Drug compounds containing albumin-binding moieties

Abstract

The present invention relates to formula (Ia) or (Ib) (wherein each -D- is an independent drug part; each -AB) 1 and -AB 2 These are independently albumin-binding moieties; each -L 1 - is a linker portion that is independently and covalently and reversibly bonded to -D-; each -L 2 - is a spacer independently or not present; x and y are integers) a compound or a pharmaceutically acceptable salt thereof; relating to pharmaceutical compositions comprising at least one such compound and the use thereof. [Formula 1] TIFF2026509773000238.tif23160

Description

[Technical Field]

[0001] The present invention relates to a compound of formula (Ia) or (Ib) or a pharmaceutically acceptable salt thereof, wherein each -D- is independently a drug part, and each -AB 1 and -AB 2 These are independently albumin-binding moieties, and each -L 1 - is a linker portion that is independently and covalently and reversibly bonded to -D-, and each -L 2 - relates to compounds or salts, at least one such compound, comprising a compound or salt, where x and y are integers, and to pharmaceutical compositions comprising such compounds and the use thereof. [Background technology]

[0002] While some classes of therapeutic proteins, including antibodies, have long intrinsic half-lives, many other molecules, particularly proteins or peptide hormones, are often sensitive to enzymatic degradation, renal clearance, and / or rapid receptor-mediated clearance, which leads to short plasma elimination half-lives. Furthermore, due to difficulties associated with oral delivery, the vast majority of peptide or protein-based drugs require parenteral administration, which, combined with their short half-lives, necessitates frequent infusions, causing discomfort and inconvenience to patients. This can negatively impact compliance and ultimately limit therapeutic efficacy and outcomes.

[0003] Infusion of lipid-derived peptides has been shown to have a longer circulating half-life compared to non-derivative peptides, due to slower absorption from subcutaneous tissue and reversible binding to albumin. The half-life of endogenous albumin in circulation is approximately three weeks. This long half-life may be a result of both its large molecular size, which minimizes renal clearance, and recycling via the neonatal Fc receptor (FcRn). In circulation, the large molecular size protects the bound peptide from renal clearance and reduces its distribution rate to the extravascular compartment.

[0004] The slower absorption is thought to be due to a decrease in the diffusion rate in tissues, mediated by mechanisms including the interaction of fatty acid side chains with proteins such as albumin present in the cell membrane and / or injection site. The diffusion rate in tissues and passage through capillary walls after injection will be reduced, as expected, due to the large molecular size of the albumin-peptide complex. Molecules with a molecular size larger than approximately 16 kDa are preferentially and alternatively absorbed via the lymphatic pathway compared to direct absorption into the bloodstream through capillary walls.

[0005] Therefore, slow absorption and reversible albumin binding have allowed for extensions of the dosing interval for drugs such as peptide drugs, up to a maximum of one week. However, further extensions of the dosing interval would also be desirable. [Overview of the project] [Problems that the invention aims to solve]

[0006] The objective of this invention is to overcome, at least partially, the shortcomings of current therapies. [Means for solving the problem]

[0007] The purpose is to determine the compounds of formula (Ia) or (Ib). [ka] (In the formula, Each -D- is an independent drug portion. Each-AB 1 and -AB 2 This is an independently albumin-binding moiety, Each-L 1 - is a linker portion that is independently and covalently and reversibly bonded to -D-. Each-L 2 - is either an independent spacer or does not exist. x is an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 and 25, y is an integer selected from the group consisting of 2, 3, 4 and 5) or achieved by its pharmaceutically acceptable salt.

[0008] The compounds of formula (Ia) and (Ib) may also be referred to as "prodrugs". They release the drug moiety - AB 2 (where H- is hydrogen), which may also be described as 2 a conjugate.

[0009] The applicant has discovered that the compounds of the present invention have an extended half-life that allows for a reduced dosing frequency.

[0010] This leads to compounds that exhibit increased albumin binding and a slowed absorption of the macromolecular drug-albumin complex. Such compounds also demonstrate a reduced absorption from the site of administration, such as from the subcutaneous tissue, compared to the administration of the corresponding unconjugated drug. For this reason, such compounds have an extended half-life compared to the corresponding unconjugated drug.

Mode for Carrying Out the Invention

[0011] In the present invention, terms having the following meanings are used.

[0012] As used herein, the term “GLP-1 receptor agonist” refers to an agonist of the GLP-1 receptor (GLP1R) and, optionally, an agonist of one or more other receptors, such as the receptor for gastric suppressor polypeptide (GIPR), the receptor for glucagon (GCGR), the receptor for amyrin, the receptor for peptide YY (PYYR), or the receptor for glucagon-like peptide 2 (GLP2R). An “agonist” of a receptor, such as a GLP-1 receptor agonist, is a compound that activates such a receptor to produce a biological response. If a GLP-1 receptor agonist is also an agonist of one other receptor besides GLP1R, such as a GIPR, GCGR, amyrin receptor, PYYR, or GLP2R agonist, such a GLP-1 receptor agonist is also called a “dual GLP-1 receptor agonist” or simply a “dual agonist.” Similarly, if a GLP-1 receptor agonist is not only a GLP1R agonist but also an agonist of two other receptors selected from the group consisting of GIPR, GCGR, amyrin receptor, PYYR, or GLP2R, such a GLP-1 receptor agonist is also called a “triple GLP-1 receptor agonist” or simply a “triple agonist.”

[0013] As used herein, the term "peptide" refers to a chain of at least two and up to 50 amino acid monomer moieties linked by peptide (amide) bonds, which may also be called "amino acid residues." Amino acid monomers may be selected from the group consisting of protein-constitutive amino acids and non-protein-constitutive amino acids, and may be D- or L-amino acids. The term "peptide" also includes peptide mimes, such as peptoids, beta-peptides, cyclic peptides, and depsipeptides, encompassing such peptide mimetics chains having up to 50 monomer moieties. Cyclic peptides may be monocyclic, bicyclic, tricyclic, or tetracyclic peptides. The term "peptide" also includes lasso peptides.

[0014] As used herein, the term "protein" preferably refers to a chain of more than 50 amino acid monomers linked by peptide bonds, in which 12,000 or fewer amino acid monomers, for example, 10,000 or fewer amino acid monomer portions, 8,000 or fewer amino acid monomer portions, 5,000 or fewer amino acid monomer portions, or 2,000 or fewer amino acid monomer portions are linked by peptide bonds. These amino acid monomer portions may also be called "amino acid residues."

[0015] As used herein, the term "small molecule drug" refers to a drug that is an organic compound having a molecular weight of less than 1000 Da, for example, less than 900 Da or less than 800 Da. It is understood that drug moieties based on nucleobases, such as adenine or guanine analogs, can also be a type of small molecule drug.

[0016] As used herein, the terms "medium-sized molecular drug" or "medium-sized molecular drug" refer to a drug that is neither a peptide nor a protein, but an organic compound having a molecular weight in the range of 1 kDa to 7.5 kDa.

[0017] As used herein, the term “oligonucleotide” refers to double-stranded or single-stranded RNA and DNA, preferably containing 2 to 1000 nucleotides, and any modifications thereof. Modifications include, for example, those that impart other chemical groups to the nucleic acid ligand base or to the nucleic acid ligand as a whole, incorporating additional charge, polarity, hydrogen bonding, electrostatic interactions, and fluxionality. Such modifications include, for example, 2'-position sugar modifications, 5-position pyrimidine modifications, 8-position purine modifications, extracyclic amine modifications, 4-thiouridine substitutions, 5-bromo or 5-iodouracil substitutions; skeletal modifications, methylation, unusual pair-forming combinations, such as the isobases isocytidine and isoguanidine. Modifications also include 3' and 5' modifications such as capping, and stereochemical changes. The term also includes aptamers.

[0018] As used herein, the term "peptide nucleic acid" refers to an organic polymer having a peptide backbone, i.e., a backbone in which monomers are linked to one another via peptide bonds, to which nucleic acid bases such as adenine, cytosine, guanine, thymine, and uracil are bonded. In certain embodiments, the peptide backbone includes N-(2-aminoethyl)-glycine.

[0019] As used herein, the term "random coil" refers to a conformation of any polymer molecule, including proteins, in which individual monomer elements forming a polymer structure are essentially randomly oriented toward adjacent monomer elements, while still chemically bonded to them. In particular, polypeptides or proteins having a random coil conformation substantially lack defined secondary and tertiary structures. The properties of polypeptide random coils and methods for their experimental identification are known to those skilled in the art. In particular, the absence of secondary and tertiary structures in proteins can be determined by circular dichroism (CD) measurements. CD spectroscopy represents optical absorption spectroscopy in which the difference in absorption of right-circularly polarized and left-circularly polarized light by a substance is measured. The secondary structure of a protein can be determined by CD spectroscopy using far-ultraviolet spectra with wavelengths of approximately 190–250 nm. At these wavelengths, the different secondary structures commonly found in conformations each produce characteristic shapes and amplitudes in the CD spectrum. Thus, by using CD spectroscopy, those skilled in the art can easily determine whether an amino acid polymer adopts a random coil conformation under physiological conditions.

[0020] When determining whether a peptide or protein adopts random coil conformation under experimental conditions using the methods described herein, biophysical parameters such as temperature, pH, osmotic pressure, and protein content may differ from the physiological conditions typically found in vivo. Temperatures of 1°C to 42°C, or preferably 4°C to 25°C, can be considered useful for testing and / or verifying the biophysical properties and biological activity of peptides or proteins under physiological conditions in vitro.

[0021] In particular, several buffers in the buffers, solvents and / or excipients of pharmaceutical compositions in experimental settings (e.g., in determining protein structure, especially in circular dichroism (CD) measurements and other methods that enable those skilled in the art to determine the structural properties of protein / polypeptide or peptide elongations) are considered to represent “physiological solutions” or “physiological conditions” in vitro. Examples of such buffers include, for example, phosphate-buffered saline (PBS: 115 mM NaCl, 4 mM KH2PO4, 16 mM Na2HPO4 pH 7.4), Tris buffer, acetate buffer, citrate buffer, or similar buffers used in the accompanying examples. Generally, the pH of the buffer representing physiological conditions should be in the range of 6.5 to 8.5, preferably 7.0 to 8.0, and most preferably 7.2 to 7.7, and the osmotic pressure should be in the range of 10 to 1000 mmol / kg H2O, more preferably 50 to 500 mmol / kg H2O, and most preferably 200 to 350 mmol / kg H2O. In some cases, the protein content of the buffer representing physiological conditions can be in the range of 0 to 100 g / L, ignoring the biologically active proteins themselves, thereby allowing the use of typical stabilizing proteins, such as human or bovine serum albumin.

[0022] Other established biophysical methods for determining random coil conformation include nuclear magnetic resonance (NMR) spectroscopy, absorption spectroscopy, infrared and Raman spectroscopy, hydrodynamic volume measurement via size exclusion chromatography, analytical ultracentrifugation and dynamic / static light scattering, and measurement of friction coefficient or intrinsic viscosity.

[0023] As used herein, the term "physiological conditions" refers to an aqueous buffer solution at pH 7.4 and 37°C.

[0024] As used herein, the term “pharmaceutical composition” means a composition comprising one or more active ingredients, such as at least one compound of the present invention, and one or more excipients, and any products directly or indirectly arising from combinations, complexes, or aggregations of any two or more components of the composition, or from the dissociation of one or more of the components, or from other types of reactions or interactions of one or more of the components. Accordingly, the pharmaceutical compositions of the present invention encompass any composition produced by mixing one or more compounds of the present invention with one or more pharmaceutically acceptable excipients.

[0025] As used herein, the term “excipient” refers to a therapeutic agent, such as a diluent, adjuvant, or vehicle on which a drug or prodrug is administered. Such pharmaceutical excipients may be sterile solutions, such as water and oils (petroleum, animal, plant, or synthetic oils, including, but not limited to, peanut oil, soybean oil, mineral oil, and sesame oil). Water is an example of an excipient when the pharmaceutical composition is administered orally. Saline solutions and dextrose aqueous solutions are examples of excipients when the pharmaceutical composition is administered intravenously. Saline solutions, as well as dextrose aqueous solutions and glycerol solutions, are used as liquid excipients for injectable solutions in certain embodiments. Suitable pharmaceutical excipients include starch, glucose, lactose, sucrose, mannitol, trehalose, gelatin, malt, rice, wheat flour, chalk, silica gel, sodium stearate, glyceryl monostearate, talc, sodium chloride, skim milk powder, glycerol, propylene glycol, water, and ethanol. The pharmaceutical composition may also optionally contain small amounts of wetting or emulsifying agents, pH buffers such as acetates, succinates, tris, carbonates, phosphates, HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), MES (2-(N-morpholino)ethanesulfonic acid), or surfactants such as Tween, poloxamer, poloxamine, CHAPS, Igepal, or amino acids such as glycine, lysine, or histidine. These pharmaceutical compositions may take the form of solutions, suspensions, emulsions, tablets, pills, capsules, powders, or sustained-release formulations. The above pharmaceutical compositions may be formulated as suppositories with traditional binders and excipients, such as triglycerides. Oral formulations may contain standard excipients, such as pharmaceutical-grade mannitol, lactose, starch, magnesium stearate, sodium saccharin, cellulose, magnesium carbonate, etc. Such compositions will contain a therapeutically effective amount of the drug or drug portion, along with a suitable amount of excipients to provide a form for appropriate administration to the patient. The formulation should be suitable for the mode of administration.

[0026] As used herein, the term "liquid composition" refers to a mixture comprising a water-soluble compound and one or more solvents, such as water.

[0027] The term "suspension composition" refers to a mixture comprising at least one water-insoluble compound and one or more solvents, such as water.

[0028] As used herein, the term “dried composition” means that the pharmaceutical composition is provided in a dry form. Preferred drying methods are spray drying and freeze-drying. Such a dried composition has a residual moisture content of up to 10%, for example, less than 5% or less than 2%, as determined by Karl Fischer. In certain embodiments, such a dried pharmaceutical composition is dried by freeze-drying.

[0029] As used herein, the term “drug” refers to a substance used in the treatment, cure, prevention, or diagnosis of a disease, or used in any other way to enhance physical or mental well-being. When a drug is conjugated into another part, the resulting product portion derived from that drug is referred to as the “drug portion.”

[0030] As used herein, the term "prodrug" refers to a covalent conjugate in which a drug moiety is reversibly and covalently bonded to a special protecting group via a reversible linker moiety, also called a "reversible prodrug linker moiety" or "reversible linker moiety," which conjugates the drug moiety by reversible bonding, and the special protecting group alters or removes undesirable properties in the parent molecule. This includes enhancing desirable properties and suppressing undesirable properties in the drug. The special non-toxic protecting group is called a "carrier." A prodrug releases a reversibly and covalently bonded drug moiety in the form of its corresponding drug. In other words, a prodrug is a conjugate containing a drug moiety covalently and reversibly conjugated to a carrier moiety via a reversible linker moiety, where the covalent and reversible conjugation of the carrier to the reversible linker moiety is direct or spacer-mediated. Such a conjugate releases a previously conjugated drug moiety in the form of a free, unmodified drug.

[0031] A "reversible bond" is a bond that is degradable, or cleavable, in the absence of an enzyme and under physiological conditions (aqueous buffer, pH 7.4, 37°C), with a half-life of 1 hour to 3 months. Therefore, a "stable bond" is a bond that has a half-life of more than 3 months under physiological conditions (aqueous buffer, pH 7.4, 37°C) and in the absence of an enzyme.

[0032] As used herein, the terms “trace-free prodrug linker” or “trace-free linker” mean a reversible prodrug linker that releases the drug in its free form when cleaved, i.e., a linker portion that reversibly and covalently binds the drug portion to the carrier. As used herein, the terms “free form” or “free drug” mean the drug in its unmodified, pharmacologically active form.

[0033] As used herein, the term “reagent” means a compound containing at least one functional group for reaction with the functional group of another compound or drug. Drugs containing a functional group such as a primary or secondary amine or a hydroxyl functional group are also understood to be reagents.

[0034] As used herein, the term “part” means a portion of a molecule that lacks one or more atoms compared to the corresponding reagent. For example, when a reagent of formula “HXH” reacts with another reagent and becomes part of a reaction product, the corresponding part of the reaction product has the structure “HX-” or “-X-”, where each “-” indicates a bond to another part. Thus, the drug part is released as a drug from the prodrug.

[0035] If the chemical structure of an atomic group bonded to at least one other part is provided, unless otherwise explicitly stated, the chemical structure may be bonded to at least one other part in any orientation. For example, part "-C(O)N(R 1 )-" is "-C(O)N(R 1 )-" or "-N(R 1 )C(O)-" may be joined to two parts. Similarly, part [ka] teeth, [ka] as, or [ka] It may be combined into two parts.

[0036] As used herein, the term "functional group" means a group of atoms that can react with other groups of atoms. Functional groups are selected from the group consisting of, for example, the following groups: carboxylic acids, primary or secondary amines, maleimides, thiols, sulfonic acids, carbonates, carbamates, hydroxyls, aldehydes, ketones, hydrazines, isocyanates, isothiocyanates, phosphoric acids, phosphonic acids, haloacetyls, alkyl halides, acryloyls, aryl fluorides, hydroxylamines, disulfides, sulfonamides, sulfuric acids, vinyl sulfones, vinyl ketones, diazoalkanes, oxiranes, and aziridines.

[0037] As used herein, the term "pharmaceutically acceptable salt" refers to a salt that retains the biological efficacy or properties of the compound and is not typically biologically or otherwise undesirable. In certain embodiments, a compound may form an acid / or base salt in the presence of an amino and / or carboxyl functional group or a similar group. Pharmaceutically acceptable acid addition salts can be formed using inorganic or organic acids, such as acetates, aspartates, benzoates, besilates, bromides / hydrobroms, bicarbonates / carbonates, bisulfates / sulfates, camphor sulfons, chlorides / hydrochlorides, chlortheophyllinates, citrates, ethanedisulfons, fumarates, gluceptates, glucons, glucurons, hippurates, hydroiodides / iodides, etc. These may be cetionic acid, lactate, lactobionate, lauryl sulfate, malate, maleate, malonate, mandelate, mesylate, methyl sulfate, naphthoate, napsylate, nicotinate, nitrate, octadecanoate, oleate, oxalate, palmitate, pamoate, phosphate / hydrogen phosphate / dihydrogen phosphate, polygalacturonate, propionate, stearate, succinate, subsalicylate, tartrate, tosylate, and trifluoroacetate. Examples of inorganic acids from which salts can be derived include hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid. Examples of organic acids from which salts can be derived include acetic acid, propionic acid, glycolic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, toluenesulfonic acid, and sulfosalicylic acid. Pharmaceutically acceptable base addition salts can be formed using inorganic and organic bases. Examples of inorganic bases from which salts can be derived include ammonium salts and metals from columns I to XII of the periodic table. In certain embodiments, salts are derived from sodium, potassium, ammonium, calcium, magnesium, iron, silver, zinc, and copper, with ammonium, potassium, sodium, calcium, and magnesium salts being particularly preferred.Examples of organic bases from which salts can be derived include primary, secondary, and tertiary amines, naturally occurring substituted amines and other substituted amines, cyclic amines, and basic ion exchange resins. Specific organic amines include isopropylamine, benzathine, cholinate, diethanolamine, diethylamine, lysine, meglumine, piperazine, or tromethamine. Pharmaceutically acceptable salts can be synthesized from the parent compound, basic or acidic moiety by conventional chemical methods.

[0038] The term "pharmaceutically acceptable" means a substance that does not cause harm when administered to a patient, and in certain embodiments, means that it is authorized for use in animals, and in particular for use in humans, by a regulatory body, such as the EMA (Europe) and / or the FDA (United States) and / or any other national regulatory body.

[0039] In this specification, the terms “about” or “approximately” in combination with numerical values ​​are used to indicate not only the numerical value itself, but also a range of plus or minus 10% or less of the said numerical value. For example, the phrase “about 200” or “approximately 200” is used to mean a range of 200 ± 10%, i.e., a range of 180 to 220. A percentage expressed as “about 20%” or “approximately 20%” is understood not to mean “20% ± 10%,” i.e., a range of 10 to 30%, but rather to mean a range of 18 to 22%, i.e., a range of plus or minus 10% of the numerical value 20.

[0040] As used herein, the term “polymer” means a molecule comprising repeating structural units, i.e., monomers, linked by linear, cyclic, branched, crosslinked, or dendrimeric chemical bonds or combinations thereof, which may be of synthetic or biological origin, or a combination of both. It is understood that polymers may also include one or more other chemical groups and / or parts, such as one or more functional groups. In certain embodiments, soluble polymers have a molecular weight of at least 0.5 kDa, e.g., at least 1 kDa, at least 2 kDa, at least 3 kDa, or at least 5 kDa. If the polymer is soluble, in certain embodiments, the polymer may have a molecular weight of up to 1000 kDa, e.g., up to 750 kDa, e.g., up to 500 kDa, e.g., up to 300 kDa, e.g., up to 200 kDa, or e.g., up to 100 kDa. For non-water-soluble polymers, e.g., hydrogels, it is understood that a meaningful molecular weight range may not be provided. Peptides or proteins are understood to be polymers in which amino acids are repeating structural units, even though the side chains of each amino acid may differ.

[0041] As used herein, the term “polymeric” means a reagent or part comprising one or more polymers or polymeric parts. A polymeric reagent or part may optionally include one or more other parts, which in particular embodiments are selected from the group consisting of: - C 1-50 Alkyl, C 2-50 Alkenil, C 2-50 Alkinyl, C 3-10 Cycloalkyls, 3-10 membered heterocyclyls, 8-11 membered heterobicyclyls, phenyl, naphthyl, indenyl, indanyl, and tetralinyl, and - A combination selected from the group including the following: [ka] (In the formula, The dashed line indicates binding to a portion or the remainder of the reagent. -R and -R a (These are independently selected from the group consisting of -H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-methylbutyl, 2,2-dimethylpropyl, n-hexyl, 2-methylpentyl, 3-methylpentyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, and 3,3-dimethylpropyl).

