PCTA derivatives, conjugates thereof and uses thereof

Abstract

The present disclosure relates to compounds comprising macrocyclic chelators and their conjugates with target-binding moieties. In particular, the present disclosure relates to PCTA derivatives and conjugates thereof.

Description

[Technical Field]

[0001] The present disclosure relates to compounds comprising a macrocyclic chelator and a target-binding moiety, and conjugates thereof (eg, with radioisotopes). [Background technology]

[0002] Over the years, a variety of macrocyclic chelators have been developed. The ability of these chelators to complex with several different metal ions has attracted considerable interest. The ability of these macrocyclic chelators to complex with radionuclides allows them to be used in a variety of biomedical applications, such as diagnostics and therapeutics.

[0003] Some of the most commonly used macrocyclic chelators are DOTA (2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid) and NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid). These chelators have been widely developed and used in a variety of applications, including radioligand therapy and imaging.

[0004] Radioligand therapy and / or diagnosis (RLT, RLD) typically have two main moieties: a chelator that conjugates a radionuclide (such as DOTA) and a target-binding moiety that selectively binds to a specific marker on target cells (such as cancer cells). RLTs and RLDs may further include a linker or spacer, e.g., a molecular entity used to increase the distance of the target-binding moiety from the chelator to prevent steric effects on cellular receptors and loss of activity upon functionalization. The length and composition of the linker can affect the binding affinity of the radiopharmaceutical to the receptor, the accumulation of the radionuclide in tumor cells, and the pharmacokinetic properties.

[0005] Used to treat cancers that express somatostatin receptors ( 177 Lu) oxodotreotide (or [ 177This approach has been particularly successful in the past for RLTs and RLDs, such as [Lu]-DOTA-TATE).

[0006] In recent years, PCTA (3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid)-based chelators have been developed; however, they have been less studied than others. The development of PCTA derivatives that can be conjugated to target-binding moieties and thus potentially used in diagnosis and / or therapy would be advantageous. Furthermore, PCTA derivatives that can chelate radionuclides at low temperatures (e.g., ≦60°C) in high yields (e.g., ≧85%) would offer further advantages. Summary of the Invention

[0007] The present disclosure provides a compound of formula (I) [ka] or a pharmaceutically acceptable salt thereof (In the formula, [ka] is a single or double bond, [ka] is a single bond, X is -O- or [ka] and [ka] is a double bond, then X is ═N—, and Z and Z together with the N atom form a heteroaryl having 5 or 6 ring atoms, otherwise Z and Z are each independently selected from the group consisting of H, an albumin binder, and —X1-L1-X2-L2-A; each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 aryl, and heteroaryl having 5 to 10 ring atoms, or any combination thereof; Z1, Z2, Z3, Z4, and Z6 are each independently selected from the group consisting of H, an albumin binder, and -X1-L1-X2-L2-A, with the proviso that at least one of Z1, Z2, Z3, Z4, Z5, Z6, and Z7 is a -X1-L1-X2-L2-A group; X1 is either present or absent, and if present: X1 is selected from the group consisting of -O-, -NR'-, -C(=O)NR'-, -NR'C(=O)-, -OC(=O)-, -C(=O)O-, -OC(=O)NR'-, -NR'C(=O)O-, -CH2-O-, and -NR'C(=O)NR'-, with the proviso that when X1 is NR', R4 is not H; L1 is C1-C5 alkylene, (-CH2CH2O) n , C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10 a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is a target-binding moiety selected from the group comprising, for example, peptides, polypeptides, protein peptidomimetics, antibodies and antigen-binding fragments, aptamers, DARPins, antisense oligonucleotides, siNAs, small molecules, microparticles or nanoparticles).

[0008] The compounds of formula (I) have pharmacological properties that make them suitable for use in radioligand therapy. Indeed, the compounds of formula (I) can be used to bind radionuclides, e.g. 68 Ga and 177 It can be easily labeled with Lu. The labeled compound also has good stability and good biodistribution. DETAILED DESCRIPTION OF THE INVENTION

[0009] definition Various embodiments of the present disclosure are described herein, and it will be recognized that the features specified in each embodiment may be combined with other specified features to provide further embodiments.

[0010] The term "about" is used herein to mean that the following value may vary by ±20%, preferably ±10%, and more preferably ±5%.

[0011] Unless otherwise defined, "%" as used herein has the meaning of weight percent (wt%) of yield percentage, also referred to as weight / weight percent (w / w%).

[0012] The present disclosure encompasses the compounds of the present disclosure, their stereoisomers, tautomers, enantiomers, diastereomers, racemates or mixtures thereof, and hydrates, solvates or pharmaceutically acceptable salts thereof.

[0013] "Pharmaceutically" or "pharmaceutically acceptable" refers to molecular entities and compositions that do not produce adverse, allergic, or other untoward reactions when administered to a mammal, particularly a human, as appropriate. A pharmaceutically acceptable carrier or excipient refers to a non-toxic solid, semi-solid, or liquid filler, diluent, encapsulating material, or formulation auxiliary of any type.

[0014] The term "pharmaceutically acceptable salt" refers to a salt that retains the biological effectiveness and properties of the compounds of the present disclosure and is typically not biologically or otherwise undesirable. In many cases, the compounds of the present disclosure are capable of forming acid and / or base salts due to the presence of amino and / or carboxyl groups or groups similar thereto. Pharmaceutically acceptable acid addition salts can be formed with organic and / or inorganic acids. Pharmaceutically acceptable base addition salts can be formed with organic and / or inorganic bases. Such salts are well known to those skilled in the art. Examples of pharmaceutically acceptable salts include trifluoroacetic acid (TFA), acetate, or hydrochloride salts.

[0015] As used herein, "alkyl" and "C1-C x The term "alkyl," by itself or as part of another substituent, refers to a straight-chain or branched alkyl functional group having 1 to x carbon atoms, e.g., 1 to 24, 1 to 20, 1 to 12, 1 to 6, or 1 to 5 carbon atoms. Suitable alkyl groups include methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, and t-butyl, pentyl and its isomers (e.g., n-pentyl, isopentyl), and hexyl and its isomers (e.g., n-hexyl, isohexyl).

[0016] Alkylene, used alone or as part of, for example, alkylene glycol, refers to a divalent saturated, straight chain or branched alkyl group as defined herein.

[0017] As used herein, the terms "cycloalkyl" and "carbocycle" refer to a saturated or partially unsaturated cyclic group. In one embodiment, a cycloalkyl has 3 to 8 carbon atoms or 3 to 6 carbon atoms. A cycloalkyl can have a single ring or multiple rings fused together. A cycloalkyl can also include spirocycles. Suitable cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0018] As used herein, the terms "cycloalkylene" and "carbocyclo" refer to a divalent cycloalkyl as defined herein.

[0019] As used herein, the term "halogen" refers to a fluoro (-F), chloro (-Cl), bromo (-Br), or iodo (-I) group.

[0020] As used herein, the term "heteroalkyl" refers to a straight or branched hydrocarbon chain consisting of 1 to 12 carbon atoms, e.g., 1 to 10 carbon atoms, or 1 to 6 carbon atoms, and 1 to 3 heteroatoms selected from the group consisting of O, N, Si, and S, where the nitrogen and sulfur atoms can be optionally oxidized (e.g., sulfoxide or sulfone) and the nitrogen heteroatom can be optionally quaternized. The heteroatoms O, N, and S can be placed at any interior position of the heteroalkyl group or at the position at which the alkyl group is attached to the remainder of the molecule.

[0021] Heteroalkylene refers to a divalent heteroalkyl as defined above. For heteroalkylene groups, heteroatoms can also occupy either or both of the chain termini.

[0022] As used herein, the term "aryl" refers to a polyunsaturated aromatic hydrocarbyl group having a single ring or multiple aromatic rings fused together, wherein at least one ring is aromatic. In one embodiment, an aryl contains 5 to 10 ring atoms. The aromatic ring may optionally contain one to two additional rings (cycloalkyl, heterocyclyl, or heteroaryl, as defined herein) fused thereto. Suitable aryl groups include phenyl, naphthyl, and phenyl rings fused to a heterocyclyl, such as benzopyranyl, benzodioxolyl, benzodioxanyl, and the like.

[0023] As used herein, the term "heteroaryl" refers to a polyunsaturated aromatic ring system having a single ring or multiple aromatic rings fused together or covalently linked. In one embodiment, a heteroaryl contains 5 to 10 ring atoms, wherein at least one ring atom is a heteroatom selected from N, O, and S. The nitrogen and sulfur heteroatoms may be optionally oxidized, and the nitrogen heteroatom may be optionally quaternized. Such rings may be fused to an aryl ring, a cycloalkyl ring, or a heterocyclyl ring. Non-limiting examples of such heteroaryls include furanyl, thiophenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, oxatriazolyl, thiatriazolyl, pyridinyl, pyrimidyl, pyrazinyl, pyridazinyl, oxazinyl, dioxinyl, thiazinyl, triazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothiophenyl, isobenzothiophenyl, indazolyl, benzimidazolyl, benzoxazolyl, purinyl, benzothiadiazolyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, and quinoxalinyl.

[0024] As used herein, the terms "heterocyclyl" and "heterocycloalkyl" refer to saturated or unsaturated cyclic groups. In one embodiment, a heterocyclyl contains 3 to 10 ring atoms (or 3 to 8 ring atoms, or 3 to 6 ring atoms), wherein at least one ring atom is a heteroatom selected from N, O, and S. The nitrogen and sulfur heteroatoms may optionally be oxidized, and the nitrogen heteroatom may optionally be quaternized. Heterocycles may include fused or bridged rings and spirocycles. Examples of heterocycles include, but are not limited to, tetrahydropyridyl, piperidinyl, morpholinyl, tetrahydrofuranyl, tetrahydrothienyl, piperazinyl, 1-azepanyl, imidazolinyl, 1,4-dioxanyl, and the like.

[0025] As used herein, the term "heterocyclo" or "heterocycloalkylene" refers to a divalent heterocycle, as defined herein.

[0026] Furthermore, alkyl, aryl, alkylene, arylene, heteroalkyl, heteroalkylene, C3-C8 carbocycle, C3-C8 carbocyclo, C3-C8 heterocycle, C3-C8 heterocyclo, and polyether are each independently selected from the group consisting of -X, -R', -O-, -OR', =O, -SR', -S-, -NR'2, -NR'3, =NR', -CX3, -CN, -OCN, -SCN, -N=C=O, -NCS, -NO, -NO2, =N2, -N3, -NRC(=O)R', -C(=O)R', -C(=O)NR'2, -SO3-, -SO3H, -S(=O)2R', -OS(= and C(=NR')NR', ​​where each X is independently a halogen atom; and each R' is independently selected from -H, -C1-C2, -C1-C3, -C1-C4, -C1-C5, -C1-C6, -C1-C7, -C1-C8, -C1-C9, -C1-C10, -C1-C11, -C1-C12, -C1-C13, -C1-C14, -C1-C15, -C1-C16, -C1-C17, -C1-C18, -C1-C19, -C1-C20, -C1-C21, -C1-C22, -C1-C23, -C1-C24, -C1-C25, -C1-C26, -C1-C27, -C1-C28, -C1-C29 ...9, -C1-C29, -C1-C29, -C1-C29, -C1-C29, -C1-C29, -C1-C29, -C1-C29, -C1-C29, -C1-C29, - 20 Alkyl, -C6~C 10 Aryl or -C3~C 10 It is a heterocycle.

[0027] As used herein, the term "spacer" refers to a chemical structure that covalently links two moieties, such as a chelator and A.

[0028] As used herein, the term "linker" refers to a chemical structure connecting moieties such as X1 and X2. The linker can increase the distance of the target-binding moiety from the chelator to prevent steric effects on cellular receptors and loss of activity upon functionalization. The length and composition of the linker affect the binding affinity of the radiopharmaceutical to the receptor, pharmacokinetics, plasma stability, and radionuclide accumulation in tumor cells. The linker can be inert or functionalized. Linkers can also be classified as cleavable or non-cleavable. Cleavable linkers can be cleaved, for example, in the acidic environment of the lysosome.

[0029] A non-exhaustive list of linkers includes: alkylene, heteroalkylene (thus alkylene interrupted by at least one heteroatom selected from Si, N, O, and S); alkoxy; polyethers such as polyalkylene glycols and typically polyethylene glycol; one or more natural or unnatural amino acids, for example, glycine, alanine, proline, lysine, valine, N-methylglycine; C3-C8 heterocyclo; C3-C8 carbocyclo; arylene, and any combination thereof. For example, the linker is a divalent linear alkylene group.

[0030] In some embodiments, the linker is -C 10 Alkylene-, -C1~C 10 Heteroalkylene-, -C3-C8 carbocyclo-, -O-(C1C8 alkyl)-, -arylene-, -C1-C 10 Alkylene-arylene-, -arylene-C1-C 10 Alkylene-, -C1~C 10 Alkylene-(C3-C8 carbocyclo)-, -(C3-C8 carbocyclo)-C1-C 10 Alkylene-, -C3-C8 heterocyclo-, -C1-C 10 Alkylene-(C3-C8 heterocyclo)-, -(C3-C8 heterocyclo)-C1-C 10 Alkylene-, -C1~C 10 Alkylene -C(=O)-, -C1 to C10 Heteroalkylene-C(=O)-, -C3-C8 carbocyclo-C(=O)-, -O-(C1-C8 alkyl)-C(=O)-, -arylene-C(=O)-, -C1-C 10 Alkylene-arylene-C(=O)-, -arylene-C1-C 10 Alkylene -C(=O)-, -C1 to C 10 Alkylene-(C3-C8 carbocyclo)-C(=O)-, -(C3-C8 carbocyclo)-C1-C 10 Alkylene-C(=O)-, -C3-C8 heterocyclo-C(=O)-, -C1-C 10 Alkylene-(C3-C8 heterocyclo)-C(=O)-, -(C3-C8 heterocyclo)-C1-C 10 Alkylene -C(=O)-, -C1 to C 10 Alkylene-NH-, -C1~C 10 Heteroalkylene-NH-, -C3-C8 carbocyclo-NH-, -O-(C1-C8 alkyl)-NH-, -arylene-NH-, -C1-C 10 Alkylene-arylene-NH-, -arylene-C1-C 10 Alkylene-NH-, -C1~C 10 Alkylene-(C3-C8 carbocyclo)-NH-, -(C3-C8 carbocyclo)-C1-C 10 Alkylene-NH-, -C3-C8 heterocyclo-NH-, -C1-C 10 Alkylene-(C3-C8 heterocyclo)-NH-, -(C3-C8 heterocyclo)-C1-C 10 Alkylene-NH-, -C1~C 10 Alkylene-S-, -C1~C 10 Heteroalkylene-S-, -C3-C8 carbocyclo-S-, -O-(C1-C8 alkyl)-S-, -arylene-S-, -C1-C 10 Alkylene-arylene-S-, -arylene-C1-C 10 Alkylene-S-, -C1~C 10 Alkylene-(C3-C8 carbocyclo)-S-, -(C3-C8 carbocyclo)-C1-C 10 Alkylene-S-, -C3-C8 heterocyclo-S-, -C1-C 10Alkylene-(C3-C8 heterocyclo)-S-, -(C3-C8 heterocyclo)-C1-C 10 Alkylene-S-, -C1~C 10 Alkylene-OC(=O)-, -C3-C8 carbocyclo-OC(=O)-, -O-(C1-C8 alkyl)-OC(=O)-, -arylene-OC(=O)-, -C1-C 10 Alkylene-arylene-OC(=O)-, -arylene-C1-C 10 Alkylene -OC(=O)-, -C1 to C 10 Alkylene-(C3-C8 carbocyclo)-OC(=O)-, -(C3-C8 carbocyclo)-C1-C 10 Alkylene-OC(=O)-, -C3-C8 heterocyclo-OC(=O)-, -C1-C 10 Alkylene-(C3-C8 heterocyclo)-OC(=O)-, -(C3-C8 heterocyclo)-C1-C 10 alkylene -OC(=O)-, and any combination thereof.

[0031] Additionally, in one embodiment, any of the linkers disclosed herein may be selected from the group consisting of an albumin binder, -X, -R', -O-, -OR', =O, -SR', -S-, -NR'2, -NR'3 + , =NR', -CX3, -CN, -OCN, -SCN, -N=C=O, -NCS, -NO, -NO2, =N2, -N3, -NR'C(=O)R', -C(=O)R', -C(=O)NR'2, -SO3 - , -SO3H, -S(=O)2R', -OS(=O)2OR', -S(=O)2NR', -S(=O)R', -OP(=O)(OR')2, -P(=O)(OR')2, -PO3 - , -PO3H2, -C(=O)X, -C(=S)R', -CO2R', -CO2, -C(=S)OR', C(=O)SR', C(=S)SR', C(=O)NR'2, C(=S)NR'2, and C(=NR')NR'2, where each X is independently a halogen: -F, -CI, -Br, or -I; and each R' is independently -H, -C1-C 20 Alkyl, -C6~C10 Aryl or -C3~C 10 It is a heterocycle.

