flick procedure for 3-NOPA-BL34L2

[0640] Flick and Gallium Chelation: Approximately 2 μmol of crude peptide (lyophilized, in a 15 mL Falcon tube) was dissolved in 400 μL of 2 M HEPES (pH 9) and 80 μL of 3-NOPA in EtOH (0.05 M) was added. The solution was allowed to react overnight at room temperature. The reaction mixture was then diluted with 1 M HCl. (水溶液) Acidify the solution to pH 4 with 300 μL of Ga(NO) in 1 M HCl. 2 ) 3 (0.0282M) was added (pH approx. 3) and then transferred to a scintillation vial and heated in a microwave at 20% power for 1 min. The entire reaction mixture was then directly purified by RP-HPLC using Method A (below).

[0641] Flick only: 4 μmol of pure peptide dissolved in 1 mL of borate buffer (pH approx. 9.5), 120 uL of 0.05 M 3-NOPA in EtOH was added, the reaction was vortexed and allowed to react for 4 h at room temperature, 10 μL of formic acid was then added and the entire reaction mixture was directly purified by RP-HPLC using method A.

[0642] Reinject the following pure peptides:

[0643] LRMS(C 86 H 124 GaN 21 O 22 S 2 ):(M+2H) 2+ / 2 Measured value: 969.8, Calculated value: 969.4(1 13 In the case of C)

[0644] HPLC retention time: (Method A) 27.6 minutes

[0645] Method A: 15 mL / min, 50 x 21 mm C18, Solvent A: H with 0.1% formic acid 2Solvent B: MeCN containing 0.1% formic acid

[0646] 0-7.5 minutes: 95:5 A / B to 65:35 A / B

[0647] 7.5 to 8.0 minutes: 65:35 A / B to 0:1 A / B

[0648] 8.0 minutes to 9.5 minutes is 0:1 A / B

[0649] HPLC Method B: 2 mL / min, 9.4 x 250 mm C18, Solvent A: H with 0.1% formic acid 2 O, Solvent B: MeCN with 0.1% formic acid.

[0650] 0-12 minutes: 80:20 A / B to 60:40 A / B

[0651] From 12 minutes to 15 minutes, the ratio changes from 60:40 A / B to 0:1 A / B.

[0652] 15-20 minutes: 0:1 A / B

[0653] 20 minutes to 23 minutes: 0:1 A / B to 80:20 A / B

[0654] 23 minutes to 29 minutes is 80:20 A / B

[0655] Synthesis of BL34T1 [ka]

[0656] On a 0.05 mmol scale, Rink Amide Protide resin was deprotected by treating the resin with 20% piperidine in DMF (3 × 8 min). Fmoc-Lys(iPr,Boc)-OH was then attached to the resin, followed by coupling of Fmoc-D-Glu(OAll)-OH, Fmoc-D-Ala-OH, Fmoc-2-Nal-OH, Fmoc-D-Arg(Pbf)-OH, Fmoc-Lys(iPr,Boc)-OH, Fmoc-Tyr(tBu)-OH, and Fmoc-Lys(ivDde)-OH via solid-phase peptide synthesis using Fmoc-based chemistry. All couplings were performed in DMF using Fmoc-protected amino acids (4 equiv.), HATU (4 equiv.), and DIEA (7 equiv.). The -OAll group was converted to 1,2-dichlorophenyl ether (Pd(PPh 3 ) 4 / phenylsilane (0.25 / 24 equiv.) (30 min, ×2) followed by Fmoc deprotection. Cyclization was performed with HATU / HOAt / DIPEA (3 / 3 / 6 equiv.) and coupling for 12 h. The ivDde group was removed with 2% hydrazine in DMF (5 × 5 min). Fmoc-Lys(ivDde)-OH, Fmoc-GlyOH, and p-chloro 4-phenylbutyric acid were then coupled to this sequence as described above. After selective removal of the ivDde protecting group with 2% hydrazine in DMF (5 × 5 min), Fmoc-cysteic acid was coupled to the Lys side chain. Crown(tBu) using HATU / DIPEA (4 / 7 equiv.) 3 The synthesis continued with the coupling of (4 equiv.). The peptide was then deprotected and simultaneously cleaved from the resin by treatment with 95 / 5 trifluoroacetic acid (TFA) / triisopropylsilane (TIS) for 2 h at room temperature. After filtration, the peptide was precipitated by adding cold diethyl ether to the TFA solution. The crude peptide was purified by HPLC using a semi-preparative column. The HPLC conditions were 28% acetonitrile with 0.1% TFA at a flow rate of 4.5 mL / min. The retention time was 12.7 min. The eluate containing the desired peptide was collected, pooled and lyophilized. Calculated mass (M+2H) 2+ / 2: 1044.0 m / z; measured value (M+2H)2+ / 2:1044.0m / z.

[0657] Synthesis of BL34L20S [ka]

[0658] On a 0.05 mmol scale, Rink Amide Protide resin was deprotected by treating the resin with 20% piperidine in DMF (3 × 8 min). Fmoc-Lys(iPr,Boc)-OH was then attached to the resin, followed by coupling of Fmoc-D-Glu(OAll)-OH, Fmoc-D-Ala-OH, Fmoc-2-Nal-OH, Fmoc-D-Arg(Pbf)-OH, Fmoc-Lys(iPr,Boc)-OH, Fmoc-Tyr(tBu)-OH, and Fmoc-Lys(ivDde)-OH via solid-phase peptide synthesis using Fmoc-based chemistry. All couplings were performed in DMF using Fmoc-protected amino acids (4 equiv.), HATU (4 equiv.), and DIEA (7 equiv.). The -OAll group was converted to 1,2-dichlorophenyl ether (Pd(PPh 3 ) 4 / phenylsilane (0.25 / 24 equiv.) (30 min, ×2) followed by Fmoc deprotection. Cyclization was performed with HATU / HOAt / DIPEA (3 / 3 / 6 equiv.) and coupled for 12 h. The ivDde group was removed with 2% hydrazine in DMF (5 × 5 min). Fmoc-cysteic acid and Fmoc-Lys(ivDde)-OH were then coupled as described above. The synthesis continued with coupling of DOTA (4 equiv.) using HATU / DIPEA (4 / 7 equiv.), followed by ivDde deprotection and coupling of 4-(4-bromophenyl)butanoic acid with HATU / DIPEA (4 / 7 equiv.). The peptide was then deprotected and simultaneously cleaved from the resin by treatment with 95 / 5 trifluoroacetic acid (TFA) / triisopropylsilane (TIS) for 2 h at room temperature. After filtration, the peptide was precipitated by adding cold diethyl ether to the TFA solution. The crude peptide was purified by HPLC using a semi-preparative column. The HPLC conditions were 29% acetonitrile with 0.1% TFA at a flow rate of 4.5 mL / min. The retention time was 13.2 min. The eluate containing the desired peptide was collected, pooled and lyophilized. Calculated mass (M+2H) 2+ / 2: 1037.5 m / z; measured value (M+2H) 2+ / 2:1038.0 m / z.

[0659] Activity Data cell culture

[0660] The Z138 mantle cell lymphoma cell line was purchased from the American Type Culture Collection (ATCC® CRL-3001). The cell line was cultured in IMDM medium supplemented with 10% fetal bovine serum, 100 I.U. / mL penicillin, and 100 μg / mL streptomycin in a humidified incubator at 5% CO. 2 The culture was performed at 37°C.

[0661] Competitive binding assay

[0662] CHO:CXCR4 cells were cultured at 1 × 10 5 Cells / well were seeded at a density of 1000 μg / well. 125 Cells were incubated with [I]SDF-1α (0.01 nM, PerkinElmer) and competing non-radioactive ligand (1 μM-0.1 pM). Cells, radioligand, and competing peptide were incubated for 1 h at 27 °C with gentle shaking. After the incubation period, the supernatant was aspirated, followed by three washes with 1 mL ice-cold PBS. Cells were harvested with 200 μL trypsin and counted in a γ-counter. Data were plotted in GraphPad Prism 7 to determine IC 50 Values ​​were determined (GraphPad Software, Inc., La Jolla, Calif.) and are reported as the mean ± standard deviation. Results for a subset of compounds are shown in Table 7.

[0663] radioactive label

[0664] [ 68 Ga]GaCl 3 The eluted [ 68 Ga]GaCl 3 The solution was added to 2 mL of concentrated HCl. This radioactive mixture was then added to a DGA resin column and washed with 3 mL of 5 M HCl. The column was then air dried and [ 68 Ga]GaCl 3 (0.10-0.50 GBq) was eluted with 0.5 mL of water into a vial containing a solution of unlabeled precursor (25 μg) in 0.7 mL of HEPES buffer (2 M, pH 5.3). The reaction mixture was heated in a microwave oven (Danby, DMW7700WDB) at power setting 2 for 1 min. The mixture was purified by semi-preparative HPLC and quality control was performed by analytical HPLC co-injecting unlabeled standards with 1 / 12 of the radioactive tracer. Radiochemical yields (after decay correction) were >50% and radiochemical purity was >95%.

[0665] Animal models

[0666] Animal studies were performed according to the guidelines established by the Canadian Council on Animal Care, with study protocols approved by the Animal Ethics Committee of the University of British Columbia. For all studies, male NOD.Cg-Rag1tm1MomIl2rgtm1Wjl / SzJ (NRG) mice were used, and cells were injected in 100 μL of a 1:1 PBS / Matrigel solution. For preclinical imaging and biodistribution studies, Z138 was administered at 5 × 10 6 Cells were inoculated subcutaneously into the left or right flank at 100 x 100 cells, and tumors were grown to 200–300 mm 3 The cells were grown to a size of 100 μg / ml.

[0667] PET / CT Imaging

[0668] PET / CT imaging experiments were performed using a Siemens Inveon small animal PET / CT scanner. Each tumor-bearing mouse was injected with approximately 6–8 MBq of CT-CT DNA via the lateral tail vein. 68 Ga-labeled tracer was injected, and 50 min after injection, a 10-min CT scan was first performed for post-segmentation localization and attenuation correction to reconstruct PET images, followed by a 10-min static PET acquisition.

[0669] 177 Radiolabeling with Lu

[0670] For compounds conjugated to DOTA chelators, 177 Lu]LuCl 3(740–925 MBq) was added to a solution of the precursor (10 nmol) in sodium acetate buffer (0.5 mL, 0.1 M, pH 4.5). The mixture was incubated at 90 °C for 15 min and then purified by HPLC using a semi-preparative column. For the compounds conjugated to crown chelators, [ 177 Lu]LuCl 3 (810 MBq) was added to a solution of precursor (10 nmol) in ammonium acetate buffer (0.5 mL, 0.1 M, pH 5.5) containing 10% ethanol. The mixture was incubated at 37° C. for 30 min and then purified by HPLC using a semi-preparative column. The elution fractions containing the radiolabeled product were collected, diluted with water (50 mL) and passed through a C18 Sep-Pak cartridge pre-washed with ethanol (1 mL) and water (1 mL×2). 177 The Lu-labeled product was eluted from the cartridge with ethanol (0.4 mL) and diluted with saline in 1% ascorbic acid for imaging and biodistribution. Quality control and co-injection of natLu-labeled standards with radioactive tracer were performed using an analytical column.

