Compounds targeting CXCR4 and methods of making and using same

Abstract

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

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Application No. 63 / 332,885, filed on April 20, 2022, the disclosure of which is incorporated herein by reference in its entirety. Technical Field

[0003] The present invention relates to novel peptide compounds, in particular compounds that target CXCR4 for purposes such as imaging and / or therapy. Background Art

[0004] CXC chemokine receptor type 4 (CXCR4) is a G protein-coupled transmembrane receptor expressed in the blood and immune tissues and systems. 1,2 CXCR4 has only one chemokine as a substrate, stromal-derived factor-1 (SDF-1), also known as CXCL12. 3 Aberrant expression of CXCR4 is involved in many important pathologies involving inflammation and immune cell trafficking, including atherosclerosis, 4 Systemic lupus erythematosus 5,6 , cancer, etc. Importantly, CXCR4 has been found to play a key role in tumorigenesis, chemoresistance, and metastasis, and its expression has been detected in more than twenty different cancer subtypes associated with poor prognosis. 7–12 Therefore, non-invasive in vivo molecular probes are needed to image CXCR4-expressing tumors for better detection, staging, and monitoring of aggressive cancers. 13–16 Such imaging agents enable rapid assessment of a patient's expression of specific biomarkers without the need for invasive biopsy procedures, which may not always correctly capture the heterogeneity of a patient's disease. Furthermore, given the very poor efficacy of CXCR4 inhibitors in clinical trials, an alternative strategy is to couple the inhibitors to radiotherapeutic isotopes to deliver ionized beta, alpha, or Auger electrons to the site of disease.

[0005] LY2510924 (cyclo[Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-D-Glu]-Lys(iPr)-NH2) is a cyclic peptide that has been reported to block the binding of SDF-1α to CXCR4. 50 The value is 79pM 17 LY2510924 was reported to inhibit the growth of non-Hodgkin lymphoma, renal cTbaell carcinoma, lung cancer, colorectal cancer, and breast cancer xenograft models. LY2510924 was not able to enhance the therapeutic efficacy of carboplatin / etoposide chemotherapy in patients with small cell lung cancer. 18 .

[0006] Many CXCR4 peptide-based inhibitors rely on key amino acid residues, including 1) one or more cationic side chain residues to contact several anionic residues present in the CXCR4 pocket, 2) tyrosine residues, and 3) naphthalene-based unnatural amino acids to maintain good binding affinity to CXCR4. 19 This was exemplified in the development of T140, which systematically replaced every amino acid of a prototype peptide (T22) based on a natural peptide with HIV inhibitory activity through CXCR4 antagonism. 19 This led to the development of a number of potent antagonists of CXCR4, including FC131 (later repurposed as Pentixafor and Pentixather for imaging and radionuclide therapy purposes, respectively) and LY2510924 for radiotheranostic purposes. 20

[0007] Thus, there is an unmet need in the art for improved compounds targeting CXCR4, such as imaging agents and therapeutic agents for in vivo diagnosis and treatment, respectively, of diseases / disorders characterized by expression of CXCR4.

[0008] Any of the foregoing information is not necessarily intended, and should not be construed, to constitute prior art against the present invention. Summary of the Invention

[0009] The present disclosure relates to compounds that are useful as imaging and / or therapeutic agents.

[0010] In some embodiments, the present disclosure provides a compound of Formula A, Formula B, or Formula C, or a salt or solvate thereof:

[0011]

[0012] in:

[0013] R 2a It is -(CH2)-(R 2b )-(phenyl), wherein R 2b Absent, is -CH2-, -NH-, -S- or -O-, wherein the phenyl group is optionally replaced by -NH2, -NO2, -OH, -OR 2c 、-SH、-SR 2c , -N3, -CN or -O-phenyl 4-substituted, wherein the phenyl group is optionally substituted with halogen or -OH 3-substituted, wherein the phenyl group is optionally substituted with halogen or -OH 5-substituted, wherein the -O-phenyl ring is optionally substituted with -NH2, -NO2, -OH, -OR 2c 、-SH、-SR 2c, -N3 or -CN 4-, wherein the -O-phenyl ring is optionally substituted by halogen or -OH 3-, wherein the -O-phenyl ring is optionally substituted by halogen or -OH 5-, wherein each R 2c are independently C1-C3 straight or branched chain alkyl groups;

[0014] R 3a is a C1-C5 alkyl group or R 3b R 3c , where R 3b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbon atoms in C2-C5 are independently replaced by one or more N, S and / or O heteroatoms, wherein R 3c Yes – N(R 3d ) 2-3 or guanidino, where each R 3d are independently -H or linear or branched C1-C3 alkyl;

[0015] R 4a It is R 4b R 4c , where R 4b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbon atoms in C2-C5 are independently replaced by one or more N, S and / or O heteroatoms, wherein R 4c Yes – N(R 4d ) 2-3 or guanidino, where each R 4d are independently -H or linear or branched C1-C3 alkyl;

[0016] R 5a Yes - (CH2) 1-3 -R 5b , where -(CH2) 2-3 - is optionally replaced by a N, S or O heteroatom, wherein R 5b yes:

[0017] Phenyl optionally substituted with one or a combination of:

[0018] -NH2, -NO2, -OH, -OR 5c 、-SH、-SR 5c , -N3, -CN or -O-phenyl 4-substituted; substituted by halogen or -OH 3-; and / or substituted by halogen or -OH 5-; wherein the -O-phenyl ring is optionally substituted by -NH2, -NO2, -OH, -OR 5c , -SH, –SR 5c, -N3 or -CN 4-, wherein the -O-phenyl ring is optionally substituted with halogen or -OH 3-, wherein the -O-phenyl ring is optionally substituted with halogen or -OH 5-; or

[0019] Fused bicyclic or fused tricyclic aryl or heteroaryl rings, each optionally substituted by halogen, -OH, -OR 5c , amino, -NHR 5c and / or N(R 5c ) One or more substitutions in 2;

[0020] Each R 5c are independently C1-C3 straight or branched chain alkyl groups;

[0021] R 6a H, methyl, ethyl, -C≡CH, -CH=CH2, -C≡C-(CH2) 1-3 -OH,-C≡C-(CH2) 1-3 -SH, -C≡C-(CH2) 1-3 -NH2, -C≡C-(CH2) 1-3 -COOH,-C≡C-(CH2) 1-3 -CONH2, -C≡C-(CH2) 1-3 R 6b R 6c , -CH=CH-(CH2) 1-3 -OH,-CH=CH-(CH2) 1-3 -SH, -CH=CH-(CH2) 1-3 -NH2, -CH=CH-(CH2) 1-3 -COOH,-CH=CH-(CH2) 1-3 -CONH2,-CH=CH-(CH2) 1-3 R 6b R 6c ,-CH2-R 6b -OH,-CH2-R 6b -COOH,-CH2-(R 6b ) 1-3 -NH2, -CH2-R 6b -CONH2 or -CH2-R 6b R 6c , where each R 6b are independently absent, are -CH2-, -NH-, -S- or -O-, and wherein R 6c yes:

[0022] a 5- or 6-membered aromatic ring in which one or more carbon atoms are optionally independently replaced by N, S and / or O heteroatoms, and optionally substituted by one or more groups independently selected from oxo, hydroxy, thiol, nitro, amino and / or halogen;

[0023] or -NH-CH(R 6a )-C(O)-NH- is replaced by:

[0024]

[0025] R A7a is a straight chain C1-C5 alkylene group, wherein 0-2 carbon atoms in C2-C5 are independently replaced by one or more N, S and / or O heteroatoms;

[0026] R 8a It is R 8b R 8c , where R 8b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbon atoms in the C2-C5 alkylene, alkenylene or alkynylene are independently replaced by one or more N, S and / or O heteroatoms, wherein R 8c Yes – N(R 8d ) 2-3 or guanidino, where each R 8d are independently -H or linear or branched C1-C3 alkyl;

[0027] R 9a -C(O)NH2、-C(O)-OH、-CH2-C(O)NH2、-CH2-C(O)-OH、-CH2-NH2、-CH2-OH、-CH2-CH2-NH2、-R 9b -R 9c or -R 9b -[Connector]-R X n1 ,in:

[0028] R 9bis -CH2-NH-C(O)-, -CH2-C(O)-, -CH2-O-, -C(O)NH-, -C(O)-N(CH3)-, -CH2-NHC(S)-, -C(S) NH-,-CH2-N(CH3)C(S)-,-C(O)N(CH3)-,-CH2-N(CH3)C(O)-,-C(S)N(CH3)-,-CH2-NHC(S) NH-,-CH2-NHC(O)NH-,-CH2-S-,-CH2-S(O)-,-CH2-S(O)2-,-CH2-S(O)2-NH-,-CH2-S(O)- NH-,-CH2-Se-,-CH2-Se(O)-,-CH2-Se(O)2-,-CH2-NHNHC(O)-,-C(O)NHNH-,-CH2-OP(O)(O - )O-, -CH2-phosphoramide-, -CH2-thiophosphate diester-, -CH2-S-tetrafluorophenyl-S-, or polyethylene glycol; and

[0029] R 9c is hydrogen or a linear, branched and / or cyclic C1-C 20 Alkyl, alkenyl or alkynyl, wherein C2-C 20 0-6 carbon atoms are independently replaced by N, S and / or O heteroatoms, and 0-3 groups are independently selected from one or a combination of oxo, hydroxyl, thiol, halogen, guanidino, carboxylic acid, sulfonic acid, sulfinic acid and / or phosphoric acid;

[0030] R A10 Does not exist or is -[connector]-R X n1 ;

[0031] When R A10 If it does not exist, then R A1a yes:

[0032] Straight chain C1-C5 alkyl, C2-C5 alkenyl or C2-C5 alkynyl, wherein 0-2 carbons in the C2-C5 alkyl, alkenyl or alkynyl are independently replaced by one or more N, S and / or O heteroatoms, optionally C-substituted by a monosubstituent selected from the group consisting of -SH, -OH, amino, carboxyl, guanidino, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH3) 1-2 、-NH2-CH3、-N(CH3) 2-3 , -S-CH3 or -O-CH3;

[0033] Branched chain C1-C 10 Alkyl, alkenyl or alkynyl, wherein C2-C 10 0-3 carbon atoms in are independently replaced by one or more N, S and / or O heteroatoms; or

[0034] R A1b R A1c , where R A1b is a straight chain C1-C3 alkylene, wherein C2 alkylene or C3 alkylene is optionally replaced by N, S or O heteroatom, wherein R A1c yes:

[0035] a 5- or 6-membered aromatic ring in which one or more carbons are optionally independently replaced by N, S and / or O heteroatoms, and optionally substituted by one or more groups independently selected from oxo, hydroxy, thiol, nitro, amino and / or halogen; or

[0036] Fused bicyclic or fused tricyclic aryl groups, wherein one or more carbons are optionally independently replaced by N, S and / or O heteroatoms, and are optionally independently selected from halogen, -OH, -OR A1d , amino, -NHR A1d and / or N(R A1d )2 is substituted with one or more groups, wherein each R A1d are independently C1-C3 straight or branched chain alkyl groups;

[0037] When R A10 Yes-[Connector]-R X n1 When R A1a It is R A1e R A1f , where R A1e is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbon atoms in the C2-C5 alkylene, alkenylene or alkynylene are independently replaced by N, S and / or O heteroatoms, and R A1f is -NH-C(O)-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C(S)NH-, -N(CH3)C(S)-, -C(O)N(CH3)-, -N(CH3)C(O)-, -C(S)N(CH3)-, -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-, -phosphoramide-, -phosphorothioate diester-, -S-tetrafluorophenyl-S-, or polyethylene glycol;

[0038] R B1a It is a linear, branched and / or cyclic C1-C 10 Alkylene, C2-C 10 Alkenylene or C2-C 10 Alkynylidene, wherein C2-C 10 One or more carbon atoms in the alkylene, alkenylene, and alkynylene groups are optionally independently replaced by N, S, and / or O heteroatoms;

[0039] R B1-7 yes wherein the indole ring and the isoindole ring are each optionally substituted with -F, -Br, -Cl, -I, -OH, -OR B1-7b , -CO-, -COOH, -CONH2, -CN, -O-aryl, -NH2, -NHR B1-7b , N3, -NO2, -NH, -CHO and / or -R B1-7b One or more substitutions, wherein each R B1-7b is a straight-chain or branched C1-C3 alkyl, C2-C3 alkenyl or C2-C3 alkynyl group;

[0040] R B7a is a straight chain C1-C5 alkylene group, wherein 0-2 carbon atoms in the C2-C5 alkylene group are independently replaced by one or more N, S and / or O heteroatoms;

[0041] R B10a It is an amine, -NH-(CH3) 1-2 、-N(CH3) 2-3 , -NH-C(O)-CH3, -NH-C(O)-(phenyl) or –R B10b -[Connector]-R X n1 , where R B10b yes:

[0042] -NH-C(O)-,-C(O)-,-O-,-C(O)NH–,-C(O)-N(CH3)-,-NHC(S)-,-C(S)NH-,-N(CH3)C(S)-,-C(O)N(CH3)-,-N(CH3)C(O)-,-C(S)N(CH3)-,-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-, -phosphoramide-, -phosphorothioate diester-, -S-tetrafluorophenyl-S-,

[0043] or polyethylene glycol;

[0044] R C1a yes wherein the indole, isoindole and triazole rings are each optionally substituted with -F, -Br, -Cl, -I, -OH, -OR C1b ,-CO-,-COOH,-CONH2,-CN,-O-aryl,-NH2,-NHR C1b ,N3,-NO2,-NH,-CHO and / or –R C1b One or more substitutions, wherein each R C1b is a straight-chain or branched C1-C3 alkyl, C2-C3 alkenyl or C2-C3 alkynyl group;

[0045] R C7a is a straight chain C1-C5 alkylene group, wherein optionally, 0-2 carbon atoms in the C2-C5 alkylene group are independently replaced by one or more N, S and / or O heteroatoms;

[0046] R C10a It is R C10b -R C10c -[Connector]-R X n1 or R C10d ,in:

[0047] R C10b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbon atoms in the C2-C5 alkylene, alkenylene or alkynylene are independently replaced by N, S and / or O heteroatoms;

[0048] R C10cis -NH-C(O)-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C(S)NH-, -N(CH3)C(S)-, -C(O)N(CH3)-, -N(CH3)C(O)-, -C(S)N(CH3)-, -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-, -phosphoramide-, -phosphorothioate diester-, -S-tetrafluorophenyl-S-, or polyethylene glycol; and

[0049] R C10d yes:

[0050] Straight chain C1-C5 alkyl, C2-C5 alkenyl or C2-C5 alkynyl, wherein 0-2 carbons in the C2-C5 alkyl, alkenyl or alkynyl are independently replaced by N, S and / or O heteroatoms, optionally C-substituted by a monosubstituent selected from the group consisting of -SH, -OH, amino, carboxyl, guanidino, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH3) 1-2 、-NH2-CH3、-N(CH3) 2-3 , -S-CH3 or -O-CH3;

[0051] Branched chain C1-C 10 Alkyl, C2-C 10 Alkenyl or C2-C 10 Alkynyl, where C2-C 10 0-3 carbon atoms in the alkyl, alkenyl or alkynyl group are independently replaced by N, S and / or O heteroatoms; or

[0052] R C10e R C10f , where R C10e is a straight chain C1-C3 alkyl group, wherein the C2 alkyl group or the C3 alkyl group is optionally replaced by a N, S or O heteroatom, wherein R C10f yes:

[0053] a 5- or 6-membered aromatic ring in which one or more carbon atoms are optionally independently replaced by N, S and / or O heteroatoms, and optionally substituted by one or more groups independently selected from oxo, hydroxy, thiol, nitro, amino and / or halogen;

[0054] Fused bicyclic or fused tricyclic aryl groups, wherein one or more carbons are optionally independently replaced by N, S and / or O heteroatoms, and are optionally independently selected from halogen, -OH, -OR C10g , amino, -NHR C10g and / or N(R C10g )2 is substituted with one or more groups, wherein R C10g is a C1-C3 straight or branched chain alkyl group;

[0055] R y is hydrogen or R 3e R 3f , where R 3e is a straight chain C1-C5 alkylene group, wherein R 3f Yes – N(R 3g ) 2-3 , where each R 3g are independently -H or linear or branched C1-C3 alkyl;

[0056] Each n1 is independently 0, 1, or 2;

[0057] Each R X is an albumin binder, a therapeutic moiety, a fluorescent label, a radiolabeled group, or a group capable of being radiolabeled; wherein 0-3 peptide backbone amides are independently Amidine or thioamide substitution;

[0058] wherein 0-3 peptide backbone amides are N-methylated; and

[0059] wherein the C-terminus is optionally amidated.

[0060] In some embodiments, the present disclosure relates to a compound selected from Table 2 or a salt or solvate thereof. In some embodiments, the compound is optionally conjugated to a radiolabeling group, a group capable of being radiolabeled, or an albumin binder.

[0061] In some embodiments, the present disclosure relates to a compound selected from Table 4 or a salt or solvate thereof.

[0062] In some embodiments of the compounds of the present disclosure, the compounds are complexed with a radioactive isotope.

[0063] In some embodiments, the present disclosure relates to the use of any of the compounds disclosed herein for imaging CXCR4-expressing tissue in a subject.

[0064] In some embodiments, the present disclosure relates to the use of any of the compounds disclosed herein for imaging an inflammatory condition or disease.

[0065] In some embodiments, the present disclosure provides a method of treating a disease or condition characterized by expression of CXCR4 in a subject, the method comprising administering to the subject in need thereof an effective amount of the compound. In some embodiments, the disease or condition is a cancer that expresses CXCR4.

[0066] In some embodiments, the present disclosure provides a method of imaging CXCR4-expressing tissue in a subject, the method comprising administering to a subject in need of such imaging an effective amount of the compound. BRIEF DESCRIPTION OF THE DRAWINGS

[0067] Features of the present invention will become apparent from the following description with reference to the accompanying drawings, in which:

[0068] Figure 1 Shown are the [ 68 Representative PET / CT images of Ga]Ga-BL34L11. Scale bars are in ID / g%.

[0069] Figure 2 The results show that the expression of [ 177 Representative SPECT / CT images of Lu]Lu-BL34L11. The scale bar is in ID / g%.

[0070] Figure 3 The results show that the expression of [ 177 Representative SPECT / CT images of Lu]Lu-BL34L20. The scale bar is in ID / g%.

[0071] Figure 4 The results show that the expression of [ 177 Representative SPECT / CT images of Lu]Lu-crown-BL34. The scale bar is in ID / g%.

[0072] Figure 5 Shown are the [ 68 Representative PET / CT images of Ga]Ga-BL34N1. The scale bar is in ID / g%.

[0073] Figure 6 Shown are the [ 68Representative PET / CT images of Ga]Ga-BL34T1. The scale bar is in ID / g%.

[0074] Figure 7 Shown are the [ 177 Representative SPECT / CT images of Lu]Lu-BL34T1. The scale bar is in ID / g%.

[0075] Figure 8 Shown are the [ 177 Representative SPECT / CT images of Lu]Lu-BL34L20S. The scale bar is in ID / g%. DETAILED DESCRIPTION

[0076] All publications, patents, and patent applications herein (including any figures and appendices) are incorporated by reference in their entirety for all purposes to the same extent as if each individual publication, patent or patent application, figure or appendix was specifically and individually indicated to be incorporated by reference in its entirety for all purposes.

[0077] definition

[0078] As used herein, the terms "comprising," "having," "including," and "containing," and their grammatical variants, are inclusive or open-ended and do not exclude additional unenumerated elements and / or method steps. The term "consisting essentially of ... ", if used in conjunction with a composition, use, or method herein, represents that additional elements and / or method steps may be present, but these additions do not substantially affect the manner in which the enumerated composition, method, or use function. The term "consisting of ... ", if used in conjunction with a composition, use, or method herein, excludes the presence of additional elements and / or method steps. In certain embodiments, the compositions, uses, or methods described herein that include certain elements and / or steps may also consist essentially of those elements and / or steps, and in other embodiments, consist of those elements and / or steps, regardless of whether these embodiments are specifically mentioned. In certain embodiments, the uses or methods described herein that include certain elements and / or steps may also consist essentially of those elements and / or steps, and in other embodiments, consist of those elements and / or steps, regardless of whether these embodiments are specifically mentioned.

[0079] Reference to an element by the indefinite article "a" does not exclude the possibility that more than one of the element is present, unless the context clearly requires the presence of one and only one of the element. The singular forms "a", "an", and "the" include plural referents unless the content clearly dictates otherwise. When used in this document in conjunction with the term "comprising", the use of the words "a" or "an" can mean "one", but it is also consistent with the meaning of "one or more", "at least one", and "one or more than one".

[0080] Unless otherwise indicated, "certain embodiments," "various embodiments," "one embodiment," and similar terms include particular features of that embodiment described alone or in combination with any other embodiment or embodiments described herein, whether or not directly or indirectly referenced to other embodiments, and whether or not the feature or embodiment is described in the context of a method, product, use, composition, compound, etc.

[0081] As used herein, the terms "treat," "treatment," "therapeutic," and the like include ameliorating symptoms, reducing disease progression, improving prognosis, and reducing recurrence (eg, reducing cancer recurrence).

[0082] As used herein, the term "diagnostic agent" encompasses "imaging agent." Thus, "diagnostic radiometal" includes radiometals suitable for use as imaging agents, and "diagnostic radioisotope" includes radioisotopes suitable for use as imaging agents. Without limitation, diagnostic agents and imaging agents include compounds comprising at least one fluorescent moiety and / or at least one radioisotope suitable for imaging.

[0083] The term "subject" refers to an animal (e.g., a mammal or non-mammal). The subject can be a human or a non-human primate. The subject can be a laboratory mammal (e.g., a mouse, rat, rabbit, hamster, etc.). The subject can be an agricultural animal (e.g., a horse, sheep, cattle, pig, camel, etc.) or a domestic animal (e.g., a dog, cat, etc.). In some embodiments, the subject is a human.

[0084] The compounds disclosed herein may also include their free base form, salts or pharmaceutically acceptable salts. Unless otherwise indicated, the compounds claimed and described herein are meant to include all racemic mixtures and all individual enantiomers or combinations thereof, whether or not they are explicitly indicated herein.

[0085] Compounds disclosed herein can be shown as having one or more charged groups, can be shown as having ionizable groups in an uncharged (e.g., protonated) state, or can be shown as not specifying a formal charge. As will be appreciated by those skilled in the art, the ionization state of certain groups within a compound (such as, but not limited to, carboxylic acid, sulfonic acid, sulfinic acid, phosphoric acid, etc.) depends, in particular, on the pKa of the group and the pH of the position. For example, but not limited to, a carboxylic acid group (i.e., COOH) is generally understood to be deprotonated (and negatively charged) at neutral pH and most physiological pH values, unless the protonation state is stable. Similarly, sulfonic acid groups, sulfinic acid groups, and phosphate groups are generally deprotonated (and negatively charged) at neutral and physiological pH values.

[0086] As used herein, the terms "salt" and "solvate" have their common meanings in chemistry. Therefore, when a compound is a salt or a solvate, it is associated with a suitable counterion. How to prepare a salt or exchange counterions is well known in the art. Typically, such salts can be prepared by reacting the free acid form of these compounds with a stoichiometric suitable base (such as, but not limited to, Na, Ca, Mg or K hydroxides, carbonates, bicarbonates, etc.) or by reacting the free base form of these compounds with a stoichiometric suitable acid. Such reactions are typically carried out in water or an organic solvent or a mixture of the two. For example, the counterion can be changed by ion exchange techniques (such as ion exchange chromatography). Solvates can be prepared by any method known in the art, for example, by dissolving the compound in a hot solvent (for example, water or other solvents), followed by cooling and / or evaporation. Unless otherwise indicated, all zwitterions, salts, solvates, and counterions are intended.

[0087] In certain embodiments, salt or counterion can be pharmaceutically 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, tonicity agent, cryoprotectant, lyoprotectant, suspending agent, emulsifier, antimicrobial agent, preservative, chelating agent, binding agent, surfactant, wetting agent, non-aqueous vehicle (such as fixed oil) or polymer for sustained or controlled release. 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., ed. Lippincott Williams & Wilkins Philadelphia), each of which is incorporated by reference in its entirety.

[0088] As used herein, the expression "Cy-Cz" where y and z are integers (e.g., C1-C 15 , C1-C5, etc.), refers to the number of carbons in a compound, R-group or substituent, or refers to the number of carbons plus heteroatoms when a certain number of carbons are specified to be replaced (or optionally replaced) by heteroatoms. The heteroatoms can include any, some or all possible heteroatoms. For example, in some embodiments, the heteroatoms are selected from N, O, S, P and Se. In some embodiments, the heteroatoms are selected from N, S and O. Unless otherwise stated, such embodiments are non-restrictive. When a carbon is replaced with a heteroatom, it should be understood that the replacement only includes those replacements that are reasonably made by those skilled in the art. For example, -OO- bonds are explicitly excluded. The expression "C1-C5 ... wherein one or more carbons in C2-C5 are optionally independently replaced by N, S and / or O heteroatoms" and similar expressions are intended to specify that the C1 carbon (i.e., the first carbon in the defined group, and therefore the carbon directly bonded to the rest of the compound) is not replaced. Such expressions are also intended to include replacement of one carbon and replacement of multiple carbons with the same heteroatom (eg, one of N, S, or O) or with a combination of different heteroatoms (eg, a combination of N, S, and / or O in appropriate configurations).

[0089] Unless otherwise expressly stated, the term "alkyl" includes any reasonable combination of the following: (1) straight or branched chain; (2) acyclic or cyclic, the latter of which may include polycyclic rings (fused rings, multiple non-fused rings, or combinations thereof); and (3) unsubstituted or substituted. In the context of the expression "alkyl, alkenyl, or alkynyl" and similar expressions, "alkyl" should be understood to be a saturated alkyl group. As used herein, the term "straight chain" can be used as commonly understood by those skilled in the art and generally refers to a chemical entity comprising a skeleton or main chain that is not split into more than one continuous chain. Non-limiting examples of straight chain alkyl groups include methyl, ethyl, n-propyl, and n-butyl. As used herein, the term "branched chain" can be used as commonly understood by those skilled in the art and generally refers to a chemical entity comprising a skeleton or main chain that is split into more than one continuous chain. The portion of the skeleton or main chain that is split in more than one direction can be straight chain, cyclic, or any combination thereof. Non-limiting examples of branched chain alkyl groups include tert-butyl and isopropyl.

[0090] The term "alkylene" refers to a divalent analog of an alkyl group. In the context of the expression "alkylene, alkenylene or alkynylene" and similar expressions, "alkylene" is understood to be a saturated alkylene group.

[0091] As used herein, when referring to chemical entities, the term "saturated" may be used as commonly understood by those skilled in the art and generally refers to chemical entities that include only single bonds and may contain linear, branched, and / or cyclic groups. 20 Non-limiting examples of alkyl groups can include methyl, ethyl, n-propyl, isopropyl, sec-propyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, tert-pentyl, n-hexyl, isohexyl, 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, tert-hexyl, n-heptyl, isoheptyl, sec-heptyl, tert-heptyl, n-octyl, isooctyl, sec-octyl, tert-octyl, n-nonyl, isononyl, sec-nonyl, tert-nonyl, n-decyl, isodecyl, sec-decyl, tert-decyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, etc. Unless otherwise specified, C1-C 20 Alkylene thus encompasses, but is not limited to, all divalent analogs of the saturated alkyl groups listed above.

[0092] As used herein, expressions such as “C3-C5 alkylene, alkenylene or alkynylene” are understood to mean C3-C5 alkylene, C3-C5 alkenylene or C3-C5 alkynylene, and expressions such as “C1-C5 alkylene, alkenylene or alkynylene” are understood to mean C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene. Similarly, as used herein, expressions such as “C5-C 20 "Alkyl, alkenyl or alkynyl" is understood to mean C5-C 20 Alkyl, C5-C 20 Alkenyl or C5-C 20 Alkynyl, and expressions such as "C1-C 20 "Alkyl, alkenyl or alkynyl" is understood to mean C1-C 20 Alkyl, C2-C 20 Alkenyl or C2-C 20 Alkynyl.

[0093] As used herein, when referring to a chemical entity, the term "unsaturated" may be used as generally understood by those skilled in the art and generally refers to a chemical entity that includes at least one double bond or triple bond and may contain linear, branched, and / or cyclic groups. 20Non-limiting examples of alkenyl groups can 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, cyclooctyl, cyclononenyl, cyclodecenyl, and the like. Unless otherwise specified, C1-C 20 Alkenylene thus encompasses, but is not limited to, all divalent analogs of the alkenyl groups listed above. 20 Non-limiting examples of alkynyl groups can include ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, decynyl, and the like. Unless otherwise specified, C1-C 20 Alkyneylene thus encompasses, but is not limited to, all divalent analogs of the alkynyl groups listed above.

[0094] When specifying that one or more carbons in alkyl, alkenyl, alkynyl, alkylene, alkenylene, alkynylene etc. are independently replaced by heteroatoms, those skilled in the art will understand that various combinations of different heteroatoms can be used. Non-limiting examples of non-aromatic heterocyclic groups include aziridinyl, azetidinyl, diazetidinyl, pyrrolidinyl, pyrrolinyl, piperidinyl, piperazinyl, imidazolinyl, pyrazolidinyl, imidazolidinyl, phthalimido, succinimidyl, oxiranyl, tetrahydropyranyl, oxetane, dioxane, thietanyl, thiocycloheptatrienyl, morpholinyl, oxathiolanyl etc. The expression "straight chain, branched and / or cyclic ... alkyl, alkenyl or alkynyl" especially includes aryl. Unless otherwise stated, "aryl" groups include single aromatic rings and fused rings containing at least one aromatic ring. C3-C 20 Non-limiting examples of aryl groups include phenyl (Ph), pentalenyl, indenyl, naphthyl, and azulenyl. 20Non-limiting examples of aromatic rings include pyrrolyl, imidazolyl, pyrazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pirazinyl, quinolinyl, isoquinolinyl, acridinyl, indolyl, isoindolyl, indolizinyl, purinyl, carbazolyl, indazolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, pteridinyl, phenanthridinyl, phenazinyl, phenanthrolinyl, perimidinyl, furanyl, dibenzofuranyl, xanthenyl, benzofuranyl, thienyl, thianthrenyl, benzothienyl, phosphinyl, phospholinyl, phosphindolyl, thiazolyl, oxazolyl, isoxazolyl, and the like. Likewise, the expression "straight-chain, branched and / or cyclic ... alkylene, alkenylene or alkynylene" especially comprises divalent analogs of the above-defined straight-chain, branched and / or cyclic alkyl, alkenyl or alkynyl groups, including all aryl groups encompassed therein.

[0095] As used herein, term " substituted " is as those skilled in the art usually understand use, and generally refers to a chemical group by different chemical groups to replace the compound or chemical entity.Unless otherwise noted, otherwise substituted alkyl is an alkyl in which one or more hydrogen atoms are each independently replaced by non-hydrogen atoms.For example, chloromethyl is a non-limiting example of substituted alkyl, more specifically the example of substituted methyl.Aminoethyl is another non-limiting example of substituted alkyl, more specifically the example of substituted ethyl.Unless otherwise noted, otherwise substituted compound or group (for example, alkyl, alkylidene, aryl etc.) can be replaced by any chemical group reasonable to those skilled in the art. For example, but not limited to, a hydrogen bonded to a carbon or heteroatom (e.g., N) can be replaced by a halide (e.g., F, I, Br, Cl), an amine, an amide, an oxo, a hydroxyl, a thiol (mercapto), a phosphate (or phosphoric acid), a phosphonate, a sulfate, SO2H (sulfinic acid), SO3H (sulfonic acid), an alkyl, an aryl, a ketone, a carboxaldehyde, a carboxylic acid, a carboxamide, a nitrile, a guanidino, a monohalomethyl, a dihalomethyl, or a trihalomethyl group.

[0096] As used herein, the term "guanidino" refers to the group -NHC(═NH)NH2 or -NHC(═NR)NR2, where each R is independently H or alkyl.

[0097] As used herein, the term "unsubstituted" is used as commonly understood by those skilled in the art. Non-limiting examples of unsubstituted alkyl groups include methyl, ethyl, tert-butyl, pentyl, etc. The expression "optionally substituted" is used interchangeably with the expression "unsubstituted or substituted."

[0098] In the structures provided herein, hydrogen may or may not be shown. In some embodiments, hydrogen (whether shown or implied) may be protium (i.e. 1 H), deuterium (i.e. 2 H) or 1 H and 2 Used to 1 H and 2 H exchange methods are well known in the art. For solvent exchangeable hydrogen, 1 H and 2 The exchange of H atoms occurs readily in the presence of a suitable deuterium source and does not require any catalyst. The use of acids, bases, or metal catalysts, along with elevated temperature and pressure, can promote the exchange of non-exchangeable hydrogen atoms, typically resulting in the exchange of all hydrogen atoms in the molecule. 1 H to 2 Exchange of H.

[0099] The compounds disclosed herein incorporate amino acids, for example, as residues in a peptide chain (straight or branched) or as other parts of a compound. Amino acids have both an amino group and a carboxylic acid group, one or both of which can be used for covalent attachment. Upon attachment to the rest of the compound, the amino group and / or the carboxylic acid group can be converted to an amide or other structure; for example, the carboxylic acid group of a first amino acid is converted to an amide (e.g., a peptide bond) when bonded to the amino group of a second amino acid. Thus, an amino acid residue can have the formula –N(R a )R b C(O)–, where R a and R b is an R group. a Typically hydrogen or methyl. The amino acid residue of a peptide may comprise a typical peptide (amide) bond and may further comprise a bond between a side chain functional group and the side chain or main chain functional group of another amino acid. For example, a side chain formate of an amino acid residue in a peptide (e.g., Asp, Glu, etc.) may be bonded to an amine of another amino acid residue in the peptide (e.g., Dap, Dab, Orn, Lys). More further details are provided below. The term "amino acid" includes proteinogenic amino acids and non-proteinogenic amino acids. Non-limiting examples of non-proteinogenic amino acids are shown in Table 1 and include: D amino acids (including but not limited to any D forms 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, β-(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-NH2), Phe(4-NO2), N ε、N ε 、N ε -trimethyl-lysine, homoarginine (hArg), 2-amino-4-guanidinobutyric acid (Agb), 2-amino-3-guanidinopropionic acid (Agp), β-alanine, 4-aminobutyric acid, 5-aminopentanoic 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)propionic acid, 2-amino-3-(anthracen-9-yl)propionic acid, 2-amino-3-(pyren-1-yl)propionic acid, Trp(5-Br), Trp(5-OCH3), Trp(6-F), Trp(5-OH) or Trp(CHO), 2-aminoadipic acid (2

[0015] The present invention further includes amino acids 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, 90, 81, 82, 83, 84, 59, 71, 72, 73, 74, 75

[0100] Table 1: List of non-limiting examples of non-proteinogenic amino acids.

[0101]

[0102]

[0103] As used herein, "peptide backbone amide" refers to an amide (-C(O)-NH-) as shown in the structure of Formula AI, A-II, A-III, A-III, A-IV, B or C, for example, including 2a 、R 3a 、R 4a 、R 5a 、R 6a 、R A7a 、R B7a and R C7a Unless otherwise discussed herein, one or more peptide backbone amides may be methylated or N-methylated. For example, with R 2a 、R 3a 、R 4a 、R 5a 、R 6a 、R A7a 、RB7a and R C7a The amide bond between the bonded carbon atoms may be methylated (-C(O)-NCH3-).

[0104] In the chemical formula (for example, in the definition of L 1 A wavy line appears in the middle of the key or at the end of the key. The notation is intended to define the R group on one side of the wavy line without changing 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. Thus, only the atoms between the two wavy lines constitute the definition of the R group. When no atoms are shown outside the wavy lines, or for chemical groups that do not show wavy lines but have bonds on multiple sides (e.g., –C(O)NH–), the chemical group should be read from left to right, matching the orientation in the formula to which the group refers (e.g., for the formula –R a –R b –R c –, define R as –C(O)NH– b Incorporated – R a –C(O)NH–R c – instead of –R a –NHC(O)–R c –).

[0105] Compound

[0106] In various aspects, disclosed is a compound of Formula A, Formula B, or Formula C, or a salt or solvate of Formula A, Formula B, or Formula C:

[0107]

[0108]

[0109] Wherein, the R group is defined as follows:

[0110] 0-3 peptide backbone amides are independently

[0111] Amidine or thioamide substitution;

[0112] wherein 0-3 peptide backbone amides are N-methylated; and

[0113] wherein the C-terminus is optionally amidated.

[0114] In some embodiments, the compound has the 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.