[0032] As used herein, the term "protecting group" refers to a chemical substituent that can be selectively removed by readily available reagents that do not attack the regenerated functional group or other functional groups in the molecule. Suitable protecting groups are known in the art and continue to be developed. Suitable protecting groups can be found, for example, in Wutz et al. ("Greene's Protective Groups in Organic Synthesis, Fourth Edition," Wiley-Interscience, 2007).

[0033] Protecting groups for protecting carboxyl groups, such as those described by Wutz et al. (pages 533-643), are used in certain embodiments. In some embodiments, the protecting group is removable by treatment with acid. Representative examples of carboxyl protecting groups include, but are not limited to, benzyl, p-methoxybenzyl (PMB), tertiary butyl (t-Bu), methoxymethyl (MOM), methoxyethoxymethyl (MEM), methylthiomethyl (MTM), tetrahydropyranyl (THP), tetrahydrofuranyl (THF), benzyloxymethyl (BOM), trimethylsilyl (TMS), triethylsilyl (TES), t-butyldimethylsilyl (TBDMS), and triphenylmethyl (trityl, Tr). Those skilled in the art will recognize the appropriate situations in which a protecting group is required.

[0034] Protecting groups for protecting amino groups, such as those described by Wutz et al. (pages 696-927), are used in certain embodiments. Representative examples of amino-protecting groups include, but are not limited to, t-butyloxycarbonyl (Boc), 9-fluorenylmethoxycarbonyl (Fmoc), allyloxycarbonyl (alloc), N-(1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl) (Dde), 1-(1-adamantyl)-1-methylethoxycarbonyl (Adpoc), N-(1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-3-methylbutyl) (ivDde), monomethoxytrityl (MMt), and 4-methyltrityl (Mtt). Those skilled in the art will recognize the appropriate situations in which protecting groups are required.

[0035] As used herein, the term "activated carboxylic acid" refers to a carboxylic acid group of the general formula -CO-X, where X is a leaving group. For example, activated forms of the carboxylic acid group can include, but are not limited to, acyl chlorides, symmetrical or asymmetrical anhydrides, and esters. In some embodiments, the activated carboxylic acid group is an ester with pentafluorophenol, nitrophenol, benzotriazole, azabenzotriazole, thiophenol, or N-hydroxysuccinimide (NHS) as the leaving group.

[0036] As used herein, the term cation refers to an ion that has one or more positive charges. Examples of cations include H + , Na + , Li + , K. + , Ca 2+ , Mg 2+ , and ammonium.

[0037] As used herein, the expressions "target binding moiety" and "targeting ligand" are used interchangeably herein and refer to a part of a molecule that specifically binds to a target, e.g., an antigen, cell, cell type, tissue, organ, region or compartment of the body, typically a protein or receptor, typically a receptor on the surface of a cell, particularly a cancer cell.

[0038] Target binding moieties and targeting ligands include peptides, polypeptides, proteins (antibodies, antibody fragments (Fab, F(ab') 2 , monospecific or bispecific Fab 2 , trispecific Fab 3 These include, but are not limited to, scFv, dsFv, scFv-Fc, bispecific diabodies, trispecific triabodies, minibodies, fragments of IgNAR (e.g., V-NAR), fragments of hclgG (e.g., VhH), bis-scFv), affibodies, or fibronectin type III domains, peptidomimetics, fusion proteins / polypeptides, aptamers, DARPins, antisense oligonucleotides, siNA, small molecules, microparticles, or nanoparticles.

[0039] In some embodiments, the target binding moiety associated with the linker L is of the formula -L-R2-C(O)-R1; L is absent or present; R1 is an amino acid residue linked via its amino group to the adjacent -C(O)- group (carbonyl group); R2 is an amino acid residue that is bonded via its amino group to the adjacent -C(O)- group.

[0040] In some embodiments, R1 is a glutamic acid residue; and R2 is a glutamic acid residue or a lysine residue.

[0041] As used herein, the term "amino acid" refers to naturally occurring and unnatural amino acids, as well as amino acid analogs and amino acid mimetics that function similarly to naturally occurring amino acids. Naturally occurring amino acids, including those encoded by the genetic code, as well as later-modified amino acids, such as hydroxyproline, 2-carboxyglutamate, and O-phosphoserine, are examples of amino acid analogs. Amino acid analogs refer to compounds that have the same basic chemical structure as a naturally occurring amino acid, i.e., an α-carbon bonded to a hydrogen, a carboxyl group, an amino group, and an R group, e.g., homoserine, norleucine, methionine sulfoxide, and methionine methylsulfonium. Such analogs have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid. Amino acid mimetics refer to compounds that have a structure that differs from the general chemical structure of an amino acid but that function similarly to a naturally occurring amino acid.

[0042] The terms "polypeptide" and "peptide" are used interchangeably herein to refer to polymers of amino acids of any length. The polymer can be linear or branched, it can include non-natural amino acids, and it can be interrupted by non-amino acids. The term also encompasses amino acid polymers that have been modified (e.g., by disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation, such as conjugation with a labeling component). In various embodiments, the polypeptide can be isolated from a natural source, produced by recombinant technology from a eukaryotic or prokaryotic host, or the product of a synthetic process. The polypeptides or peptides described herein can be any polypeptide or peptide known in the art, or derivatives or analogs thereof, particularly those that target receptors overexpressed in cancer. Non-limiting examples of receptor targets and corresponding targets that bind to the polypeptides or peptides are provided in Table 1 below.

[0043] [Table 1]

[0044] [Table 2]

[0045] As used herein, the term "protein" refers to any organic compound made from amino acids arranged in one or more linear chains and folded into a three-dimensional conformation. The amino acids in the polymer chain are linked together by peptide bonds between the carboxyl and amino groups of adjacent amino acid residues. The term "protein" also includes, but is not limited to, peptides, single-chain polypeptides, or any complex molecule composed primarily of two or more chains of amino acids. It also includes, but is not limited to, glycoproteins or other known post-translational modifications. It also includes, but is not limited to, known natural or artificial chemical modifications of natural proteins, such as glycoengineering, pegylation, incorporation of unnatural amino acids, and amino acid modifications for chemical conjugation with another molecule.

[0046] As used herein, the term "peptidomimetic" refers to a synthetic compound that has substantially the same functional characteristics as a natural or non-natural polypeptide, but different (although typically similar) structural characteristics. Such non-peptide compounds are referred to as "peptide mimetics" or "peptidomimetics." Fauchere, J. Adv. Drug Res. 15:29 (1986); Veber and Freidinger TINS ​​p. 392 (1985); Evans et al. J. Med. Chem. 30:1229 (1987). Peptide mimetics that are structurally similar to therapeutically useful peptides can be used to achieve equivalent or enhanced therapeutic or prophylactic effects. In general, a peptidomimetic is structurally similar to a paradigm polypeptide (i.e., a polypeptide having biological or pharmacological activity) as found in the polypeptide of interest, but has one or more peptide bonds optionally replaced by a bond selected from the group consisting of, for example, -CHNH-, -CHS-, -CH=CH- (cis and trans), -C(=O)CH-, -CH(OH)CH-, -CHSO-, and -CHSO-. The mimetic can be entirely composed of synthetic, non-natural analogues of amino acids, or it can be a chimeric molecule of partly natural peptide amino acids and partly non-natural analogs of amino acids. The mimetic can also incorporate any amount of natural amino acid conservative substitutions as long as such substitutions also do not substantially alter the mimetic's structure and / or activity.

[0047] As used herein, the terms "fusion protein" and "fusion polypeptide" refer to a polypeptide having at least two covalently linked portions, each of which is a polypeptide with a distinct property. The property can be a biological property, such as in vitro or in vivo activity. The property can also be a simple chemical or physical property, such as binding to a target molecule or catalysis of a reaction. The two portions can be linked directly by a single peptide bond or via a peptide linker, but are in reading frame with each other. Alternatively, a fusion protein refers to a protein containing at least two different protein domains, where the two different protein domains do not naturally occur in nature. An example of a fusion protein is an Fc-fusion protein, which contains the Fc fragment of an antibody fused to a non-antibody protein with target-binding properties, also known as an immunoadhesin.

[0048] As used herein, the term "antibody" refers to a polypeptide (or set of polypeptides) of the immunoglobulin family that can non-covalently, reversibly, and specifically bind to an antigen. For example, a naturally occurring "antibody" of the IgG type is a tetramer comprising at least two heavy (H) chains and two light (L) chains interconnected by disulfide bonds. Each heavy chain is composed of a heavy chain variable region (abbreviated herein as VH) and a heavy chain constant region. The heavy chain constant region is composed of three domains: CH1, CH2, and CH3. Each light chain is composed of a light chain variable region (abbreviated herein as VL) and a light chain constant region. The light chain constant region is composed of one domain (abbreviated herein as CL). The VH and VL regions can be further subdivided into regions of hypervariability called complementarity-determining regions (CDRs), interspersed with more conserved regions called framework regions (FRs). Each VH and each VL is composed of three CDRs and four FRs arranged in the following order from amino-terminus to carboxy-terminus: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The variable regions of the heavy and light chains contain a binding domain that interacts with an antigen. The constant region of the antibody may mediate the binding of the immunoglobulin to various cells of the host tissue or immune system (e.g., effector cells) and factors including the first component (Clq) of the classical complement system. The term "antibody" includes, but is not limited to, monoclonal antibodies, human antibodies, humanized antibodies, camelized antibodies, chimeric antibodies, bispecific or multispecific antibodies, and anti-idiotypic (anti-Id) antibodies (including, for example, anti-Id antibodies to the antibodies of the present disclosure). The antibody can be of any isotype / class (e.g., IgG, IgE, IgM, IgD, IgA, and IgY) or subclass (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2).

[0049] Both light and heavy chains are divided into structurally and functionally homologous regions. The terms "constant" and "variable" are used functionally. In this regard, it will be understood that both the variable domain of the light chain portion (VL) and the variable domain of the heavy chain portion (VH) determine antigen recognition and specificity. For clarity, this variable domain derived from a heavy chain molecule naturally lacking a light chain is known herein as a VHH or nanobody to distinguish it from the conventional VH of four-chain immunoglobulins. Such VHH molecules can be derived from Camelidae species, such as camel, llama, dromedary, alpaca, and guanaco. Other species outside the Camelidae family may produce heavy chain molecules naturally lacking a light chain; such VHHs are within the scope of the present invention. Conversely, the constant domain of the light chain (CL) and the constant domain of the heavy chain (CH1, CH2, or CH3) confer important biological properties (e.g., secretion, transplacental mobility, Fc receptor binding, complement fixation, and the like). By convention, the numbering of constant regions increases as one moves away from the antigen-binding site or amino-terminus of the antibody. In wild-type antibodies, the N-terminus is the variable region and the C-terminus is the constant region; the CH3 domain and CL domain actually comprise the carboxy-terminus of the heavy and light chains, respectively. The antibodies described herein can be any antibody known in the art. Non-limiting examples of antibodies are provided in Table 2 below.

[0050] [Table 3]

[0051] [Table 4]

[0052] [Table 5]

[0053] As used herein, the term "antibody fragment" or "antigen-binding fragment" of an antibody refers to one or more portions of an antibody. In some embodiments, these portions are portions of the contact domain of an antibody. In some other embodiments, these portions are antigen-binding fragments that retain the ability to non-covalently, reversibly, and specifically bind to an antigen, and may be referred to herein as "antigen-binding fragment," "antigen-binding fragment thereof," "antigen-binding portion," or the like. Examples of binding fragments include, but are not limited to, single-chain Fv (scFv), Fab fragments, monovalent fragments consisting of the VL, VH, CL, and CH1 domains, F(ab)2 fragments, which are bivalent fragments comprising two Fab fragments linked by a disulfide bridge at the hinge region, Fd fragments consisting of the VH and CH1 domains, Fv fragments consisting of the VL and VH domains of a single antibody arm, dAb fragments consisting of the VH domain (Ward et al., (1989) Nature; 341:544-546), and isolated complementarity-determining regions (CDRs). Thus, the term "antibody fragment" encompasses both proteolytic fragments of antibodies (e.g., Fab and F(ab)2 fragments) and engineered proteins comprising one or more portions of an antibody (e.g., scFv).

[0054] Antibody fragments can also be incorporated into single domain antibodies, maxibodies, minibodies, intrabodies, diabodies, triabodies, tetrabodies, v-NARs, and bis-scFvs (see, e.g., Hollinger and Hudson, 2005 Nature Biotechnology 23:1126-1136). Antibody fragments can be grafted onto scaffolds based on polypeptides such as fibronectin type III (Fn3) (see U.S. Pat. No. 6,703,199, which describes fibronectin polypeptide monobodies).

[0055] Antibody fragments can be assembled into single-chain molecules comprising a pair of tandem Fv segments (e.g., VH-CH1-VH-CH1) which, in combination with complementary light chain polypeptides (e.g., VL-VC-VL-VC), form a pair of antigen-binding regions (Zapata et al., 1995, Protein Eng. 8:1057-1062; and U.S. Pat. No. 5,641,870).

[0056] As used herein, the term "affibody" refers to a family of antibody mimics derived from the Z domain of Staphylococcus aureus protein A. Structurally, affibody molecules are based on a three-helix bundle domain that can also be incorporated into fusion proteins. Affibodies themselves have a molecular weight of approximately 6 kDa and are stable at high temperatures and under acidic or alkaline conditions. Target specificity is achieved by randomizing 13 amino acids located in two α-helices involved in the binding activity of the parent protein domain (Feldwisch J, Tolmachev V.; (2012) Methods Mol Biol. 899:103-26).

[0057] As used herein, the term "bispecific antibody" refers to an antibody that binds to two or more different epitopes. In some embodiments, a bispecific antibody binds to two different targets. In some embodiments, a bispecific antibody binds to two different epitopes on a single target molecule. An antibody that binds to two different epitopes on a single target molecule is also known as a "biparatopic antibody."

[0058] As used herein, the term "fibronectin type III domain" refers to an evolutionarily conserved protein domain found in a wide variety of extracellular proteins. Fibronectin type III domains have been used as molecular scaffolds to generate molecules capable of selectively binding to specific antigens. Fibronectin type III domain (FN3) variants engineered for selective binding may also be referred to as monobodies. FN3 domains can be biologically engineered by site-directed mutagenesis or mutagenesis screening (e.g., CIS-display, phage display, yeast display, bacterial display, mRNA display, ribosome display).

[0059] As used herein, the term "DARPin" refers to an artificial polypeptide prepared by genetic engineering that has high specificity and high binding affinity for a target protein. DARPins are derived from natural ankyrin proteins and have a structure in which at least two or at least three ankyrin repeat motifs, for example, three, four, or five ankyrin repeat motifs, are repeated. For example, DARPins containing three, four, or five ankyrin repeat motifs may have molecular weights of approximately 10 kDa, approximately 14 kDa, and approximately 18 kDa, respectively. DARPins comprise a core portion that performs a structural function and a target-binding portion outside the core that binds to the target. The core portion contains a conserved amino acid sequence, while the target-binding portion contains a different amino acid sequence depending on the target.

[0060] As used herein, the term "aptamer" refers to a single-stranded oligonucleotide (a single-stranded DNA or RNA molecule) that can specifically bind to its target with high affinity. The aptamers described herein can be any aptamer known in the art. Non-limiting examples of aptamers and their targets are provided in Table 3 below.

[0061] [Table 6]

[0062] [Table 7]

[0063] As used herein, the term "antisense oligonucleotide" refers to a single-stranded nucleic acid molecule having a nucleobase sequence that allows hybridization to a corresponding segment of a target nucleic acid. Non-limiting examples of antisense oligonucleotides and their targets are provided in Table 4 below.

[0064] [Table 8]

[0065] As used herein, the term "small interfering nucleic acid" (siNA) refers to any nucleic acid molecule that can inhibit or downregulate gene expression or viral replication by mediating RNA interference (RNAi) or gene silencing in a sequence-specific manner. It includes small interfering RNA (siRNA), microRNA (miRNA), small interfering oligonucleotides, and chemically modified small interfering nucleic acid molecules. siNAs are involved in RNA interference, a process of sequence-specific post-transcriptional gene silencing in animals and plants. siNAs are generated by RNase III cleavage from long double-stranded RNA (dsRNA) that is homologous to or specific for the silenced gene target. The siNAs described herein can be any siNA known in the art, particularly those targeted to tumor targets. Non-limiting examples of siNA gene-protein targets and their cellular functions are provided in Table 5 below.

[0066] [Table 9]

[0067] As used herein, the term "small molecule" refers to a substance or compound having a relatively low molecular weight (e.g., less than 4,000 daltons, particularly less than 2000 daltons). Typically, small molecules are organic but not proteins, polypeptides, or nucleic acids, although they may be amino acids or dipeptides. The small molecules described herein may be any small molecule known in the art, particularly those that target tumor targets. Non-limiting examples of small molecules and their targets are provided in Table 6 below.