[0671] SPECT / CT Imaging

[0672] SPECT / CT imaging experiments were performed using a MILabs U-SPECT-II / CT scanner. Tumor-bearing mice were infused with approximately 18.5–37 MBq of CT-T cells via the lateral tail vein. 177 Lu-labeled compounds were injected. Mice were imaged at 1, 4, 24, 72, and 120 hours post-injection. At each time point, a 5-minute CT scan was first performed for anatomical reference, followed by two 30-minute static emission scans acquired in list mode. The following subset of compounds: 68 Ga]Ga-BL34L11, [ 177 Lu]Lu-BL34L11, and [ 177 Lu]Lu-BL34L20, [ 177 Lu]Lu-Crown-BL34,[ 68 Ga]Ga-BL34N1, [ 68Ga]Ga-BL34T1, [ 177 Lu]Lu- BL34T1, and [ 177 Lu]Lu- The results for BL34L20S are shown in Figures 1 to 8, respectively.

[0673] Biodistribution

[0674] Under isoflurane anesthesia (2 L / min O 2 Mice were then incubated with 2–2.5% isoflurane in a 35% CO2 incubator. 68 Ga]Ga-BL34L6 or [ 68 Mice were anesthetized with isoflurane and then intravenously injected with CO 2 Mice were euthanized by inhalation. Tissues were harvested, washed in PBS, tapped dry, weighed, and then assayed for radioactivity on a gamma counter. Counted radioactivity was converted to percent injected dose per gram of tissue (%ID / g) using a calibration curve. Results are shown in Tables 8-17 for a subset of compounds.

[0675] [Table 7]

[0676] [Table 8]

[0677] [Table 9]

[0678] [Table 10]

[0679] [Table 11]

[0680] [Table 12]

[0681] [Table 13]

[0682] [Table 14]

[0683] [Table 15]

[0684] [Table 16]

[0685] [Table 17]

[0686] Incorporation by Reference

[0687] All references, articles, publications, patents, patent publications, and patent applications cited herein are incorporated by reference in their entirety for all purposes. However, mention of any references, articles, publications, patents, patent publications, and patent applications cited herein is not to be construed as an admission or any form of suggestion that they constitute valid prior art or form part of the common general knowledge in any country throughout the world.

[0688] References 1.Murdoch,C.CXCR4:chemokine receptor extraordinaire.Immunol.Rev.177,175-184(2000). 2.Griffith,J.W.,Sokol,C.L.& Luster,A.D.Chemokines and Chemokine Receptors:Positioning Cells for Host Defense and Immunity.Annu.Rev.Immunol.32,659-702(2014). 3.Ratajczak,M.Z.et al.The pleiotropic effects of the SDF-1-CXCR4 axis in organogenesis,regeneration and tumorigenesis.Leukemia 20,1915-1924(2006). 4.George,J.et al.Transfer of Endothelial Progenitor and Bone Marrow Cells Influences Atherosclerotic Plaque Size and Composition in Apolipoprotein E Knockout Mice.Arterioscler.Thromb.Vasc.Biol.25,2636-2641(2005). 5.Wang,A.et al.CXCR4 / CXCL12 Hyperexpression Plays a Pivotal Role in the Pathogenesis of Lupus.J.Immunol.182,4448-4458(2009). 6.Wang,A.et al.Dysregulated expression of CXCR4 / CXCL12 in subsets of patients with systemic lupus erythematosus.Arthritis Rheum.62,3436-3446(2010). 7.Guo,F.et al.CXCL12 / CXCR4:a symbiotic bridge linking cancer cells and their stromal neighbors in oncogenic communication networks.Oncogene 35,816-26(2016). 8.Jacobson,O.& Weiss,I.D.CXCR4 chemokine receptor overview:biology,pathology and applications in imaging and therapy.Theranostics 3,1-2(2013). 9.Balkwill,F.Cancer and the chemokine network.Nat.Rev.Cancer 4,540-550(2004). 10.Zlotnik,A.,Burkhardt,A.M.& Homey,B.Homeostatic chemokine receptors and organ-specific metastasis.Nat.Rev.Immunol.11,597-606(2011). 11.Domanska,U.M.et al.A review on CXCR4 / CXCL12 axis in oncology:No place to hide.Eur.J.Cancer 49,219-230(2013). 12.Zhao,H.et al.CXCR4 over-expression and survival in cancer:a system review and meta-analysis.Oncotarget 6,5022-40(2015). 13.Woodard,L.E.& Nimmagadda,S.CXCR4-Based Imaging Agents.J.Nucl.Med.52,1665-1669(2011). 14.Kuil,J.,Buckle,T.& van Leeuwen,F.W.B.Imaging agents for the chemokine receptor 4(CXCR4).Chem.Soc.Rev.41,5239(2012). 15.Weiss,I.D.& Jacobson,O.Molecular Imaging of Chemokine Receptor CXCR4.Theranostics 3,76-84(2013). 16.George,G.P.C.,Pisaneschi,F.,Nguyen,Q.-D.& Aboagye,E.O.Positron Emission Tomographic Imaging of CXCR4 in Cancer:Challenges and Promises.Mol.Imaging 14,7290.2014.00041(2015). 17.Peng,S.et al.Identification of LY2510924 ,a Novel Cyclic Peptide CXCR4 Antagonist That Exhibits Antitumor Activities in Solid Tumor and Breast Cancer Metastatic Models.Mol.Cancer Ther.14,480-491(2015). 18.Salgia,R.et al.A randomized phase II study of LY2510924 and carboplatin / etoposide versus carboplatin / etoposide in extensive-disease small cell lung cancer.Lung Cancer 105,7-13(2017). 19.Tamamura,H.et al.A Low-Molecular-Weight Inhibitor against the Chemokine Receptor CXCR4:A Strong Anti-HIV Peptide T140.Biochem.Biophys.Res.Commun.253,877-882(1998). 20.Fujii,N.et al.Molecular-Size Reduction of a Potent CXCR4-Chemokine Antagonist Using Orthogonal Combination of Conformation- and Sequence-Based Libraries.Angew.Chemie Int.Ed.42,3251-3253(2003). 21.Todorovic,M.et al.Fluorescent Isoindole Crosslink(FlICk)Chemistry:A Rapid,User-friendly Stapling Reaction.Angew.Chemie Int.Ed.58,14120-14124(2019).