[0115] In some embodiments, the compound has the structure of Formula A or a salt or solvate thereof: in:

[0116] R 2a It is -(CH2)-(R 2b )-(phenyl), wherein R 2b Absent, is -CH2-, -NH-, -S- or -O-, wherein the phenyl group is optionally replaced by -NH2, -NO2, -OH, -OR 2c 、-SH、-SR 2c , -N3, -CN or -O-phenyl 4-substituted, wherein the phenyl group is optionally substituted with halogen or -OH 3-substituted, wherein the phenyl group is optionally substituted with halogen or -OH 5-substituted, wherein the -O-phenyl ring is optionally substituted with -NH2, -NO2, -OH, -OR 2c , -SH, -N3, -CN or -SR 2c 4-substituted, wherein the -O-phenyl ring is optionally substituted with halogen or -OH 3-substituted, wherein the -O-phenyl ring is optionally substituted with halogen or -OH 5-substituted, wherein each R 2c are independently C1-C3 straight or branched chain alkyl groups;

[0117] R 3a is a C1-C5 alkyl group or R 3b R 3c , where R 3b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbon atoms in C2-C5 are independently replaced by one or more N, S and / or O heteroatoms, wherein R 3c Yes – N(R 3d ) 2-3 or guanidino, where each R 3d are independently -H or linear or branched C1-C3 alkyl;

[0118] R 4a It is R 4b R 4c , where R 4b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbon atoms in C2-C5 are independently replaced by one or more N, S and / or O heteroatoms, wherein R 4c Yes – N(R 4d ) 2-3 or guanidino, where each R 4d are independently -H or linear or branched C1-C3 alkyl;

[0119] R 5a Yes - (CH2) 1-3 -R5b , where -(CH2) 2-3 - is optionally replaced by a N, S or O heteroatom, wherein R 5b yes:

[0120] Phenyl optionally substituted with one or a combination of:

[0121] -NH2, -NO2, -OH, -OR 5c 、-SH、-SR 5c , -N3, -CN or -O-phenyl 4-substituted; substituted by halogen or -OH 3-; and / or substituted by halogen or -OH 5-; wherein the -O-phenyl ring is optionally substituted by -NH2, -NO2, -OH, -OR 5c , -SH, –SR 5c , -N3 or -CN 4-, wherein the -O-phenyl ring is optionally substituted with halogen or -OH 3-, wherein the -O-phenyl ring is optionally substituted with halogen or -OH 5-; or

[0122] Fused bicyclic or fused tricyclic aryl or heteroaryl rings, each optionally substituted by halogen, -OH, -OR 5c , amino, -NHR 5c and / or N(R 5c ) One or more substitutions in 2;

[0123] Each R 5c are independently C1-C3 straight or branched chain alkyl groups;

[0124] R 6a H, methyl, ethyl, -C≡CH, -CH=CH2, -C≡C-(CH2) 1-3 -OH,-C≡C-(CH2) 1-3 -SH, -C≡C-(CH2) 1-3 -NH2, -C≡C-(CH2) 1-3 -COOH,-C≡C-(CH2) 1-3 -CONH2, -C≡C-(CH2) 1-3 R 6b R 6c , -CH=CH-(CH2) 1-3 -OH,-CH=CH-(CH2) 1-3 -SH, -CH=CH-(CH2) 1-3 -NH2, -CH=CH-(CH2) 1-3 -COOH,-CH=CH-(CH2) 1-3 -CONH2,-CH=CH-(CH2) 1-3 R6b R 6c ,-CH2-R 6b -OH,-CH2-R 6b -COOH,-CH2-(R 6b ) 1-3 -NH2, -CH2-R 6b -CONH2 or -CH2-R 6b R 6c , where each R 6b are independently absent, are -CH2-, -NH-, -S- or -O-, and wherein R 6c yes:

[0125] a 5- or 6-membered aromatic ring in which one or more carbon atoms are optionally independently replaced by N, S and / or O heteroatoms, and optionally substituted by one or more groups independently selected from oxo, hydroxy, thiol, nitro, amino and / or halogen;

[0126] or -NH-CH(R 6a )-C(O)-NH- Replacement;

[0127] R A7a is a straight chain C1-C5 alkylene group, wherein 0-2 carbon atoms in C2-C5 are independently replaced by one or more N, S and / or O heteroatoms;

[0128] R 8a It is R 8b R 8c , where R 8b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbon atoms in the C2-C5 alkylene, alkenylene or alkynylene are independently replaced by one or more N, S and / or O heteroatoms, wherein R 8c Yes – N(R 8d ) 2-3 or guanidino, where each R 8d are independently -H or linear or branched C1-C3 alkyl;

[0129] R 9a It is -C(O)NH2, -C(O)-OH, -CH2-C(O)NH2, -CH2-C(O)-OH, -CH2-NH2, -CH2-OH, -CH2-CH2-NH2, -R 9b -R 9c or -R 9b -[Connector]-R X n1 ,in:

[0130] R9b is -CH2-NH-C(O)-,-CH2-C(O)-,-CH2-O-,-C(O)NH-,-C(O)-N(CH3)-,-CH2-NHC(S)-,-C(S) NH-,-CH2-N(CH3)C(S)-,-C(O)N(CH3)-,-CH2-N(CH3)C(O)-,-C(S)N(CH3)-,-CH2-NHC(S) NH-,-CH2-NHC(O)NH-,-CH2-S-,-CH2-S(O)-,-CH2-S(O)2-,-CH2-S(O)2-NH-,-CH2-S(O)- NH-,-CH2-Se-,-CH2-Se(O)-,-CH2-Se(O)2-,-CH2-NHNHC(O)-,-C(O)NHNH-,-CH2-OP(O)(O - )O-, -CH2-phosphoramide-, -CH2-thiophosphate diester-, -CH2-S-tetrafluorophenyl-S-, or polyethylene glycol; and

[0131] R 9c is hydrogen or a linear, branched and / or cyclic C1-C 20 Alkyl, alkenyl or alkynyl, wherein C2-C 20 0-6 carbon atoms are independently replaced by N, S and / or O heteroatoms, and 0-3 groups are independently selected from one or a combination of oxo, hydroxyl, thiol, halogen, guanidino, carboxylic acid, sulfonic acid, sulfinic acid and / or phosphoric acid;

[0132] R A10 Does not exist or is -[connector]-R X n1 ;

[0133] When R A10 If it does not exist, then R A1a yes:

[0134] Straight chain C1-C5 alkyl, C2-C5 alkenyl or C2-C5 alkynyl, wherein 0-2 carbons in the C2-C5 alkyl, alkenyl or alkynyl are independently replaced by one or more N, S and / or O heteroatoms, optionally C-substituted by a monosubstituent selected from the group consisting of -SH, -OH, amino, carboxyl, guanidino, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH3) 1-2 、-NH2-CH3、-N(CH3) 2-3 , -S-CH3 or -O-CH3;

[0135] Branched chain C1-C 10 Alkyl, alkenyl or alkynyl, wherein C2-C 10 0-3 carbon atoms in are independently replaced by one or more N, S and / or O heteroatoms; or

[0136] R A1b R A1c , where R A1b is a straight chain C1-C3 alkylene, wherein C2 alkylene or C3 alkylene is optionally replaced by N, S or O heteroatom, wherein R A1c yes:

[0137] a 5- or 6-membered aromatic ring in which one or more carbons are optionally independently replaced by N, S and / or O heteroatoms, and optionally substituted by one or more groups independently selected from oxo, hydroxy, thiol, nitro, amino and / or halogen; or

[0138] Fused bicyclic or fused tricyclic aryl groups, wherein one or more carbons are optionally independently replaced by N, S and / or O heteroatoms, and are optionally independently selected from halogen, -OH, -OR A1d , amino, -NHR A1d and / or N(R A1d )2 is substituted with one or more groups, wherein each R A1d are independently C1-C3 straight or branched chain alkyl groups;

[0139] When R A10 Yes-[Connector]-R X n1 When R A1a It is R A1e R A1f , where R A1e is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbon atoms in the C2-C5 alkylene, alkenylene or alkynylene are independently replaced by N, S and / or O heteroatoms, and R A1f is -NH-C(O)-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C(S)NH-, -N(CH3)C(S)-, -C(O)N(CH3)-, -N(CH3)C(O)-, -C(S)N(CH3)-, -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-, -phosphoramide-, -phosphorothioate diester-, -S-tetrafluorophenyl-S-, or polyethylene glycol;

[0140] R y is hydrogen or R 3e R 3f , where R 3e is a straight chain C1-C5 alkylene group, wherein R 3f Yes – N(R 3g ) 2-3 , where each R 3g are independently -H or linear or branched C1-C3 alkyl;

[0141] Each n1 is independently 0, 1, or 2;

[0142] Each R X is an albumin binder, a therapeutic moiety, a fluorescent label, a radiolabeled group, or a group capable of being radiolabeled;

[0143] 0-3 peptide backbone amides are independently

[0144] Amidine or thioamide substitution;

[0145] wherein 0-3 peptide backbone amides are N-methylated; and

[0146] wherein the C-terminus is optionally amidated.

[0147] In some embodiments of the compound of Formula A, the compound does not have the following combination: -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; and R 6a It’s H.

[0148] In some embodiments of the compound of Formula A,

[0149] R A10 Yes-[Connector]-R X n1 ;

[0150] The linker is X 1 L 1 、X 1 L 1 X 1 L 1 or X 1 L 1 X 1L 1 X 1 L 1 ;

[0151] X 1 are independently -CH2-,

[0152] L 1 each independently represents –NH–, –C(O)–, –NHC(O)–, –C(O)NH–, –N(CH 3 )C(O)–, or –C(O)N(CH 3 )–;

[0153] R 11 are each independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid; and

[0154] R Z Each is independently an albumin binder.

[0155] In some embodiments of the compound of Formula A, R y It is R 3e R 3f .

[0156] In some embodiments of the compound of Formula A, the compound comprises an albumin binder.

[0157] In some embodiments, the compound has the 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.

[0158] In some embodiments, the compound has the structure of Formula B, or a salt or solvate thereof: in:

[0159] R 2a It is -(CH2)-(R 2b )-(phenyl), wherein R 2b Absent, is -CH2-, -NH-, -S- or -O-, wherein the phenyl group is optionally replaced by -NH2, -NO2, -OH, -OR 2c 、-SH、-SR 2c , -N3, -CN or -O-phenyl 4-substituted, wherein the phenyl group is optionally substituted with halogen or -OH 3-substituted, wherein the phenyl group is optionally substituted with halogen or -OH 5-substituted, wherein the -O-phenyl ring is optionally substituted with -NH2, -NO2, -OH, -OR 2c 、-SH、-SR 2c , -N3 or -CN 4-, wherein the -O-phenyl ring is optionally substituted by halogen or -OH 3-, wherein the -O-phenyl ring is optionally substituted by halogen or -OH 5-, wherein each R 2care independently C1-C3 straight or branched chain alkyl groups;

[0160] R 3a is a C1-C5 alkyl group or R 3b R 3c , where R 3b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbon atoms in C2-C5 are independently replaced by one or more N, S and / or O heteroatoms, wherein R 3c Yes – N(R 3d ) 2-3 or guanidino, where each R 3d are independently -H or linear or branched C1-C3 alkyl;

[0161] R 4a It is R 4b R 4c , where R 4b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbon atoms in C2-C5 are independently replaced by one or more N, S and / or O heteroatoms, wherein R 4c Yes – N(R 4d ) 2-3 or guanidino, where each R 4d are independently -H or linear or branched C1-C3 alkyl;

[0162] R 5a Yes - (CH2) 1-3 -R 5b , where -(CH2) 2-3 - is optionally replaced by a N, S or O heteroatom, wherein R 5b yes:

[0163] Phenyl optionally substituted with one or a combination of:

[0164] -NH2, -NO2, -OH, -OR 5c 、-SH、-SR 5c , -N3, -CN or -O-phenyl 4-substituted; substituted by halogen or -OH 3-; and / or substituted by halogen or -OH 5-; wherein the -O-phenyl ring is optionally substituted by -NH2, -NO2, -OH, -OR 5c , -SH, –SR 5c , -N3 or -CN 4-, wherein the -O-phenyl ring is optionally substituted with halogen or -OH 3-, wherein the -O-phenyl ring is optionally substituted with halogen or -OH 5-; or

[0165] Fused bicyclic or fused tricyclic aryl or heteroaryl rings, each optionally substituted by halogen, -OH, -OR 5c , amino, -NHR 5c and / or N(R 5c ) One or more substitutions in 2;

[0166] Each R 5c are independently C1-C3 straight or branched chain alkyl groups;

[0167] R 6a H, methyl, ethyl, -C≡CH, -CH=CH2, -C≡C-(CH2) 1-3 -OH,-C≡C-(CH2) 1-3 -SH, -C≡C-(CH2) 1-3 -NH2, -C≡C-(CH2) 1-3 -COOH,-C≡C-(CH2) 1-3 -CONH2, -C≡C-(CH2) 1-3 R 6b R 6c , -CH=CH-(CH2) 1-3 -OH,-CH=CH-(CH2) 1-3 -SH, -CH=CH-(CH2) 1-3 -NH2, -CH=CH-(CH2) 1-3 -COOH,-CH=CH-(CH2) 1-3 -CONH2,-CH=CH-(CH2) 1-3 R 6b R 6c ,-CH2-R 6b -OH,-CH2-R 6b -COOH,-CH2-(R 6b ) 1-3 -NH2,-CH2-R 6b -CONH2 or -CH2-R 6b R 6c , where each R 6b are independently absent, are -CH2-, -NH-, -S- or -O-, and wherein R 6c yes:

[0168] a 5- or 6-membered aromatic ring in which one or more carbon atoms are optionally independently replaced by N, S and / or O heteroatoms, and optionally substituted by one or more groups independently selected from oxo, hydroxy, thiol, nitro, amino and / or halogen;

[0169] or -NH-CH(R 6a )-C(O)-NH- Replacement;

[0170] R 8a It is R 8b R 8c , where R 8b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbon atoms in the C2-C5 alkylene, alkenylene or alkynylene are independently replaced by one or more N, S and / or O heteroatoms, wherein R 8c Yes – N(R 8d ) 2-3 or guanidino, where each R 8d are independently -H or linear or branched C1-C3 alkyl;

[0171] R 9a -C(O)NH2、-C(O)-OH、-CH2-C(O)NH2、-CH2-C(O)-OH、-CH2-NH2、-CH2-OH、-CH2-CH2-NH2、-R 9b -R 9c or -R 9b -[Connector]-R X n1 ,in:

[0172] R 9b is -CH2-NH-C(O)-,-CH2-C(O)-,-CH2-O-,-C(O)NH-,-C(O)-N(CH3)-,-CH2-NHC(S)-,-C(S) NH-,-CH2-N(CH3)C(S)-,-C(O)N(CH3)-,-CH2-N(CH3)C(O)-,-C(S)N(CH3)-,-CH2-NHC(S) NH-,-CH2-NHC(O)NH-,-CH2-S-,-CH2-S(O)-,-CH2-S(O)2-,-CH2-S(O)2-NH-,-CH2-S(O)- NH-,-CH2-Se-,-CH2-Se(O)-,-CH2-Se(O)2-,-CH2-NHNHC(O)-,-C(O)NHNH-,-CH2-OP(O)(O - )O-, -CH2-phosphoramide-, -CH2-thiophosphate diester-, -CH2-S-tetrafluorophenyl-S-, or polyethylene glycol; and

[0173] R 9c is hydrogen or a linear, branched and / or cyclic C1-C 20 Alkyl, alkenyl or alkynyl, wherein C2-C 200-6 carbon atoms are independently replaced by N, S and / or O heteroatoms, and 0-3 groups are independently selected from one or a combination of oxo, hydroxyl, thiol, halogen, guanidino, carboxylic acid, sulfonic acid, sulfinic acid and / or phosphoric acid;

[0174] R B1a It is a linear, branched and / or cyclic C1-C 10 Alkylene, C2-C 10 Alkenylene or C2-C 10 Alkynylidene, wherein C2-C 10 One or more carbon atoms in the alkylene, alkenylene, and alkynylene groups are optionally independently replaced by N, S, and / or O heteroatoms;

[0175] R B1-7 yes wherein the indole ring and the isoindole ring are each optionally substituted with -F, -Br, -Cl, -I, -OH, -OR B1-7b ,-CO-,-COOH,-CONH2,-CN,-O-aryl,-NH2,-NHR B1-7b , N3, -NO2, -NH, -CHO and / or -R B1-7b One or more substitutions, wherein each R B1-7b is a straight-chain or branched C1-C3 alkyl, C2-C3 alkenyl or C2-C3 alkynyl group;

[0176] R B7a is a straight chain C1-C5 alkylene group, wherein 0-2 carbon atoms in the C2-C5 alkylene group are independently replaced by one or more N, S and / or O heteroatoms;

[0177] R B10a It is an amine, -NH-(CH3) 1-2 、-N(CH3) 2-3 , -NH-C(O)-CH3, -NH-C(O)-(phenyl) or –R B10b -[Connector]-R X n1 , where R B10b yes:

[0178] -NH-C(O)-,-C(O)-,-O-,-C(O)NH–,-C(O)-N(CH3)-,-NHC(S)-,-C(S)NH-,-N(CH3)C(S)-,-C(O)N(CH3)-,-N(CH3)C(O)-,-C(S)N(CH3)-,-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-, -phosphoramide-, -phosphorothioate diester-, -S-tetrafluorophenyl-S-, or polyethylene glycol;

[0179] Each n1 is independently 0, 1, or 2;

[0180] Each R X is an albumin binder, a therapeutic moiety, a fluorescent label, a radiolabeled group, or a group capable of being radiolabeled;

[0181] 0-3 peptide backbone amides are independently

[0182] Amidine or thioamide substitution;

[0183] wherein 0-3 peptide backbone amides are N-methylated; and

[0184] wherein the C-terminus is optionally amidated.

[0185] In some embodiments, the compound has the 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.

[0186] In some embodiments, the compound has the structure of Formula C or a salt or solvate thereof:

[0187] in:

[0188] R 2a It is -(CH2)-(R 2b )-(phenyl), wherein R 2b Absent, is -CH2-, -NH-, -S- or -O-, wherein the phenyl group is optionally replaced by -NH2, -NO2, -OH, -OR 2c 、-SH、-SR 2c, -N3, -CN or -O-phenyl 4-substituted, wherein the phenyl group is optionally substituted with halogen or -OH 3-substituted, wherein the phenyl group is optionally substituted with halogen or -OH 5-substituted, wherein the -O-phenyl ring is optionally substituted with -NH2, -NO2, -OH, -OR 2c 、-SH、-SR 2c , -N3 or -CN 4-, wherein the -O-phenyl ring is optionally substituted by halogen or -OH 3-, wherein the -O-phenyl ring is optionally substituted by halogen or -OH 5-, wherein each R 2c are independently C1-C3 straight or branched chain alkyl groups;

[0189] R 3a is a C1-C5 alkyl group or R 3b R 3c , where R 3b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbon atoms in C2-C5 are independently replaced by one or more N, S and / or O heteroatoms, wherein R 3c Yes – N(R 3d ) 2-3 or guanidino, where each R 3d are independently -H or linear or branched C1-C3 alkyl;

[0190] R 4a It is R 4b R 4c , where R 4b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbon atoms in C2-C5 are independently replaced by one or more N, S and / or O heteroatoms, wherein R 4c Yes – N(R 4d ) 2-3 or guanidino, where each R 4d are independently -H or linear or branched C1-C3 alkyl;

[0191] R 5a Yes - (CH2) 1-3 -R 5b , where -(CH2) 2-3 - is optionally replaced by a N, S or O heteroatom, wherein R 5b yes:

[0192] Phenyl optionally substituted with one or a combination of:

[0193] -NH2, -NO2, -OH, -OR 5c 、-SH、-SR 5c, -N3, -CN or -O-phenyl 4-substituted; substituted by halogen or -OH 3-; and / or substituted by halogen or -OH 5-; wherein the -O-phenyl ring is optionally substituted by -NH2, -NO2, -OH, -OR 5c , -SH, –SR 5c , -N3 or -CN 4-, wherein the -O-phenyl ring is optionally substituted with halogen or -OH 3-, wherein the -O-phenyl ring is optionally substituted with halogen or -OH 5-; or

[0194] Fused bicyclic or fused tricyclic aryl or heteroaryl rings, each optionally substituted by halogen, -OH, -OR 5c , amino, -NHR 5c and / or N(R 5c ) One or more substitutions in 2;

[0195] Each R 5c are independently C1-C3 straight or branched chain alkyl groups;

[0196] R 6a H, methyl, ethyl, -C≡CH, -CH=CH2, -C≡C-(CH2) 1-3 -OH,-C≡C-(CH2) 1-3 -SH, -C≡C-(CH2) 1-3 -NH2, -C≡C-(CH2) 1-3 -COOH,-C≡C-(CH2) 1-3 -CONH2, -C≡C-(CH2) 1-3 R 6b R 6c , -CH=CH-(CH2) 1-3 -OH,-CH=CH-(CH2) 1-3 -SH, -CH=CH-(CH2) 1-3 -NH2, -CH=CH-(CH2) 1-3 -COOH,-CH=CH-(CH2) 1-3 -CONH2,-CH=CH-(CH2) 1-3 R 6b R 6c ,-CH2-R 6b -OH,-CH2-R 6b -COOH,-CH2-(R 6b ) 1-3 -NH2,-CH2-R 6b -CONH2 or -CH2-R 6b R 6c , where each R 6bare independently absent, are -CH2-, -NH-, -S- or -O-, and wherein R 6c yes:

[0197] a 5- or 6-membered aromatic ring in which one or more carbon atoms are optionally independently replaced by N, S and / or O heteroatoms, and optionally substituted by one or more groups independently selected from oxo, hydroxy, thiol, nitro, amino and / or halogen;

[0198] or -NH-CH(R 6a )-C(O)-NH- Replacement;

[0199] R A7a is a straight chain C1-C5 alkylene group, wherein 0-2 carbon atoms in C2-C5 are independently replaced by one or more N, S and / or O heteroatoms;

[0200] R 8a It is R 8b R 8c , where R 8b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbon atoms in the C2-C5 alkylene, alkenylene or alkynylene are independently replaced by one or more N, S and / or O heteroatoms, wherein R 8c Yes – N(R 8d ) 2-3 or guanidino, where each R 8d are independently -H or linear or branched C1-C3 alkyl;

[0201] R 9a It is -C(O)NH2, -C(O)-OH, -CH2-C(O)NH2, -CH2-C(O)-OH, -CH2-NH2, -CH2-OH, -CH2-CH2-NH2, -R 9b -R 9c or -R 9b -[Connector]-R X n1 ,in:

[0202] R 9bis -CH2-NH-C(O)-, -CH2-C(O)-, -CH2-O-, -C(O)NH-, -C(O)-N(CH3)-, -CH2-NHC(S)-, -C(S) NH-,-CH2-N(CH3)C(S)-,-C(O)N(CH3)-,-CH2-N(CH3)C(O)-,-C(S)N(CH3)-,-CH2-NHC(S) NH-,-CH2-NHC(O)NH-,-CH2-S-,-CH2-S(O)-,-CH2-S(O)2-,-CH2-S(O)2-NH-,-CH2-S(O)- NH-,-CH2-Se-,-CH2-Se(O)-,-CH2-Se(O)2-,-CH2-NHNHC(O)-,-C(O)NHNH-,-CH2-OP(O)(O - )O-, -CH2-phosphoramide-, -CH2-thiophosphate diester-, -CH2-S-tetrafluorophenyl-S-, or polyethylene glycol; and

[0203] R 9c is hydrogen or a linear, branched and / or cyclic C1-C 20 Alkyl, alkenyl or alkynyl, wherein C2-C 20 0-6 carbon atoms are independently replaced by N, S and / or O heteroatoms, and 0-3 groups are independently selected from one or a combination of oxo, hydroxyl, thiol, halogen, guanidino, carboxylic acid, sulfonic acid, sulfinic acid and / or phosphoric acid;

[0204] R C1a yes wherein the indole, isoindole and triazole rings are each optionally substituted with -F, -Br, -Cl, -I, -OH, -OR C1b ,-CO-,-COOH,-CONH2,-CN,-O-aryl, -NH2,-NHR C1b ,N3,-NO2,-NH,-CHO and / or –R C1b One or more substitutions, wherein each R C1b is a straight-chain or branched C1-C3 alkyl, C2-C3 alkenyl or C2-C3 alkynyl group;

[0205] R C7a is a straight chain C1-C5 alkylene group, wherein optionally, 0-2 carbon atoms in the C2-C5 alkylene group are independently replaced by one or more N, S and / or O heteroatoms;

[0206] R C10a It is R C10b -R C10c -[Connector]-R Xn1 or R C10d ,in:

[0207] R C10b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbon atoms in the C2-C5 alkylene, alkenylene or alkynylene are independently replaced by N, S and / or O heteroatoms;

[0208] R C10c is -NH-C(O)-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C(S)NH-, -N(CH3)C(S)-, -C(O)N(CH3)-, -N(CH3)C(O)-, -C(S)N(CH3)-, -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-, -phosphoramide-, -phosphorothioate diester-, -S-tetrafluorophenyl-S-, or polyethylene glycol; and

[0209] R C10d yes:

[0210] Straight chain C1-C5 alkyl, C2-C5 alkenyl or C2-C5 alkynyl, wherein 0-2 carbons in the C2-C5 alkyl, alkenyl or alkynyl are independently replaced by N, S and / or O heteroatoms, optionally C-substituted by a monosubstituent selected from the group consisting of -SH, -OH, amino, carboxyl, guanidino, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH3) 1-2 、-NH2-CH3、-N(CH3) 2-3 , -S-CH3 or -O-CH3;

[0211] Branched chain C1-C 10 Alkyl, C2-C 10 Alkenyl or C2-C 10 Alkynyl, where C2-C 10 0-3 carbon atoms in the alkyl, alkenyl or alkynyl group are independently replaced by N, S and / or O heteroatoms; or

[0212] R C10e R C10f, where R C10e is a straight chain C1-C3 alkyl group, wherein the C2 alkyl group or the C3 alkyl group is optionally replaced by a N, S or O heteroatom, wherein R C10f yes:

[0213] a 5- or 6-membered aromatic ring in which one or more carbon atoms are optionally independently replaced by N, S and / or O heteroatoms, and optionally substituted by one or more groups independently selected from oxo, hydroxy, thiol, nitro, amino and / or halogen;

[0214] Fused bicyclic or fused tricyclic aryl groups, wherein one or more carbons are optionally independently replaced by N, S and / or O heteroatoms, and are optionally independently selected from halogen, -OH, -OR C10g , amino, -NHR C10g and / or N(R C10g )2 is substituted with one or more groups, wherein R C10g is a C1-C3 straight or branched chain alkyl group;

[0215] Each n1 is independently 0, 1, or 2;

[0216] Each R X is an albumin binder, a therapeutic moiety, a fluorescent label, a radiolabeled group, or a group capable of being radiolabeled;

[0217] 0-3 peptide backbone amides are independently

[0218] Amidine or thioamide substitution;

[0219] wherein 0-3 peptide backbone amides are N-methylated; and

[0220] wherein the C-terminus is optionally amidated.

[0221] In some embodiments of the compound of Formula A, B, and / or C, the compound comprises an albumin binder.

[0222] In some embodiments of compounds of Formula A, B, and / or C, R 9a It is R 9b -[Connector]R x n1 In some embodiments of compounds of Formula A, B and / or C, R 3a is C1-C5 alkyl. 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 replaced by an amidine.

[0223] In some embodiments of compounds of Formula A, B, and / or C, one peptide backbone amide is 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.

[0224] In some embodiments of the compounds of Formula A, B and / or C, at least one peptide backbone 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.

[0225] In some embodiments of compounds of Formula A, B, and / or C, at least one peptide backbone amide is replaced by an amidine. In some embodiments, one peptide backbone amide is replaced by an amidine. In some embodiments, two peptide backbone amides are each replaced by an amidine. In some embodiments, three peptide backbone amides are each replaced by an amidine. In some embodiments, zero peptide backbone amides are each replaced by an amidine.

[0226] In some embodiments, R 3a and R 4a ; R 4a and R 5a ; or R 5a and R 6a The peptide backbone carbonyl groups are replaced by imino groups (-CH(R 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 )-) substitution. In some embodiments, R 3a and R 4a The peptide backbone carbonyl groups are replaced by imino groups ((-CH(R 3a )-C(=N)-NH-CH(R 4a )-) substitution. In some embodiments, R 4a and R 5a The peptide backbone carbonyl groups are replaced by imino groups (-CH(R 4a )-C(=N)-NH-CH(R 5a )-) substitution. In some embodiments, R 5a and R 6a The peptide backbone carbonyl groups are replaced by imino groups (-CH(R 5a )-C(=N)-NH-CH(R 6a )-)Alternative.

[0227] In some embodiments of compounds of Formula A, B, and / or C, R 2a It is -(CH2)-(R 2b )-(phenyl), wherein R 2b Not present, -CH2-, -NH-, -S- or -O-, in which the phenyl group is replaced by -NH2, -NO2, -OH, -OR 2c ,-SH,-SR 2c , -N3, -CN or -O-phenyl 4-substituted, wherein the phenyl group is optionally substituted with halogen or -OH 3-, wherein the phenyl group is optionally substituted with halogen or -OH 5-, wherein the -O-phenyl ring is optionally substituted with -NH2, -NO2, -OH, -OR 2c ,-SH,-SR 2c , -N3 or -CN 4-substituted, wherein the -O-phenyl ring is optionally substituted by halogen or -OH 3-, wherein the -O-phenyl ring is optionally substituted by halogen or -OH 5-, wherein each R 2c are independently C1-C3 straight or branched chain alkyl groups.

[0228] In some embodiments of compounds of Formula A, B, and / or C, R 2b In some embodiments, R 2b In some embodiments, R 2b In some embodiments, R 2b In some embodiments, R 2b Yes -O-.

[0229] In some embodiments of compounds of Formula A, B, and / or C, R 2a It is -(CH2)-(R 2b )-(phenyl), wherein R 2b Not present or -CH2-, where the phenyl group is replaced by -NH2, -NO2, -OH, -OR 2c ,-SH,-SR 2cIn some embodiments, the phenyl group is 4-substituted with -NH2, -CN, or -O-phenyl. In some embodiments, the phenyl group is 4-substituted with -NH2. In some embodiments, the phenyl group is 4-substituted with -NO2. In some embodiments, the phenyl group is 4-substituted with -OH. In some embodiments, the phenyl group is 4-substituted with -SH. In some embodiments, the phenyl group is 4-substituted with -O-phenyl. In some embodiments, the phenyl group is 3,5-unsubstituted. In some embodiments, the phenyl group is 3-substituted. In some embodiments, the phenyl group is 5-substituted. In some embodiments, the phenyl group is 3,5-substituted. In some embodiments, the halogen substituent is iodine. The 3,5-substituents can be the same or different (e.g., different halogens or a mixture of halogens and -OH).

[0230] In some embodiments of 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)- forms a (4-NO2)-Phe residue. In some embodiments, -NH-CH(R 2a )-C(O)- forms a (4-NH2)-Phe residue. In some embodiments, -NH-CH(R 2a )-C(O)- forms an 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.

[0231] In some embodiments of compounds of Formula A, B, and / or C, R 3a is a C1-C5 alkyl group or R 3b R 3c , where R 3bis a straight chain C1-C5 alkylene, alkenylene or alkynylene group, wherein 0-2 carbon atoms in the C2-C5 alkylene, alkenylene or alkynylene group are independently replaced by one or more N, S and / or O heteroatoms, wherein R 3c Yes – N(R 3d ) 2-3 or guanidino, where each R 3d are independently -H or a linear or branched C1-C3 alkyl group.

[0232] In some embodiments of compounds of Formula A, B, and / or C, R 3a It is R 3b R 3c , where R 3b is a straight chain C1-C5 alkylene, alkenylene or alkynylene group, wherein 0-2 carbon atoms in the C2-C5 alkylene, alkenylene or alkynylene group are independently replaced by one or more N, S and / or O heteroatoms, wherein R 3c Yes – N(R 3d ) 2-3 or guanidino, where each R 3d are independently -H or a linear or branched C1-C3 alkyl group.

[0233] In some embodiments of compounds of Formula A, B, and / or C, R 3b is a straight chain C1-C5 alkylene, alkenylene, or alkynylene group (i.e., no heteroatoms). 3b In any of the C2-C5 alkylene, alkenylene or alkynylene groups, a single heteroatom (N, S or O) is included. In some embodiments, R 3b It is a straight chain C1-C5 alkylene group.

[0234] In some embodiments of compounds of Formula A, B, and / or C, R 3c In some embodiments, R 3c Yes-N(R 3d ) 2-3 In some embodiments, R 3c Yes-N(R 3d ) 2-3 , where each R 3d is a straight chain or branched C1-C3 alkyl group. 3c Yes-N(R 3d ) 2-3 , where each R 3d In some embodiments, R 3c Yes-N(R 3d ) 2-3 , where each R 3d In some embodiments, R3c It is -NH2 or -NH3.

[0235] In some embodiments of compounds of Formula A, B, and / or C, R 3a is C1-C5 alkyl. In some embodiments, R 3a In some embodiments, R 3a In some embodiments, R 3a In some embodiments, R 3a In some embodiments, R 3a It is pentyl.

[0236] 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)- forms an Arg(Me)2 (asymmetric) residue. In some embodiments, -NR y -CH(R 3a )-C(O)- forms an Arg(Me) residue.

[0237] 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)- forms an Arg(Me)2 (asymmetric) residue. In some embodiments, -NH-CH(R 3a )-C(O)- forms an Arg(Me) residue.

[0238] In some embodiments of the compound of Formula A, NR y -CH(R3a )-C(O)-is-NCH3-CH(R 3a )-C(O)-. In some embodiments, -NCH3-CH(R 3a )-C(O)- forms an L amino acid residue. In some embodiments, -NCH3-CH(R 3a )-C(O)- forms a D amino acid residue. In some embodiments, -NCH3-CH(R 3a )-C(O)- forms a Lys(iPr) residue. In some embodiments, -NCH3-CH(R 3a )-C(O)- forms an Arg(Me)2 (asymmetric) residue. In some embodiments, -NCH3-CH(R 3a )-C(O)- forms an Arg(Me) residue.

[0239] In some embodiments of Formula A, R y is hydrogen, C1-C5 alkyl or R 3e R 3f , where R 3e is a straight chain C1-C5 alkylene group, wherein R 3f Yes – N(R 3g ) 2-3 , where each R 3g are independently -H or a linear or branched C1-C3 alkyl group.

[0240] In some embodiments of Formula A, R y is hydrogen. In some embodiments of Formula A, R y is C1-C5 alkyl. In some embodiments, R y It's methyl.

[0241] In some embodiments of Formula A, R y It is R 3e R 3f , where R 3e is a straight chain C1-C5 alkylene group, wherein R 3f Yes – N(R 3g ) 2-3 , where each R 3g is independently -H or a linear or branched C1-C3 alkyl group. y Yes (C 1-5 Alkylene)-NH(C 2-3 In some embodiments, R y It is (C4 alkylene)-NH(isopropyl).

[0242] In some embodiments of 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)- forms an Arg(Me)2 (asymmetric) residue. In some embodiments, -NH-CH(R 3a )-C(O)- forms an Arg(Me) residue.

[0243] In some embodiments of compounds of Formula A, B, and / or C, R 4a It is R 4b R 4c , where R 4b is a straight chain C1-C5 alkylene, alkenylene or alkynylene group, wherein 0-2 carbon atoms in C2-C5 are independently replaced by one or more N, S and / or O heteroatoms, wherein R 4c Yes – N(R 4d ) 2-3 or guanidino, where each R 4d are independently -H or a linear or branched C1-C3 alkyl group.

[0244] In some embodiments of compounds of Formula A, B, and / or C, R 4b is a straight chain C1-C5 alkylene, alkenylene, or alkynylene group (i.e., no heteroatoms). 4b A single heteroatom (N, S, or O) is included in any of C2-C5. In some embodiments, R 4b It is a straight chain C1-C5 alkylene group.

[0245] In some embodiments of compounds of Formula A, B, and / or C, R 4c In some embodiments, R 4c Yes-N(R 4d ) 2-3 In some embodiments, R 4c Yes-N(R 4d ) 2-3 , where each R 4d is a straight chain or branched C1-C3 alkyl group. 4c Yes-N(R 4d ) 2-3 , where each R 4d In some embodiments, R 4c Yes-N(R 4d ) 2-3 , where each R4d In some embodiments, R 4c It is -NH2 or -NH3.

[0246] In some embodiments of 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.

[0247] In some embodiments of Formula A, B, and / or C, -NH-CH(R 4a )-C(O)- carbonyl group is replaced by imino group 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.

[0248] In some embodiments of compounds of Formula A, B, and / or C, R 5a Yes - (CH2) 1-3 -R 5b , where -(CH2) 2-3 - is optionally replaced by a N, S or O heteroatom, wherein R 5b yes:

[0249] Phenyl optionally substituted by one or a combination of: -NH2, -NO2, -OH, -OR 5c ,-SH,-SR 5c , -N3, -CN or -O-phenyl 4-substituted; substituted by halogen or -OH 3-; and / or substituted by halogen or -OH 5-; wherein the -O-phenyl ring is optionally substituted by -NH2, -NO2, -OH, -OR 5c ,-SH,–SR 5c, -N3 or -CN 4-, wherein the -O-phenyl ring is optionally substituted by halogen or -OH 3-, wherein the -O-phenyl ring is optionally substituted by halogen or -OH 5-; or

[0250] Fused bicyclic or fused tricyclic aryl groups wherein one or more carbon atoms are optionally independently replaced by N, S and / or O heteroatoms and independently optionally replaced by halogen, -OH, -OR 5c , amino, -NHR 5c and / or N(R 5c )2 or a combination thereof;

[0251] Each R 5c are independently C1-C3 straight or branched chain alkyl groups.

[0252] In some embodiments of compounds of Formula A, B, and / or C, R 5a Yes-CH2-R 5b In some embodiments, R 5a is -CH2-CH2-R 5b In some embodiments, R 5a is -CH2-CH2-CH2-R 5b .

[0253] In some embodiments of compounds of Formula A, B, and / or C, R 5b is phenyl optionally substituted by one or a combination of: -NH2, -NO2, -OH, -OR 5c ,-SH,-SR 5c , -N3, -CN or -O-phenyl 4-substituted; substituted by halogen or -OH 3-; and / or substituted by halogen or -OH 5-; wherein the -O-phenyl ring is optionally substituted by -NH2, -NO2, -OH, -OR 5c ,-SH,–SR 5c , -N3 or -CN 4-substituted, wherein the -O-phenyl ring is optionally substituted by halogen or -OH 3-, wherein the -O-phenyl ring is optionally substituted by halogen or -OH 5-. In some embodiments, R 5b is phenyl optionally substituted with one or a combination of: 4-substituted with -NH2, -NO2, -OH, -SH, -N3, -CN, or -O-phenyl; 3-substituted with halogen or -OH; and / or 5-substituted with halogen or -OH. In some embodiments, the phenyl group is 4-unsubstituted. In some embodiments, the phenyl group is 4-substituted with -NH2. In some embodiments, the phenyl group is 4-substituted with -NO2. In some embodiments, the phenyl group is 4-substituted with -OH. In some embodiments, the phenyl group is 5-substituted with -OR 5cIn some embodiments, the phenyl group is substituted with -SH 4-. In some embodiments, the phenyl group is substituted with -SR 5c In some embodiments, phenyl is 4-substituted with -N3. In some embodiments, phenyl is 4-substituted with -CN. In some embodiments, phenyl is 4-substituted with -O-phenyl. In some embodiments, each R 5c are independently C1-C3 straight or branched chain alkyl. 5c is methyl. In some embodiments, the phenyl group is 3-unsubstituted. In some embodiments, the phenyl group is 3-substituted with halogen. In some embodiments, the phenyl group is 3-substituted with –OH. In some embodiments, the phenyl group is 5-substituted with halogen. In some embodiments, phenyl-OH is 5-substituted. In some embodiments, the halogen is iodine. In some embodiments, the -O-phenyl ring is unsubstituted. In some embodiments, the -O-phenyl ring is 4-substituted. In some embodiments, the -O-phenyl ring is 3-substituted. In some embodiments, the -O-phenyl ring is 5-substituted.