[0068] [Table 10]

[0069] [Table 11]

[0070] [Table 12]

[0071] [Table 13]

[0072] [Table 14]

[0073] As used herein, the term "nanoparticle" refers to a material structure that is less than about 1 μm in size in any dimension (e.g., the x, y, and z Cartesian dimensions), e.g., less than about 500 nm, or less than about 200 nm, or less than about 100 nm, and greater than about 5 nm. Nanoparticles can have a variety of geometric shapes, e.g., spherical, ellipsoidal.

[0074] As used herein, the term "microparticle" refers to a material structure having a size in any dimension (e.g., the Cartesian dimensions of x, y, and z) of less than about 10 μm, e.g., less than about 150 μm, or less than about 100 μm, or less than about 20 μm, and greater than about 10 μm. Microparticles can have a variety of geometric shapes, e.g., spherical, ellipsoidal, etc.

[0075] As used herein, the term "subject" includes human and non-human animals. Non-human animals include all vertebrates, e.g., mammals and non-mammals, such as non-human primates, sheep, dogs, cows, chickens, amphibians, and reptiles. Except where noted, the terms "patient" and "subject" are used interchangeably herein.

[0076] As used herein, the term "therapeutically effective amount" refers to an amount effective, at dosages and for periods of time necessary, to achieve a desired therapeutic result.

[0077] As used herein, the terms "treat," "treatment," and "treating" refer to a reduction or amelioration of the progression, severity, and / or duration of a proliferative disorder, or an amelioration of one or more symptoms (e.g., one or more discernible symptoms) of a proliferative disorder, brought about by the administration of one or more antigen-binding molecules. In some embodiments, the terms "treat," "treatment," and "treating" refer to an improvement in at least one measurable physical parameter of a proliferative disorder, such as tumor growth, which is not necessarily discernible by the patient. In other embodiments, the terms "treat," "treatment," or "treating" refer to an inhibition of the progression of a proliferative disorder, either physically, e.g., by stabilization of a discernible symptom, physiologically, e.g., by stabilization of a physical parameter, or both. In other embodiments, the terms "treat," "treatment," or "treating" refer to a reduction or stabilization of tumor size or the number of cancerous cells.

[0078] The term "tumor" is used interchangeably herein with the term "cancer," e.g., both terms encompass solid and liquid tumors, e.g., diffuse or circulating tumors. As used herein, the term "cancer" or "tumor" includes pre-cancerous and malignant cancers and tumors.

[0079] As used herein, the term "target" refers to, but is not limited to, an antigen, a cell, a cell type, a tissue, an organ, a region or compartment of the body. The antigens described herein can be any antigen known in the art, particularly cancer antigens. Non-limiting examples of targets and cancers that express the targets are provided in Table 7 below.

[0080] [Table 15]

[0081] [Table 16]

[0082] [Table 17]

[0083] [Table 18]

[0084] [Table 19]

[0085] [Table 20]

[0086] [Table 21]

[0087] [Table 22]

[0088] [Table 23]

[0089] As used herein, the term "albumin binder" refers to a group that binds non-covalently to human serum albumin (typically with a binding affinity of less than about 10 μm). Albumin binding properties can be measured by surface plasmon resonance, as described in J. Biol. Chem. 277(38), 35035-35042, (2002). Typical albumin binders suitable for use in the present invention include linear and branched lipophilic groups having 12 to 40 carbon atoms and a distal acidic group. Albumin binders suitable for use in the compounds of the present invention are selected from the examples provided in Table 8 below.

[0090] [ka] [ka]

[0091] As used herein, the term "disease" or "disorder" refers to a condition for which treatment is necessary and / or desirable.

[0092] As used herein, the terms "cancer" and "tumor" encompass solid cancers and hematological / lymphatic cancers, as well as malignant, precancerous, and benign tumors such as dysplasia. Also included within this definition are cells with abnormal growth unchecked by the immune system (e.g., immune evasion and immune evasion mechanisms). Exemplary cancers include, but are not limited to, basal cell carcinoma, biliary tract cancer; bladder cancer; osteosarcoma; brain and central nervous system cancer; breast cancer; cancer of the peritoneum; cervical cancer; choriocarcinoma; colon and rectal cancer; connective tissue cancer; cancer of the digestive system; endometrial cancer; esophageal cancer; eye cancer; cancer of the head and neck; gastric cancer (including gastrointestinal cancer); glioblastoma; liver cancer; hepatocellular carcinoma; intraepithelial neoplasia; kidney or renal cancer; laryngeal cancer; vitiligo; liver cancer; lung cancer (e.g., small cell lung cancer, non-small cell lung cancer, lung adenocarcinoma, and squamous cell carcinoma of the lung); melanoma; myeloma; neuroblastoma; oral cancer (e.g., tongue and pharynx); ovarian cancer; pancreatic cancer; prostate cancer; retinoblastoma; rectal cancer; cancer of the respiratory system; salivary gland cancer; sarcoma; skin cancer; squamous cell carcinoma; stomach cancer; testicular cancer; thyroid cancer; uterine cancer or ovarian cancer. endometrial cancer; cancer of the urinary system; vulvar cancer; lymphomas, including Hodgkin's and non-Hodgkin's lymphomas, and B-cell lymphomas (including low-grade / follicular non-Hodgkin's lymphoma (NHL); small lymphocytic (SL) NHL; intermediate-grade / follicular NHL; intermediate-grade diffuse NHL; high-grade immunoblastic NHL; high-grade lymphoblastic NHL; high-grade small non-cleaved cell NHL; giant mass disease NHL; mantle cell lymphoma, AIDS-related lymphoma; and Waldenstrom's macroglobulinemia; chronic lymphocytic leukemia (CLL); acute lymphoblastic leukemia (ALLH), hairy cell leukemia; chronic myeloblastic leukemia; and other carcinomas and sarcomas; and post-transplant lymphoproliferative disorders (PTLD), and abnormal blood vessel growth associated with nematoses.

[0093] Compounds of formula (I) are conjugates between compounds of formula (II) and a target-binding moiety A. Compounds of formula (I) can be synthesized from compounds of formula (II) by reacting them with a target-binding moiety A using techniques well known to those skilled in the art.

[0094] Typically, compounds of formula (II) can be prepared according to the scheme provided below.

[0095] The following general schemes are provided as a guide to synthetic chemists of ordinary skill in the art, who will readily understand that variations in solvents, concentrations, reagents, protecting groups, order of synthetic steps, times, temperatures, and the like may be made as necessary.

[0096] The schemes provided below are intended to represent single diastereomers / enantiomers as well as their isomeric mixtures. The resolution of diastereomers / enantiomers can be carried out according to the methods described herein. Unless otherwise defined, in the general schemes described below, the substituents Z4, Z5 are as defined herein.

[0097] Scheme-1: [ka] Scheme 1 provides a synthetic route for preparing compounds of Formula IIa disclosed herein. An appropriate amino alcohol (1) is treated with a protecting group such as benzyl chloroformate. In Step B, the alcohol is converted to a leaving group, such as a halo (chloro, bromo, etc.) methanesulfonate or p-toluenesulfonate, in the presence of a suitable base. In Step C, ethane-1,2-diamine is introduced and used as a solvent. In Step D, the protecting group is removed under appropriate conditions depending on the protecting group used. For example, the carbamate of compound (4) is removed under conditions known in the art, such as hydrogen gas and palladium on carbon, to give compound (5). In Step E, compound (5) is treated with 2-nitrobenzenesulfonyl chloride and a suitable base, such as sodium bicarbonate. Macrocyclization Step F is carried out by condensing compound (6) with 2,6-bis(bromomethyl)pyridine in the presence of excess sodium carbonate as a base, in a solvent such as acetonitrile, at reflux. In step G, removal of the nosylate group is carried out by treatment with thiophenol in the presence of a base such as potassium carbonate. In step H, alkylation is achieved using an appropriate reagent such as tert-butyl bromoacetate, di-tert-butyl (S)-2-bromosuccinate, or di-tert-butyl (R)-2-bromosuccinate in the presence of a base such as potassium carbonate in a solvent such as DMF. In step I, the protecting group is removed under appropriate conditions depending on the protecting group used. For example, the Boc group of compound (9) is removed using an organic acid such as trifluoroacetic acid in a solvent such as dichloromethane or an inorganic acid such as hydrochloric acid in a solvent such as 1,4-dioxane to give compound (10). In step J, introduction of the maleimide is carried out stepwise. Treatment of compound (10) with maleic anhydride in the presence of a base such as triethylamine provides an intermediate which can be cyclized in the presence of an activating group such as pentafluorophenol and a base such as diisopropylmethanediimine to provide compound (11). Alternatively, treatment of compound (10) with maleic anhydride in acetic anhydride in the presence of sodium acetate provides compound (11).In Step K, the protecting group is removed using trifluoroacetic acid in water.

[0098] Scheme-2: [ka] Scheme 2 provides a synthetic route for preparing compounds of Formula IIb and IIc disclosed herein. A suitable heteroaromatic compound (1), such as methyl 2,6-bis(bromomethyl)isonicotinate, is reacted with a suitable diamine (2), such as tetra-tert-butyl 2,2'-((oxybis(ethane-2,1-diyl))bis(azanediyl))(2R,2'R)-disuccinate, in the presence of a base such as sodium carbonate to give compound (4) after hydrolysis. In step C, a linker is introduced by reaction with a suitable maleimide-functionalized linker, such as 4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)butan-1-aminium chloride, followed by deprotection of the tert-butyl ester using, for example, trifluoroacetic acid.

[0099] Scheme-3: [ka] Scheme 3 provides a synthetic route for preparing compounds of Formula IIc disclosed herein. A suitable heteroaromatic compound (1), such as 3-(benzyloxy)-2,6-bis(bromomethyl)pyridine, is reacted with a suitable diamine (2), such as tetra-tert-butyl 2,2'-((oxybis(ethane-2,1-diyl))bis(azanediyl))(2R,2'R)-disuccinate, in the presence of a base such as sodium carbonate to give compound (4) after reduction. In step C, a linker is introduced by alkylation with a suitable N-Boc linker, such as tert-butyl(3-bromopropyl)carbamate, followed by deprotection of the amine to give compound (5). In step D, the introduction of a phthalimide is carried out stepwise. Treatment of compound (5) with maleic anhydride in the presence of a base such as triethylamine gives an intermediate which, in the presence of an activating group such as pentafluorophenol and a base such as diisopropylmethanediimine, cyclizes to give compound (6) after deprotection of the tert-butyl ester.

[0100] Scheme-4: [ka] Scheme 4 provides a synthetic route for preparing compounds of formula IIb disclosed herein. An appropriate heteroaromatic compound (1), such as 3-(benzyloxy)-2,6-bis(bromomethyl)pyridine, is reacted with an appropriate diamine (2), such as di-tert-butyl 2,2'-((((2-(tert-butoxy)-2-oxoethyl)azanediyl)bis(ethane-2,1-diyl))bis(azanediyl))diacetate, in the presence of a base such as sodium carbonate to give compound (4) after deprotection. In Step C, maleimide is introduced stepwise. Treatment of compound (5) with maleic anhydride in the presence of a base such as triethylamine gives an intermediate, which undergoes cyclization in the presence of an activating group such as pentafluorophenol and a base such as diisopropylmethanediimine to give compound (5) after deprotection of the tert-butyl ester.

[0101] Scheme-5: [ka] Compound (2), as shown and described above in Scheme 4, is a useful intermediate for preparing compounds from formula (IIb, IIc). Compound 3 can be prepared by reacting amine 1, such as tert-butylglycinic acid hydrochloride, with compound 2, such as tert-butyl N-benzyl-N-(2-bromoethyl)glycinate (wherein LG is a leaving group, such as halo (bromo, etc.), in the presence of a suitable base, such as potassium carbonate. In the second step, the protecting group is removed under appropriate conditions. For example, the benzyl group can be removed under reductive conditions using palladium on carbon and hydrogen gas.

[0102] Scheme-6: [ka] Compound (1), shown and described above for Scheme 6, is a useful intermediate for the preparation of compounds from formulas (IIb, IIc). N-Alkylation of compound (1) can be carried out by treating a nitrobenzenesulfonamide (1), such as di-tert-butyl((2-nitrophenyl)sulfonyl)-D-aspartate, with an alcohol (2), such as 2,2'-oxybis(ethan-1-ol), in the presence of triphenylphosphine and di-tert-butyl azodicarboxylate under Mitsunobu conditions. The nosyl group is removed with a thiolate nucleophile, such as thiophenol or thioglycolic acid, in the presence of a base to give compound (3).

[0103] Pharmaceutical Composition The present disclosure also relates to pharmaceutical compositions comprising a compound of Formula (I) or (II) disclosed herein and at least one pharmaceutically acceptable carrier.

[0104] The form of the pharmaceutical composition, the route of administration, the dosage and the regimen will, of course, depend on the condition to be treated, the severity of the disease, the age, weight and sex of the patient, etc.

[0105] The pharmaceutical compositions of the present disclosure may be formulated for intravenous, intramuscular, or subcutaneous administration, etc.

[0106] The pharmaceutical composition may take the form of an aqueous solution, for example an injectable formulation, containing at least one compound according to the present disclosure.

[0107] Preferably, the pharmaceutical composition contains a pharmaceutically acceptable vehicle for an injectable preparation, which may be in particular isotonic sterile saline (such as mono- or di-sodium phosphate, sodium chloride, potassium chloride, calcium chloride or magnesium chloride, or a mixture of such salts), or a dry, in particular lyophilized, composition that, when optionally added with sterile water or saline, allows the constitution of an injectable solution.

[0108] Sterile injection solution can be prepared by adding the required amount of active compound to a suitable solvent, optionally with some of the other ingredients listed above, and then sterilizing by filtration.Generally, dispersion is prepared by adding various sterilized active ingredients to a sterile vehicle that contains a basic dispersion medium and other desired ingredients from the ingredients listed above.For the sterile powder used to prepare sterile injection solution, the preferred preparation method is vacuum drying and freeze-drying, which can obtain powder of active ingredient and any other desired ingredients from the solution that has been previously sterilized and filtered.When formulated, solution can be administered in a therapeutically effective amount in a manner that is compatible with dosage preparation.Preparation can be easily administered in various dosage forms, such as the type of injection solution described above.

[0109] For example, for parenteral administration in an aqueous solution, the solution may be suitably buffered and the liquid diluent first rendered isotonic with sufficient saline or glucose. These particular aqueous solutions are particularly suitable for intravenous, intramuscular, subcutaneous, and intraperitoneal administration. In this regard, sterile aqueous media that can be used will be known to those skilled in the art in light of the present disclosure. For example, one dose can be dissolved in 1 ml of isotonic NaCl solution and added to 1000 ml of hypodermic fluid or injected at the proposed infusion site (see, e.g., "Remington's Pharmaceutical Sciences," 15th Edition, pages 1035-1038 and 1570-1580). Some variation in dosage will necessarily occur depending on the condition of the subject being treated. The person administering will, in any event, determine the appropriate dose for the individual subject.

[0110] In certain embodiments, the pharmaceutical composition comprises one or more excipients selected from stabilizers against radiolysis, sequestering agents, and mixtures thereof.

[0111] As used herein, "radiolytic stabilizer" refers to a stabilizer that protects organic molecules from radiolysis; for example, when gamma rays emitted from a radionuclide break the bonds between atoms of an organic molecule and radicals are formed, these radicals are then trapped by a stabilizer that prevents the radicals from undergoing any other chemical reactions that may result in the molecule being undesirable, ineffective, or even toxic. Therefore, these stabilizers are also called "free radical scavengers" or "radical scavengers" for short. Other terms for these stabilizers are "radiostability enhancers," "radiolytic stabilizers," or simply "quenchers."

[0112] As used herein, "sequestering agent" refers to a chelating agent suitable for complexing free radionuclide metal ions (those not complexed with radiolabeled peptides) in the formulation.

[0113] The dosage used for administration can be adapted depending on various parameters, in particular depending on the method of administration used, the associated pathology, or the desired duration of treatment. It will be understood that appropriate dosages of compounds and compositions containing compounds may vary from patient to patient. Determining the optimal dosage generally involves balancing the level of therapeutic benefit against any risk or deleterious side effects of the treatments described herein.

[0114] Compounds of formula (I) or (II) for use as a medicament The present disclosure also relates to compounds of formula (I) or (II) disclosed herein for use as a medicament. Compounds of formula (I) or (II) exhibit useful pharmacological properties as shown in the tests provided in the Examples and are therefore indicated for use in therapy.

[0115] The present disclosure also relates to compounds of Formula (I) or (II) for use in the treatment of cancer.

[0116] As used herein, the term "cancer" has its common meaning in the art and includes an abnormal state or condition characterized by rapidly proliferating cell proliferation. The term is intended to include all types of cancerous growths or oncogenic processes, metastatic tissues, or malignantly transformed cells, tissues, or organs, regardless of histopathological type or invasive stage. The term cancer includes malignancies of various organ systems, such as skin, lung, breast, thyroid, lymphatic system, gastrointestinal tract, and genitourinary tract, as well as adenocarcinomas, including most colon cancers, renal cell carcinoma, prostate cancer, and / or testicular cancer, non-small cell carcinoma of the lung, cancer of the small intestine, and cancer of the esophagus.