[0042] Those skilled in the art will understand that polymerization products obtained from polymerization reactions do not necessarily all have the same molecular weight, but rather exhibit a molecular weight distribution. For this reason, the molecular weight range, molecular weight, range of monomer numbers in a polymer, and number of monomers in a polymer as used herein refer to the number-average molecular weight and number-average monomers, i.e., the arithmetic mean of the molecular weight of the polymer or polymer part, and the arithmetic mean of the number of monomers in the polymer or polymer part.

[0043] Therefore, in a polymer portion containing "x" monomer units, any integer represented as "x" corresponds to the arithmetic mean of the monomers. Any range of integers represented as "x" provides a range of integers within which the arithmetic mean of the monomers lies. An integer "x" represented as "about x" means that the arithmetic mean of the monomers lies within the range of integers x ± 10%, x ± 8% in a particular embodiment, x ± 5% in a particular embodiment, and x ± 2% in a particular embodiment.

[0044] As used herein, the term "number-mean molecular weight" refers to the usual arithmetic mean of the molecular weights of individual polymers.

[0045] As used herein with respect to the compounds of the present invention, the term "water-soluble" means that at least 1 g of the compound can dissolve in 1 liter of water at 20°C to form a homogeneous solution. Therefore, the term "water-insoluble" with respect to the compounds means that less than 1 g of the compound can dissolve in 1 liter of water at 20°C to form a homogeneous solution.

[0046] As used herein with respect to a portion or reagent, the term “PEG-based” means that the portion or reagent contains PEG. In certain embodiments, a PEG-based portion or reagent contains at least 90% (w / w) PEG, such as at least 10% (w / w) PEG, e.g., at least 20% (w / w) PEG, e.g., at least 30% (w / w) PEG, e.g., at least 40% (w / w) PEG, e.g., at least 50% (w / w), e.g., at least 60% (w / w) PEG, e.g., at least 70% (w / w) PEG, e.g., at least 80% (w / w) PEG, e.g., at least 95%, etc. The remaining weight percentage of a PEG-based portion or reagent is, in certain embodiments, other portions selected from the following portions and conjugates: - C 1-50 Alkyl, C 2-50 Alkenil, C 2-50 Alkinyl, C 3-10 Cycloalkyls, 3-10 membered heterocyclyls, 8-11 membered heterobicyclyls, phenyl, naphthyl, indenyl, indanyl, and tetralinyl, and - A combination selected from the group including the following: [ka] (In the formula, The dashed line indicates binding to a portion or the remainder of the reagent. -R and -R a (These are independently selected from the group consisting of -H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-methylbutyl, 2,2-dimethylpropyl, n-hexyl, 2-methylpentyl, 3-methylpentyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, and 3,3-dimethylpropyl).

[0047] The term "hyaluronic acid-based" is used accordingly.

[0048] As used herein, the term "substituted" means that one or more -H atoms in a molecule or part are substituted by different atoms or groups of atoms, which are called "substituents."

[0049] In certain embodiments, one or more further optional substituents may be halogen, -CN, or -COOR, independently of each other. x1 , -OR x1 , -C(O)R x1 ,-C(O)N(R x1 R x1a ), -S(O)2N(R x1 R x1a ), -S(O)N(R x1 R x1a ), -S(O)2R x1 ,-S(O)R x1 , -N(R x1 )S(O)2N(R x1a R x1b ), -SR x1 , -N(R x1 R x1a ), -NO2, -OC(O)R x1 , -N(R x1 )C(O)R x1a , -N(R x1 )S(O)2R x1a , -N(R x1 )S(O)R x1a , -N(R x1 )C(O)OR x1a , -N(R x1 )C(O)N(R x1a R x1b ), -OC(O)N(R x1 R x1a ), -T 0 , C 1-50 Alkyl, C 2-50 Alkenyl and C 2-50 Selected from the group consisting of alkynnyls, where -T 0 , C 1-50 Alkyl, C 2-50 Alkenyl and C 2-50 Alkinyl has one or more -Rs, which may be the same or different. x2 In some cases, it is replaced by C 1-50 Alkyl, C 2-50Alkenyl, and C 2-50 Alkynyl may optionally be interrupted by one or more groups selected from the group consisting of -T 0 -, -C(O)O-, -O-, -C(O)-, -C(O)N(R x3 )-, -S(O)2N(R x3 )-, -S(O)N(R x3 )-, -S(O)2-, -S(O)-, -N(R x3 )S(O)2N(R x3a )-, -S-, -N(R x3 )-, -OC(OR x3 ​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​)- may intersect with one or more groups selected from the group consisting of, Each T 0 These are independently phenyl, naphthyl, indenyl, indanyl, tetralinyl, and C 3-10 Selected from the group consisting of cycloalkyls, 3-10 membered heterocyclyls, and 8-11 membered heterobicyclyls, each T 0 These are independently one or more -Rs, the same or different. x2 It is sometimes replaced by, Each-R x2 These are, independently, halogen, -CN, oxo (=O), and -COOR. x4 , -OR x4 , -C(O)R x4 ,-C(O)N(R x4 R x4a ), -S(O)2N(R x4 R x4a ), -S(O)N(R x4 R x4a ), -S(O)2R x4 ,-S(O)R x4 , -N(R x4 )S(O)2N(R x4a R x4b ), -SR x4 , -N(R x4 R x4a ), -NO2, -OC(O)R x4 , -N(R x4 )C(O)R x4a , -N(R x4 )S(O)2R x4a , -N(R x4 )S(O)R x4a , -N(R x4 )C(O)OR x4a , -N(R x4 )C(O)N(R x4a R x4b ), -OC(O)N(R x4 R x4a ), and C 1-6 Selected from the group consisting of alkyl groups, C 1-6 Alkyl is optionally substituted with one or more halogens, either the same or different. Each-R x3 ,-R x3a ,-Rx4 ,-R x4a ,-R x4b These are independently -H and C 1-6 Selected from the group consisting of alkyl groups, where C 1-6 Alkyl atoms are sometimes substituted with one or more halogens, either the same or different.

[0050] In certain embodiments, one or more further optional substituents may be halogen, -CN, or -COOR, independently of each other. x1 , -OR x1 , -C(O)R x1 ,-C(O)N(R x1 R x1a ), -S(O)2N(R x1 R x1a ), -S(O)N(R x1 R x1a ), -S(O)2R x1 ,-S(O)R x1 , -N(R x1 )S(O)2N(R x1a R x1b ), -SR x1 , -N(R x1 R x1a ), -NO2, -OC(O)R x1 , -N(R x1 )C(O)R x1a , -N(R x1 )S(O)2R x1a , -N(R x1 )S(O)R x1a , -N(R x1 )C(O)OR x1a , -N(R x1 )C(O)N(R x1a R x1b ), -OC(O)N(R x1 R x1a ), -T 0 , C 1-10 Alkyl, C 2-10 Alkenyl and C 2-10 Selected from the group consisting of alkynnyls, where -T 0 , C 1-10 Alkyl, C 2-10 Alkenyl and C 2-10 Alkinyl has one or more -Rs, which may be the same or different.x2 In some cases, it is replaced by C 1-10 Alkyl, C 2-10 Alkenyl and C 2-10 Alkinyl has -T 0 -, -C(O)O-, -O-, -C(O)-, -C(O)N(R x3 )-,-S(O)2N(R x3 )-,-S(O)N(R x3 )-, -S(O)2-, -S(O)-, -N(R x3 )S(O)2N(R x3a )-, -S-, -N(R x3 )-, -OC(OR x3 )(R x3a )-,-N(R x3 )C(O)N(R x3a )-, and -OC(O)N(R x3 )- may intersect with one or more groups selected from the group consisting of, Each-R x1 ,-R x1a ,-R x1b ,-R x3 ,-R x3a These are independently -H, halogen, and C 1-6 Alkyl, C 2-6 Alkenyl and C 2-6 Selected from the group consisting of alkynnyls, Each T 0 These are independently phenyl, naphthyl, indenyl, indanyl, tetralinyl, and C 3-10 Selected from the group consisting of cycloalkyls, 3-10 membered heterocyclyls, and 8-11 membered heterobicyclyls, where each T 0 These are independently one or more -Rs, the same or different. x2 It is sometimes replaced by, Each-R x2 These are, independently, halogen, -CN, oxo (=O), and -COOR. x4 , -OR x4 , -C(O)R x4 ,-C(O)N(R x4 R x4a ), -S(O)2N(R x4 R x4a ), -S(O)N(R x4 Rx4a ), -S(O)2R x4 ,-S(O)R x4 , -N(R x4 )S(O)2N(R x4a R x4b ), -SR x4 , -N(R x4 R x4a ), -NO2, -OC(O)R x4 , -N(R x4 )C(O)R x4a , -N(R x4 )S(O)2R x4a , -N(R x4 )S(O)R x4a , -N(R x4 )C(O)OR x4a , -N(R x4 )C(O)N(R x4a R x4b ), -OC(O)N(R x4 R x4a ), and C 1-6 Selected from the group consisting of alkyl groups, C 1-6 Alkyl is optionally substituted with one or more halogens, either the same or different. Each-R x4 ,-R x4a ,-R x4b These are independently -H, halogen, and C 1-6 Alkyl, C 2-6 Alkenyl and C 2-6 Selected from the group consisting of alkynnyls.

[0051] In certain embodiments, one or more further optional substituents may be halogen, -CN, or -COOR, independently of each other. x1 , -OR x1 , -C(O)R x1 ,-C(O)N(R x1 R x1a ), -S(O)2N(R x1 R x1a ), -S(O)N(R x1 R x1a ), -S(O)2R x1 ,-S(O)R x1 , -N(R x1 )S(O)2N(R x1a Rx1b ), -SR x1 , -N(R x1 R x1a ), -NO2, -OC(O)R x1 , -N(R x1 )C(O)R x1a , -N(R x1 )S(O)2R x1a , -N(R x1 )S(O)R x1a , -N(R x1 )C(O)OR x1a , -N(R x1 )C(O)N(R x1a R x1b ), -OC(O)N(R x1 R x1a ), -T 0 , C 1-6 Alkyl, C 2-6 Alkenyl and C 2-6 Selected from the group consisting of alkynnyls, where -T 0 , C 1-6 Alkyl, C 2-6 Alkenyl and C 2-6 Alkinyl has one or more -Rs, which may be the same or different. x2 In some cases, it is replaced by C 1-6 Alkyl, C 2-6 Alkenyl and C 2-6 Alkinyl has -T 0 -, -C(O)O-, -O-, -C(O)-, -C(O)N(R x3 )-,-S(O)2N(R x3 )-,-S(O)N(R x3 )-, -S(O)2-, -S(O)-, -N(R x3 )S(O)2N(R x3a )-, -S-, -N(R x3 )-, -OC(OR x3 )(R x3a )-,-N(R x3 )C(O)N(R x3a )-, and -OC(O)N(R x3 )- may intersect with one or more groups selected from the group consisting of, Each-R x1 ,-R x1a ,-R x1b ,-Rx2 ,-R x3 ,-R x3a These are independently -H, halogen, and C 1-6 Alkyl, C 2-6 Alkenyl and C 2-6 Selected from the group consisting of alkynnyls, Each T 0 These are independently phenyl, naphthyl, indenyl, indanyl, tetralinyl, and C 3-10 Selected from the group consisting of cycloalkyls, 3-10 membered heterocyclyls, and 8-11 membered heterobicyclyls, where each T 0 These are independently one or more -Rs, the same or different. x2 It is sometimes replaced.

[0052] In certain embodiments, up to six -H atoms of the optionally substituted molecule are independently substituted by substituents, for example, five -H atoms are independently substituted by substituents, four -H atoms are independently substituted by substituents, three -H atoms are independently substituted by substituents, two -H atoms are independently substituted by substituents, or one -H atom is independently substituted by substituents.

[0053] The term “inserted” means that a portion is inserted between two carbon atoms, or, if the insertion is at one of the ends of the portion, between a carbon or heteroatom and a hydrogen atom, or in certain embodiments, between a carbon and a hydrogen atom.

[0054] The term "C" as used herein 1-4 "Alkyl" refers to a linear or branched alkyl moiety, either alone or in combination, having 1 to 4 carbon atoms. When present at the end of a molecule, it refers to a linear or branched C 1-4 Examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and tert-butyl. Two parts of the molecule are C 1-4 If bonded by an alkyl group, such C 1-4Examples of alkyl groups are -CH2-, -CH2-CH2-, -CH(CH3)-, -CH2-CH2-CH2-, -CH(C2H5)-, and -C(CH3)2-. 1-4 Each hydrogen atom of the alkyl carbon may optionally be substituted with a substituent as defined above. Optionally, C 1-4 Alkyl may have one or more parts, as defined below, interspersed within it.

[0055] As used herein, the term "nucleophile" refers to a reagent or functional group that forms a bond with its reaction partner, i.e., an electrophile, by donating both bonding electrons.

[0056] The term "C" as used herein 1-6 "Alkyl" refers to a linear or branched alkyl moiety, either alone or in combination, having 1 to 6 carbon atoms. When present at the end of a molecule, it refers to linear and branched C atoms. 1-6 Examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-methylbutyl, 2,2-dimethylpropyl, n-hexyl, 2-methylpentyl, 3-methylpentyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, and 3,3-dimethylpropyl. Two parts of the molecule are C 1-6 If bonded by an alkyl group, such C 1-6 Examples of alkyl groups are -CH2-, -CH2-CH2-, -CH(CH3)-, -CH2-CH2-CH2-, -CH(C2H5)-, and -C(CH3)2-. 1-6 Each hydrogen atom of carbon may optionally be substituted with a substituent as defined above. 1-6 Alkyl may have one or more parts, as defined below, interspersed within it.

[0057] Therefore, "C 1-10 "Alkyl", "C 1-20 "Alkyl" or "C 1-50 "Alkyl" refers to an alkyl chain having 1 to 10, 1 to 20, or 1 to 50 carbon atoms, respectively.1-10 , C 1-20 or C 1-50 Each hydrogen atom of carbon may optionally be substituted with a substituent as defined above. 1-10 or C 1-50 Alkyl may have one or more parts, as defined below, interspersed within it.

[0058] The term "C" as used herein 2-6 An "alkenyl" refers to a straight-chain or branched hydrocarbon moiety, either alone or in combination, containing 2 to 6 carbon atoms and at least one carbon-carbon double bond. When present at the ends of a molecule, examples include -CH=CH2, -CH=CH-CH3, -CH2-CH=CH2, -CH=CHCH2-CH3, and -CH=CH-CH=CH2. Two parts of a molecule are C 2-6 When bonded by an alkenyl group, such C 2-6 An example of an alkenil is -CH=CH-. 2-6 Each hydrogen atom of the alkenyl moiety may optionally be substituted with a substituent as defined above. Optionally, C 2-6 An alkenil may have one or more parts, as defined below, inserted into it.

[0059] Therefore, the term "C 2-10 Alkenil, "C 2-20 "Alkenil" or "C 2-50 "Alkenyl" means a linear or branched hydrocarbon moiety, either alone or in combination, having 2 to 10, 2 to 20, or 2 to 50 carbon atoms and containing at least one carbon-carbon double bond. 2-10 Alkenil, C 2-20 Alkenyl or C 2-50 Each hydrogen atom of the alkenyl group may optionally be substituted with a substituent as defined above. Optionally, C 2-10 Alkenil, C 2-20 Alkenyl or C 2-50 An alkenil may have one or more parts, as defined below, inserted into it.

[0060] The term "C" as used herein 2-6 "Alkynyl" refers to a linear or branched hydrocarbon moiety, either alone or in combination, containing 2 to 6 carbon atoms and at least one carbon-carbon triple bond. When present at the end of a molecule, examples include -C≡CH, -CH2-C≡CH, CH2-CH2-C≡CH, and CH2-C≡C-CH3. When two parts of a molecule are linked by an alkynyl group, an example is -C≡C-. 2-6 Each hydrogen atom of the alkynyl group may optionally be substituted with a substituent as defined above. Optionally, one or more double bonds may be present. Optionally, C 2-6 Alkinyl may have one or more parts, as defined below, inserted into it.

[0061] Therefore, the term "C" as used herein 2-10 Alkinyl, C 2-20 "Alkinyl" and "C 2-50 "Alkynyl" means a linear or branched hydrocarbon moiety, either alone or in combination, containing at least one carbon-carbon triple bond, each having 2 to 10, 2 to 20, or 2 to 50 carbon atoms, respectively. 2-10 Alkinyl, C 2-20 Alkinyl or C 2-50 Each hydrogen atom of the alkynyl group may optionally be substituted with a substituent as defined above. Optionally, one or more double bonds may be present. Optionally, C 2-10 Alkinyl, C 2-20 Alkinyl or C 2-50 Alkinyl may have one or more parts, as defined below, inserted into it.

[0062] As stated above, C 1-4 Alkyl, C 1-6 Alkyl, C 1-10 Alkyl, C 1-20 Alkyl, C 1-50 Alkyl, C 2-6 Alkenil, C 2-10 Alkenil, C 2-20 Alkenil, C 2-50 Alkenil, C 2-6Alkinyl, C 2-10 Alkinyl, C 2-20 Alkenyl or C 2-50 Alkinyl may have one or more parts interspersed in it, and in certain embodiments, these one or more parts are [ka] (In the formula, The dashed line indicates binding to a portion or the remainder of the reagent. -R and -R a (These are independently selected from the group consisting of -H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-methylbutyl, 2,2-dimethylpropyl, n-hexyl, 2-methylpentyl, 3-methylpentyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, and 3,3-dimethylpropyl.) It is selected from the group consisting of the following.

[0063] The term "C" as used herein 3-10 "Cycloalkyl" means a cyclic alkyl chain having 3 to 10 carbon atoms, which may be saturated or unsaturated, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, cyclononyl, or cyclodecyl. 3-10 Each hydrogen atom of the cycloalkyl carbon may be substituted with a substituent as defined above. 3-10 "Cycloalkyl" also includes cross-linked birings such as norbornane or norbornene.

[0064] The term “8-30 membered carbopolycyclil” or “8-30 membered carbopolycycle” refers to a cyclic portion of two or more rings having 8 to 30 ring atoms, where two adjacent rings share at least one ring atom and may contain up to a maximum number of double bonds (fully saturated, partially saturated, or unsaturated aromatic or non-aromatic rings). In certain embodiments, an 8-30 membered carbopolycyclil refers to a cyclic portion of 2, 3, 4, or 5 rings, and in certain embodiments, a cyclic portion of 2, 3, or 4 rings.

[0065] As used herein, the terms “3- to 10-membered heterocyclil” or “3- to 10-membered heterocycle” mean a ring (fully saturated, partially saturated, or unsaturated aromatic or non-aromatic ring) having 3, 4, 5, 6, 7, 8, 9, or 10 ring atoms and potentially containing up to a maximum number of double bonds, wherein at least one ring atom and up to four ring atoms are substituted with heteroatoms selected from the group consisting of sulfur (including -S(O)- and -S(O)2-), oxygen, and nitrogen (including =N(O)-), and the ring is bonded to the remainder of the molecule via carbon or nitrogen atoms. Examples of heterocycles with 3 to 10 members include, but are not limited to, aziridine, oxirane, thiirane, azirine, oxilen, thiirane, azetidine, oxetane, thietan, furan, thiophene, pyrrole, pyrroline, imidazole, imidazoline, pyrazole, pyrazoline, oxazole, oxazoline, isoxazole, isoxazoline, thiazole, thiazoline, isothiazole, isothiazoline, thiadiazole, thiadiazole, tetrahydrofuran Examples include tetrahydrothiophene, pyrrolidine, imidazolidine, pyrazolidine, oxazolidine, isoxazolidine, thiazolidin, isothiazolidine, thiadiazolidin, sulfolane, pyran, dihydropyran, tetrahydropyran, imidazolidine, pyridine, pyridazine, pyrazine, pyrimidine, piperazine, piperidine, morpholine, tetrazole, triazole, triazolidine, tetrazolidin, diazepane, azepine and homopiperazine. Each hydrogen atom of a 3-10 membered heterocyclyl or 3-10 membered heterocyclic group may be substituted with substituents defined below.

[0066] As used herein, the terms “8- to 11-membered heterobicyryl” or “8- to 11-membered heterobicyclic” mean a bicyclic heterocyclic portion having 8 to 11 ring atoms (fully saturated, partially saturated, or unsaturated aromatic or non-aromatic ring) in which at least one ring atom is shared by both rings and may contain up to a maximum number of double bonds, wherein at least one ring atom and up to six ring atoms are substituted with heteroatoms selected from the group consisting of sulfur (including -S(O)-, -S(O)2-), oxygen, and nitrogen (including =N(O)-), and the ring is bonded to the remainder of the molecule via carbon or nitrogen atoms. Examples of 8- to 11-membered heterobicyclic compounds include indole, indoline, benzofuran, benzothiophene, benzoxazole, benzoisoxazole, benzothiazole, benzoisothiazole, benzimidazole, benzimidazolin, quinoline, quinazoline, dihydroquinazoline, quinoline, dihydroquinoline, tetrahydroquinoline, decahydroquinoline, isoquinoline, decahydroisoquinoline, tetrahydroisoquinoline, dihydroisoquinoline, benzazepine, purine, and pteridine. The term 8- to 11-membered heterobicyclic compound also includes bicyclic spiro structures such as 1,4-dioxa-8-azaspiro[4.5]decane, or bridging heterocyclic compounds such as 8-aza-bicyclo[3.2.1]octane. Each hydrogen atom of the carbon atom of an 8- to 11-membered heterobicyclyl or 8- to 11-membered heterobicyclic compound may be substituted with substituents as defined below.