[0254] In some embodiments of compounds of Formula A, B, and / or C, R 5b is a fused bicyclic or fused tricyclic aryl group in which one or more carbon atoms are optionally independently replaced by N, S and / or O heteroatoms and optionally independently replaced by halogen, -OH, -OR 5c , amino, -NHR 5c and / or N(R 5c ) 2 or a combination thereof. In some embodiments, each R 5c are independently C1-C3 straight or branched chain alkyl. 5c In some embodiments, R 5b is a fused bicyclic or fused tricyclic aryl group, wherein 0-3 carbon atoms are independently replaced by N, S and / or O heteroatoms, and are optionally independently substituted by one or a combination of halogen, -OH and / or amino. 5b is a fused bicyclic or fused tricyclic aryl group optionally substituted independently by one or a combination of halogen, -OH and / or amino. 5b is a fused bicyclic or fused tricyclic aryl group optionally substituted independently by 0-3 groups selected from halogen, -OH and / or amino. In some embodiments, R 5b is a fused bicyclic or fused tricyclic aryl. In some embodiments, R 5b9-linked anthracenyl groups are excluded. In some embodiments, each ring in the fused bicyclic or fused tricyclic aryl group independently has 4, 5, or 6 ring carbons, of which 0-3 carbons are independently replaced by N, S, and / or O heteroatoms; such embodiments may be substituted or unsubstituted, as defined above.

[0255] In some embodiments of 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)- to form a (4-NH2)Phe residue. In some embodiments, -NH-CH(R 5a )-C(O)- forms an hTyr residue. In some embodiments, -NH-CH(R 5a )-C(O)- forms a Tyr residue.

[0256] In some embodiments of Formula A, B, and / or C, -NH-CH(R 5a )-C(O)- carbonyl group is replaced by imino group to form -NH-CH(R 5a )-C(=NH)-. In some embodiments of Formula A, B and / or C, -NH-CH(R 5a The main chain amide of )-C(O)- is replaced by amidine to form -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 by an amidine. In some embodiments, -NH-CH(R 5a )-C(O)- forms a D amino acid residue and the backbone amide is replaced by an amidine. In some embodiments, -NH-CH(R 5a )-C(O)- forms a 2-(Ant)Ala residue and the backbone amide is replaced by an amidine. In some embodiments, -NH-CH(R 5a )-C(O)- forms a 2-Nal residue and the backbone amide is replaced by an amidine. In some embodiments, -NH-CH(R 5a)-C(O)- forms a Trp residue and the backbone amide is replaced by an amidine. In some embodiments, -NH-CH(R 5a )-C(O)- forms a (4-NH2)Phe residue, and the backbone amide is replaced by an amidine. In some embodiments, -NH-CH(R 5a )-C(O)- forms an hTyr residue and the backbone amide is replaced by an amidine. In some embodiments, -NH-CH(R 5a )-C(O)- forms a Tyr residue, and the backbone amide is replaced by an amidine.

[0257] In some embodiments of the compound of Formula A, B and / or C,

[0258] (a)R 6a H, methyl, ethyl, -C≡CH, -CH=CH2, -C≡C-(CH2) 1-3 -OH,-C≡C-(CH2) 1-3 -SH,-C≡C-(CH2) 1-3 -NH2, -C≡C-(CH2) 1-3 -COOH,-C≡C-(CH2) 1-3 -CONH2, -C≡C-(CH2) 1-3 R 6b R 6c ,-CH=CH-(CH2) 1-3 -OH,-CH=CH-(CH2) 1-3 -SH, -CH=CH-(CH2) 1-3 -NH2, -CH=CH-(CH2) 1-3 -COOH,-CH=CH-(CH2) 1-3 -CONH2,-CH=CH-(CH2) 1-3 R 6b R 6c ,-CH2-R 6b -OH,-CH2-R 6b -COOH,-CH2-(R 6b ) 1-3 -NH2,-CH2-R 6b -CONH2 or -CH2-R 6b R 6c , where each R 6b independently absent, is -CH2-, -NH-, -S- or -O-, wherein R 6c yes:

[0259] a 5- or 6-membered aromatic ring in which one or more carbons are optionally independently replaced by N, S and / or O heteroatoms, and optionally substituted by one or more groups independently selected from oxo, hydroxy, thiol, nitro, amino and / or halogen; or

[0260] (b)-NH-CH(R 6a )-C(O)-NH- Alternative.

[0261] In some embodiments of compounds of Formula A, B, and / or C, R 6a is H. In some embodiments, R 6a In some embodiments, R 6a In some embodiments, R 6a is -C≡CH. In some embodiments, R 6a is -CH=CH2. In some embodiments, R 6a Yes-CH2-R 6b -OH. In some embodiments, R 6a Yes-CH2-R 6b -COOH. In some embodiments, R 6a It is -CH2-(R 6b ) 1-3 -NH2. In some embodiments, R 6a Yes-CH2-R 6b -CONH2. In some embodiments, R 6a is -C≡C-(CH2) 1-3 -OH. In some embodiments, R 6a is -C≡C-(CH2) 1-3 -SH. In some embodiments, R 6a is -C≡C-(CH2) 1-3 -NH2. In some embodiments, R 6a is -C≡C-(CH2) 1-3 -COOH. In some embodiments, R 6a is -C≡C-(CH2) 1-3 -CONH2. In some embodiments, R 6a is -C≡C-(CH2) 1- 3R 6b R 6c In some embodiments, R 6a is -CH=CH-(CH2) 1-3 -OH. In some embodiments, R 6a is -CH=CH-(CH2) 1-3-SH. In some embodiments, R 6a is -CH=CH-(CH2) 1-3 -NH2. In some embodiments, R 6a is -CH=CH-(CH2) 1-3 -COOH. In some embodiments, R 6a is -CH=CH-(CH2) 1-3 -CONH2. In some embodiments, R 6a is -CH=CH-(CH2) 1-3 R 6b R 6c Each R 6b In some embodiments, R 6b In some embodiments, R 6b It is -CH2-.

[0262] In some embodiments of compounds of Formula A, B, and / or C, R 6a H, methyl, ethyl, -C≡CH, -CH=CH2, -CH2-R 6b -OH,-CH2-R 6b -COOH,-CH2-(R 6b ) 1-3 -NH2,-CH2-R 6b -CONH2 or -CH2-R 6b R 6c In some embodiments, R 6a Yes-CH2-R 6b R 6c Each R 6b In some embodiments, R 6b In some embodiments, R 6b In some embodiments, R 6c is a 5- or 6-membered aromatic ring in which 0-3 carbons are independently replaced by N, S, and / or O heteroatoms, and is optionally substituted by 0-3 groups independently selected from oxo, hydroxy, thiol, nitro, amino, and / or halogen; in some embodiments, the ring is unsubstituted. In some embodiments, R 6c is a 5- or 6-membered aryl group optionally substituted with 0-3 groups independently selected from oxo, hydroxy, thiol, nitro, amino, and / or halogen; in some embodiments, the aryl group is unsubstituted.

[0263] In some embodiments of compounds of Formula A, B, and / or C, -NH-CH(R 6a)-C(O)-NH- In some embodiments, -NH-CH(R 6a )-C(O)-NH- Alternative.

[0264] In some embodiments of 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.

[0265] In some embodiments of compounds of Formula A, B, and / or C, R 8a It is R 8b R 8c , where R 8b is a straight chain C1-C5 alkylene, alkenylene or alkynylene group, wherein 0-2 carbon atoms in C2-C5 are independently replaced by one or more N, S and / or O heteroatoms, wherein R 8c Yes – N(R 8d ) 2-3 or guanidino, where each R 8d are independently -H or a linear or branched C1-C3 alkyl group.

[0266] In some embodiments of compounds of Formula A, B, and / or C, R 8b is a straight chain C1-C5 alkylene, alkenylene, or alkynylene group (i.e., no heteroatoms).8b A single heteroatom (N, S, or O) is included in any of C2-C5. In some embodiments, R 8b It is a straight chain C1-C5 alkylene group.

[0267] In some embodiments of compounds of Formula A, B, and / or C, R 8c In some embodiments, R 8c Yes-N(R 8d ) 2-3 In some embodiments, R 8c Yes-N(R 8d ) 2-3 , where each R 8d is a straight chain or branched C1-C3 alkyl group. 8c Yes-N(R 8d ) 2-3 , where each R 8d In some embodiments, R 8c Yes-N(R 8d ) 2-3 , where each R 8d In some embodiments, R 8c It is -NH2 or -NH3.

[0268] In some embodiments of 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 )-C(O)- forms a Lys(iPr) residue. As used herein, in the expression "-NH-CH(R)" with respect to Formula A, AI, A-II, A-III, A-IV, B and / or C, 8a )-C(O)-”, it should be understood that the -C(O)- part is R 9a For example, in some embodiments, -NH-CH(R 8a )-with R 9a The -C(O)- of the alkylene group and the alkylene group together form an L amino acid residue, a D amino acid residue or a Lys(iPr) residue.

[0269] In some embodiments of compounds of Formula A, B, and / or C, -NH-CH(R 8a )-with R 9a In some embodiments, -NH-CH(R 8a )-with R9a The amino acid residue formed by -C(O)- is amidated. In some embodiments, -NH-CH(R 8a )-with R 9a In some embodiments, -NH-CH(R 8a )-with R 9a The -C(O)- of the -NH-CH(R)- is taken together to form a Lys(iPr) residue which is amidated. 8a )-with R 9a The -C(O)- together form Lys(iPr)-NH2.

[0270] In some embodiments of compounds of Formula A, B, and / or C, R 9a are: -C(O)NH2,-C(O)-OH,-CH2-C(O)NH2,-CH2-C(O)-OH,-CH2-NH2,-CH2-OH,-CH2-CH2-NH2,-R 9b -R 9c or -R 9b -[Connector]-R X n1 ,in:

[0271] R 9b is -CH2-NH-C(O)-,-CH2-C(O)-,-CH2-O-,-C(O)NH-,-C(O)-N(CH3)-,-CH2-NHC(S)-,-C(S) NH-,-CH2-N(CH3)C(S)-,-C(O)N(CH3)-,-CH2-N(CH3)C(O)-,-C(S)N(CH3)-,-CH2-NHC(S) NH-,-CH2-NHC(O)NH-,-CH2-S-,-CH2-S(O)-,-CH2-S(O)2-,-CH2-S(O)2-NH-,-CH2-S(O)- NH-,-CH2-Se-,-CH2-Se(O)-,-CH2-Se(O)2-,-CH2-NHNHC(O)-,-C(O)NHNH-,-CH2-OP(O)(O - )O-, -CH2-phosphoramide-, -CH2-thiophosphate diester-, -CH2-S-tetrafluorophenyl-S-, or polyethylene glycol; and

[0272] R 9c is hydrogen or a linear, branched and / or cyclic C1-C 20 Alkyl, alkenyl or alkynyl, wherein C2-C 200-6 carbon atoms in the alkylene group are independently replaced by N, S and / or O heteroatoms, and 0-3 groups are independently selected from one or a combination of oxo, hydroxyl, thiol, halogen, guanidino, carboxylic acid, sulfonic acid, sulfinic acid and / or phosphoric acid.

[0273] In some embodiments of compounds of Formula A, B, and / or C, R 9a In some embodiments, R 9a Yes-R 9b -R 9c , where R 9b It is –C(O)NH–.

[0274] In some embodiments of compounds of Formula A, B, and / or C, R 9c yes where R 9d is a straight or branched C1-C5 alkylene, alkenylene or alkynylene group, wherein 0-2 carbon atoms in C2-C5 are independently replaced by N, S and / or O heteroatoms, wherein R 9e is carboxylic acid, sulfonic acid, sulfinic acid, phosphoric acid, amino, guanidino, -SH, -OH, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-CH3, -N(CH3)2, -S-CH3, -O-CH3 and phenyl, and wherein R 9f is amino or -OH. In some embodiments, R 9d is a straight or branched C1-C5 alkylene, alkenylene or alkynylene group (i.e., no heteroatoms). 9d It is a straight chain or branched C1-C5 alkylene group.

[0275] In some embodiments of compounds of Formula A, B, and / or C, R 9a Yes-R 9b -[Connector]-R X n1 In some of these embodiments, R 9b It is -C(O)NH-.

[0276] In some embodiments of compounds of Formula A, B, and / or C: R 9a It is -C(O)NH2, -C(O)-OH, -R 9b -R 9c or -R 9b -[Connector]-R X n1 ; and R9b is -C(O)NH-, -C(O)-N(CH3)-, -C(O)N(CH3)- or -C(O)NHNH-.

[0277] In some embodiments of the compound of Formula A, R A7a is a straight chain C1-C5 alkylene group, wherein 0-2 carbon atoms in C2-C5 are independently replaced by one or more N, S and / or O heteroatoms. A7a is a straight chain C1-C5 alkylene group (i.e., no heteroatoms). A7a is a straight chain C1-C5 alkylene group, wherein one carbon in C2-C5 is a heteroatom selected from N, S or O. In some embodiments, R A7a is -CH2-. In some embodiments, R A7a It is –CH2-CH2–.

[0278] 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.

[0279] In some embodiments, -NH-CH(R A7a )-C(O)- forms a D amino acid residue, and R A7a Is C1-C3 alkylene. In some embodiments, -NH-CH(R A7a )-C(O)- forms an L amino acid residue, and R A7a It is a C1-C3 alkylene group.

[0280] In some embodiments of the compound of Formula A, R A10 Does not exist or is -[connector]-R X n1 .

[0281] In some embodiments of the compound of Formula A, when R A10 If it does not exist, then R A1a :

[0282] Straight chain C1-C5 alkyl, alkenyl or alkynyl, wherein 0-2 carbons in C2-C5 are independently replaced by one or more N, S and / or O heteroatoms, optionally C-substituted by a monosubstituent selected from the group consisting of -SH, -OH, amino, carboxyl, guanidino, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH3)1-2 、-NH2-CH3、-N(CH3) 2-3 , -S-CH3 or -O-CH3;

[0283] Branched chain C1-C 10 Alkyl, alkenyl or alkynyl, wherein C2-C 10 0-3 carbon atoms in are independently replaced by one or more N, S and / or O heteroatoms; or

[0284] R A1b R A1c , where R A1b is a straight chain C1-C3 alkylene, wherein C2 alkylene or C3 alkylene is optionally replaced by N, S or O heteroatom, wherein R A1c yes:

[0285] a 5- or 6-membered aromatic ring in which one or more carbons are optionally independently replaced by N, S and / or O heteroatoms, and optionally substituted by one or more groups independently selected from oxo, hydroxy, thiol, nitro, amino and / or halogen; or

[0286] Fused bicyclic or fused tricyclic aryl groups, wherein one or more carbons are optionally independently replaced by N, S and / or O heteroatoms, and are optionally independently selected from halogen, -OH, -OR A1d , amino, -NHR A1d and / or N(R A1d )2 is substituted with one or more groups, wherein each R A1d are independently C1-C3 straight or branched chain alkyl groups.

[0287] In some embodiments of the compound of Formula A, when R A10 Yes-[Connector]-R X n1 When R A1a It is R A1e R A1f , where R A1e is a straight chain C1-C5 alkylene, alkenylene or alkynylene group, wherein 0-2 carbon atoms in C2-C5 are independently replaced by N, S and / or O heteroatoms, and R A1fis -NH-C(O)-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C(S)NH-, -N(CH3)C(S)-, -C(O)N(CH3)-, -N(CH3)C(O)-, -C(S)N(CH3)-, -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-, -phosphoramide-, -phosphorothioate diester-, -S-tetrafluorophenyl-S-, polyethylene glycol,

[0288] 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(R A1a )-C(O)- forms a D amino acid residue.

[0289] In some embodiments of the compound of Formula A, R A10 Does not exist.

[0290] In some embodiments of the compound of Formula A, when R A10 When it does not exist, R A1a is a straight-chain C1-C5 alkyl, alkenyl or alkynyl group, optionally substituted with a monosubstituent selected from the group consisting of -SH, -OH, amino, carboxyl, guanidino, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH3) 1-2 、-NH2-CH3、-N(CH3) 2-3 , -S-CH3 or -O-CH3. In R A10 In some embodiments where R A1a is a straight-chain C1-C5 alkyl group, optionally substituted with a monosubstituent selected from the group consisting of -SH, -OH, amino, carboxyl, guanidino, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH3) 1-2 、-NH2-CH3、-N(CH3) 2-3, -S-CH3 or -O-CH3.

[0291] In some embodiments of the compound of Formula A, when R A10 When it does not exist, R A1a It is a branched chain C1-C 10 Alkyl, alkenyl or alkynyl. A10 In some embodiments where R A1a It is a branched chain C1-C 10 alkyl.

[0292] In some embodiments of the compound of Formula A, when R A10 When it does not exist, R A1a It is R A1b R A1c In some embodiments, R A1b is a straight chain C1-C3 alkylene. A1c is a 5- or 6-membered aromatic ring in which 0-4 carbon atoms are independently replaced by N, S and / or O heteroatoms and substituted by 0-4 groups independently selected from oxo, hydroxy, thiol, nitro, amino and / or halogen. In some embodiments, R A1c is a fused bicyclic or fused tricyclic aryl group wherein 0-6 carbon atoms are independently replaced by N, S and / or O heteroatoms and are optionally independently selected from halogen, -OH, -OR A1d , amino, -NHR A1d and / or N(R A1d ) 2 is substituted with 0-6 groups. In some embodiments, R A1d In some embodiments, each ring in the fused bicyclic or fused tricyclic aryl group independently has 4, 5, or 6 ring carbons, of which 0-3 carbons are independently replaced by N, S, and / or O heteroatoms; such embodiments can be substituted or unsubstituted, as defined above.

[0293] 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(RA1a )-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 an 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.

[0294] In some embodiments of the compound of Formula A, R A10 Yes-[Connector]-R X n1 , and R A1a It is R A1e R A1f In some embodiments, R A1e is a straight chain C1-C5 alkylene, alkenylene or alkynylene. A1e is a straight chain C1-C5 alkylene. A1f is -NH-C(O)-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C(S)NH-, -N(CH3)C(S)-, -C(O)N(CH3)-, -N(CH3)C(O)-, -C(S )N(CH3)-, -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,

[0295] All embodiments of Formula A described herein may be embodiments of Formula AI, Formula A-II, Formula III, and / or Formula A-IV, as long as the definitions are encompassed by Formula AI, Formula A-II, Formula III, and / or Formula A-IV.

[0296] In some embodiments of the compound of Formula B, R B1a It is a linear, branched and / or cyclic C1-C 10 Alkylene, alkenylene or alkynylene, wherein C2-C 10 One or more carbons in are optionally independently replaced by N, S and / or O heteroatoms.

[0297] In some embodiments of the compound of Formula B, R B1-7 yes: wherein indole and isoindole are optionally substituted with -F, -Br, -Cl, -I, -OH, -OR B1-7b ,-CO-,-COOH,-CONH2,-CN,-O-aryl, -NH2,-NHR B1-7b ,N3,-NO2,-NH,-CHO and / or -R B1-7b One or more substitutions, wherein each R B1-7b is a straight or branched C1-C3 alkyl, alkenyl or alkynyl. In some embodiments, indole and isoindole are unsubstituted. In some embodiments, indole and isoindole are selected from -F, -Br, -Cl, -I, -OH, -OR C1b ,-CO-,-COOH,-CONH2,-CN,-O-aryl,-NH2,-NHR C1b ,N3,-NO2,-NH,-CHO and / or -R C1b In some embodiments, each R C1b In some embodiments, aryl is a 5- or 6-membered aromatic ring.

[0299] In some embodiments of the compound of Formula B, R B7a is a straight chain C1-C5 alkylene group, wherein optionally, 0-2 carbon atoms in C2-C5 are independently replaced by one or more N, S and / or O heteroatoms. In some embodiments, R B7a is a straight chain C1-C5 alkylene group (i.e., no heteroatoms). B7a is a straight chain C1-C5 alkylene group, wherein one carbon in C2-C5 is a heteroatom selected from N, S or O. In some embodiments, R B7a is -CH2-. In some embodiments, R B7aIn 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.

[0300] In some embodiments of the compound of Formula B, R B1-7 yes wherein indole and isoindole are optionally substituted with -F, -Br, -Cl, -I, -OH, -OR B1-7b ,-CO-,-COOH,-CONH2,-CN,--O-aryl, -NH2, -NHR B1-7b , N3, -NO2, -NH, -CHO and / or -R B1-7b One or more substitutions, wherein each R B1-7b is a straight or branched C1-C3 alkyl, alkenyl or alkynyl. In some embodiments, indole and isoindole are selected from -F, -Br, -Cl, -I, -OH, -OR C1b ,-CO-,-COOH,-CONH2,-CN,-O-aryl,-NH2,-NHR C1b ,N3,-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 yes

[0301] In some embodiments of the compound of Formula B, R B1a Yes – (CH2) 1-2 -, R B1-7 yes And R B7a Yes – (CH2) 1-2 -.

[0302] In some embodiments of the compound of Formula B, R B1a -R B1-7 -R B7a yes

[0303] 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.

[0304] In some embodiments of the compound of Formula B, R B10a It is an amine, -NH-(CH3) 1-2 、-N(CH3) 2-3 , -NH-C(O)-CH3, -NH-C(O)-(phenyl) or –R B10b -[Connector]-R X n1 , where R B10b yes:

[0305] -NH-C(O)-,-C(O)-,-O-,-C(O)NH–,-C(O)-N(CH3)-,-NHC(S)-,-C(S)NH-,-N(CH3)C(S)-,-C(O)N(CH3)-,-N(CH3)C(O)-,-C(S)N(CH3)-,-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-, -phosphoramide-, -phosphorothioate diester-, -S-tetrafluorophenyl-S-, or polyethylene glycol.

[0306] In some embodiments of the compound of Formula B, R B10a It is an amine, -NH-(CH3) 1-2 、-N(CH3) 2-3 , -NH-C(O)-CH3 or -NH-C(O)-(phenyl).

[0307] In some embodiments of the compound of Formula B, R B10a Yes-R B10b -[Connector]-R X n1 In some of these embodiments, R B10b are: -NH-C(O)-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C(S)NH-, -N(CH3)C(S)-, -C( O)N(CH3)-, -N(CH3)C(O)-, -C(S)N(CH3)-, -NHC(S)NH-, -NHC(O)NH-, -NHNHC(O)-, -C(O)NHNH-, Or polyethylene glycol. In some embodiments, R B10aYes-NHC(O)-[Connector]-R X n1 or -N(CH3)C(O)-[Linker]-R X n1 .

[0308] 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 ;

[0309] X 1 are independently -CH2-,

[0310] L 1 each independently represents –NH–, –C(O)–, –NHC(O)–, –C(O)NH–, –N(CH 3 )C(O)–, or –C(O)N(CH 3 )–;

[0311] R 11 are each independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid; and

[0312] R Z Each is independently an albumin binder.

[0313] In some embodiments, the linker is X 1a L 1a X 1b L 1b ;

[0314] X 1a yes

[0315] L 1a is –NH– or –NHC(O)–;

[0316] X 1b yes and

[0317] L 1b It is –NH– or –NHC(O)–.

[0318] In some embodiments, the linker is X 1a L 1a X 1b L 1b ;

[0319] X 1a yes

[0320] L 1a is –NH– or –NHC(O)–;

[0321] X 1b yes and

[0322] L 1b It is –NH– or –NHC(O)–.

[0323] In some embodiments, R B10a Yes-NHC(O)-[Connector]-R X n1 , the connector is X 1a L 1a X 1b L 1b ,

[0324] X 1a is C1-C2 alkenyl; L 1a is -NH-C(O); X 1b yes And L 1b is -NH-, and R 11 are independently carboxylic acid, sulfonic acid, sulfinic acid or phosphoric acid. 11 It is sulfonic acid (-SO3H).

[0325] In some embodiments of the compound of Formula C, R C1a yes:

[0326] wherein the indole, isoindole and triazole rings are optionally replaced by -F, -Br, -Cl, -I, -OH, -OR C1b ,-CO-,-COOH,-CONH2,-CN,-O-aryl,-NH2,-NHR C1b , N3, -NO2, -NH, -CHO and / or -R C1b One or more substitutions, wherein each R C1b is a straight or branched C1-C3 alkyl, alkenyl or alkynyl group; provided that the compound of formula C is not cyclo(isoindole)[Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-D-Cys]-Lys(iPr)-NH2, cyclo(isoindole)[Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-Cys]-Lys(iPr)-NH2, cyclo(isoindole)[Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-Cys]-Lys(iPr)-NH2, cyclo(isoindole N a-S)[Lys(Cys(acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH2, Cyclo(Me-isoindole N a -S)[Lys(Cys(acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH2, Cyclo(NO2-isoindole N a -S)[Lys(Cys(acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH2 and cyclo(NO2-isoindole N a -S)[Lys(Cys(acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-hCys]-Lys(iPr)-NH2. In some embodiments, indole and isoindole are unsubstituted. In some embodiments, indole and isoindole are selected from -F, -Br, -Cl, -I, -OH, -OR C1b ,-CO-,-COOH,-CONH2,-CN,-O-aryl,-NH2,-NHR C1b , N3, -NO2, -NH, -CHO and / or -R C1b In some embodiments, each R C1b In some embodiments, aryl is a 5- or 6-membered aromatic ring.

[0327] In some embodiments of the compound of Formula C, R C1a yes:

[0328] wherein indole and isoindole are optionally substituted with -F, -Br, -Cl, -I, -OH, -OR C1b , -CO-, -COOH, -CONH2, -CN, -O-aryl, -NH2, -NHR C1b , N3, -NO2, -NH, -CHO and / or -R C1b One or more substitutions, wherein each R C1bis a straight or branched C1-C3 alkyl, alkenyl or alkynyl group; provided that the compound of formula C is not cyclo(isoindole)[Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-D-Cys]-Lys(iPr)-NH2, cyclo(isoindole)[Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-Cys]-Lys(iPr)-NH2, cyclo(isoindole)[Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-Cys]-Lys(iPr)-NH2, cyclo(isoindole N a -S)[Lys(Cys(acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH2, Cyclo(Me-isoindole N a -S)[Lys(Cys(acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH2, Cyclo(NO2-isoindole N a -S)[Lys(Cys(acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH2 and cyclo(NO2-isoindole N a -S)[Lys(Cys(acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-hCys]-Lys(iPr)-NH2. In some embodiments, indole and isoindole are unsubstituted. In some embodiments, indole and isoindole are selected from -F, -Br, -Cl, -I, -OH, -OR C1b , -CO-, -COOH, -CONH2, -CN, -O-aryl, -NH2, -NHR C1b , N3, -NO2, -NH, -CHO and / or -R C1b In some embodiments, each R C1b In some embodiments, aryl is a 5- or 6-membered aromatic ring.

[0329] In some embodiments of the compound of Formula C, R C1a yes:

[0330]

[0331] In some embodiments of the compound of Formula C, R C1a yes:

[0332] Provided that the compound of formula C is not cyclo(isoindole)[Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-D-Cys]-Lys(iPr)-NH2, cyclo(isoindole)[Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-Cys]-Lys(iPr)-NH2, cyclo(isoindole)[Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-Cys]-Lys(iPr)-NH2,

[0333] N a -S)[Lys(Cys(acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH2, Cyclo(Me-isoindole N a -S)[Lys(Cys(acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH2, Cyclo(NO2-isoindole N a -S)[Lys(Cys(acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH2 and cyclo(NO2-isoindole N a -S)[Lys(Cys(acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-hCys]-Lys(iPr)-NH2.

[0334] In some embodiments of the compound of Formula C, R C7a is a straight chain C1-C5 alkylene group, wherein optionally, 0-2 carbon atoms in C2-C5 are independently replaced by one or more N, S and / or O heteroatoms. In some embodiments, R C7a is a straight chain C1-C5 alkylene group (i.e., no heteroatoms). C7a is a straight chain C1-C2 alkylene group. C7a is a straight chain C1-C5 alkylene group, wherein one carbon in C2-C5 is a heteroatom selected from N, S or O. In some embodiments, R C7a Yes – (CH2) 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.

[0335] In some embodiments of the compound of Formula C, R C1a yes:

[0336]

[0337] And R C7a It is a straight chain C1-C2 alkylene group.

[0338] In some embodiments of the compound of Formula C, R C1a yes:

[0339] And R C7a is a straight chain C1-C2 alkylene group, provided that the compound of formula C is not cyclo(isoindole)[Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-D-Cys]-Lys(iPr)-NH2, cyclo(isoindole)[Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-Cys]-Lys(iPr)-NH2, cyclo(isoindole)[Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-Cys]-Lys(iPr)-NH2, cyclo(isoindole N a -S)[Lys(Cys(acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH2, Cyclo(Me-isoindole N a -S)[Lys(Cys(acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH2, Cyclo(NO2-isoindole N a -S)[Lys(Cys(acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH2 and cyclo(NO2-isoindole N a -S)[Lys(Cys(acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-hCys]-Lys(iPr)-NH2.

[0340] In some embodiments of the compound of Formula C, R C10a It is R C10b -R C10c -[Connector]-R X n1 or R C10d ,in:

[0341] R C10b is a straight chain C1-C5 alkylene, alkenylene or alkynylene group, wherein 0-2 carbon atoms in C2-C5 are independently replaced by N, S and / or O heteroatoms;

[0342] R C10cis -NH-C(O)-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C(S)NH-, -N(CH3)C(S)-, -C(O)N(CH3)-, -N(CH3)C(O)-, -C(S)N(CH3)-, -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-, -phosphoramide-, -phosphorothioate diester-, -S-tetrafluorophenyl-S-, or polyethylene glycol; and

[0343] R C10d yes:

[0344] Straight chain C1-C5 alkyl, alkenyl or alkynyl, wherein 0-2 carbons in C2-C5 are independently replaced by N, S and / or O heteroatoms, optionally C-substituted by a monosubstituent selected from the group consisting of -SH, -OH, amino, carboxyl, guanidino, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH3) 1-2 、-NH2-CH3、-N(CH3) 2-3 , -S-CH3 or -O-CH3;

[0345] Branched chain C1-C 10 Alkyl, alkenyl or alkynyl, wherein C2-C 10 0-3 carbon atoms in are independently replaced by N, S and / or O heteroatoms; or

[0346] R C10e R C10f , where R C10e is a straight chain C1-C3 alkyl group, wherein the C2 alkyl group or the C3 alkyl group is optionally replaced by a N, S or O heteroatom, wherein R C10f yes:

[0347] a 5- or 6-membered aromatic ring in which one or more carbons are optionally independently replaced by N, S and / or O heteroatoms, and optionally substituted by one or more groups independently selected from oxo, hydroxy, thiol, nitro, amino and / or halogen; or

[0348] Fused bicyclic or fused tricyclic aryl groups, wherein one or more carbons are optionally independently replaced by N, S and / or O heteroatoms, and are optionally independently selected from halogen, -OH, -OR C10g , amino, -NHR C10g and / or N(R C10g )2 is substituted with one or more groups, wherein R C10g It is a C1-C3 straight chain or branched chain alkyl group.

[0349] In some embodiments of the compound of Formula C, R C10a It is R C10b -R C10c -[Connector]-R X n1 In some embodiments, R C10b is a straight chain C1-C5 alkylene, alkenylene or alkynylene. C10b is a straight chain C1-C5 alkylene. C10c are: -NH-C(O)-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C(S)NH-, -N(CH3)C(S)-, -C( O)N(CH3)-, -N(CH3)C(O)-, -C(S)N(CH3)-, -NHC(S)NH-, -NHC(O)NH-, -NHNHC(O)-, -C(O)NHNH-, Or polyethylene glycol. In some embodiments, R C10c It is –NHC(O)- or -N(CH3)C(O)-.

[0350] 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 ;

[0351] X 1 are independently -CH2-,

[0352] L 1 each independently represents –NH–, –C(O)–, –NHC(O)–, –C(O)NH–, –N(CH 3 )C(O)–, or –C(O)N(CH 3 )–;

[0353] R 11 are each independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid; and

[0354] R Z Each is independently an albumin binder.

[0355] In some embodiments, the linker is X 1a L 1a X 1b L 1b ;

[0356] X 1a yes

[0357] L 1a is –NH– or –NHC(O)–;

[0358] X 1b yes and

[0359] L 1b It is –NH– or –NHC(O)–.

[0360] In some embodiments, the linker is X 1a L 1a X 1b L 1b ;

[0361] X 1a yes

[0362] L 1a is –NH– or –NHC(O)–;

[0363] X 1b yes and

[0364] L 1b It is –NH– or –NHC(O)–.

[0365] In some embodiments, the linker is X 1a L 1a X 1b L 1b ;

[0366] X 1a yes

[0367] L 1a is –NH– or –NHC(O)–;

[0368] X 1b yes and

[0369] L 1b It is –NH– or –NHC(O)–.

[0370] In some embodiments, the linker is X 1a L 1a X 1b L 1b X 1c L 1c ;

[0371] X 1a yes

[0372] L 1a is –NH– or –NHC(O)–;

[0373] X 1b yes

[0374] L 1b is –NH– or –NHC(O)–;

[0375] X 1c is –CH2–; and

[0376] L 1c It is –NH– or –NHC(O)–.

[0377] In some embodiments, the linker is X 1a L 1a X 1b L 1b X 1c L 1c ;

[0378] X 1a yes

[0379] L 1a is –NH– or –NHC(O)–;

[0380] X 1b is –CH2–;

[0381] L 1b is –NH– or –NHC(O)–;

[0382] X 1c yes and

[0383] L 1c It is –NH– or –NHC(O)–.

[0384] In some embodiments, R C10aYes-NHC(O)-[Connector]-R X n1 , the connector is X 1a L 1a X 1b L 1b ,

[0385] X 1a is C1-C2 alkenyl; L 1a is -NH-C(O); X 1b yes And L 1b is -NH-, and R 11 is independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid.

[0386] In some embodiments, R 11 It is sulfonic acid (-SO3H).

[0387] In some embodiments of the compound of Formula C, R C10a It is R C10d .

[0388] In some embodiments of the compound of Formula C, R C10d is a straight chain C1-C5 alkyl, alkenyl or alkynyl group, wherein 0-2 carbons in C2-C5 are independently replaced by N, S and / or O heteroatoms, optionally C-substituted by a monosubstituent selected from the group consisting of: -SH, -OH, amino, carboxyl, guanidino, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH3) 1-2 、-NH2-CH3、-N(CH3) 2-3 , -S-CH3 and -O-CH3.

[0389] In some embodiments of the compound of Formula C, R C10d is a straight-chain C1-C5 alkyl, alkenyl or alkynyl group, optionally C-substituted with a monosubstituent selected from the group consisting of: -SH, -OH, amino, carboxyl, guanidino, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH3) 1-2 、-NH2-CH3、-N(CH3) 2-3 , -S-CH3 and -O-CH3. In some embodiments, R C10dis a straight-chain C1-C5 alkyl group, optionally C-substituted with a monosubstituent selected from the group consisting of: -SH, -OH, amino, carboxyl, guanidino, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH3) 1-2 、-NH2-CH3、-N(CH3) 2-3 , -S-CH3 and -O-CH3.

[0390] In some embodiments of the compound of Formula C, R C10d It is a branched chain C1-C 10 Alkyl, alkenyl or alkynyl, wherein C2-C 10 0-3 carbon atoms in are independently replaced by N, S and / or O heteroatoms. In some embodiments, R C10d It is a branched chain C1-C 10 In some embodiments, R C10d It is a branched chain C1-C 10 alkyl.

[0391] In some embodiments of the compound of Formula C, R C10d It is R C10e R C10f In some embodiments, R C10e is a straight chain C1-C3 alkyl group. In some embodiments, R C10f is a 5- or 6-membered aromatic ring in which 0-4 carbon atoms are independently replaced by N, S and / or O heteroatoms and substituted by 0-4 groups independently selected from oxo, hydroxy, thiol, nitro, amino and / or halogen. In some embodiments, R C10f is a fused bicyclic or tricyclic aryl group in which 0-6 carbon atoms are independently replaced by N, S and / or O heteroatoms and are independently selected from halogen, -OH, -OR C10g , amino, -NHR C10g and / or N(R C10g )2 is substituted with 0-6 groups, wherein R C10g is a C1-C3 straight or branched chain alkyl group. C10g In some embodiments, each ring in the fused bicyclic or fused tricyclic aryl group independently has 4, 5, or 6 ring carbons, of which 0-3 carbons are independently replaced by N, S, and / or O heteroatoms; such embodiments can be substituted or unsubstituted, as defined above.

[0392] In some embodiments of the compound of Formula A: -NH-CH(R 2a)-C(O)- forms a (3-I)Tyr residue; -NH-CH(R 3a )-C(O)- forms Lys(iPr) residues; -NH-CH(R 4a )-C(O)- forms a D-Arg residue; -NH-CH(R 5a )-C(O)- forms 2-Nal or (4-NH2)Phe residues; -NH-CH(R 6a )-C(O)- forms a Gly residue; -NH-CH(R A7a )-C(O)- forms D amino acids, where R A7a is C1-C3 alkylene; 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)- to form a (4-NH2)Phe residue.

[0393] In some embodiments of the compound of Formula A: -NH-CH(R 2a )-C(O)- forms a Tyr residue; -NH-CH(R 3a )-C(O)- forms Lys(iPr) residues; -NH-CH(R 4a )-C(O)- forms a D-Arg residue; -NH-CH(R 5a )-C(O)- forms a 2-Nal residue or a (4-NH2)Phe residue; -NH-CH(R 6a )-C(O)- forms a D-Ala residue; -NH-CH(R A7a )-C(O)- forms a D amino acid residue, where R A7a is C1-C3 alkylene; 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)- to form a (4-NH2)Phe residue.

[0394] In some embodiments of the compound of Formula A: -NH-CH(R 2a )-C(O)- forms a (4-NH2)Phe residue; -NH-CH(R 3a )-C(O)- forms Lys(iPr) residues; -NH-CH(R 4a)-C(O)- forms a D-Arg residue; -NH-CH(R 5a )-C(O)- forms a 2-Nal residue or a (4-NH2)Phe residue; -NH-CH(R 6a )-C(O)- forms a Gly residue; -NH-CH(R A7a )-C(O)- forms a D amino acid residue, where R A7a is C1-C3 alkylene; 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)- to form a (4-NH2)Phe residue.