Claims

1. A compound of formula A, formula B, or formula C, or a salt or solvate thereof, 【Chemistry 1】 During the ceremony, R ２ａ is -(CH ２ )-(R ２ｂ )-(phenyl), wherein R ２ｂ is absent or -CH ２ -, -NH-, -S-, or -O-, wherein the phenyl may be substituted at the 4-position with -NH ２ , -NO ２ , -OH, -OR ２ｃ , -SH, -SR ２ｃ , -N ３ , -CN, or -O-phenyl, and the phenyl may be substituted at the 3-position with halogen or -OH, and the phenyl may be substituted at the 5-position with halogen or -OH, and the -O-phenyl ring may be substituted at the 4-position with -NH ２ , -NO ２ , -OH, -OR ２ｃ , -SH, -SR ２ｃ , -N ３ , or -CN, and the -O-phenyl ring may be substituted at the 3-position with halogen or -OH, and the -O-phenyl ring may be substituted at the 5-position with halogen or -OH, and each R ２ｃ is independently a straight-chain or branched alkyl group of C １ to C ３ . R ３ａ C １ ~C ５ Alkyl or R ３ｂ R ３ｃ And in the formula, R ３ｂ is a straight chain of C １ ~C ５ Alkylenyl, C ２ ~C ５ alkenyl, or C ２ ~C ５ It is alkynylenel, and in the formula, C ２ ~C ５ The 0 to 2 carbon atoms in the compound are independently substituted with one or more N, S, and / or O heteroatoms, in the formula R ３ｃ is -N(R ３ｄ ) ２～３ or guanidino, where each R ３ｄ These are independently -H or linear or branched C １ ~C ３ It is alkyl, R ４ａ R ４ｂ R ４ｃ And in the formula, R ４ｂ is a straight chain of C １ ~C ５ Alkirenyl, C ２ ~C ５ Alkenylenyl, or C ２ ~C ５ This is alkynirenyl, and here C ２ ~C ５ The 0 to 2 carbon atoms in the compound are independently substituted with one or more N, S, and / or O heteroatoms, in the formula R ４ｃ is -N(R ４ｄ ) ２～３ or guanidino, where each R ４ｄ These are independently -H or linear or branched C １ ~C ３ It is alkyl, R ５ａ is, -(CH ２ ) １～３ -R ５ｂ And in the formula, -(CH ２ ) ２～３ - One of the carbon atoms may be substituted with an N, S, or O heteroatom, in the formula R ５ｂ teeth, Phenyl, -NH ２ , -NO ２ -OH, -OR ５ｃ -SH, -SR ５ｃ , -N ３ Substitution at the 4-position of -CN or -O-phenyl, substitution at the 3-position of halogen or -OH, and / or substitution at the 5-position of halogen or -OH, wherein the -O-phenyl ring is -NH ２ , -NO ２ -OH, -OR ５ｃ -SH, -SR ５ｃ , -N ３ , or -CN may be substituted at position 4, where the -O-phenyl ring may be substituted at position 3 with a halogen or -OH, where the -O-phenyl ring may be substituted at position 5 with a halogen or -OH, or a phenyl that is substituted with one or a combination of these substitutions, or a condensed bicyclic or tricyclic aryl or heteroaryl ring, each of which is a halogen, -OH, -OR ５ｃ , amino, -NHR ５ｃ , and / or N(R ５ｃ ) ２ A fused bicyclic or tricyclic aryl or heteroaryl ring which may be substituted with one or more of the following: In the formula, each R ５ｃ Independently, C １ ~C ３ It is a linear or branched alkyl group, Any R ６ａ is H, methyl, ethyl, -C≡CH, -CH=CH ２ , -C≡C-(CH ２ ) １～３ -OH, -C≡C-(CH ２ ) １～３ -SH, -C≡C-(CH ２ ) １～３ -NH ２ , -C≡C-(CH ２ ) １～３ -COOH, -C≡C-(CH ２ ) １～３ -CONH ２ , -C≡C-(CH ２ )<​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​ A 5- or 6-membered aromatic ring, wherein one or more carbon atoms may be independently substituted with N, S, and / or O heteroatoms, or substituted with one or more groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen groups, or -NH-CH(R ６ａ )-C(O)-NH- is replaced by the following: 【Chemistry 2】 R Ａ７ａ is a linear C １ ~C ５ It is an alkylenyl, and in the formula, C ２ ~C ５ The 0 to 2 carbon atoms in the molecule are independently substituted with one or more N, S, and / or O heteroatoms. R ８ａ R ８ｂ R ８ｃ And in the formula, R ８ｂ is a straight chain of C １ ~C ５ Alkirenyl, C ２ ~C ５ Alkenylenyl, or C ２ ~C ５ This is alkynirenyl, and here C ２ ~C ５ In the alkylenyl, alkenylenyl, or alkynylenyl, 0 to 2 carbon atoms are independently substituted with one or more N, S, and / or O heteroatoms, where R ８ｃ is -N(R ８ｄ ) ２～３ or guanidino, where each R ８ｄ These are independently -H or linear or branched C １ ~C ３ It is alkyl, R ９ａ is -C(O)NH ２ , -C(O)-OH, -CH ２ -C(O)NH ２ ien-CH ２ -C(O)-OH, -CH ２ -NH ２ ien-CH ２ -OH, -CH ２ -CH ２ -NH ２ , -R ９ｂ -R ９ｃ , or -R ９ｂ - [Linker] - R Ｘ ｎ１ And in the formula, R ９ｂ は、-CH ２ -NHH-C(O)-、-CH ２ -C(O)-、-CH ２ -O-、-C(O)NH-、-C(O)-N(CH ３ )-、-CH ２ -NHC(S)-、-C(S)NH-、-CH ２ -N(CH) ３ )C(S)-、-C(O)N(CH ３ )-、-CH ２ -N(CH) ３ )C(O)-、-C(S)N(CH ３ )-、-CH ２ -NHC(S)NH-, -CH ２ -NHC(O)NH-,!CH ２ -S-,-CH ２ -S(O)-、-CH ２ -S(O) ２ -CH ２ -S(O) ２ -NHH-、-CH ２ -S(O)-NH-、-CH ２ -Se-,-CH ２ -Se(O)-、-CH ２ -Se(O) ２ -CH ２ -NHNHC(O)!-C(O)NHNH!-CH ２ -OP(O)(O － )O-、-CH ２ -ホスファミド-、-CH ２ -チオホスホジエステル-、-CH ２ -S-テトラフルオロフェニル-S-、 【Transformation 3】 or polyethylene glycol, and R ９ｃ is hydrogen, or linear, branched, and / or cyclic C １ ~C ２０ It is an alkyl, alkenyl, or alkynyl, where C ２ ~C ２０ The 0 to 6 carbon atoms in the molecule are independently substituted with N, S, and / or O heteroatoms, and are substituted with 0 to 3 groups independently selected from one or a combination of oxo, hydroxyl, sulfhydryl, halogen, guanidino, carboxylic acid, sulfonic acid, sulfinic acid, and / or phosphoric acid. R Ａ１０ It does not exist, or -[linker]-R Ｘ ｎ１ And, R Ａ１０ If it does not exist, R Ａ１ａ teeth, Linear C １ ~C ５ Alkyl, C ２ ~C ５ Alkenyl, or C ２ ~C ５ It is an alkynyl, and in the formula, C ２ ~C ５ In the alkyl, alkenyl, or alkynyl compounds, 0 to 2 carbon atoms are independently substituted with one or more N, S, and / or O heteroatoms, where C is -SH, -OH, amino, carboxy, guanidino, -NH-C(O)-CH ３ , -S-C(O)-CH ３ , -OC(O)-CH ３ -NH-C(O)-(phenyl), -S-C(O)-(phenyl), -O-C(O)-(phenyl), -NH-(CH ３ ) １～２ , -NH ２ -CH ３ , -N(CH ３ ) ２～３ , -S-CH ３ , or -O-CH ３ It may be substituted with one substituent selected from the following: Branch C １ ~C １０ It is an alkyl, alkenyl, or alkynyl of the formula, where C ２ ~C １０ The 0 to 3 carbon atoms in the molecule are independently substituted with one or more N, S, and / or O heteroatoms, or R Ａ１ｂ R Ａ１ｃ And in the formula, R Ａ１ｂ is a linear C １ ~C ３ It is an alkylenyl, and in the formula, C ２ Alkyrenyl or C ３ The alkylenyl may be substituted with an N, S, or O heteroatom, where R Ａ１ｃ teeth, A 5- or 6-membered aromatic ring, wherein one or more carbon atoms may be independently substituted with N, S, and / or O heteroatoms, or may be substituted with one or more groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen, or A fused bicyclic or tricyclic aryl group, wherein one or more carbon atoms may be independently substituted with N, S, and / or O heteroatoms, and also with halogens, -OH, -OR Ａ１ｄ , amino, -NHR Ａ１ｄ , and / or N(R Ａ１ｄ ) ２ It may be substituted with one or more groups independently selected from R, where each R Ａ１ｄ C １ ~C ３ A linear or branched alkyl group, a fused bicyclic or tricyclic aryl group, R Ａ１０ ga-[linker]-R Ｘ ｎ１ If so, R Ａ１ａ R Ａ１ｅ R Ａ１ｆ And in the formula, R Ａ１ｅ is a straight chain of C １ ~C ５ Alkirenyl, C ２ ~C ５ Alkenylenyl, or C ２ ~C ５ This is alkynirenyl, and here C ２ ~C ５ In the alkylenyl, alkenylenyl, and alkynylenyl compounds, 0 to 2 carbon atoms are independently substituted with N, S, and / or O heteroatoms, and R Ａ１ｆ -NH-C(O)-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH ３ )-, -NHC(S)-, -C(S)NH-, -N(CH ３ )C(S)-, -C(O)N(CH ３ )-,-N(CH ３ )C(O)-, -C(S)N(CH ３ )-, -NHC(S)NH-, -NHC(O)NH-, -S-, -S(O)-, -S(O)-O-, -S(O) ２ -, -S(O) ２ -O-, -S(O) ２ -NH-, -S(O)-NH-, -Se-, -Se(O)-, -Se(O) ２ -, -NHNHC(O)-, -C(O)NHNH-, -OP(O)(O － ) O-,-phosphamide-,-thiophosphodiester-,-S-tetrafluorophenyl-S-, 【Chemistry 4】 or polyethylene glycol, R Ｂ１ａ C is a linear, branched, and / or cyclic C １ ~C １０ Alkirenyl, C ２ ~C １０ Alkenylenyl, or C ２ ~C １０ It is alkynirenyl, and in the formula, C ２ ~C １０ In the alkylenyl, alkenylenyl, and alkynylenyl compounds, one or more carbon atoms may be independently substituted with N, S, and / or O heteroatoms. R Ｂ１－７ teeth, 【Transformation 5】 In the formula, the indole ring and isoindole ring are represented by -F, -Br, -Cl, -I, -OH, and -O-R, respectively. Ｂ１－７ｂ , -CO-, -COOH, -CONH ２ -CN, -O-aryl, -NH ２ , - NHR Ｂ１－７ｂ , N ３ , -NO ２ -NH, -CHO, and / or -R Ｂ１－７ｂ It is also possible that one or more of them are substituted, and in the formula, each R Ｂ１－７ｂ C is a linear or branched C １ ~C ３ Alkyl, C ２ ~C ３ Alkenyl, or C ２ ~C ３ It is alkinyl, R Ｂ７ａ is a linear C １ ~C ５ It is an alkylenyl, and in the formula, C ２ ~C ５ In the alkylenyl, 0 to 2 carbon atoms are independently substituted with one or more N, S, and / or O heteroatoms. R Ｂ１０ａ is an amine, -NH-(CH ３ ) １～２ , -N(CH ３ ) ２～３ , -NH-C(O)-CH ３ -NH-C(O)-(phenyl), or -R Ｂ１０ｂ - [Linker] - R Ｘ ｎ１ And in the formula, R Ｂ１０ｂ teeth, -NHH-C(O)-、-C(O)-、-O-、-C(O)NHH-、-C(O)-N(CH ３ )-、-NHC(S)-、-C(S)NH-、-N(CH ３ )C(S)-、-C(O)N(CH ３ )-、-N(CH ３ )C(O)-、-C(S)N(CH ３ )-、-NHC(S)NH-、-NHC(O)NH-、-S-、-S(O)-、-S(O)-、-S(O)-O-、-S(O) ２ -、-S(O) ２ -O-、-S(O) ２ -NHH-、-S(O)-NHH-、-Se-、-Se(O)-、-Se(O) ２ -、-NHNHC(O)-、-C(O)NHNH-、-OP(O)(O － )O-、-ホスファミド-、-チオホスホジエステル-、-S-テトラフルオロフェニル-S-、 【Transformation 6】 or polyethylene glycol, R Ｃ１ａ teeth, 【Transformation 7】 In the formula, the indole, isoindole, and triazole rings are -F, -Br, -Cl, -I, -OH, and -O-R, respectively. Ｃ１ｂ , -CO-, -COOH, -CONH ２ -CN, -O-aryl, -NH ２ , - NHR Ｃ１ｂ , N ３ , -NO ２ -NH, -CHO, and / or -R Ｃ１ｂ It is also possible that one or more of them are substituted, and in the formula, each R Ｃ１ｂ C is a linear or branched C １ ~C ３ Alkyl, C ２ ~C ３ Alkenyl, or C ２ ~C ３ It is alkinyl, R Ｃ７ａ is a linear C １ ~C ５ It is an alkylenyl, and in the formula, C ２ ~C ５ The 0 to 2 carbon atoms in the alkylenyl may be independently substituted with one or more N, S, and / or O heteroatoms. R Ｃ１０ａ R Ｃ１０ｂ -R Ｃ１０ｃ - [Linker] - R Ｘ ｎ１ or R Ｃ１０ｄ And in the formula, R Ｃ１０ｂ is a straight chain of C １ ~C ５ Alkirenyl, C ２ ~C ５ Alkenylenyl, or C ２ ~C ５ This is alkynirenyl, and here C ２ ~C ５ In the alkylenyl, alkenylenyl, and alkynylenyl compounds, 0 to 2 carbon atoms are independently substituted with N, S, and / or O heteroatoms. R Ｃ１０ｃ -NH-C(O)-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH ３ )-, -NHC(S)-, -C(S)NH-, -N(CH ３ )C(S)-, -C(O)N(CH ３ )-,-N(CH ３ )C(O)-, -C(S)N(CH ３ )-, -NHC(S)NH-, -NHC(O)NH-, -S-, -S(O)-, -S(O)-O-, -S(O) ２ -, -S(O) ２ -O-, -S(O) ２ -NH-, -S(O)-NH-, -Se-, -Se(O)-, -Se(O) ２ -, -NHNHC(O)-, -C(O)NHNH-, -OP(O)(O － ) O-,-phosphamide-,-thiophosphodiester-,-S-tetrafluorophenyl-S-, 【Transformation 8】 or polyethylene glycol, and R Ｃ１０ｄ teeth, Linear C １ ~C ５ Alkyl, C ２ ~C ５ Alkenyl, or C ２ ~C ５ It is an alkynyl, and in the formula, C ２ ~C ５ In the alkyl, alkenyl, or alkynyl compounds, 0 to 2 carbon atoms are independently substituted with N, S, and / or O heteroatoms, where C is -SH, -OH, amino, carboxy, guanidino, -NH-C(O)-CH ３ , -S-C(O)-CH ３ , -OC(O)-CH ３ -NH-C(O)-(phenyl), -S-C(O)-(phenyl), -O-C(O)-(phenyl), -NH-(CH ３ ) １～２ , -NH ２ -CH ３ , -N(CH ３ ) ２～３ , -S-CH ３ , or -O-CH ３ It may be substituted with one substituent selected from the following: Branch C １ ~C １０ Alkyl, C ２ ~C １０ Alkenyl, or C ２ ~C １０ It is an alkynyl, and in the formula, C ２ ~C １０ The alkyl, alkenyl, or alkynyl compounds have 0 to 3 carbon atoms that are independently substituted with N, S, and / or O heteroatoms, or R Ｃ１０ｅ R Ｃ１０ｆ And in the formula, R Ｃ１０ｅ is a linear C １ ~C ３ Alkyl, C ２ Alkyl or C ３ The alkyl group may be substituted with an N, S, or O heteroatom, where R Ｃ１０ｆ teeth, A 5- or 6-membered aromatic ring, wherein one or more carbon atoms may be independently substituted with N, S, and / or O heteroatoms, or substituted with one or more groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen groups, A fused bicyclic or tricyclic aryl group, wherein one or more carbon atoms may be independently substituted with N, S, and / or O heteroatoms, and also with halogens, -OH, -OR Ｃ１０ｇ , amino, -NHR Ｃ１０ｇ , and / or N(R Ｃ１０ｇ ) ２ It may be substituted with one or more groups independently selected from, where R Ｃ１０ｇ C １ ~C ３ A linear or branched alkyl group, a fused bicyclic or tricyclic aryl group, R ｙ is hydrogen or R ３ｅ R ３ｆ And in the formula, R ３ｅ is a linear C １ ~C ５ It is an alkylenyl, and in the formula, R ３ｆ is -N(R ３ｇ ) ２～３ And in the formula, each R ３ｇ These are independently -H or linear or branched C １ ~C ３ It is alkyl, Each n1 is independently 0, 1, or 2. Each R Ｘ is an albumin binder, therapeutic moiety, fluorescent label, radiolabeling group, or radiolabelable group, wherein 0 to 3 peptide backbone amides are independently 【Chemistry 9】 Substituted with amidine or thioamide, In the formula, 0 to 3 amides in the peptide backbone are N-methylated, and A compound in which the C-terminus may be amidated.