[0067] Similarly, the term “8-30 membered heteropolycyclil” or “8-30 membered heteropolycycle” means a heterocyclic moiety (fully saturated, partially saturated, or unsaturated aromatic or non-aromatic ring) having more than two rings, or in particular embodiments, three, four, or five rings, wherein two adjacent rings share at least one ring atom and may contain up to a maximum number of double bonds, wherein at least one ring atom, up to a maximum of ten ring atoms, is substituted with a heteroatom selected from the group consisting of sulfur (including -S(O)- and -S(O)2-), oxygen, and nitrogen (including =N(O)-), and the ring is bonded to the remainder of the molecule via carbon or nitrogen atoms.

[0068] structure [ka] Regarding the part, "Pair R x / R y Together with the atoms to which they are bonded, C 3-10 The phrase "forms a cycloalkyl or a 3-10 member heterocycline" is R x and R y However, it is understood that this means forming the following structure: [ka] (In the formula, R is C 3-10 (It is a cycloalkyl or a 3- to 10-membered heterocycline.)

[0069] structure [ka] Regarding the part, "Pair R x / R y The phrase "they, together with the atoms to which they are bonded, form ring A" is R x and R y However, it is also understood that this means forming the following structure: [ka] As used herein, "halogen" means fluoro, chloro, bromo, or iodine. In certain embodiments, the halogen is fluoro or chloro.

[0070] Generally, the terms "comprise" or "comprising" also include "consist of" or "consisting of."

[0071] In a particular embodiment, the compound is of formula (Ia). In a particular embodiment, x in formula (Ia) is 1. In a particular embodiment, x in formula (Ia) is 2. In a particular embodiment, x in formula (Ia) is 3. In a particular embodiment, x in formula (Ia) is 4. In a particular embodiment, x in formula (Ia) is 5. In a particular embodiment, x in formula (Ia) is 6. In a particular embodiment, x in formula (Ia) is 7. In a particular embodiment, x in formula (Ia) is 8. In a particular embodiment, x in formula (Ia) is 9. In a particular embodiment, x in formula (Ia) is 10. In a particular embodiment, x in formula (Ia) is 11. In a particular embodiment, x in formula (Ia) is 12. In a particular embodiment, x in formula (Ia) is 13. In a particular embodiment, x in formula (Ia) is 14. In a particular embodiment, x in formula (Ia) is 15. In a particular embodiment, x in formula (Ia) is 16. In a particular embodiment, x in formula (Ia) is 17. In a particular embodiment, x in formula (Ia) is 18. In a particular embodiment, x in formula (Ia) is 19. In a particular embodiment, x in formula (Ia) is 20. In a particular embodiment, x in formula (Ia) is 21. In a particular embodiment, x in formula (Ia) is 22. In a particular embodiment, x in formula (Ia) is 23. In a particular embodiment, x in formula (Ia) is 24. In a particular embodiment, x in formula (Ia) is 25.

[0072] In a particular embodiment, the compound is of formula (Ia) with x=1.

[0073] In certain embodiments, the compound is of formula (Ib). In certain embodiments, y in formula (Ib) is 1. In certain embodiments, y in formula (Ib) is 2. In certain embodiments, y in formula (Ib) is 3. In certain embodiments, y in formula (Ib) is 4. In certain embodiments, y in formula (Ib) is 5. In certain embodiments, y in formula (Ib) is 6. In certain embodiments, y in formula (Ib) is 7. In certain embodiments, y in formula (Ib) is 8. In certain embodiments, y in formula (Ib) is 9. In certain embodiments, y in formula (Ib) is 10. In certain embodiments, y in formula (Ib) is 11. In certain embodiments, y in formula (Ib) is 12. In certain embodiments, y in formula (Ib) is 13. In certain embodiments, y in formula (Ib) is 14. In a particular embodiment, y in formula (Ib) is 15. In a particular embodiment, y in formula (Ib) is 16. In a particular embodiment, y in formula (Ib) is 17. In a particular embodiment, y in formula (Ib) is 18. In a particular embodiment, y in formula (Ib) is 19. In a particular embodiment, y in formula (Ib) is 20. In a particular embodiment, y in formula (Ib) is 21. In a particular embodiment, y in formula (Ib) is 22. In a particular embodiment, y in formula (Ib) is 23. In a particular embodiment, y in formula (Ib) is 24. In a particular embodiment, y in formula (Ib) is 25.

[0074] In certain embodiments, the compound is of formula (Ib) having y=2.

[0075] In a particular embodiment, -D- is a drug moiety selected from the group consisting of a small molecule drug moiety, a medium-sized molecule drug moiety, an oligonucleotide drug moiety, a peptide nucleic acid drug moiety, a peptide drug moiety, and a protein drug moiety.

[0076] In certain embodiments, -D- is a peptide drug moiety. In certain embodiments, -D- is a small molecule drug moiety. In certain embodiments, -D- is a medium-sized drug moiety. In certain embodiments, -D- is an oligonucleotide drug moiety. In certain embodiments, -D- is a peptide nucleic acid drug moiety. In certain embodiments, -D- is a protein drug moiety.

[0077] In certain embodiments, -D- or -D-AB 2 This is the GLP-1 receptor agonist moiety. Therefore, the conjugate of the present invention may be a GLP-1 receptor agonist conjugate.

[0078] In certain embodiments, -D- or -D-AB 2 It is a mono agonist of the GLP-1 receptor, meaning it activates only the GLP-1 receptor.

[0079] In certain embodiments, -D- or -D-AB 2 It is an agonist of the GLP-1 receptor and an agonist of further receptors, namely -D- or -D-AB. 2 It is a dual GLP-1 receptor agonist. Further such receptors can be selected from the group consisting of GIP receptors, GCG receptors, amyrin receptors, PYY receptors, and GLP-2 receptors.

[0080] In certain embodiments, -D- or -D-AB 2 It is an agonist of the GLP-1 receptor and the GIP receptor. In certain embodiments, -D- or -D-AB 2 It is an agonist of the GLP-1 receptor and the GCG receptor. In certain embodiments, -D- or -D-AB 2 It is an agonist of the GLP-1 receptor and the amyrin receptor. In certain embodiments, -D- or -D-AB 2It is an agonist of the GLP-1 receptor and the PYY receptor. In certain embodiments, -D- or -D-AB 2 It is an agonist of the GLP-1 receptor and the GLP-2 receptor.

[0081] In certain embodiments, -D- or -D-AB 2 It is a GLP-1 receptor agonist and growth / differentiation factor 15 (GDF15). In certain embodiments, -D- or -D-AB 2 It is a GLP-1 receptor agonist and fibroblast growth factor 21 (FGF21).

[0082] In certain embodiments, -D- or -D-AB 2 It is an agonist of the GLP-1 receptor and an agonist of two further receptors, namely -D- or -D-AB. 2 It is a triple GLP-1 receptor agonist. These further receptors are selected in certain embodiments from the group consisting of GIP receptor (GIPR), GCG receptor (GCGR), amyrin receptor, PYY receptor (PYYR), and GLP-2 receptor (GLP2R).

[0083] In certain embodiments, -D- or -D-AB 2 It is a triple GLP-1 receptor agonist that activates the GLP-1 receptor, GIP receptor, and GCG receptor. In certain embodiments, it is -D- or -D-AB. 2 It is a triple GLP-1 receptor agonist that activates the GLP-1 receptor, GIP receptor, and amyrin receptor. In certain embodiments, it is -D- or -D-AB. 2 It is a triple GLP-1 receptor agonist that activates the GLP-1 receptor, GIP receptor, and PYY receptor. In certain embodiments, it is -D- or -D-AB. 2 It is a triple GLP-1 receptor agonist that activates the GLP-1 receptor, GIP receptor, and GLP-2 receptor. In certain embodiments, it is -D- or -D-AB. 2It is a triple GLP-1 receptor agonist that activates the GLP-1 receptor, GCG receptor, and amyrin receptor. In certain embodiments, it is -D- or -D-AB. 2 It is a triple GLP-1 receptor agonist that activates the GLP-1 receptor, GCG receptor, and PYY receptor. In certain embodiments, it is -D- or -D-AB. 2 It is a triple GLP-1 receptor agonist that activates the GLP-1 receptor, GCG receptor, and GLP-2 receptor. In certain embodiments, it is -D- or -D-AB. 2 It is a triple GLP-1 receptor agonist that activates the GLP-1 receptor, amyrin receptor, and PYY receptor. In certain embodiments, it is -D- or -D-AB. 2 It is a triple GLP-1 receptor agonist that activates the GLP-1 receptor, amyrin receptor, and GLP-2 receptor. In certain embodiments, it is -D- or -D-AB. 2 It is a triple GLP-1 receptor agonist that activates the GLP-1 receptor, PYY receptor, and GLP-2 receptor.

[0084] In a particular embodiment, -D- is human GLP-1 of Sequence ID No. 1: HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG In certain embodiments, -D- is a human GLP-1 analog of SEQ ID NO: 1, wherein the peptide sequence may contain one or more amino acid changes compared to SEQ ID NO: 1. Such amino acid changes may be the addition of one or more amino acid residues, the deletion of one or more amino acid residues, the substitution of one or more amino acid residues, or a combination thereof. Such amino acid changes may be at the N-terminus, C-terminus, and / or internal sites of GLP-1 of SEQ ID NO: 1. In certain embodiments, such a human GLP-1 analog may have up to three amino acid changes compared to SEQ ID NO: 1, i.e., up to three amino acids are added, deleted, or substituted compared to the sequence of SEQ ID NO: 1.

[0085] In a particular embodiment, -D- is an array HX1EGTFTSDVSSYLEGQAAKEFIAWLVRGRG(Sequence ID 2) (In the formula, X1 is 2-aminoisobutyric acid (Aib)) It has.

[0086] In a particular embodiment, -D- is an array HX1EGTFTSDVSSYLEGQAAKEFIAWLVRGRG(Sequence ID 3) (In the formula, X1 is Aib, and the C-terminal glycine, i.e., the glycine at position 31, is amidated as a C-terminal primary amide.) It has.

[0087] In certain embodiments, -D- is exenatide. Exenatide is sequence HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS(Sequence No. 4) It has.

[0088] In a particular embodiment, -D- is an array HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS(Sequence No. 5) (In the formula, the C-terminal serine, i.e., the serine at position 39, is amidated as a C-terminal primary amide.) It has.

[0089] In certain embodiments, -D- is lixisenatide. Lixisenatide is sequence HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPSKKKKKK(Sequence No. 6) (In the formula, the C-terminal lysine, i.e., the lysine at position 44, is amidated as a C-terminal primary amide.) It has.

[0090] In a particular embodiment, -D- is an array HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPSKKKKKK(Sequence ID 7) It has.

[0091] In a particular embodiment, -D- is an array HX1EGTFTSDLSKQX2EEEAVRLFIEWLKQGGPSSGAPPPC (Sequence ID 8) (In the formula, X1 is D-alanine and X2 is norleucine (Nle)) It has.

[0092] In a particular embodiment, -D- is an array HX1EGTFTSDLSKQX2EEEAVRLFIEWLKQGGPSSGAPPPC (Sequence ID 9) (In the formula, X1 is D-alanine, X2 is Nle, and the C-terminal cysteine, i.e., the cysteine ​​at position 39, is amidated as a C-terminal primary amide.) It has.

[0093] In certain embodiments, -D- is PEG-loxenatide. PEG-loxenatide is sequence HX1EGTFTSDLSKQX2EEEAVRLFIEWLKQGGPSSGAPPPC (Sequence ID 10) [In the formula, X1 is D-alanine, X2 is Nle, and the cysteine ​​at position 39 is, [ka] (In the formula, the dashed line indicates the bond of the cysteine ​​side chain of the cysteine ​​at position 39 to the thiol group, and each mPEG is methoxypoly(ethylene glycol) with a molecular weight of approximately 20 kDa.) [It is chemically modified through the conjugation of the cysteine ​​side chain to the thiol group.] It has.

[0094] In a particular embodiment, -D- is an array HX1EGTFTSDLSKQX2EEEAVRLFIEWLKQGGPSSGAPPPC (Sequence ID 11) [In the formula, X1 is D-alanine, X2 is Nle, and the cysteine ​​at position 39 is, [ka] (In the formula, the dashed line indicates the bond of the cysteine ​​side chain of the cysteine ​​at position 39 to the thiol group, each mPEG is a methoxypoly(ethylene glycol) with a molecular weight of approximately 20 kDa, and the C-terminal cysteine, i.e., the cysteine ​​at position 39, is amidated as a C-terminal primary amide.) [It is chemically modified through the conjugation of the cysteine ​​side chain to the thiol group.] It has.

[0095] In a particular embodiment, -D- is an array HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG(Sequence ID 12) It has.

[0096] In a particular embodiment, -D- is an array HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG(Sequence ID 13) It has a C-terminal glycine, i.e., the glycine at position 31, which is amidated as a C-terminal primary amide.

[0097] In a particular embodiment, -D- is an array HVEGTFTSDVSSYLEEQAAREFIKWLVRGRG (Sequence ID 14) It has.

[0098] In a particular embodiment, -D- is an array HVEGTFTSDVSSYLEEQAAREFIKWLVRGRG (Sequence ID 15) (In the formula, the C-terminal glycine, i.e., the glycine at position 31, is amidated as a C-terminal primary amide.) It has.

[0099] In a particular embodiment, -D- is an array HGEGTFTSDVSSYLEGQAAKEFIAWLVRGRG(Sequence ID 16) It has.

[0100] In a particular embodiment, -D- is an array HGEGTFTSDVSSYLEGQAAKEFIAWLVRGRG(Sequence ID 17) It has a C-terminal glycine, i.e., the glycine at position 31, which is amidated as a C-terminal primary amide.

[0101] In a particular embodiment, -D- is an array HX1EGTFTSDVSSYLEGQAAKEFIAWLVRGRGL (Sequence ID 18) (In the equation, X1 is Aib) It has.

[0102] In a particular embodiment, -D- is an array HX1EGTFTSDVSSYLEGQAAKEFIAWLVRGRGL (Sequence ID 19) (In the formula, X1 is Aib, and the C-terminal leucine, i.e., the leucine at position 32, is amidated as a C-terminal primary amide.) It has.

[0103] In a particular embodiment, -D- is an array YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS(Sequence ID 20) (In the formula, X1 is Aib, X2 is Aib, and the C-terminal serine, i.e., the serine at position 39, is amidated as a C-terminal primary amide.) It has.

[0104] In a particular embodiment, -D- is an array YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS(Sequence ID 21) (In the equation, X1 is Aib and X2 is Aib.) It has.

[0105] In a particular embodiment, -D- is an array HSQGTFTSDKSEYLDSERARDFVAWLEAGG (Sequence ID 22) It has.

[0106] In a particular embodiment, -D- is an array HSQGTFTSDKSEYLDSERARDFVAWLEAGG (Sequence ID 23) (In the formula, the C-terminal glycine, i.e., the glycine at position 30, is amidated as a C-terminal primary amide.) It has.

[0107] In a particular embodiment, -D- is an array HX1QGTFTSDYSKYLDERAAKDFIKWLESA (Sequence ID 24) (In the formula, X1 is 1-aminocyclobutanecarboxylic acid (Ac4c), and the C-terminal alanine, i.e., the alanine at position 29, is amidated as a C-terminal primary amide.) It has.

[0108] In a particular embodiment, -D- is an array HX1QGTFTSDYSKYLDERAAKDFIKWLESA (Sequence ID 25) (In the formula, X1 is 1-amino-cyclobutanecarboxylic acid (Ac4c)) It has.

[0109] In a particular embodiment, -D- is an array HX1QGTFTSDYSKYLDEKAAKEFIQWLLQT (Sequence ID 26) (In the formula, X1 is Aib, and the glutamic acid at position 16 and the lysine at position 20 are linked via a lactam crosslink.) It has.

[0110] In a particular embodiment, -D- is an array HX1QGTFTSDYSKYLDEKAAKEFIQWLLQT (Sequence ID 27) (In the formula, X1 is Aib, and the glutamic acid at position 16 and the lysine at position 20 are linked via a lactam crosslink, and the C-terminal threonine, i.e., the threonine at position 29, is amidated as a C-terminal primary amide.) It has.

[0111] In a particular embodiment, -D- is an array HX1QGTFTSDYSKYLDEKKAKEFVEWLLEGGPSSG (Sequence ID 28) (In the formula, X1 is Aib, and the C-terminal glycine, i.e., the glycine at position 34, is amidated as a C-terminal primary amide.) It has.

[0112] In a particular embodiment, -D- is an array HX1QGTFTSDYSKYLDEKKAKEFVEWLLEGGPSSG (Sequence ID 29) (In the equation, X1 is Aib) It has.

[0113] In a particular embodiment, -D- is an array HX1EGSFTSELATILDKQAARDFIAWLIQHKITD (Sequence ID 30) (In the equation, X1 is Aib) It has.

[0114] In a particular embodiment, -D- is an array HX1EGSFTSELATILDKQAARDFIAWLIQHKITD (Sequence ID 31) (In the formula, X1 is Aib, and the C-terminal aspartic acid, i.e., the aspartic acid at position 33, is amidated as a C-terminal primary amide.) It has.

[0115] In a particular embodiment, -D- is an array YX1QGTFTSDYSIX2LDKKAQX3AFIEYLLEGGPSSGAPPPS (Sequence ID 32) (In the formula, X1 is Aib, X2 is α-methylleucine (αMeL), X3 is Aib, and the C-terminal serine, i.e., the serine at position 39, is amidated as a C-terminal primary amide.) It has.

[0116] In a particular embodiment, -D- is an array YX1QGTFTSDYSIX2LDKKAQX3AFIEYLLEGGPSSGAPPPS (Sequence ID 33) (In the formula, X1 is Aib, X2 is α-methylleucine (αMeL), and X3 is Aib.) It has.

[0117] In a particular embodiment, -D- is an array HX1EGTFTSDVSSYLEEEAAKEFIAWLVRGGPSSGAPPPSK (Sequence ID 54) (In the equation, X1 is Aib) It has.

[0118] In a particular embodiment, -D- is an array HX1EGTFTSDVSSYLEEQAAKEFIAWLVRGGG (Sequence ID 55) (In the equation, X1 is Aib) It has.

[0119] In a particular embodiment, -D- is an array HX1EGTFTSDVSSYLEEQAAKEFIAWLVRGGGGAQPGAQPGAQPGAQPGAQPGAQPGAQPGAQPGAQPGQKP(Sequence ID 56) (In the equation, X1 is Aib) It has.

[0120] In a particular embodiment, -D- is an array YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS (Sequence ID 57) (In the formula, both X1 and X2 are Aib.) It has.

[0121] In certain embodiments, -D- is a drug selected from the group consisting of insulin, amylin and amylin / calcitonin, PYY, GIP, MSH, C5a binders, GDF15, PCSK9 I, immunostimulants, urocortin 2, MIC-1, IL-1R antagonists, leptin, gastrin, glucagon, exendin-4, GLP-1, GLP-2, and GIP.

[0122] In certain embodiments, -D- is a drug portion selected from the group consisting of insulin, insulin analogs, amylin, biamylin / calcitonin agonists, PYY, GIP, MSH, C5 inhibitors or modifiers, GDF15, PCSK9 inhibitors (inhibitors), immunostimulants, urocortin II, MIC-1, IL-1R antagonists, leptin, gastrin, glucagon, oxytomodulin, neurokinin A, tachykinin / neurokinin receptor 2 (NK2R) agonists, neurokinin receptor (NKR) agonists, and GLP-2.

[0123] In certain embodiments, -D- is insulin, e.g., insulin detemir, insulin degludec, or insulin. In certain embodiments, -D- is amylin or amylin / calcitonin, e.g., caglilintide. In certain embodiments, -D- is PYY, e.g., NNC0165-1875. In certain embodiments, -D- is GIP. In certain embodiments, -D- is MSH. In certain embodiments, -D- is a C5a binder, e.g., zircoplan. In certain embodiments, -D- is GDF15, e.g., NN LA-GDF15. In certain embodiments, -D- is PCSK9 i. In certain embodiments, -D- is an immunostimulant, e.g., romultide or mifamultide. In certain embodiments, -D- is muramyl dipeptide. In certain embodiments, -D- is urocortin 2. In certain embodiments, -D- is MIC-1. In certain embodiments, -D- is an IL-1R antagonist. In certain embodiments, -D- is leptin. In certain embodiments, -D- is gastrin.

[0124] In certain embodiments, -D- is selected from a list consisting of growth hormones, such as human growth hormone, FGF21, EGF(a), and coagulation factors.

[0125] In certain embodiments, -D- is a growth hormone, e.g., human growth hormone, e.g., somapsitan. In certain embodiments, -D- is FGF21, e.g., NNC0194 0499. In certain embodiments, -D- is EGF(a). In certain embodiments, -D- is a coagulation factor.

[0126] In certain embodiments, -D- is selected from cytotoxic small molecule drugs, chemotherapeutic small molecule drugs, and immunoactivating small molecule drugs.

[0127] In certain embodiments, -D- is a cytotoxic small molecule drug. In certain embodiments, -D- is a chemotherapeutic small molecule drug. In certain embodiments, -D- is an immunoactivating small molecule drug, such as tellatrimod.

[0128] In certain embodiments, -D- is paclitaxel. In certain embodiments, -D- is doxorubicin. In certain embodiments, -D- is 5-FU.

[0129] In certain embodiments, -D- is the PTH portion.

[0130] Part-AB 1 is, -L 2 -L 1 - is conjugated to -D- via -L 2 - is - AB 1 Conjugate to -L 1 - conjugates to -D- -L 1 When the bond between - and -D- is broken, part -AB 1 is, -L 2 - Remains conjugated to -AB. 2 For example, it is directly conjugated to -D- through a stable bond. This is -L 1 When the bond between - and -D- is broken, the conjugate HD-AB 2 This means that hydrogen is released, and in the formula, H- represents hydrogen. Therefore, the part "HD-AB" 2 " is part -D-AB 2 It is also called the corresponding free drug.