[0395] In some embodiments of the compound of Formula A: -NH-CH(R 2a )-C(O)- forms (4-NO2)Phe residue; -NH-CH(R 3a )-C(O)- forms Lys(iPr) residues; -NH-CH(R 4a )-C(O)- forms a D-Arg residue; -NH-CH(R 5a )-C(O)- forms a 2-Nal residue or a (4-NH2)Phe residue; -NH-CH(R 6a )-C(O)- forms a Gly residue; -NH-CH(R A7a )-C(O)- forms a D amino acid residue, where R A7a is C1-C3 alkylene; 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)- to form a (4-NH2)Phe residue.

[0396] In some embodiments of the compound of Formula A: -NH-CH(R 2a )-C(O)- forms hTyr residue; -NH-CH(R 3a )-C(O)- forms Lys(iPr) residues; -NH-CH(R 4a )-C(O)- forms a D-Arg residue; -NH-CH(R 5a )-C(O)- forms a 2-Nal residue or a (4-NH2)Phe residue; -NH-CH(R 6a)-C(O)- forms a Gly residue; -NH-CH(R A7a )-C(O)- forms a D amino acid residue, where R A7a is C1-C3 alkylene; 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)- to form a (4-NH2)Phe residue.

[0397] In some embodiments of the compound of Formula A: -NH-CH(R 2a )-C(O)- forms a Tyr residue; -NH-CH(R 3a )-C(O)- forms Lys(iPr) residues; -NH-CH(R 4a )-C(O)- forms a D-Arg residue; -NH-CH(R 5a )-C(O)- forms a 2-Nal residue or a (4-NH2)Phe residue; -NH-CH(R 6a )-C(O)- forms a D-His residue; -NH-CH(R A7a )-C(O)- forms a D amino acid residue, where R A7a is C1-C3 alkylene; 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)- to form a (4-NH2)Phe residue.

[0398] In some embodiments of the compound of Formula A: -NH-CH(R 2a )-C(O)- forms a Tyr residue; -NH-CH(R 3a )-C(O)- forms Lys(iPr) residues; -NH-CH(R 4a )-C(O)- forms a D-Arg residue; -NH-CH(R 5a )-C(O)- forms a 2-Nal residue or a (4-NH2)Phe residue; -NH-CH(R 6a )-C(O)- forms a His residue; -NH-CH(R A7a )-C(O)- forms a D amino acid residue, where R A7a is C1-C3 alkylene; and -NH-CH(R8a )-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)- to form a (4-NH2)Phe residue.

[0399] In some embodiments of the compound of Formula A: -NH-CH(R 2a )-C(O)- forms a Tyr residue; -NH-CH(R 3a )-C(O)- forms Lys(iPr) residues; -NH-CH(R 4a )-C(O)- forms a D-Arg residue; -NH-CH(R 5a )-C(O)- forms a 2-Nal residue or a (4-NH2)Phe residue; -NH-CH(R 6a )-C(O)- forms D-Ser residue; -NH-CH(R A7a )-C(O)- forms a D amino acid residue, where R A7a is C1-C3 alkylene; 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)- to form a (4-NH2)Phe residue.

[0400] In some embodiments of the compound of Formula A: -NH-CH(R 2a )-C(O)- forms a Tyr residue; -NH-CH(R 3a )-C(O)- forms Lys(iPr) residues; -NH-CH(R 4a )-C(O)- forms a D-Arg residue; -NH-CH(R 5a )-C(O)- forms a 2-Nal residue or a (4-NH2)Phe residue; -NH-CH(R 6a )-C(O)- forms a D-Glu residue; -NH-CH(R A7a )-C(O)- forms a D amino acid residue, where R A7a is C1-C3 alkylene; 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)- to form a (4-NH2)Phe residue.

[0401] In some embodiments of the compound of Formula A: -NH-CH(R 2a )-C(O)- forms a Tyr residue; -NH-CH(R 3a )-C(O)- forms Lys(iPr) residues; -NH-CH(R 4a )-C(O)- forms a D-Arg residue; -NH-CH(R 5a )-C(O)- forms a 2-Nal residue or a (4-NH2)Phe residue; -NH-CH(R 6a )-C(O)- forms a D-His residue; -NH-CH(R A7a )-C(O)- forms a D amino acid residue, where R A7a is C1-C3 alkylene; 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)- to form a (4-NH2)Phe residue.

[0402] In some embodiments of the compound of Formula A: -NH-CH(R 2a )-C(O)- forms a Tyr residue; -NH-CH(R 3a )-C(O)- forms Lys(iPr) residues; -NH-CH(R 4a )-C(O)- forms a D-Arg residue; -NH-CH(R 5a )-C(O)- forms (2-Ant)Ala residue; -NH-CH(R 6a )-C(O)- forms a Gly residue; -NH-CH(R A7a )-C(O)- forms a D amino acid residue, where R A7a is C1-C3 alkylene; 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)- to form a (4-NH2)Phe residue.

[0403] In some embodiments of the compound of Formula A: -NH-CH(R 2a )-C(O)- forms a Tyr residue; -NH-CH(R 3a )-C(O)- forms Lys(iPr) residues; -NH-CH(R 4a )-C(O)- forms a D-Arg residue; -NH-CH(R 5a )-C(O)- forms a 2-Nal residue or a (4-NH2)Phe residue; -NH-CH(R 6a )-C(O)- forms a D-Ala residue; -NH-CH(R A7a )-C(O)- forms a D amino acid residue, where R A7a is C1-C3 alkylene; 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)- to form a (4-NH2)Phe residue.

[0404] In some embodiments of the compound of Formula A: -NH-CH(R 2a )-C(O)- forms a Tyr residue; -NH-CH(R 3a )-C(O)- forms Lys(iPr) residues; -NH-CH(R 4a )-C(O)- forms a D-Arg residue; -NH-CH(R A7a )-C(O)- forms a D amino acid residue, where R A7a is C1-C3 alkylene; 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)- to form a (4-NH2)Phe residue. In some of these embodiments, -NH-CH(R A1a )-C(O)- forms a Phe residue, and R A10 In some embodiments, R A10 Yes-[Connector]-R Xn1 , RA 1e is a straight chain C1-C5 alkylene group, and R A1f It is -NHC(O).

[0405] In some embodiments of the compound of Formula A, one or more of the following conditions are met:

[0406] a)-NH-CH(R 2a )-C(O)- forms a Tyr residue;

[0407] b)-NH-CH(R 3a )-C(O)- forms Lys(iPr) residues;

[0408] c)-NH-CH(R 4a )-C(O)- forms a D-Arg residue;

[0409] d)-NH-CH(R 5a )-C(O)- to form a 2-Nal residue; and / or

[0410] e)-NH-CH(R 6a )-C(O)- forms a D-Ala residue.

[0411] In some embodiments of the compound of Formula A, -NH-CH(R 2a )-C(O)- forms a Tyr residue; -NH-CH(R 3a )-C(O)- forms Lys(iPr) residues; -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 a D-Ala residue.

[0412] In some embodiments of the compound of Formula A, -NH-CH(R 2a )-C(O)- forms a Tyr residue; -NH-CH(R 3a )-C(O)- forms Lys(iPr) residues; -NH-CH(R 4a )-C(O)- forms a D-Arg residue; -NH-CH(R A7a )-C(O)- forms a D amino acid residue, where R A7a is C1-C3 alkylene; and -NH-CH(R 8a )-with R 9a In some embodiments, -NH-CH(R 6a)-C(O)- forms a Gly residue, a D-Ala residue, a D-Gln residue, or a D-Asn residue. In some embodiments, -NH-CH(R A1a )-C(O)- forms a Phe residue, and R 10A In some embodiments, R A10 Yes-[Connector]-R X n1 , R A1e is a straight chain C1-C5 alkylene group, and R A1f It is -NH-C(O)-.

[0413] In some embodiments of the compound of Formula A: -NH-CH(R 2a )-C(O)- forms a Tyr residue; -NCH3-CH(R 3a )-C(O)- forms Lys(iPr) residues; -NH-CH(R 4a )-C(O)- forms a D-Arg residue; -NH-CH(R 5a )-C(O)- forms 2-Nal residue; -NH-CH(R 6a )-C(O)- forms D-Ala; -NH-CH(R A7a )-C(O)- forms a D amino acid residue, where R A7a is C1-C3 alkylene; and -NH-CH(R 8a )-with R 9a In some embodiments, -NH-CH(R 8a )-with R 9a The -C(O)- of the -NH-CH(R)- is taken together to form a Lys(iPr) residue which is amidated. 8a )-with R 9a The -C(O)- together form Lys(iPr)-NH2.

[0414] In some embodiments of the compound of Formula A: -NH-CH(R 2a )-C(O)- forms a Tyr residue; -NH-CH(R 3a )-C(O)- forms Lys(iPr) residues; -NH-CH(R 4a )-C(O)- forms a D-Arg residue; -NH-CH(R 5a )-C(=NH)- 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, where R A7a is C1-C3 alkylene; and -NH-CH(R 8a )-with R 9a In some embodiments of the compound of formula A: -NH-CH(R 2a )-C(O)- forms a Tyr residue; -NH-CH(R 3a )-C(O)- forms Lys(iPr) residues; -NH-CH(R 4a )-C(O)- forms a D-Arg residue; -NH-CH(R 5a )-C(O)- forms a 2-Nal residue and the main chain amide is replaced by amidine; -NH-CH(R 6a )-C(O)- forms D-Ala; -NH-CH(R A7a )-C(O)- forms a D amino acid residue, where R A7a is C1-C3 alkylene; and -NH-CH(R 8a )-with R 9a In some embodiments of the compound of formula A: -NH-CH(R 2a )-C(O)- forms a Tyr residue; -NH-CH(R 3a )-C(O)- forms Lys(iPr) residues; -NH-CH(R 4a )-C(O)- forms a D-Arg residue; -NH-CH(R 5a )-C(=NH)-, wherein R 5a is -CH2(2-naphthyl); -NH-CH(R 6a )-C(O)- forms D-Ala; -NH-CH(R A7a )-C(O)- forms a D amino acid residue, where R A7a is C1-C3 alkylene; and -NH-CH(R 8a )-with R 9a In some embodiments, -NH-CH(R 8a )-with R 9a The -C(O)- of the -NH-CH(R)- is taken together to form a Lys(iPr) residue which is amidated. 8a )-with R 9a The -C(O)- together form Lys(iPr)-NH2.

[0415] In some embodiments of the compound of Formula A: -NH-CH(R2a )-C(O)- forms a Tyr residue; -NH-CH(R 3a )-C(O)- forms Lys(iPr) residues; -NH-CH(R 4a )-C(=NH)- forms a D-Arg residue; -NH-CH(R 5a )-C(O)- forms 2-Nal residue; -NH-CH(R 6a )-C(O)- forms D-Ala; -NH-CH(R A7a )-C(O)- forms a D amino acid residue, where R A7a is C1-C3 alkylene; and -NH-CH(R 8a )-with R 9a In some embodiments of the compound of formula A: -NH-CH(R 2a )-C(O)- forms a Tyr residue; -NH-CH(R 3a )-C(O)- forms Lys(iPr) residues; -NH-CH(R 4a )-C(O)- forms a D-Arg residue and the backbone amide is replaced by amidine; -NH-CH(R 5a )-C(O)- forms 2-Nal residue; -NH-CH(R 6a )-C(O)- forms D-Ala; -NH-CH(R A7a )-C(O)- forms a D amino acid residue, where R A7a is C1-C3 alkylene; and -NH-CH(R 8a )-with R 9a In some embodiments of the compound of formula A: -NH-CH(R 2a )-C(O)- forms a Tyr residue; -NH-CH(R 3a )-C(O)- forms Lys(iPr) residues; -NH-CH(R 4a )-C(=NH)-, wherein R 4a is –(CH2)3NHC(=NH)NH2; -NH-CH(R 5a )-C(O)- forms 2-Nal residue; -NH-CH(R 6a )-C(O)- forms D-Ala; -NH-CH(R A7a )-C(O)- forms a D amino acid residue, where R A7a is C1-C3 alkylene; and -NH-CH(R 8a )-with R 9aIn some embodiments, -NH-CH(R 8a )-with R 9a The -C(O)- of the -NH-CH(R)- is taken together to form a Lys(iPr) residue which is amidated. 8a )-with R 9a The -C(O)- together form Lys(iPr)-NH2.

[0416] In some embodiments of the compound of Formula A: -NH-CH(R 2a )-C(O)- forms a Tyr residue; -NH-CH(R 3a )-C(=NH)- forms Lys(iPr) residue; -NH-CH(R 4a )-C(O)- forms a D-Arg residue; -NH-CH(R 5a )-C(O)- forms 2-Nal residue; -NH-CH(R 6a )-C(O)- forms D-Ala; -NH-CH(R A7a )-C(O)- forms a D amino acid residue, where R A7a is C1-C3 alkylene; and -NH-CH(R 8a )-with R 9a In some embodiments of the compound of formula A: -NH-CH(R 2a )-C(O)- forms a Tyr residue; -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue and the main chain amide is replaced by amidine; -NH-CH(R 4a )-C(O)- forms a D-Arg residue; -NH-CH(R 5a )-C(O)- forms 2-Nal residue; -NH-CH(R 6a )-C(O)- forms D-Ala; -NH-CH(R A7a )-C(O)- forms a D amino acid residue, where R A7a is C1-C3 alkylene; and -NH-CH(R 8a )-with R 9a In some embodiments of the compound of formula A: -NH-CH(R 2a )-C(O)- forms a Tyr residue; -NH-CH(R 3a )-C(=NH)-, wherein R 3a is –(CH2)4NH(iPr);-NH-CH(R4a )-C(O)- forms a D-Arg residue; -NH-CH(R 5a )-C(O)- forms 2-Nal residue; -NH-CH(R 6a )-C(O)- forms D-Ala; -NH-CH(R A7a )-C(O)- forms a D amino acid residue, where R A7a is C1-C3 alkylene; and -NH-CH(R 8a )-with R 9a In some embodiments, -NH-CH(R 8a )-with R 9a The -C(O)- of the -NH-CH(R)- is taken together to form a Lys(iPr) residue which is amidated. 8a )-with R 9a The -C(O)- together form Lys(iPr)-NH2.

[0417] In some embodiments of the compound of Formula B: -NH-CH(R 2a )-C(O)- forms a Tyr residue; -NH-CH(R 3a )-C(O)- forms Lys(iPr) residues; -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 residue, a D-Ala residue, a D-Gln residue or a D-Asn residue; and -NH-CH(R 5a )-C(O)- forms a 2-Nal residue, a (2-Ant)Ala residue or a (4-NH2)Phe residue.

[0418] In embodiments of compounds of Formula B: -NH-CH(R 2a )-C(O)- forms a Tyr residue; -NH-CH(R 3a )-C(O)- forms Lys(iPr) residues; -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.

[0419] In some embodiments of the compound of Formula C: -NH-CH(R2a )-C(O)- forms a Tyr residue; -NH-CH(R 3a )-C(O)- forms Lys(iPr) residues; -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.

[0420] In some embodiments of the compound of Formula A, the compound has the structure of Formula AI or a salt or solvate thereof:

[0421]

[0422] in:

[0423] R 2a It is -(CH2)-(R 2b )-(phenyl), wherein R 2b Absent, is -CH2-, -NH-, -S- or -O-, wherein the phenyl group is optionally replaced by -NH2, -NO2, -OH, -OR 2c 、-SH、-SR 2c , -N3, -CN or -O-phenyl 4-, or optionally substituted by halogen or -OH 3-, wherein each R 2c are independently C1-C3 straight or branched chain alkyl groups;

[0424] R 3a It is R 3b R 3c , where R 3b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein R 3c Yes – N(R 3d ) 2-3 or guanidino, where each R 3d are independently -H or linear or branched C1-C3 alkyl;

[0425] R 4a It is R 4b R 4c , where R 4b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein R 4c Yes – N(R 4d ) 2-3 or guanidino, where each R 4d are independently -H or linear or branched C1-C3 alkyl;

[0426] R5a Yes - (CH2) 1-3 -R 5b , where R 5b yes:

[0427] Phenyl optionally substituted with one or more of: 4-substituted with -NH2, -NO2, -OH, -SH, -N3, -CN, or -O-phenyl; 3-substituted with halogen or -OH; and / or 5-substituted with halogen or -OH;

[0428] A fused bicyclic or fused tricyclic aryl or heteroaryl ring, optionally substituted by halogen, -OH, -OR 5c , amino, -NHR 5c and / or N(R 5c )2 in one or more substitutions; and

[0429] where R 5c Each is independently a C1-C3 straight or branched chain alkyl group;

[0430] R 6a Methyl, ethyl, -C≡CH, -CH=CH2, -CH2-R 6b -OH,-CH2-R 6b -COOH,-CH2-(R 6b ) 1-3 -NH2,-CH2-R 6b -CONH2 or -CH2-R 6b R 6c , where each R 6b are independently absent and are -CH2-, -NH-, -S- or -O-; and wherein R 6c is a 5- or 6-membered aromatic ring in which 0-3 carbons are independently replaced by N, S and / or O heteroatoms, and is optionally substituted by 0-3 groups independently selected from oxo, hydroxy, thiol, nitro, amino and / or halogen;

[0431] R 8a It is R 8b R 8c , where R 8b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein R 8c Yes – N(R 8d ) 2-3 or guanidino, where each R 8d are independently -H or linear or branched C1-C3 alkyl;

[0432] R 9a are: -C(O)NH2, -C(O)-OH, -CH2-C(O)NH2, -CH2-C(O)-OH, -R9b -R 9c or -R 9b -[Connector]-R X n1 ; where R 9b is –C(O)NH–; and R 9c yes where R 9d is a straight or branched C1-C5 alkylene group, R 9e is carboxylic acid, sulfonic acid, sulfinic acid, phosphoric acid, amino, guanidino, -SH, -OH, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-CH3, -N(CH3)2, -S-CH3, -O-CH3 or phenyl, and R 9f is amino or –OH;

[0433] R A7a is C1-C3 alkylene;

[0434] R A10 Does not exist or is -[connector]-R X n1 ;

[0435] When R A10 If it does not exist, then R A1a yes:

[0436] Straight chain C1-C5 alkyl, alkenyl or alkynyl, wherein 0-2 carbons in C2-C5 are independently replaced by one or more N, S and / or O heteroatoms, optionally C-substituted by a monosubstituent selected from the group consisting of -SH, -OH, amino, carboxyl, guanidino, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH3) 1-2 、-NH2-CH3、-N(CH3) 2-3 , -S-CH3 or -O-CH3;

[0437] Branched chain C1-C 10 Alkyl, alkenyl or alkynyl, wherein C2-C 10 0-3 carbon atoms in are independently replaced by one or more N, S and / or O heteroatoms; or

[0438] R A1b R A1c , where R A1bis a straight chain C1-C3 alkylene, wherein C2 alkylene or C3 alkylene is optionally replaced by N, S or O heteroatom, wherein R A1c yes:

[0439] a 5- or 6-membered aromatic ring in which one or more carbons are optionally independently replaced by N, S and / or O heteroatoms, and optionally substituted by one or more groups independently selected from oxo, hydroxy, thiol, nitro, amino and / or halogen; or

[0440] Fused bicyclic or fused tricyclic aryl groups, wherein one or more carbons are optionally independently replaced by N, S and / or O heteroatoms, and are optionally independently selected from halogen, -OH, -OR A1d , amino, -NHR A1d and / or N(R A1d )2 is substituted with one or more groups, wherein each R A1d are independently C1-C3 straight or branched chain alkyl groups;

[0441] When R A10 Yes-[Connector]-R X n1 When R A1a It is R A1e R A1f , where R A1e is a straight chain C1-C5 alkylene, alkenylene or alkynylene group, wherein 0-2 carbon atoms in C2-C5 are independently replaced by N, S and / or O heteroatoms, and R A1f is -NH-C(O)-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C(S)NH-, -N(CH3)C(S)-, -C(O)N(CH3)-, -N(CH3)C(O)-, -C(S)N(CH3)-, -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-, -phosphoramide-, -phosphorothioate diester-, -S-tetrafluorophenyl-S-, or polyethylene glycol;

[0442] The connector is X 1 L 1 、X 1 L 1 X 1 L 1 , or X 1 L1 X 1 L 1 X 1 L 1 ;

[0443] X 1 are independently -CH2-,

[0444] L 1 each independently represents –NH–, –C(O)–, –NHC(O)–, –C(O)NH–, –N(CH 3 )C(O)–, or –C(O)N(CH 3 )–;

[0445] R 11 are each independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid; and

[0446] R Z each independently an albumin binder;

[0447] Each n1 is independently 0, 1, or 2;

[0448] Each R X is an albumin binder, a therapeutic moiety, a fluorescent label, a radiolabeled group, or a group capable of being radiolabeled;

[0449] 0-3 peptide backbone amides are independently

[0450] Amidine or thioamide substitution;

[0451] wherein 0-3 peptide backbone amides are N-methylated; and

[0452] wherein the C-terminus is optionally amidated.

[0453] In some embodiments of the compound of Formula A or AI, -NH-CH(R A1a )-C(O)- forms an L amino acid residue.

[0454] 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.

[0455] In some embodiments of the compound of Formula A or AI, R A10 Yes-[Connector]-R X n1 , and R 9a It is -C(O)NH2, -C(O)-OH, -CH2-C(O)NH2 or -CH2-C(O)-OH.

[0456] In some embodiments of the compound of Formula A, the compound has the structure of Formula A-II or a salt or solvate thereof:

[0457]

[0458] in:

[0459] -NH-CH(R 2a )-C(O)- forms a Tyr residue, a Phe residue, a (4-NO2)-Phe residue, a (4-NH2)-Phe residue, an hTyr residue, a (3-I)Tyr residue, a Glu residue, a Gln residue or a D-Tyr residue;

[0460] -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, an Arg(Me)2 (asymmetric) residue, or an Arg(Me) residue;

[0461] -NH-CH(R 4a )-C(O)- forms a D-Arg residue or a D-hArg residue;

[0462] -NH-CH(R 5a )-C(O)- forms a 2-(Ant)Ala residue, a 2-Nal residue, a Trp residue, a (4-NH2)Phe residue, an hTyr residue, or a Tyr residue;

[0463] -NH-CH(R 6a )-C(O)- forms a His residue, a D-His residue, a D-Glu residue, a D-Gln residue, a D-Ala residue, a D-Phe residue, a D-Ser residue, a D-Dab residue, or a D-Dap residue;

[0464] R 8aIt is R 8b R 8c , where R 8b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein R 8c Yes – N(R 8d ) 2-3 or guanidino, where each R 8d are independently -H or linear or branched C1-C3 alkyl;

[0465] R 9a is -C(O)NH2, -C(O)-OH, -CH2-C(O)NH2, -CH2-C(O)-OH or -R 9b -[Connector]-R X n1 ;

[0466] R 9b is –C(O)NH–;

[0467] R A7a is C1-C3 alkylene;

[0468] R A10 Does not exist or is -[connector]-R X n1 ;

[0469] When R A10 If it does not exist, then R A1a is a straight-chain C1-C5 alkyl group, optionally substituted with a monosubstituent selected from the group consisting of -SH, -OH, amino, carboxyl, guanidino, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH3) 1-2 、-NH2-CH3、-N(CH3) 2-3 , -S-CH3, or -O-CH3 or branched C1-C 10 alkyl, alkenyl or alkynyl;

[0470] When R A10 Yes-[Connector]-R X n1 , then R A1a It is R A1e R A1f , where R A1e is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, and R A1fis -NH-C(O)-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C(S)NH-, -N(CH3)C(S)-, -C(O)N(CH3)-, -N(CH3)C(O)-, -C (S)N(CH3)-, -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-, or polyethylene glycol; the linkers are each independently 1-10 units of X 1 L 1 and / or X 1 (L 1 )2 is a straight or branched chain, wherein:

[0471] Each X 1 are independently linear, branched and / or cyclic C1-C 15 Alkylene, C2-C 15 Alkenylene or C2-C 15 Alkyne, wherein 0-6 carbon atoms are independently replaced by N, S and / or O heteroatoms, and 0-3 groups are substituted independently by one or a combination of oxo, hydroxyl, thiol, halogen, guanidino, carboxylic acid, sulfonic acid, sulfinic acid and / or phosphoric acid;

[0472] Each L 1 Independently -NH-C(O)-, -NH-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C (S)NH-,-N(CH3)C(S)-,-C(O)N(CH3)-,-N(CH3)C(O)-,-C(S)N(CH3)-,-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-, -phosphoramide-, -phosphorothioate diester-, -S-tetrafluorophenyl-S-, or polyethylene glycol;

[0473] The connector is X 1 L 1 、X 1 L 1 X 1 L 1 , or X 1L 1 X 1 L 1 X 1 L 1 ;

[0474] X 1 are independently -CH2-,

[0475] L 1 each independently represents –NH–, –C(O)–, –NHC(O)–, –C(O)NH–, –N(CH 3 )C(O)–, or –C(O)N(CH 3 )–;

[0476] R 11 are each independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid; and

[0477] R Z each independently an albumin binder;

[0478] Each n1 is independently 0, 1, or 2;

[0479] Each R X is an albumin binder, a therapeutic moiety, a fluorescent label, a radiolabeled group, or a group capable of being radiolabeled;

[0480] 0-3 peptide backbone amides are independently

[0481] Amidine or thioamide substitution;

[0482] wherein 0-3 peptide backbone amides are N-methylated; and

[0483] wherein the C-terminus is optionally amidated.

[0484] In some embodiments of the compound of Formula A, the compound has the structure of Formula A-III or a salt or solvate thereof:

[0485]

[0486] in:

[0487] R 2a It is -(CH2)-(R 2b )-(phenyl), wherein R 2b Absent, is -CH2-, -NH-, -S- or -O-, wherein the phenyl group is optionally replaced by -NH2, -NO2, -OH, -OR 2c 、-SH、-SR 2c , -N3, -CN or -O-phenyl 4-, or optionally substituted by halogen or -OH 3-, wherein each R 2care independently C1-C3 straight or branched chain alkyl groups;

[0488] R 3a is a C1-C5 alkyl group;

[0489] R y is hydrogen or R 3e R 3f , where R 3e is a straight chain C1-C5 alkylene group, wherein R 3f Yes – N(R 3g ) 2-3 , where each R 3g are independently -H or linear or branched C1-C3 alkyl;

[0490] R 4a It is R 4b R 4c , where R 4b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein R 4c Yes – N(R 4d ) 2-3 or guanidino, where each R 4d are independently -H or linear or branched C1-C3 alkyl;

[0491] R 5a Yes - (CH2) 1-3 -R 5b , where R 5b yes:

[0492] Phenyl optionally substituted with one or more of: 4-substituted with -NH2, -NO2, -OH, -SH, -N3, -CN, or -O-phenyl; 3-substituted with halogen or -OH; and / or 5-substituted with halogen or -OH;

[0493] A fused bicyclic or fused tricyclic aryl or heteroaryl ring, optionally substituted by halogen, -OH, -OR 5c , amino, -NHR 5c and / or N(R 5c )2 in one or more substitutions; and

[0494] where R 5c Each is independently a C1-C3 straight or branched chain alkyl group;

[0495] R 6a H, methyl, ethyl, -C≡CH, -CH=CH2, -CH2-R 6b -OH, -CH2-R 6b -COOH, -CH2-(R 6b ) 1-3-NH2, -CH2-R 6b -CONH2 or -CH2-R 6b R 6c , where each R 6b are independently absent and are -CH2-, -NH-, -S- or -O-; and wherein R 6c is a 5- or 6-membered aromatic ring in which 0-3 carbons are independently replaced by N, S and / or O heteroatoms, and is optionally substituted by 0-3 groups independently selected from oxo, hydroxy, thiol, nitro, amino and / or halogen;

[0496] R 8a It is R 8b R 8c , where R 8b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein R 8c Yes – N(R 8d ) 2-3 or guanidino, where each R 8d are independently -H or linear or branched C1-C3 alkyl;

[0497] R 9a It is -C(O)NH2, -C(O)-OH, -CH2-C(O)NH2, -CH2-C(O)-OH, -R 9b -R 9c or -R 9b -[Connector]-R X n1 ; where R 9b is –C(O)NH–; and R 9c yes where R 9d is a straight or branched C1-C5 alkylene group, R 9e is carboxylic acid, sulfonic acid, sulfinic acid, phosphoric acid, amino, guanidino, -SH, -OH, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-CH3, -N(CH3)2, -S-CH3, -O-CH3 or phenyl, and R 9f is amino or –OH;

[0498] R A7a is C1-C3 alkylene;

[0499] R A10 Does not exist or is -[connector]-R X n1 ;

[0500] When RA10 If it does not exist, then R A1a yes:

[0501] Straight chain C1-C5 alkyl, C2-C5 alkenyl or C2-C5 alkynyl, wherein 0-2 carbons in the C2-C5 alkyl, alkenyl or alkynyl are independently replaced by one or more N, S and / or O heteroatoms, optionally C-substituted by a monosubstituent selected from the group consisting of -SH, -OH, amino, carboxyl, guanidino, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH3) 1-2 、-NH2-CH3、-N(CH3) 2-3 , -S-CH3 or -O-CH3;

[0502] Branched chain C1-C 10 Alkyl, alkenyl or alkynyl, wherein C2-C 10 0-3 carbon atoms in R are independently replaced by one or more N, S and / or O heteroatoms; or A1b R A1c , where R A1b is a straight chain C1-C3 alkylene, wherein C2 alkylene or C3 alkylene is optionally replaced by N, S or O heteroatom, wherein R A1c yes:

[0503] a 5- or 6-membered aromatic ring in which one or more carbons are optionally independently replaced by N, S and / or O heteroatoms, and optionally substituted by one or more groups independently selected from oxo, hydroxy, thiol, nitro, amino and / or halogen; or

[0504] Fused bicyclic or fused tricyclic aryl groups, wherein one or more carbons are optionally independently replaced by N, S and / or O heteroatoms, and are optionally independently selected from halogen, -OH, -OR A1d , amino, -NHR A1d and / or N(R A1d )2 is substituted with one or more groups, wherein each R A1d are independently C1-C3 straight or branched chain alkyl groups;

[0505] When R A10 Yes-[Connector]-R X n1 When R A1a It is R A1e R A1f ,in:

[0506] R A1eis a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbon atoms in the C2-C5 alkylene, alkenylene or alkynylene are independently replaced by N, S and / or O heteroatoms;

[0507] R A1f is -NH-C(O)-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C(S)NH-, -N(CH3)C(S)-, -C(O)N(CH3)-, -N(CH3)C(O)-, -C(S)N(CH3)-, -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-, -phosphoramide-, -phosphorothioate diester-, -S-tetrafluorophenyl-S-, or polyethylene glycol;

[0508] The connector 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 ;

[0509] X 1 are independently -CH2-,

[0510] L 1 each independently represents –NH–, –C(O)–, –NHC(O)–, –C(O)NH–, –N(CH 3 )C(O)–, or –C(O)N(CH 3 )–;

[0511] R 11 are each independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid; and

[0512] R Z each independently an albumin binder;

[0513] Each n1 is independently 0, 1, or 2;

[0514] Each R Xis an albumin binder, a therapeutic moiety, a fluorescent label, a radiolabeled group, or a group capable of being radiolabeled;

[0515] 0-3 peptide backbone amides are independently

[0516] Amidine or thioamide substitution;

[0517] wherein 0-3 peptide backbone amides are N-methylated; and

[0518] wherein the C-terminus is optionally amidated.

[0519] In some embodiments of the compound of Formula A, the compound has the structure of Formula A-IV or a salt or solvate thereof:

[0520]

[0521] in:

[0522] -NH-CH(R 2a )-C(O)- forms a Tyr residue, a Phe residue, a (4-NO2)-Phe residue, a (4-NH2)-Phe residue, an hTyr residue, a (3-I)Tyr residue, a Glu residue, a Gln residue or a D-Tyr residue;

[0523] -NH-CH(R 4a )-C(O)- forms a D-Arg residue or a D-hArg residue;

[0524] -NH-CH(R 5a )-C(O)- forms a 2-(Ant)Ala residue, a 2-Nal residue, a Trp residue, a (4-NH2)Phe residue, an hTyr residue, or a Tyr residue;

[0525] -NH-CH(R 6a )-C(O)- forms a His residue, a D-His residue, a D-Glu residue, a D-Gln residue, a D-Ala residue, a D-Phe residue, a D-Ser residue, a D-Dab residue, or a D-Dap residue;

[0526] R 3a is a C1-C5 alkyl group;

[0527] R y is hydrogen or R 3e R 3f , where R 3e is a straight chain C1-C5 alkylene group, wherein R 3f Yes – N(R 3g )2-3 , where each R 3g are independently -H or linear or branched C1-C3 alkyl;

[0528] R 8a It is R 8b R 8c , where R 8b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein R 8c Yes – N(R 8d ) 2-3 or guanidino, where each R 8d are independently -H or linear or branched C1-C3 alkyl;

[0529] R 9a is -C(O)NH2, -C(O)-OH, -CH2-C(O)NH2, -CH2-C(O)-OH or -R 9b -[Connector]-R X n1 ;

[0530] R 9b is –C(O)NH–;

[0531] R A7a is C1-C3 alkylene;

[0532] R A10 Does not exist or is -[connector]-R X n1 ;

[0533] When R A10 If it does not exist, then R A1a is a straight-chain C1-C5 alkyl group, optionally substituted with a monosubstituent selected from the group consisting of -SH, -OH, amino, carboxyl, guanidino, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH3) 1-2 、-NH2-CH3、-N(CH3) 2-3 , -S-CH3, -O-CH3 or branched C1-C 10 alkyl, alkenyl or alkynyl;

[0534] When R A10 Yes-[Connector]-R X n1 When R A1a It is R A1e R A1f ,in:

[0535] RA1e is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbon atoms in the C2-C5 alkylene, alkenylene or alkynylene are independently replaced by N, S and / or O heteroatoms;

[0536] R A1f is -NH-C(O)-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C(S)NH-, -N(CH3)C(S)-, -C(O)N(CH3)-, -N(CH3)C(O)-, -C(S)N(CH3)-, -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-, -phosphoramide-, -phosphorothioate diester-, -S-tetrafluorophenyl-S-, or polyethylene glycol;

[0537] The connector 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 ;

[0538] X 1 are independently -CH2-,

[0539] L 1 each independently represents –NH–, –C(O)–, –NHC(O)–, –C(O)NH–, –N(CH 3 )C(O)–, or –C(O)N(CH 3 )–;

[0540] R 11 are each independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid; and

[0541] R Z each independently an albumin binder;

[0542] Each n1 is independently 0, 1, or 2;

[0543] Each R Xis an albumin binder, a therapeutic moiety, a fluorescent label, a radiolabeled group, or a group capable of being radiolabeled;

[0544] 0-3 peptide backbone amides are independently

[0545] Amidine or thioamide substitution;

[0546] wherein 0-3 peptide backbone amides are N-methylated; and

[0547] wherein the C-terminus is optionally amidated.

[0548] In some embodiments of the compound of Formula A, A-III, or A-IV: -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 2-Nal residue; -NH-CH(R 6a )-C(O)- forms D-Ala; -NH-CH(R A7a )-C(O)- forms a D amino acid residue, where R A7a is C1-C3 alkylene; and -NH-CH(R 8a )-with R 9a -C(O)- together form a Lys(iPr) residue; and wherein R y is -(CH2)4-NH-(iPr) and R 3a Yes-CH 3。

[0549] The various embodiments of Formula A discussed herein may also apply to compounds of Formula AI, A-II, A-III, and / or A-IV.

[0550] In some embodiments of the compound of Formula A, AI, A-II, A-III, A-IV, B or C, -NH-CH(R 6a )-C(O)- forms a Gly residue, a D-Ala residue, a D-Gln residue or a D-Asn residue.

[0551] In some embodiments of the compound 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 In some embodiments, R A10 Yes-[Connector]-R X n1 , R A1eis a straight chain C1-C5 alkylene group, and R A1f It is -NH-C(O)-.

[0552] The term "linker" represents a linker, which can be any linker. Non-limiting examples include peptide and polyethylene glycol-based linkers.

[0553] In some embodiments of the compound of Formula A, AI, A-II, A-III, A-IV, B or C, R X n1 In some embodiments, 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.

[0554] 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 marker, a radiolabeled group, or a group capable of being radiolabeled. X is a therapeutic moiety, a fluorescent label, a radiolabeled group, or a group capable of being radiolabeled.

[0555] The present disclosure also relates to one or more compounds comprising a compound selected from Table 2 or a salt or solvate thereof; wherein the compound is optionally conjugated to a radiolabeled group, a group capable of being radiolabeled, or an albumin binding group via a linker. In one embodiment, the compound of the present disclosure is optionally conjugated to a metal chelator and / or an albumin binder via one or more linkers. In one embodiment, the compound of the present disclosure is optionally conjugated to a metal chelator and an albumin binder via one or more linkers.

[0556] The present disclosure also relates to one or more compounds selected from Table 2 or salts or solvates thereof; wherein the compound is optionally conjugated to a radiolabeled group, a group capable of being radiolabeled, or an albumin binding group via a linker. In one embodiment, the compounds of the present disclosure are optionally conjugated to a metal chelator and / or an albumin binder via one or more linkers. In one embodiment, the compounds of the present disclosure are optionally conjugated to a metal chelator and an albumin binder via one or more linkers.

[0557] Table 2: Exemplary compounds

[0558]

[0559] 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 1-10 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 is a straight or branched chain, wherein:

[0560] Each X 1 are independently linear, branched and / or cyclic C1-C 15 Alkylene, alkenylene or alkynylene, wherein 0-6 carbon atoms are independently replaced by N, S and / or O heteroatoms, and 0-3 groups are substituted independently by one or a combination of oxo, hydroxyl, thiol, halogen, guanidino, carboxylic acid, sulfonic acid, sulfinic acid and / or phosphoric acid;

[0561] Each L 1 Independently -NH-,-NH-C(O)-,-C(O)-,-O-,-C(O)NH–,-C(O)-N(CH3)-,-NHC(S)-,-C (S)NH-,-N(CH3)C(S)-,-C(O)N(CH3)-,-N(CH3)C(O)-,-C(S)N(CH3)-,-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-, -phosphoramide-, -phosphorothioate diester-, -S-tetrafluorophenyl-S-, or polyethylene glycol.

[0562] In some embodiments, each L 1Independently are –S–, –NHC(O)–, –C(O)NH–, –N(CH3)C(O)–, –C(O)N(CH3)–, –NHC(S)–, –C(S)NH–, –N(CH3)C(S)–, –C(S)N( CH3)–,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-、

[0563] In some embodiments, each L 1 are independently –S–, –NHC(O)–, –C(O)NH–, –N(CH3)C(O)–, –C(O)N(CH3)–,

[0564] In some embodiments, each L 1 are independently -NH-, -C(O)-, -NHC(O)-, -C(O)NH-, -N(CH3)C(O)-, or -C(O)N(CH3)-.