2. The aforementioned compound has the structure of formula A-I below, or a salt or solvate thereof, 【Chemistry 10】 During the ceremony, R ２ａ is, -(CH ２ ) - (R ２ｂ )-(phenyl), where R ２ｂ It does not exist, or -CH ２ -, -NH-, -S-, or -O-, where the phenyl is -NH ２ , -NO ２ -OH, -OR ２ｃ -SH, -SR ２ｃ , -N ３ The 4th position may be substituted with -CN or -O-phenyl, or the 3rd position may be substituted with a halogen or -OH, in the formula, each R ２ｃ Independently, C １ ~C ３ It is a linear or branched alkyl group, R ３ａ R ３ｂ R ３ｃ And in the formula, R ３ｂ is a straight chain of C １ ~C ５ Alkirenyl, C ２ ~C ５ Alkenylenyl, or C ２ ~C ５ It is an alkynirenyl, and in the formula, R ３ｃ is -N(R ３ｄ ) ２～３ or guanidino, where each R ３ｄ These are independently -H or linear or branched C １ ~C ３ It is alkyl, R ４ａ R ４ｂ R ４ｃ And in the formula, R ４ｂ is a straight chain of C １ ~C ５ Alkirenyl, C ２ ~C ５ Alkenylenyl, or C ２ ~C ５ It is an alkynirenyl, and in the formula, R ４ｃ is -N(R ４ｄ ) ２～３ or guanidino, where each R ４ｄ These are independently -H or linear or branched C １ ~C ３ It is alkyl, R ５ａ is, -(CH ２ ) １～３ -R ５ｂ And in the formula, R ５ｂ teeth, Phenyl, -NH ２ , -NO ２ , -OH, -SH, -N ３ A phenyl which may be substituted with one or more of the following: substitution at the 4-position of -CN or -O-phenyl, substitution at the 3-position of a halogen or -OH, and / or substitution at the 5-position of a halogen or -OH. A fused bicyclic or tricyclic aryl or heteroaryl ring, comprising a halogen, -OH, -OR ５ｃ , amino, -NHR ５ｃ , and / or N(R ５ｃ ) ２ A fused bicyclic or tricyclic aryl or heteroaryl ring which may be substituted with one or more of the following, and In the formula, R ５ｃ Each of them independently, C １ ~C ３ It is a linear or branched alkyl group, R ６ａ H, methyl, ethyl, -C≡CH, -CH=CH ２ ien-CH ２ -R ６ｂ -OH, -CH ２ -R ６ｂ -COOH, -CH ２ - (R ６ｂ ) １～３ -NH ２ ien-CH ２ -R ６ｂ -CONH ２ , or -CH ２ -R ６ｂ R ６ｃ And in the formula, each R ６ｂ Independently, does not exist, -CH ２ -, -NH-, -S-, or -O-, and in the formula, R ６ｃ is a 5- or 6-membered aromatic ring, where 0 to 3 carbon atoms are independently substituted with N, S, and / or O heteroatoms, and may also be substituted with 0 to 3 groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen groups. R ８ａ R ８ｂ R ８ｃ And in the formula, R ８ｂ is a straight chain of C １ ~C ５ Alkirenyl, C ２ ~C ５ Alkenylenyl, or C ２ ~C ５ It is an alkynirenyl, and in the formula, R ８ｃ is -N(R ８ｄ ) ２～３ or guanidino, where each R ８ｄ These are independently -H or linear or branched C １ ~C ３ It is alkyl, R ９ａ is -C(O)NH ２ , -C(O)-OH, -CH ２ -C(O)NH ２ ien-CH ２ -C(O)-OH, -R ９ｂ -R ９ｃ , or -R ９ｂ - [Linker] - R Ｘ ｎ１ And in the formula, R ９ｂ is -C(O)NH- and also R ９ｃ teeth, 【Chemistry 11】 And in the formula, R ９ｄ C is a linear or branched C １ ~C ５ It is an alkylenyl, R ９ｅ These are carboxylic acids, sulfonic acids, sulfinic acids, phosphoric acids, amino acids, guanidino, -SH, -OH, -NH-C(O)-CH ３ , -S-C(O)-CH ３ , -OC(O)-CH ３ -NH-C(O)-(phenyl), -S-C(O)-(phenyl), -O-C(O)-(phenyl), -NH-CH ３ , -N(CH ３ ) ２ , -S-CH ３ , -O-CH ３ , or phenyl, and also R ９ｆ is amino or -OH, R Ａ７ａ C １ ~C ３ It is an alkylenyl, R Ａ１０ It does not exist, or -[linker]-R Ｘ ｎ１ And, R Ａ１０ If it does not exist, R Ａ１ａ teeth, Linear C １ ~C ５ Alkyl, C ２ ~C ５ Alkenyl, or C ２ ~C ５ It is an alkynyl, and in the formula, C ２ ~C ５ In the alkyl, alkenyl, or alkynyl compounds, 0 to 2 carbon atoms are independently substituted with one or more N, S, and / or O heteroatoms, where C is -SH, -OH, amino, carboxy, guanidino, -NH-C(O)-CH ３ , -S-C(O)-CH ３ , -OC(O)-CH ３ -NH-C(O)-(phenyl), -S-C(O)-(phenyl), -O-C(O)-(phenyl), -NH-(CH ３ ) １～２ , -NH ２ -CH ３ , -N(CH ３ ) ２～３ , -S-CH ３ , or -O-CH ３ It may be substituted with one substituent selected from the following: Branch C １ ~C １０ It is an alkyl, alkenyl, or alkynyl of the formula, where C ２ ~C １０ The 0 to 3 carbon atoms in the molecule are independently substituted with one or more N, S, and / or O heteroatoms, or R Ａ１ｂ R Ａ１ｃ And in the formula, R Ａ１ｂ is a linear C １ ~C ３ It is an alkylenyl, and in the formula, C ２ Alkyrenyl or C ３ The alkylenyl may be substituted with an N, S, or O heteroatom, where R Ａ１ｃ teeth, A 5- or 6-membered aromatic ring, wherein one or more carbon atoms may be independently substituted with N, S, and / or O heteroatoms, or may be substituted with one or more groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen, or A fused bicyclic or tricyclic aryl group, wherein one or more carbon atoms may be independently substituted with N, S, and / or O heteroatoms, and also with halogens, -OH, -OR Ａ１ｄ , amino, -NHR Ａ１ｄ , and / or N(R Ａ１ｄ ) ２ It may be substituted with one or more groups independently selected from R, where each R Ａ１ｄ C １ ~C ３ A linear or branched alkyl group, a fused bicyclic or tricyclic aryl group, R Ａ１０ However, -[linker]-R Ｘ ｎ１ If so, R Ａ１ａ R Ａ１ｅ R Ａ１ｆ And in the formula, R Ａ１ｅ is a straight chain of C １ ~C ５ Alkirenyl, C ２ ~C ５ Alkenylenyl, or C ２ ~C ５ This is alkynirenyl, and here C ２ ~C ５ In the alkylenyl, alkenylenyl, or alkynylenyl, 0 to 2 carbon atoms are independently substituted with N, S, and / or O heteroatoms. R Ａ１ｆ -NH-C(O)-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH ３ )-, -NHC(S)-, -C(S)NH-, -N(CH ３ )C(S)-, -C(O)N(CH ３ )-,-N(CH ３ )C(O)-, -C(S)N(CH ３ )-, -NHC(S)NH-, -NHC(O)NH-, -S-, -S(O)-, -S(O)-O-, -S(O) ２ -, -S(O) ２ -O-, -S(O) ２ -NH-, -S(O)-NH-, -Se-, -Se(O)-, -Se(O) ２ -, -NHNHC(O)-, -C(O)NHNH-, -OP(O)(O － ) O-,-phosphamide-,-thiophosphodiester-,-S-tetrafluorophenyl-S-, 【Chemistry 12】 or polyethylene glycol, The aforementioned linker is X １ L １ , X １ L １ X １ L １ , or X １ L １ X １ L １ X １ L １ And, X １ Each of them independently, -CH ２ - 【Chemistry 13】 And, L １ These are, independently, -NH-, -C(O)-, -NHC(O)-, -C(O)NH-, and -N(CH ３ )C(O)-, or -C(O)N(CH ３ ) - and R １１ Each of these is independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid, and R Ｚ Each of these is an albumin binder, independently of the others. Each n1 is independently 0, 1, or 2. Each R Ｘ This is an albumin binder, therapeutic moiety, fluorescent label, radiolabeling group, or group that can be radiolabeled. In the formula, 0 to 3 peptide backbone amides are independently 【Chemistry 14】 Substituted with amidine or thioamide, In the formula, 0 to 3 amides in the peptide backbone are N-methylated, and The compound according to claim 1, wherein the C-terminus may be amidated.