[0131] Part-AB 1 and -AB 2 It binds to albumin, such as human albumin, under physiological conditions (aqueous buffer solution, pH 7.4, 37.4°C).

[0132] In a particular embodiment, -AB 1 and -AB 2They have different structures. In certain embodiments, -AB 1 and -AB 2 They have the same structure.

[0133] Each-AB 1 and -AB 2 These can independently be a fatty acid-based albumin-binding moiety or a peptidolytic albumin-binding moiety.

[0134] In a particular embodiment, -AB 1 and -AB 2 This is independently an albumin-binding moiety based on fatty acids. In certain embodiments, -AB 1 and -AB 2 Both are albumin-binding moieties based on fatty acids and have the same structure. In certain embodiments, -AB 1 and -AB 2 Both are albumin-binding moieties based on fatty acids, but they have different structures.

[0135] In a particular embodiment, -AB 1 and / or -AB 2 Independently, equation (A): [ka] [In the formula, The dashed lines represent -L 2 - or -D- indicates binding to D-, -F 0 is equation (a-1) [ka] (In the formula, The dashed line is -L A - indicates binding to -R 0 -CR 1 R 1a R 1b ,-COOR 1 , [ka] Selected from the group consisting of, -R 1 ,-R 1a and -R 1b It is selected from the group consisting of -H, methyl, ethyl, propyl and isopropyl, n is an integer between 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, and 22. It is, -L A - is either nonexistent or expression (a-2) [ka] (In the formula, Dashed lines without a mark are -L B - indicates binding to The dashed line with an asterisk indicates -F 0 This shows a connection to, -R a -teeth, [ka] (In the formula, The dashed line with an asterisk indicates -F 0 This shows a connection to, Dashed lines without a mark are -L A (Indicates connection to the remainder) Selected from the group consisting of, -R b -teeth, [ka] And, m is an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10. p is an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10. It is, -L B - is either nonexistent or expression (a-3) [ka] (In the formula, Dashed lines without a mark are -L 2 - or -D- indicates binding to D-, The dashed line with an asterisk indicates -L A This shows a connection to, -R c -teeth, [ka] And, -R d - is C 1-50 Alkyl, C 2-50 Alkenyl and C 2-50 Selected from the group consisting of alkynnyls, where C 1-50 Alkyl, C 2-50 Alkenyl and C 2-50 Alkinyl can have one or more -Rs, which may be the same or different. 1 It can be replaced with C 1-50 Alkyl, C 2-50 Alkenyl or C 2-50 Alkinyls include -T-, -C(O)O-, -O-, -C(O)-, and -C(O)N(R) 2 )-,-S(O)2N(R 2 )-,-S(O)N(R 2 )-, -S(O)2-, -S(O)-, -N(R 2 )S(O)2N(R 2a )-, -S-, -N(R 2 )-, -OC(OR 2 )(R 2a )-,-N(R 2 )C(O)N(R 2a )-, and -OC(O)N(R 2 )- may have one or more groups selected from the group consisting of these groups, Each -T- is independently phenyl, naphthyl, indenyl, indanyl, tetralinyl, C 3-10 Selected from the group consisting of cycloalkyls, 3-10 membered heterocyclils, 8-11 membered heterobicyclils, 8-30 membered carbopolycyclils, and 8-30 membered heteropolycyclils, where each -T- is independently one or more -R which may be the same or different. 1It can be replaced with Each-R 1 These are, independently, halogen, -CN, oxo (=O), and -COOR. 3 , -OR 3 , -C(O)R 3 ,-C(O)N(R 3 R 3a ), -S(O)2N(R 3 R 3a ), -S(O)N(R 3 R 3a ), -S(O)2R 3 ,-S(O)R 3 , -N(R 3 )S(O)2N(R 3a R 3b ), -SR 3 , -N(R 3 R 3a ), -NO2, -OC(O)R 3 , -N(R 3 )C(O)R 3a , -N(R 3 )S(O)2R 3a , -N(R 3 )S(O)R 3a , -N(R 3 )C(O)OR 3a , -N(R 3 )C(O)N(R 3a R 3b ), -OC(O)N(R 3 R 3a ), and C 1-6 Selected from the group consisting of alkyl groups, where C 1-6 Alkyl is optionally substituted with one or more halogens, either the same or different. Each-R 2 ,-R 2a ,-R 3 ,-R 3a and -R 3b These are independently -H and C 1-6 Selected from the group consisting of alkyl groups, where C 1-6 Alkyl can be substituted with one or more halogens, which may be the same or different. -R e - is -CH2-, [ka] (Selected from the group consisting of) [It belongs to] It belongs to them.

[0136] -R b -but [ka] and -L B -If not absent, -R c -teeth [ka] And, -R b -but [ka] and -L B -If not absent, -R c -teeth [ka] That is the case.

[0137] In certain embodiments, -L A - is of formula (a-2), i.e., not absent. In certain embodiments, -L A - does not exist.

[0138] In certain embodiments, -R a -teeth, [ka] (In the formula, the dashed line with an asterisk indicates -F) 0 The dashed line without a mark indicates a connection to -L. A (Indicates connection to the remainder) That is the case.

[0139] In certain embodiments, -R a -teeth, [ka] (In the formula, the dashed line with an asterisk indicates -F) 0 The dashed line without a mark indicates a connection to -L. A (Indicates connection to the remainder) That is the case.

[0140] In certain embodiments, -R b -teeth, [ka] In certain embodiments, -R b -teeth, [ka] That is the case.

[0141] In a particular embodiment, m in formula (a-2) is 1. In a particular embodiment, m in formula (a-2) is 2. In a particular embodiment, m in formula (a-2) is 3. In a particular embodiment, m in formula (a-2) is 4. In a particular embodiment, m in formula (a-2) is 5. In a particular embodiment, m in formula (a-2) is 6. In a particular embodiment, m in formula (a-2) is 7. In a particular embodiment, m in formula (a-2) is 8. In a particular embodiment, m in formula (a-2) is 9. In a particular embodiment, m in formula (a-2) is 10.

[0142] In a particular embodiment, p in formula (a-2) is 1. In a particular embodiment, p in formula (a-2) is 2. In a particular embodiment, p in formula (a-2) is 3. In a particular embodiment, p in formula (a-2) is 4. In a particular embodiment, p in formula (a-2) is 5. In a particular embodiment, p in formula (a-2) is 6. In a particular embodiment, p in formula (a-2) is 7. In a particular embodiment, p in formula (a-2) is 8. In a particular embodiment, p in formula (a-2) is 9. In a particular embodiment, p in formula (a-2) is 10.

[0143] In certain embodiments, -L B - is from formula (a-3). In a particular embodiment, -L B - does not exist. -L B If - does not exist, the unmarked dashed lines in equation (a-2) represent -L respectively. 2 - Indicates a binding to -D-

[0144] In certain embodiments, -R c -teeth, [ka] In certain embodiments, -R c -teeth, [ka] That is the case.

[0145] In certain embodiments, -R e - is -CH2-. In certain embodiments, -R e -teeth, [ka] In certain embodiments, -R e -teeth, [ka] That is the case.

[0146] In certain embodiments, -L A - and -L B -Neither exists. -L A - and -L B If neither of the - lines exists, the dashed lines in equation (a-1) represent -L, respectively. 2 - Indicates a binding to -D-

[0147] In a particular embodiment, -F 0 teeth, [ka] TIFF2026509773000037.tif245163TIFF2026509773000038.tif245163TIFF2026509773000039.tif136163(In the formula, the dashed line is -L) A (Indicates a connection to -) It is selected from the group consisting of the following.

[0148] -L A If - does not exist, the dashed line in equations (a-4) to (a-39) represents -L B - Indicates a binding to -L A - and -L B If neither of the above exists, the dashed lines in equations (a-4) to (a-39) indicate a connection to -D-.

[0149] In a particular embodiment, -F 0 This is the formula (a-4). In a particular embodiment, -F 0 This is the one in formula (a-5). In a particular embodiment, -F 0 This is the one in formula (a-6). In a particular embodiment, -F 0 This is the formula (a-7). In a particular embodiment, -F 0 This is the formula (a-8). In a particular embodiment, -F 0 This is the formula (a-9). In a particular embodiment, -F 0 This is the formula (a-10). In a particular embodiment, -F 0 This is the formula (a-11). In a particular embodiment, -F 0 This is the formula (a-12). In a particular embodiment, -F 0 This is the formula (a-13). In a particular embodiment, -F 0 This is the formula (a-14). In a particular embodiment, -F 0 This is the formula (a-15). In certain embodiments, -F 0 This is the formula (a-16). In a particular embodiment, -F 0This is the formula (a-17). In a particular embodiment, -F 0 This is the formula (a-18). In a particular embodiment, -F 0 This is the formula (a-19). In a particular embodiment, -F 0 This is the formula (a-20). In a particular embodiment, -F 0 This is the formula (a-21). In a particular embodiment, -F 0 This is the formula (a-22). In certain embodiments, -F 0 This is the formula (a-23). ​​In a particular embodiment, -F 0 This is the formula (a-24). In a particular embodiment, -F 0 This is the formula (a-25). In certain embodiments, -F 0 This is the formula (a-26). In certain embodiments, -F 0 This is the formula (a-27). In a particular embodiment, -F 0 This is the formula (a-28). In a particular embodiment, -F 0 This is the formula (a-29). In a particular embodiment, -F 0 This is the formula (a-30). In a particular embodiment, -F 0 This is the formula (a-31). In a particular embodiment, -F 0 This is the formula (a-32). In a particular embodiment, -F 0 This is the formula (a-33). In a particular embodiment, -F 0 This is the formula (a-34). In a particular embodiment, -F 0 This is the formula (a-35). In a particular embodiment, -F 0 This is the formula (a-36). In a particular embodiment, -F 0 This is the formula (a-37). In a particular embodiment, -F 0 This is the formula (a-38). In a particular embodiment, -F 0 This is the result of equation (a-39).

[0150] In a particular embodiment, -F 0 This is from equation (a-4), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-5), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-6), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-7), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-8), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-9), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-10), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-11), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-12), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-13), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-14), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-15), and -L A- and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-16), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-17), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-18), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-19), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-20), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-21), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-22), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-23), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-24), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-25), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-26), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0This is from equation (a-27), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-28), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-29), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-30), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-31), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-32), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-33), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-34), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-35), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-36), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-37), and -L A - and -L B -Neither of these exists. In certain embodiments, -F 0 This is from equation (a-38), and -L A - and -L B-Neither of these exists. In certain embodiments, -F 0 This is from equation (a-39), and -L A - and -L B -Neither exists.

[0151] In certain embodiments, -L A -teeth, [ka] TIFF2026509773000041.tif220163TIFF2026509773000042.tif40160(In the formula, the dashed line with an asterisk is -F) 0 The dashed line without a mark indicates a connection to -L. B - Indicates bonding to the remainder. -L B (If no dash is present, an unmarked dashed line indicates a connection to -D-) It is selected from the group consisting of the following.

[0152] In certain embodiments, -L A - is from formula (a-40). In a particular embodiment, -L A - is from formula (a-41). In a particular embodiment, -L A - is from formula (a-42). In a particular embodiment, -L A - is from formula (a-43). In a particular embodiment, -L A - is from formula (a-44). In a particular embodiment, -L A - is from formula (a-45). In a particular embodiment, -L A - is from formula (a-46). In a particular embodiment, -L A - is from formula (a-47). In a particular embodiment, -L A - is from formula (a-48). In a particular embodiment, -L A - is from formula (a-49). In a particular embodiment, -L A - is from formula (a-50). In a particular embodiment, -L A- is from formula (a-51). In a particular embodiment, -L A - is from formula (a-52). In a particular embodiment, -L A - is from formula (a-53). In a particular embodiment, -L A - is from formula (a-54). In a particular embodiment, -L A - is from formula (a-55). In a particular embodiment, -L A - is from formula (a-56). In certain embodiments, -L A - is from formula (a-57). In a particular embodiment, -L A - is from formula (a-58). In certain embodiments, -L A - is from formula (a-59). In a particular embodiment, -L A - is from formula (a-60). In certain embodiments, -L A - is from formula (a-61). In certain embodiments, -L A - is from formula (a-62). In certain embodiments, -L A - is from formula (a-63). In certain embodiments, -L A - is from formula (a-64). In a particular embodiment, -L A - is from formula (a-65). In certain embodiments, -L A - is from formula (a-66). In certain embodiments, -L A - is from formula (a-67). In a particular embodiment, -L A - is from formula (a-68). In a particular embodiment, -L A - is from formula (a-69). In certain embodiments, -L A - is from formula (a-70). In a particular embodiment, -L A - is from formula (a-71). In a particular embodiment, -L A - is from formula (a-72). In a particular embodiment, -L A - is from formula (a-73). In a particular embodiment, -LA - is from formula (a-74). In a particular embodiment, -L A - is from formula (a-75). In a particular embodiment, -L A - is from formula (a-76). In certain embodiments, -L A - is from formula (a-77). In a particular embodiment, -L A - is of formula (a-78). In a particular embodiment, -L A - is from formula (a-79). In a particular embodiment, -L A - is from formula (a-80). In a particular embodiment, -L A - is of formula (a-81). In a particular embodiment, -L A - is from equation (a-82).

[0153] In certain embodiments, -L B -teeth, [ka] TIFF2026509773000044.tif66162(in the formula, The dashed line with an asterisk indicates -L A - indicates binding to The dashed lines without a mark are -L 2 - or -D- indicates binding to D-, (q is an integer between 2 and 50) It is selected from the group consisting of the following.

[0154] -L A If - does not exist, the dashed lines with asterisks in equations (a-83) to (a-94) represent -F 0 This indicates a connection to [the specified location].

[0155] In a particular embodiment, q in formula (a-84) is an integer between 3 and 45. In a particular embodiment, q in formula (a-84) is an integer between 4 and 40. In a particular embodiment, q in formula (a-84) is an integer between 5 and 35. In a particular embodiment, q in formula (a-84) is an integer between 6 and 30. In a particular embodiment, q in formula (a-84) is an integer between 7 and 25. In a particular embodiment, q in formula (a-84) is an integer between 10 and 20. In a particular embodiment, q in formula (a-84) is 23.

[0156] In certain embodiments, -L B - is from formula (a-83). In a particular embodiment, -L B - is from formula (a-84). In a particular embodiment, -L B - is from equation (a-84) where q=23. In certain embodiments, -L B - is from formula (a-85). In a particular embodiment, -L B - is from formula (a-86). In certain embodiments, -L B - is from formula (a-87). In a particular embodiment, -L B - is from formula (a-88). In a particular embodiment, -L B - is from formula (a-89). In a particular embodiment, -L B - is from formula (a-90). In certain embodiments, -L B - is of formula (a-91). In a particular embodiment, -L B - is from formula (a-92). In certain embodiments, -L B - is from formula (a-93). In certain embodiments, -L B - is from equation (a-94).

[0157] In a particular embodiment, -AB 1 and / or -AB 2 is equation (i) [ka] (In the formula, the dashed lines represent -L, respectively) 2 - or -D- indicates binding to D-, n is an integer between 14 and 22. (The stereocenter marked with an asterisk is either in S or R configuration.) It belongs to them.

[0158] In a particular embodiment, -AB 1 and / or -AB 2 is the one in equation (i), where n is 14. In a particular embodiment, -AB 1 and / or -AB 2 is the one in formula (i), where n is 15. In a particular embodiment, -AB 1 and / or -AB 2 is the one in equation (i), where n is 16. In a particular embodiment, -AB 1 and / or -AB 2 is the one in formula (i), where n is 17. In a particular embodiment, -AB 1 and / or -AB 2 is the one in formula (i), where n is 18. In a particular embodiment, -AB 1 and / or -AB 2 is the one in formula (i), where n is 19. In a particular embodiment, -AB 1 and / or -AB 2 is the one in equation (i), where n is 20. In a particular embodiment, -AB 1 and / or -AB 2 is the one in formula (i), where n is 21. In a particular embodiment, -AB 1 and / or -AB 2 The expression is from equation (i), where n is 22.

[0159] In a particular embodiment, -AB 1 and / or -AB 2 is from equation (i), where n is 14, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2This is from equation (i), where n is 15, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (i), where n is 16, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 is from equation (i), where n is 17, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 is from equation (i), where n is 18, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 is from equation (i), where n is 19, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 is from equation (i), where n is 20, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 is from equation (i), where n is 21, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (i), where n is 22, and the solid centers marked with an asterisk are in R configuration.

[0160] In a particular embodiment, -AB 1 and / or -AB 2 is from equation (i), where n is 14, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 is from equation (i), where n is 15, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2This is from equation (i), where n is 16, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 is from equation (i), where n is 17, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 is from equation (i), where n is 18, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (i), where n is 19, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 is from equation (i), where n is 20, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 is from equation (i), where n is 21, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (i), where n is 22, and the solid centers marked with an asterisk are in an S configuration.

[0161] In a particular embodiment, -AB 1 and / or -AB 2 Equation (ia): [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0162] In a particular embodiment, -AB 1 and / or -AB 2 The formula is (ib): [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0163] In a particular embodiment, -AB 1 and / or -AB 2 The formula is (ic): [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0164] In a particular embodiment, -AB 1 and / or -AB 2 The expression (id): [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0165] In a particular embodiment, -AB 1 and / or -AB 2 is the formula (ie): [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0166] In a particular embodiment, -AB 1 and / or -AB 2 The expression (if): [ka] (In the formula, The dashed lines represent -L2 (Indicates a bond to -or-D-) It belongs to them.

[0167] In a particular embodiment, -AB 1 and / or -AB 2 is equation (ii) [ka] (In the formula, The dashed lines represent -L 2 - or -D- indicates binding to D-, n is an integer between 14 and 22. (The stereocenter marked with an asterisk is either in S or R configuration.) It belongs to them.

[0168] In a particular embodiment, -AB 1 and / or -AB 2 is of formula (ii), where n is 14. In certain embodiments, - and / or -AB 2 is the one in formula (ii), where n is 15. In a particular embodiment, -AB 1 and / or -AB 2 is the one in formula (ii), where n is 16. In a particular embodiment, -AB 1 and / or -AB 2 is the one in formula (ii), where n is 17. In a particular embodiment, -AB 1 and / or -AB 2 is the one in formula (ii), where n is 18. In a particular embodiment, -AB 1 and / or -AB 2 is the one in formula (ii), where n is 19. In a particular embodiment, -AB 1 and / or -AB 2 is the one in formula (ii), where n is 20. In a particular embodiment, -AB 1 and / or -AB 2 is the one in formula (ii), where n is 21. In a particular embodiment, -AB 1 and / or -AB 2The expression is from equation (ii), where n is 22.

[0169] In a particular embodiment, -AB 1 and / or -AB 2 This is the result of equation (ii), where n is 14, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is the result of equation (ii), where n is 15, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (ii), where n is 16, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (ii), where n is 17, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (ii), where n is 18, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is the result of equation (ii), where n is 19, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is the result of equation (ii), where n is 20, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is the result of equation (ii), where n is 21, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (ii), where n is 22, and the solid centers marked with an asterisk are in R configuration.

[0170] In a particular embodiment, -AB 1 and / or -AB 2is of formula (ii), n is 14, and the asterisked stereocenter is in the S configuration. In certain embodiments, -AB 1 and / or -AB 2 is of formula (ii), n is 15, and the asterisked stereocenter is in the S configuration. In certain embodiments, -AB 1 and / or -AB 2 is of formula (ii), n is 16, and the asterisked stereocenter is in the S configuration. In certain embodiments, -AB 1 and / or -AB 2 is of formula (ii), n is 17, and the asterisked stereocenter is in the S configuration. In certain embodiments, -AB 1 and / or -AB 2 is of formula (ii), n is 18, and the asterisked stereocenter is in the S configuration. In certain embodiments, -AB 1 and / or -AB 2 is of formula (ii), n is 19, and the asterisked stereocenter is in the S configuration. In certain embodiments, -AB 1 and / or -AB 2 is of formula (ii), n is 20, and the asterisked stereocenter is in the S configuration. In certain embodiments, -AB 1 and / or -AB 2 is of formula (ii), n is 21, and the asterisked stereocenter is in the S configuration. In certain embodiments, -AB 1 and / or -AB 2 is of formula (ii), n is 22, and the asterisked stereocenter is in the S configuration.

[0171] In certain embodiments, -AB 1 and / or -AB 2 is of formula (ii-a):

Chemical formula

[0172] In a particular embodiment, -AB 1 and / or -AB 2 Equation (ii-b): [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0173] In a particular embodiment, -AB 1 and / or -AB 2 Equation (ii-c): [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0174] In a particular embodiment, -AB 1 and / or -AB 2 Equation (ii-d): [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0175] In a particular embodiment, -AB 1 and / or -AB 2 Equation (ii-e): [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0176] In a particular embodiment, -AB 1 and / or -AB 2 Equation (ii-f): [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0177] In a particular embodiment, -AB 1 and / or -AB 2 is equation (iii) [ka] (In the formula, The dashed lines represent -L 2 - or -D- indicates binding to D-, t is an integer between 14 and 22. (The stereocenter marked with an asterisk is either in S or R configuration.) It belongs to them.

[0178] In a particular embodiment, -AB 1 and / or -AB 2 is the one in formula (iii), where t is 14. In a particular embodiment, -AB 1 and / or -AB 2 is the one in formula (iii), where t is 15. In a particular embodiment, -AB 1 and / or -AB 2 is the one in formula (iii), where t is 16. In a particular embodiment, -AB 1 and / or -AB 2 is of formula (iii), where t is 17. In a particular embodiment, -AB 1 and / or -AB 2 is of formula (iii), where t is 18. In a particular embodiment, -AB 1 and / or -AB2 is of formula (iii), and t is 19. In certain embodiments, -AB 1 and / or -AB 2 is of formula (iii), and t is 20. In certain embodiments, -AB 1 and / or -AB 2 is of formula (iii), and t is 21. In certain embodiments, -AB 1 and / or -AB 2 is of formula (iii), and t is 22.