[0565] In some embodiments, the linker is X 1 L 1 , where X 1 Yes - (CH2) 1-5 -、-CH(COOH)-(CH2) 0-4 - or -CH(CONH2)-(CH2) 0-4 -; and L 1 is –NH–, –C(O)–, –NHC(O)–, –C(O)NH–, –N(CH3)C(O)–, or –C(O)N(CH3)–.

[0566] 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 at least one carboxylic acid, sulfonic acid, sulfinic acid, or phosphoric acid and has a net negative charge at physiological pH.

[0567] 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 at least one chemical group having a net positive charge at physiological pH, such as a guanidine group or an amino group.

[0568] 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 consists of 1 to 8 units of X 1 L 1 and 0-2 units of X 1 (L 1 )2 components.

[0569] In some embodiments, each X 1 are independently linear, branched and / or cyclic C1-C 15 Alkylene.

[0570] In some embodiments, each X 1 are independently: -CH2-; Each R 11 are independently carboxylic, sulfonic, sulfinic, or phosphoric acids;

[0571] In some embodiments, two X 1 Each L between the groups 1 are independently –NHC(O)–, –C(O)NH–, –N(CH3)C(O)– or –C(O)N(CH3)–, and each R X L 1 are independently –S–, –NHC(O)–, –C(O)NH–, –N(CH3)C(O)–, –C(O)N(CH3)–,

[0572]

[0573] 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 the same or different, and each L 1 Same or different.

[0574] In one embodiment, X 1 yes Each R 11 are independently carboxylic acid, sulfonic acid, sulfinic acid or phosphoric acid. In one embodiment, X 1 yes Each R 11 is independently a carboxylic acid, a sulfonic acid, a sulfinic acid, or a phosphoric acid.

[0575] In one embodiment, X 1 yes Each R 11 In one embodiment, X 1 yes Each R 11 is independently guanidinyl or amino.

[0576] In one embodiment, X 1 yes Each R Z are independently albumin binders. In some embodiments, L1 is -NH-, -NHC(O)-, or -C(O)NH-.

[0577] In one embodiment, X 1 yes Each R Z are independently albumin binders. In some embodiments, L1 is -NH-, -NHC(O)-, or -C(O)NH-.

[0578] In one embodiment, the linker is X 1 L 1 , where X 1 yes Each R 11 are independently carboxylic acid, sulfonic acid, sulfinic acid or phosphoric acid; and L 1 It is –NH– or –NHC(O)–.

[0579] In one embodiment, the linker is X 1a L 1a X 1b L 1b , where X 1a yes Each R 11 are independently carboxylic acid, sulfonic acid, sulfinic acid or phosphoric acid; L 1a is –NH– or –NHC(O)–; X 1b yes Each R Z are independently albumin binders; and L 1b is -NH- or -NHC(O)-. In some embodiments, L1 is -NH-, -NHC(O)- or -C(O)NH-.

[0580] In one embodiment, the linker is X 1a L 1a X1b L 1b , where X 1a yes Each R Z is independently an albumin binder; L 1a is –NH– or –NHC(O)–; X 1b yes Each R 11 are independently carboxylic acid, sulfonic acid, sulfinic acid or phosphoric acid; and L 1b is -NH- or -NHC(O)-. In some embodiments, L1 is -NH-, -NHC(O)- or -C(O)NH-.

[0581] In one embodiment, the linker is X 1a L 1a X 1b L 1b , where X 1a yes Each R 11 are independently carboxylic acid, sulfonic acid, sulfinic acid or phosphoric acid; L 1a is –NH– or –NHC(O)–; X 1b yes Each R Z are independently albumin binders and L1 is –NH–, –NHC(O)–, or –C(O)NH–; and L 1b It is –NH– or –NHC(O)–.

[0582] In one embodiment, the linker is X 1a L 1a X 1b L 1b , where X 1a yes Each R Z are independently albumin binders and L1 is –NH–, –NHC(O)– or –C(O)NH–; L 1a is –NH– or –NHC(O)–; X 1b yes Each R 11 are independently carboxylic acid, sulfonic acid, sulfinic acid or phosphoric acid; and L 1b It is –NH– or –NHC(O)–.

[0583] In one embodiment, the linker is X 1a L 1a X 1b L 1b X 1c L 1c , where X 1a yes Each R Z are independently albumin binders and L1 is –NH–, –NHC(O)– or –C(O)NH–; L 1a is –NH– or –NHC(O)–; X 1b is -CH2-; L 1b is –NH– or –NHC(O)–; X 1c yes Each R 11 are independently carboxylic acid, sulfonic acid, sulfinic acid or phosphoric acid; and L 1c It is –NH– or –NHC(O)–.

[0584] In one embodiment, the linker is X 1a L 1a X 1b L 1b X 1c L 1c , where X 1a yes Each R Z are independently albumin binders and L1 is –NH–, –NHC(O)– or –C(O)NH–; L 1a is –NH– or –NHC(O)–; X 1b yes Each R 11 are independently carboxylic acid, sulfonic acid, sulfinic acid or phosphoric acid; L 1b is –NH– or –NHC(O)–; X 1c is -CH2-; and L 1c It is –NH– or –NHC(O)–.

[0585] 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 they form a linear or branched peptide linker (Xaa) 1-5 , wherein each Xaa is independently selected from a proteinogenic amino acid residue or a non-proteinogenic amino acid residue; and wherein the amino group in each Xaa is optionally methylated. In one embodiment, the amino group in each Xaa is optionally N-methylated.

[0586] 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 they form 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 in each Xaa is optionally methylated. In one embodiment, the amino group in each Xaa is optionally N-methylated.

[0587] 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 they form a single amino acid residue selected from cysteic acid, Glu, Asp or 2-aminoadipic acid (2-Aad); and wherein the amino group in each Xaa is optionally methylated. In one embodiment, the amino group in each Xaa is optionally N-methylated.

[0588] 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 they form a linear or branched peptide linker (Xaa) 1-5 , wherein at least one Xaa is selected from Dap, Dab, Orn, Arg, hArg, Agb, Agp, Acp, Pip or N ε ,N ε ,N ε -trimethyl-lysine; and wherein the amino group in each Xaa is optionally methylated. In one embodiment, the amino group in each Xaa is optionally N-methylated.

[0589] 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 they form a single 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.

[0590] 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 proteinogenic amino acid residues and / or non-proteinogenic amino acid residues listed in Table 1.

[0591] In some embodiments of the compounds of Formula A, AI, A-II, A-III, A-IV, B or C, the two X in the linker are 1 Each L between the groups 1 is methylated or unmethylated, and wherein each R X L 1are independently –S–, –NHC(O)–, –C(O)NH–, –N(CH3)C(O)–, –C(O)N(CH3)–,

[0592] In some embodiments, two X 1 Each L between the groups 1 It is an unmethylated amide.

[0593] 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 1 to 3 amino acids selected from one or a combination of cysteic acid, Glu, Asp and / or 2-aminoadipic acid (2-Aad) connected by amide bonds. In some embodiments, the linker forms a single 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.

[0594] In some embodiments, each linker R X L 1 are independently -NHC(O)-, -C(O)NH-, In some embodiments, each linker R X L1 is independently -NHC(O)- or -C(O)NH-.

[0595] 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 linked to the L 1 linkage, wherein the albumin binder is: -(CH2) n2 -CH3, where n2 is 8-20; -(CH2) n3 -C(O)OH, wherein n3 is 8-20, or Where n4 = 1-4 and R 12 is I, Br, F, Cl, H, OH, OCH3, NH2, NO2 or CH3.

[0596] In some embodiments of the compound of Formula A, AI, A-II, A-III, A-IV, B or C, at least one R X It is an albumin binder, the L of the albumin binder and the linker 1 The bond, and albumin binder is: -(CH2) 8-20 -CH3, -(CH2) 8-20 -C(O)OH or where R 12is I, Br, F, Cl, H, OH, OCH3, NH2, NO2 or CH3. In some embodiments, the albumin binder is where R 12 is I, Br, F, Cl, H, OH, OCH3, NH2, NO2 or CH3. In some embodiments, the albumin binder is where R 12 It is I, Br, Cl, H, OCH3, NO2 or CH3.

[0597] In some embodiments of the compound of Formula A, AI, A-II, A-III, A-IV, B, or C, the albumin binder is

[0598] In some embodiments of the compound of Formula A, AI, A-II, A-III, A-IV, B, or C, the albumin binder is

[0599] 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 capable of being radiolabeled (eg, by conjugation to a radiometal or a radiolabeled prosthetic group, or by an isotope-radioisotope exchange reaction).

[0600] In some embodiments of the compound of Formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2, the compound comprises a first linker bonded to a radiolabeling group or a group capable of being radiolabeled, and further comprises a second linker bonded to an albumin binder.

[0601] In some embodiments of the compound of Formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2, the compound comprises a first linker bonded to a first radiolabeling group or a first group capable of being radiolabeled, and further comprises a second linker bonded to a second radiolabeling group or a second group capable of being radiolabeled, wherein the compound optionally further comprises an albumin binder attached to one or both of the first linker and the second linker.

[0602] In some embodiments of the compound of Formula A, AI, A-II, A-III, A-IV, B or C, or Table 2, the compound comprises only a single linker bonded to 1-2 groups consisting of a radiolabeling group and / or a group capable of being radiolabeled, which linker is optionally further bonded to an albumin binder.

[0603] In some embodiments of compounds of Formula A, AI, A-II, A-III, A-IV, B or C, or Table 2, each group capable of being radiolabeled is independently selected from: a metal chelator complexed with a metal optionally bound to a radiometal or radioisotope; a prosthetic group containing trifluoroborate (BF); or a prosthetic group containing a silicon-fluorine-acceptor moiety, a sulfonyl fluoride, or a phosphoryl fluoride.

[0604] In some embodiments of the compounds of Formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2, R X comprising, optionally with a radioactive metal (e.g. 68 Ga or 177 Lu) complexed or bound to a radioactive isotope (e.g., Al 18 F) complexed metal chelators. 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 optionally with a radioactive metal (e.g. 68 Ga or 177 Lu) complexed or bound to a radioactive isotope (e.g., Al 18F) complexing metal chelators. The chelating agent can be any metal chelator (e.g., polyurethane, etc.) suitable for binding to a radioactive metal or a metal-containing prosthetic group bonded to a radioisotope. Many suitable chelating agents are known, for example, as summarized 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; sarcophagine and sarcophagine derivatives, optionally selected from SarAr, SarAr-NCS, diamSar, A mBaSar and BaBaSar; TRAP; AAZTA; DATA and DATA derivatives; H2-macropa or its derivatives; H2dedpa, H4octapa, H4py4pa, H4Pypa, H2azapa, H5decapa and other picolinic acid derivatives; CP256; PCTA; C-NETA; C-NE3TA; HBED; SHBED; BCPA; CP256; YM103; deferoxamine (DFO) and DFO derivatives; and H6phospa. Illustrative, non-limiting examples of suitable chelators and examples of radioisotopes (radiometallics) chelated by these chelators are shown in Table 3. In alternative embodiments, R X The chelating agent comprises a chelating agent selected from those listed above or in Table 3, or any other suitable chelating agent. One skilled in the art can substitute another chelating agent for any of the chelating agents listed herein.

[0605] Table 3: Exemplary chelators and exemplary isotopes bound to the chelators.

[0606]

[0607]

[0608]

[0609]

[0610]

[0611]

[0612] It will be understood by those skilled in the art how metal chelators (such as those listed in Table 3) can be linked to the linkers or peptides of the present disclosure by forming a link by replacing one or more atoms or chemical groups of the metal chelator. For example, a carboxylic acid present in the metal chelator structure can form an amide bond or an ester bond with the linker or peptide. In one embodiment, the link formed between the linker and the metal chelator can be covered by the definition of a linker, such as L 1 (For example, if an amide bond connects the metal chelator to the linker, the definition of L1(-NH-C(O)-) can encompass the amide in Formula A, AI, A-II, A-III, A-IV, B, or C, even though the carbonyl group can be from a metal chelator shown in Table 3).

[0613] In some embodiments of the compound of Formula A, AI, A-II, A-III, A-IV, B or C, the compound does not include compounds disclosed in International Application No. PCT / CA2021 / 051486, which is incorporated herein by reference in its entirety for all purposes. In some embodiments, the compound is not cyclo[Phe-(4-NH2)Phe-Lys(iPr)-D-Arg-2-Nal-Gly-D-Glu]-Lys(iPr), cyclo[Phe-(4-NO2)Phe-Lys(iPr)-D-Arg-2-Nal-Gly-D-Glu]-Lys(iPr), cyclo[Phe-hTyr-Lys(iPr)-D-Arg-2-Nal-Gly-D-Glu]-Lys(iPr), cyclo[Phe-(3-I)Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-D-Glu]-Lys(iPr), Cyclo[Phe-Tyr-Arg(Me)2(asymmetric)-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), Ring [Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-His-D-Glu]-Lys(iPr), Ring [Phe-Tyr-Lys(iPr)-D-Arg-2Nal-His-D-Glu]-Lys(iPr), Ring [Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Phe-D-Glu]-Lys(iPr), Ring [Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Leu-D-Glu]-Lys(iPr), Ring[Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Glu-D-Glu]-Lys(iPr) , Ring [Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Dab-D-Glu]-Lys(iPr) , Ring [Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Dap-D-Glu]-Lys(iPr) ,Ring [Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ser-D-Glu]-Lys(iPr), Ring [Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Gln-D-Glu]-Lys(iPr), Ring [Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Asn-D-Glu]-Lys(iPr), Ring [1Nal-Tyr-Lys(iPr)-D-Arg-2Nal-Gly-D-Glu]-Lys(iPr), Ring [Tyr-Tyr-Lys(iPr)-D-Arg-2Nal-Gly-D-Glu]-Lys(iPr) , Cyclic [Trp-Tyr-Lys(iPr)-D-Arg-2Nal-Gly-D-Glu]-Lys(iPr), cyclo(isoindole)[Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-D-Cys]-Lys(iPr), cyclo(isoindole)[Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-Cys]-Lys(iPr), cyclo[Phe-Tyr-Lys(iPr)-D-Arg-(carboxyl-m-carborane)Dap-Gly-D-Glu]-Lys(iPr ), ring [Lys(Ac)-Tyr-Lys(iPr)-D-Arg-2Nal-Gly-D-Glu]-Lys(iPr), ring [Phe-D-Tyr-Lys(iPr)-DArg-2Nal-D-Ala-D-Glu]-Lys(iPr) , cyclo[Phe-Tyr-Lys(iPr)-DArg-(4-NH2)Phe-D-Ala-D-Glu]-Lys(iPr), cyclo[Phe-Tyr-Lys(iPr)-DArg-hTyr-D-Ala-D-Glu]-Lys(iPr) , cyclo[Phe-Tyr-Lys(iPr)-DArg-(COOH)Phe-D-Ala-D-Glu]-Lys(iPr), cyclo[Phe-Tyr-Lys(iPr)-DArg-Thyronine-D-Ala-D-Glu]-Lys(iPr), Ring [Phe-Tyr-Arg(Me)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr), Ring [Lys(Ac)-Gln-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr), Ring [Lys(Ac)-Glu-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr),Cyclo[Phe-(4-NH2)Phe-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Glu]-Lys(iPr), Cyclo[Lys(Ac)-Tyr-Lys(iPr)-D-Arg-Trp-D-Ala-D-Glu]-Lys(iPr), Cyclo[Lys(D-Glu-Ac)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr), Cyclo[Lys(Ac-D-Arg)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr), Cyclo[Lys(Ac-D-Arg)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr), Cyclo[Lys(Ac-D-Phe)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr), Cyclo[Lys(CysAcid-CysAcid-CysAcid-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr), Cyclo[Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr)-Lys(Glu-Ac), Cyclo[Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr)-Lys(Ac), Cyclo[Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr)-Lys(Glu-Glu-Ac), Cyclo[Phe-(4NH2)Phe-Lys(iPr)-D-Arg-2Nal-Gly-D-Glu]-Lys(iPr)-Lys(Glu-Glu-Glu-DOTA-Ga), Cyclo[Phe-(4-NH2)Phe-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr)-Lys(Glu-Glu-Glu-DOTA-Ga), Cyclo[Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr)-Lys(Glu-Glu-Glu-DOTA-Ga), cyclo[Phe-hTyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr)-Lys(Glu-Glu-Glu-DOTA-Ga), cyclo(aminocarboxyethylthiotryptophan)[Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Cys]-Lys(iPr), cyclo(isoindole N a -S)[Lys(Cys(Acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cy s]-Lys(iPr), Cyclo(Me-isoindole N a -S)[Lys(Cys(Acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cy s]-Lys(iPr), Cyclo(NO2-Isoindole N a -S)[Lys(Cys(Acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr), Cyclo(NO2-Isoindole N a -S)[Lys(Cys(Acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-hC ys]-Lys(iPr), cyclo[Lys(CysAcid2-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-L ys(iPr), cyclo[Lys(CysAcid-DOTA)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr), cyclo

[0614] [Lys(CysAcid-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(i Pr), ring [Lys(CysAcid-DOTA-Lu)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(i Pr), cyclo[Lys(CysAcid-DOTA)-(4-NH2)Phe-Lys(iPr)-D-Arg-2Nal-Gly-D-Glu]-Lys(iPr), cyclo[Lys(CysAcid-DOTA)-(4-NH2)Phe- Lys(iPr)-D-Arg-2Nal-Gly-D-Glu]-Lys(iPr), cyclo[Lys(CysAcid-DOTA)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Asn-D-Glu]-Lys(iPr), cyclo

[0615] [Lys(CysAcid-DOTA)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Asn-D-Glu]-Lys(iPr), ring

[0616] [Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Asn-D-Glu]-Lys(iPr)-Lys(CysAcid-DOTA), ring [Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Asn-D-Glu]-Lys(iPr)-Lys(CysAcid-D OTA), cyclo[Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Asn-D-Glu]-Lys(iPr)-Lys(CysAcid2-DOTA), cyclo[Phe-Tyr-Lys(iPr)-D-Arg-2Nal-D-Asn-D-Glu]-Lys(iPr)-Lys(CysAcid2-DOTA-Ga), cyclo[Lys(CysAcid-amido-N,N-dimethyl-aminomethyl-trifluoroborate)-Tyr -Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr), cyclo[Lys(CysAcid-triazole-N,N-dimethyl-aminomethyl-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

[0617] [Lys(D-Arg-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr), ring [Lys(CysAcid-DOTA) -(3-I)Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr), cyclo[Lys(CysAcid-DOTA-Ga)-(3-I)Tyr-Ly [Orn(CysAcid-DOTA)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr), or [Dap(CysAcid-DOTA)-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]-Lys(iPr). In some embodiments of the present disclosure, the compound includes a compound of Table 4 or a salt or solvate thereof. In some embodiments, the compound is complexed with a radioactive isotope.

[0618] In some embodiments of the present disclosure, the compound is selected from Table 4 or a salt or solvate thereof. In some embodiments, the compound is complexed with a radioactive isotope.

[0619] 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 complexed with a radioactive isotope.

[0620] In some embodiments, the compound is selected from [ 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.

[0621] Table 4. Exemplary compounds

[0622]

[0623] In some embodiments, the compounds of the present disclosure comprise a group capable of being radiolabeled. In some embodiments, the compounds of the present disclosure comprise a metal chelator.

[0624] In some embodiments, the compounds of the present disclosure comprise DOTA as a metal chelator. In some embodiments, the compounds of the present disclosure comprising DOTA as a metal chelator are complexed 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, 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. 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 Cu. In one embodiment, the radioisotope complexed with DOTA is 68 Ga or 67 Ga.

[0625] In some embodiments of the compound of Formula A, AI, A-II, A-III, A-IV, B or C, R X is a polyurethane chelating agent. In some such embodiments, the chelating agent 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]-pentadecan-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 In some embodiments, R X is a chelating agent moiety that complexes with a radioisotope X, wherein 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 Re. In some embodiments, X is 177 Lu. In some embodiments, R X is a chelating agent moiety that complexes with a radioisotope X, wherein X is 64 Cu, 68 Ga, 86 Y. 111 In, 94m Tc, 44 Sc, 89 Zr or 99m In some embodiments, X is 68 Ga.

[0626] In some embodiments, the chelator is conjugated to a radioisotope. The conjugated radioisotope can be, but is not limited to 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, 114mIn et al. In some embodiments, the chelator is a chelator of Table 3 and the conjugated radioisotope is a radioisotope shown in Table 3 as a binding agent for the chelator.

[0627] In some embodiments, the chelator is not conjugated to a radioisotope.

[0628] In some embodiments, the chelating agent 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 Cu-conjugated DOTA or its derivatives; and 225 Ac-conjugated H2-MACROPA; 227 Th-conjugated Me-3,2-HOPO; 225 Ac, 227 Th or 177 Lu-conjugated H4py4pa; 177 Lu-conjugated H4pypa; 68 Ga-conjugated NODAGA; with 111 In-conjugated DTPA; or 89 Zr-conjugated DFO.

[0629] In some embodiments, the chelating agent is TETA, SarAr, NOTA, TRAP, HBED, 2,3-HOPO, PCTA, DFO, DTPA, OCTAPA, or another picolinic acid derivative.

[0630] In some embodiments, the compounds of the present disclosure comprise a crown as a metal chelator. In some embodiments, the compounds of the present disclosure comprising a crown as a metal chelator are complexed with a radioisotope. In some embodiments, the radioisotope is225 Ac. In some embodiments, the radioisotope is 227 Th. In some embodiments, the radioisotope is 152 Tb, 155 Tb, 149 Tb or 161 Tb.

[0631] In some embodiments of the compound of Formula A, AI, A-II, A-III, A-IV, B or C, R X It is used for 99m Tc, 94m Tc, 186 Re or 188 Re is radiolabeled with chelating agents such as mercaptoacetyl, hydrazinonicotinamide, dimercaptosuccinic acid, 1,2-ethylenediylbis-L-cysteine ​​diethyl ester, methylenediphosphonate, hexamethylpropyleneamide oxime, and hexa(methoxyisobutylisonitrile). In some embodiments, R X is a chelating agent, wherein the chelating agent is mercaptoacetyl, hydrazinonicotinamide, dimercaptosuccinic acid, 1,2-ethylenediylbis-L-cysteine ​​diethyl ester, methylenediphosphonate, hexamethylpropyleneamide oxime, and hexa(methoxyisobutylisocyanide). In some of these embodiments, the chelating agent is bound to a radioisotope. In some such embodiments, the radioisotope is 99m Tc, 94m Tc, 186 Re or 188 Re.

[0632] 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., wherein the compound of Table 2 is optionally bound via a linker to a radiolabeled group or a group capable of being 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. 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 Cu.

[0633] In one embodiment of the compounds of Formula A, AI, A-II, A-III, A-IV, B or C, or Table 2 or derivatives thereof, or Table 4, at least one R X The compound comprises or is complexed with an imaging radioisotope, the compound is bound to a metal chelator that is complexed with the imaging radioisotope, or the compound is bound to a prosthetic group containing BF3 that comprises the imaging radioisotope.

[0634] In one embodiment of the compound of Formula A, AI, A-II, A-III, A-IV, B or C, or Table 2 or a derivative thereof, or 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 As. 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.

[0635] In one embodiment of the compounds of Formula A, AI, A-II, A-III, A-IV, B or C, or Table 2 or derivatives thereof, or Table 4, at least one R X The compound may contain an imaging radioisotope or be complexed with a therapeutic radioisotope, or the compound may be associated with a metal chelator that is complexed with a therapeutic radioisotope.

[0636] In one embodiment of the compound of Formula A, AI, A-II, A-III, A-IV, B or C, or Table 2 or a derivative thereof, or Table 4, the therapeutic radioisotope is 165 Second, 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 Cu.

[0637] In some embodiments of the compound of Formula A, AI, A-II, A-III, A-IV, B or C, R X Can be combined 18 F-aluminum fluoride ([ 18 F]AlF) chelating agent, such as 1,4,7-triazacyclononane-1,4-diacetate (NODA) and the like. In some embodiments, the chelating agent is NODA. In some embodiments, the chelating agent is [ 18 F]AlF combination.

[0638] In some embodiments of the compound of Formula A, AI, A-II, A-III, A-IV, B or C, R X Can be combined 72 As or 77 In some embodiments, the chelating agent is a trithiol chelate. In some embodiments, the chelating agent is a trithiol chelate. 72 In some embodiments, the chelating agent is conjugated to 77 As conjugation.

[0639] In some embodiments of the compound of Formula A, AI, A-II, A-III, A-IV, B or C, R X It contains trifluoroborate (BF3) as a cofactor, capable of 18 F / 19 F exchange radiolabeling. X The group can be the only R X (n1=1), or you can add another R X groups, which can be combined with the first R X The same or different. The auxiliary group can be -R 13 R14 BF3, where R 13 independently –(CH2) 1-5 – and – R 14 The BF3 groups may be independently selected from Table 5 (below), Table 6 (below) or One or a combination of those groups listed in 15 and each R 16 are independently C1-C5 straight or branched chain alkyl. For Tables 5 and 6, R in the pyridine substituted with –OR, –SR, –NR–, –NHR or –NR2 groups is C1-C5 branched or straight chain alkyl.

[0640] In some embodiments of the compounds of Formula A, AI, A-II, A-III, A-IV, B, or C, Table 2 or derivatives thereof, or Table 4, -R 14 BF3 is selected from those groups listed in Table 5. In some embodiments, -R 14 BF3 is independently selected from one or a combination of those groups listed in Table 6. In some embodiments, at least one fluorine is 18 F. In some embodiments, all three fluorines are 19 F.

[0641] Table 5. Exemplary R 14 BF3 group.

[0642]

[0643]

[0644] Table 6. Exemplary R 14 BF3 group.

[0645]

[0646]

[0647]

[0648] In some embodiments, R 14 BF3 can form

[0649]

[0650]

[0651] Wherein R (when present) in the pyridine substituted with –OR, –SR, –NR–, –NHR or –NR2 is a branched or straight chain C1-C5 alkyl group. In some embodiments, R is a branched or straight chain C1-C5 saturated alkyl group. 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 F.

[0652] In some embodiments, R 14 BF3 can form

[0653]

[0654] Wherein R (when present) in the pyridine substituted with OR, –SR, –NR– or –NR2 is a branched or straight chain C1-C5 alkyl group. In some embodiments, R is a branched or straight chain C1-C5 saturated alkyl group. 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 BF3 is In some embodiments, one fluorine is 18 F. In some embodiments, all three fluorines are 19 F.

[0655] In some embodiments, -R 14 BF3 is In some embodiments, R 15 In some embodiments, R 15 In some embodiments, R 15 In some embodiments, R 15 In some embodiments, R 15 In some embodiments, R 15 In some embodiments, R 15 In some embodiments, R 16 In some embodiments, R 16 In some embodiments, R 16 In some embodiments, R 16 In some embodiments, R 16In some embodiments, R 16 In some embodiments, R 16 In some embodiments, R 15 and R 16 In some embodiments, at least one fluoro is 18 F. In some embodiments, all three fluorines are 19 F.

[0656] In some embodiments of the compound 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 in the silicon-fluorine-acceptor moiety is 18 F. The prosthetic group containing the silicon-fluorine-acceptor moiety can be independently selected from one or a combination of the following: where R 17 and R 18 are independently linear or branched, cyclic or acyclic, and / or aromatic or non-aromatic C1-C 10 In some embodiments, R 17 and R 18 are independently selected from the group consisting of phenyl, tert-butyl, sec-propyl, isopropyl, methyl, pyridyl, 2-indolyl, and 3-indolyl. In some embodiments, the prosthetic group is In some embodiments, the prosthetic group is In some embodiments, the prosthetic group is In some embodiments, the prosthetic group is In some embodiments, the prosthetic group is heteroarylated, as exemplified by but not limited to:

[0657] wherein R is hydrogen, alkyl or aryl.

[0658] In some embodiments of the compound of Formula A, AI, A-II, A-III, A-IV, B or C, R X The therapeutic moiety includes any chemical moiety capable of producing a therapeutic effect, such as a small molecule drug.

[0659] In some embodiments of the compound of Formula A, AI, A-II, A-III, A-IV, B or C, R X It is a fluorescent marker.

[0660] The present disclosure also relates to a composition comprising any one of the compounds of Formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2 or a derivative thereof, or Table 4 as described herein.

[0661] In some embodiments of the compound of Formula A, the compound is:

[0662]

[0663]

[0664]

[0665]

[0666]

[0667]

[0668] A salt or solvate thereof. In some embodiments, the compound is complexed with a radioactive isotope.

[0669] In some embodiments of the compound of Formula A, the compound is:

[0670] or a salt or solvate thereof.In some embodiments, the compound is complexed with a radioactive isotope.

[0671] In some embodiments of the compound of Formula B, the compound is:

[0672]

[0673] or a salt or solvate thereof.In some embodiments, the compound is complexed with a radioactive isotope.

[0674] In some embodiments of the compound of Formula C, the compound is:

[0675]

[0676]

[0677]

[0678] or a salt or solvate thereof.In some embodiments, the compound is complexed with a radioactive isotope.

[0679] How to use

[0680] The present disclosure also relates to any of the compounds of Formula A, AI, A-II, A-III, A-IV, B or C, or Table 2 or derivatives thereof, or Table 4 as described herein for use in imaging CXCR4-expressing tissue in a subject or for imaging an inflammatory condition or disease. In one embodiment, the compound comprises at least one R X , which contains or is complexed with an imaging radioisotope, the compound is conjugated to a metal chelator which is complexed with the imaging radioisotope, or the compound is conjugated to a prosthetic group containing BF3 which contains an imaging radioisotope. 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, 18 F, 131 I, 123 I, 124 I, 152 Tb, 155 Tb or 72 As. 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.

[0681] The present disclosure also relates to a method of imaging tissue expressing CXCR4, comprising administering to a subject in need of such imaging an effective amount of any of the compounds of Formula A, AI, A-II, A-III, A-IV, B or C, or Table 2 or derivatives thereof, or Table 4 as described herein. In one embodiment, the compound comprises at least one R X, which contains or is complexed with an imaging radioisotope, the compound is conjugated to a metal chelator which is complexed with the imaging radioisotope, or the compound is conjugated to a prosthetic group containing BF3 which contains an imaging radioisotope. 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, 18 F. 131 I. 123 I. 124 I. 152 Tb, 155 Tb or 72 As. 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.

[0682] The present disclosure also relates to any of the compounds of Formula A, AI, A-II, A-III, A-IV, B or C, or Table 2 or derivatives thereof, or Table 4 as 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 a compound complexed with a therapeutic radioisotope, or a compound associated with a metal chelator complexed with a therapeutic radioisotope. In one embodiment, the therapeutic radioisotope is 165 Second, 212 Bi, 211 At, 166 Ho, 149 Pm, 159 Gd, 105Rh, 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 Cu.

[0683] 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 thereof an effective amount of any one of Formula A, AI, A-II, A-III, A-IV, B or C, or Table 2 or a derivative thereof, or 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 a compound complexed with a therapeutic radioisotope, or a compound associated with a metal chelator complexed with a therapeutic radioisotope. In one embodiment, the therapeutic radioisotope is 165 Second, 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, 224Ra, 225 Ac, 227 Th, 223 Ra, 77 As、 131 I. 64 Cu or 67 Cu.

[0684] In some embodiments, the compounds of Formula A, AI, A-II, A-III, A-IV, B, or C, or Table 2 or derivatives thereof, or Table 4 inhibit the binding of SDF-1α to CXCR4 in vitro, IC 50 In some embodiments, the compound inhibits the binding of SDF-1α to CXCR4 in vitro, IC 50 In some embodiments, the compound inhibits the binding of SDF-1α to CXCR4 in vitro, IC 50 10 nM or lower.

[0685] CXCR4 overexpression has been observed in more than 23 types of malignant tumors, including brain cancer, breast cancer, and prostate cancer. In addition, leukemias, lymphomas, and myelomas have significant CXCR4 expression. Retrospective studies have shown that CXCR4 expression is associated with decreased survival in patients with prostate and melanoma. In addition, CXCR4 expression is a prognostic factor for disease relapse in acute and chronic myeloid leukemias, acute myeloid leukemia, and multiple myeloma. The SDF-1 / CXCR4 axis mediates cancer growth, enhances metastasis, recruits stromal cells and immune cells to support malignant growth, and confers chemotherapy resistance. Radiolabeled CXCR4 probes can be used for early diagnosis of solid and hematological malignancies that express CXCR4. Such imaging agents can be used to confirm the diagnosis of malignant tumors or, if the disease is localized, to guide local ablative therapy. Such ligands can also be used to monitor treatment response by providing an independent assessment of the residual cell content of tumors known to overexpress CXCR4. [ 68 Ga]Ga-Pentixafor has been used by Wester's group for cancer imaging and identification of potential responders to intracavitary radiotherapy.

[0686] Dysregulation of the SDF-1 / CXCR4 axis also mediates many inflammatory conditions. In rheumatoid arthritis (RA), SDF-1 / CXCR4 signaling is responsible for the proinflammatory migration of activated T cells to sites of inflammation; specifically, the synovium of patients with RA shows the presence of T cells with increased CXCR4 expression. Given the burden that RA imposes on the population in terms of morbidity and mortality, there has been a significant amount of research focused on developing therapies that mediate the inflammatory response, particularly with the new biologics approved by the FDA in the past few years. Radiolabeled CXCR4 probes for positron emission tomography imaging will enable the diagnosis and prognosis of rheumatoid arthritis and also be used to monitor treatment with emerging disease-modifying antirheumatic drugs in clinical trials. PET imaging has been used [ 68 Ga]Ga-Pentixafor detected CXCR4 expression in diseases with an inflammatory component, including infectious bone disease, urinary tract infection (UTI) following renal transplantation, myocardial infarction, and ischemic stroke. In the future, CXCR4 imaging could play a key role in the diagnosis and monitoring of other inflammatory diseases.

[0687] In the field of cardiac pathology, inflammatory diseases of the cardiac vessel wall are mediated in part by dysregulation of the SDF-1 / CXCR4 axis. In the early stages of atherosclerosis, the SDF-1 / CXCR4 axis recruits endothelial progenitor cells to sites of peripheral vascular injury, thereby initiating plaque formation, although there is some evidence of anti-atherosclerotic effects. Atherosclerotic plaques are characterized by the presence of hypoxia, which has been shown to upregulate CXCR4 expression and affect cellular trafficking. Finally, in a rabbit model of atherosclerosis, [ 68 Ga]Ga-Pentixafor was able to visualize atherosclerotic plaques by PET. 68 Ga]Ga-Pentixafor identified atherosclerotic plaques in patients with a history of atherosclerosis. Therefore, PET diagnostic agents targeting CXCR4 may be feasible as an alternative approach to diagnose and obtain prognostic information in atherosclerosis.

[0688] In some embodiments, the disease or condition characterized by expression of CXCR4 is leukemia, lymphoma, and myeloma. In some embodiments, the disease or condition characterized by expression of CXCR4 is a hematological malignancy. In some embodiments, the disease or condition characterized by expression of CXCR4 is an inflammatory disease. In some embodiments, the inflammatory disease is atherosclerosis.

[0689] In some embodiments, the disease or disorder characterized by expression of CXCR4 is cardiovascular disease.

[0690] In some embodiments, the disease or disorder characterized by expression of CXCR4 is a disease or disorder characterized by overexpression of CXCR4 or aberrant expression of CXCR4.

[0691] In some embodiments, the CXCR4-expressing cancer is a hematological malignancy. In some embodiments, the CXCR4-expressing cancer is a leukemia, lymphoma, and myeloma.

[0692] In certain embodiments, a compound of Formula A, AI, A-II, A-III, A-IV, B, or C is conjugated to a radioisotope for use in positron emission tomography (PET) or single photon emission computed tomography (SPECT) imaging of tissue expressing CXCR4 or for use in imaging inflammatory conditions or diseases (e.g., rheumatoid arthritis or cardiovascular disease), wherein the compound is conjugated to a radioisotope that is a positron emitter or a gamma emitter. Without limitation, the positron- or gamma-emitting radioisotope can be 68 Ga, 67 Ga, 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 As.

[0693] When the radioisotope (e.g., X) is a diagnostic radioisotope, the use of certain embodiments of the compound for preparing a radiolabeled tracer for imaging is disclosed. Also disclosed is a method for imaging a subject's CXCR4-expressing tissue or inflammatory condition or disease, wherein the method comprises: administering to the subject a composition comprising certain embodiments of the compound and a pharmaceutically acceptable excipient; and imaging the subject, for example, using positron emission tomography (PET). When the tissue is a diseased tissue (e.g., a cancer expressing CXCR4), then CXCR4 targeted therapy can be selected to treat the subject. Therefore, disclosed is the use of certain compounds of the present invention in imaging a subject's CXCR4-expressing cancer, wherein R X comprising or complexed with a diagnostic or imaging radioisotope. In some embodiments, the subject is a human.

[0694] Given that CXCR4 is widely expressed in cancer, there has been a strong push to develop therapies that target CXCR4. Although CXCR4 inhibitors have shown efficacy in treating tumors and preventing metastasis in mouse tumor models, very few agents have demonstrated efficacy in clinical trials. Plerixafor, also known as AMD3100, was originally developed for HIV treatment and is the only FDA-approved CXCR4 antagonist to date. AMD3100 is administered to patients with lymphoma and multiple myeloma to mobilize hematopoietic stem cells into the peripheral blood for collection and autologous transplantation, rather than as a direct treatment approach. There is an unmet clinical need for treatments for cancers that express CXCR4, many of which are resistant to today's available standards of care.

[0695] Cancers that are CXCR4 positive may be sensitive to intracavitary radiotherapy. In this application, a peptide targeting CXCR4 is radiolabeled with a radioisotope (usually a beta- or alpha-particle emitter) to deliver a high localized dose of radiation to the lesion. These radioactive emissions typically cause DNA damage, thereby inducing cell death. This treatment approach has been used in oncology, with somatostatin receptor (for neuroendocrine tumors) and prostate-specific membrane antigen (for metastatic castration-resistant prostate cancer) being two examples. Unlike external beam radiotherapy, this systemic treatment can be effective even in the setting of metastases. Therapeutic radioisotopes include, but are not limited to 177 Lu, 90 Y. 225 Ac and 64 Cu.