[0117] Examples of cancers include, but are not limited to, hematological malignancies such as B-cell lymphoid neoplasms, T-cell lymphoid neoplasms, non-Hodgkin's lymphoma (NHL), B-NHL, T-NHL, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), NK-cell lymphoid neoplasms, and myeloid neoplasms. Examples of non-hematological cancers include, but are not limited to, skin cancer, colon cancer, breast cancer, lung cancer, brain cancer, prostate cancer, head and neck cancer, pancreatic cancer, bladder cancer, colorectal cancer, osteosarcoma, cervical cancer, liver cancer, oral cancer, esophageal cancer, thyroid cancer, kidney cancer, stomach cancer, and testicular cancer.

[0118] The terms "tumor" and "cancer" are used interchangeably herein, e.g., both terms encompass solid and liquid, e.g., diffuse or circulating, tumors. As used herein, the term "cancer" or "tumor" includes precancerous as well as malignant cancers and tumors and benign cancers. As used herein, the term "cancer" includes primary malignant cells or tumors (e.g., those in which cells have not metastasized to sites within a subject's body other than the site of the original malignant tumor or tumor) and secondary malignant cells or tumors (e.g., those resulting from metastasis, which is the metastasis of malignant cells or tumor cells to a secondary site different from the site of the original tumor).

[0119] Accordingly, the present disclosure also relates to a method for treating cancer, comprising contacting cancer cells with a therapeutically effective amount of a compound of Formula (I) or (II) described herein.

[0120] As used herein, the term "contacting" refers to any action that results in at least one compound, including a therapeutic agent of the presently disclosed subject matter, coming into physical contact with at least one cancer cell. Contacting can include exposing a cell or tumor to a compound in an amount sufficient to result in contact between the at least one compound and the at least one cell or tumor. The method can be performed in vitro or ex vivo by introducing and preferably mixing the compound and the cell or tumor in a controlled environment, such as a culture dish or tube. The method can be performed in vivo, in which case contacting refers to exposing at least one cell or tumor in a subject to at least one compound of the presently disclosed subject matter, for example, by administering the compound to the subject via any suitable route.

[0121] The present disclosure also relates to a method for treating cancer, comprising administering to a subject, preferably a human, in need thereof a therapeutically effective amount of a compound of Formula (I) or (II) described herein.

[0122] As used herein, the term "treating" includes halting, alleviating, inhibiting the progression of, preventing, or reducing the likelihood of the disease, disorder, or condition to which such term applies, or one or more symptoms or signs of such disease, disorder, or condition. Preventing refers to not causing the occurrence of a disease, disorder, condition, or a symptom or sign thereof, or a worsening of their severity. Thus, the compounds of the present disclosure can be administered prophylactically to prevent or reduce the occurrence or recurrence of a disease, disorder, or condition.

[0123] As used herein, the term "therapeutically effective amount" of a compound refers to an amount of compound that elicits a biological or medical response in a subject, e.g., ameliorates symptoms, alleviates a condition, slows or delays the progression of a disease, or prevents a disease.

[0124] The present disclosure also relates to the use of a compound of formula (I) or (II) for the manufacture of a medicament.

[0125] The present disclosure also relates to the use of a compound of Formula (I) or (II) for the manufacture of a medicament for the treatment of cancer.

[0126] Compounds of Formula (I) or (II) for Use in Imaging and Methods Thereof The present disclosure also relates to compounds of formula (I) or (II) for use in imaging, preferably in vivo imaging.

[0127] In certain embodiments, the imaging method in which the compounds of formula (I) or (II) are used is PET (positron emission tomography) or SPECT (single photon emission computed tomography).

[0128] Accordingly, the present disclosure also relates to a method for imaging, comprising contacting cancer cells with an effective amount of a compound of formula (I) or (II).

[0129] The method may further comprise the step of detecting a signal resulting from the decay of a radionuclide present in said compound.

[0130] In certain embodiments, the present disclosure provides a method for detecting the presence or absence of a tumor in a subject, comprising: (i) administering a compound of formula (I) or (II) to said subject, for example, as an intravenous injection; (ii) acquiring images, typically by PET or SPECT imaging; and (iii) detecting the presence or absence of a tumor in said subject.

[0131] The present disclosure also relates to compounds of formula (I) or (II) for use in diagnosis, typically for use in diagnosing cancer diseases.

[0132] The present disclosure also relates to a method for diagnosing and / or detecting cancer cells in a subject, comprising administering to said subject, preferably a human, an effective amount of a compound of formula (I) or (II) and detecting a signal resulting from the decay of a radionuclide present in said compound.

[0133] The present disclosure provides the following exemplary embodiments.

[0134] 1. a) at least a chelating agent of formula (C): [ka] (In the formula, [ka] is a single or double bond, [ka] is a single bond, X is -O- or [ka] and [ka] is a double bond, X is =N-; Each m is 0 to 5; each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is selected from the group consisting of H and C1-C6 alkyl; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 aryl, heteroaryl having 5 to 10 ring atoms, or any combination thereof), and b) a target binding moiety; and c) optionally, a spacer covalently linking C to the target binding moiety A, said spacer preferably comprising or consisting of an optionally substituted alkyl, heteroalkyl, cycloalkyl, cycloheteroalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, alkenyl, heteroalkenyl, cycloalkenyl, cycloheteroalkenyl, alkynyl, sulfonyl, amine, ether, thioether, phosphine, phosphoramidate, carboxamide, ester, imidoester, amidine, thioester, sulfonamide, carbamate, urea, guanidine, thiourea, one or more natural or unnatural amino acids, such as glycine, alanine, proline, valine; or a pharmaceutically acceptable salt thereof, A chelating agent of formula (C) is a compound, or a pharmaceutically acceptable salt thereof, that is optionally chelated to a radionuclide.

[0135] 2. The compound of embodiment 1, or a pharmaceutically acceptable salt thereof, wherein the chelating agent of formula (C) is capable of chelating a radionuclide in a yield of ≧85%, more preferably ≧90%, and even more preferably ≧95%, at a temperature of ≦60°C, more preferably ≦55°C, and even more preferably ≦50°C.

[0136] 3. The compound of embodiment 1 or 2, or a pharmaceutically acceptable salt thereof, wherein the chelating agent of Formula (C) is capable of chelating a radionuclide in ≦60 minutes.

[0137] 4. Formula (Ca), (Cb), or (Cc) [ka] wherein Ch is a chelating agent of formula (C); S is, independently at each occurrence, a bond or a spacer; A, independently at each occurrence, is a target binding moiety; n is 1, 2, 3, 4, 5, 6, or 7 or a pharmaceutically acceptable salt thereof.

[0138] 5. Formula (I) [ka] or a pharmaceutically acceptable salt thereof, During the ceremony, [ka] is a single or double bond, [ka] is a single bond, X is -O- or [ka] and [ka] is a double bond, then X is ═N—, and Z and Z together with the N atom form a heteroaryl having 5 or 6 ring atoms, otherwise Z and Z are each independently selected from the group consisting of H, an albumin binder, and —X1-L1-X2-L2-A; each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 aryl, and heteroaryl having 5 to 10 ring atoms, or any combination thereof; Z1, Z2, Z3, Z4, and Z6 are each independently selected from the group consisting of H, an albumin binder, and -X1-L1-X2-L2-A, with the proviso that at least one of Z1, Z2, Z3, Z4, Z5, Z6, and Z7 is a -X1-L1-X2-L2-A group; X1 is either present or absent, and if present: X1 is selected from the group consisting of -O-, -NR'-, -C(=O)NR'-, -NR'C(=O)-, -OC(=O)-, -C(=O)O-, -OC(=O)NR'-, -NR'C(=O)O-, -CH2-O-, and -NR'C(=O)NR'-, with the proviso that when X1 is NR', R4 is not H; L1 is C1-C5 alkylene, (-CH2CH2O) n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; The compound of any one of embodiments 1-4, or a pharmaceutically acceptable salt thereof, wherein A is a target binding moiety.

[0139] 6. A compound of formula (I), as defined in embodiment 5, wherein R is H; or a pharmaceutically acceptable salt thereof.

[0140] 7. The compound of formula (I), as defined in embodiment 5 or 6, or a pharmaceutically acceptable salt thereof, wherein each R1 is independently selected from the group consisting of H, C1-C6 alkyl, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, and heteroaryl having 5 to 10 ring atoms.

[0141] 8. A compound of formula (I), as defined in any one of embodiments 5-7, or a pharmaceutically acceptable salt thereof, wherein each R1 is independently selected from the group consisting of H, CH3, C(=O)OH, CH2C(=O)OH, and pyridyl.

[0142] 9. A compound of formula (I) according to any one of embodiments 5 to 8, or a pharmaceutically acceptable salt thereof, wherein R3 is selected from the group consisting of H, C1-C3 alkyl, and C(=O)OR.

[0143] 10. A compound of formula (I) according to any one of embodiments 5 to 9, or a pharmaceutically acceptable salt thereof, wherein R3 is selected from the group consisting of H, CH3 and C(=O)OH.

[0144] 11. A compound of formula (I) according to any one of embodiments 5 to 10, or a pharmaceutically acceptable salt thereof, wherein R4 is selected from the group consisting of H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR and heteroaryl having 5 to 10 ring atoms.

[0145] 12. A compound of formula (I) according to any one of embodiments 5 to 11, or a pharmaceutically acceptable salt thereof, wherein R4 is selected from the group consisting of H, C(=O)OH, CH2C(=O)OH and pyridyl.

[0146] 13. A compound of formula (I) according to any one of embodiments 5 to 12, or a pharmaceutically acceptable salt thereof, wherein only one of Z1, Z2, Z3, Z4, Z5, Z6, and Z7 is -X1-L1-X2-L2-A, and the other Z groups are H.

[0147] 14. A compound of formula (I) according to any one of embodiments 5 to 13, or a pharmaceutically acceptable salt thereof, wherein X1 is selected from the group consisting of -O-, -N(CH3)-, and -C(=O)NH-, or absent.

[0148] 15. Compounds of formula (Ia): [ka] or a pharmaceutically acceptable salt thereof (In the formula, [ka] is a single or double bond, [ka] is a single bond, X is -O- or [ka] and [ka] is a double bond, then X is ═N— and the N atom and the two carbon atoms to which it is attached form a heteroaryl having 5 or 6 ring atoms; each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10aryl, and heteroaryl having 5 to 10 ring atoms, or any combination thereof; X1 is either present or absent, and if present: X1 is selected from the group consisting of -O-, -NR'-, -C(=O)NR'-, -NR'C(=O)-, -OC(=O)-, -C(=O)O-, -OC(=O)NR'-, -NR'C(=O)O-, -CH2-O-, and -NR'C(=O)NR'-, with the proviso that when X1 is NR', R4 is not H; L1 is C1-C5 alkylene, (-CH2CH2O) n , C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10 a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0149] 16. Compounds of formula (Ib): [ka] or a pharmaceutically acceptable salt thereof (In the formula, [ka] is a single or double bond, [ka] is a single bond, X is -O- or [ka] and [ka] is a double bond, then X is ═N— and the N atom and the two carbon atoms to which it is attached form a heteroaryl having 5 or 6 ring atoms; each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 aryl, and heteroaryl having 5 to 10 ring atoms, or any combination thereof; X1 is either present or absent, and if present: X1 is selected from the group consisting of -O-, -NR'-, -C(=O)NR'-, -NR'C(=O)-, -OC(=O)-, -C(=O)O-, -OC(=O)NR'-, -NR'C(=O)O-, -CH2-O-, and -NR'C(=O)NR'-, with the proviso that when X1 is NR', R4 is not H; L1 is C1-C5 alkylene, (-CH2CH2O) n , C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10 a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0150] 17. Compound of formula (Ic): [ka] or a pharmaceutically acceptable salt thereof (In the formula, [ka] is a single or double bond, [ka] is a single bond, X is -O- or [ka] and [ka] is a double bond, then X is ═N— and the N atom and the two carbon atoms to which it is attached form a heteroaryl having 5 or 6 ring atoms; each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 aryl, and heteroaryl having 5 to 10 ring atoms, or any combination thereof; X1 is either present or absent, and if present: X1 is selected from the group consisting of -O-, -NR'-, -C(=O)NR'-, -NR'C(=O)-, -OC(=O)-, -C(=O)O-, -OC(=O)NR'-, -NR'C(=O)O-, -CH2-O-, and -NR'C(=O)NR'-, with the proviso that when X1 is NR', R4 is not H; L1 is C1-C5 alkylene, (-CH2CH2O) n , C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10 a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0151] 18. Compounds of formula (Id): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 aryl, and heteroaryl having 5 to 10 ring atoms, or any combination thereof; Z1, Z2, Z3, Z4, and Z6 are each independently selected from the group consisting of H, an albumin binder, and -X1-L1-X2-L2-A, with the proviso that at least one of Z1, Z2, Z3, Z4, Z5, Z6, and Z7 is a -X1-L1-X2-L2-A group; X1 is either present or absent, and if present: X1 is selected from the group consisting of -O-, -NR'-, -C(=O)NR'-, -NR'C(=O)-, -OC(=O)-, -C(=O)O-, -OC(=O)NR'-, -NR'C(=O)O-, -CH2-O-, and -NR'C(=O)NR'-, with the proviso that when X1 is NR', R4 is not H; L1 is C1-C5 alkylene, (-CH2CH2O) n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0152] 19. Compounds of formula (Ie): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; Z1, Z2, Z3, Z4, and Z6 are each independently selected from the group consisting of H, an albumin binder, and -X1-L1-X2-L2-A, with the proviso that at least one of Z1, Z2, Z3, Z4, Z5, Z6, and Z7 is a -X1-L1-X2-L2-A group; X1 is either present or absent, and if present: X1 is selected from the group consisting of -O-, -NR'-, -C(=O)NR'-, -NR'C(=O)-, -OC(=O)-, -C(=O)O-, -OC(=O)NR'-, -NR'C(=O)O-, -CH2-O-, and -NR'C(=O)NR'-, with the proviso that when X1 is NR', R4 is not H; L1 is C1-C5 alkylene, (-CH2CH2O) n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0153] 20. A compound of formula (If): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; Z1, Z2, Z3, Z4, and Z6 are each independently selected from the group consisting of H, an albumin binder, and -X1-L1-X2-L2-A, with the proviso that at least one of Z1, Z2, Z3, Z4, Z5, Z6, and Z7 is a -X1-L1-X2-L2-A group; X1 is either present or absent, and if present: X1 is selected from the group consisting of -O-, -NR'-, -C(=O)NR'-, -NR'C(=O)-, -OC(=O)-, -C(=O)O-, -OC(=O)NR'-, -NR'C(=O)O-, -CH2-O-, and -NR'C(=O)NR'-, with the proviso that when X1 is NR', R4 is not H; L1 is C1-C5 alkylene, (-CH2CH2O) n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0154] 21. Compound of formula (Ig): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 aryl, and heteroaryl having 5 to 10 ring atoms, or any combination thereof; L1 is C1-C5 alkylene, (-CH2CH2O) n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0155] 22. Compound of formula (Ih): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 aryl, and heteroaryl having 5 to 10 ring atoms, or any combination thereof; X1 is either present or absent, and if present: X1 is selected from the group consisting of -O-, -NR'-, -C(=O)NR'-, -NR'C(=O)-, -OC(=O)-, -C(=O)O-, -OC(=O)NR'-, -NR'C(=O)O-, -CH2-O-, and -NR'C(=O)NR'-, with the proviso that when X1 is NR', R4 is not H; L1 is C1-C5 alkylene, (-CH2CH2O) n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0156] 23. Compound of formula (Ii): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 aryl, and heteroaryl having 5 to 10 ring atoms, or any combination thereof; L1 is C1-C5 alkylene, (-CH2CH2O) n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0157] 24. Compound of formula (Ij): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 aryl, and heteroaryl having 5 to 10 ring atoms, or any combination thereof; L1 is C1-C5 alkylene, (-CH2CH2O) n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0158] 25. Compound of formula (Ik): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 aryl, and heteroaryl having 5 to 10 ring atoms, or any combination thereof; L1 is C1-C5 alkylene, (-CH2CH2O) n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0159] 26. Compound of formula (Im): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 aryl, and heteroaryl having 5 to 10 ring atoms, or any combination thereof; L1 is C1-C5 alkylene, (-CH2CH2O) n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0160] 27. Compounds of formula (In): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 aryl, and heteroaryl having 5 to 10 ring atoms, or any combination thereof; L1 is C1-C5 alkylene, (-CH2CH2O) n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0161] 28. Compound of formula (Io): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 aryl, and heteroaryl having 5 to 10 ring atoms, or any combination thereof; L1 is C1-C5 alkylene, (-CH2CH2O) n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0162] 29. Compound of formula (Ip): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 aryl, and heteroaryl having 5 to 10 ring atoms, or any combination thereof; L1 is C1-C5 alkylene, (-CH2CH2O) n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0163] 30. Compound of formula (Iq): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 aryl, and heteroaryl having 5 to 10 ring atoms, or any combination thereof; L1 is C1-C5 alkylene, (-CH2CH2O) n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0164] 31. Compound of formula (Ig'): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; L1 is C1-C5 alkylene, (-CH2CH2O) n , C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10 a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0165] 32. Compound of formula (Ih'): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; L1 is C1-C5 alkylene, (-CH2CH2O) n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0166] 33. Compound of formula (Ii'): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; L1 is C1-C5 alkylene, (-CH2CH2O) n , C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10 a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0167] 34. Compound of formula (Ij'): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; L1 is C1-C5 alkylene, (-CH2CH2O) n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0168] 35. Compound of formula (Ik'): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; L1 is C1-C5 alkylene, (-CH2CH2O) n , C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10 a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0169] 36. Compound of formula (Im'): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; L1 is C1-C5 alkylene, (-CH2CH2O) n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0170] 37. Compounds of formula (In'): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; L1 is C1-C5 alkylene, (-CH2CH2O) n , C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10 a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0171] 38. Compound of formula (Io'): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; L1 is C1-C5 alkylene, (-CH2CH2O) n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0172] 39. Compound of formula (Ip'): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; L1 is C1-C5 alkylene, (-CH2CH2O) n , C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10 a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0173] 40. Compound of formula (Iq') [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; L1 is C1-C5 alkylene, (-CH2CH2O) n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0174] 41. Compound of formula (Ig″): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; L1 is C1-C5 alkylene, (-CH2CH2O) n , C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10 a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0175] 42. Compound of formula (Ih″): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; L1 is C1-C5 alkylene, (-CH2CH2O) n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0176] 43. Compound of formula (Ii″): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; L1 is C1-C5 alkylene, (-CH2CH2O) n , C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10 a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0177] 44. Compound of formula (Ij″): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; L1 is C1-C5 alkylene, (-CH2CH2O) n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0178] 45. Compound of formula (Ik''): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; L1 is C1-C5 alkylene, (-CH2CH2O) n , C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10 a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0179] 46. ​​Compound of formula (Im″): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; L1 is C1-C5 alkylene, (-CH2CH2O) n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0180] 47. Compound of formula (In″): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; L1 is C1-C5 alkylene, (-CH2CH2O) n , C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10 a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0181] 48. Compound of formula (Io″): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; L1 is C1-C5 alkylene, (-CH2CH2O) n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0182] 49. Compound of formula (Ip″): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; L1 is C1-C5 alkylene, (-CH2CH2O) n , C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10 a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0183] 50. Compound of formula (Iq''): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; L1 is C1-C5 alkylene, (-CH2CH2O) n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are selected from the group consisting of an albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', optionally substituted with one or more substituents selected from -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN, and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X2 is selected from the group consisting of: [ka] L2 is a bond, one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C1-C 12 Alkylene, optionally substituted C-C 10a linker comprising alkenylene, an optionally substituted arylene having 6 to 10 ring atoms, an optionally substituted C3-C8 cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein the alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from -O-, -S-, -C(=O)-, -NR''-, -C(=O)NR''-, -NR''-C(=O)-, -NR''-C(=O)-NR'''-, -NR''-C(=O)-O-, -OC(=O)NR''-; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is the target binding moiety).