[0179] In certain embodiments, -AB 1 and / or -AB 2 is of formula (iii), t is 14, and the stereocenter marked with an asterisk is in the R configuration. In certain embodiments, -AB 1 and / or -AB 2 is of formula (iii), t is 15, and the stereocenter marked with an asterisk is in the R configuration. In certain embodiments, -AB 1 and / or -AB 2 is of formula (iii), t is 16, and the stereocenter marked with an asterisk is in the R configuration. In certain embodiments, -AB 1 and / or -AB 2 is of formula (iii), t is 17, and the stereocenter marked with an asterisk is in the R configuration. In certain embodiments, -AB 1 and / or -AB 2 is of formula (iii), t is 18, and the stereocenter marked with an asterisk is in the R configuration. In certain embodiments, -AB 1 and / or -AB 2 is of formula (iii), t is 19, and the stereocenter marked with an asterisk is in the R configuration. In certain embodiments, -AB 1 and / or -AB 2 is of formula (iii), t is 20, and the stereocenter marked with an asterisk is in the R configuration. In certain embodiments, -AB 1 and / or -AB[[ID=)48]] 2This is the result of equation (iii), where t is 21, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (iii), where t is 22, and the solid centers marked with an asterisk are in R configuration.

[0180] In a particular embodiment, -AB 1 and / or -AB 2 This is the result of equation (iii), where t is 14, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is the result of equation (iii), where t is 15, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (iii), where t is 16, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is the result of equation (iii), where t is 17, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is the result of equation (iii), where t is 18, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (iii), where t is 19, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is the result of equation (iii), where t is 20, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is the result of equation (iii), where t is 21, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2This is from equation (iii), where t is 22, and the solid centers marked with an asterisk are in an S configuration.

[0181] In a particular embodiment, -AB 1 and / or -AB 2 is equation (iii-a) [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0182] In a particular embodiment, -AB 1 and / or -AB 2 is equation (iii-b) [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0183] In a particular embodiment, -AB 1 and / or -AB 2 is equation (iii-c) [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0184] In a particular embodiment, -AB 1 and / or -AB 2 is equation (iii-d) [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0185] In a particular embodiment, -AB 1 and / or -AB 2 is equation (iii-e) [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0186] In a particular embodiment, -AB 1 and / or -AB 2 is equation (iii-f) [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0187] In a particular embodiment, -AB 1 and / or -AB 2 is equation (iv) [ka] (In the formula, The dashed lines represent -L 2 - or -D- indicates binding to D-, (u is an integer between 14 and 22) It belongs to them.

[0188] In a particular embodiment, -AB 1 and / or -AB 2 is from formula (iv), where u is 14. In a particular embodiment, -AB 1 and / or -AB 2 is from formula (iv), where u is 15. In a particular embodiment, -AB 1 and / or -AB 2is from formula (iv), where u is 16. In a particular embodiment, -AB 1 and / or -AB 2 is from formula (iv), where u is 17. In a particular embodiment, -AB 1 and / or -AB 2 is from formula (iv), where u is 18. In a particular embodiment, -AB 1 and / or -AB 2 is from formula (iv), where u is 19. In a particular embodiment, -AB 1 and / or -AB 2 is from equation (iv), where u is 20. In a particular embodiment, -AB 1 and / or -AB 2 is of formula (iv), where u is 21. In a particular embodiment, -AB 1 and / or -AB 2 is from equation (iv), where u is 22.

[0189] In a particular embodiment, -AB 1 and / or -AB 2 is equation (v) [ka] (In the formula, The dashed lines represent -L 2 - or -D- indicates binding to D-, v is an integer between 14 and 22. (The stereocenter marked with an asterisk is either in S or R configuration.) It belongs to them.

[0190] In a particular embodiment, -AB 1 and / or -AB 2 is of formula (v), where v is 14. In a particular embodiment, -AB 1 and / or -AB 2 is of formula (v), where v is 15. In a particular embodiment, -AB 1 and / or -AB 2is of formula (v), where v is 16. In a particular embodiment, -AB 1 and / or -AB 2 is of equation (v), where v is 17. In a particular embodiment, -AB 1 and / or -AB 2 is of formula (v), where v is 18. In a particular embodiment, -AB 1 and / or -AB 2 is of formula (v), where v is 19. In a particular embodiment, -AB 1 and / or -AB 2 is the expression of equation (v), where v is 20. In a particular embodiment, -AB 1 and / or -AB 2 is of equation (v), where v is 21. In a particular embodiment, -AB 1 and / or -AB 2 The expression is from equation (v), where v is 22.

[0191] In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (v), where v is 14, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is the result of equation (v), where v is 15, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (v), where v is 16, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is the result of equation (v), where v is 17, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (v), where v is 18, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2This is the result of equation (v), where v is 19, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is the result of equation (v), where v is 20, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is the result of equation (v), where v is 21, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (v), where v is 22, and the solid centers marked with an asterisk are in R configuration.

[0192] In a particular embodiment, -AB 1 and / or -AB 2 This is the result of equation (v), where v is 14, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is the result of equation (v), where v is 15, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is the result of equation (v), where v is 16, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (v), where v is 17, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (v), where v is 18, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (v), where v is 19, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2This is the result of equation (v), where v is 20, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is the result of equation (v), where v is 21, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 The expression is from equation (v), where v is 22, and the solid centers marked with an asterisk are in an S configuration.

[0193] In a particular embodiment, -AB 1 and / or -AB 2 is equation (va) [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0194] In a particular embodiment, -AB 1 and / or -AB 2 is the expression (vb) [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0195] In a particular embodiment, -AB 1 and / or -AB 2 is the formula (vc) [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0196] In a particular embodiment, -AB1 and / or -AB 2 is equation (vd) [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0197] In a particular embodiment, -AB 1 and / or -AB 2 is equation (vi-e) [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0198] In a particular embodiment, -AB 1 and / or -AB 2 is equation (vi-f) [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0199] In a particular embodiment, -AB 1 and / or -AB 2 is equation (vii) [ka] (In the formula, The dashed lines represent -L 2 - or -D- indicates binding to D-, w is an integer between 14 and 22. (The stereocenter marked with an asterisk is either in S or R configuration.) It belongs to them.

[0200] In a particular embodiment, -AB 1 and / or -AB 2 is of formula (vii), where w is 14. In a particular embodiment, -AB 1 and / or -AB 2 is of formula (vii), where w is 15. In a particular embodiment, -AB 1 and / or -AB 2 is of formula (vii), where w is 16. In a particular embodiment, -AB 1 and / or -AB 2 is of formula (vii), where w is 17. In a particular embodiment, -AB 1 and / or -AB 2 is of formula (vii), where w is 18. In a particular embodiment, -AB 1 and / or -AB 2 is of formula (vii), where w is 19. In a particular embodiment, -AB 1 and / or -AB 2 is of formula (vii), where w is 20. In a particular embodiment, -AB 1 and / or -AB 2 is of formula (vii), where w is 21. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (vii), where w is 22.

[0201] In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (vii), where w is 14, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (vii), where w is 15, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (vii), where w is 16, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB1 and / or -AB 2 This is from equation (vii), where w is 17, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (vii), where w is 18, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (vii), where w is 19, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (vii), where w is 20, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (vii), where w is 21, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (vii), where w is 22, and the solid centers marked with an asterisk are in R configuration.

[0202] In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (vii), where w is 14, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (vii), where w is 15, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (vii), where w is 16, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (vii), where w is 17, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1and / or -AB 2 This is from equation (vii), where w is 18, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (vii), where w is 19, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (vii), where w is 20, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (vii), where w is 21, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (vii), where w is 22, and the solid centers marked with an asterisk are in an S configuration.

[0203] In a particular embodiment, -AB 1 and / or -AB 2 Equation (vii-a): [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0204] In a particular embodiment, -AB 1 and / or -AB 2 Equation (vii-b): [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0205] In a particular embodiment, -AB 1and / or -AB 2 This is equation (vii-c): [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0206] In a particular embodiment, -AB 1 and / or -AB 2 The equation is (vii-d): [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0207] In a particular embodiment, -AB 1 and / or -AB 2 This is equation (vii-e): [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0208] In a particular embodiment, -AB 1 and / or -AB 2 This is equation (vii-f): [ka] (In the formula, The dashed lines represent -L 2 (Indicates a bond to -or-D-) It belongs to them.

[0209] In a particular embodiment, -AB 1 and / or -AB 2 is equation (viii) [ka] (In the formula, the dashed lines represent -L, respectively) 2 - or -D- indicates binding to D-, w is an integer between 14 and 22. (The stereocenter marked with an asterisk is either in S or R configuration.) It belongs to them.

[0210] In a particular embodiment, -AB 1 and / or -AB 2 is the one in equation (viii), where x is 14. In a particular embodiment, -AB 1 and / or -AB 2 is the one in equation (viii), where x is 15. In a particular embodiment, -AB 1 and / or -AB 2 is the one in equation (viii), where x is 16. In a particular embodiment, -AB 1 and / or -AB 2 is the one in equation (viii), where x is 17. In a particular embodiment, -AB 1 and / or -AB 2 is the one in equation (viii), where x is 18. In a particular embodiment, -AB 1 and / or -AB 2 is the one in equation (viii), where x is 19. In a particular embodiment, -AB 1 and / or -AB 2 is the expression of formula (viii), where x is 20. In a particular embodiment, -AB 1 and / or -AB 2 is the one in equation (viii), where x is 21. In a particular embodiment, -AB 1 and / or -AB 2 This is the same as in equation (viii), where x is 22.

[0211] In a particular embodiment, -AB 1 and / or -AB 2This is from equation (viii), where x is 14, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (viii), where x is 15, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (viii), where x is 16, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (viii), where x is 17, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (viii), where x is 18, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (viii), where x is 19, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (viii), where x is 20, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (viii), where x is 21, and the stereocenters marked with an asterisk are in the R configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (viii), where x is 22, and the solid center marked with an asterisk is in R configuration.

[0212] In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (viii), where x is 14, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2This is from equation (viii), where x is 15, and the stereocenters marked with an asterisk are in an S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (viii), where x is 16, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (viii), where x is 17, and the stereocenters marked with an asterisk are in an S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (viii), where x is 18, and the stereocenters marked with an asterisk are in an S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (viii), where x is 19, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (viii), where x is 20, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (viii), where x is 21, and the stereocenters marked with an asterisk are in the S configuration. In a particular embodiment, -AB 1 and / or -AB 2 This is from equation (viii), where x is 22, and the solid centers marked with an asterisk are in an S configuration.

[0213] In a particular embodiment, -AB 1 and / or -AB 2 is equation (viii-a) [ka] (In the formula, the dashed lines represent -L, respectively) 2 (Indicates a bond to -or-D-) It belongs to them.

[0214] In a particular embodiment, -AB 1 and / or -AB 2 is equation (viii-b) [ka] (In the formula, the dashed lines represent -L, respectively) 2 (Indicates a bond to -or-D-) It belongs to them.

[0215] In a particular embodiment, -AB 1 and / or -AB 2 is equation (viii-c) [ka] (In the formula, the dashed lines represent -L, respectively) 2 (Indicates a bond to -or-D-) It belongs to them.

[0216] In a particular embodiment, -AB 1 and / or -AB 2 is equation (viii-d) [ka] (In the formula, the dashed lines represent -L, respectively) 2 (Indicates a bond to -or-D-) It belongs to them.

[0217] In a particular embodiment, -AB 1 and / or -AB 2 is equation (viii-e) [ka] (In the formula, the dashed lines represent -L, respectively) 2 (Indicates a bond to -or-D-) It belongs to them.

[0218] In a particular embodiment, -AB 1 and / or -AB 2 is equation (viii-f) [ka] (In the formula, the dashed lines represent -L, respectively) 2 (Indicates a bond to -or-D-) It belongs to them.

[0219] In a particular embodiment, -AB 1 and / or -AB 2 is equation (ix-i) [ka] (In the formula, X 1 -teeth, [ka] And, -X 2 teeth, [ka] And, Ph stands for phenyl, a is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. b is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. c is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. d is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. m is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. n is 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24. p is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. It belongs to them.

[0220] In a particular embodiment, -AB 1 and / or -AB 2 This is the equation (ix-i) where a is 1, b is 1, c is 1, d is 1, m is 1, n is 18, and m is 1.

[0221] In a particular embodiment, -AB 1 and / or -AB 2 is of equation (ix-i), and X 1 -teeth, [ka] And -X 2 teeth, [ka] In a particular embodiment, -AB 1 and / or -AB 2 is of equation (ix-i), and X 1 -teeth, [ka] And -X 2 teeth, [ka] In a particular embodiment, -AB 1 and / or -AB 2 is of equation (ix-i), and X 1 -teeth, [ka] And -X 2 teeth, [ka] In a particular embodiment, -AB 1 and / or -AB 2 is of equation (ix-i), and X 1 -teeth, [ka] And -X 2 teeth, [ka] In a particular embodiment, -AB 1 and / or -AB 2 is of equation (ix-i), and X 1 -teeth, [ka] And -X 2 teeth, [ka] In a particular embodiment, -AB 1 and / or -AB 2 is of equation (ix-i), and X 1 -teeth, [ka] And -X 2 teeth, [ka] In a particular embodiment, -AB 1 and / or -AB 2 is of equation (ix-i), and X 1 -teeth, [ka] And -X 2 teeth, [ka] In a particular embodiment, -AB 1 and / or -AB 2 is of equation (ix-i), and X 1 -teeth, [ka] And -X 2 teeth, [ka] In a particular embodiment, -AB 1and / or -AB 2 is of equation (ix-i), and X 1 -teeth, [ka] And -X 2 teeth, [ka] In a particular embodiment, -AB 1 and / or -AB 2 is of equation (ix-i), and X 1 -teeth, [ka] And -X 2 teeth, [ka] In a particular embodiment, -AB 1 and / or -AB 2 is of equation (ix-i), and X 1 -teeth, [ka] And -X 2 teeth, [ka] In a particular embodiment, -AB 1 and / or -AB 2 is of equation (ix-i), and X 1 -teeth, [ka] And -X 2 teeth, [ka] That is the case.

[0222] In a particular embodiment, -AB1 and / or -AB 2 This is the peptidolytic albumin-binding moiety.

[0223] -D- is a peptide or protein drug portion, then the peptide portion -AB 2 is direct or -D- and -AB 2 It can be fused to the N or C terminus of -D-, either with a peptide spacer between them.

[0224] In a particular embodiment, -AB 1 and / or -AB 2 teeth, WWEQDRDWDFDVFGGGTP (Sequence ID 34), DICLPRWGCLW (Sequence ID 35) (In the formula, the cysteine ​​at positions 3 and 9 are linked via disulfide bridges.) RLIEDICLPRWGCLWEDD (Sequence ID 36) (In the formula, the cysteine ​​at positions 7 and 13 are linked via disulfide bridges.) LAEAKVLANRELDKYGVSDFYKRLINKAKTVEGVEALKLHILAALP (Sequence ID 37), IAEAKEAANAELDSYGVSDFYKRLIDKAKTVEGVEALKDAILAALP (Sequence ID 38), and X1EYEX2EYE (Sequence ID 39) (In the formula, X1 is fluorescein-(AEEA), X2 is K(palmitate), and AEEA is 2-(2-(2-aminoethoxy)acetyl) It is selected from the group consisting of the following.

[0225] In a particular embodiment, -AB 1 and / or -AB 2 This is the one shown in sequence number 34. In certain embodiments, -AB 1 and / or -AB 2 This is the one shown in sequence number 35. In certain embodiments, -AB 1and / or -AB 2 This is the one shown in sequence number 36. In certain embodiments, -AB 1 and / or -AB 2 This is the one shown in sequence number 37. In a particular embodiment, -AB 1 and / or -AB 2 This is the one shown in sequence number 38. In certain embodiments, -AB 1 and / or -AB 2 This is sequence number 39.

[0226] In a particular embodiment, -AB 1 is equation (XIX) [ka] (In the formula, The dashed line is -L 2 - indicates binding to (a is 14, 15, 16, 17, 18, 19, 20, 21, or 22) It belongs to them.

[0227] In a particular embodiment, a in formula (XIX) is 18.

[0228] In a particular embodiment, -AB 1 and / or -AB 2 is equation (Aa) [ka] (In the formula, The dashed lines represent -L 2 - or -D- indicates binding to D-, -F 0 and -L A - is used as defined in equation (A), -L B' - is the polymer part.) It belongs to them.

[0229] Part-L B'- indicates a polymer portion, which means that it contains at least one polymer portion. In a particular embodiment, one or more polymer portions have a molecular weight of at least 450 kDa. In a particular embodiment, one or more polymer portions have a molecular weight of at least 1 kDa. In a particular embodiment, one or more polymer portions have a molecular weight of at least 1.5 kDa. In a particular embodiment, one or more polymer portions have a molecular weight of at least 2 kDa. In a particular embodiment, one or more polymer portions have a molecular weight of at least 2.5 kDa. In a particular embodiment, one or more polymer portions have a molecular weight of at least 3 kDa. In a particular embodiment, one or more polymer portions have a molecular weight of at least 3.5 kDa. In a particular embodiment, one or more polymer portions have a molecular weight of at least 4 kDa. In a particular embodiment, one or more polymer portions have a molecular weight of at least 5 kDa. In a particular embodiment, one or more polymer portions have a maximum molecular weight of 160 kDa. In a particular embodiment, one or more polymer portions have a maximum molecular weight of 120 kDa. In a particular embodiment, one or more polymer portions have a maximum molecular weight of 100 kDa. In certain embodiments, one or more polymer portions have a maximum molecular weight of 80 kDa. In certain embodiments, one or more polymer portions have a maximum molecular weight of 70 kDa. In certain embodiments, one or more polymer portions have a maximum molecular weight of 60 kDa. In certain embodiments, one or more polymer portions have a maximum molecular weight of 50 kDa. In certain embodiments, one or more polymer portions have a maximum molecular weight of 40 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 450 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 1 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 1.5 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 2 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 2.5 kDa.In certain embodiments, one or more polymer portions have a molecular weight of approximately 3 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 3.5 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 4 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 4.5 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 5 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 5.5 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 6 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 6.5 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 7 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 7.5 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 8 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 8.5 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 9 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 9.5 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 10 kDa. -L. B' -If - contains one polymer moiety, the minimum and maximum molecular weights provided above apply to this one polymer moiety, -L B' If - contains two or more polymer moieties, it is understood that the minimum and maximum molecular weights provided above refer to the minimum and maximum molecular weights of all polymer moieties combined.

[0230] In certain embodiments, -L B' -One or more polymer portions have a flowy radius of at least 1.2 nm. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of at least 1.5 nm. In certain embodiments, -L B'-One or more polymer portions have a flowy radius of at least 2 nm. In certain embodiments, -L B' -One or more polymer portions have a flowy radius of at least 2.5 nm. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of at least 3 nm. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of at least 3.5 nm. In certain embodiments, -L B' -One or more polymer portions have a flory radius of at least 4 nm. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of at least 4.5 nm. In certain embodiments, -L B' -One or more polymer portions have a flory radius of at least 5 nm. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of 200 nm or less. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of 175 nm or less. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of 150 nm or less. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of 125 nm or less. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of 100 nm or less. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of 75 nm or less. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of 50 nm or less. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of 45 nm or less. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of 40 nm or less. In certain embodiments, -L B'-One or more polymer portions have a flowly radius of 35 nm or less. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of 30 nm or less. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of approximately 1.2 nm. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of about 1.5 nm. In certain embodiments, -L B' -One or more polymer portions have a flowy radius of about 2 nm. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of approximately 2.5 nm. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of about 3 nm. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of approximately 3.5 nm. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of about 4 nm. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of approximately 4.5 nm. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of about 5 nm. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of approximately 5.5 nm. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of about 6 nm. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of approximately 6.5 nm. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of about 7 nm. In certain embodiments, -L B' -One or more polymer portions have a flowly radius of approximately 8.5 nm. In certain embodiments, -L B'-One or more polymer portions have a flowly radius of about 9 nm. In certain embodiments, -L B' -One or more polymer portions have a flory radius of approximately 10 nm. -L B' -If it contains one polymer portion, the flory radius provided above applies to this one polymer portion, -L B' If - contains two or more polymer parts, it is understood that the flory radius provided above refers to the flory radius of all combined polymer parts.

[0231] -L B'- is one or more polymer moieties, for example, poly(2-methacryloyloxyethylphosphoryl(phosphoyl)choline), poly(acrylic acid), poly(acrylate), poly(acrylamide), poly(alkyloxy)polymer, poly(amide), poly(amideamine), poly(amino acid), poly(acid anhydride), poly(aspartamide), poly(butyric acid), poly(glycolic acid), polybutylene terephthalate, poly(caprolactone), poly(carbonate), poly(cyanoacrylate), poly(dimethylacrylamide), poly(ester), poly(ethylene), poly(ethylene glycol), poly(ethylene oxide), poly(ethyl phosphate), poly(ethyl oxazoline), poly(glycolic acid), poly(hydroxyethyl acrylate), poly(hydroxyethyl oxazoline), poly(hydroxymethacrylate), poly(hydroxypropyl methacrylamide), poly(hydroxypropyl methacrylate), The polymer contains polymer portions selected from the group consisting of poly(hydroxypropyl oxazoline), poly(iminocarbonate), poly(lactic acid), poly(lactic acid-co-glycolic acid), poly(methacrylamide), poly(methacrylate), poly(methyl oxazoline), poly(organophosphazene), poly(orthoester), poly(oxazoline), poly(propylene glycol), poly(siloxane), poly(urethane), poly(vinyl alcohol), poly(vinylamine), poly(vinyl methyl ether), poly(vinylpyrrolidone), silicone, cellulose, carbomethylcellulose, hydroxypropyl methylcellulose, chitin, chitosan, dextran, dextrin, gelatin, hyaluronic acid and derivatives, functionalized hyaluronic acid, alginate, mannan, pectin, rhamnogalacturonan, starch, hydroxyalkyl starch, hydroxyethyl starch and other carbohydrate polymers, xylan, and copolymers thereof.