[0696] Regarding cardiac pathology, a study using [ 90 Y]Y-or[ 177 A small retrospective study of intracavitary radiotherapy with Lu-Pentixather demonstrated regression of CXCR4 expression and activity in patients with previously identified atherosclerotic plaques. Thus, radionuclide therapy may provide a new therapeutic approach for inflammatory diseases such as atherosclerosis.

[0697] In certain embodiments, a compound of Formula A, AI, A-II, A-III, A-IV, B, or C is conjugated to a radioactive isotope useful for therapy (e.g., cancer therapy). Such radioactive isotopes include radioactive isotopes such as 165 Second, 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 Cu.

[0698] When the radioisotope (e.g., X) is a therapeutic radioisotope, certain embodiments of the compound (or its pharmaceutical composition) are disclosed for use in treating a disease or condition characterized by expression of CXCR4 in a subject. Therefore, there is provided the use of a compound in the preparation of a medicament for treating a disease or condition characterized by expression of CXCR4 in a subject. Also provided is a method for treating a disease or condition characterized by expression of CXCR4 in a subject, wherein the method comprises: 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 pharmaceutically acceptable excipient. For example, but not limited to, the disease can be a cancer expressing CXCR4 (e.g., non-Hodgkin's lymphoma, lymphoma, multiple myeloma, leukemia, adrenocortical carcinoma, lung cancer, breast cancer, renal cell carcinoma, colorectal cancer). Therefore, disclosed are the uses of certain compounds of the present invention for treating a cancer expressing CXCR4 in a subject, wherein R X comprising or complexed with a therapeutic radioisotope. In some embodiments, the subject is a human.

[0699] Preparation method

[0700] The compounds presented herein are incorporated with peptides that can be synthesized by any of the various methods established in the art. Such methods include, but are not limited to, liquid and solid phase peptide synthesis using methods employing 9-fluorenylmethoxycarbonyl (Fmoc) and / or tert-butyloxycarbonyl (Boc) chemical reactions, and / or other synthetic methods.

[0701] Solid phase peptide synthesis methods and techniques are generally recognized in the art. For example, peptides can be synthesized by sequentially incorporating the amino acid residue of interest one at a time. In such methods, peptide synthesis is typically started by attaching the C-terminal amino acid of the peptide of interest to a suitable resin. Prior to this, the reactive side chain and α-amino groups of amino acid are protected by suitable blocking groups and do not react, only allowing the α-carboxyl group to react with the functional group (such as amine, hydroxyl or alkyl halide) on the solid support. After the C-terminal amino acid is coupled to the support, the blocking group and / or α-amino groups on the amino acid side chain are selectively removed, thereby allowing the next amino acid of interest to be coupled. Repeat this process until the desired peptide is fully synthesized, at which point the peptide can be deprotected and cut and purified from the support. The non-limiting example of an instrument for solid phase peptide synthesis is an Aapptec Endeavor 90 peptide synthesizer.

[0702] To allow coupling of additional amino acids, the Fmoc protecting group can be removed from the amino acid on the solid support, for example under mild basic conditions such as piperidine in DMF (20-50% v / v). The amino acid to be added must also have been activated for coupling (for example at the alpha formate position). Non-limiting examples of activation reagents 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), and benzotriazol-1-yl-oxy-tris(pyrrolidinyl)phosphonium hexafluorophosphate (PyBOP). Racemization is minimized by using triazoles such as 1-hydroxy-benzotriazole (HOBt) and 1-hydroxy-7-aza-benzotriazole (HOAt). The coupling can be performed in the presence of a suitable base such as N,N-diisopropylethylamine (DIPEA / DIEA), etc. For long peptides or if necessary, peptide synthesis and ligation can be used.

[0703] In addition to forming typical peptide bonds to extend the peptide, the peptide can also be extended in a branched manner by attaching to side chain functional groups (e.g., carboxylic acid groups or amino groups) (either side chain to side chain; or side chain to backbone amino groups or formate). Coupling to amino acid side chains can be performed by any known method and can be performed on or off the resin. Non-limiting examples include: the formation of amides between amino acid side chains containing carboxylic acids (e.g., Asp, D-Asp, Glu, D-Glu, Aad, etc.) and amino acid side chains containing amino groups (e.g., Lys, D-Lys, Orn, D-Orn, Dab, D-Dab, Dap, D-Dap, etc.) or the N-terminus of a peptide; the formation of amides between amino acid side chains containing amino groups (e.g., Lys, D-Lys, Orn, D-Orn, Dab, D-Dab, Dap, D-Dap, etc.) and carboxyl amino acid side chains (e.g., Asp, D-Asp, Glu, D-Glu, etc.) or the C-terminus of a peptide; and the formation of 1,2,3-triazoles by click chemistry between amino acid side chains containing azide groups (e.g., Lys(N3), D-Lys(N3), etc.) and alkyne groups (e.g., Pra, D-Pra, etc.). Before amide bond formation, the protecting groups on the appropriate functional groups must be selectively removed, whereas the reaction between alkynes and azide groups to form 1,2,3-triazoles via a click reaction 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) and 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 weakly acidic conditions such as 2.5% trifluoroacetic acid (TFA) in DCM. The Alloc blocking group can be selectively deprotected using tetrakis(triphenylphosphine)palladium(0) and phenylsilane in DCM. The Dde and ivDde blocking groups can be selectively deprotected using 2-5% hydrazine in DMF. The deprotected side chains of Asp / Glu (L-form or D-form) and Lys / Orn / Dab / Dap (L-form or D-form) can then be coupled, for example, using the coupling reaction conditions described above.

[0704] Compounds of Formula A, AI, A-II, A-III, and A-IV can be cyclized by attaching the peptide N-terminus to the side chain carboxylate (at residue 7 in the peptide) using the techniques discussed above (exemplary reaction conditions are described in the Examples). Compounds of Formula B can be cyclized using the intracyclic aminocarboxyethylthiotryptophan stapling reaction or the isoindole stapling reaction (known as FlICk). 21 ) to link the side chains of residues 1 and 7 in the peptide (exemplary reaction conditions are described in the Examples); the resulting isoindole has inherent fluorescent properties for imaging. The compound of formula C can be similarly cyclized using thiolactic acid amino acids at residue 1 in the peptide, for example, as shown in the following scheme:

[0705]

[0706] The peptide backbone amide can be N-methylated (i.e., α-aminomethylated). This can be achieved by directly using Fmoc-N-methylated amino acids during peptide synthesis. Alternatively, N-methylation can be performed under Mitsunobu conditions. First, a solution of 4-nitrobenzenesulfonyl chloride (Ns-Cl) and 2,4,6-trimethylpyridine (collidine) in NMP is used to protect the free primary amine group. N-methylation can be achieved in the presence of triphenylphosphine, diisopropyl azodicarboxylate (DIAD) and methanol. Subsequently, N-deprotection can be performed using mercaptoethanol and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in NMP. In order to couple the protected amino acid to the N-methylated α-amino group, HATU, HOAt and DIEA can be used.

[0707] Thioether (-S-) bonds (e.g. L 1 The formation of () can be realized in solid phase or in solution phase. For example, the formation of thioether (-S-) bond can be achieved by coupling between a thiol-containing compound (such as, a thiol group on a cysteine ​​side chain) and a haloalkyl (such as, 3-(Fmoc-amino)propyl bromide) in the presence of a base (such as, N, N-diisopropylethylamine, etc.) in a suitable solvent (such as, N, N-dimethylformamide, etc.). If the reaction is carried out in solution phase, the reactants used are preferably in an equivalent molar ratio (1 to 1), and the desired product can be purified by flash column chromatography or high performance liquid chromatography (HPLC). If the reaction is carried out on a solid phase, it means that one reactant has been attached to the solid phase, then the other reactant will typically be used in excess (≥3 equivalents of reactants attached to the solid phase). After the reaction, the solid phase (resin) can be sequentially washed with a combination of solvents (e.g., N, N-dimethylformamide, methanol and dichloromethane) to remove excess unreacted reactants and reagents.

[0708] The bond between the thiol group and the maleimide group (eg L 1 The formation of (-S-) can be carried out using the conditions described above for forming a thioether (-S-) bond, simply by replacing the alkyl halide with a maleimide-containing compound. Similarly, this reaction can be carried out in solid phase or solution phase. If the reaction is carried out in solution phase, the reactants used are preferably in an equivalent molar ratio (1 to 1), and the desired product can be purified by flash column chromatography or high performance liquid chromatography (HPLC). If the reaction is carried out on a solid phase, it means that one reactant has been attached to the solid phase, then the other reactant will typically be used in excess (≥3 equivalents of reactants attached to the solid phase). After the reaction, the solid phase (resin) can be removed by sequentially washing with a combination of solvents (e.g., N, N-dimethylformamide, methanol and dichloromethane) to remove excess unreacted reactants and reagents.

[0709] The non-peptide portion (e.g., a radiolabeled 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 readily accomplished when the non-peptide portion comprises an activated formate (and a protecting group if necessary) so that coupling can be performed on a resin. For example, but not limited to, bifunctional chelators such as tri(tert-butyl) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)) can be activated to couple to the peptide in the presence of N-hydroxysuccinimide (NHS) and N,N'-dicyclohexylcarbodiimide (DCC). Alternatively, the non-peptide portion can be incorporated into the compound by a copper-catalyzed click reaction under liquid or solid phase conditions. Copper-catalyzed click reactions are well-known in the art. For example, 2-azidoacetic acid is first activated by NHS and DCC and coupled to the peptide. Then, in the presence of Cu 2+ In the case of sodium ascorbate, the alkyne-containing non-peptide moiety can be clicked into the azide-containing peptide in water and organic solvents such as acetonitrile (ACN) and DMF. The non-peptide moiety can also be added in solution phase, which is conventionally performed.

[0710] The synthesis of chelating agents is well known and many are commercially available (e.g., from Sigma-Aldrich TM / Milipore Sigma TMetc.). Protocols for conjugating radioactive metals to chelating agents are also well known (e.g., see Example 1 below). The synthesis of the silicon-fluorine-acceptor moiety can be achieved according to previously reported procedures (e.g., Bernard-Gauthier et al. Biomed Res Int. 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). Synthesis or access to radioisotope-substituted aryl groups is equally easy.

[0711] R on the compound 13 R 14 The synthesis of the BF3 component can be achieved 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, the BF3-containing motif can be coupled to the linker by click chemistry, by forming a 1,2,3-triazole ring between the BF3-containing azide (or alkynyl) group and the alkynyl (or azido) group on the linker, or by forming an amide bond between the BF3-containing formate and the amino group on the linker. To prepare azides, alkynes, or formates containing BF3, a boronate-containing azide, alkyne, or formates is first prepared, and the boronate is subsequently converted to BF3 in a mixture of HCl, DMF, and KHF2. For alkyl BF3, boronate-containing azides, alkynes, or formates can be prepared by coupling a boronate-containing alkyl halide (such as iodomethyl pinacol borate) with an amine-containing azide, alkyne, or formates (such as N,N-dimethylpropargylamine). For aryl BF3, boronates can be prepared by Suzuki coupling using an aryl halide (iodine or bromine) and bis(pinacol)diboron.

[0712] 通过18 F- 19The 18F-fluorination of BF3-containing compounds by F isotope exchange reaction can be achieved according to previously published procedures (Liu et al., Experimental Manual of Nature, 2015, 10: 1423-1432, which is incorporated by reference in its entirety). Typically, about 100 nmol of BF3-containing compounds were dissolved in a mixture of 15 μl of pyridazine-HCl buffer (pH = 2.0–2.5, 1 M), 15 μl of DMF, and 1 μl of 7.5 mM KHF2 aqueous solution. 18 F-fluoride solution (in saline, 60 μl) is added to the reaction mixture, and the resulting solution is heated at 80° C. for 20 minutes. At the end of the reaction, the desired product can be purified by solid phase extraction or by reverse phase high performance liquid chromatography (HPLC) using a mixture of water and acetonitrile as the mobile phase.

[0713] When the peptide is fully synthesized on a solid support, the desired peptide can be cleaved from the solid support using suitable reagents such as TFA, triisopropylsilane (TIS) and water. Side chain protecting groups such as Boc, pentamethyldihydrobenzofuran-5-sulfonyl (Pbf), trityl (Trt) and tert-butyl (tBu) are simultaneously removed (i.e., deprotection). The crude peptide can be precipitated and collected 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 identity of the purified peptide can be confirmed by mass spectrometry or other similar methods.

[0714] The invention will be further illustrated in the following examples where specific compounds are synthesized and evaluated.

[0715] Example

[0716] Chemical synthesis

[0717] experiment :

[0718] Unless otherwise noted, reagents and solvents were purchased from commercial sources and used without further purification. Peptides were synthesized on a Liberty Blue automated microwave peptide synthesis (CEM Corporations) or PurePep Chorus GT (Gyros Protein Technologies). High performance liquid chromatography (HPLC) was performed on the following equipment: (1) an Agilent 1260 infinity system equipped with a 1200 quaternary pump, a 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 1260 Infinity II preparative binary pump, a 1260 Infinity variable wavelength detector (set to 220 nm), and a 1290 Infinity II preparative open fraction collector. The HPLC columns used for the synthesis were semi-preparative columns (Agilent Eclipse XDB-C18, 5 μm, 9.4 × 250 mm) or preparative columns (Gemini, NX-C18, 5 μm, Mass analysis was performed using an AB SCIEX 4000QTRAP mass spectrometer system or a Waters-Micromass ZQ mass spectrometer system with an ESI source or a Waters 2695 separation module.

[0719] Synthesis of BL34L6

[0720]

[0721] 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 x 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 MOxyma (1 mL / 0.5 mL) in DMF, followed by Fmoc-deprotection as described above. In a similar manner, 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 coupled continuously. -OAll (allyloxy) groups were removed (35 ° C, 6 min, x2) with Pd (PPh ) / phenylsilane (0.25 / 15 equivalents) followed by Fmoc-deprotection. Cyclization was carried out at 75 ° C (12 min, x3) with HATU / HOAt / DIPEA (1 / 1 / 2 equivalents). The ivDde group was removed with 2% hydrazine in DMF (3 mL, room temperature, 5 min, x5). As described above, Fmoc-cysteic acid and Fmoc-Lys(ivDde)-OH were coupled. The synthesis was continued by coupling DOTA (4 equiv.) using HATU / HOAt / DIPEA (4 / 4 / 8 equiv.), followed by ivDde deprotection and coupling of 4-(4-methoxyphenyl)butanoic acid using HATU / HOAt / DIPEA (4 / 4 / 8 equiv.). The peptide was cleaved from the resin with TFA / TIPs / H2O / phenol (90 / 2.5 / 2.5 / 5%) at 35°C for 3h. The crude peptide was precipitated in cold diethyl ether, washed with ether (x2) and lyophilized in a H2O / MeCN mixture. The crude peptide was purified by semi-preparative HPLC column using solvents A:H2O / 0.1% TFA and B:MeCN / 0.1% TFA (4.5 mL / min) (31% B in 20 min, t R =7.189min) was purified. The sample was lyophilized to a white solid. Calculated mass (M+H + ): 2026.08m / z; found (M+3H + ) / 3: 676.21m / z.

[0722] Synthesis of BL34L7

[0723]

[0724] 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 x 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 MOxyma (1 mL / 0.5 mL) in DMF, followed by Fmoc-deprotection as described above. In a similar manner, 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 coupled continuously. -OAll group was removed (35°C, 6 min, x2) with Pd (PPh ) / phenylsilane (0.25 / 15 equivalents) followed by Fmoc-deprotection. Cyclization was carried out at 75°C (12 min, x3) with HATU / HOAt / DIPEA (1 / 1 / 2 equivalents). ivDde group was removed with 2% hydrazine in DMF (3 mL, room temperature, 5 min, x5). As described above, Fmoc-Lys(ivDde)-OH and Fmoc cysteic acid were coupled. The synthesis was continued by coupling DOTA (4 equivalents) using HATU / HOAt / DIPEA (4 / 4 / 8 equivalents), followed by ivDde deprotection and 4-(4-methoxyphenyl)butanoic acid coupling using HATU / HOAt / DIPEA (4 / 4 / 8 equivalents). The peptide was cleaved from the resin with TFA / TIPs / H2O / phenol (90 / 2.5 / 2.5 / 5%) for 3 h at 35°C. The crude peptide was precipitated in cold diethyl ether, washed with ether (x2) and lyophilized in a H2O / ACN mixture. The crude peptide was purified by semi-preparative HPLC column using solvents A:H2O / 0.1% TFA and B:MeCN / 0.1% TFA (4.5 mL / min) (31% B in 20 min, t R =6.796min) purification. The sample was lyophilized to a white solid. Calculated mass (M+H + ): 2026.08 m / z; found (M+3H) 3+ / 3: 676.21m / z.

[0725] Synthesis of BL34L8

[0726]

[0727] Under 0.1mmol scale, Rink Amide Protide resin is deprotected with 20% piperidines-DMF (3mL) at 90 ℃ (1min), then washed with DMF (3mL x3).Then, under 75 ℃ (12min), use HATU / HOAt / DIPEA (5 / 5 / 10 equivalent) to couple Fmoc-Lys (Mtt) -OH (5 equivalents, 0.5mmol, 0.2M in DMF) twice.Resin is deprotected with 20% piperidines-DMF (3mL) at 90 ℃ (1min), then washed with DMF (3mL x3).Then, under 90 ℃ (4min), use 1M DIC / 1M Oxyma (1mL / 0.5mL) in DMF to couple Fmoc-Lys (iPr, Boc) -OH (5 equivalents, 0.5mmol, 0.2M in DMF), subsequently as mentioned above, carry out Fmoc-deprotection. In a similar manner, 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 coupled continuously. Pd (PPh ) / phenylsilane (0.25 / 15 equivalent) was used to remove the -OAll group (35°C, 6 min, x2), followed by Fmoc-deprotection. Cyclization was performed at 75°C using HATU / HOAt / DIPEA (1 / 1 / 2 equivalent) (12 min, x3). The ivDde group was removed using 2% hydrazine in DMF (3 mL, room temperature, 5 min, x5). As described above, Fmoc-cysteic acid was coupled. After Fmoc-deprotection, DOTA (4 equivalents) was coupled using HATU / HOAt / DIPEA (4 / 4 / 8 equivalents). Afterwards, the Mtt protecting group was removed using 2% TFA (4 mL, room temperature, 2 min, x8) in DCM, washed with DCM (3 mL x 5) and DMF (4 mL x 5). The resin was neutralized with 10% DIPEA (5 mL, 5 min, twice) in DMF and 4-(4-methoxyphenyl)butanoic acid was coupled. The peptide was cut from the resin using TFA / TIPs / H at 35°C for 3 hours using O / phenol (90 / 2.5 / 2.5 / 5%). The crude peptide was precipitated in cold diethyl ether, washed with ether (x2) and lyophilized in a H O / MeCN mixture. The crude peptide was purified by semi-preparative HPLC using solvents A: H2O / 0.1% TFA and B: MeCN / 0.1% TFA (4.5 mL / min) (31% B in 20 min, t R =5.827min) purification. Calculated mass (M+H+ ): 2026.08 m / z; found (M+3H) 3+ / 3: 676.41m / z.

[0728] Synthesis of BL34L11

[0729]

[0730] 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 x 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 MOxyma (1 mL / 0.5 mL) in DMF, followed by Fmoc-deprotection as described above. In a similar manner, 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 coupled continuously. -OAll group was removed (35°C, 6 min, x2) with Pd (PPh ) / phenylsilane (0.25 / 15 equivalents) followed by Fmoc-deprotection. Cyclization was carried out at 75°C (12 min, x3) with HATU / HOAt / DIPEA (1 / 1 / 2 equivalents). ivDde group was removed with 2% hydrazine in DMF (3 mL, room temperature, 5 min, x5). As described above, Fmoc-Lys (ivDde) ​​-OH and Fmoc cysteic acid were coupled. The synthesis was continued by coupling DOTA (4 equivalents) using HATU / HOAt / DIPEA (4 / 4 / 8 equivalents), followed by ivDde deprotection and coupling of 4- (4-iodophenyl) butyric acid with HATU / HOAt / DIPEA (4 / 4 / 8 equivalents). The peptide was cleaved from the resin with TFA / TIPs / H2O / phenol (90 / 2.5 / 2.5 / 5%) for 3 h at 35°C. The crude peptide was precipitated in cold diethyl ether, washed with ether (x2) and lyophilized in a H2O / MeCN mixture. The crude peptide was purified by preparative HPLC using solvents A: H2O / 0.1% TFA and B: MeCN / 0.1% TFA (30 mL / min) (31% B in 15 min, t R =8.617min) was purified. The sample was lyophilized to a white solid. Calculated mass (M+H +): 2121.96 m / z; found (M+2H) 2+ / 2:1061.98m / z.

[0731] Synthesis of compound A

[0732]

[0733] Synthesis of MT16-145-L-HpiMBHA Rink Amide (0.04 mmol) resin was dissolved in 3 mL of DMF, mixed for 20 min by bubbling N2, and then drained. The resin was resuspended in 3 mL of 20% piperidine-DMF and mixed for 1 min by bubbling N2 at 50°C. The solution was drained and the process was repeated with fresh 3 mL portions of DMF. The resin was washed three times with 3 mL portions of DMF (mixed by bubbling N2, then drained). The resin was resuspended in 3 mL of DMF containing Fmoc-Xaa-OH (100 mM), HCTU (100 mM), N-methyl-morpholine (200 mM), and an initial resin loading of at least 7.5 equivalents of amino acid and coupling agent. The resin suspended in the coupling solution was mixed for 5 min at 50°C by bubbling N2. The exception was the following: the Fmoc-aza-Xaa-OH dipeptide was mixed for 50 min at 50°C by bubbling N2. With Fmoc-Hpi-OH at room temperature through bubbling N Mix 1h.With the DMF (x3) washing resin of 3mL part (through N Bubbling mixes, then drains.) after the last coupling, then with the DCM (x4) washing resin of 3mL part (through N Bubbling mixes, then drains.) then with resin by using N Rinse dry 20min.On synthesizer, manually resin is suspended among the 5mL DMF, use N Bubbling mixes 20min, on synthesizer, Fmoc deprotection is washed with DMF (x3), then.The solution of 74.1mg Fmoc-β-Ala-OH, 102.2mg COMU, 0.12mL DIEA in 1mDMF is added in reaction vessel, bubbling is about 1-1.5h.Per hour prepare fresh coupling solution.Repeat this process three times, the total reaction time is 5.5h.After last round coupling, with DCM (x4) washing resin and on peptide synthesizer dry 20min. On the synthesizer, the straight-chain peptide of resin binding is manually suspended in 5mL DMF and mixed with N2 bubbling for 20min.Fmoc deprotection is carried out by processing with 20% piperidine-DMF (3mL), mixed by N2 bubbling.The resin is washed with DMF (x3).Hatched together with 1:2:2Ac2O / EtOAc / collidine (5mL) on the synthesizer for 30min, then washed with DMF (x3), then washed with DCM (x4), then dried for 20min.In a round-bottom flask, the dried resin is stirred overnight with 2mL TFA.In the morning, 50 μL TIS and 50 μL H2O are added until the bright yellow color disappears. TFA was filtered into a 15 mL falcon tube, triturated with Et2O (x3), the precipitate was air dried and dissolved in H2O / MeCN 0.1% FA and purified by HPLC on C18 using 0.1% FA H2O / MeCN gradient elution on a 50x21 mm column.Pure fractions were collected, frozen, and lyophilized. The pure peptide was re-injected onto an Agilent Eclipse XDDC18 C18 column (9.4 x 250 mm) using solvents A: H2O / 0.1% FA and B: MeCN / 0.1% FA, eluting first with 95% H2O to 65% H2O (containing 0.1% FA) over a period of 0-32 min, then with 65% to 0% H2O (containing 0.1% FA) over a period of 32-35 min at a flow rate of 2 mL / min. (t. R =23.362min). LRMS-ESI(m / z):C 68 H 98 N 16 O 11 S(M+2H) 2+ / 2Calculated 673.4m / zObserved 673.7m / z.

[0734] Synthesis of compound A : Starting from MT16-145-L-Hpi synthesis, after attaching Fmoc-β-Ala-OH, by treating with 20% piperidine-DMF (3mL), Fmoc is deprotected, by N2 bubbling mixing. Resin is washed with DMF (x3). Fmoc-cysteic acid is coupled, and DOTA is then coupled at room temperature using HATU and DIEA (using 4 / 4 / 8 equivalents) in DMF. In a round-bottom flask, dried resin is stirred overnight with 2mL TFA. In the morning, 50 μL TIS and 50 μL H2O are added until the bright yellow color disappears. TFA is filtered into a 15mL falcon tube, ground with Et2O (x3), and the precipitate is dried in air.

[0735] Synthesis of compound B

[0736]

[0737] Synthesis of MT16-145-D-HpiSynthesize from MT16-145-L-Hpi, substitute Fmoc-L-Hpi, with Fmoc-D-Hpi-OH by N2 bubbling at room temperature mixed 1 hour.With the DMF (x3) washing resin of 3mL part (by N2 bubbling mixing, then draining.) after the last coupling, then with the DCM (x4) washing resin of 3mL part (by N2 bubbling mixing, then draining.) resin is passed through with N2 flushing dry 20min.On synthesizer, manually resin is suspended among the 5mL DMF, with N2 bubbling mixing 20min.On synthesizer, Fmoc deprotection is then washed with DMF (x3).The 74.1mg Fmoc-β-Ala-OH, 102.2mg COMU, 0.12mL DIEA in the 1mL DMF are added in the reaction vessel, bubbling is about 1-1.5h.Per hour, prepare fresh coupling solution.Repeat x3, total reaction time is 5.5h. After the last round of coupling, the resin was washed with DCM (x4) and dried on a peptide synthesizer for 20 min. The straight-chain peptide bound to the resin was manually suspended in 5 mL DMF on the synthesizer and mixed with N2 bubbling for 20 min. Fmoc deprotection was carried out by processing with 20% piperidine-DMF (3 mL), mixed with N2 bubbling. The resin was washed with DMF (x3). On the synthesizer, the resin was incubated with 1:2:2Ac2O / EtOAc / collidine (5 mL) for 30 min, then washed with DMF (x3), then washed with DCM (x4), then dried for 20 min. In a round-bottom flask, the dried resin was stirred overnight with 2 mL TFA. In the morning, 50 μ L TIS and 50 μ L H2O were added until the bright yellow color disappeared. The TFA was filtered into a 15 mL falcon tube, triturated with Et2O (x3), the precipitate was air dried and dissolved in H2O / MeCN 0.1% FA and purified by HPLC on C18 using a gradient elution of 0.1% FA H2O / MeCN on a 50x21 mm column. The pure fractions were collected, frozen and lyophilized. The pure peptide was re-injected on an Agilent Eclipse XDDC18 C18 column (9.4x250 mm) using solvents A: H2O / 0.1% FA and B: MeCN / 0.1% FA, eluting first with 95% H2O to 65% H2O (with 0.1% FA) for 0-32 min and then with 65%-0% H2O (with 0.1% FA) for 32-35 min at a flow rate of 2 mL / min. (t R =24.171min). LRMS-ESI(m / z):C 68 H 98 N 16 O 11 S(M+2H) 2+ / 2Calculated 673.4m / zObserved 673.6m / z.

[0738] Synthesis of compound B : Starting from MT16-145-D-Hpi synthesis, after attaching Fmoc-β-Ala-OH, by treating with 20% piperidine-DMF (3mL), Fmoc is deprotected, by N2 bubbling mixing. Resin is washed with DMF (x3). Fmoc-cysteic acid is coupled, then DOTA is coupled using HATU and DIEA (using 4 / 4 / 8 equivalent) in DMF at room temperature. In a round-bottom flask, dry resin is stirred overnight with 2mL TFA. In the morning, 50 μL TIS and 50 μL H2O are added until bright yellow disappears. TFA is filtered into a 15mL falcon tube, ground with Et2O (x3), and the precipitate is dried in air.

[0739] Synthesis of BL34N1

[0740]

[0741] At 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 at room temperature for 30 minutes and washed seven 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 hour. After each deprotection, the resin was washed seven times with 3 mL of DMF. The Fmoc group was removed with 20% v / v piperidine in DMF for 25 minutes. Following a similar procedure, 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.

[0742] The resin (0.15 mmol) was treated with o-nitrobenzenesulfonyl chloride (3 equivalents) and 2,4,6-collidine (5 equivalents) in CHCl (0.1 M) for 2 h at room temperature. After washing the resin (CHCl x3, DMF x3, and THF x3), MeOH (5 equivalents), PPh (5 equivalents), and diethyl azodicarboxylate (5 equivalents) were added to a suspension of the N-Ns-protected resin in anhydrous THF (0.1 M) at 0°C. The mixture was shaken at room temperature for 2 h, followed by washing the resin (THF x3 and CHCl x3). The N-methylated resin was treated with DBU (5 equivalents) and 2-mercaptoethanol (10 equivalents) at room temperature for 1.5 h to yield a protected peptide resin with an N-methyl amino acid at the N-terminus. To couple the Fmoc amino acid to the N-methyl amino acid, HATU and 1-hydroxy-7-azabenzotriazole (HOAt) were used. The Fmoc group was deprotected by treatment with 20% (v / v) piperidine-DMF for 20 min. In this case, it would be Fmoc-Tyr(tBu)-OH. Fmoc-Lys(ivDde)-OH (x2) was sequentially coupled to the peptidyl resin using 4 / 8 / 4 equivalents of Fmoc-AA-OH / DIC / Oxyma in DMF and shaken for 1 h. The –OAll protecting group on D-Glu was removed using Pd(PPh3)4 (30 mg) / phenylsilane (450 μL) in DCM (6 mL) (4 x 25 min at room temperature). The N on Lys(ivDde) ​​was then removed. a -Fmoc, and use DIC / HOBt in DMF for cyclization (2x 2h, at room temperature). After cyclization, remove the ivDde group for 10 minutes, 4 cycles by adding 2% N2H4 in 3mL DMF. Couple Fmoc-cysteic acid, then use HATU and DIEA (using 4 / 4 / 8 equivalents) in DMF to couple DOTA(tBu)3 at room temperature. By treating with 92.5 / 2.5 / 2.5TFA / TIS / H2O mixed solution for 5h at room temperature, the peptide is deprotected and simultaneously cut from the resin. After filtration, TFA is removed in vacuo, and the peptide is precipitated by adding cold diethyl ether. The crude peptide is purified by semi-preparative HPLC using a semi-preparative column, first eluted with 5% MeCN (containing 0.1% TFA) in H2O for 0-7min, then eluted with 5%-35% MeCN for 7-8min, then eluted with 35%-100% MeCN for 8-9min, flow rate 15mL / min (t R =5.167min). C 80 H 126 N 20 O 21 S calculated mass: [M+2H] 2+ / 2:868.5m / z; found [M+2H] 2+ / 2:869.0m / z.

[0743] Synthesis of BL34P1

[0744]

[0745] Starting from the BL34N1 synthesis, after removal of the Fmoc group of Fmoc-D-Arg-OH at a 0.05 mmol scale, 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, the resin was washed seven times, and then treated with o-nitrobenzenesulfonyl chloride (3 equivalents) and 2,4,6-collidine (5 equivalents) in CHCl (0.1 M) at room temperature for 2 h. After washing the resin (CHCl x3, DMF x3, and THF x3), tBu-(4-hydroxybutyl)(isopropyl)carbamate (5 equivalents), PPh (5 equivalents), and diethyl azodicarboxylate (5 equivalents) were added to a suspension of the N-Ns-protected resin in anhydrous THF (0.1 M) at 0°C. The mixture was shaken at room temperature for 2 hours, followed by washing the resin (THF x3 and CHCl x3). This cycle was repeated three times to complete the alkylation. The N-alkylated resin was treated with DBU (5 equivalents) and 2-mercaptoethanol (10 equivalents) at room temperature for 1.5 hours to obtain a protected peptide resin with an N-methyl amino acid at the N-terminus. To couple the Fmoc amino acid to the N-methyl amino acid, HATU and HOAt were used. The Fmoc group was deprotected by treatment with 20% (v / v) piperidine-DMF for 20 minutes. In this case, it would be Fmoc-Tyr(tBu)-OH. Fmoc-Lys(ivDde)-OH (x2) was coupled to the peptidyl resin using 4 / 8 / 4 equivalents of Fmoc-AA-OH / DIC / Oxyma in DMF and shaken for 1 h. The –OAll protecting group on D-Glu was removed using Pd(PPh3)4 (10 mg) / phenylsilane (150 μL) in DCM (5 mL) (4 x 25 min at room temperature). The N-terminal residue on Lys(ivDde) ​​was then removed. aIn the 40mL DMF of 40mL HCl, 4% HCl is added to the 40mL DMF of HCl.Then HCl is added to the HCl of HCl.-Fmoc, and uses the DIC / HOBt in DMF to carry out cyclization (2x 2h, at room temperature).After cyclization, by adding 2% N in 3mL DMF H Remove ivDde group 10min, 4 circulations.Couple Fmoc-cysteic acid-OH, then at room temperature use HATU and DIEA (using 4 / 4 / 8 equivalent) in DMF to couple DOTA(tBu) 3.By at room temperature using 92.5 / 2.5 / 2.5TFA / TIS / H o mixed solution is processed 5h, with peptide deprotection and simultaneously cut from resin.After filtration, vacuum removes TFA, and by adding cold diethyl ether precipitation peptide.

[0746] The crude peptide was purified by semi-preparative HPLC using a semi-preparative column, eluting first with 5% acetonitrile (containing 0.1% TFA) in water for 0-7 min, then 5%-35% acetonitrile for 7-8 min, and then 35%-100% acetonitrile for 8-9 min at a flow rate of 15 mL / min (t R =5.478min). ESI-MS: BL34P1C 81 H 128 N 20 O 21 Calculation of SNaK [M+Na+K] 2+ / 2 906.1m / z; found [M+Na+K] 2+ / 2 906.6m / z.

[0747] Synthesis of BL34L16

[0748]

[0749] 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 x 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 MOxyma (1 mL / 0.5 mL) in DMF, followed by Fmoc-deprotection as described above. In a similar manner, 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 coupled continuously. -OAll group was removed (35°C, 6 min, x2) with Pd (PPh ) / phenylsilane (0.25 / 15 equivalents) followed by Fmoc-deprotection. Cyclization was carried out at 75°C (12 min, x3) with HATU / HOAt / DIPEA (1 / 1 / 2 equivalents). ivDde group was removed with 2% hydrazine in DMF (3 mL, room temperature, 5 min, x5). As described above, Fmoc-Lys (ivDde) ​​-OH and Fmoc cysteic acid are coupled. Use HATU / HOAt / DIPEA (4 / 4 / 8 equivalents) to carry out DOTA (4 equivalents) coupling and continue synthesis, then carry out ivDde deprotection, and carry out 4- (4-chlorophenyl) butyric acid coupling with HATU / HOAt / DIPEA (4 / 4 / 8 equivalents). Use TFA / TIPs / H at 35 ℃ O / phenol (90 / 2.5 / 2.5 / 5%) to cut the peptide from the resin and continue 3h. The crude peptide is precipitated in cold diethyl ether, washed with ether (x2) and lyophilized in H O / MeCN mixture. The crude peptide is used with preparative HPLC using solvent A: H O / 0.1% TFA and B: MeCN / 0.1% TFA, 30mL / min (20%-40% B in 15min, tR=7.82min). The sample is lyophilized to a white solid. Calculated mass (M+H+): 2030.03 m / z; found (M+3H)3+ / 3: 677.81 m / z.

[0750] Synthesis of compounds C and D

[0751]

[0752]

[0753] Compounds C and D can be prepared according to the exemplary synthetic route for BL34L16 outlined above.

[0754] Synthesis of BL34L20

[0755]

[0756] 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 x 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 MOxyma (1 mL / 0.5 mL) in DMF, followed by Fmoc-deprotection as described above. In a similar manner, 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 coupled continuously. -OAll group was removed (35°C, 6 min, x2) with Pd (PPh ) / phenylsilane (0.25 / 15 equivalents) followed by Fmoc-deprotection. Cyclization was carried out at 75°C (12 min, x3) with HATU / HOAt / DIPEA (1 / 1 / 2 equivalents). ivDde group was removed with 2% hydrazine in DMF (3 mL, room temperature, 5 min, x5). As described above, Fmoc-Lys (ivDde) ​​-OH and Fmoc cysteic acid are coupled. Use HATU / HOAt / DIPEA (4 / 4 / 8 equivalents) to carry out DOTA (4 equivalents) coupling and continue synthesis, then carry out ivDde deprotection, and carry out 4- (4-bromophenyl) butyric acid coupling with HATU / HOAt / DIPEA (4 / 4 / 8 equivalents). Use TFA / TIPs / H at 35 ℃ O / phenol (90 / 2.5 / 2.5 / 5%) to cut the peptide from the resin and continue 3h. The crude peptide is precipitated in cold diethyl ether, washed with ether (x2) and lyophilized in H O / MeCN mixture. The crude peptide is used with preparative HPLC using solvent A: H O / 0.1% TFA and B: MeCN / 0.1% TFA, 30mL / min (25%-35% B in 15min, tR=6.00min). The sample is lyophilized to a white solid. Calculated mass (M+H+): 2073.98 m / z; found (M+2H)2+ / 2: 1038.29 m / z.

[0757] Synthesis of Crown-BL34

[0758]

[0759] At 0.05 mmol scale, the 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 coupled to the resin, followed by solid phase peptide synthesis using Fmoc-based chemistry to couple 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. All couplings were performed in DMF using Fmoc-protected amino acids (4 equivalents), HATU (4 equivalents), and DIEA (7 equivalents). With Pd (PPh 3 ) 4 / phenylsilane (0.25 / 24 equivalent) remove-OAll group (30min, x2), carry out Fmoc-deprotection subsequently.Use HATU / HOAt / DIPEA (3 / 3 / 6 equivalent) to carry out cyclization, and couple 12h.With 2% hydrazine (5x 5min) in DMF remove ivDde group.As mentioned above, couple Fmoc-cysteic acid.Use HATU / DIPEA (4 / 7 equivalent) to carry out crown (tBu) 3 (4 equivalent) coupling and continue synthesis.Then, by at room temperature with 95 / 5 trifluoroacetic acid (TFA) / triisopropylsilane (TIS) process 2h, by peptide deprotection and simultaneously from resin cutting.After filtration, by adding cold diethyl ether to TFA solution, precipitate peptide.Crude peptide is used semi-preparative column purification by HPLC. HPLC conditions were 13% acetonitrile (containing 0.1% formic acid) in trace metal water at a flow rate of 4.5 mL / min. The retention time was 9.7 min. The eluate containing the desired peptide was collected, combined, and lyophilized. The calculated mass (M+H+) was 1809.96 m / z; the observed mass (M+2H) was 1809.96 m / z. 2+ / 2:905.72m / z.