[0184] 51. A compound of formula (I) according to any one of embodiments 6 to 56, or a pharmaceutically acceptable salt thereof, wherein R is H.

[0185] 52. A compound of formula (I), according to any one of embodiments 6-57, or a pharmaceutically acceptable salt thereof, wherein each R1 is independently selected from the group consisting of H, C1-C6 alkyl, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, and heteroaryl having 5 to 10 ring atoms.

[0186] 53. A compound of formula (I), according to any one of embodiments 6-58, or a pharmaceutically acceptable salt thereof, wherein each R1 is independently selected from the group consisting of H, CH3, C(=O)OH, CH2C(=O)OH, and pyridyl.

[0187] 54. A compound of formula (I) according to any one of embodiments 6-59, or a pharmaceutically acceptable salt thereof, wherein L1 is C1-C5 alkylene.

[0188] 55. A compound of formula (I) according to any one of embodiments 5-60, or a pharmaceutically acceptable salt thereof, wherein L2 is a bond.

[0189] 56.X2 is [ka] 62. The compound of formula (I) according to any one of embodiments 5 to 61, wherein:

[0190] 57. A compound of formula (I) according to any one of embodiments 5 to 62, or a pharmaceutically acceptable salt thereof, wherein A is a target-binding moiety comprising a peptide, polypeptide, protein, peptidomimetic, aptamer, DARPin, antisense oligonucleotide, siNA, small molecule, microparticle or nanoparticle.

[0191] 58. A compound of formula (I) according to any one of embodiments 5 to 63, or a pharmaceutically acceptable salt thereof, wherein A is a target binding moiety comprising a peptide, polypeptide or protein.

[0192] 59. A compound of formula (I) according to any one of embodiments 5 to 64, or a pharmaceutically acceptable salt thereof, wherein A is a target-binding moiety comprising an antibody, a VhH antibody, a nanobody, a single domain antibody, a protein comprising the antigen-binding region of an antibody, or a fusion protein.

[0193] 60. The compound of formula (I) according to any one of embodiments 5 to 65, wherein A is a target-binding moiety comprising nimotuzumab, trastuzumab, sacituzumab, ramucirumab, cetuximab, enoblitutumab, tusamitamab, amivantamab, or datopotamab.

[0194] 61. The compound is 111 In, 99m Tc, 94m Tc, 67 Ga, 66 Ga, 68 Ga, 52 Fe,169 Er, 72 As, 97 Ru, 203 Pb, 62 Cu, 64 Cu, 67 Cu, 186 Re, 188 Re, 86 Y, 90 Y, 51 Cr, 52m Mn, 177 Lu, 161 Tb, 169 Yb, <00​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​The compound of formula (I) according to any one of embodiments 4 to 66, complexed with a radionuclide selected from Tb.

[0195] 62. A compound of formula (I) according to any one of embodiments 5 to 14, selected from: [ka] [ka] [ka] or a pharmaceutically acceptable salt thereof, wherein A is a target binding moiety as defined in any one of embodiments 63 to 66; The compound is 111 In, 99m Tc, 94m Tc, 67 Ga, 66 Ga, 68 Ga, 52 Fe, 169 Er, 72 As, 97 Ru, 203 Pb, 62 Cu, 64 Cu, 67 Cu, 186 Re, 188 Re, 86 Y, 90 Y, 51 Cr, 52m Mn, 177 Lu, 161 Tb, 169 Yb, 175 Yb, 105 Rh, 166 Dy, 166 Ho, 153 Sm, 149 Pm, 151 Pm, 172 Tm, 121 Sn, 117m Sn, 213 Bi, 142 Pr,143 Pr, 198 Au, 199 Au, 123 I, 124 I, 125 I, 18 F, 149 Tb, 152 Tb, 155 Tb, 47 Sc, 44 Sc, 43 Sc, 225 Ac, 212 Pb, 211 At, 223 Ra, 227 Th, 131 I, 82 Rb, 76 As, 89 Zr, 111 Ag, 165 Er, 227 Ac, 61 Cu, preferably 68 Ga, 64 Cu, 90 Y, 177 Lu, 212 Pb, 225 Ac and 161 The compound of formula (I) according to any one of embodiments 5 to 14, or a pharmaceutically acceptable salt thereof, optionally complexed with a radionuclide selected from Tb.

[0196] 63. The compound according to embodiment 68, selected from: [ka] [ka] or a pharmaceutically acceptable salt thereof.

[0197] 64. Compounds of formula (Cd) or (Ce) [ka] or a pharmaceutically acceptable salt thereof, wherein Ch is a chelator compound of formula (C) as defined in any one of embodiments 1-3, optionally chelated to a radionuclide; S is, independently at each occurrence, a bond, H, or a spacer; e.g., a spacer as defined in embodiment 1; n is 1, 2, 3, 4, 5, 6 or 7, or a pharmaceutically acceptable salt thereof.

[0198] 65. The compound according to embodiment 70, which is a compound of formula (II) [ka] or a pharmaceutically acceptable salt thereof (In the formula, [ka] is a single or double bond, where: [ka] is a single bond, X is -O- or [ka] and [ka] is a double bond, then X is =N-, and Z5' and Z7' together with the N atom form a heteroaryl having 5 or 6 ring atoms, otherwise Z5' and Z7' are each independently selected from the group consisting of H, an albumin binder, and -X1-L1-X2'; each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms, or any combination thereof; Z1', Z2', Z3', Z4', and Z6' are each independently selected from the group consisting of H, an albumin binder H, or a group -X1-L1-X2', with the proviso that at least one of Z1', Z2', Z3', Z4', Z5', Z6', Z7' is a group -X1-L1-X2'; X1 is either present or absent, and if present: X1 is selected from the group consisting of -O-, -NR'-, -C(=O)NR', ​​-NR'C(=O)-, -OC(=O)-, -C(=O)O-, -OC(=O)NR'-, -NR'C(=O)O-; -CH2-O-; and -NR'C(=O)NR', ​​provided that when X1 is NR', R4 is not H; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0199] 66. A compound of formula (I) as defined in embodiment 71, wherein R is H, or a pharmaceutically acceptable salt thereof.

[0200] 67. A compound of formula (II), as defined in embodiment 71 or 72, or a pharmaceutically acceptable salt thereof, wherein each R1 is independently selected from the group consisting of H, C1-C6 alkyl, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, and heteroaryl having 5 to 10 ring atoms.

[0201] 68. A compound of formula (II), as defined in any one of embodiments 71-73, or a pharmaceutically acceptable salt thereof, wherein each R1 is independently selected from the group consisting of H, CH3, C(=O)OH, CH2C(=O)OH, and pyridyl.

[0202] 69. A compound of formula (II) according to any one of embodiments 71-74, or a pharmaceutically acceptable salt thereof, wherein R3 is selected from the group consisting of H, C1-C3 alkyl, and C(=O)OR.

[0203] 70. A compound of formula (II) according to any one of embodiments 71-75, or a pharmaceutically acceptable salt thereof, wherein R3 is selected from the group consisting of H, CH3 and C(=O)OH.

[0204] 71. A compound of formula (II) according to any one of embodiments 71-76, wherein R4 is selected from the group consisting of H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR and heteroaryl having 5 to 10 ring atoms, or a pharmaceutically acceptable salt thereof.

[0205] 72. A compound of formula (II) according to any one of embodiments 71-77, or a pharmaceutically acceptable salt thereof, wherein R4 is selected from the group consisting of H, C(=O)OH, CH2C(=O)OH and pyridyl.

[0206] 73. A compound of formula (I) according to any one of embodiments 71 to 78, or a pharmaceutically acceptable salt thereof, wherein only one of Z'1, Z'2, Z'3, Z'4, Z'5, Z'6, and Z'7 is -X1-L1-X'2, and the other Z' groups are H.

[0207] 74. A compound of formula (I) according to any one of embodiments 71-79, or a pharmaceutically acceptable salt thereof, wherein X1 is selected from the group consisting of -O-, -N(CH3)-, and -C(=O)NH-, or absent.

[0208] 75. Compound of formula (IIa): [ka] or a pharmaceutically acceptable salt thereof (In the formula, [ka] is a single or double bond, where: [ka] is a single bond, X is -O- or [ka] and [ka] is a double bond, then X is ═N—, and the N atom together with the two carbon atoms to which it is attached forms a heteroaryl having 5 or 6 ring atoms; each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms, or any combination thereof; X1 is either present or absent, and if present: X1 is selected from the group consisting of -O-, -NR'-, -C(=O)NR', ​​-NR'C(=O)-, -OC(=O)-, -C(=O)O-, -OC(=O)NR'-, -NR'C(=O)O-; -CH2-O-; and -NR'C(=O)NR', ​​provided that when X1 is NR', R4 is not H; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0209] 76. Compound of formula (IIb): [ka] or a pharmaceutically acceptable salt thereof (In the formula, [ka] is a single or double bond, where: [ka] is a single bond, X is -O- or [ka] and [ka] is a double bond, then X is ═N—, and the N atom together with the two carbon atoms to which it is attached forms a heteroaryl having 5 or 6 ring atoms; each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms, or any combination thereof; X1 is either present or absent, and if present: X1 is selected from the group consisting of -O-, -NR'-, -C(=O)NR', ​​-NR'C(=O)-, -OC(=O)-, -C(=O)O-, -OC(=O)NR'-, -NR'C(=O)O-; -CH2-O-; and -NR'C(=O)NR', ​​provided that when X1 is NR', R4 is not H; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0210] 77. Compound of formula (IIc): [ka] or a pharmaceutically acceptable salt thereof (In the formula, [ka] is a single or double bond, where: [ka] is a single bond, X is -O- or [ka] and [ka] is a double bond, then X is ═N—, and the N atom together with the two carbon atoms to which it is attached forms a heteroaryl having 5 or 6 ring atoms; each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms, or any combination thereof; X1 is either present or absent, and if present: X1 is selected from the group consisting of -O-, -NR'-, -C(=O)NR', ​​-NR'C(=O)-, -OC(=O)-, -C(=O)O-, -OC(=O)NR'-, -NR'C(=O)O-; -CH2-O-; and -NR'C(=O)NR', ​​provided that when X1 is NR', R4 is not H; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0211] 78. Compound of formula (IId): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms, or any combination thereof; Z1', Z2', Z3', Z4', Z5', Z6', and Z7' are each independently from the group consisting of H, an albumin binder H, or a group -X1-L1-X2', provided that at least one of Z1', Z2', Z3', Z4', Z5', Z6', or Z7' is a -X1-L1-X2' group; X1 is either present or absent, and if present: X1 is selected from the group consisting of -O-, -NR'-, -C(=O)NR', ​​-NR'C(=O)-, -OC(=O)-, -C(=O)O-, -OC(=O)NR'-, -NR'C(=O)O-; -CH2-O-; and -NR'C(=O)NR', ​​provided that when X1 is NR', R4 is not H; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0212] 79. Compound of formula (IIe): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; Z1', Z2', Z3', Z4', Z5', Z6', and Z7' are each independently from the group consisting of H, an albumin binder H, or a group -X1-L1-X2', provided that at least one of Z1', Z2', Z3', Z4', Z5', Z6', or Z7' is a -X1-L1-X2' group; X1 is either present or absent, and if present: X1 is selected from the group consisting of -O-, -NR'-, -C(=O)NR', ​​-NR'C(=O)-, -OC(=O)-, -C(=O)O-, -OC(=O)NR'-, -NR'C(=O)O-; -CH2-O-; and -NR'C(=O)NR', ​​provided that when X1 is NR', R4 is not H; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0213] 80. Compound of formula (IId): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; Z1', Z2', Z3', Z4', Z5', Z6', and Z7' are each independently from the group consisting of H, an albumin binder H, or a group -X1-L1-X2', provided that at least one of Z1', Z2', Z3', Z4', Z5', Z6', or Z7' is a -X1-L1-X2' group; X1 is either present or absent, and if present: X1 is selected from the group consisting of -O-, -NR'-, -C(=O)NR', ​​-NR'C(=O)-, -OC(=O)-, -C(=O)O-, -OC(=O)NR'-, -NR'C(=O)O-; -CH2-O-; and -NR'C(=O)NR', ​​provided that when X1 is NR', R4 is not H; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0214] 81. Compound of formula (IIg): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms, or any combination thereof; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0215] 82. Compound of formula (IIh): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms, or any combination thereof; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0216] 83. Compound of formula (IIi): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms, or any combination thereof; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0217] 84. Compound of formula (IIj): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms, or any combination thereof; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0218] 85. Compound of formula (IIk): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms, or any combination thereof; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0219] 86. Compound of formula (IIm): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms, or any combination thereof; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0220] 87. Compound of formula (IIn): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms, or any combination thereof; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0221] 88. Compound of formula (IIo): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms, or any combination thereof; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0222] 89. Compound of formula (IIp): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms, or any combination thereof; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0223] 90. Compound of formula (IIq): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms, or any combination thereof; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0224] 91. Compound of formula (IIg'): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0225] 92. Compound of formula (IIh'): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0226] 93. Compound of formula (IIi'): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0227] 94. Compound of formula (IIj'): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0228] 95. Compound of formula (IIk'): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0229] 96. Compound of formula (IIm'): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0230] 97. Compound of formula (IIn′): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0231] 98. Compound of formula (IIo'): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0232] 99. Compound of formula (IIp'): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0233] 100. Compound of formula (IIq') [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0234] 101. Compound of formula (IIg″): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0235] 102. Compound of formula (IIh″): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0236] 103. Compound of formula (IIi″): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0237] 104. Compound of formula (IIj″): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0238] 105. Compound of formula (IIk″): [ka] or a pharmaceutically acceptable salt thereof (wherein each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0239] 106. Compound of formula (IIm″): [ka] or a pharmaceutically acceptable salt thereof (wherein each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0240] 107. Compound of formula (IIn″): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0241] 108. Compound of formula (IIo″): [ka] or a pharmaceutically acceptable salt thereof (In the formula, each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0242] 109. Compound of formula (IIp″): [ka] or a pharmaceutically acceptable salt thereof (wherein each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0243] 110. Compound of formula (IIq''): [ka] or a pharmaceutically acceptable salt thereof (wherein each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

[0244] 111. A compound of formula (II) according to any one of embodiments 71-119, wherein R is H, or a pharmaceutically acceptable salt thereof.