[0232] In certain embodiments, -L B' - contains a PEG-based polymer. In certain embodiments, -L B' - contains a hyaluronic acid-based polymer. In certain embodiments, -L B'- comprises a random coil polymer. In certain embodiments, -L B' - contains polysarcosine polymer.

[0233] In certain embodiments, the distance between any two albumin-binding moieties of a compound is such that they can bind to two different binding sites on the same albumin molecule, or to two different albumin molecules. All or some of the albumin-binding moieties can bind to different albumin molecules, and / or two or more albumin-binding moieties can bind to one albumin molecule. Generally, if a compound has x albumin-binding moieties, they can bind to up to x albumin molecules. It is understood that not all albumin-binding moieties of a compound can be bound to one albumin molecule at any given time.

[0234] If the compound is of formula (Ia) with x=1, then part -AB 1 It can be bound to the first albumin molecule, and also partially -AB 2 It can be bound to a second albumin molecule that is different from the first albumin molecule. Alternatively, if the compound is of formula (Ia) with x=1, then part -AB 1 It can bind to a first binding site on the first albumin molecule, and also partially -AB 2 It can bind to a second binding site on the same albumin molecule, but different from the first binding site.

[0235] The ability to bind to two or more different albumin molecules significantly increases the molecular weight of the compound, which has a favorable effect on its cyclic half-life.

[0236] In a particular embodiment, -L of formula (Aa) B' - is equation (a-3') [ka] (In the formula, Dashed lines without a mark are -L2 - or -D- indicates binding to D-, The dashed line with an asterisk indicates -L A This shows a connection to, -R c -teeth, [ka] And, -R d' - is the polymer part, -R e - is -CH2-, [ka] (Selected from the group consisting of) It belongs to them.

[0237] -R of equation (Aa) b -but [ka] If so, then -R in equation (a-3') c -teeth [ka] And the -R of equation (Aa) b -but [ka] If so, then -R in equation (a-3') c -teeth [ka] That is the case.

[0238] Part of equation (a-3') -R d'- indicates a polymer portion, meaning that it contains at least one polymer portion. In certain embodiments, one or more polymer portions have a molecular weight of at least 450 kDa. In certain embodiments, one or more polymer portions have a molecular weight of at least 1 kDa. In certain embodiments, one or more polymer portions have a molecular weight of at least 1.5 kDa. In certain embodiments, one or more polymer portions have a molecular weight of at least 2 kDa. In certain embodiments, one or more polymer portions have a molecular weight of at least 2.5 kDa. In certain embodiments, one or more polymer portions have a molecular weight of at least 3 kDa. In certain embodiments, one or more polymer portions have a molecular weight of at least 3.5 kDa. In certain embodiments, one or more polymer portions have a molecular weight of at least 4 kDa. In certain embodiments, one or more polymer portions have a molecular weight of at least 5 kDa. In certain embodiments, one or more polymer portions have a maximum molecular weight of 160 kDa. In certain embodiments, one or more polymer portions have a maximum molecular weight of 120 kDa. In certain embodiments, one or more polymer portions have a maximum molecular weight of 100 kDa. In certain embodiments, one or more polymer portions have a maximum molecular weight of 80 kDa. In certain embodiments, one or more polymer portions have a maximum molecular weight of 70 kDa. In certain embodiments, one or more polymer portions have a maximum molecular weight of 60 kDa. In certain embodiments, one or more polymer portions have a maximum molecular weight of 50 kDa. In certain embodiments, one or more polymer portions have a maximum molecular weight of 40 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 450 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 1 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 1.5 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 2 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 2.5 kDa.In certain embodiments, one or more polymer portions have a molecular weight of approximately 3 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 3.5 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 4 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 4.5 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 5 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 5.5 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 6 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 6.5 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 7 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 7.5 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 8 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 8.5 kDa. In certain embodiments, one or more polymer portions have a molecular weight of approximately 9 kDa. In certain embodiments, one or more polymer moieties have a molecular weight of approximately 9.5 kDa. In certain embodiments, one or more polymer moieties have a molecular weight of approximately 10 kDa. -R of formula (a-3'). d' -If it contains one polymer moiety, the minimum and maximum molecular weights provided above apply to this one polymer moiety, and -R of formula (a-3') d' If - contains two or more polymer moieties, it is understood that the minimum and maximum molecular weights provided above refer to the minimum and maximum molecular weights of all polymer moieties combined.

[0239] In certain embodiments, the -R of formula (a-3') d'-One or more polymer portions have a flowly radius of at least 1.2 nm. In a particular embodiment, one or more polymer portions have a flowly radius of at least 1.5 nm. In a particular embodiment, one or more polymer portions have a flowly radius of at least 2 nm. In a particular embodiment, one or more polymer portions have a flowly radius of at least 2.5 nm. In a particular embodiment, one or more polymer portions have a flowly radius of at least 3 nm. In a particular embodiment, one or more polymer portions have a flowly radius of at least 3.5 nm. In a particular embodiment, one or more polymer portions have a flowly radius of at least 4 nm. In a particular embodiment, one or more polymer portions have a flowly radius of at least 4.5 nm. In a particular embodiment, one or more polymer portions have a flowly radius of at least 5 nm. In a particular embodiment, one or more polymer portions have a flowly radius of 200 nm or less. In a particular embodiment, one or more polymer portions have a flowly radius of 175 nm or less. In a particular embodiment, one or more polymer portions have a flowly radius of 150 nm or less. In a particular embodiment, one or more polymer portions have a flowly radius of 125 nm or less. In certain embodiments, one or more polymer portions have a flowly radius of 100 nm or less. In certain embodiments, one or more polymer portions have a flowly radius of 75 nm or less. In certain embodiments, one or more polymer portions have a flowly radius of 50 nm or less. In certain embodiments, one or more polymer portions have a flowly radius of 45 nm or less. In certain embodiments, one or more polymer portions have a flowly radius of 40 nm or less. In certain embodiments, one or more polymer portions have a flowly radius of 35 nm or less. In certain embodiments, one or more polymer portions have a flowly radius of 30 nm or less. In certain embodiments, one or more polymer portions have a flowly radius of approximately 1.2 nm. In certain embodiments, one or more polymer portions have a flowly radius of approximately 1.5 nm.In certain embodiments, one or more polymer portions have a flowly radius of approximately 2 nm. In certain embodiments, one or more polymer portions have a flowly radius of approximately 2.5 nm. In certain embodiments, one or more polymer portions have a flowly radius of approximately 3 nm. In certain embodiments, one or more polymer portions have a flowly radius of approximately 3.5 nm. In certain embodiments, one or more polymer portions have a flowly radius of approximately 4 nm. In certain embodiments, one or more polymer portions have a flowly radius of approximately 4.5 nm. In certain embodiments, one or more polymer portions have a flowly radius of approximately 5 nm. In certain embodiments, one or more polymer portions have a flowly radius of approximately 5.5 nm. In certain embodiments, one or more polymer portions have a flowly radius of approximately 6 nm. In certain embodiments, one or more polymer portions have a flowly radius of approximately 6.5 nm. In certain embodiments, one or more polymer portions have a flowly radius of approximately 7 nm. In certain embodiments, one or more polymer portions have a flowly radius of approximately 8.5 nm. In certain embodiments, one or more polymer portions have a flowly radius of approximately 9 nm. In certain embodiments, one or more polymer moieties have a flowly radius of approximately 10 nm. -R of formula (a-3'). d' -If it contains one polymer part, the flory radius provided above applies to this one polymer part and the -R of formula (a-3') d' If - contains two or more polymer parts, it is understood that the flory radius provided above refers to the flory radius of all combined polymer parts.

[0240] -R in equation (a-3') d'- is one or more polymer moieties, for example, poly(2-methacryloyl-oxyethyl phosphorylcholine), poly(acrylic acid), poly(acrylate), poly(acrylamide), poly(alkyloxy)polymer, poly(amide), poly(amideamine), poly(amino acid), poly(acid anhydride), poly(aspartamide), poly(butyric acid), poly(glycolic acid), polybutylene terephthalate, poly(caprolactone), poly(carbonate), poly(cyanoacrylate), poly(dimethylacrylamide), poly(ester), poly(ethylene), poly(ethylene glycol), poly(ethylene oxide), poly(ethyl phosphate), poly(ethyl oxazoline), poly(glycolic acid), poly(hydroxyethyl acrylate), poly(hydroxyethyl oxazoline), poly(hydroxymethacrylate), poly(hydroxypropyl methacrylamide), poly(hydroxypropyl methacrylate), poly(hydroxypropyl methacrylate), poly(hydroxypropyl methacrylate) The polymer contains polymer portions selected from the group consisting of oxypropyl oxazoline, poly(iminocarbonate), poly(lactic acid), poly(lactic acid-co-glycolic acid), poly(methacrylamide), poly(methacrylate), poly(methyloxazoline), poly(organophosphazene), poly(orthoester), poly(oxazoline), poly(propylene glycol), poly(siloxane), poly(urethane), poly(vinyl alcohol), poly(vinylamine), poly(vinyl methyl ether), poly(vinylpyrrolidone), silicone, cellulose, carbomethylcellulose, hydroxypropylmethylcellulose, chitin, chitosan, dextran, dextrin, gelatin, hyaluronic acid and derivatives, functionalized hyaluronic acid, alginate, mannan, pectin, rhamnogalacturonan, starch, hydroxyalkyl starch, hydroxyethyl starch and other carbohydrate polymers, xylan, and copolymers thereof.

[0241] In certain embodiments, the -R of formula (a-3') d' - contains PEG-based polymers. In certain embodiments, -R of formula (a-3') d'- contains a hyaluronic acid-based polymer. In certain embodiments, -R of formula (a-3') d' - comprises a random coil polymer. In certain embodiments, -R of formula (a-3') d' - contains polysarcosine polymer.

[0242] In certain embodiments, -D- is a protein or peptide drug portion, and -AB 2 It is conjugated to a -D- functional group provided by a side chain of an N-terminal amine, C-terminal carboxyl, or amino acid residue. In certain embodiments, -AB 2 It is conjugated to the N-terminal amine functional group of -D-. In certain embodiments, -AB 2 It is conjugated to the C-terminal carboxyl functional group. In certain embodiments, -AB 2 It is conjugated by an amino acid residue of -D- to a functional group provided by, for example, lysine, serine, aspartic acid, glutamic acid, arginine, histidine, threonine, glutamine, asparagine, cysteine, proline, tyrosine, or tryptophan. In certain embodiments, -AB 2 It is conjugated to the functional group of the side chain of -D-lysine. In certain embodiments, -AB 2 It is conjugated to the functional group of the serine side chain of -D-. In certain embodiments, -AB 2 It is conjugated to the functional group of the side chain of -D- aspartic acid. In certain embodiments, -AB 2 It is conjugated to the functional group of the side chain of -D-glutamic acid. In certain embodiments, -AB 2 It is conjugated to the functional group of the side chain of -D- arginine. In certain embodiments, -AB 2 It is conjugated to the functional group of the side chain of the -D- histidine. In certain embodiments, -AB 2 It is conjugated to the functional group of the side chain of -D- threonine. In certain embodiments, -AB 2It is conjugated to the functional group of the side chain of glutamine -D-. In certain embodiments, -AB 2 It is conjugated to the functional group of the side chain of -D- asparagine. In certain embodiments, -AB 2 It is conjugated to the functional group of the side chain of -D- cysteine. In certain embodiments, -AB 2 It is conjugated to the functional group of the side chain of -D- proline. In certain embodiments, -AB 2 It is conjugated to the functional group of the tyrosine side chain of -D-. In certain embodiments, -AB 2 It is conjugated to the functional group of the side chain of -D- tryptophan.

[0243] In a particular embodiment, -D-AB 2 The drug is selected from the group consisting of semaglutide, liraglutide, echnoglutide, GZR18, GL0034, tilzepatide, cotadutide, BI-456906, pembidutide, mazdutide, dapiglutide, and letatoltide.

[0244] In a particular embodiment, -D-AB 2 The substance is selected from the group consisting of semaglutide, liraglutide, echnoglutide, GZR18, and GL0034.

[0245] In a particular embodiment, -D-AB 2 It is semaglutide. Semaglutide is given by formula HX1EGTFTSDVSSYLEGQAAKEFIAWLVRGRG (Sequence ID 40) [In the formula, X1 is α-aminoisobutyric acid (Aib), Lysine, ranked 20th, [ka] (In the formula, (The dashed line indicates the bond of the lysine side chain of lysine at position 20 to the ε-amine group.) [It is chemically modified via conjugation of the lysine side chain to the ε-amine group.] It is a compound of [the compound].

[0246] Semaglutide can be prepared using methods known to those skilled in the art, such as those described in WO2006 / 097537.

[0247] In a particular embodiment, -D-AB 2 It is liraglutide. Liraglutide is, formula HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG(Sequence ID 41) [In the formula, Lysine, ranked 20th, [ka] (In the formula, (The dashed line indicates the bond of the lysine side chain of lysine at position 20 to the ε-amine group.) [It is chemically modified via conjugation of the lysine side chain to the ε-amine group.] It is a compound of [the compound].

[0248] In a particular embodiment, -D-AB 2 It is echnoglutide. Echnoglutide is, formula HVEGTFTSDVSSYLEEQAAREFIKWLVRGRG (Sequence ID 42) [In the formula, Lysine, ranked 24th, [ka] (In the formula, the dashed line indicates the bond of the lysine side chain of lysine at position 24 to the ε-amine group.) [It is chemically modified via conjugation of the lysine side chain to the ε-amine group.] It is a compound of [the compound].

[0249] In a particular embodiment, -D-AB 2 It is GZR18. GZR18 is formula HGEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (Sequence No. 43) [In the formula, Lysine, ranked 20th, [ka] (In the formula, the dashed line indicates the bond of the lysine side chain of lysine at position 20 to the ε-amine group.) [It is chemically modified via conjugation of the lysine side chain to the ε-amine group.] It is a compound of [the compound].

[0250] In a particular embodiment, -D-AB 2 This is GL0034. GL0034 is also known as utreglutide, and its formula is HX1EGTFTSDVSSYLEGQAAKEFIAWLVRGRGL (Sequence ID 44) [In the formula, X1 is Aib, Lysine, ranked 20th, [ka] (In the formula, the dashed line indicates the bond of the lysine side chain of lysine at position 20 to the ε-amine group.) [It is chemically modified via conjugation of the lysine side chain to the ε-amine group.] It is a compound of [the compound].

[0251] In a particular embodiment, -D-AB 2 It is a dual GLP-1 receptor agonist selected from the group consisting of tylzepatide, cotadutide, BI-456906, pembidutide, and mazdutide.

[0252] In a particular embodiment, -D-AB 2 It is a dual GLP-1 receptor agonist that activates both the GLP-1 receptor and the GIP receptor. An example of such a dual GLP-1 receptor agonist is tilzepatide. In certain embodiments, -D-AB 2It is tilzepatide. Tilzepatide is formula YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS(Sequence ID 45) (In the formula, X1 is Aib, X2 is Aib, Lysine, ranked 20th, is ([2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(γGlu)1-CO-(CH2) 18 It is chemically modified via conjugation of the lysine side chain to the ε-amine group by -CO2H, The C-terminal serine, specifically the serine at position 39, is amidated as a C-terminal primary amide. It is a compound of [the compound].

[0253] Partial ([2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(γGlu)1-CO-(CH2) 18 -CO2H has the following structure [ka] (In the formula, the dashed line indicates a connection to -D-) It has.

[0254] In a particular embodiment, -D-AB 2 It is a dual GLP-1 receptor agonist that activates both the GLP-1 receptor and the glucagon receptor, selected from the group consisting of cotadutide, BI-456906, pembidutide, and mazdutide.

[0255] In a particular embodiment, -D-AB 2 It is cotaducide. Cotaducide is, formula HSQGTFTSDKSEYLDSERARDFVAWLEAGG (Sequence ID 46) (In the formula, The lysine at position 10 is chemically modified via conjugation of the lysine side chain to the ε-amine group by γ-Glu-palmitoyl. It is a compound of [the compound].

[0256] Partial γ-Glu-palmitoyl has the following structure: [ka] (In the formula, the dashed line indicates a connection to -D-) It has.

[0257] In a particular embodiment, -D-AB 2 This is BI-456906. BI-456906 is also known as sulvodutide, and its formula is HX1QGTFTSDYSKYLDERAAKDFIKWLESA (Sequence ID 47) (In the formula, X1 is 1-amino-cyclobutanecarboxylic acid (Ac4c), The lysine at position 24 is chemically modified via conjugation of the lysine side chain to the ε-amine group by [l7-carboxy-heptadecanoyl]-isoGlu-GSGSGG. The C-terminal alanine, specifically the alanine at position 29, is amidated as a primary C-terminal amide. It is a compound of [the compound].

[0258] The partial [l7-carboxy-heptadecanoyl]-isoGlu-GSGSGG has the following structure: [ka] (In the formula, the dashed line indicates a connection to -D-) It has.

[0259] In a particular embodiment, -D-AB 2 It is pembidute. Pembidute is formula HX1QGTFTSDYSKYLDEKAAKEFIQWLLQT (Sequence ID 48) [In the formula, X1 is Aib, The glutamic acid at position 16 and the lysine at position 20 are linked via lactam crosslinking. Lysine, ranked 17th, is... [ka] (In the formula, the dashed line indicates the bond of lysine at position 17 to the ε-amine group.) This part is chemically modified via conjugation of the ε-amine group of the lysine side chain by glucuronic acid C-18. The C-terminal threonine, specifically the threonine at position 29, is amidated as a primary amide at the C-terminus. It is a compound of [the compound].

[0260] In a particular embodiment, -D-AB 2 This is mazduchid. Mazduchid is, formula HX1QGTFTSDYSKYLDEKKAKEFVEWLLEGGPSSG (Sequence ID 49) (In the formula, X1 is Aib, Lysine, ranked 20th, is ([2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(γGlu)-CO-(CH2) 18 It is chemically modified by conjugation of the ε-amine group of the lysine side chain with -CO2H, The C-terminal glycine, specifically the glycine at position 34, is amidated. It is a compound of [the compound].

[0261] Partial ([2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(γGlu)-CO-(CH2) 18 -CO2H has the following structure: [ka] (In the formula, the dashed line indicates a connection to -D-) It has.

[0262] In a particular embodiment, -D-AB 2 It is a dual GLP-1 receptor agonist that activates both GLP-1 and GLP-2 receptors, such as dapiglutide. Dapiglutide is formulated as follows: HX1EGSFTSELATILDKQAARDFIAWLIQHKITD (Sequence ID 50) (In the formula, X1 is Aib, The lysine at position 16 is chemically modified by conjugation of the ε-amine group of the lysine side chain with [17-carboxy-heptadecanoyl]-isoGlu. It is a compound of [the compound].

[0263] The partial [17-carboxy-heptadecanoyl]-isoGlu has the following structure: [ka] (In the formula, the dashed line indicates a connection to -D-) It has.

[0264] In a particular embodiment, -D-AB 2 Letatoltide is a triple GLP-1 receptor agonist that activates the GLP-1 receptor, GIP receptor, and GCG receptor. Letatoltide is formulated as follows: YX1QGTFTSDYSIX2LDKKAQX3AFIEYLLEGGPSSGAPPPS (Sequence ID 51) (In the formula, X1 is Aib, X2 is α-methylleucine (αMeL), X3 is Aib, Lysine, ranked 17th, is (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(γGlu)-CO-(CH2) 18 It is chemically modified by conjugation of the ε-amine group of the lysine side chain with -CO2H, The C-terminal serine, specifically the serine at position 39, is amidated. It is a compound of [the compound].

[0265] Letatoltide is Y-Aib-QGTFTSDYSI-αMeL-LDKK ((2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(γGlu)-CO-(CH2) 18It can also be written as -CO2H) AQ-Aib-AFIEYLLEGGPSSGAPPPS-NH2 (Sequence ID 51).

[0266] Partial (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(γGlu)-CO-(CH2) 18 -CO2H has the following structure: [ka] It has.

[0267] In a particular embodiment, -D-AB 2 This is noiiglutide, also known as SHR20004.

[0268] In a particular embodiment, -D-AB 2 This is ZT002.

[0269] In a particular embodiment, -D-AB 2 is equation (b-1) [ka] (In the formula, X 1 -teeth, [ka] And, -X 2 teeth, [ka] And, (Ph stands for phenyl) It belongs to them.

[0270] Part D of formula (b-1) has sequence YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS, sequence number 57, where X1 and X2 are Aib.

[0271] The compound of formula (b-1) is disclosed in WO2022159395 and WO2023 / 044290, the contents of which are incorporated herein by reference in their entirety.

[0272] In certain embodiments, -D-AB is of formula (b-1), and X 1 -teeth [ka] And -X 2 teeth [ka] In a particular embodiment, -D-AB is of formula (b-1), and X 1 -teeth [ka] And -X 2 teeth [ka] In a particular embodiment, -D-AB is of formula (b-1), and X 1 -teeth [ka] And -X 2 teeth [ka] In a particular embodiment, -D-AB is of formula (b-1), and X 1 -teeth [ka] And -X 2 teeth [ka] In a particular embodiment, -D-AB is of formula (b-1), and X 1 -teeth [ka] And -X 2 teeth [ka] In a particular embodiment, -D-AB is of formula (b-1), and X 1 -teeth [ka] And -X 2 teeth [ka] In a particular embodiment, -D-AB is of formula (b-1), and X 1 -teeth [ka] And -X 2 teeth [ka] In a particular embodiment, -D-AB is of formula (b-1), and X 1 -teeth [ka] And -X 2 teeth [ka] In a particular embodiment, -D-AB is of formula (b-1), and X 1 -teeth [ka] And -X 2 teeth [ka] In a particular embodiment, -D-AB is of formula (b-1), and X 1 -teeth [ka] And -X 2 teeth [ka] In a particular embodiment, -D-AB is of formula (b-1), and X 1 -teeth [ka] And -X 2 teeth [ka] In a particular embodiment, -D-AB is of formula (b-1), and X 1 -teeth [ka] And -X 2 teeth [ka] That is the case.