[0760] Synthesis of 3NOPA-BL34L2

[0761]

[0762]

[0763] Program: 3-NOPA-BL34L2 Flickr

[0764] Flick and gallium chelation: About 2 μmole of crude peptide (lyophilized, in a 15 mL falcon tube) was dissolved in 400 μL of 2M HEPES (pH 9) and 80 μL of 0.05 M 3-NOPA in EtOH was added. The solution was allowed to react overnight at room temperature. The solution was then eluted with 1 M HCl. (aq) The reaction mixture was acidified to pH approximately 4, 300 μL of Ga(NO 2 ) 3 in 1M HCl (0.0282 M) (pH approximately 3) were added, 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 (as follows).

[0765] Flick only: 4 μmole of pure peptide was dissolved in 1 mL of borate buffer (pH approximately 9.5), 120 μL of 0.05 M 3-NOPA in EtOH was added, the reaction was vortexed and allowed to react at room temperature for 4 hours. 10 μL of formic acid was then added, and the entire reaction mixture was directly purified by RP-HPLC using Method A.

[0766] Pure peptide reinjection:

[0767] LRMS(C 86 H 124 GaN 21 O 22 S2): (M+2H) 2+ / 2 Observed: 969.8, calculated: 969.4(1 13 C)

[0768] HPLC retention time: (Method A) 27.6 min

[0769] Method A: 15 mL / min 50x21 mm C18 Solvent A: 0.1% formic acid in H2O Solvent B: 0.1% formic acid in MeCN

[0770] 0-7.5min 95:5A / B-65:35A / B

[0771] 7.5min-8.0min 65:35A / B-0:1A / B

[0772] 8.0min-9.5min 0:1A / B

[0773] HPLC method B: 2 mL / min 9.4 x 250 mm C18 solvent A: 0.1% formic acid in H2O, solvent B: 0.1% formic acid in MeCN.

[0774] 0-12min 80:20A / B-60:40A / B

[0775] 12min-15min 60:40A / B-0:1A / B

[0776] 15min-20min 0:1A / B

[0777] 20min-23min 0:1A / B-80:20A / B

[0778] 23min-29min 80:20A / B

[0779] Synthesis of BL34T1

[0780]

[0781] At 0.05 mmol scale, the 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 coupled to the resin, followed by solid phase peptide synthesis using Fmoc-based chemistry to couple 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. All couplings were performed in DMF using Fmoc-protected amino acids (4 equivalents), HATU (4 equivalents), and DIEA (7 equivalents). The -OAll group was removed with Pd(PPh3)4 / phenylsilane (0.25 / 24 equivalents) (30 min, x2) followed by Fmoc-deprotection. Cyclization was performed with HATU / HOAt / DIPEA (3 / 3 / 6 equivalents) and coupled for 12 h. The ivDde group was removed with 2% hydrazine in DMF (5x5 min). As described above, Fmoc-Lys(ivDde)-OH, Fmoc-GlyOH and p-chloro-4-phenylbutyric acid were then coupled to the sequence. After selective removal of the ivDde-protecting group with 2% hydrazine in DMF (5 x 5 min), Fmoc-cysteic acid was then coupled to the Lys side chain. The synthesis was continued by coupling with crown (tBu)3 (4 equivalents) using HATU / DIPEA (4 / 7 equivalents). The peptide was then deprotected and simultaneously cleaved from the resin by treatment with 95 / 5 trifluoroacetic acid (TFA) / triisopropylsilane (TIS) at room temperature for 2 h. 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 (containing 0.1% TFA) at a flow rate of 4.5 mL / min. The retention time was 12.7 min. The eluates containing the desired peptide were collected, combined, and lyophilized. Calculated mass (M+2H) 2+ / 2: 1044.0 m / z; found (M+2H) 2+ / 2:1044.0m / z.

[0782] Synthesis of BL34L20S

[0783]

[0784] At 0.05 mmol scale, the 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 coupled to the resin, followed by solid phase peptide synthesis using Fmoc-based chemistry to couple 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. All couplings were performed in DMF using Fmoc-protected amino acids (4 equivalents), HATU (4 equivalents), and DIEA (7 equivalents). With Pd (PPh 3 ) 4 / phenylsilane (0.25 / 24 equivalent) remove-OAll group (30min, x2), carry out Fmoc-deprotection subsequently.Carry out cyclization with HATU / HOAt / DIPEA (3 / 3 / 6 equivalent), and couple 12h.Remove ivDde group with 2% hydrazine (5x 5min) in the DMF.As mentioned above, then couple Fmoc-cysteic acid and Fmoc-Lys (ivDde)-OH.Use HATU / DIPEA (4 / 7 equivalent) to carry out DOTA (4 equivalent) coupling and continue synthesis, carry out ivDde deprotection subsequently, and carry out 4-(4-bromophenyl) butyric acid coupling with HATU / DIPEA (4 / 7 equivalent).Then, by at room temperature with 95 / 5 trifluoroacetic acid (TFA) / triisopropylsilane (TIS) handle 2h, with peptide deprotection and simultaneously cut from resin. 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 (containing 0.1% TFA) and a flow rate of 4.5 mL / min. The retention time was 13.2 min. The eluates containing the desired peptide were collected, combined, and lyophilized. Calculated mass (M+2H) 2+ / 2: 1037.5m / z; found (M+2H) 2+ / 2:1038.0m / z.

[0785] Activity data

[0786] Cell culture

[0787] Z138 mantle cell lymphoma cell line was purchased from the American Type Culture Collection ( CRL-3001). The cell line was cultured in a humidified incubator at 37°C in a 5% CO2 atmosphere using IMDM medium supplemented with 10% fetal bovine serum, 100 I.U. / mL penicillin, and 100 μg / mL streptomycin.

[0788] Competitive binding assay

[0789] CHO:CXCR4 cells were cultured at 1×10 5 Cells were seeded at a density of 10 cells / well into 24-well poly-D-lysine-coated plates (Corning BioCoat) and [ 125 I] SDF-1α (0.01 nM, PerkinElmer) and competing non-radioactive ligands (1 μM to 0.1 pM) were incubated together. Cells, radioligands, and competing peptides were incubated at 27°C for 1 h with gentle shaking. After the incubation period, the supernatant was aspirated and the cells were washed three times with 1 mL of ice-cold PBS. Cells were harvested with 200 μL of trypsin and counted in a gamma counter. Data were plotted in GraphPad Prism 7 to determine IC 50 Values ​​were obtained using GraphPad Software, Inc., La Jolla, CA. These values ​​are reported as mean ± standard deviation. The results for a subset of compounds are shown in Table 7.

[0790] Radiolabeling

[0791] Elution was performed from an iThemba Labs generator with a total of 4 mL of 0.1 M HCl. 68 Ga]GaCl3. The eluted [ 68 The Ga]GaCl3 solution was added to 2 mL of concentrated HCl. The radioactive mixture was then added to a DGA resin column and washed with 3 mL of 5M HCl. The column was then air-dried and the [ 68 Ga]GaCl3 (0.10–0.50 GBq) was eluted with 0.5 mL of water into a vial containing an 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 controlled by analytical HPLC, with unlabeled standards co-injected with one-twelfth the radiotracer. The radiochemical yield (decay-corrected) was >50%, and the radiochemical purity was >95%.

[0792] Animal models

[0793] Animal experiments were performed in accordance with the guidelines established by the Canadian Council on Animal Care under research 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 into 100 μL of a 1:1 PBS / Matrigel solution. For preclinical imaging and biodistribution studies, 5 × 10 6 Z138 cells were inoculated subcutaneously in the left or right flank and the tumors were grown to 200-300 mm. 3 size.

[0794] PET / CT imaging

[0795] PET / CT imaging experiments were performed using a Siemens Inveon small animal PET / CT scanner. Approximately 6–8 MBq of CT was injected into each tumor-bearing mouse via the external caudal vein. 68 Ga-labeled tracer. 50 min after injection, a 10-min CT scan was performed for localization and attenuation correction after segmentation for reconstructing PET images; this scan was followed by a 10-min static PET acquisition.

[0796] use 177 Lu radiolabeling

[0797] For compounds conjugated with DOTA chelators, [ 177 Lu]LuCl3 (740-925 MBq) was added to a solution of the precursor (10 nmole) 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 compounds conjugated with crown chelators, [ 177 Lu]LuCl3 (810 MBq) was added to a solution of the precursor (10 nmole) 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 eluent fractions containing the radiolabeled product were collected, diluted with water (50 mL), and passed through a C18 Sep-Pak column pre-washed with ethanol (1 mL) and water (1 mL x 2). 177 The Lu-labeled product was eluted from the column with ethanol (0.4 mL) and diluted with 1% ascorbate in saline for imaging and biodistribution.Quality control and co-injection of natLu-labeled standards with the radiotracer were performed using an analytical column.

[0798] SPECT / CT imaging

[0799] SPECT / CT imaging experiments were performed using a MILabs U-SPECT-II / CT scanner. Tumor-bearing mice were injected with approximately 18.5-37 MBq of 177 Lu-labeled compounds. Mice were imaged 1, 4, 24, 72, and 120 h after injection. At each time point, a 5-min CT scan was first performed for anatomical reference; thereafter, two 30-min static emission scans were acquired in list mode. Results for 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, [ 68 Ga]Ga-BL34T1, [ 177 Lu]Lu-BL34T1 and [ 177 Lu]Lu-BL34L20S are respectively Figure 1-8 Displayed in.

[0800] Biodistribution

[0801] Under isoflurane anesthesia (2%-2.5% isoflurane in 2 L / min O2), mice were injected intravenously with [ 68 Ga]Ga-BL34L6 or [ 68 Ga]Ga-BL34L7. After anesthesia with isoflurane, mice were euthanized by inhalation of CO2. Tissues were harvested, washed with PBS, patted dry, weighed, and then radioactivity was determined on a gamma counter. The radioactivity counts were converted to percent injected dose per gram of tissue (ID / g%) using a calibration curve. The results for the compound subsets are shown in Tables 8-17.

[0802] Table 7: Binding affinity of BL34L6, BL34L7 and BL34L8 to hCXCR4

[0803] peptides <![CDATA[IC 50 (nM)]]> BL34L6 10-50 BL34L7 10-50 BL34L8 >100

[0804] Table 8: 68 Biodistribution data of Ga]Ga-BL34L6 in Z138 tumor-bearing mice at 1 h (pi) (ID / g%)

[0805]

[0806] Table 9: 68Biodistribution data of Ga]Ga-BL34L7 in Z138 tumor-bearing mice at 1 h (pi) (ID / g%)

[0807]

[0808]

[0809] Table 10: 68 Biodistribution data (ID / g%) of Ga]Ga-BL34L11 in Z138 tumor-bearing mice at 1 h and 3 h (pi)

[0810]

[0811] Table 11: 177 Biodistribution data (ID / g%) of Lu]Lu-BL34L11 in Z138 tumor-bearing mice at 1 h, 3 h, 24 h, 72 h, and 120 h (pi)

[0812]

[0813] Table 12: 68 Biodistribution data (ID / g%) of Ga]Ga-BL34L16 in Z138 tumor-bearing mice at 1 h and 3 h (pi)

[0814]

[0815]

[0816] Table 13: 177 Biodistribution data (ID / g%) of Lu]Lu-BL34L20 in Z138 tumor-bearing mice at 1 h, 3 h, 24 h, 72 h, and 120 h (pi)

[0817]

[0818] Table 14: 68 Biodistribution data of Ga]Ga-3NOPA-BL34L2 in Z138 tumor-bearing mice at 1 h (pi) (ID / g%)

[0819]

[0820]

[0821] Table 15: 177 Biodistribution data (ID / g%) of Lu]Lu-crown-BL34 in Z138 tumor-bearing mice at 1 h, 3 h, 24 h, 72 h, and 120 h (pi)

[0822]

[0823]

[0824] Table 16: 68 Biodistribution data of Ga]Ga-BL34N1 in Z138 tumor-bearing mice at 1 h (pi) (ID / g%)

[0825]

[0826] Table 17: 68 Biodistribution data of Ga]Ga-BL34T1 in Z138 tumor-bearing mice at 1 h and 3 h (pi) (ID / g%)

[0827]

[0828]

[0829] Incorporated by reference

[0830] All references, articles, publications, patents, patent publications and patent applications cited herein are incorporated by reference in their entirety for all purposes. However, the mention of any reference, article, publication, patent, patent publication and patent application cited herein is not, and should not be taken as, an admission or any form of representation that they constitute available prior art or form part of the common general knowledge in any country in the world.

[0831] References

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[0848] 17.Peng,S.et al.Identification of LY2510924,a Novel Cyclic PeptideCXCR4 Antagonist That Exhibits Antitumor Activities in Solid Tumor and BreastCancer Metastatic Models.Mol.Cancer Ther.14,480–491(2015).

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Claims

1. A compound of formula A, formula B or formula C or a salt or solvate thereof: in: R 2a Yes -(CH2)-(R 2b )-(phenyl), where R 2b is absent, is -CH2-, -NH-, -S- or -O-, wherein the phenyl group is optionally replaced by -NH2, -NO2, -OH, -OR 2c , -SH, -SR 2c , -N3, -CN or -O-phenyl 4-substituted, wherein the phenyl is optionally substituted with halogen or -OH 3-substituted, wherein the phenyl is optionally substituted with halogen or -OH 5-substituted, wherein the -O-phenyl ring is optionally substituted with -NH2, -NO2, -OH, -OR 2c , -SH, -SR 2c , -N3 or -CN 4-, wherein the -O-phenyl ring is optionally substituted by halogen or -OH 3-, wherein the -O-phenyl ring is optionally substituted by halogen or -OH 5-, wherein each R 2c are independently C1-C3 straight or branched chain alkyl; R 3a is C1-C5 alkyl or R 3b R 3c , where R 3b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbon atoms in C2-C5 are independently replaced by one or more N, S and / or O heteroatoms, wherein R 3c Yes – N(R 3d ) 2-3 or guanidino, where each R 3d is independently -H or a linear or branched C1-C3 alkyl group; R 4a YesR 4b R 4c , where R 4b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbon atoms in C2-C5 are independently replaced by one or more N, S and / or O heteroatoms, wherein R 4c Yes – N(R 4d ) 2-3 or guanidino, where each R 4d is independently -H or a linear or branched C1-C3 alkyl group; R 5a Yes - (CH2) 1-3 -R 5b , where -(CH2) 2-3 - is optionally replaced by a N, S or O heteroatom, wherein R 5b yes: Phenyl optionally substituted with one or a combination of: -NH2, -NO2, -OH, -OR 5c , -SH, -SR 5c , -N3, -CN or -O-phenyl 4-substituted; 3-substituted by halogen or -OH; and / or 5-substituted by halogen or -OH; wherein the -O-phenyl ring is optionally substituted by -NH2, -NO2, -OH, -OR 5c , -SH, –SR 5c , -N3 or -CN 4-, wherein the -O-phenyl ring is optionally substituted by halogen or -OH 3-, wherein the -O-phenyl ring is optionally substituted by halogen or -OH 5-; or A fused bicyclic or fused tricyclic aryl or heteroaryl ring, each optionally substituted by halogen, -OH, -OR 5c , amino, -NHR 5c and / or N(R 5c ) One or more substitutions in 2; Each R 5c are independently C1-C3 straight or branched chain alkyl; R 6a H, methyl, ethyl, -C≡CH, -CH=CH2, -C≡C-(CH2) 1-3 -OH, -C≡C-(CH2) 1-3 -SH, -C≡C-(CH2) 1-3 -NH2, -C≡C-(CH2) 1-3 -COOH, -C≡C-(CH2) 1-3 -CONH2, -C≡C-(CH2) 1-3 R 6b R 6c 、-CH=CH-(CH2) 1-3 -OH, -CH=CH-(CH2) 1-3 -SH, -CH=CH-(CH2) 1-3 -NH2, -CH=CH-(CH2) 1-3 -COOH, -CH=CH-(CH2) 1-3 -CONH2, -CH=CH-(CH2) 1-3 R 6b R 6c 、-CH2-R 6b -OH, -CH2-R 6b -COOH, -CH2-(R 6b ) 1-3 -NH2, -CH2-R 6b -CONH2 or -CH2-R 6b R 6c , where each R 6b are independently absent, are -CH2-, -NH-, -S- or -O-, and wherein R 6c yes: a 5- or 6-membered aromatic ring in which one or more carbons are optionally independently replaced by N, S and / or O heteroatoms, and optionally substituted by one or more groups independently selected from oxo, hydroxyl, thiol, nitro, amino and / or halogen; or -NH-CH(R 6a )-C(O)-NH- is replaced by: R A7a is a straight chain C1-C5 alkylene group, wherein 0-2 carbons in C2-C5 are independently replaced by one or more N, S and / or O heteroatoms; R 8a YesR 8b R 8c , where R 8b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbon atoms in the C2-C5 alkylene, alkenylene or alkynylene are independently replaced by one or more N, S and / or O heteroatoms, wherein R 8c Yes – N(R 8d ) 2-3 or guanidino, where each R 8d is independently -H or a linear or branched C1-C3 alkyl group; R 9a It is -C(O)NH2, -C(O)-OH, -CH2-C(O)NH2, -CH2-C(O)-OH, -CH2-NH2, -CH2-OH, -CH2-CH2-NH2, -R 9b -R 9c or -R 9b -[Connector]-R X n1 ,in: R 9b is -CH2-NH-C(O)-, -CH2-C(O)-, -CH2-O-, -C(O)NH-, -C(O)-N(CH3)-, -CH2-NHC(S)-, -C(S) NH-, -CH2-N(CH3)C(S)-, -C(O)N(CH3)-, -CH2-N(CH3)C(O)-, -C(S)N(CH3)-, -CH2-NHC(S) NH-, -CH2-NHC(O)NH-, -CH2-S-, -CH2-S(O)-, -CH2-S(O)2-, -CH2-S(O)2-NH-, -CH2-S(O)- NH-, -CH2-Se-, -CH2-Se(O)-, -CH2-Se(O)2-, -CH2-NHNHC(O)-, -C(O)NHNH-, -CH2-OP(O)(O - )O-, -CH2-phosphoramide-, -CH2-thiophosphate diester-, -CH2-S-tetrafluorophenyl-S-, or polyethylene glycol; and R 9c is hydrogen or a linear, branched and / or cyclic C1-C 20 Alkyl, alkenyl or alkynyl, wherein C2-C 20 0-6 carbon atoms in the is independently replaced by N, S and / or O heteroatoms, and 0-3 groups independently selected from one or a combination of oxo, hydroxyl, thiol, halogen, guanidino, carboxylic acid, sulfonic acid, sulfinic acid and / or phosphoric acid are substituted; R A10 Does not exist or -[connector]-R X n1 ; When R A10 If it does not exist, then R A1a yes: Straight chain C1-C5 alkyl, C2-C5 alkenyl or C2-C5 alkynyl, wherein 0-2 carbons in the C2-C5 alkyl, alkenyl or alkynyl are independently replaced by one or more N, S and / or O heteroatoms, optionally C-substituted by a monosubstituent selected from the following: -SH, -OH, amino, carboxyl, guanidino, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH3) 1-2 、-NH2-CH3、-N(CH3) 2-3 , -S-CH3 or -O-CH3; Branched chain C1-C 10 Alkyl, alkenyl or alkynyl, wherein C2-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 straight chain C1-C3 alkylene group, wherein the C2 alkylene group or the C3 alkylene group is optionally replaced by a N, S or O heteroatom, wherein R A1c yes: A 5 or 6 membered aromatic ring in which one or more carbons are optionally independently replaced by N, S and / or O heteroatoms, and optionally substituted by one or more groups independently selected from oxo, hydroxyl, thiol, nitro, amino and / or halogen; or A fused bicyclic or fused tricyclic aryl group wherein one or more carbon atoms are optionally independently replaced by N, S and / or O heteroatoms and optionally independently selected from halogen, -OH, -OR A1d , amino, -NHR A1d and / or N(R A1d )2 is substituted with one or more groups, wherein each R A1d are independently C1-C3 straight or branched chain alkyl; When R A10 Yes-[Connector]-R X n1 , then R A1a YesR A1e R A1f , where R A1e is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbon atoms in the C2-C5 alkylene, alkenylene or alkynylene are independently replaced by N, S and / or O heteroatoms, and R A1f is -NH-C(O)-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C(S)NH-, -N(CH3)C(S)-, -C(O)N(CH3)-, -N(CH3)C(O)-, -C(S)N(CH3)-, -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-, -phosphoramide-, -phosphorothioate diester-, -S-tetrafluorophenyl-S-, or polyethylene glycol; R B1a It is a straight chain, branched chain and / or cyclic C1-C 10 Alkylene, C2-C 10 Alkenylene or C2-C 10 Alkyne, where C2-C 10 One or more carbon atoms in the alkylene, alkenylene, alkynylene groups are optionally independently replaced by N, S and / or O heteroatoms; R B1-7 yes wherein the indole ring and the isoindole ring are each optionally substituted with -F, -Br, -Cl, -I, -OH, -OR B1-7b , -CO-, -COOH, -CONH2, -CN, -O-aryl, -NH2, -NHR B1-7b , N3, -NO2, -NH, -CHO and / or -R B1-7b One or more substitutions in which each R B1-7b is a straight or branched C1-C3 alkyl, C2-C3 alkenyl or C2-C3 alkynyl; R B7a is a straight chain C1-C5 alkylene group, wherein 0-2 carbons in the C2-C5 alkylene group are independently replaced by one or more N, S and / or O heteroatoms; R B10a It is an amine, -NH-(CH3) 1-2 、-N(CH3) 2-3 , -NH-C(O)-CH3, -NH-C(O)-(phenyl) or –R B10b -[Connector]-R X n1 , where R B10b yes: -NH-C(O)-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C(S)NH-, -N(CH3)C(S)-, -C(O)N(CH3)-, -N(CH3)C(O)-, -C(S)N(CH3)-, -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-, -phosphoramide-, -phosphorothioate diester-, -S-tetrafluorophenyl-S-, or polyethylene glycol; R C1a yes wherein the indole, the isoindole and the triazole ring are each optionally substituted with -F, -Br, -Cl, -I, -OH, -OR C1b , -CO-, -COOH, -CONH2, -CN, -O-aryl, -NH2, -NHR C1b , N3, -NO2, -NH, -CHO and / or –R C1b One or more substitutions in which each R C1b is a straight or branched C1-C3 alkyl, C2-C3 alkenyl or C2-C3 alkynyl; R C7a is a straight chain C1-C5 alkylene group, wherein optionally, 0-2 carbons in the C2-C5 alkylene group are independently replaced by one or more N, S and / or O heteroatoms; R C10a YesR C10b -R C10c -[Connector]-R X n1 or R C10d ,in: R C10b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbon atoms in the C2-C5 alkylene, alkenylene or alkynylene are independently replaced by N, S and / or O heteroatoms; R C10c is -NH-C(O)-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C(S)NH-, -N(CH3)C(S)-, -C(O)N(CH3)-, -N(CH3)C(O)-, -C(S)N(CH3)-, -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-, -phosphoramide-, -phosphorothioate diester-, -S-tetrafluorophenyl-S-, or polyethylene glycol; and R C10d yes: Straight chain C1-C5 alkyl, C2-C5 alkenyl or C2-C5 alkynyl, wherein 0-2 carbons in the C2-C5 alkyl, alkenyl or alkynyl are independently replaced by N, S and / or O heteroatoms, optionally C-substituted by a monosubstituent selected from the following: -SH, -OH, amino, carboxyl, guanidino, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH3) 1-2 、-NH2-CH3、-N(CH3) 2-3 , -S-CH3 or -O-CH3; Branched chain C1-C 10 Alkyl, C2-C 10 Alkenyl or C2-C 10 Alkynyl, where C2-C 10 0-3 carbons in the alkyl, alkenyl or alkynyl group are independently replaced by N, S and / or O heteroatoms; or R C10e R C10f , where R C10e is a straight chain C1-C3 alkyl group, wherein the C2 alkyl group or the C3 alkyl group is optionally replaced by a N, S or O heteroatom, wherein R C10f yes: a 5- or 6-membered aromatic ring in which one or more carbons are optionally independently replaced by N, S and / or O heteroatoms, and optionally substituted by one or more groups independently selected from oxo, hydroxyl, thiol, nitro, amino and / or halogen; A fused bicyclic or fused tricyclic aryl group wherein one or more carbon atoms are optionally independently replaced by N, S and / or O heteroatoms and optionally independently selected from halogen, -OH, -OR C10g , amino, -NHR C10g and / or N(R C10g )2 is substituted with one or more groups, wherein R C10g is a C1-C3 straight or branched chain alkyl group; R y is hydrogen or R 3e R 3f , where R 3e is a straight chain C1-C5 alkylene group, wherein R 3f Yes – N(R 3g ) 2-3 , where each R 3g is independently -H or a linear or branched C1-C3 alkyl group; Each n1 is independently 0, 1 or 2; Each R X is an albumin binder, a therapeutic moiety, a fluorescent marker, a radiolabeled group, or a group capable of being radiolabeled; wherein 0-3 peptide backbone amides are independently Amidine or thioamide substitution; wherein 0-3 of the peptide backbone amides are N-methylated; and wherein the C-terminus is optionally amidated.

2. The compound of claim 1, wherein: R A10 Yes-[Connector]-R X n1 ; The connector is X 1 L 1 , X 1 L 1 X 1 L 1 , X 1 L 1 X 1 L 1 X 1 L 1 ; X 1 are independently -CH2-, L 1 each independently is –NH–, –C(O)–, –NHC(O)–, –C(O)NH–, –N(CH3)C(O)– or –C(O)N(CH3)–; R 11 are each independently a carboxylic acid, a sulfonic acid, a sulfinic acid or a phosphoric acid; and R Z Each is independently an albumin binder.

3. The compound according to claim 1 or 2, wherein: a) R 9a YesR 9b -[Connector]R x n1 ; b) R 3a is a C1-C5 alkyl group; c) R y YesR 3e R 3f ; d) at least one peptide backbone amide is N-methylated; or e) At least one peptide backbone amide is replaced by an amidine.

4. The compound according to any one of claims 1 to 3, wherein: a) R C1a yes b) R C1a yes wherein the indole ring and the isoindole ring are each optionally substituted with -F, -Br, -Cl, -I, -OH, -OR C1b , -CO-, -COOH, -CONH2, -CN, -O-aryl, -NH2, -NHR C1b , N3, -NO2, -NH, -CHO and / or –R C1b One or more substitutions in which each R C1b is a straight or branched C1-C3 alkyl, C2-C3 alkenyl or C2-C3 alkynyl group; provided that the compound of formula C is not cyclo(isoindole)[Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-D-Cys]-Lys(iPr)-NH2, cyclo(isoindole)[Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-Cys]-Lys(iPr)-NH2, cyclo(isoindole)[Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-Cys]-Lys(iPr)-NH2, cyclo(isoindole)[Phe-Tyr-Lys(iPr)-D-Arg-2-Nal-Gly-Cys]-Lys(iPr)-NH2, a -S)[Lys(Cys(acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH2, Cyclo(Me-isoindole N a -S)[Lys(Cys(acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH2, Cyclo(NO2-isoindole N a -S)[Lys(Cys(acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-Cys]-Lys(iPr)-NH2 and cyclo(NO2-isoindole N a -S)[Lys(Cys(acid)-DOTA-Ga)-Tyr-Lys(iPr)-D-Arg-2-Nal-D-Ala-D-hCys]-Lys(iPr)-NH2.

5. The compound of any one of claims 1 to 4, wherein R C1a yes 6. The compound of claim 1, wherein R C1a yes 7. The compound according to claim 5 or 6, wherein R C7a It is a straight chain C1-C2 alkylene group.

8. The compound of claim 2, wherein at least one X 1 yes 9. The compound of claim 2 or 8, wherein the linker is X 1 L 1 ;X 1 yes And L 1 It is –NH– or –NHC(O)–.

10. The compound of claim 2 or 8, wherein: The connector is X 1a L 1a X 1b L 1b ; X 1a yes L 1a is –NH– or –NHC(O)–; X 1b yes and L 1b It is –NH– or –NHC(O)–.

11. The compound of claim 2 or 8, wherein: The connector is X 1a L 1a X 1b L 1b ; X 1a yes L 1a is –NH– or –NHC(O)–; X 1b yes and L 1b It is –NH– or –NHC(O)–.

12. The compound of claim 2, wherein: The connector is X 1a L 1a X 1b L 1b ; X 1a yes L 1a is –NH– or –NHC(O)–; X 1b yes and L 1b It is –NH– or –NHC(O)–.

13. The compound of claim 2 or 8, wherein: The connector is X 1a L 1a X 1b L 1b X 1c L 1c ; X 1a yes L 1a is –NH– or –NHC(O)–; X 1b yes L 1b is –NH– or –NHC(O)–; X 1c is –CH2–; and L 1c It is –NH–– or –NHC(O)–.

14. The compound of claim 2 or 8, wherein: The connector is X 1a L 1a X 1b L 1b X 1c L 1c ; X 1a yes L 1a is –NH– or –NHC(O)–; X 1b is –CH2–; L 1b is –NH– or –NHC(O)–; X 1c yes and L 1c It is –NH– or –NHC(O)–.

15. A compound as described in any one of claims 2 and 8-14, wherein R 11 It is sulfonic acid (-SO3H).

16. The compound of any one of claims 1 to 15, wherein: R 9a YesR 9b -[Connector]-R x n1 ; R 9b is -C(O)NH-; The connector is X 1 L 1 ; X 1 Yes - (CH2) 1-5 -、-CH(COOH)-(CH2) 0-4 -or-CH(CONH2)-(CH2) 0-4 -;and L 1 Each is independently –NH–, –C(O)–, –NHC(O)–, –C(O)NH–, –N(CH 3 )C(O)–, or –C(O)N(CH 3 )–.

17. The compound of claim 16, wherein R x n1 It is an albumin binder.

18. The compound of any one of claims 1 to 17, wherein the albumin binder is -(CH2) 8-20 -CH3, -(CH2) 8-20 -C(O)OH or Where R 12 It is I, Br, F, Cl, H, OH, OCH3, NH2, NO2 or CH3.

19. The compound of claim 18, wherein the albumin binder is Where R 12 It is I, Br, F, Cl, H, OH, OCH3, NH2, NO2 or CH3.

20. The compound of any one of claims 1-19, wherein at least one peptide backbone amide is N-methylated.

21. A compound as described in any one of claims 1 to 20, wherein R y It's methyl.

22. The compound of any one of claims 1-21, wherein at least one peptide backbone amide is replaced by an amidine.

23. A compound as described in any one of claims 1 to 22, wherein R 3a and R 4a ; R 4a and R 5a ; or R 5a and R 6a The amide backbone between them is amidine (-CH(R 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 )-) alternative.

24. A compound as described in any one of claims 1 to 23, wherein R y YesR 3e R 3f , where R 3e is a straight chain C1-C5 alkylene group, wherein R 3f Yes – N(R 3g )2, where each R 3g are independently -H or a linear or branched C1-C3 alkyl group.

25. The compound of claim 24, wherein R 3a It's methyl.

26. The compound of claim 1, wherein R 2a Yes -(CH2)-(R 2b )-(phenyl), where R 2b is absent, is -CH2-, -NH-, -S- or -O-, wherein the phenyl group is optionally replaced by -NH2, -NO2, -OH, -OR 2c , -SH, -SR 2c , -N3, -CN or -O-phenyl 4-, or optionally substituted by halogen or -OH 3-, wherein each R 2c are independently C1-C3 straight or branched chain alkyl.

27. A compound as described in any one of claims 1-26, wherein -NH-CH (R 2a )-C(O)- to form an L amino acid residue.

28. A compound as described in any one of claims 1 to 27, wherein -NH-CH (R 2a )-C(O)- forms a Tyr residue, a Phe residue, a (4-NO2)-Phe residue, a (4-NH2)-Phe residue, an hTyr residue, a (3-I)Tyr residue, a Glu residue, a Gln residue or a D-Tyr residue.

29. A compound as described in any one of claims 1-22 and 26-28, wherein R 3a YesR 3b R 3c , where R 3b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein R 3c Yes – N(R 3d ) 2-3 or guanidino, where each R 3d are independently -H or a linear or branched C1-C3 alkyl group.

30. A compound as described in any one of claims 1-29, wherein -NR y -CH(R 3a )-C(O)- or -NH-CH(R) of formula B or C 3a )-C(O)- to form an L amino acid residue.

31. A compound as described in any one of claims 1-29, wherein -NR of formula A y -CH(R 3a )-C(O)- or -NH-CH(R) of formula B or C 3a )-C(O)- forms a Lys(iPr) residue, an Arg(Me)2 (asymmetric) residue or an Arg(Me) residue.

32. A compound as described in any one of claims 1 to 31, wherein R 4a YesR 4b R 4c , where R 4b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein R 4c Yes – N(R 4d ) 2-3 or guanidino, where each R 4d are independently -H or a linear or branched C1-C3 alkyl group.

33. A compound as described in any one of claims 1-32, wherein -NH-CH (R 4a )-C(O)- forms a D amino acid residue.

34. A compound as described in any one of claims 1-33, wherein -NH-CH(R 4a )-C(O)- forms a D-Arg residue or a D-hArg residue.

35. A compound as described in any one of claims 1 to 34, wherein R 5a Yes - (CH2) 1-3 -R 5b , where R 5b yes: Phenyl optionally substituted by one or more of: 4-substituted by -NH2, -NO2, -OH, -SH, -N3, -CN or -O-phenyl; 3-substituted by halogen or -OH; and / or 5-substituted by halogen or -OH; or A fused bicyclic or fused tricyclic aryl or heteroaryl ring, which is optionally substituted by halogen, -OH, -OR 5c , amino, -NHR 5c and / or N(R 5c )2 in one or more substitutions; and Where R 5c Each is independently a C1-C3 straight or branched chain alkyl group.

36. A compound as described in any one of claims 1-35, wherein -NH-CH (R 5a )-C(O)- to form an L amino acid residue.

37. A compound as described in any one of claims 1-36, wherein -NH-CH (R 5a )-C(O)- forms a 2-(Ant)Ala residue, a 2-Nal residue, a Trp residue, a (4-NH2)Phe residue, an hTyr residue or a Tyr residue.

38. A compound as described in any one of claims 1 to 37, wherein R 6a H, methyl, ethyl, -C≡CH, -CH=CH2, -CH2-R 6b -OH, -CH2-R 6b -COOH, -CH2-(R 6b ) 1-3 -NH2, -CH2-R 6b -CONH2 or -CH2-R 6b R 6c , where each R 6b independently absent, is -CH2-, -NH-, -S- or -O-; and wherein R 6c is a 5- or 6-membered aromatic ring in which 0-3 carbons are independently replaced by N, S and / or O heteroatoms, and is optionally substituted by 0-3 groups independently selected from oxo, hydroxy, thiol, nitro, amino and / or halogen.

39. A compound as described in any one of claims 1-37, wherein -NH-CH (R 6a )-C(O)-NH- is replaced by:

40. A compound as described in any one of claims 1-39, wherein -NH-CH (R 6a )-C(O)- forms a D amino acid residue.

41. A compound as described in any one of claims 1-40, wherein -NH-CH (R 6a )-C(O)- forms a His residue, a D-His residue, a D-Glu residue, a D-Gln residue, a D-Ala residue, a D-Phe residue, a D-Ser residue, a D-Dab residue, or a D-Dap residue.

42. A compound as described in any one of claims 1 to 41, wherein R 8a YesR 8b R 8c , where R 8b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein R 8c Yes – N(R 8d ) 2-3 or guanidino, where each R 8d are independently -H or a linear or branched C1-C3 alkyl group.

43. The compound of any one of claims 1 to 42, wherein: R 9a It is -C(O)NH2, -C(O)-OH, -R 9b -R 9c or -R 9b -[Connector]-R X n1 ;and R 9b CH3-C(O)NH-、-C(O)-N(CH3)-、-C(O)N(CH3)- 44. A compound as described in any one of claims 1-43, wherein -NH-CH (R 8a )-with R 9a -C(O)- together with the -C(O)- to form an L amino acid residue.

45. The compound of any one of claims 1-44, wherein -NH-CH (R 8a )-with R 9a The -C(O)- of the two molecules together form a Lys(iPr) residue.

46. ​​A compound as described in any one of claims 1-45, wherein R 9a is -C(O)NH2, -C(O)-OH, -CH2-C(O)NH2, -CH2-C(O)-OH or -R 9b -R 9c ; R 9b is –C(O)NH–; and R 9c yes Where R 9d is a straight chain or branched C1-C5 alkylene group, R 9e is carboxylic acid, sulfonic acid, sulfinic acid, phosphoric acid, amino, guanidino, -SH, -OH, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-CH3, -N(CH3)2, -S-CH3, -O-CH3 or phenyl, and R 9f It is amino or –OH.

47. A compound as described in any one of claims 1-45, wherein R 9a Yes-R 9b -[Connector]-R X n1 .

48. A compound as described in any one of claims 1-47, wherein R 9b It is –C(O)NH–.

49. A compound as described in any one of claims 1-48, wherein -NH-CH (R A1a )-C(O)- to form an L amino acid residue.

50. A compound as described in any one of claims 1-49, wherein -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.

51. A compound as described in any one of claims 1-50, wherein R A10 Yes-[Connector]-R X n1 .

52. A compound as described in any one of claims 1-51, wherein -NH-CH (R A7a )-C(O)- forms a D amino acid residue.

53. A compound as described in any one of claims 1-52, wherein R A7a It is a C1-C3 alkyl group.

54. A compound as described in any one of claims 1-53, wherein R B1-7 yes 55. A compound as described in any one of claims 1-48, wherein R B1a Yes – (CH2) 1-2 -, R B1-7 yes And R B7a Yes – (CH2) 1-2 -.

56. A compound as described in any one of claims 1-47, wherein R B1a -R B1-7 -R B7a yes 57. A compound as described in any one of claims 1-48 and 54-56, wherein -NH-CH (R B7a )-C(O)- forms a D amino acid residue.

58. A compound as described in any one of claims 1-48 and 54-57, wherein R B10a It is an amine, -NH-(CH3) 1-2 、-N(CH3) 2-3 , -NH-C(O)-CH3 or -NH-C(O)-(phenyl).