3. The aforementioned compound has the structure of formula A-II below, or a salt or solvate thereof, 【Chemistry 15】 During the ceremony, Formula A-II -NH-CH(R ２ａ )-C(O)- is a Tyr residue, a Phe residue, (4-NO ２ )-Phe residue, (4-NH ２ ) -Phe residue, hTyr residue, (3-I)Tyr residue, Glu residue, Glun residue, or D-Tyr residue, Formula A-II -NH-CH(R ３ａ )-C(O)- is a Lys(iPr) residue, Arg(Me) ２ Forms an (asymmetric) residue, or an Arg(Me) residue, Formula A-II -NH-CH(R ４ａ )-C(O)- forms a D-Arg residue or a D-hArg residue, Formula A-II -NH-CH(R ５ａ )-C(O)- consists of a 2-(Ant)Ala residue, a 2-Nal residue, a Trp residue, and (4-NH ２ ) Forms a Phe residue, an hTyr residue, or a Tyr residue, Formula A-II -NH-CH(R ６ａ )-C(O)- forms His residues, D-His residues, D-Glu residues, D-Gln residues, D-Ala residues, D-Phe residues, D-Ser residues, D-Dab residues, and D-Dap residues. R ８ａ R ８ｂ R ８ｃ And in the formula, R ８ｂ is a straight chain of C １ ~C ５ Alkirenyl, C ２ ~C ５ Alkenylenyl, or C ２ ~C ５ It is an alkynirenyl, and in the formula, R ８ｃ is -N(R ８ｄ ) ２～３ or guanidino, where each R ８ｄ These are independently -H or linear or branched C １ ~C ３ It is alkyl, R ９ａ is -C(O)NH ２ , -C(O)-OH, -CH ２ -C(O)NH ２ ien-CH ２ -C(O)-OH, or -R ９ｂ - [Linker] - R Ｘ ｎ１ And, R ９ｂ is -C(O)NH-, R Ａ７ａ C １ ~C ３ It is an alkylenyl, R Ａ１０ It does not exist, or -[linker]-R Ｘ ｎ１ And, R Ａ１０ If it does not exist, R Ａ１ａ is a linear C １ ~C ５ Alkyl, -SH, -OH, amino, carboxy, guanidino, -NH-C(O)-CH ３ , -S-C(O)-CH ３ , -OC(O)-CH ３ -NH-C(O)-(phenyl), -S-C(O)-(phenyl), -O-C(O)-(phenyl), -NH-(CH ３ ) １～２ , -NH ２ -CH ３ , -N(CH ３ ) ２～３ , -S-CH ３ , -O-CH ３ , or branch C １ ~C １０ A linear C molecule may be substituted with one substituent selected from alkyl, alkenyl, or alkynyl atoms. １ ~C ５ It is alkyl, R Ａ１０ However, -[linker]-R Ｘ ｎ１ If so, R Ａ１ａ R Ａ１ｅ R Ａ１ｆ And in the formula, R Ａ１ｅ is a straight chain of C １ ~C ５ Alkirenyl, C ２ ~C ５ Alkenylenyl, or C ２ ~C ５ This is alkynirenyl, and here C ２ ~C ５ In the alkylenyl, alkenylenyl, or alkynylenyl, 0 to 2 carbon atoms are independently substituted with N, S, and / or O heteroatoms. R Ａ１ｆ -NH-C(O)-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH ３ )-, -NHC(S)-, -C(S)NH-, -N(CH ３ )C(S)-, -C(O)N(CH ３ )-,-N(CH ３ )C(O)-, -C(S)N(CH ３ )-, -NHC(S)NH-, -NHC(O)NH-, -S-, -S(O)-, -S(O)-O-, -S(O) ２ -, -S(O) ２ -O-, -S(O) ２ -NH-, -S(O)-NH-, -Se-, -Se(O)-, -Se(O) ２ -, -NHNHC(O)-, -C(O)NHNH-, -OP(O)(O － ) O-,-phosphamide-,-thiophosphodiester-,-S-tetrafluorophenyl-S-, 【Chemistry 16】 or polyethylene glycol, The aforementioned linker is X １ L １ , X １ L １ X １ L １ , or X １ L １ X １ L １ X １ L １ And, X １ Each of them independently, -CH ２ - 【Chemistry 17】 And, L １ These are, independently, -NH-, -C(O)-, -NHC(O)-, -C(O)NH-, and -N(CH ３ )C(O)-, or -C(O)N(CH ３ ) - and R １１ Each of these is independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid, and R Ｚ Each of these is an albumin binder, independently of the others. Each n1 is independently 0, 1, or 2. Each R Ｘ This is an albumin binder, therapeutic moiety, fluorescent label, radiolabeling group, or group that can be radiolabeled. In the formula, 0 to 3 peptide backbone amides are independently [Chemistry 18] Substituted with amidine or thioamide, In the formula, 0 to 3 amides in the peptide backbone are N-methylated, and In the formula, the C-terminus may be amidated. The compound according to claim 1 or 2.

4. Formula A-I or Formula A-II -NH-CH(R Ａ１ａ )-C(O)- forms a Phe residue, 1-Nal residue, 2-Nal residue, Tyr residue, Trp residue, Lys residue, hLys residue, Lys(Ac) residue, Dap residue, Dab residue, or Orn residue, and / or R A10 is -[linker]-R X n1, and R 9a is -C(O)NH2, -C(O)-OH, -CH2-C(O)NH2, or -CH2-C(O)-OH. The compound according to claim 2 or 3.

5. (a) at least one X １ but, 【Chemistry 19】 is, or (b) The linker is X1L1, where X1 is 【Chemistry 20】 And L1 is either -NH- or -NHC(O)- or (c) The linker is X 1a L 1a X 1b L 1b, X 1a is, 【Chemistry 21】 And, L1a is -NH- or -NHC(O)-, X 1b is, 【Chemistry 22】 And also L1b is -NH- or -NHC(O)- or (d) The linker is X 1a L 1a X 1b L 1b, X 1a is, 【Chemistry 23】 And, L1a is -NH- or -NHC(O)-, X 1b is, 【Chemistry 24】 And also L1b is -NH- or -NHC(O)- or (e) The linker is X 1a L 1a X 1b L 1b, X 1a is, 【Chemistry 25】 And, L1a is -NH- or -NHC(O)-, X 1b is, 【Chemistry 26】 And also L1b is -NH- or -NHC(O)- or (f) The linker is X 1a L 1a X 1b L 1b X 1c L 1c, X 1a is, 【Chemistry 27】 And, L1a is -NH- or -NHC(O)-, X 1b is, 【Chemistry 28】 And, L1b is -NH- or -NHC(O)-, X1c is -CH2-, and L1c is -NH- or -NHC(O)- or (g) The linker is X 1a L 1a X 1b L 1b X 1c L 1c, X 1a is, 【Chemistry 29】 And, L1a is -NH- or -NHC(O)-, X 1b is -CH 2-, L1b is -NH- or -NHC(O)-, X 1c is, 【Transformation 30】 And also L1c is -NH- or -NHC(O)-. The compound according to any one of claims 2 to 4.

6. R １１ is sulfonic acid (-SO ３ The compound according to any one of claims 2 to 5, wherein H)

7. R ９ａ R ９ｂ - [Linker] - R ｘ ｎ１ And, R ９ｂ is -C(O)NH-, The aforementioned linker is X １ L １ And, X １ is, -(CH ２ ) １～５ -, -CH(COOH)-(CH ２ ) ０～４ -, or -CH(CONH ２ )-(CH ２ ) ０～４ - and also L １ These are, independently, -NH-, -C(O)-, -NHC(O)-, -C(O)NH-, and -N(CH ３ )C(O)-, or -C(O)N(CH ３ The compound according to any one of claims 2 to 6, wherein the compound is:

8. (a) R ｘ It is an albumin binder, The albumin binder is -(CH₂)₃-20-CH₃, -(CH₂)₃-20-C(O)OH, or 【Chemistry 31】 It may also be (wherein R 12 is I, Br, F, Cl, H, OH, OCH3, NH2, NO2, or CH3), The albumin binder is, 【Chemistry 32】 It may also be (wherein R 12 is I, Br, F, Cl, H, OH, OCH3, NH2, NO2, or CH3), and / or (b) The amide of one peptide backbone is N-methylated and / or (c) One of the carbonyl groups in the peptide skeleton is replaced by an imino. The compound according to claim 7.