[0273] In a particular embodiment, -D-AB 2 The drug is selected from the group consisting of semaglutide, liraglutide, echnoglutide, GZR18, GL0034, tilzepatide, cotadutide, BI-456906, pembidutide, mazdutide, dapiglutide, and letatoltide.

[0274] In a particular embodiment, -D-AB 2 is, formula k(γE-(miniPEG)2-γE-COC 16 H 32 CO2H)(N-Me)GSVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHK(γE-(miniPEG)2-γE-COC16 H 32 CO2H)-OH (SEQ ID NO: 52) (In the formula, k is d-Lys, γE is the l-isomer of gamma glutamic acid, miniPEG is COCH2OCH2CH2OCH2CH2NH, COC 16 H 32 CO2H is a C18 diacid. (N-Me)G is sarcosine, K is the l-isomer of lysine, -OH indicates that the C-terminal amino acid has a terminal carboxylic acid. It belongs to them.

[0275] In a particular embodiment, -D-AB 2 is, formula k(γE-(miniPEG)2-γE-COC 16 H 32 CO2H)(N-Me)GSVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHK(γE-(miniPEG)2-γE-COC 16 H 32 CO2H)-OH (SEQ ID NO: 53) (In the formula, k is d-Lys, γE is the l-isomer of gamma glutamic acid, (miniPEG)2 is COCH2OCH2CH2OCH2CH2NH, COC 16 H 32 CO2H is a C18 diacid. (N-Me)G is sarcosine, K is the l-isomer of lysine, -OH indicates that the C-terminal amino acid has a terminal carboxylic acid. It belongs to them.

[0276] -D- is a peptide or protein drug portion, -L 1- is conjugated to a functional group in the side chain of an amino acid residue of -D-, or to the N-terminal amine functional group or C-terminal carboxyl functional group of -D-, or to a nitrogen atom in the backbone chain of -D-.

[0277] -D- is a peptide or protein drug portion, -L 1 -In certain embodiments, -D- is conjugated to a functional group selected from the group consisting of carboxylic acids, primary amines, secondary amines, maleimides, thiols, sulfonic acids, carbonates, carbamates, hydroxyls, aldehydes, ketones, hydrazines, isocyanates, isothiocyanates, phosphoric acids, phosphonic acids, haloacetyls, alkyl halides, acryloyls, aryl fluorides, hydroxylamines, sulfates, disulfides, vinyl sulfones, vinyl ketones, diazoalkanes, oxiranes, guanidines, and aziridines.When -D- is a peptide or protein drug moiety, -L 1 - is conjugated in certain embodiments to a functional group of -D- selected from the group consisting of hydroxyl, primary amine, secondary amine, and guanidine. When -D- is a peptide or protein drug moiety, -L 1 - is conjugated in certain embodiments to a functional group of -D- selected from the group consisting of primary and secondary amines. When -D- is a peptide or protein drug moiety, -L 1 - is conjugated to a primary amine -D- in certain embodiments.

[0278] -D- is a peptide or protein drug portion, -L 1 - can be conjugated to a functional group on the side chain of an amino acid residue of -D-, which may be a protein-constituting amino acid residue or a non-protein-constituting amino acid residue.

[0279] -D- is a peptide or protein drug portion, -L 1- is conjugated in certain embodiments to the functional group of the side chain of the protein constituent amino acid residue of -D-. In certain embodiments, such amino acid residues are selected from the group consisting of histidine, lysine, tryptophan, serine, threonine, tyrosine, aspartic acid, glutamic acid, and arginine. In certain embodiments, such amino acid residues are selected from the group consisting of lysine, aspartic acid, arginine, and serine. In certain embodiments, such amino acid residues are selected from the group consisting of lysine, arginine, and serine.

[0280] -D- is a peptide or protein drug portion, -L 1 - is conjugated to the functional group of the lysine residue of -D- in certain embodiments. When -D- is a peptide or protein drug moiety, -L 1 - is conjugated to the functional group of the histidine residue of -D- in certain embodiments. When -D- is a peptide or protein drug moiety, -L 1 - is conjugated to the functional group of the tryptophan residue of -D- in certain embodiments. When -D- is a peptide or protein drug moiety, -L 1 - is conjugated to the functional group of the serine residue of -D- in certain embodiments. When -D- is a peptide or protein drug moiety, -L 1 - is conjugated to the threonine residue functional group of -D- in certain embodiments. When -D- is a peptide or protein drug moiety, -L 1 - is conjugated to the functional group of the tyrosine residue of -D- in certain embodiments. When -D- is a peptide or protein drug moiety, -L 1 - is conjugated to the functional group of the aspartic acid residue of -D- in certain embodiments. When -D- is a peptide or protein drug moiety, -L 1 - is conjugated to the functional group of the glutamic acid residue of -D- in certain embodiments. When -D- is a peptide or protein drug moiety, -L 1- is conjugated to the functional group of the arginine residue of -D- in certain embodiments.

[0281] -D- is a peptide or protein drug portion, -L 1 - is conjugated in certain embodiments to the functional group of the side chain of a non-protein constituent amino acid residue of -D-.

[0282] It should be understood that not all peptide or protein drug moieties -D- may contain all of these amino acid residues.

[0283] -D- is a peptide or protein drug portion, -L 1 - is conjugated to the N-terminal amine functional group of -D- in certain embodiments.

[0284] -D- is a peptide or protein drug portion, -L 1 - is conjugated to the C-terminal functional group of -D- in certain embodiments.

[0285] Part-L 1 - can be coupled to -D- by any type of coupling, provided that it is reversible. In certain embodiments, -L 1 - is bonded to -D- by a bond selected from the group consisting of amide, ester, carbamate, acetal, aminal, imine, oxime, hydrazone, disulfide, and acylguanidine. In certain embodiments, -L 1 - is bonded to -D- by a bond selected from the group consisting of amides, esters, carbamates, and acylguanidines. Some of these bonds are not reversible in themselves, however, in this invention -L 1 It is understood that the adjacent groups present in the - group make these bonds reversible.

[0286] In certain embodiments, -L 1 - is bonded to -D- by an amide bond. In certain embodiments, -L 1- is bonded to -D- by a carbamate bond. In certain embodiments, -L 1 - is bonded to -D- by an ester bond. In certain embodiments, -L 1 - is attached to -D- by an acylguanidine bond.

[0287] Part-L 1 - is a drug, namely HD-AB 2 This is a reversible prodrug linker released therefrom in its free form, i.e., a traceless prodrug linker. The "H-" in "HD-AB" is understood to be hydrogen. Suitable prodrug linkers, such as the reversible prodrug linker portions disclosed in WO 2005 / 099768 A2, WO 2006 / 136586 A2, WO 2011 / 089216 A1 and WO 2013 / 024053 A1, are known in the art and are incorporated herein by reference.

[0288] In certain embodiments, -L 1 - is disclosed in WO 2009 / 095479 A2. Therefore, in certain embodiments, part -L 1 - is equation (II): [ka] (In the formula, The dashed line indicates the bond of -D to nitrogen, hydroxyl, or thiol. -X- is -C(R 4 R 4a )-,-N(R 4 )-, -O-, -C(R 4 R 4a )-C(R 5 R 5a )-,-C(R 5 R 5a )-C(R 4 R 4a )-,-C(R 4 R 4a )-N(R 6 )-,-N(R 6 )-C(R4 R 4a )-,-C(R 4 R 4a )-O-, -OC(R 4 R 4a )-, and -C(R 7 R 7a Selected from the group consisting of )-, X 1 It is selected from the group consisting of C and S(O), -X 2 - is -C(R 8 R 8a )-, and -C(R 8 R 8a )-C(R 9 R 9a Selected from the group consisting of )-, =X 3 It is selected from the group consisting of =O, =S, and =N-CN, -R 1 ,-R 1a ,-R 2 ,-R 2a ,-R 4 ,-R 4a ,-R 5 ,-R 5a ,-R 6 ,-R 8 ,-R 8a ,-R 9 , and -R 9a These are independently -H and C 1-6 Selected from the group consisting of alkyl groups, -R 3 and -R 3a These are independently -H and C 1-6 Selected from the group consisting of alkyl, except -R 3 ,-R 3a If one or both of them are not -H, then they are SP to the N to which they are bonded. 3 Bonded by hybrid carbon atoms, -R 7 is -N(R 10 R 10a ), and -NR 10 -(C=O)-R 11 Selected from the group consisting of, -R 7a ,-R 10,-R 10a , and -R 11 These are, independently of each other, -H and C 1-6 Selected from the group consisting of alkyl groups, Depending on the circumstances, Pair-R 1a / -R 4a ,-R 1a / -R 5a ,-R 1a / -R 7a ,-R 4a / -R 5a , and -R 8a / -R 9a One or more of them form a chemical bond, Depending on the circumstances, Pair-R 1 / -R 1a ,-R 2 / -R 2a ,-R 4 / -R 4a ,-R 5 / -R 5a ,-R 8 / -R 8a , and -R 9 / -R 9a One or more of them, together with the atom they are bonded to, C 3-10 Forming a cycloalkyl or 3-10 membered heterocycline, Depending on the circumstances, Pair-R 1 / -R 4 ,-R 1 / -R 5 ,-R 1 / -R 6 ,-R 1 / -R 7a ,-R 4 / -R 5 ,-R 4 / -R 6 ,-R 8 / -R 9 , and -R 2 / -R 3 One or more of these, together with the atoms to which they are bonded, form ring A. Depending on the case, R 3 / R 3a These, together with the nitrogen atoms to which they are bonded, form a heterocycle of 3 to 10 members. A is phenyl, naphthyl, indenyl, indanyl, tetralinyl, C 3-10 (Selected from the group consisting of cycloalkyls, 3-10 membered heterocyclyls, and 8-11 membered heterobicyclyls.) It is, Here, -L 1 - is at least one -L 2 - is replaced by -L 1 - is sometimes further substituted, except that the hydrogen with an asterisk in formula (II) is -L 2 -or not substituted by substituents.

[0289] In a particular embodiment, -L of formula (II) 1 - is one part -L 2 It is replaced with -.

[0290] In a particular embodiment, -L of formula (II) 1 - has not been further replaced.

[0291] -R in equation (II) 3 / -R 3a However, when they combine with the nitrogen atom to which they are bonded to form a 3-10 member heterocycle, the atom directly bonded to the nitrogen is SP 3 It is understood that only such 3- to 10-membered heterocycles, which are hybrid carbon atoms, can be formed. In other words, -R 3 / -R 3a As a result, such 3- to 10-membered heterocycles formed together with the nitrogen atoms to which they are bonded have the following structure: [ka] (In the formula, The dashed line is -L 1 - indicates the connection to the remainder, The ring contains 3 to 10 atoms, including at least one nitrogen atom. R # and R ## is, sp 3 This refers to hybridized carbon atoms.

[0292] It is also understood that the above 3- to 10-member complex rings can be further permuted.

[0293] -R in equation (II) 3 / -R 3a The following are exemplary embodiments of preferred 3- to 10-membered heterocycles formed by these together with the nitrogen atoms to which they are bonded: [ka] (In the formula, The dashed line indicates the bond to the rest of the molecule. -R is -H and C 1-6 (Selected from the group consisting of alkyl groups).

[0294] -L in equation (II) 1 - may be further substituted depending on the case. In general, any substituent can be used as long as it does not affect the principle of cleavage, i.e., the hydrogen with an asterisk in formula (II) is not substituted and part of formula (II) [ka] The nitrogen remains as part of the primary, secondary, or tertiary amine, i.e., -R 3 and -R 3a These are either -H independently of each other, or sp 3 It is bonded to -N< via hybridized carbon atoms.

[0295] In one embodiment, the -R of formula (II) 1 or -R 1a is, -L 2 It is replaced by -. In another embodiment, the -R of formula (II) 2 or -R 2a is, -L 2 It is replaced by -. In another embodiment, the -R of formula (II) 3 or -R 3a is, -L 2 It is replaced by -. In another embodiment, the -R of formula (II) 4 is, -L2 It is replaced by -. In another embodiment, the -R of formula (II) 5 or -R 5a is, -L 2 It is replaced by -. In another embodiment, the -R of formula (II) 6 is, -L 2 It is replaced by -. In another embodiment, the -R of formula (II) 7 or -R 7a is, -L 2 It is replaced by -. In another embodiment, the -R of formula (II) 8 or -R 8a is, -L 2 It is replaced by -. In another embodiment, the -R of formula (II) 9 or -R 9a is, -L 2 It is replaced by -R 10 is, -L 2 It is replaced by -R 11 is, -L 2 It is replaced by - in certain embodiments, -R in formula (II) 3 is, -L 2 It is replaced with -.

[0296] In a particular embodiment, -X- in formula (II) is -C(R 4 R 4a )-,-N(R 4 )- and -C(R 7 R 7a Selected from the group consisting of )-. In a particular embodiment, -X- in formula (II) is -C(R 4 R 4a )-. In a particular embodiment, -X- in formula (II) is -C(R 7 R 7a )-is.

[0297] In certain embodiments, -R of formula (II) 7 -NR 10 -(C=O)-R 11 That is the case.

[0298] In certain embodiments, -R of formula (II) 7a is selected from -H, methyl and ethyl. In certain embodiments, -R of formula (II) 7a It is -H.

[0299] In certain embodiments, -R 10 is selected from -H, methyl and ethyl. In certain embodiments, -R 10 It is methyl.

[0300] In certain embodiments, -R 11 is selected from -H, methyl and ethyl. In certain embodiments, -R 11 is -H. In certain embodiments, -R 11 is, -L 2 It is replaced with -.

[0301] In a particular embodiment, -X- in formula (II) is -N(R 4 )-is.

[0302] In certain embodiments, -R 4 is selected from the group consisting of -H, methyl, and ethyl. In certain embodiments, -R 4 It is -H.

[0303] In a particular embodiment, X of formula (II) 1 It is C.

[0304] In a particular embodiment, equation (II) = X 3 The answer is = O.

[0305] In a particular embodiment, -X of formula (II) 2 - is -C(R 8 R 8a )-is.

[0306] In certain embodiments, -R of formula (II) 8 and -R 8aThe is independently selected from the group consisting of -H, methyl, and ethyl. In certain embodiments, the -R of formula (II) 8 and -R 8a At least one of them is -H. In certain embodiments, -R of formula (II) 8 and -R 8a Both are -H.

[0307] In certain embodiments, -R of formula (II) 1 and -R 1a This is independently selected from the group consisting of -H, methyl, and ethyl.

[0308] In certain embodiments, -R of formula (II) 1 and -R 1a At least one of them is -H. In certain embodiments, -R of formula (II) 1 and -R 1a It is -H.

[0309] In certain embodiments, -R of formula (II) 1 and -R 1a At least one of them is methyl. In certain embodiments, -R of formula (II) 1 and -R 1a Both are methyl.

[0310] In certain embodiments, -R of formula (II) 2 and -R 2a The is independently selected from the group consisting of -H, methyl, and ethyl. In certain embodiments, the -R of formula (II) 2 and -R 2a At least one of them is -H. In certain embodiments, -R of formula (II) 2 and -R 2a Both are H.

[0311] In certain embodiments, -R of formula (II) 3 and -R 3a This is independently selected from the group consisting of -H, methyl, ethyl, propyl, and butyl.

[0312] In certain embodiments, -R of formula (II) 3 and -R 3a At least one of them is methyl. In certain embodiments, -R of formula (II) 3 It is methyl, and -R in formula (II) 3a is -H.

[0313] In certain embodiments, -R of formula (II) 3 and -R 3a Both are -H.

[0314] In certain embodiments, -D- is linked to -L via nitrogen by forming an amide bond. 1 It is connected to -.

[0315] In certain embodiments, -L 1 - is from equation (II), where X is -C(R 7 R 7a )- and X 1 is C, and -X 2 - is -C(R 8 R 8a )-C(R 9 R 9a )- and =X 3 is = O, and -R 1 and -R 1a is -H and -R 2 and -R 2a is -H and -R 3 and -R 3a It is methyl, and -R 7 is -N(R 10 R 10a ) and -R 7a is -H and -R 8 ,-R 8a ,-R 9 and -R 9a is -H and -R 10 It is methyl, and -R 10a is -H.

[0316] In certain embodiments, -L 1 - is equation (IIa) [ka] (In the formula, The dashed line with an asterisk indicates the bond to nitrogen of -D-. Dashed lines without a mark are -L 2 (Indicates a connection to -) It belongs to them.

[0317] In certain embodiments, -L 1 - is equation (IIa-a) [ka] (In the formula, The dashed line with an asterisk indicates the bond to nitrogen of -D-. Dashed lines without a mark are -L 2 (Indicates a connection to -) It belongs to them.

[0318] In certain embodiments, -L 1 - is equation (IIa-b) [ka] (In the formula, The dashed line with an asterisk indicates the bond to nitrogen of -D-. Dashed lines without a mark are -L 2 (Indicates a connection to -) It belongs to them.

[0319] The parts of formulas (IIa), (IIa-a), and (IIa-b) are bonded to -D- via amide bonds formed by the nitrogen of the amine functional group and the carbonyl to the left of the dashed line with an asterisk.

[0320] In certain embodiments, -L 1 - is from equation (II), where X is -C(R 7 R 7a )- and X 1 is C, and -X 2 - is -C(R8 R 8a )-C(R 9 R 9a )- and =X 3 is = O, and -R 1 and -R 1a is -H and -R 2 and -R 2a is -H and -R 3 and -R 3a It is methyl, and -R 7 -NR 10 -(C=O)-R 11 And, -R 7a is -H and -R 8 ,-R 8a ,-R 9 and -R 9a is -H and -R 10 It is methyl, and -R 11 is -H.

[0321] In certain embodiments, -L 1 - is from equation (II), where X is -C(R 7 R 7a )- and X 1 is C, and -X 2 - is -C(R 8 R 8a )-C(R 9 R 9a )- and =X 3 is = O, and -R 1 and -R 1a is -H and -R 2 and -R 2a is -H and -R 3 and -R 3a It is methyl, and -R 7 -NR 10 -(C=O)-R 11 And, -R 7a is -H and -R 8 ,-R 8a ,-R 9 and -R 9a is -H and -R 10 H is H, and -R 11 is -H.

[0322] In certain embodiments, -L 1 - is equation (IIab) [ka] (In the formula, The dashed line with an asterisk indicates the bond to nitrogen of -D-. Dashed lines without a mark are -L 2 (Indicates a connection to -) It belongs to them.

[0323] In certain embodiments, -L 1 - is equation (IIab-a) [ka] (In the formula, The dashed line with an asterisk indicates the bond to nitrogen of -D-. Dashed lines without a mark are -L 2 (Indicates a connection to -) It belongs to them.

[0324] In certain embodiments, -L 1 - is equation (IIab-b) [ka] (In the formula, The dashed line with an asterisk indicates the bond to nitrogen of -D-. Dashed lines without a mark are -L 2 (Indicates a connection to -) It belongs to them.

[0325] The parts of formulas (IIab), (IIab-a), and (IIab-b) are bonded to -D- via amide bonds formed by the nitrogen of the amine functional group and the carbonyl to the left of the dashed line with an asterisk.