59. A compound as described in any one of claims 1-48 and 54-58, wherein R B10a Yes-R B10b -[Connector]-R X n1 .

60. The compound of claim 59, wherein R B10b yes: -NH-C(O)-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C(S)NH-, -N(CH3)C(S)-, -C(O)N(CH3)-, -N(CH3)C(O)-, -C(S)N(CH3)-, -NHC(S)NH-, -NHC(O)NH-, -NHNHC(O)-, -C(O)NHNH-, or polyethylene glycol.

61. The compound of claim 59, wherein R B10a Yes – NHC(O)-[Connector]-R X n1 or –N(CH3)C(O)-[Linker]-R X n1 .

62. A compound as described in any one of claims 1-48, wherein -NH-CH (R C7a )-C(O)- forms a D amino acid residue.

63. A compound as described in any one of claims 1-48 and 62, wherein R C7a It is a straight chain C1-C5 alkylene group.

64. A compound as described in any one of claims 1-48 and 62-63, wherein R C10a YesR C10b -R C10c -[Connector]-R X n1 .

65. The compound of claim 64, wherein R C10b is a straight chain C1-C5 alkylene group; and R C10c yes: -NH-C(O)-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C(S)NH-, -N(CH3)C(S)-, -C(O)N(CH3)-, -N(CH3)C(O)-, -C(S)N(CH3)-, -NHC(S)NH-, -NHC(O)NH-, -NHNHC(O)-, -C(O)NHNH-, or polyethylene glycol.

66. A compound as described in any one of claims 1-48 and 61-63, wherein R C10a YesR C10d , where R C10d yes: a) straight-chain C1-C5 alkyl, C2-C5 alkenyl or C2-C5 alkynyl, optionally C-substituted with a monosubstituent selected from the group consisting of -SH, -OH, amino, carboxyl, guanidino, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH3) 1-2 、-NH2-CH3、-N(CH3) 2-3 , -S-CH3, -O-CH3; b) Branched chain C1-C 10 Alkyl, C2-C 10 Alkenyl or C2-C 10 Alkynyl; or c)R C10e R C10f ; Where R C10e is a straight chain C1-C3 alkyl group; and R C10f yes (i) a 5- or 6-membered aromatic ring in which 0-4 carbons are independently replaced by N, S and / or O heteroatoms and substituted by 0-4 groups independently selected from oxo, hydroxyl, thiol, nitro, amino and / or halogen; or (ii) a fused bicyclic or tricyclic aryl group, wherein 0-6 carbon atoms are independently replaced by N, S and / or O heteroatoms and are independently selected from halogen, -OH, -OR C10g , amino, -NHR C10g and / or N(R C10g )2 is substituted with 0 to 6 groups, wherein R C10g It is a C1-C3 straight chain or branched chain alkyl group.

67. The compound of claim 1, wherein the compound has a structure of Formula AI or a salt or solvate thereof: in: R 2a Yes -(CH2)-(R 2b )-(phenyl), where R 2b is absent, is -CH2-, -NH-, -S- or -O-, wherein the phenyl group is optionally replaced by -NH2, -NO2, -OH, -OR 2c , -SH, -SR 2c , -N3, -CN or -O-phenyl4-, or optionally substituted by halogen or -OH3-, wherein each R 2c are independently C1-C3 straight or branched chain alkyl; R 3a YesR 3b R 3c , where R 3b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein R 3c Yes – N(R 3d ) 2-3 or guanidino, where each R 3d is independently -H or a linear or branched C1-C3 alkyl group; R 4a YesR 4b R 4c , where R 4b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein R 4c Yes – N(R 4d ) 2-3 or guanidino, where each R 4d is independently -H or a linear or branched C1-C3 alkyl group; R 5a Yes - (CH2) 1-3 -R 5b , where R 5b yes: Phenyl optionally substituted with one or more of: 4-substituted with -NH2, -NO2, -OH, -SH, -N3, -CN or -O-phenyl; 3-substituted with halogen or -OH; and / or 5-substituted with halogen or -OH; A fused bicyclic or fused tricyclic aryl or heteroaryl ring, which is optionally substituted by halogen, -OH, -OR 5c , amino, -NHR 5c and / or N(R 5c )2 in one or more substitutions; and Where R 5c Each is independently a C1-C3 straight or branched chain alkyl; R 6a H, methyl, ethyl, -C≡CH, -CH=CH2, -CH2-R 6b -OH, -CH2-R 6b -COOH, -CH2-(R 6b ) 1-3 -NH2, -CH2-R 6b -CONH2 or -CH2-R 6b R 6c , where each R 6b independently absent, is -CH2-, -NH-, -S- or -O-; and wherein R 6c is a 5- or 6-membered aromatic ring in which 0-3 carbons are independently replaced by N, S and / or O heteroatoms, and is optionally substituted by 0-3 groups independently selected from oxo, hydroxyl, thiol, nitro, amino and / or halogen; R 8a YesR 8b R 8c , where R 8b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein R 8c Yes – N(R 8d ) 2-3 or guanidino, where each R 8d is independently -H or a linear or branched C1-C3 alkyl group; R 9a It is -C(O)NH2, -C(O)-OH, -CH2-C(O)NH2, -CH2-C(O)-OH, -R 9b -R 9c or -R 9b -[Connector]-R X n1 ; where R 9b is –C(O)NH–; and R 9c yes Where R 9d is a straight chain or branched C1-C5 alkylene group, R 9e is carboxylic acid, sulfonic acid, sulfinic acid, phosphoric acid, amino, guanidino, -SH, -OH, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-CH3, -N(CH3)2, -S-CH3, -O-CH3 or phenyl, and R 9f is amino or –OH; R A7a is C1-C3 alkylene; R A10 Does not exist or -[connector]-R X n1 ; When R A10 If it does not exist, then R A1a yes: Straight chain C1-C5 alkyl, C2-C5 alkenyl or C2-C5 alkynyl, wherein 0-2 carbons in the C2-C5 alkyl, alkenyl or alkynyl are independently replaced by one or more N, S and / or O heteroatoms, optionally C-substituted by a monosubstituent selected from the following: -SH, -OH, amino, carboxyl, guanidino, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH3) 1-2 、-NH2-CH3、-N(CH3) 2-3 , -S-CH3 or -O-CH3; Branched chain C1-C 10 Alkyl, alkenyl or alkynyl, wherein C2-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 straight chain C1-C3 alkylene group, wherein the C2 alkylene group or the C3 alkylene group is optionally replaced by a N, S or O heteroatom, wherein R A1c yes: A 5 or 6 membered aromatic ring in which one or more carbons are optionally independently replaced by N, S and / or O heteroatoms, and optionally substituted by one or more groups independently selected from oxo, hydroxyl, thiol, nitro, amino and / or halogen; or A fused bicyclic or fused tricyclic aryl group wherein one or more carbon atoms are optionally independently replaced by N, S and / or O heteroatoms and optionally independently selected from halogen, -OH, -OR A1d , amino, -NHR A1d and / or N(R A1d )2 is substituted with one or more groups, wherein each R A1d are independently C1-C3 straight or branched chain alkyl; When R A10 Yes-[Connector]-R X n1 When R A1a YesR A1e R A1f ,in: R A1e is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbons in the C2-C5 alkylene, alkenylene or alkynylene are independently replaced by N, S and / or O heteroatoms; R A1f is -NH-C(O)-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C(S)NH-, -N(CH3)C(S)-, -C(O)N(CH3)-, -N(CH3)C(O)-, -C(S)N(CH3)-, -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-, -phosphoramide-, -phosphorothioate diester-, -S-tetrafluorophenyl-S-, or polyethylene glycol; The connector 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 ; X 1 are independently -CH2-, L 1 each independently is –NH–, –C(O)–, –NHC(O)–, –C(O)NH–, –N(CH3)C(O)– or –C(O)N(CH3)–; R 11 are each independently a carboxylic acid, a sulfonic acid, a sulfinic acid or a phosphoric acid; and R Z each independently is an albumin binder; Each n1 is independently 0, 1 or 2; Each R X is an albumin binder, a therapeutic moiety, a fluorescent label, a radiolabeled group, or a group capable of being radiolabeled; 0-3 peptide backbone amides are independently Amidine or thioamide substitution; wherein 0-3 of the peptide backbone amides are N-methylated; and wherein the C-terminus is optionally amidated.

68. The compound of claim 1 or 67, wherein the compound has a structure of Formula A-II or a salt or solvate thereof: in: -NH-CH(R 2a )-C(O)- forms a Tyr residue, a Phe residue, a (4-NO2)-Phe residue, a (4-NH2)-Phe residue, an hTyr residue, a (3-I)Tyr residue, a Glu residue, a Gln residue or a D-Tyr residue; -NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue, an Arg(Me)2(asymmetric) residue or an Arg(Me) residue; -NH-CH(R 4a )-C(O)- forms a D-Arg residue or a D-hArg residue; -NH-CH(R 5a )-C(O)- forms a 2-(Ant)Ala residue, a 2-Nal residue, a Trp residue, a (4-NH2)Phe residue, an hTyr residue or a Tyr residue; -NH-CH(R 6a )-C(O)- forms a His residue, a D-His residue, a D-Glu residue, a D-Gln residue, a D-Ala residue, a D-Phe residue, a D-Ser residue, a D-Dab residue, or a D-Dap residue; R 8a YesR 8b R 8c , where R 8b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein R 8c Yes – N(R 8d ) 2-3 or guanidino, where each R 8d is independently -H or a linear or branched C1-C3 alkyl group; R 9a is -C(O)NH2, -C(O)-OH, -CH2-C(O)NH2, -CH2-C(O)-OH or -R 9b -[Connector]-R X n1 ; R 9b is –C(O)NH–; R A7a is C1-C3 alkylene; R A10 Does not exist or -[connector]-R X n1 ; When R A10 If it does not exist, then R A1a is a straight chain C1-C5 alkyl group, optionally substituted by a monosubstituent selected from the group consisting of -SH, -OH, amino, carboxyl, guanidino, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH3) 1-2 、-NH2-CH3、-N(CH3) 2-3 , -S-CH3, -O-CH3 or branched C1-C 10 alkyl, alkenyl or alkynyl; When R A10 Yes-[Connector]-R X n1 When R A1a YesR A1e R A1f ,in: R A1e is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbons in the C2-C5 alkylene, alkenylene or alkynylene are independently replaced by N, S and / or O heteroatoms; R A1f is -NH-C(O)-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C(S)NH-, -N(CH3)C(S)-, -C(O)N(CH3)-, -N(CH3)C(O)-, -C(S)N(CH3)-, -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-, -phosphoramide-, -phosphorothioate diester-, -S-tetrafluorophenyl-S-, or polyethylene glycol; The connector 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 ; X 1 are independently -CH2-, L 1 each independently is –NH–, –C(O)–, –NHC(O)–, –C(O)NH–, –N(CH3)C(O)– or –C(O)N(CH3)–; R 11 are each independently a carboxylic acid, a sulfonic acid, a sulfinic acid or a phosphoric acid; and R Z each independently is an albumin binder; Each n1 is independently 0, 1 or 2; Each R X is an albumin binder, a therapeutic moiety, a fluorescent label, a radiolabeled group, or a group capable of being radiolabeled; 0-3 peptide backbone amides are independently Amidine or thioamide substitution; wherein 0-3 of the peptide backbone amides are N-methylated; and wherein the C-terminus is optionally amidated.

69. The compound of claim 67 or 68, wherein -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.

70. A compound as described in any one of claims 67-69, wherein R A10 Yes-[Connector]-R X n1 , and R 9a It is -C(O)NH2, -C(O)-OH, -CH2-C(O)NH2 or -CH2-C(O)-OH.

71. The compound of any one of claims 67-70, wherein at least one X 1 yes 72. The compound of any one of claims 67-70, wherein the linker is X 1 L 1 ;X 1 yes And L 1 It is –NH– or –NHC(O)–.

73. The compound of any one of claims 67-70, wherein: The connector is X 1a L 1a X 1b L 1b ; X 1a yes L 1a is –NH– or –NHC(O)–; X 1b yes and L 1b It is –NH– or –NHC(O)–.

74. The compound of any one of claims 67-70, wherein: The connector is X 1a L 1a X 1b L 1b ; X 1a yes L 1a is –NH– or –NHC(O)–; X 1b yes and L 1b It is –NH– or –NHC(O)–.

75. The compound of any one of claims 67-70, wherein: The connector is X 1a L 1a X 1b L 1b ; X 1a yes L 1a is –NH– or –NHC(O)–; X 1b yes and L 1b It is –NH– or –NHC(O)–.

76. The compound of any one of claims 67-70, wherein: The connector is X 1a L 1a X 1b L 1b X 1c L 1c ; X 1a yes L 1a is –NH– or –NHC(O)–; X 1b yes L 1b is –NH– or –NHC(O)–; X 1c is –CH2–; and L 1c It is –NH– or –NHC(O)–.

77. The compound of any one of claims 67-70, wherein: The connector is X 1a L 1a X 1b L 1b X 1c L 1c ; X 1a yes L 1a is –NH– or –NHC(O)–; X 1b is –CH2–; L 1b is –NH– or –NHC(O)–; X 1c yes and L 1c It is –NH– or –NHC(O)–.

78. A compound as described in any one of claims 67-77, wherein R 11 It is sulfonic acid (-SO3H).

79. The compound of any one of claims 67-78, wherein: R 9a YesR 9b -[Connector]-R x n1 ; R 9b is -C(O)NH-; The connector is X 1 L 1 ; X 1 Yes - (CH2) 1-5 -、-CH(COOH)-(CH2) 0-4 -or-CH(CONH2)-(CH2) 0-4 -;and L 1 Each is independently –NH–, –C(O)–, –NHC(O)–, –C(O)NH–, –N(CH 3 )C(O)–, or –C(O)N(CH 3 )–.

80. The compound of claim 79, wherein R x It is an albumin binder.

81. The compound of any one of claims 67-80, wherein the albumin binder is -(CH2) 8-20 -CH3, -(CH2) 8-20 -C(O)OH or Where R 12 It is I, Br, F, Cl, H, OH, OCH3, NH2, NO2 or CH3.

82. The compound of claim 81, wherein the albumin binder is Where R 12 It is I, Br, F, Cl, H, OH, OCH3, NH2, NO2 or CH3.

83. The compound of any one of claims 67-82, wherein one peptide backbone amide is N-methylated.

84. A compound as described in any one of claims 67-83, wherein one of the peptide backbone carbonyl groups is replaced by an imino group.

85. The compound of claim 1, wherein the compound has a structure of Formula A-III or a salt or solvate thereof: in: R 2a Yes -(CH2)-(R 2b )-(phenyl), where R 2b is absent, is -CH2-, -NH-, -S- or -O-, wherein the phenyl group is optionally replaced by -NH2, -NO2, -OH, -OR 2c , -SH, -SR 2c , -N3, -CN or -O-phenyl4-, or optionally substituted by halogen or -OH3-, wherein each R 2c are independently C1-C3 straight or branched chain alkyl; R 3a is a C1-C5 alkyl group; R y is hydrogen or R 3e R 3f , where R 3e is a straight chain C1-C5 alkylene group, wherein R 3f Yes – N(R 3g ) 2-3 , where each R 3g is independently -H or a linear or branched C1-C3 alkyl group; R 4a YesR 4b R 4c , where R 4b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein R 4c Yes – N(R 4d ) 2-3 or guanidino, where each R 4d is independently -H or a linear or branched C1-C3 alkyl group; R 5a Yes - (CH2) 1-3 -R 5b , where R 5b yes: Phenyl optionally substituted with one or more of: 4-substituted with -NH2, -NO2, -OH, -SH, -N3, -CN or -O-phenyl; 3-substituted with halogen or -OH; and / or 5-substituted with halogen or -OH; A fused bicyclic or fused tricyclic aryl or heteroaryl ring, which is optionally substituted by halogen, -OH, -OR 5c , amino, -NHR 5c and / or N(R 5c )2 in one or more substitutions; and Where R 5c Each is independently a C1-C3 straight or branched chain alkyl; R 6a H, methyl, ethyl, -C≡CH, -CH=CH2, -CH2-R 6b -OH, -CH2-R 6b -COOH, -CH2-(R 6b ) 1-3 -NH2, -CH2-R 6b -CONH2 or -CH2-R 6b R 6c , where each R 6b independently absent, is -CH2-, -NH-, -S- or -O-; and wherein R 6c is a 5- or 6-membered aromatic ring in which 0-3 carbons are independently replaced by N, S and / or O heteroatoms, and is optionally substituted by 0-3 groups independently selected from oxo, hydroxyl, thiol, nitro, amino and / or halogen; R 8a YesR 8b R 8c , where R 8b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein R 8c Yes – N(R 8d ) 2-3 or guanidino, where each R 8d is independently -H or a linear or branched C1-C3 alkyl group; R 9a It is -C(O)NH2, -C(O)-OH, -CH2-C(O)NH2, -CH2-C(O)-OH, -R 9b -R 9c or -R 9b -[Connector]-R X n1 ; where R 9b is –C(O)NH–; and R 9c yes Where R 9d is a straight chain or branched C1-C5 alkylene group, R 9e is carboxylic acid, sulfonic acid, sulfinic acid, phosphoric acid, amino, guanidino, -SH, -OH, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-CH3, -N(CH3)2, -S-CH3, -O-CH3 or phenyl, and R 9f is amino or –OH; R A7a is C1-C3 alkylene; R A10 Does not exist or -[connector]-R X n1 ; When R A10 If it does not exist, then R A1a yes: Straight chain C1-C5 alkyl, C2-C5 alkenyl or C2-C5 alkynyl, wherein 0-2 carbons in the C2-C5 alkyl, alkenyl or alkynyl are independently replaced by one or more N, S and / or O heteroatoms, optionally C-substituted by a monosubstituent selected from the following: -SH, -OH, amino, carboxyl, guanidino, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH3) 1-2 、-NH2-CH3、-N(CH3) 2-3 , -S-CH3 or -O-CH3; Branched chain C1-C 10 Alkyl, alkenyl or alkynyl, wherein C2-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 straight chain C1-C3 alkylene group, wherein the C2 alkylene group or the C3 alkylene group is optionally replaced by a N, S or O heteroatom, wherein R A1c yes: A 5 or 6 membered aromatic ring in which one or more carbons are optionally independently replaced by N, S and / or O heteroatoms, and optionally substituted by one or more groups independently selected from oxo, hydroxyl, thiol, nitro, amino and / or halogen; or A fused bicyclic or fused tricyclic aryl group wherein one or more carbon atoms are optionally independently replaced by N, S and / or O heteroatoms and optionally independently selected from halogen, -OH, -OR A1d , amino, -NHR A1d and / or N(R A1d )2 is substituted with one or more groups, wherein each R A1d are independently C1-C3 straight or branched chain alkyl; When R A10 Yes-[Connector]-R X n1 When R A1a YesR A1e R A1f ,in: R A1e is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbons in the C2-C5 alkylene, alkenylene or alkynylene are independently replaced by N, S and / or O heteroatoms; R A1f is -NH-C(O)-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C(S)NH-, -N(CH3)C(S)-, -C(O)N(CH3)-, -N(CH3)C(O)-, -C(S)N(CH3)-, -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-, -phosphoramide-, -phosphorothioate diester-, -S-tetrafluorophenyl-S-, or polyethylene glycol; The connector 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 ; X 1 are independently -CH2-, L 1 each independently is –NH–, –C(O)–, –NHC(O)–, –C(O)NH–, –N(CH3)C(O)– or –C(O)N(CH3)–; R 11 are each independently a carboxylic acid, a sulfonic acid, a sulfinic acid or a phosphoric acid; and R Z each independently is an albumin binder; Each n1 is independently 0, 1 or 2; Each R X is an albumin binder, a therapeutic moiety, a fluorescent label, a radiolabeled group, or a group capable of being radiolabeled; 0-3 peptide backbone amides are independently Amidine or thioamide substitution; wherein 0-3 of the peptide backbone amides are N-methylated; and wherein the C-terminus is optionally amidated.

86. The compound of claim 1 or 85, wherein the compound has a structure of Formula A-IV or a salt or solvate thereof: in: -NH-CH(R) in Formula A-IV 2a )-C(O)- forms a Tyr residue, a Phe residue, a (4-NO2)-Phe residue, a (4-NH2)-Phe residue, an hTyr residue, a (3-I)Tyr residue, a Glu residue, a Gln residue or a D-Tyr residue; -NH-CH(R) in Formula A-IV 4a )-C(O)- forms a D-Arg residue or a D-hArg residue; -NH-CH(R) in Formula A-IV 5a )-C(O)- forms a 2-(Ant)Ala residue, a 2-Nal residue, a Trp residue, a (4-NH2)Phe residue, an hTyr residue or a Tyr residue; -NH-CH(R) in Formula A-IV 6a )-C(O)- forms a His residue, a D-His residue, a D-Glu residue, a D-Gln residue, a D-Ala residue, a D-Phe residue, a D-Ser residue, a D-Dab residue, or a D-Dap residue; R 3a is a C1-C5 alkyl group; R y is hydrogen or R 3e R 3f , where R 3e is a straight chain C1-C5 alkylene group, wherein R 3f Yes – N(R 3g ) 2-3 , where each R 3g is independently -H or a linear or branched C1-C3 alkyl group; R 8a YesR 8b R 8c , where R 8b is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein R 8c Yes – N(R 8d ) 2-3 or guanidino, where each R 8d is independently -H or a linear or branched C1-C3 alkyl group; R 9a is -C(O)NH2, -C(O)-OH, -CH2-C(O)NH2, -CH2-C(O)-OH or -R 9b -[Connector]-R X n1 ; R 9b is –C(O)NH–; R A7a is C1-C3 alkylene; R A10 Does not exist or -[connector]-R X n1 ; When R A10 If it does not exist, then R A1a is a straight chain C1-C5 alkyl group, optionally substituted by a monosubstituent selected from the group consisting of -SH, -OH, amino, carboxyl, guanidino, -NH-C(O)-CH3, -SC(O)-CH3, -OC(O)-CH3, -NH-C(O)-(phenyl), -SC(O)-(phenyl), -OC(O)-(phenyl), -NH-(CH3) 1-2 、-NH2-CH3、-N(CH3) 2-3 , -S-CH3, -O-CH3 or branched C1-C 10 alkyl, alkenyl or alkynyl; When R A10 Yes-[Connector]-R X n1 When R A1a YesR A1e R A1f ,in: R A1e is a straight chain C1-C5 alkylene, C2-C5 alkenylene or C2-C5 alkynylene, wherein 0-2 carbons in the C2-C5 alkylene, alkenylene or alkynylene are independently replaced by N, S and / or O heteroatoms; R A1f is -NH-C(O)-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C(S)NH-, -N(CH3)C(S)-, -C(O)N(CH3)-, -N(CH3)C(O)-, -C(S)N(CH3)-, -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-, -phosphoramide-, -phosphorothioate diester-, -S-tetrafluorophenyl-S-, or polyethylene glycol; The connector is X 1 L 1 , X 1 L 1 X 1 L 1 or X 1 LX 1 L 1 X 1 L 1 ; X 1 are independently -CH2-, L 1 each independently is –NH–, –C(O)–, –NHC(O)–, –C(O)NH–, –N(CH3)C(O)– or –C(O)N(CH3)–; R 11 are each independently a carboxylic acid, a sulfonic acid, a sulfinic acid or a phosphoric acid; and R Z each independently is an albumin binder; Each n1 is independently 0, 1 or 2; Each R X is an albumin binder, a therapeutic moiety, a fluorescent label, a radiolabeled group, or a group capable of being radiolabeled; 0-3 peptide backbone amides are independently Amidine or thioamide substitution; wherein 0-3 of the peptide backbone amides are N-methylated; and wherein the C-terminus is optionally amidated.

87. The compound of claim 85 or 86, wherein -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.

88. A compound as described in any one of claims 85-87, wherein R y YesR 3b R 3c , where R 3b is a straight chain C1-C5 alkylene group, wherein R 3c Yes – N(R 3d )2, where each R 3d are independently -H or a linear or branched C1-C3 alkyl group.

89. The compound of claim 88, wherein R 3a It's methyl.

90. The compound of any one of claims 85-89, wherein the linker is X 1 L 1 ;X 1 yes And L 1 It is –NH– or –NHC(O)–.

91. A compound as described in any one of claims 85-90, wherein R 11 It is sulfonic acid (-SO3H).

92. The compound of any one of claims 1-89, wherein: R 9a It is -C(O)NH2, -C(O)-OH, -R 9b -R 9c or -R 9b -[Connector]-R X n1 ;and R 9b It is -C(O)NH-.

93. The compound of any one of claims 1-92, wherein zero peptide backbone amides are replaced.

94. The compound of any one of claims 1-93, wherein one peptide backbone amide is N-methylated.

95. The compound of any one of claims 1-19, 21-82, and 84-93, wherein zero of the peptide backbone amides are N-methylated.

96. The compound of any one of claims 1-95, wherein the compound of Formula A, Formula AI, or Formula A-II, Formula A-III, Formula A-IV, or a salt or solvate thereof has the following combination: -NH-CH(R 2a )-C(O)- forms a Tyr residue; 1)-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, where R A7a is C1-C3 alkylene; and -NH-CH(R 8a )-with 9a The -C(O)- together form a Lys(iPr) residue; -NH-CH(R 2a )-C(O)- forms a Tyr residue; 2)-NCH3-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, where R A7a is C1-C3 alkylene; and -NH-CH(R 8a )-with 9a The -C(O)- together form a Lys(iPr) residue; -NH-CH(R 2a )-C(O)- forms a Tyr residue; 3)-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)-, where R 5a is -CH2(2-naphthyl); -NH-CH(R 6a )-C(O)- forms D-Ala; -NH-CH(R A7a )-C(O)- forms a D amino acid residue, where R A7a is C1-C3 alkylene; and -NH-CH(R 8a )-with 9a The -C(O)- together form a Lys(iPr) residue; -NH-CH(R 2a )-C(O)- forms a Tyr residue; 4)-NH-CH(R 3a )-C(O)- forms a Lys(iPr) residue; -NH-CH(R 4a )-C(=NH)-, where R 4a is –(CH2)3NHC(=NH)NH2; -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, where R A7a is C1-C3 alkylene; and -NH-CH(R 8a )-with 9a The -C(O)- together form a Lys(iPr) residue; -NH-CH(R 2a )-C(O)- forms a Tyr residue; 5)-NH-CH(R 3a )-C(=NH)-, where R 3a is –(CH2)4NH(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, where R A7a is C1-C3 alkylene; and -NH-CH(R 8a )-with 9a -C(O)- together with the -C(O)- to form a Lys(iPr) residue; or -NH-CH(R 2a )-C(O)- forms a Tyr residue; 6)-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, where R A7a is C1-C3 alkylene; and -NH-CH(R 8a )-with 9a -C(O)- together with the -C(O)- to form a Lys(iPr) residue; and Where R y is -(CH2)4-NH-(iPr), and R 3a Yes-CH 3。 97. A compound as described in any one of claims 1 to 66 and 93 to 95, wherein the compound of formula B or a salt or solvate thereof has the following composition: -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)- to form a 2-Nal residue; and -NH-CH(R 6a )-C(O)- forms D-Ala.

98. A compound as described in any one of claims 1 to 66 and 93 to 95, wherein the compound of formula C or a salt or solvate thereof has the following composition: -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)- to form a 2-Nal residue; and -NH-CH(R 6a )-C(O)- forms D-Ala.

99. The compound of any one of claims 1 to 98, wherein at least one R X is a radiolabeled group or a group capable of being radiolabeled.

100. A compound as described in any one of claims 1 to 99, wherein each group capable of being radiolabeled is independently selected from: a metal chelator complexed with a metal optionally bound to a radioactive metal or a radioisotope; a prosthetic group containing trifluoroborate (BF3); or a prosthetic group containing a silicon-fluorine-acceptor moiety, a sulfonyl fluoride or a phosphoryl fluoride.

101. The compound of claim 100, wherein the metal chelator is complexed with a radioisotope.

102. The compound of claim 100 or 101, wherein the metal chelator is a polyurethane chelator.

103. The compound of claim 100 or 101, wherein the metal chelator is DOTA, MACROPA or a derivative thereof.

104. The compound of claim 100 or 101, wherein the metal chelator is selected from Table 3.

105. The compound of claim 100, wherein the prosthetic group containing BF3 is -R 13 R 14 BF3, where R 13 Yes – (CH2) 1-5 – and –R 14 BF3 is selected from Table 5 or Table 6 or Each R 15 and each R 16 are independently branched or straight chain C1-C5 alkyl groups.

106. The compound of claim 105, wherein -R 14 BF3 is 107. The compound of claim 106, wherein R 15 and R 16 Each is a methyl group.

108. A compound as described in any one of claims 100 and 105-107, wherein the prosthetic group containing BF3 comprises at least one 18 F.

109. The compound of any one of claims 1-108, wherein at least one R X It’s the treatment part.

110. The compound of any one of claims 1-109, wherein at least one R X It is a fluorescent marker.

111. A compound selected from one or more of the following: Cyclo[Lys-Tyr-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2; ring [Lys-Tyr-NMe-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2; ring [Lys-NH2-Tyr-NMe-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2; ring [Lys(ivDde)-Tyr-NMe-Lys(iPr)-D-Arg-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2; Cyclo[Lys-Tyr-(N-isopropylbutyl-1-amine)-D-Ala-D-Arg-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2; Cyclo[Lys-NH2-Tyr-(N-isopropylbutyl-1-amine)-D-Ala-D-Arg-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2; Cyclo[Lys(ivDde)-Tyr-(N-isopropylbutyl-1-amine)-D-Ala-D-Arg-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2; ring (Ttn)[β-Ala(iPr)-Tyr-Lys(iPr)-D-Arg-2NaI-D-Ala-Cys]Lys(iPr)-NH2; ring (Ttn)[D-β-Ala(iPr)-Tyr-Lys(iPr)-D-Arg-2NaI-D-Ala-Cys]Lys(iPr)-NH2; Cyclo[Lys-Tyr-(N-isopropylbutyl-1-amine)-Ala-D-Arg-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2; Cyclo[Lys-NH2-Tyr-(N-isopropylbutyl-1-amine)-Ala-D-Arg-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2; Cyclo[Lys(ivDde)-Tyr-(N-isopropylbutyl-1-amine)-Ala-D-Arg-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2; ring [Lys-Tyr-Lys(iPr)-D-Arg-2Nal-Ψ-D-Ala-D-Glu]Lys(iPr)-NH2; ring [Lys-NH2-Tyr-Lys(iPr)-D-Arg-2Nal-Ψ-D-Ala-D-Glu]Lys(iPr)-NH2; ring [Lys(ivDde)-Tyr-Lys(iPr)-D-Arg-2Nal-Ψ-D-Ala-D-Glu]Lys(iPr)-NH2; ring [Lys-Tyr-Lys(iPr)-D-Arg-Ψ-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2; ring [Lys-NH2-Tyr-Lys(iPr)-D-Arg-Ψ-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2; ring [Lys(ivDde)-Tyr-Lys(iPr)-D-Arg-Ψ-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2; ring [Lys-Tyr-Lys(iPr)-Ψ-D-Arg-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2; ring [Lys-NH2-Tyr-Lys(iPr)-Ψ-D-Arg-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2; or ring [Lys(ivDde)-Tyr-Lys(iPr)-Ψ-D-Arg-2Nal-D-Ala-D-Glu]Lys(iPr)-NH2; or a salt or solvate thereof; Wherein the compound is optionally bound to a radiolabeling group, a group capable of being radiolabeled and / or an albumin binder, optionally via one or more linkers.

112. The compound of claim 111, wherein each of the linkers is independently 1-10 units of X 1 L 1 and / or X 1 (L 1 )2 is a straight or branched chain, wherein: Each X 1 are independently linear, branched and / or cyclic C1-C 15 Alkylene, C2-C 15 Alkenylene or C2-C 15 Alkyne, wherein 0-6 carbons are independently replaced by N, S and / or O heteroatoms, and 0-3 groups are independently selected from one or a combination of oxo, hydroxyl, thiol, halogen, guanidino, carboxylic acid, sulfonic acid, sulfinic acid and / or phosphoric acid; and Each L 1 Independently -NH-C(O)-, -NH-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C (S)NH-, -N(CH3)C(S)-, -C(O)N(CH3)-, -N(CH3)C(O)-, -C(S)N(CH3)-, -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-, -phosphoramide-, -phosphorothioate diester-, -S-tetrafluorophenyl-S-, or polyethylene glycol; or Alternatively, the linker is a linear or branched peptide linker (Xaa) 1-5 , wherein each Xaa is independently selected from a proteinogenic amino acid residue or a non-proteinogenic amino acid residue; and wherein the amino group in each Xaa is optionally methylated.

113. The compound of claim 111 or 112, wherein 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 the same or different, and each L 1 the same or different; of which: Each X 1 are independently linear, branched and / or cyclic C1-C 15 Alkylene, C2-C 15 Alkenylene or C2-C 15 Alkyne, wherein 0-6 carbons are independently replaced by N, S and / or O heteroatoms, and 0-3 groups are independently selected from one or a combination of oxo, hydroxyl, thiol, halogen, guanidino, carboxylic acid, sulfonic acid, sulfinic acid and / or phosphoric acid; and Each L 1 Independently -NH-C(O)-, -C(O)-, -O-, -C(O)NH–, -C(O)-N(CH3)-, -NHC(S)-, -C(S)NH-, -N(CH3)C(S)-, -C(O)N(CH3)-, -N(CH3)C(O)-, -C(S)N(CH3)-, -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-, -phosphoramide-, -phosphorothioate diester-, -S-tetrafluorophenyl-S-, or polyethylene glycol.

114. The compound of claim 112 or 113, wherein 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 the same or different, and each L 1 the same or different; and X 1 yes Each R 11 are independently carboxylic, sulfonic, sulfinic or phosphoric acids.

115. The compound of claim 112 or 113, wherein each X 1 yes Each R 11 are independently carboxylic, sulfonic, sulfinic or phosphoric acids.

116. The compound of claim 112, wherein the linker is 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 in each Xaa is optionally methylated.

117. The compound of claim 112, wherein the linker is a single amino acid residue selected from cysteic acid, Glu, Asp, or 2-aminoadipic acid (2-Aad); and wherein the amino group in the single amino acid residue is optionally methylated.

118. The compound of claim 112, wherein the linker is a linear or branched peptide linker (Xaa) 1-5 , wherein at least one Xaa is selected from Dap, Dab, Orn, Arg, hArg, Agb, Agp, Acp, Pip or N ε ,N ε ,N ε -trimethyl-lysine; and wherein each amino group in Xaa is optionally methylated.

119. The compound of claim 112, wherein the linker is a single amino acid residue selected from D-Arg, L-Arg, D-hArg, L-hArg or Pip; and wherein the amino group in the single amino acid residue is optionally methylated.

120. A compound as described in any of claims 111-119, wherein the group capable of being radiolabeled is independently selected from: a metal chelator complexed with a metal optionally bound to a radioactive metal or a radioisotope; a prosthetic group containing trifluoroborate (BF3); or a prosthetic group containing a silicon-fluorine-acceptor moiety, a sulfonyl fluoride or a phosphoryl fluoride.

121. The compound of claim 120, wherein the metal chelator is complexed with a radioisotope.

122. The compound of claim 120 or 121, wherein the metal chelator is DOTA, H2-MACROPA or a derivative thereof.

123. The compound of claim 120 or 121, wherein the metal chelator is selected from Table 3.

124. The compound of claim 120, wherein the prosthetic group containing BF3 is -R 13 R 14 BF3, where R 13 Yes – (CH2) 1-5 – and –R 14 BF3 is selected from Table 5 or Table 6 or Each R 15 and each R 16 are independently branched or straight chain C1-C5 alkyl groups.

125. The compound of claim 124, wherein -R 14 BF3 is Where R 15 and R 16 Each is a methyl group.

126. A compound as described in any one of claims 120, 124 and 125, wherein the prosthetic group containing BF3 comprises at least one 18 F.

127. The compound of any one of claims 100-104 and 120-123, wherein the radioisotope is 64 Cu, 67 Cu, 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 Cu, 67 Ga, 99m Tc, 111 In, 44 Sc, 86 Y. 89 Zr, 90 Nb, 117m Sn, 165 2. 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.

128. The compound of claim 127, wherein 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, 161 Tb, 165 2. 224 Ra, 212 Bi, 227 Th, 223 Ra, 64 Cu, 155 Tb, 155 Tb or 67 Cu.

129. The compound of formula A as claimed in claim 1, which has the following chemical formula: or a salt or solvate thereof.

130. The compound of formula A as claimed in claim 1, which has the following chemical formula: or a salt or solvate thereof.

131. The compound of formula A as claimed in claim 1, which has the following chemical formula: or a salt or solvate thereof.

132. The compound of formula A as claimed in claim 1, which has the following chemical formula: or a salt or solvate thereof.

133. The compound of formula B as claimed in claim 1, which has the following chemical formula: or a salt or solvate thereof.

134. A compound having the following chemical formula: or a salt or solvate thereof.

135. A compound as described in any one of claims 1-134 for use in imaging a CXCR4-expressing tissue in a subject or for imaging an inflammatory condition or disease, wherein at least one R X Contains or is complexed with an imaging radioisotope.

136. The compound of claim 135, wherein 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 As.

137. A compound as described in any one of claims 1-136 for use in imaging a tissue expressing CXCR4 in a subject or for imaging an inflammatory condition or disease, wherein the compound is optionally bound via a linker to a metal chelator complexed with an imaging radioisotope; or the compound is optionally bound via a linker to a radiolabeled chelator comprising at least one 18 F contains a BF3 cofactor.

138. The compound of claim 137, wherein 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. 152 Tb, 155 Tb or 72 As.

139. A compound as described in any one of claims 1-134 for use in treating a disease or condition characterized by expression of CXCR4 in a subject, wherein at least one R X Containing or complexed with a therapeutic radioisotope, or at least one R X Contains treatment component.

140. A compound as described in any one of claims 1-134 for use in treating a disease or condition characterized by expression of CXCR4 in a subject, wherein the compound is optionally conjugated via a linker to a metal chelator complexed to a therapeutic radioisotope.

141. The compound of claim 139 or 140, wherein the therapeutic radioisotope is 165 2. 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 Cu.

142. The compound of any one of claims 139-141, wherein the disease or condition is a cancer expressing CXCR4.

143. A method of imaging a tissue expressing CXCR4, the method comprising administering to a subject in need of such imaging an effective amount of a compound as described in any one of claims 137-138.

144. 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 thereof an effective amount of a compound as described in any one of claims 139-142.

145. The compound of claim 144, wherein the disease or condition is a cancer expressing CXCR4.

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