9. The aforementioned compound has the structure of formula A-III below, or a salt or solvate thereof, 【Transformation 33】 During the ceremony, R ２ａ is, -(CH ２ ) - (R ２ｂ )-(phenyl), where R ２ｂ It does not exist, or -CH ２ -, -NH-, -S-, or -O-, where the phenyl is -NH ２ , -NO ２ -OH, -OR ２ｃ -SH, -SR ２ｃ , -N ３ The 4th position may be substituted with -CN or -O-phenyl, or the 3rd position may be substituted with a halogen or -OH, in the formula, each R ２ｃ Independently, C １ ~C ３ It is a linear or branched alkyl group, R ３ａ C １ ~C ５ It is alkyl, R ｙ is hydrogen or R ３ｅ R ３ｆ And in the formula, R ３ｅ is a linear C １ ~C ５ It is an alkylenyl, and in the formula, R ３ｆ is -N(R ３ｇ ) ２～３ And in the formula, each R ３ｇ These are independently -H or linear or branched C １ ~C ３ It is alkyl, R ４ａ R ４ｂ R ４ｃ And in the formula, R ４ｂ is a straight chain of C １ ~C ５ Alkirenyl, C ２ ~C ５ Alkenylenyl, or C ２ ~C ５ It is an alkynirenyl, and in the formula, R ４ｃ is -N(R ４ｄ ) ２～３ or guanidino, where each R ４ｄ These are independently -H or linear or branched C １ ~C ３ It is alkyl, R ５ａ is, -(CH ２ ) １～３ -R ５ｂ And in the formula, R ５ｂ teeth, Phenyl, -NH ２ , -NO ２ , -OH, -SH, -N ３ A phenyl which may be substituted with one or more of the following: substitution at the 4-position of -CN or -O-phenyl, substitution at the 3-position of a halogen or -OH, and / or substitution at the 5-position of a halogen or -OH. A fused bicyclic or tricyclic aryl or heteroaryl ring, comprising a halogen, -OH, -OR ５ｃ , amino, -NHR ５ｃ , and / or N(R ５ｃ ) ２ A fused bicyclic or tricyclic aryl or heteroaryl ring which may be substituted with one or more of the following, and In the formula, R ５ｃ Each of them independently, C １ ~C ３ It is a linear or branched alkyl group, R ６ａ H, methyl, ethyl, -C≡CH, -CH=CH ２ ien-CH ２ -R ６ｂ -OH, -CH ２ -R ６ｂ -COOH, -CH ２ - (R ６ｂ ) １～３ -NH ２ ien-CH ２ -R ６ｂ -CONH ２ , or -CH ２ -R ６ｂ R ６ｃ And in the formula, each R ６ｂ Independently, does not exist, -CH ２ -, -NH-, -S-, or -O-, and in the formula, R ６ｃ is a 5- or 6-membered aromatic ring, where 0 to 3 carbon atoms are independently substituted with N, S, and / or O heteroatoms, and may also be substituted with 0 to 3 groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen groups. R ８ａ R ８ｂ R ８ｃ And in the formula, R ８ｂ is a straight chain of C １ ~C ５ Alkirenyl, C ２ ~C ５ Alkenylenyl, or C ２ ~C ５ It is an alkynirenyl, and in the formula, R ８ｃ is -N(R ８ｄ ) ２～３ or guanidino, where each R ８ｄ These are independently -H or linear or branched C １ ~C ３ It is alkyl, R ９ａ is -C(O)NH ２ , -C(O)-OH, -CH ２ -C(O)NH ２ ien-CH ２ -C(O)-OH, -R ９ｂ -R ９ｃ , or -R ９ｂ - [Linker] - R Ｘ ｎ１ And in the formula, R ９ｂ is -C(O)NH- and also R ９ｃ teeth, 【Transformation 34】 And in the formula, R ９ｄ C is a linear or branched C １ ~C ５ It is an alkylenyl, R ９ｅ These are carboxylic acids, sulfonic acids, sulfinic acids, phosphoric acids, amino acids, guanidino, -SH, -OH, -NH-C(O)-CH ３ , -S-C(O)-CH ３ , -OC(O)-CH ３ -NH-C(O)-(phenyl), -S-C(O)-(phenyl), -O-C(O)-(phenyl), -NH-CH ３ , -N(CH ３ ) ２ , -S-CH ３ , -O-CH ３ , or phenyl, and also R ９ｆ is amino or -OH, R Ａ７ａ C １ ~C ３ It is an alkylenyl, R Ａ１０ It does not exist, or -[linker]-R Ｘ ｎ１ And, R Ａ１０ If it does not exist, R Ａ１ａ teeth, Straight-chain C １ ~C ５ alkyl, C ２ ~C ５ alkenyl, or C ２ ~C ５ alkynyl, wherein 0 to 2 carbons in the C ２ ~C ５ alkyl, alkenyl, or alkynyl are independently substituted with one or more N, S, and / or O heteroatoms, and this is C being -SH, -OH, amino, carboxy, guanidino, -NH-C(O)-CH ３ , -S-C(O)-CH ３ , -O-C(O)-CH ３ , -NH-C(O)-(phenyl), -S-C(O)-(phenyl), -O-C(O)-(phenyl), -NH-(CH ３ ) １～２ , -NH ２ -CH ３ , -N(CH ３ ) ２～３ , -S-CH ３ , or -O-CH ３ and may be substituted with one substituent selected therefrom, Branch C １ ~C １０ It is an alkyl, alkenyl, or alkynyl of the formula, where C ２ ~C １０ The 0 to 3 carbon atoms in the molecule are independently substituted with one or more N, S, and / or O heteroatoms, or R Ａ１ｂ R Ａ１ｃ And in the formula, R Ａ１ｂ is a linear C １ ~C ３ It is an alkylenyl, and in the formula, C ２ Alkyrenyl or C ３ The alkylenyl may be substituted with an N, S, or O heteroatom, where R Ａ１ｃ teeth, A 5- or 6-membered aromatic ring, wherein one or more carbon atoms may be independently substituted with N, S, and / or O heteroatoms, or may be substituted with one or more groups independently selected from oxo, hydroxyl, sulfhydryl, nitro, amino, and / or halogen, or A fused bicyclic or tricyclic aryl group, wherein one or more carbon atoms may be independently substituted with N, S, and / or O heteroatoms, and also with halogens, -OH, -OR Ａ１ｄ , amino, -NHR Ａ１ｄ , and / or N(R Ａ１ｄ ) ２ It may be substituted with one or more groups independently selected from R, where each R Ａ１ｄ C １ ~C ３ A linear or branched alkyl group, a fused bicyclic or tricyclic aryl group, R Ａ１０ However, -[linker]-R Ｘ ｎ１ If so, R Ａ１ａ R Ａ１ｅ R Ａ１ｆ And in the formula, R Ａ１ｅ is a straight chain of C １ ~C ５ Alkirenyl, C ２ ~C ５ Alkenylenyl, or C ２ ~C ５ This is alkynirenyl, and here C ２ ~C ５ In the alkylenyl, alkenylenyl, or alkynylenyl, 0 to 2 carbon atoms are independently substituted with N, S, and / or O heteroatoms. R Ａ１ｆ -NH-C(O)-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH ３ )-, -NHC(S)-, -C(S)NH-, -N(CH ３ )C(S)-, -C(O)N(CH ３ )-,-N(CH ３ )C(O)-, -C(S)N(CH ３ )-, -NHC(S)NH-, -NHC(O)NH-, -S-, -S(O)-, -S(O)-O-, -S(O) ２ -, -S(O) ２ -O-, -S(O) ２ -NH-, -S(O)-NH-, -Se-, -Se(O)-, -Se(O) ２ -, -NHNHC(O)-, -C(O)NHNH-, -OP(O)(O － ) O-,-phosphamide-,-thiophosphodiester-,-S-tetrafluorophenyl-S-, 【Chemistry 35】 or polyethylene glycol, The linker is X １ L １ 、X １ L １ X １ L １ 、or X １ L １ X １ L １ X １ L １ and X １ Each of them independently, -CH ２ - 【Transformation 36】 And, L １ These are, independently, -NH-, -C(O)-, -NHC(O)-, -C(O)NH-, and -N(CH ３ )C(O)-, or -C(O)N(CH ３ ) - and R １１ Each of these is independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid, and R Ｚ Each of these is an albumin binder, independently of the others. Each n1 is independently 0, 1, or 2. Each R Ｘ This is an albumin binder, therapeutic moiety, fluorescent label, radiolabeling group, or group that can be radiolabeled. In the formula, 0 to 3 peptide backbone amides are independently 【Chemistry 37】 Substituted with amidine or thioamide, In the formula, 0 to 3 amides in the peptide backbone are N-methylated, and The compound according to claim 1, wherein the C-terminus may be amidated.

10. The aforementioned compound has the structure of formula A-IV below, or a salt or solvate thereof, 【Transformation 38】 During the ceremony, Formula A-IV -NH-CH(R ２ａ )-C(O)- is a Tyr residue, a Phe residue, (4-NO ２ )-Phe residue, (4-NH ２ ) -Phe residue, hTyr residue, (3-I)Tyr residue, Glu residue, Glun residue, or D-Tyr residue, Formula A-IV -NH-CH(R ４ａ )-C(O)- forms a D-Arg residue or a D-hArg residue, Formula A-IV -NH-CH(R ５ａ )-C(O)- consists of a 2-(Ant)Ala residue, a 2-Nal residue, a Trp residue, and (4-NH ２ ) Forms a Phe residue, an hTyr residue, or a Tyr residue, Formula A-IV -NH-CH(R ６ａ )-C(O)- forms His residues, D-His residues, D-Glu residues, D-Gln residues, D-Ala residues, D-Phe residues, D-Ser residues, D-Dab residues, and D-Dap residues. R ３ａ C １ ~C ５ It is alkyl, R ｙ is hydrogen or R ３ｅ R ３ｆ And in the formula, R ３ｅ is a linear C １ ~C ５ It is an alkylenyl, and in the formula, R ３ｆ is -N(R ３ｇ ) ２～３ And in the formula, each R ３ｇ These are independently -H or linear or branched C １ ~C ３ It is alkyl, R ８ａ R ８ｂ R ８ｃ And in the formula, R ８ｂ is a straight chain of C １ ~C ５ Alkirenyl, C ２ ~C ５ Alkenylenyl, or C ２ ~C ５ It is an alkynirenyl, and in the formula, R ８ｃ is -N(R ８ｄ ) ２～３ or guanidino, where each R ８ｄ These are independently -H or linear or branched C １ ~C ３ It is alkyl, R ９ａ is -C(O)NH ２ , -C(O)-OH, -CH ２ -C(O)NH ２ ien-CH ２ -C(O)-OH, or -R ９ｂ - [Linker] - R Ｘ ｎ１ And, R ９ｂ is -C(O)NH-, R Ａ７ａ C １ ~C ３ It is an alkylenyl, R Ａ１０ It does not exist, or -[linker]-R Ｘ ｎ１ And, R Ａ１０ If it does not exist, R Ａ１ａ is a linear C １ ~C ５ Alkyl, -SH, -OH, amino, carboxy, guanidino, -NH-C(O)-CH ３ , -S-C(O)-CH ３ , -OC(O)-CH ３ -NH-C(O)-(phenyl), -S-C(O)-(phenyl), -O-C(O)-(phenyl), -NH-(CH ３ ) １～２ , -NH ２ -CH ３ , -N(CH ３ ) ２～３ , -S-CH ３ , -O-CH ３ , or branch C １ ~C １０ A linear C molecule may be substituted with one substituent selected from alkyl, alkenyl, or alkynyl atoms. １ ~C ５ It is alkyl, R Ａ１０ However, -[linker]-R Ｘ ｎ１ If so, R Ａ１ａ R Ａ１ｅ R Ａ１ｆ And in the formula, R Ａ１ｅ is a straight chain of C １ ~C ５ Alkirenyl, C ２ ~C ５ Alkenylenyl, or C ２ ~C ５ This is alkynirenyl, and here C ２ ~C ５ In the alkylenyl, alkenylenyl, or alkynylenyl, 0 to 2 carbon atoms are independently substituted with N, S, and / or O heteroatoms. R Ａ１ｆ -NH-C(O)-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH ３ )-, -NHC(S)-, -C(S)NH-, -N(CH ３ )C(S)-, -C(O)N(CH ３ )-,-N(CH ３ )C(O)-, -C(S)N(CH ３ )-, -NHC(S)NH-, -NHC(O)NH-, -S-, -S(O)-, -S(O)-O-, -S(O) ２ -, -S(O) ２ -O-, -S(O) ２ -NH-, -S(O)-NH-, -Se-, -Se(O)-, -Se(O) ２ -, -NHNHC(O)-, -C(O)NHNH-, -OP(O)(O － ) O-,-phosphamide-,-thiophosphodiester-,-S-tetrafluorophenyl-S-, 【Chemistry 39】 or polyethylene glycol, The aforementioned linker is X １ L １ , X １ L １ X １ L １ , or X １ LX １ L １ X １ L １ And, X １ Each of them independently, -CH ２ - 【Chemistry 40】 And, L １ These are, independently, -NH-, -C(O)-, -NHC(O)-, -C(O)NH-, and -N(CH ３ )C(O)-, or -C(O)N(CH ３ ) - and R １１ Each of these is independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid, and R Ｚ Each of these is an albumin binder, independently of the others. Each n1 is independently 0, 1, or 2. Each R Ｘ This is an albumin binder, therapeutic moiety, fluorescent label, radiolabeling group, or group that can be radiolabeled. In the formula, 0 to 3 peptide backbone amides are independently 【Chemistry 41】 Substituted with amidine or thioamide, In the formula, 0 to 3 amides in the peptide backbone are N-methylated, and The compound according to claim 1 or 9, wherein the C-terminus may be amidated.