[0245] 112. A compound of formula (II), according to any one of embodiments 71-120, or a pharmaceutically acceptable salt thereof, wherein each R1 is independently selected from the group consisting of H, C1-C6 alkyl, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, and heteroaryl having 5 to 10 ring atoms.

[0246] 113. A compound of formula (II), according to any one of embodiments 71-121, or a pharmaceutically acceptable salt thereof, wherein each R1 is independently selected from the group consisting of H, CH3, C(=O)OH, CH2C(=O)OH, and pyridyl.

[0247] 114. A compound of formula (II) according to any one of embodiments 71-122, or a pharmaceutically acceptable salt thereof, wherein L1 is C1-C5 alkylene.

[0248] 115.X'2 is [ka] 124. The compound of formula (II) according to any one of embodiments 71 to 123, wherein:

[0249] 116. The compound is 111 In, 99m Tc, 94m Tc, 67 Ga, 66 Ga, 68 Ga, 52 Fe, 169 Er, 72 As, 97 Ru, 203 Pb, 62 Cu, 64 Cu, 67 Cu, 186 Re, 188 Re, 86 Y, 90 Y,51 Cr, 52m Mn, 177 Lu, 161 Tb, 169 Yb, 175 Yb, 105 Rh, 166 Dy, 166 Ho, 153 Sm, 149 Pm, 151 Pm, 172 Tm, 121 Sn, 117m Sn, 213 Bi, 142 Pr, 143 Pr, 198 Au, 199 Au, 123 I, 124 I, 125 I, 18 F, 149 Tb, 152 Tb, 155 Tb, 47 Sc, 44 Sc, 43 Sc, 225 Ac, 212 Pb, 211 At, 223 Ra, 227 Th, 131 I, 82 Rb, 76 As, 89 Zr, 111 Ag, 165 Er, 227 Ac, 61 Cu, preferably selected from: 68 Ga, 64 Cu, 90 Y, 177 Lu, 212 Pb, 225 Ac and 161 The compound of formula (II) according to any one of embodiments 71 to 124, complexed with a radionuclide selected from Tb.

[0250] 117. A compound of formula (II) according to any one of embodiments 71 to 80 selected from the following: [ka] [ka] [ka] or a pharmaceutically acceptable salt thereof, wherein the compound is 111 In, 99m Tc, 94m Tc, 67 Ga, 66 Ga, 68 Ga, 52 Fe, 169 Er, 72 As, 97 Ru, 203 Pb, 62 Cu, 64 Cu, 67 Cu, 186 Re, 188 Re, 86 Y, 90 Y, 51 Cr, 52m Mn, 177 Lu, 161 Tb, 169 Yb, 175 Yb, 105 Rh, 166 Dy, 166 Ho, 153 Sm, 149 Pm, 151 Pm, 172 Tm, 121 Sn, 117m Sn, 213 Bi, 142 Pr, 143 Pr, 198 Au, 199 Au, 123 I, 124 I, 125 I, 18 F, 149 Tb, 152 Tb, 155 Tb, 47 Sc, 44 Sc, 43 Sc, 225 Ac, 212 Pb, 211 At,223 Ra, 227 Th, 131 I, 82 Rb, 76 As, 89 Zr, 111 Ag, 165 Er, 227 Ac, 61 Cu, preferably selected from: 68 Ga, 64 Cu, 90 Y, 177 Lu, 212 Pb, 225 Ac, and 161 81. A compound of formula (II) according to any one of embodiments 71 to 80, or a pharmaceutically acceptable salt thereof, optionally labeled with a radionuclide selected from Tb.

[0251] 118. The compound according to embodiment 68, selected from: [ka] [ka] or a pharmaceutically acceptable salt thereof.

[0252] 119. A pharmaceutical composition comprising a compound according to any one of embodiments 1-127 and at least one pharmaceutically acceptable carrier.

[0253] 120. A compound according to any one of embodiments 1-127, or a pharmaceutically acceptable salt thereof, for use as a medicament.

[0254] 121. The compound for use according to embodiment 129, or a pharmaceutically acceptable salt thereof, for use in the treatment of cancer.

[0255] 122. A method for treating cancer, comprising contacting cancer cells with a therapeutically effective amount of a compound according to any one of embodiments 1-127, or a pharmaceutically acceptable salt thereof.

[0256] 123. A compound according to any one of embodiments 1-127, or a pharmaceutically acceptable salt thereof, for use in imaging.

[0257] 124. A method of imaging, comprising contacting cancer cells with an effective amount of a compound according to any one of embodiments 1 to 127, or a pharmaceutically acceptable salt thereof.

[0258] 125. A compound according to any one of embodiments 1-127, or a pharmaceutically acceptable salt thereof, for use in diagnosis, typically for use in diagnosing a cancer disease.

[0259] 126. A method for diagnosing and / or detecting cancer cells in a subject, comprising administering to said subject, preferably a human, an effective amount of a compound according to any one of embodiments 1 to 127, or a pharmaceutically acceptable salt thereof.

[0260] 127. Use of a compound of formula (I) as defined in claim 5 or a compound of formula (II) as defined in claim 71 for the manufacture of a pharmaceutical composition.

[0261] 128. A method for synthesizing a compound of formula (I) according to embodiment 5, comprising: reacting a targeting compound L2-A (wherein L2 is an optional linker and A is a target binding moiety) with a compound of formula (II): [ka] or a pharmaceutically acceptable salt thereof, During the ceremony, [ka] is a single or double bond, where: [ka] is a single bond, X is -O- or [ka] and [ka] is a double bond, then X is =N-, and Z5' and Z7' together with the N atom form a heteroaryl having 5 or 6 ring atoms, otherwise Z5' and Z7' are each independently selected from the group consisting of H, an albumin binder, and -X1-L1-X2'; each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10 selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is independently selected from the group consisting of H and C1-C6 alkyl; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms, or any combination thereof; Z1', Z2', Z3', Z4', and Z6' are each independently from the group consisting of H, an albumin binder H, or a group -X1-L1-X2', with the proviso that at least one of Z1', Z2', Z3', Z4', Z5', Z6', and Z7' is a group -X1-L1-X2'; X1 is either present or absent, and if present: X1 is selected from the group consisting of -O-, -NR'-, -C(=O)NR', ​​-NR'C(=O)-, -OC(=O)-, -C(=O)O-, -OC(=O)NR'-, -NR'C(=O)O-; -CH2-O-; and -NR'C(=O)NR', ​​provided that when X1 is NR', R4 is not H; L1 is a linker selected from the group consisting of C1-C5 alkylene, (-CH2CHO)n, C1-C6 heteroalkylene, C3-C6 cycloalkylene, -C3-C8 heterocycloalkylene-, heteroarylene having 5-10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably: albumin binder, C1-C6 alkyl, -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halo optionally substituted with one or more substituents selected from aryl, -SiR'R''R''', -OC(=O)R', (C1-C6 alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C1-C6 alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R'')=NR'''', -S(=O)R', -S(=O)R', -S(=O)NR'R'', -NRS(=O)R', -CN and -NO; R', R'', R''', and R'''' are each independently H, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, 3-10 membered heterocycloalkyl, C6-C 10 selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X2' is a group selected from the group consisting of: [ka] each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; The method wherein q is 1, 2, 3, 4, 5 or 5.

[0262] 129. 68 Ga and / or 177A compound capable of complexing Lu at a temperature of ≦60° C. to achieve a complexation of ≧85% of the compound in the composition, said compound being a compound of formula (C) [ka] or a pharmaceutically acceptable salt thereof (In the formula, [ka] is a single or double bond, [ka] is a single bond, X is -O- or [ka] and [ka] is a double bond, X is =N-; Each m is 0 to 5; each R is independently selected from the group consisting of H and C1-C6 alkyl; Each R1 is independently selected from H, C(=O)OR2, (C1-C6 alkyl)-C(=O)OR2, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C6-C 10selected from the group consisting of aryl, heteroaryl having 5 to 10 ring atoms, and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl, and heteroaryl are optionally substituted with one or more substituents independently selected from: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'''')═NR'''', -S(═O)R', -S(═O)R', -S(═O)NR'R'', -NRS(═O)R', -CN, and -NO; each R2 is selected from the group consisting of H and C1-C6 alkyl; R3 is selected from the group consisting of H, C1-C6 alkyl, and C(=O)OR; R4 is H, C(=O)OR, (C1-C6 alkyl)-C(=O)OR, C1-C6 alkyl, C1-C6 heteroalkyl, C3-C6 cycloalkyl, C3-C8 heterocycle, C6-C 10 aryl, heteroaryl having 5 to 10 ring atoms, or any combination thereof) Including, The compound of formula (C) is an optionally substituted compound. [Example]

[0263] General conditions: Mass spectra were acquired on LC-MS, SFC-MS, or GC-MS systems using electrospray, chemical, and electron impact ionization methods from various instruments configured as follows: Agilent 1100 HPLC system equipped with an Agilent 6110 mass spectrometer. [M+H]+ refers to the protonated molecular ion of the species.

[0264] NMR spectra were analyzed on a Bruker AVANCE 400 MHz or 500 MHz NMR mass spectrometer under TopSpin program control using ICON-NMR. Spectra were measured at 298 K unless otherwise specified and were referenced to the solvent resonance.

[0265] device LC / MS method: LC-MS-1 System: Shimadzu (2020-single quadrupole type) Column: Synergi 2.5μ MAX-RP100 A Mercury Column temperature: 40℃ Slope: 0.1 / 5, 0.5 / 5, 1.0 / 95, 1.5 / 95, 2.0 / 5, 3.0 / 5 Eluent A: 0.1% HCO2H in water Eluent B: CH3CN Flow rate: 2.0mL / min LC-MS-2 System: API 2000 Column: Kinetex EVO 2.6 μm, 50 * 4.6 mm, column temperature: 30°C Gradient: 0 / 30, 0.5 / 30, 1.5 / 95, 2.4 / 95, 2.5 / 30, 3.0 / 30 Eluent A: 0.1% HCO2H in water Eluent B: CH3CN Flow rate: 2.0mL / min LC-MS-3 System: EVO ESI 3200 Column: Kinetex EVO 2.6 μm, 50 * 4.6 mm, column temperature: 30°C Gradient: 0 / 30, 0.2 / 30, 0.7 / 95, 2.0 / 95, 2.5 / 30, 3.5 / 30 Eluent A: 0.1% HCO2H in water Eluent B: 0.1% HCO2H in CH3CN Flow rate: 2.0mL / min LC-MS-4 System: EVO ESI 3200 Column: Kinetex EVO 2.6 μm, 50 * 4.6 mm, column temperature: 30°C Slope: 0.0 / 20, 0.25 / 20, 1.0 / 95, 2.5 / 95, 3.0 / 20, 4.0 / 20, 5.0 / 20 Eluent A: 0.1% HCO2H in water Eluent B: 0.1% HCO2H in CH3CN Flow rate: 2.0mL / min

[0266] LC-MS-5 (using Shimadzu LCMA-2020): Kinetex EVO C18, particle size: 5 μm, column size: 2.1 × 30 mm, column temperature: 50 °C; flow rate: 1.5 mL / min; eluent A: 0.0375% TFA in water; eluent B: 0.01875% TFA in acetonitrile; gradient: 5% to 95% B in 0.8 min; then 95% B in acetonitrile for 0.4 min, then 95% to 5% B in 0.35 min. UPLC / MS method: An Agilent 1100 HPLC system equipped with an Agilent 6110 mass spectrometer is used. LC-MS-6: Phenomenex Gemini C18; particle size: 3.0 μm; column size: 50 × 4.6 mm; column temperature: 50 °C; flow rate: 1 mL / min; eluent A: HO + 0.1% TFA; eluent B: methanol + 0.1% TFA; gradient: 5 to 95% B in 2.0 min, then 95% B for 0.2 min. LC-MS-7: Waters BEH C18; particle size: 1.7 μm; column size: 50 × 2.1 mm; column temperature: 50 °C; flow rate: 0.8 mL / min; eluent A: HO + 0.1% TFA; eluent B: acetonitrile + 0.1% TFA; gradient: 0.20 min 5% B; 1.30 min 5% to 95% B, 0.25 min 95% B. LC-MS-8: CORTECS™ C18; particle size: 2.7 μm; column size: 50 × 2.1 mm; column temperature: 80 °C; flow rate: 1 mL / min; eluent A: HO + 4.76% isopropanol + 0.05% FA + 3.75 mM AA; eluent B: isopropanol + 0.05% FA; gradient: 1 to 50% B in 1.4 min, 50 to 98% B in 0.3 min. LC-MS-9: CORTECS™ C18; particle size: 2.7 μm; column size: 50 × 2.1 mm; column temperature: 80 °C; flow rate: 1 mL / min; eluent A: HO + 0.05% FA + 3.75 mM AA; eluent B: isopropanol + 0.05% FA; gradient: 1 to 98% B in a 1.7 min curve. LC-MS-10: CORTECS™ C18; particle size: 2.7 μm; column size: 50 × 2.1 mm; column temperature: 80 °C; flow rate: 1 mL / min; eluent A: water + 4.76% isopropanol + 0.05% FA + 3.75 mM AA; eluent B: isopropanol + 0.05% FA; gradient: 1 to 50% B in 1.4 min, 50 to 98% B in 0.3 min. LC-MS-11: ACQUITY UPLC® BEH C18; particle size: 1.7 μm; column size: 100 × 2.1 mm; column temperature: 80 °C; flow rate: 0.4 mL / min; eluent A: water + 4.76% isopropanol + 0.05% FA + 3.75 mM AA; eluent B: isopropanol + 0.05% FA; gradient: 1 to 60% B in 8.4 min, 60 to 98% B in 1.0 min. LC-MS-12: CORTECS™ C18; particle size: 2.7 μm; column size: 50 × 2.1 mm; column temperature: 80 °C; flow rate: 1 mL / min; eluent A: water + 4.76% isopropanol + 0.05% FA + 3.75 mM AA; eluent B: isopropanol + 0.05% FA; gradient: 1 to 50% B in 1.4 min, 50 to 98% B in 0.3 min; detector: ELSD LC-MS-13: CORTECS™ C18; particle size: 2.7 μm; column size: 50 × 2.1 mm; column temperature: 80 °C; flow rate: 1 mL / min; eluent A: HO + 0.05% FA + 3.75 mM AA; eluent B: isopropanol + 0.05% FA; gradient: 1 to 98% B in 1.4 min, concave LC-MS-14: CORTECS™ C18; particle size: 2.7 μm; column size: 50 × 2.1 mm; column temperature: 80 °C; flow rate: 1 mL / min; eluent A: water + 0.05% FA + 3.75 mM AA; eluent B: acetonitrile + 0.04% FA; gradient: 5 to 98% B in 1.4 min. LC-MS-15: CORTECS™ C18; particle size: 2.7 μm; column size: 50 × 2.1 mm; column temperature: 80 °C; flow rate: 1 mL / min; eluent A: HO + 0.05% FA + 3.75 mM AA; eluent B: isopropanol + 0.05% FA; gradient: 5 to 50% B in 1.4 min, 50 to 98% B in 0.3 min LC-MS-16: ACQUITY UPLC® CSH™ C18; particle size: 1.7 μm, column size: 2.1 × 100 mm, column temperature: 80.0 °C; flow rate: 0.5 mL / min; eluent A: HO + 0.05% TFA, eluent B: CHCN + 0.04% TFA; gradient: hold at 5% B for 0.2 min, 5% to 98% B in 9.2 min.

[0267] Preparative method: Flash chromatography: Normal phase chromatography was carried out on silica gel using pre-packed columns (RediSep Rf cartridges, or SNAP cartridges on Isolute or on silica gel, or applied as a solution) or using glass columns according to standard flash chromatography methods, unless otherwise stated. Systems: Teledyne ISCO, CombiFlash Rf, Biotage Isolera.