11. (a) -NH-CH(R) of formula A-III or formula A-IV Ａ１ａ )-C(O)- forms a Phe residue, 1-Nal residue, 2-Nal residue, Tyr residue, Trp residue, Lys residue, hLys residue, Lys(Ac) residue, Dap residue, Dab residue, or Orn residue, and / or (b) R y is R 3b R 3c, where R 3b is a linear C1-C5 alkylenyl, where R 3c is -N(R 3d) 2, where each R 3d is independently -H or a linear or branched C1-C3 alkyl, and R 3a may be methyl. (c) The linker is X1L1, where X1 is 【Chemistry 42】 And L 1 is -NH- or -NHC(O)-, and / or R 11 is sulfonic acid (-SO3H), The compound according to claim 9 or 10.

12. (a) R ９ａ is -C(O)NH ２ , -C(O)-OH, -R ９ｂ -R ９ｃ , or -R ９ｂ - [Linker] - R Ｘ ｎ１ And also R ９ｂ is -C(O)NH- and / or (b) The amide of the peptide backbone to be substituted is zero. The compound according to any one of claims 1 to 11.

13. (a) The amide of one peptide backbone is N-methylated, or (b) The amide of the peptide backbone to be N-methylated is zero. The compound according to any one of claims 1 to 12.

14. Compounds of formula A, formula A-I, or formula A-II, formula A-III, formula A-IV, or their salts or solvates, having the following combinations, are the compounds according to any one of claims 1 to 13: (1)-NH-CH(R ２ａ )-C(O)- forms a Tyr residue, -NH-CH(R ３ａ )-C(O)- forms a Lys(iPr) residue, -NH-CH(R ４ａ )-C(O)- forms a D-Arg residue, -NH-CH(R ５ａ )-C(O)- forms a 2-Nal residue, -NH-CH(R ６ａ )-C(O)- forms D-Ala, -NH-CH(R Ａ７ａ )-C(O)- forms a D-amino acid residue, in the formula R Ａ７ａ C １ ~C ３ It is alkyenyl, and also -NH-CH(R ８ａ ) - is R ９ａ Together with the -C(O)-, it forms a Lys(iPr) residue. (2) -NH-CH(R ２ａ )-C(O)- forms a Tyr residue, -NCH ３ -CH(R) ３ａ )-C(O)- forms a Lys(iPr) residue, -NH-CH(R ４ａ )-C(O)- forms a D-Arg residue, -NH-CH(R ５ａ )-C(O)- forms a 2-Nal residue, -NH-CH(R ６ａ )-C(O)- forms D-Ala, -NH-CH(R Ａ７ａ )-C(O)- forms a D-amino acid residue, in the formula R Ａ７ａ C １ ~C ３ It is an alkyenyl, and also -NH-CH(R ８ａ ) - is R ９ａ Together with the -C(O)-, it forms a Lys(iPr) residue. (3)-NH-CH(R ２ａ )-C(O)- forms a Tyr residue, -NH-CH(R ３ａ )-C(O)- forms a Lys(iPr) residue, -NH-CH(R ４ａ )-C(O)- forms a D-Arg residue, -NH-CH(R ５ａ ) - C (= NH) - and in the formula, R ５ａ is, -CH ２ (2-naphthyl) -NH-CH(R ６ａ )-C(O)- forms D-Ala, -NH-CH(R Ａ７ａ )-C(O)- forms a D-amino acid residue, in the formula R Ａ７ａ C １ ~C ３ It is an alkyenyl, and also -NH-CH(R ８ａ ) - is R ９ａ Together with the -C(O)-, it forms a Lys(iPr) residue. (4)-NH-CH(R ２ａ )-C(O)- forms a Tyr residue, -NH-CH(R ３ａ )-C(O)- forms a Lys(iPr) residue, -NH-CH(R ４ａ ) - C (= NH) - and in the formula, R ４ａ is, -(CH ２ ) ３ NHC (=NH)NH ２ And, -NH-CH(R ５ａ )-C(O)- forms a 2-Nal residue, -NH-CH(R ６ａ )-C(O)- forms D-Ala, -NH-CH(R Ａ７ａ )-C(O)- forms a D-amino acid residue, in the formula R Ａ７ａ C １ ~C ３ It is an alkyenyl, and also -NH-CH(R ８ａ ) - is R ９ａ Together with the -C(O)-, it forms a Lys(iPr) residue. (5)-NH-CH(R ２ａ )-C(O)- forms a Tyr residue, -NH-CH(R ３ａ ) - C (= NH) - and in the formula, R ３ａ is, -(CH ２ ) ４ NH(iPr), -NH-CH(R ４ａ )-C(O)- forms a D-Arg residue, -NH-CH(R ５ａ )-C(O)- forms a 2-Nal residue, -NH-CH(R ６ａ )-C(O)- forms D-Ala, -NH-CH(R Ａ７ａ )-C(O)- forms a D-amino acid residue, in the formula R Ａ７ａ C １ ~C ３ It is an alkyenyl, and also -NH-CH(R ８ａ ) - is R ９ａ It combines with the -C(O)- to form a Lys(iPr) residue, or (6)-NH-CH(R ２ａ )-C(O)- forms a Tyr residue, -NH-CH(R ４ａ )-C(O)- forms a D-Arg residue, -NH-CH(R ５ａ )-C(O)- forms a 2-Nal residue, -NH-CH(R ６ａ )-C(O)- forms D-Ala, -NH-CH(R Ａ７ａ )-C(O)- forms a D-amino acid residue, in the formula R Ａ７ａ C １ ~C ３ It is an alkyenyl, and also -NH-CH(R ８ａ ) - is R ９ａ Together with the -C(O)-, they form a Lys(iPr) residue. In the formula, R ｙ is, -(CH ２ ) ４ -NH-(iPr), and also R ３ａ is, -CH ３ That is the case.

15. (a) Compound of formula B, or a salt or solvate thereof, in the following combinations: -NH-CH(R ２ａ )-C(O)- forms a Tyr residue, -NH-CH(R ３ａ )-C(O)- forms a Lys(iPr) residue, -NH-CH(R ４ａ )-C(O)- forms a D-Arg residue, -NH-CH(R ５ａ )-C(O)- forms a 2-Nal residue, and -NH-CH(R ６ａ )-C(O)- forms D-Ala, Having, or (b) Compounds of formula C, or their salts or solvates, in the following combinations: -NH-CH(R2a)-C(O)- forms a Tyr residue, -NH-CH(R3a)-C(O)- forms a Lys(iPr) residue, -NH-CH(R 4a)-C(O)- forms a D-Arg residue, -NH-CH(R 5a)-C(O)- forms a 2-Nal residue, and -NH-CH(R 6a)-C(O)- forms D-Ala, Having, The compound according to any one of claims 1 and 12 to 14.

16. (a) at least one R Ｘ is a radioactively labeled group or a group that can be radioactively labeled. Each group that can be radiolabeled may be independently selected from a metal chelating agent that may form a complex with a radioactive metal or a radioisotope-bound metal, a prosthetic group containing trifluoroborate (BF3), or a prosthetic group containing a silicon-fluorine-acceptor moiety, sulfonyl fluoride, or phosphoryl fluoride. The compound according to any one of claims 1 to 15.

17. (a) The metal chelating agent forms a complex with a radioactive isotope, and / or (b) The metal chelating agent is a polyaminocarboxylate chelating agent or (c) The metal chelating agent is DOTA, MACROPA, or a derivative thereof, (d) The metal chelating agent is selected from Table 3, The compound according to claim 16.

18. BF ３ The bonding group containing -R １３ R １４ BF ３ And in the formula, R １３ is, -(CH ２ ) １～５ - and -R １４ BF ３ The selection is made from Table 5 or Table 6, or 【Chemistry 43】 And in the formula, each R １５ and each R １６ These are independently branched or linear C １ ~C ５ It is alkyl, -R 14 BF 3 is, 【Chemistry 44】 Even if that is the case, R15 and R16 may each be methyl, The bonding group containing BF3 may also contain at least one 18F. The compound according to claim 16.

19. (a) at least one R Ｘ is the therapeutic part, and / or (b) At least one RX is a fluorescent label, The compound according to any one of claims 1 to 18.

20. cyclo[Lys-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2, cyclo[Lys-Tyr-NMe-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2, cyclo[Lys-NH2-Tyr-NMe-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2, cyclo[Lys(ivDde)-Tyr-NMe-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2, Cyclo[Lys-Tyr-(N-isopropylbutan-1-amine)-D-Ala-D-Arg-2Na-D-Ala-D-Glu]Lys(iPr)-NH2, Cyclo[Lys-NH2-Tyr-(N-isopropylbutan-1-amine)-D-Ala-D-Arg-2Na-D-Ala-D-Glu]Lys(iPr)-NH2, Cyclo[Lys(ivDde)-Tyr-(N-isopropylbutan-1-amine)-D-Ala-D-Arg-2Na-D-Ala-D-Glu]Lys(iPr)-NH2, cyclo(Ttn)[β-Ala(iPr)-Tyr-Lys(iPr)-D-Arg-2NaI-D-Ala-Cys]Lys(iPr)-NH2, cyclo(Ttn)[D-β-Ala(iPr)-Tyr-Lys(iPr)-D-Arg-2NaI-D-Ala-Cys]Lys(iPr)-NH2, Cyclo[Lys-Tyr-(N-isopropylbutan-1-amine)-Ala-D-Arg-2Na-D-Ala-D-Glu]Lys(iPr)-NH2, Cyclo[Lys-NH2-Tyr-(N-isopropylbutan-1-amine)-Ala-D-Arg-2Na-D-Ala-D-Glu]Lys(iPr)-NH2, Cyclo[Lys(ivDde)-Tyr-(N-isopropylbutane-1-amine)-Ala-D-Arg-2Na-D-Ala-D-Glu]Lys(iPr)-NH2, cyclo[Lys-Tyr-Lys(iPr)-D-Arg-2Nal-Ψ-D-Ala-D-Glu]Lys(iPr)-NH2, cyclo[Lys-NH2-Tyr-Lys(iPr)-D-Arg-2Nal-Ψ-D-Ala-D-Glu]Lys(iPr)-NH2, cyclo[Lys(ivDde)-Tyr-Lys(iPr)-D-Arg-2Nal-Ψ-D-Ala-D-Glu]Lys(iPr)-NH2, cyclo[Lys-Tyr-Lys(iPr)-D-Arg-Ψ-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2, cyclo[Lys-NH2-Tyr-Lys(iPr)-D-Arg-Ψ-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2, cyclo[Lys(ivDde)-Tyr-Lys(iPr)-D-Arg-Ψ-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2, cyclo[Lys-Tyr-Lys(iPr)-Ψ-D-Arg-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2, cyclo[Lys-NH2-Tyr-Lys(iPr)-Ψ-D-Arg-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2, or cyclo[Lys(ivDde)-Tyr-Lys(iPr)-Ψ-D-Arg-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2, A compound selected from one or more of its salts or solvates, The compound may optionally be bound to a radiolabeled group, a group that can be radiolabeled, and / or an albumin binder via one or more linkers. Each linker may independently be 1 to 10 units of linear or branched X1L1 and / or X1(L1)2 (wherein, Each X1 is independently a linear, branched, and / or cyclic C1-C15 alkyrenyl, C2-C15 alkennylenyl, or C2-C15 alkynyrenyl, where 0-6 carbons are independently substituted with N, S, and / or O heteroatoms and 0-3 groups independently selected from one or a combination of oxo, hydroxyl, sulfhydryl, halogen, guanidino, carboxylic acid, sulfonic acid, sulfinic acid, and / or phosphoric acid, and Each L 1 is independently -NH-C(O)-, -NH-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH 3 )-, -NHC(S)-, -C(S)NH-, -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -N(CH 3 )C(O)-, -C(S)N(CH 3 )-, -NHC(S)NH-, -NHC(O)NH-, -S-, -S(O)-, -S(O)-O-, -S(O) 2 -, -S(O) 2 -O-, -S(O) 2 -NH-, -S(O)-NH-, -Se-, -Se(O)-, -Se(O) 2 -, -NHNHC(O)-, -C(O)NHNH-, -OP(O)(O-)O-, -phosphamide-, -thiophosphodiester-, -S-tetrafluorophenyl-S-, 【Chemistry 45】 (or polyethylene glycol) The linker is a linear or branched peptide linker (Xaa) 1 to 5, where each Xaa is independently selected from amino acid residues that constitute a protein or amino acid residues that do not constitute a protein, and the amino group in each Xaa may be methylated or The linker may be X1L1, X1L1X1L1, or X1L1X1L1X1L1 (wherein each X1 is the same or different, and each L1 is the same or different, in the formula, Each X1 is independently a linear, branched, and / or cyclic C1-C15 alkyrenyl, C2-C15 alkennylenyl, or C2-C15 alkynyrenyl, where 0-6 carbons are independently substituted with N, S, and / or O heteroatoms and 0-3 groups independently selected from one or a combination of oxo, hydroxyl, sulfhydryl, halogen, guanidino, carboxylic acid, sulfonic acid, sulfinic acid, and / or phosphoric acid, and Each L 1 is independently -NH-C(O)-, -C(O)-, -O-, -C(O)NH-, -C(O)-N(CH 3 )-, -NHC(S)-, -C(S)NH-, -N(CH 3 )C(S)-, -C(O)N(CH 3 )-, -N(CH 3 )C(O)-, -C(S)N(CH 3 )-, -NHC(S)NH-, -NHC(O)NH-, -S-, -S(O)-, -S(O)-O-, -S(O) 2 -, -S(O) 2 -O-, -S(O) 2 -NH-, -S(O)-NH-, -Se-, -Se(O)-, -Se(O) 2 -, -NHNHC(O)-, -C(O)NHNH-, -OP(O)(O-)O-, -phosphamide-, -thiophosphodiester-, -S-tetrafluorophenyl-S-, 【Chemistry 46】 (or polyethylene glycol) compound.

21. (a) The linker is X １ L １ , X １ L １ X １ L １ , or X １ L １ X １ L １ X １ L １ And in the formula, each X １ They are the same or different, and each L １ They are the same or different, and X １ teeth, 【Chemistry 47】 And in the formula, each R １１ These are independently carboxylic acids, sulfonic acids, sulfinic acids, or phosphoric acids, or (b) Each X1 is, 【Chemistry 48】 In the formula, each R11 is independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid. The compound according to claim 20.

22. (a) The linker is a linear or branched peptide linker (Xaa) １～５ In the formula, at least one Xaa is selected from cysteic acid, Glu, Asp, or 2-aminoadipic acid (2-Aad), and the amino group in each Xaa may be methylated or (b) The linker is a single amino acid residue selected from cysteic acid, Glu, Asp, or 2-aminoadipic acid (2-Aad), and the amino group, the single amino acid residue may be methylated, or (c) The linker is a linear or branched peptide linker (Xaa) 1 to 5, where at least one Xaa is selected from Dap, Dab, Orn, Arg, hArg, Agb, Agp, Acp, Pip, or Nε,Nε,Nε-trimethyllysine, and the amino group in each Xaa may be methylated or (d) The linker is a single amino acid residue selected from D-Arg, L-Arg, D-hArg, L-hArg, or Pip, and the amino group in the single amino acid residue may be methylated. The compound according to claim 20.

23. The groups that can be radiolabeled are, independently, metal chelating agents that may form complexes with radioactive metals or radioisotope-bound metals, trifluoroborate (BF ３ A compound according to any one of claims 20 to 22, selected from a conjugate containing ) or a conjugate containing a silicon-fluorine-receptor moiety, sulfonyl fluoride, or phosphoryl fluoride.

24. (a) The metal chelating agent forms a complex with the radioactive isotope, and / or (b) The metal chelating agent is DOTA, H2-MACROPA, or a derivative thereof, and / or (c) The metal chelating agent is selected from Table 3. The compound according to claim 23.

25. (a) BF ３ The bonding group containing -R １３ R １４ BF ３ And in the formula, R １３ is, -(CH ２ ) １～５ - and -R １４ BF ３ The selection is made from Table 5 or Table 6, or 【Chemistry 49】 And in the formula, each R １５ and each R １６ These are independently branched or linear C １ ~C ５ It is alkyl, -R 14 BF 3 is, [Transformation 50] It may also be (wherein R15 and R16 are methyl, respectively), and or The bonding group containing BF3 contains at least one 18F, The compound according to claim 23.

26. (a) The radioactive isotope is ６４ Cd, ６７ Cd, ９０ Y, １５３ Sm, １４９ Tb, １６１ Tb, １７７ Lu, ２２５ Ac, ２１３ Bi, ２２４ Ra, ２１２ Bi, ２１２ Pb, ２２７ Th, ２２３ Ra, ４７ Sc, １８６ Re, １８８ Re, ９４ｍ Tc, ６８ Ga, ６１ Cd, ６７ Ga, ９９ｍ Tc, １１１ In, ４４ Sc, ８６ Y, ８９ Zr, ９０ Nb, １１７ｍ Sn, １６５ Er, ２１１ At, ２０３ Pb, １６６ Ho, １４９ Pm, １５９ Gd, １０５ Rh, １０９ Pd, １９８ Au, １９９ Au, １７５ Yb, １４２ Pr, １５２ Tb, １５５ Tb, or １１４ｍ In, or (b) The radioactive isotopes are 177 Lu, 111 In, 213 Bi, 68 Ga, 67 Ga, 203 Pb, 212 Pb, 44 Sc, 47 Sc, 90 Y, 86 Y, 225 Ac, 117 m Sn, 153 Sm, 149 Tb, 161 Tb, 165 Er, 224 Ra, 212 Bi, 227 Th, 223 Ra, 64 Cu, 155 Tb, 155 Tb, or 67 Cu. The compound according to any one of claims 20, 23, and 24.

27. ​​(a) The compound of formula A has the following chemical formula: 【Chemistry 51-1】 【Chemistry 51-2】 A compound having or a salt or solvate thereof (the compound may form a complex with a radioisotope), (b) The compound of formula A has the following chemical formula: 【Chemistry 52】 A compound having or a salt or solvate thereof (the compound may form a complex with a radioisotope), (c) The compound of formula A has the following chemical formula: 【Chemistry 53】 A compound having or a salt or solvate thereof (the compound may form a complex with a radioisotope), (c) The compound of formula A has the following chemical formula: 【Chemistry 54-1】 【Chemistry 54-2】 【Chemistry 54-3】 【Chemistry 54-4】 A compound having or a salt or solvate thereof (the compound may form a complex with a radioisotope), (e) The compound of formula B has the following chemical formula: 【Transformation 55】 A compound having or a salt or solvate thereof (the compound may form a complex with a radioactive isotope), or (f) The compound has the following chemical formula: 【Transformation 56】 A compound having or a salt or solvate thereof (the compound may form a complex with a radioactive isotope), The compound according to claim 1.

28. It is intended for use in imaging CXCR4-expressing tissue in subjects, or for use in imaging inflammatory conditions or diseases. (a) at least one R Ｘ However, it contains imaging radioisotopes or forms complexes with imaging radioisotopes. The imaging radioisotopes may be 68 Ga, 67 Ga, 61 Cu, 64 Cu, 99 m Tc, 114 m In, 111 In, 44 Sc, 86 Y, 89 Zr, 90 Nb, 18 F, 131 I, 123 I, 124 I, 152 Tb, 155 Tb, or 72 As, and / or (b) For use in imaging CXCR4-expressing tissue in a subject, or for use in imaging an inflammatory condition or disease, wherein the compound is optionally bound via a linker to a metal chelating agent that complexes with the imaging radioisotope, or optionally bound via a linker to a conjugate containing at least one 18F-containing BF3. The compound according to any one of claims 1 to 27.

29. It is intended for use in the treatment of diseases or conditions characterized by CXCR4 expression in the subject, (a) at least one R Ｘ However, it contains therapeutic radioisotopes, or forms complexes with therapeutic radioisotopes, or at least one R Ｘ However, whether it includes a therapeutic component or (b) For use in the treatment of a disease or condition characterized by the expression of CXCR4 in a subject, wherein the compound is optionally bound to a metal chelating agent that complexes with a therapeutic radioisotope via a linker. The compound according to any one of claims 1 to 27.

30. (a) The therapeutic radioactive isotope is １６５ Er, ２１２ Bi, ２１１ At, １６６ Ho, １４９ Pm, １５９ Gd, １０５ Rh, １０９ Pd, １９８ Au, １９９ Au, １７５ Yb, １４２ Pr, １７７ Lu, １１１ In, ２１３ Bi, ２１２ Pb, ４７ Sc, ９０ Y, １１７ｍ Sn, １５３ Sm, １４９ Tb, １６１ Tb, ２２４ Ra, ２２５ Ac, ２２７ Th, ２２３ Ra, ７７ As, １３１ I, ６４ Cd, ６７ Cu, or 188Re, and / or (b) The disease or condition is a cancer that expresses CXCR4, The compound according to claim 29.

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