[0268] Reverse phase HPLC: RP-HPLC-1: Column: Gemini (250 x 21.2 mm, 5 μm); Mobile phase: A = 0.1% formic acid in water, B = acetonitrile; Flow rate: 18 mL / min. RP-HPLC-2: Waters; Column: XBridge Prep C18; Particle size: 5 μm; Column size: 30 × 100 mm; Flow rate: 50 mL / min; Mobile phase A: H2O + 0.1% TFA (1 / 1) and B: CH3CN; Gradient: 2 to 30% solvent A in 10 min RP-HPLC-3: ACCQ preparative column; XBridge Prep C18 column; 5 μm particle size; 30 × 100 mm column; flow rate: 50 mL / min; mobile phase A: H2O + 0.1% TFA and B: CH3CN; gradient: 2 to 20% solvent A in 10 min RP-HPLC-4: ACCQ preparative column; XBridge Prep C18 column; 5 μm particle size; column Dimensions: 30 x 100 mm; Flow rate: 50 mL / min; Mobile phase A: H2O + 0.1% TFA and B: CH3CN; Gradient: 0 to 100% solvent B in 12 min RP-HPLC-5: Sunfire preparative column; C18 OBD™ column; 5 μm particle size; column Dimensions: 30 x 100 mm; Flow rate: 30 mL / min; Mobile phase A: H2O + 0.1% TFA and B: CH3CN; Gradient: 0 to 30% solvent B in 30 min RP-HPLC-6: ACCQ preparative column; XBridge Prep C18 column; 5 μm particle size; Dimensions: 50 x 100 mm; Flow rate: 100 mL / min; Mobile phase A: H2O + 0.1% TFA and B: CH3CN; Gradient: 0 to 100% solvent B in 12 min

[0269] Abbreviation: BOC tertiary butyl carboxylate br Broad d doublet dd Doublet of Doublets DCM dichloromethane DMF N,N-dimethylformamide DMSO dimethyl sulfoxide EDTA Ethylenediaminetetraacetic acid ESI electrospray ionization EtOAc ethyl acetate h time HPLC High Pressure Liquid Chromatography LCMS Liquid Chromatography Mass Spectrometry MeOH Methanol MS mass spectrometry m multiplet mg milligram min ml milliliter mmol millimole m / z mass-to-charge ratio NMR nuclear magnetic resonance ppm parts per million rac racemic Rt retention time s singlet t triplet TFA trifluoroacetic acid THF tetrahydrofuran

[0270] The following examples are intended to illustrate the present invention and should not be construed as limiting it. Temperatures are given in degrees Celsius. Unless otherwise noted, all evaporations are carried out under reduced pressure, typically at about 15 mmHg to 100 mmHg (= 20 to 133 mbar). The structures of final products, intermediates, and starting materials are confirmed by standard analytical methods, e.g., microanalysis or spectroscopic characteristics, e.g., MS, IR, NMR. Abbreviations used are conventional in the art.

[0271] All starting materials, building blocks, reagents, acids, bases, dehydrating agents, solvents, and catalysts utilized to synthesize the compounds of the present invention are either commercially available or can be prepared by organic synthesis methods known to those skilled in the art. Additionally, the compounds of the present invention can be prepared by organic synthesis methods known to those skilled in the art, as shown in the examples below.

[0272] Preparation of intermediates Intermediate A: di-tert-butyl 2,2'-((((2-(tert-butoxy)-2-oxoethyl)azanediyl)bis(ethane-2,1-diyl))bis(azanediyl)) diacetate [ka] Step 1: Di-tert-butyl 2,2'-((((2-(tert-butoxy)-2-oxoethyl)azanediyl)bis(ethane-2,1-diyl))bis(benzylazanediyl)) diacetate To a stirred suspension of tert-butyl glycinate hydrochloride (2.55 g, 15.29 mmol) in anhydrous CH3CN (100 mL) was added anhydrous K2CO3 (21.09 g, 152.87 mmol) at room temperature. After stirring at 50 °C for 1 h, the reaction mixture was cooled to room temperature, and tert-butyl N-benzyl-N-(2-bromoethyl)glycinate (prepared according to Eur. J. Org. Chem. 2018, 1765-1773, supporting information, page 6, compound 5) (10.0 g, 30.57 mmol) in anhydrous CH3CN (20 mL) was added at room temperature. The resulting mixture was heated to reflux for 24 h and cooled to room temperature. The suspension was filtered through a short plug of Celite, and the filtrate was evaporated under reduced pressure. The residue was purified by flash chromatography using a Redisep cartridge (80 g) eluting with hexane / EtOAc to give the title compound (12 g, crude) as a pale yellow viscous oil. LC-MS-4: Rt=1.551 min, m / z: 626.50 [M+H]; 1 H NMR(400MHz,CDCl3)δ=7.31-7.25(m,10H),3.78(s,4H),3.29(s,2H),3.21(s,2H),2.74(s,8H),1.45(s,18H),1.42(s,9H).

[0273] Step 2: Di-tert-butyl 2,2'-((((2-(tert-butoxy)-2-oxoethyl)azanediyl)bis(ethane-2,1-diyl))bis(azanediyl))diacetate A solution of di-tert-butyl 2,2'-((((2-(tert-butoxy)-2-oxoethyl)azanediyl)bis(ethane-2,1-diyl))bis(benzylazanediyl))diacetate (3.0 g, 31.9 mmol) in ethanol (30 mL) was treated with 30% w / w Pd / C (900 mg) under an argon atmosphere. The reaction mixture was placed under hydrogen gas at room temperature for 16 h. The reaction mixture was filtered through a bed of Celite and washed with methanol (2 x 50 mL). The combined organic layers were evaporated to give the title compound (6.0 g, crude for 2 x 3 g batches) as a colorless oil. LC-MS-2: Rt = 0.14 min, m / z: 446.20 [M+H]; 1 H NMR(400MHz,DMSO-d6)δ=3.15-3.22(m,8H),2.61-2.62(m,4H),2.52-2.54(m,4H),1.35-1.41(m,27H).

[0274] Intermediate B: Di-tert-butyl N,N-bis(2-((2-(tert-butoxy)-2-oxoethyl)amino)ethyl)-L-aspartate [ka] Step 1: Di-tert-butyl L-aspartate To a stirred solution of L-aspartic acid (5.0 g, 37.5 mmol) in tert-butyl acetate (468 mL), 70% aqueous HClO was added dropwise, and the reaction mixture was stirred at room temperature for 16 hours. After completion, the reaction mixture was cooled to 0° C. and then extracted with cold 0.5 N aqueous HCl. The aqueous layer was neutralized with saturated NaHCO solution and extracted with EtOAc. The combined organic layers were dried using anhydrous NaSO, filtered, and concentrated under reduced pressure to give di-tert-butyl L-aspartate (3.0 g, 32.60%) as a colorless oil. LC-MS-2: Rt=0.13 min, m / z: 246.10 [M+H]; 1 H NMR(400MHz, CDCl3)δ=4.09(t,J=5.0Hz,1H),2.91(d,J=5Hz,2H),2.09(s,2H),1.46-1.48(m,18H).

[0275] Step 2: Di-tert-butyl N,N-bis(2-(benzyl(2-(tert-butoxy)-2-oxoethyl)amino)ethyl)-L-aspartate Similar to Intermediate A, Step 1, di-tert-butyl L-aspartate (1.14 g, 4.63 mmol), anhydrous KCO (6.33 g, 45.86 mmol), and tert-butyl N-benz...

Claims

1. Compounds of formula (I) 【Chemistry 1】 or a pharmaceutically acceptable salt thereof (In the formula, 【Chemistry 2】 is a single or double bond, 【Transformation 3】 is a single bond, X is —O— or 【Chemistry 4】 and 【Transformation 5】 is a double bond, X is ═N—, and Z ５ and Z ７ together with the N atom form a heteroaryl having 5 or 6 ring atoms, otherwise Z ５ and Z ７ are each independently H, an albumin binder, and -X １ -L １ -X ２ -L ２ - selected from the group consisting of A; Each R is independently H and C １ ~C ６ selected from the group consisting of alkyl; Each R １ are independently H, C(=O)OR ２ , (C １ ~C ６ alkyl)-C(=O)OR ２ , C １ ~C ６ Alkyl, C １ ~C ６ Heteroalkyl, C ３ ~C ６ Cycloalkyl, C ６ ~C １０ and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl and heteroaryl are selected from the group consisting of: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'')═NR'''', -S(═O)R', -S(═O) ２ R', -S(=O) ２ NR'R'', -NRS (=O) ２ R', -CN and -NO ２ optionally substituted with one or more substituents independently selected from Each R ２ are independently H and C １ ~C ６ selected from the group consisting of alkyl; R ３ is H, C １ ~C ６ selected from the group consisting of alkyl and C(═O)OR; R ４ is H, C(=O)OR, (C １ ~C ６ alkyl)-C(=O)OR, C １ ~C ６ Alkyl, C １ ~C ６ Heteroalkyl, C ３ ~C ６ Cycloalkyl, C ３ ~C ８ Heterocycle, C ６ ~C １０ selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms, or any combination thereof; Z １ , Z ２ , Z ３ , Z ４ , and Z ６ are each independently H, an albumin binder, and -X １ -L １ -X ２ -L ２ -A, with the proviso that Z １ , Z ２ , Z ３ , Z ４ , Z ５ , Z ６ , and Z ７ At least one of the following is -X １ -L １ -X ２ -L ２ -A group; X １ is either present or absent, and if present: X １ -O-, -NR'-, -C(=O)NR'-, -NR'C(=O)-, -OC(=O)-, -C(=O)O-, -OC(=O)NR'-, -NR'C(=O)O-, -CH ２ is selected from the group consisting of —O—, and —NR′C(═O)NR′—, with the proviso that X １ When is NR′, R ４ is not H; L １ is C １ ~C ５ Alkylene, (-CH ２ CH ２ O) ｎ , C １ ~C ６ Heteroalkylene, C ３ ~C ６ Cycloalkylene, -C ３ ~C ８ a linker selected from the group consisting of heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein the alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are independently selected from the group consisting of an albumin binder, C １ ~C ６ Alkyl, -OR', =O, =NR', =N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(=O)R', (C １ ~C ６ alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C １ ~C ６ Alkyl) -C(=O)OR', -C(=O)NR'R'', -OC(=O)NR'R'', -NR'C(=O)R', -NR'-C(=O)NR'R''', -NR'C(=O)OR', -NR'-C(NR'R''')=NR''', -S(=O)R', -S(=O) ２ R', -S(=O) ２ NR'R'', -NRS (=O) ２ R', -CN and -NO ２ optionally substituted with one or more substituents selected from R', R'', R''', and R'''' are each independently H, C １ ~C ６ Alkyl, C １ ~C ６ Heteroalkyl, C ３ ~C ６ Cycloalkyl, C ３ ~C ８ Heterocycle, C ６ ~C １０ selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X ２ is selected from the group consisting of: 【Transformation 6】 L ２ is a bond or one or more amino acids, one or more N-substituted amino acids, an optionally substituted polyether, an optionally substituted C １ ~C １２ Alkylene, optionally substituted C ２ ~C １０ alkenylene, optionally substituted arylene having 6 to 10 ring atoms, optionally substituted C ３ ~C ８ a linker comprising a cycloalkylene, an optionally substituted heterocycloalkylene having 5 to 10 ring atoms, an optionally substituted heteroarylene having 5 to 10 ring atoms, or any combination thereof, wherein said alkylene and alkenylene optionally contain one or more heteroatoms or chemical groups selected from —O—, —S—, —C(═O)—, —NR″—, —C(═O)NR″—, —NR″-C(═O)—NR′″—, —NR″-C(═O)—NR′″—, —NR″-C(═O)—O—, —O-C(═O)NR″—; each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5; A is a target binding moiety).

2. 2. The compound of claim 1, wherein R is H, or a pharmaceutically acceptable salt thereof.

3. Each R １ are independently H, C １ ~C ６ Alkyl, C(=O)OR ２ , (C １ ~C ６ alkyl)-C(=O)OR ２ 3. The compound of claim 1 or 2, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of: and heteroaryl having 5 to 10 ring atoms.

4. Each R １ are independently H, CH ３ , C(=O)OH, CH ２ 4. The compound of any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, independently selected from the group consisting of C(=O)OH and pyridyl.

5. R ３ is H, C １ ~C ３ 5. The compound of any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of alkyl, and C(=O)OR.

6. R ３ is H, CH ３ and C(=O)OH, or a pharmaceutically acceptable salt thereof.

7. R ４ is H, C(=O)OR, (C １ ~C ６ 7. The compound of any one of claims 1 to 6, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of: (alkyl)-C(=O)OR and heteroaryl having 5 to 10 ring atoms.

8. R ４ is H, C(=O)OH, CH ２ 8. The compound of any one of claims 1 to 7, or a pharmaceutically acceptable salt thereof, selected from the group consisting of C(=O)OH and pyridyl.

9. Z １ , Z ２ , Z ３ , Z ４ , Z ５ , Z ６ , and Z ７ Only one of the -X １ -L １ -X ２ -L ２ -A and the other Z group is H, or a pharmaceutically acceptable salt thereof.

10. X １ is -O-, -N(CH ３ 10. The compound of any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of -C(=O)- and -C(=O)NH- or absent.

11. L １ is C １ ~C ５ The compound according to any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof, which is alkylene.

12. X ２ teeth, 【Transformation 7】 12. The compound according to any one of claims 1 to 11, wherein:

13. 13. The compound of any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, wherein A is a target-binding moiety comprising a peptide, polypeptide, protein, peptidomimetic, aptamer, DARPin, antisense oligonucleotide, siNA, small molecule, microparticle, or nanoparticle.

14. 14. The compound of any one of claims 1 to 13, or a pharmaceutically acceptable salt thereof, wherein A is a target binding moiety comprising a peptide, polypeptide, or protein.

15. 15. The compound of any one of claims 1 to 14, or a pharmaceutically acceptable salt thereof, wherein A is a target binding moiety comprising an antibody, a VhH antibody, a nanobody, a single domain antibody, a protein comprising the antigen-binding region of an antibody, or a fusion protein.

16. 16. The compound of any one of claims 1 to 15, wherein A is a target binding moiety comprising nimotuzumab, trastuzumab, sacituzumab, ramucirumab, cetuximab, enoblitutamab, tusamitamab, amivantamab, or datopotamab.

17. A compound according to any one of claims 1 to 16 of formula (Id) 【Transformation 8】 or a pharmaceutically acceptable salt thereof.

18. Compounds according to any one of claims 1 to 16 of formula (Ie) 【Chemistry 9】 or a pharmaceutically acceptable salt thereof.

19. A compound according to any one of claims 1 to 16 of formula (If) 【Chemistry 10】 or a pharmaceutically acceptable salt thereof.

20. A compound according to any one of claims 1 to 16, selected from: 【Chemistry 11】 or a pharmaceutically acceptable salt thereof.

21. A compound according to any one of claims 1 to 16, selected from: 【Chemistry 12】 or a pharmaceutically acceptable salt thereof.

22. A compound according to any one of claims 1 to 16, selected from: 【Chemistry 13】 or a pharmaceutically acceptable salt thereof.

23. A compound according to any one of claims 1 to 16, selected from: 【Chemistry 14】 or a pharmaceutically acceptable salt thereof.

24. A compound according to any one of claims 1 to 16, selected from: 【Chemistry 15】 or a pharmaceutically acceptable salt thereof.

25. A compound according to any one of claims 1 to 16, selected from: 【Chemistry 16】 or a pharmaceutically acceptable salt thereof.

26. A compound according to any one of claims 1 to 16, selected from: 【Chemistry 17】 or a pharmaceutically acceptable salt thereof.

27. A compound according to any one of claims 1 to 16, selected from: [Chemistry 18] or a pharmaceutically acceptable salt thereof.

28. A compound according to any one of claims 1 to 16, selected from: 【Chemistry 19】 or a pharmaceutically acceptable salt thereof.

29. A compound according to any one of claims 1 to 16, selected from: 【Chemistry 20】 or a pharmaceutically acceptable salt thereof.

30. A compound according to any one of claims 1 to 16, selected from: 【Chemistry 21】 or a pharmaceutically acceptable salt thereof.

31. A compound according to any one of claims 1 to 16, selected from: 【Chemistry 22】 or a pharmaceutically acceptable salt thereof.

32. A compound according to any one of claims 1 to 16, selected from: 【Chemistry 23】 【Chemistry 24】 【Chemistry 25】 or a pharmaceutically acceptable salt thereof.

33. 33. The compound of claim 32, selected from the following: 【Chemistry 26】 【Chemistry 27】 or a pharmaceutically acceptable salt thereof wherein A is a target binding moiety as defined in any one of claims 13 to 16.

34. 34. The compound of any one of claims 1 to 33, or a pharmaceutically acceptable salt thereof, further complexed to a radionuclide.

35. The radioactive nuclide is １１１ In, ９９ｍ Tc, ９４ｍ Tc, ６７ Ga, ６６ Ga, ６８ Ga, ５２ Fe, １６９ Er, ７２ As, ９７ Ru, ２０３ Pb, ６２ Cu, ６４ Cu, ６７ Cu, １８６ Re, １８８ Re, ８６ Y, ９０ Y, ５１ Cr, ５２ｍ Mn, １７７ Lu, １６１ Tb, １６９ Yb, １７５ Yb, １０５ Rh, １６６ Dy, １６６ Ho, １５３ Sm, １４９ Pm, １５１ Pm, １７２ Tm, １２１ Sn, １１７ｍ Sn, ２１３ Bi, １４２ Pr, １４３ Pr, １９８ Au, １９９ Au, １２３ I, １２４ I, １２５ I, １８ F, Al １８ F, １４９ Tb, １５２ Tb, １５５ Tb, ４７ Sc, ４４ Sc, ４３ Sc, ２２５ Ac, ２１２ Pb, ２１１ At, ２２３ Ra, ２２７ Th, １３１ I, ８２ Rb, ７６ As, ８９ Zr, １１１ Ag, １６５ Er, ２２７ Ac, and ６１ 35. The compound of claim 34, wherein the compound is selected from the group consisting of Cu.

36. Compound of formula (II) 【Chemistry 28】 or a pharmaceutically acceptable salt thereof (In the formula, 【Chemistry 29】 is a single or double bond, where: 【Transformation 30】 is a single bond, X is —O— or 【Chemistry 31】 and 【Chemistry 32】 is a double bond, X is ═N—, and Z ５ ' and Z ７ together with the N atom form a heteroaryl having 5 or 6 ring atoms, otherwise Z ５ ' and Z ７ Each ' is independently H, an albumin binder, and -X １ -L １ -X ２ selected from the group consisting of: Each R is independently H and C １ ~C ６ selected from the group consisting of alkyl; Each R １ are independently H, C(=O)OR ２ , (C １ ~C ６ alkyl)-C(=O)OR ２ , C １ ~C ６ Alkyl, C １ ~C ６ Heteroalkyl, C ３ ~C ６ Cycloalkyl, C ６ ~C １０ and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl and heteroaryl are selected from the group consisting of: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'')═NR'''', -S(═O)R', -S(═O) ２ R', -S(=O) ２ NR'R'', -NRS (=O) ２ R', -CN and -NO ２ optionally substituted with one or more substituents independently selected from Each R ２ are independently H and C １ ~C ６ selected from the group consisting of alkyl; R ３ is H, C １ ~C ６ selected from the group consisting of alkyl, and C(═O)OR; R ４ is H, C(=O)OR, (C １ ~C ６ alkyl)-C(=O)OR, C １ ~C ６ Alkyl, C １ ~C ６ Heteroalkyl, C ３ ~C ６ Cycloalkyl, C ３ ~C ８ Heterocycle, C ６ ~C １０ selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms, or any combination thereof; Z １ ', Z ２ ', Z ３ ', Z ４ ', and Z ６ Each ' is independently H, an albumin binder H, or a group -X １ -L １ -X ２ ', wherein Z １ ', Z ２ ', Z ３ ', Z ４ ', Z ５ ', Z ６ ', and Z ７ At least one of the groups -X １ -L １ -X ２ ' and; X １ is either present or absent, and if present: X １ -O-, -NR'-, -C(=O)NR', ​​-NR'C(=O)-, -OC(=O)-, -C(=O)O-, -OC(=O)NR'-, -NR'C(=O)O-; -CH ２ -O-; and -NR'C(=O)NR', ​​provided that X １ is NR′, then R ４ is not H; L １ is C １ ~C ５ Alkylene, (-CH ２ CH ２ O)n, C １ ~C ６ Heteroalkylene, C ３ ~C ６ Cycloalkylene, -C ３ ~C ８ a linker selected from the group consisting of heterocycloalkylene-, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein said alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably selected from the group consisting of: albumin binders, C １ ~C ６ Alkyl, -OR', =O, =NR', =N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(=O)R', (C １ ~C ６ alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C １ ~C ６ Alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R''', -NR''-C(=O)OR', -NR'-C(NR''R''')=NR'''', -S(=O)R', -S(=O) ２ R', -S(=O) ２ NR'R'', -NRS (=O) ２ R', -CN and -NO ２ optionally substituted with one or more substituents selected from R', R'', R''', and R'''' are each independently H, C １ ~C ６ Alkyl, C １ ~C ６ Heteroalkyl, C ３ ~C ６ Cycloalkyl, C ３ ~C ８ Heterocycle, 3- to 10-membered heterocycloalkyl, C ６ ~C １０ selected from the group consisting of aryl and heteroaryl having 5 to 10 ring atoms; X ２ ' is a group selected from the group consisting of: 【Transformation 33】 each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5).

37. 37. The compound of claim 36, or a pharmaceutically acceptable salt thereof, wherein R is H.

38. Each R １ are independently H, C １ ~C ６ Alkyl, C(=O)OR ２ , (C １ ~C ６ alkyl)-C(=O)OR ２ and heteroaryl having 5 to 10 ring atoms, or a pharmaceutically acceptable salt thereof.

39. Each R １ are independently H, CH ３ , C(=O)OH, CH ２ 39. The compound of any one of claims 36 to 38, or a pharmaceutically acceptable salt thereof, selected from the group consisting of C(=O)OH and pyridyl.

40. R ３ is H, C １ ~C ３ 40. The compound of any one of claims 36 to 39, or a pharmaceutically acceptable salt thereof, selected from the group consisting of alkyl and C(=O)OR.

41. R ３ is H, CH ３ and C(=O)OH, or a pharmaceutically acceptable salt thereof.

42. R ４ is H, C(=O)OR, (C １ ~C ６ alkyl)-C(=O)OR ２ and heteroaryl having 5 to 10 ring atoms, or a pharmaceutically acceptable salt thereof.

43. R ４ is H, C(=O)OH, CH ２ 43. The compound of any one of claims 36 to 42, or a pharmaceutically acceptable salt thereof, selected from the group consisting of C(=O)OH and pyridyl.

44. Z １ ', Z ２ ', Z ３ ', Z ４ ', Z ５ ', Z ６ ', and Z ７ Only one of the ' is -X １ -L １ -X ２ 44. The compound of any one of claims 36 to 43, wherein:

45. X １ is -O-, -N(CH ３ 45. The compound of any one of claims 36 to 44, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of -C(=O)- and -C(=O)NH-.

46. L １ is C １ ~C ５ 46. ​​The compound of any one of claims 36 to 45, or a pharmaceutically acceptable salt thereof, which is alkylene.

47. X ２ 'teeth, 【Transformation 34】 47. The compound according to any one of claims 36 to 46, wherein:

48. A compound according to any one of claims 36 to 47, selected from: 【Chemistry 35】 【Transformation 36】 【Chemistry 37】 or a pharmaceutically acceptable salt thereof.

49. 49. The compound of claim 48, selected from: 【Transformation 38】 【Chemistry 39】 or a pharmaceutically acceptable salt thereof.

50. 50. The compound of any one of claims 36 to 49, or a pharmaceutically acceptable salt thereof, further complexed to a radionuclide.

51. The radioactive nuclide is, １１１ In, ９９ｍ Tc, ９４ｍ Tc, ６７ Ga, ６６ Ga, ６８ Ga, ５２ Fe, １６９ Er, ７２ As, ９７ Ru, ２０３ Pb, ６２ Cu, ６４ Cu, ６７ Cu, １８６ Re, １８８ Re, ８６ Y, ９０ Y, ５１ Cr, ５２ｍ Mn, １７７ Lu, １６１ Tb, １６９ Yb, １７５ Yb, １０５ Rh, １６６ Dy, １６６ Ho, １５３ Sm, １４９ Pm, １５１ Pm, １７２ Tm, １２１ Sn, １１７ｍ Sn, ２１３ Bi, １４２ Pr, １４３ Pr, １９８ Au, １９９ Au, １２３ I, １２４ I, １２５ I, １８ F, Al １８ F, １４９ Tb, １５２ Tb, １５５ Tb, ４７ Sc, ４４ Sc, ４３ Sc, ２２５ Ac, <s ２１２ Pb, ２１１ At, ２２３ Ra, ２２７ Th, １３１ I, ８２ Rb, ７６ As, ８９ Zr, １１１ Ag, １６５ Er, ２２７ Ac, and ６１ 51. The compound of claim 50, wherein the compound is selected from the group consisting of Cu.

52. 50. A compound according to any one of claims 1 to 33 and 36 to 49, or a pharmaceutically acceptable salt thereof, for use as a medicament.

53. The medicament is for treating cancer and the compound is １６９ Er, ６４ Cu, ６７ Cu, １８６ Re, １８８ Re, ９０ Y. １７７ Lu, １６１ Tb, １６９ Yb, １７５ Yb, １０５ Rh, １６６ Dy, １６６ Ho, １５３ Sm, １４９ Pm, １５１ Pm, １２１ Sn, ２１３ Bi, １４２ Pr, １４３ Pr, １９８ Au, １９９ Au, １４９ Tb, ４７ Sc, ２２５ Ac, ２１２ Pb, ２１１ At, ２２３ Ra, ２２７ Th, １３１ I, ７６ As, １１１ Ag, １６５ Er, and ２２７ 53. The compound of claim 52, or a pharmaceutically acceptable salt thereof, complexed with a radionuclide selected from the group consisting of:

54. The agent is for diagnosing a cancer disease, and the compound is １１１ In, ９９ｍ Tc, ９４ｍ Tc, ６７ Ga, ６６ Ga, ６８ Ga, ５２ Fe, ７２ As, ９７ Ru, ２０３ Pb, ６２ Cu, ６４ Cu, ８６ Y. ５１ Cr, ５２ｍ Mn, １７７ Lu, １６９ Yb, １７２ Tm, １１７ｍ Sn, １２３ I, １２４ I, １２５ I, １８ F, Al １８ F. １５２ Tb, １５５ Tb, ４４ Sc, ４３ Sc, ８２ Rb, ８９ Zr and ６１ 53. The compound of claim 52, or a pharmaceutically acceptable salt thereof, complexed with a radionuclide selected from the group consisting of Cu.

55. 50. A method for radiolabeling a compound, or a pharmaceutically acceptable salt thereof, according to any one of claims 1 to 33 and 36 to 49, comprising reacting the compound with a radionuclide to form a complex of the compound and the radionuclide, and recovering the complex, thereby obtaining the radiolabeled compound.

56. The radionuclide is １１１ In, ９９ｍ Tc, ９４ｍ Tc, ６７ Ga, ６６ Ga, ６８ Ga, ５２ Fe, １６９ Er, ７２ As, ９７ Ru, ２０３ Pb, ６２ Cu, ６４ Cu, ６７ Cu, １８６ Re, １８８ Re, ８６ Y, ９０ Y, ５１ Cr, ５２ｍ Mn, １７７ Lu, １６１ Tb, １６９ Yb, １７５ Yb, １０５ Rh, １６６ Dy, １６６ Ho, １５３ Sm, １４９ Pm, １５１ Pm, １７２ Tm, １２１ Sn, １１７ｍ Sn, ２１３ Bi, １４２ Pr, １４３ Pr, １９８ Au, １９９ Au, １２３ I, １２４ I, １２５ I, １８ F, １４９ Tb, １５２ Tb, １５５ Tb, ４７ Sc, ４４ Sc, ４３ Sc, ２２５ Ac, ２１２ Pb, ２１１ At, ２２３ Ra, ２２７ Th, １３１ I, ８２ Rb, ７６ As, ８９ Zr, １１１ Ag, １６５ Er, ２２７ Ac, and ６１ 56. The method of claim 55, wherein the compound is selected from the group consisting of Cu, or a pharmaceutically acceptable salt thereof.

57. 57. A pharmaceutical composition comprising a compound according to any one of claims 1 to 56, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

58. 58. A method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1 to 53, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 57.

59. 57. A method for imaging cancer in a subject, comprising administering to the subject a compound according to any one of claims 1 to 52 and 54, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 57.

60. 10. A method for synthesizing a compound of formula (I) of claim 1, or a pharmaceutically acceptable salt thereof, comprising: (a) reacting a target-binding compound L ２ -A (where L ２ is an optional linker and A is a target binding moiety) to a compound of formula (II): 【Chemistry 40】 (In the formula, 【Chemistry 41】 is a single or double bond, 【Chemistry 42】 is a single bond, X is —O— or 【Chemistry 43】 and 【Chemistry 44】 is a double bond, X is ═N—, and Z ５ ' and Z ７ together with the N atom form a heteroaryl having 5 or 6 ring atoms, otherwise Z ５ ' and Z ７ Each ' is independently H, an albumin binder, and -X １ -L １ -X ２ ' selected from the group consisting of: Each R is independently H and C １ ~C ６ selected from the group consisting of alkyl; Each R １ are independently H, C(=O)OR ２ , (C １ ~C ６ alkyl)-C(=O)OR ２ , C １ ~C ６ Alkyl, C １ ~C ６ Heteroalkyl, C ３ ~C ６ Cycloalkyl, C ６ ~C １０ and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl and heteroaryl are selected from the group consisting of: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'')═NR'''', -S(═O)R', -S(═O) ２ R', -S(=O) ２ NR'R'', -NRS (=O) ２ R', -CN and -NO ２ optionally substituted with one or more substituents independently selected from R ２ are independently H and C １ ~C ６ selected from the group consisting of alkyl; R ３ is H, C １ ~C ６ selected from the group consisting of alkyl and C(═O)OR; R ４ is H, C(=O)OR, (C １ ~C ６ alkyl)-C(=O)OR, (C １ ~C ６ alkyl)-C(=O)OR, C １ ~C ６ Alkyl, C １ ~C ６ Heteroalkyl, C ３ ~C ６ Cycloalkyl, C ３ ~C ８ Heterocycle, C ６ ~C １０ selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms, or any combination thereof; Z １ ', Z ２ ', Z ３ ', Z ４ ', and Z ６ Each ' is independently H, an albumin binder, and -X １ -L １ -X ２ selected from the group consisting of: X １ is either present or absent, and if present: X １ -O-, -NR'-, -C(=O)NR'-, -NR'C(=O)-, -OC(=O)-, -C(=O)O-, -OC(=O)NR'-, -NR'C(=O)O-; -CH ２ -O-; and -NR'C(=O)NR'-, provided that X １ is NR′, then R ４ is not H, preferably X １ is -O-, -N(CH ３ )—, —C(═O)NH—; L １ is C １ ~C ５ Alkylene, (-CH ２ CH ２ O)n, C １ ~C ６ Heteroalkylene, C ３ ~C ６ Cycloalkylene, -C ３ ~C ８ A linker selected from the group consisting of heterocycloalkylene, heteroarylene having 5 to 10 ring atoms, one or more natural or unnatural amino acids, and any combination thereof, wherein said alkylene, heteroalkylene, cycloalkylene, heterocycloalkylene, heteroarylene, and amino acid are preferably selected from the group consisting of: １ ~C ６ Alkyl, -OR', =O, =NR', =N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(=O)R', (C １ ~C ６ alkyl)-C(=O)OR', -C(=O)R', -C(=O)OR', (C １ ~C ６ Alkyl)-C(=O)OR'-C(=O)NR'R'', -OC(=O)NR'R'', -NR''C(=O)R', -NR'-C(=O)NR''R'”, -NR''C(=O)OR', -NR'-C(NR''R'”)=NR''”, -S(=O)R', -S(=O) ２ R', -S(=O) ２ NR'R'', -NRS (=O) ２ R', -CN and -NO ２ optionally substituted with one or more substituents selected from R', R'', R''', and R'''' are each independently H, C １ ~C ６ Alkyl, C １ ~C ６ Heteroalkyl, C ３ ~C ６ Cycloalkyl, C ３ ~C ８ Heterocycle, C ６ ~C １０ selected from the group consisting of aryl, and heteroaryl having 5 to 10 ring atoms; X ２ is selected from the group consisting of: 【Chemistry 45】 each m is independently 0 or 1; n is 1, 2, 3, 4, 5 or 6; p is 1, 2, 3, 4, 5 or 6; q is 1, 2, 3, 4, 5 or 5 reacting with; and b) recovering said compound of formula (I).

61. ６８ Ga and / or １７７ A compound capable of complexing Lu at a temperature of ≦60° C. to achieve complexation of ≧85% of the compound in the composition, said compound being a compound of formula (C) 【Chemistry 46】 or a pharmaceutically acceptable salt thereof (In the formula, 【Chemistry 47】 is a single or double bond, 【Chemistry 48】 is a single bond, X is —O— or 【Chemistry 49】 and [Transformation 50] is a double bond, then X is ═N—; each m is 0 to 5; Each R is independently H and C １ ~C ６ selected from the group consisting of alkyl; Each R １ are independently H, C(=O)OR ２ , (C １ ~C ６ alkyl)-C(=O)OR ２ , C １ ~C ６ Alkyl, C １ ~C ６ Heteroalkyl, C ３ ~C ６ Cycloalkyl, C ６ ~C １０ and any combination thereof, wherein said alkyl, heteroalkyl, cycloalkyl, aryl and heteroaryl are selected from the group consisting of: -OR', ═O, ═NR', ═N-OR', -NR'R'', -SR', -halogen, -SiR'R''R''', -OC(═O)R', -C(═O)R', -C(═O)OR', -C(═O)NR'R'', -OC(═O)NR'R'', -NR''C(═O)R', -NR'-C(═O)NR''R'''', -NR''C(═O)OR', -NR'-C(NR''R'')═NR'''', -S(═O)R', -S(═O) ２ R', -S(=O) ２ NR'R'', -NRS (=O) ２ R', -CN and -NO ２ optionally substituted with one or more substituents independently selected from Each R ２ is H and C １ ~C ６ selected from the group consisting of alkyl; R ３ is H and C １ ~C ６ selected from the group consisting of alkyl, and C(═O)OR; R ４ is H, C(=O)OR, (C １ ~C ６ alkyl)-C(=O)OR, C １ ~C ６ Alkyl, C １ ~C ６ Heteroalkyl, C ３ ~C ６ Cycloalkyl, C ３ ~C ８ Heterocycle, C ６ ~C １０ aryl, heteroaryl having 5 to 10 ring atoms, or any combination thereof) Including, The compound of formula (C) is an optionally substituted compound.

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