[0326] In certain embodiments, -L 1 - is disclosed in WO2016 / 020373A1. Therefore, in certain embodiments, part -L1 - is equation (III): [ka] (In the formula, The dashed lines indicate bonding to a primary or secondary amine or hydroxyl group of -D via an amide bond or ester bond, respectively. -R 1 ,-R 1a ,-R 2 ,-R 2a ,-R 3 and -R 3a These are -H, -C(R 8 R 8a R 8b ), -C(=O)R 8 -C≡N, -C(=NR) 8 )R 8a ,-CR 8 (=CR 8a R 8b ), -C≡CR 8 Selected from the group consisting of and -T, -R 4 ,-R 5 and -R 5a These are -H, -C(R 9 R 9a R 9b Selected from the group consisting of ) and -T, a1 and a2 are independently 0 or 1. Each-R 6 ,-R 6a ,-R 7 ,-R 7a ,-R 8 ,-R 8a ,-R 8b ,-R 9 ,-R 9a , and -R 9b These are -H, halogen, -CN, and -COOR, which are independent of each other. 10 , -OR 10 , -C(O)R 10 ,-C(O)N(R 10 R 10a ), -S(O)2N(R 10 R 10a ), -S(O)N(R 10 R10a ), -S(O)2R 10 ,-S(O)R 10 , -N(R 10 )S(O)2N(R 10a R 10b ), -SR 10 , -N(R 10 R 10a ), -NO2, -OC(O)R 10 , -N(R 10 )C(O)R 10a , -N(R 10 )S(O)2R 10a , -N(R 10 )S(O)R 10a , -N(R 10 )C(O)OR 10a , -N(R 10 )C(O)N(R 10a R 10b ), -OC(O)N(R 10 R 10a ), -T, C 1-20 Alkyl, C 2-20 Alkenyl and C 2-20 Selected from the group consisting of alkynyls, where -T, C 1-20 Alkyl, C 2-20 Alkenyl and C 2-20 Alkinyl has one or more -Rs, which may be the same or different. 11 In some cases, it is replaced by C 1-20 Alkyl, C 2-20 Alkenyl and C 2-20 Alkinyls include -T-, -C(O)O-, -O-, -C(O)-, and -C(O)N(R) 12 )-,-S(O)2N(R 12 )-,-S(O)N(R 12 )-, -S(O)2-, -S(O)-, -N(R 12 )S(O)2N(R 12a )-, -S-, -N(R 12 )-, -OC(OR 12 )(R 12a )-,-N(R 12 )C(O)N(R 12a )-, and -OC(O)N(R 12 )- may intersect with one or more groups selected from the group consisting of, Each-R 10 ,-R 10a , and -R 10b These are independently -H, -T, and C 1-20 Alkyl, C 2-20 Alkenyl and C 2-20 Selected from the group consisting of alkynyls, where -T, C 1-20 Alkyl, C 2-20 Alkenyl and C 2-20 Alkinyl has one or more -Rs, which may be the same or different. 11 In some cases, it is replaced by C 1-20 Alkyl, C 2-20 Alkenyl and C 2-20 Alkinyls include -T-, -C(O)O-, -O-, -C(O)-, and -C(O)N(R) 12 )-,-S(O)2N(R 12 )-,-S(O)N(R 12 )-, -S(O)2-, -S(O)-, -N(R 12 )S(O)2N(R 12a )-, -S-, -N(R 12 )-, -OC(OR 12 )(R 12a )-,-N(R 12 )C(O)N(R 12a )-, and -OC(O)N(R 12 )- may intersect with one or more groups selected from the group consisting of, Each T is independently phenyl, naphthyl, indenyl, indanyl, tetralinyl, C 3-10 Selected from the group consisting of cycloalkyls, 3-10 membered heterocyclyls, and 8-11 membered heterobicyclyls, each T independently has one or more identical or different -R groups. 11 It is sometimes replaced by, Each-R 11 These are, independently of each other, halogen, -CN, oxo (=O), and -COOR. 13 , -OR 13 , -C(O)R 13 ,-C(O)N(R 13 R 13a ), -S(O)2N(R 13 R 13a ), -S(O)N(R 13 R13a ), -S(O)2R 13 ,-S(O)R 13 , -N(R 13 )S(O)2N(R 13a R 13b ), -SR 13 , -N(R 13 R 13a ), -NO2, -OC(O)R 13 , -N(R 13 )C(O)R 13a , -N(R 13 )S(O)2R 13a , -N(R 13 )S(O)R 13a , -N(R 13 )C(O)OR 13a , -N(R 13 )C(O)N(R 13a R 13b ), -OC(O)N(R 13 R 13a ), and C 1-6 Selected from alkyl, where C 1-6 Alkyl is optionally substituted with one or more halogens, either the same or different. Each-R 12 ,-R 12a ,-R 13 ,-R 13a , and -R 13b These are independently -H and C 1-6 Selected from the group consisting of alkyl groups, where C 1-6 Alkyl is optionally substituted with one or more halogens, either the same or different. Depending on the circumstances, Pair-R 1 / -R 1a ,-R 2 / -R 2a ,-R 3 / -R 3a ,-R 6 / -R 6a , and -R 7 / -R 7a One or more of them, together with the atom they are bonded to, C 3-10 Forming a cycloalkyl or 3-10 membered heterocycline, Depending on the circumstances, Pair-R 1 / -R2 ,-R 1 / -R 3 ,-R 1 / -R 4 ,-R 1 / -R 5 ,-R 1 / -R 6 ,-R 1 / -R 7 ,-R 2 / -R 3 ,-R 2 / -R 4 ,-R 2 / -R 5 ,-R 2 / -R 6 ,-R 2 / -R 7 ,-R 3 / -R 4 ,-R 3 / -R 5 ,-R 3 / -R 6 ,-R 3 / -R 7 ,-R 4 / -R 5 ,-R 4 / -R 6 ,-R 4 / -R 7 ,-R 5 / -R 6 ,-R 5 / -R 7 , and -R 6 / -R 7 One or more of these, together with the atoms to which they are bonded, form ring A. A is phenyl, naphthyl, indenyl, indanyl, tetralinyl, C 3-10 Selected from the group consisting of cycloalkyls, 3-10 membered heterocyclyls, and 8-11 membered heterobicyclyls, Here, -L 1 - is at least one -L 2 - is replaced by -L 1 - is sometimes further replaced.) It belongs to them.

[0327] -L in equation (III) 1Further optional substituents of - are, in certain embodiments, as described above.

[0328] In certain embodiments, -L of formula (III) 1 - is one part -L 2 It is replaced with -.

[0329] In certain embodiments, -L of formula (III) 1 - has not been further replaced.

[0330] In certain embodiments, -L 1 - is disclosed in European Patent No. 1536334B1, WO2009 / 009712A1, WO2008 / 034122A1, WO2009 / 143412A2, WO2011 / 082368A2, and U.S. Patent No. 8,618,124B2, all of which are incorporated herein by reference.

[0331] In certain embodiments, -L 1 - is disclosed in U.S. Patent No. 8,946,405 B2 and U.S. Patent No. 8,754,190 B2, which are incorporated herein by reference in their entirety. Thus, in certain embodiments, -L 1 - is equation (IV): [ka] (In the formula, The dashed line indicates a bond to -D-, where the bond is via a functional group of -D- selected from the group consisting of -OH, -SH, and -NH2. m is either 0 or 1. -R 1 and -R 2 At least one or both of these are, independently of each other, -CN, -NO2, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alkenyl, optionally substituted alkynyl, -C(O)R 3 ,-S(O)R 3-S(O)2R 3 , and -SR 4 Selected from the group consisting of, -R 1 and -R 2 One or only one of these is selected from the group consisting of -H, optionally substituted alkyl, optionally substituted arylalkyl, and optionally substituted heteroarylalkyl. -R 3 -H, optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -OR 9 and -N(R 9 Selected from the group consisting of )2, -R 4 This is selected from the group consisting of optionally substituted alkyls, optionally substituted aryls, optionally substituted arylalkyls, optionally substituted heteroaryls, and optionally substituted heteroarylalkyls. Each-R 5 These are independently selected from the group consisting of -H, optionally substituted alkyl, optionally substituted alkenylalkyl, optionally substituted alkynylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl. -R 9 This is selected from the group consisting of -H and optionally substituted alkyl groups, -Y- does not exist, and -X- is either -O- or -S-, or -Y- is -N(Q)CH2- and -X- is -O-, Q is selected from the group consisting of optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl. Depending on the case, -R 1 and -R 2 They may come together to form a ring of 3 to 8 members. Depending on the case, both -R 9 These, together with the nitrogen atoms to which they are bonded, form a heterocyclic ring. Here, -L 1 - is at least one -L 2 - is replaced by -L 1 - is sometimes further replaced.) It belongs to them.

[0332] The term used exclusively in relation to formula (IV) has the following meanings: As used herein, the term "alkyl" includes linear, branched, or cyclic saturated hydrocarbon groups comprising 1 to 8 carbon atoms, or in certain embodiments, 1 to 6 or 1 to 4 carbon atoms.

[0333] The term "alkoxy" encompasses alkyl groups bonded to oxygen, including methoxy, ethoxy, isopropoxy, cyclopropoxy, cyclobutoxy, and similar groups.

[0334] The term "alkenyl" encompasses non-aromatic unsaturated hydrocarbons that contain a carbon-carbon double bond.

[0335] The term "alkynyl" encompasses non-aromatic unsaturated hydrocarbons that have a carbon-carbon triple bond.

[0336] The term "aryl" encompasses aromatic hydrocarbon groups with 6 to 18 carbon atoms, for example, 6 to 10 carbon atoms, and includes groups such as phenyl, naphthyl, and anthracenyl. The term "heteroaryl" encompasses aromatic rings with 3 to 15 carbon atoms containing at least one N, O, or S atom, for example, 3 to 7 carbon atoms containing at least one N, O, or S atom, and includes groups such as pyrrolyl, pyridyl, pyrimidinyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, quinolyl, indolyl, indenyl, and similar groups.

[0337] In some examples, the alkenyl, alkynyl, aryl, or heteroaryl moiety may be coupled to the rest of the molecule via an alkylene bond. In these circumstances, the substituent is called an alkenylalkyl, alkynylalkyl, arylalkyl, or heteroarylalkyl, indicating that the alkylene moiety lies between the alkenyl, alkynyl, aryl, or heteroaryl moiety and the molecule to which the alkenyl, alkynyl, aryl, or heteroaryl is coupled.

[0338] The term "halogen" includes bromo, fluoro, chloro, and iodine.

[0339] The term “heterocyclic ring” refers to a 4-8 membered aromatic or non-aromatic ring containing 3-7 carbon atoms and at least 1 N, O, or S atom. Examples include piperidinyl, piperazinyl, tetrahydropyranyl, pyrrolidine, and tetrahydrofuranyl, as well as the exemplary groups provided for the term “heteroaryl” above.

[0340] If the ring system is optionally substituted, preferred substituents are selected from the group consisting of alkyl, alkenyl, alkynyl, or further rings, each optionally further substituted. Optional substituents on any of the above-mentioned groups include halo, nitro, cyano, -OR, -SR, -NR2, -OCOR, -NRCOR, -COOR, -CONR2, -SOR, -SO2R, -SONR2, and -SO2NR2, where each R is independently alkyl, alkenyl, alkynyl, aryl, or heteroaryl, or two R groups together with the atom to which they are bonded form a ring.

[0341] In certain embodiments, -L of formula (IV) 1 - is one part -L 2 It is replaced with -.

[0342] In certain embodiments, -L of formula (IV) 1- has not been further replaced.

[0343] In certain embodiments, -L 1 - is disclosed in WO2013 / 036857A1, which is incorporated herein by reference in its entirety. Thus, in certain embodiments, -L 1 - is equation (V): [ka] (In the formula, The dashed line is HD-AB 2 It shows bonding to -D- via the amine functional group, -R 1 These include optionally substituted C1-C6 linear, branched, or cyclic alkyl groups; optionally substituted aryl groups; optionally substituted heteroaryl groups; alkoxy groups; and -NR 5 Selected from a group consisting of 2, -R 2 This is selected from the group consisting of -H, optionally substituted C1-C6 alkyl, optionally substituted aryl, and optionally substituted heteroaryl. -R 3 This is selected from the group consisting of -H, optionally substituted C1-C6 alkyl, optionally substituted aryl, and optionally substituted heteroaryl. -R 4 This is selected from the group consisting of -H, optionally substituted C1-C6 alkyl, optionally substituted aryl, and optionally substituted heteroaryl. Each-R 5 These are independently selected from the group consisting of -H, optionally substituted C1-C6 alkyl, optionally substituted aryl, and optionally substituted heteroaryl, or, if combined, two -R 5 It can be a cycloalkyl or cycloheteroalkyl, Here, -L 1 - is at least one -L 2- is replaced by -L 1 - is sometimes further replaced.) It belongs to them.

[0344] The term used exclusively in relation to the expression (V) has the following meanings: "Alkyl," "alkenyl," and "alkynyl" encompass linear, branched, or cyclic hydrocarbon groups of 1 to 8 carbon atoms, 1 to 6 carbon atoms, or 1 to 4 carbon atoms, where alkyl is a saturated hydrocarbon, alkenyl contains one or more carbon-carbon double bonds, and alkynyl contains one or more carbon-carbon triple bonds. Unless otherwise specified, these contain 1 to 6 carbon atoms.

[0345] "Aryl" refers to an aromatic hydrocarbon group containing 6 to 18 carbon atoms, for example, 6 to 10 carbon atoms, such as phenyl, naphthyl, and anthracene. "Heteroaryl" refers to an aromatic ring containing 3 to 15 carbon atoms, for example, 3 to 7 carbon atoms, containing at least one N, O, or S atom, such as pyrrolyl, pyridyl, pyrimidinyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, quinolyl, indolyl, indenyl, and similar groups.

[0346] The term "substituted" refers to an alkyl, alkenyl, alkynyl, aryl, or heteroaryl group that contains one or more substituents in place of one or more hydrogen atoms. Substituents generally include halogens (including F, Cl, Br, and I), lower alkyls (including linear, branched, and cyclic lower alkyls), lower haloalkyls (including fluoroalkyls, chloroalkyls, bromoalkyls, and iodoalkyls), OH, lower alkoxys (including linear, branched, and cyclic lower alkoxys), SH, lower alkylthios (including linear, branched, and cyclic lower alkylthios), aminos, alkylaminos, dialkylaminos, silyls (including alkylsilyls, alkoxysilyls, and arylsilyls), nitros, cyanos, carbonyls, carboxylic acids, carboxylic acid esters, carboxylic acid amides, and aminocarboxyl groups. The following can be selected: bonyl, aminoacyl, carbamate, urea, thiocarbamate, thiourea, ketone, sulfone, sulfonamide, aryl (including phenyl, naphthyl, and anthracenyl), heteroaryl (including 5-membered heteroaryls such as pyrrole, imidazole, furan, thiophene, oxazole, thiazole, isoxazole, isothiazole, thiadiazole, triazole, oxadiazole, and tetrazole, 6-membered heteroaryls such as pyridine, pyrimidine, pyrazine, and condensed heteroaryls such as benzofuran, benzothiophene, benzoxazole, benzimidazole, indole, benzothiazole, benzoisoxazole, and benzoisothiazole).

[0347] In certain embodiments, -L of formula (V) 1 - is one part -L 2 It is replaced with -.

[0348] In certain embodiments, -L of formula (V) 1 - has not been further replaced.

[0349] In certain embodiments, -L 1- is disclosed in U.S. Patent No. 7,585,837 B2, which is incorporated herein by reference in its entirety. Therefore, in certain embodiments, -L 1 - is equation (VI): [ka] (In the formula, The dashed line is HD-AB 2 It shows bonding to -D- via the amine functional group, R 1 and R 2 These are independently hydrogen, alkyl, alkoxy, alkoxyalkyl, aryl, alkalyl, aralkyl, halogen, nitro, -SO3H, -SO2HH 5 Selected from the group consisting of amino, ammonium, carboxyl, PO3H2, and OPO3H2, R 3 , R 4 , and R 5 These are independently selected from the group consisting of hydrogen, alkyl, and aryl. Here, -L 1 - is at least one -L 2 - is replaced by -L 1 - is sometimes further replaced.) It belongs to them.

[0350] Suitable substituents for formula (VI) are alkyl (e.g., C 1-6 Alkyl), alkenyl (e.g., C 2-6 Alkenyl), Alkinyl (for example, C 2-6 The moiety is an alkynyl, aryl (e.g., phenyl), heteroalkyl, heteroalkenyl, heteroalkynyl, heteroaryl (e.g., an aromatic 4-7 membered heterocycle), or halogen moiety.

[0351] The term used exclusively in relation to formula (VI) has the following meanings: The terms "alkyl," "alkoxy," "alkoxyalkyl," "aryl," "alkalil," and "aralkyl" refer to alkyl groups with 1 to 8 carbon atoms, for example, 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, and butyl, and aryl groups with 6 to 10 carbon atoms, such as phenyl and naphthyl. The term "halogen" includes bromo, fluoro, chloro, and iodine.

[0352] In certain embodiments, -L of formula (VI) 1 - is one part -L 2 It is replaced with -.

[0353] In certain embodiments, -L of formula (VI) 1 - has not been further replaced.

[0354] -L 1 Further preferred embodiments of - are disclosed in WO2002 / 089789A1, which is incorporated herein by reference in its entirety. Therefore, preferred portion - L 1 - is equation (VII): [ka] (In the formula, The dashed line is HD-AB 2 It shows bonding to -D- via the amine functional group, L1 is a bifunctional bonding group, Y1 and Y2 are independently O, S, or NR 7 And, R 2 , R 3 , R 4 , R 5 , R 6 and R 7 These are, independently, hydrogen and C 1-6 Alkyl, C 3-12 Branched alkyl, C 3-8 Cycloalkyl, C 1-6 Substituting alkyl, C 3-8 Substituted cycloalkyl, aryl, substituted aryl, aralkyl, C 1-6Heteroalkyl, substituted C 1-6 Heteroalkyl, C 1-6 Alkoxy, phenoxy, and C 1-6 Selected from the group consisting of heteroalkoxys, When Ar is included in formula (VII), it is the part that forms a polysubstituted aromatic hydrocarbon or a polysubstituted heterocyclic group. X is a chemical bond, or a portion that is actively transported to the target cell, a hydrophobic portion, or a combination thereof. y is either 0 or 1. Here, -L 1 - is at least one -L 2 - is replaced by -L 1 - is sometimes further replaced.) It belongs to them.

[0355] The term used exclusively in relation to formula (VII) has the following meanings: The term "alkyl" refers to, for example, linear, branched, or substituted C atoms. 1-12 Alkyl, for example, alkoxy, C 3-8 It will be understood that this includes cycloalkyl or substituted cycloalkyl groups, etc.

[0356] The term "substituted" should be understood to include adding one or more different atoms to one or more atoms contained in a functional group or compound, or replacing one or more atoms contained in a functional group or compound with one or more different atoms.

[0357] Substitutive alkyls include carboxyalkyl, aminoalkyl, dialkylamino, hydroxyalkyl, and mercaptoalkyl; substituted cycloalkyls include parts such as 4-chlorocyclohexyl; aryls include parts such as naphthyl; substituted aryls include parts such as 3-bromophenyl; aralkyls include parts such as toluyl; heteroalkyls include parts such as ethylthiophene; substituted heteroalkyls include parts such as 3-methoxythiophene; alkoxys include parts such as methoxy; and phenoxys include parts such as 3-nitrophenoxy. Halos are understood to include fluoro, chloro, iodo, and bromo.

[0358] In certain embodiments, -L of formula (VII) 1 - is one part -L 2 It is replaced with -.

[0359] In certain embodiments, -L of formula (VII) 1 - has not been further replaced.

[0360] In certain embodiments, -L 1 - is a substructure of equation (VIII) [ka] (In the formula, The dashed line with an asterisk indicates the bond of -D- to nitrogen via an amide bond. Dashed lines without a mark are -L 1 - indicates the connection to the remainder, Here, -L 1 - is at least one -L 2 - is replaced by -L 1 - is sometimes further replaced.) Includes.

[0361] In certain embodiments, the -L of formula (VIII) 1 - is one part -L 2 It is replaced with -.

[0362] In certain embodiments, the -L of formula (VIII) 1 - has not been further replaced.

[0363] In certain embodiments, -L 1 - is a substructure of equation (IX) [ka] (In the formula, The dashed lines with asterisks indicate the bonding of -D- to nitrogen via a carbamate bond. Dashed lines without a mark are -L 1 - Indicates connection to the remainder Here, -L 1 - is at least one -L 2 - is replaced by -L 1 - is sometimes further replaced.) Includes.

[0364] In certain embodiments, -L of formula (IX) 1 - is one part -L 2 It is replaced with -.

[0365] In certain embodiments, -L of formula (IX) 1 - has not been further replaced.

[0366] In certain embodiments, -L 1 - has the structure disclosed in WO2020 / 206358 A1. Therefore, in certain embodiments, part -L 1 - is equation (X): [ka] (In the formula, Unmarked dashed lines indicate connections to -D-. The dashed line with an asterisk indicates -L 2 - indicates binding to n is an integer selected from the group consisting of 0, 1, 2, 3, 4, 5, and 6. -R 1 and -R 2 These are independently electron-withdrawing groups, alkyl groups, or -H groups, and -R 1 or -R 2 At least one of them is an electron-withdrawing group, Each-R 4 These are independently C1-C3 alkyl or two-R 4 These, together with the carbon atoms to which they are bonded, form a ring with 3 to 6 members. -Y- is absent if -D is a drug moiety bonded via an amine, or -Y- is -N(R) if -D is a drug moiety bonded via a phenol, alcohol, thiol, thiophenol, imidazole, or non-basic amine. 6 )CH2-, where -R 6 (These are, in some cases, substituted C1-C6 alkyl groups, in some cases, substituted aryl groups, or in some cases, substituted heteroaryl groups.) It belongs to them.

[0367] In certain embodiments, n in formula (X) is an integer selected from 1, 2, 3, 4, 5, and 6. In certain embodiments, n in formula (X) is an integer selected from 1, 2, and 3. In certain embodiments, n in formula (X) is an integer from 0, 1, 2, and 3. In certain embodiments, n in formula (X) is 1. In certain embodiments, n in formula (X) is 2. In certain embodiments, n in formula (X) is 3.

[0368] In certain embodiments, -R of formula (X) 1 and -R 2 The electron-withdrawing groups are -CN;-NO2; optionally substituted aryl; optionally substituted heteroaryl; optionally substituted alkenyl; optionally substituted alkynyl;-COR 3 -SOR 3 , or -SO2R 3 A group consisting of is selected, where -R 3-H, optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -OR 8 Alternatively, -NR 8 2 (in the formula, each -R 8 These are independently -H or optionally substituted alkyl, or both -R 8 The groups, together with the nitrogen atoms to which they are bonded, form a heterocyclic ring), or -SR 9 (In the formula, -R 9 (which is optionally a substituted alkyl, optionally a substituted aryl, optionally a substituted arylalkyl, optionally a substituted heteroaryl, or optionally a substituted heteroarylalkyl).

[0369] In certain embodiments, -R of formula (X) 1 and -R 2 The electron-withdrawing group is -CN. In certain embodiments, -R of formula (X) 1 and -R 2 The electron-withdrawing group is -NO2. In certain embodiments, -R of formula (X) 1 and -R 2 The electron-withdrawing group is an optionally substituted aryl group containing 6 to 10 carbon atoms. In certain embodiments, the -R of formula (X) 1 and -R 2 The electron-withdrawing group is optionally substituted phenyl, naphthyl, or anthracenyl. In certain embodiments, -R of formula (X) 1 and -R 2 The electron-withdrawing group is an optionally substituted heteroaryl containing 3 to 7 carbon atoms and at least one N, O, or S atom. In certain embodiments, the -R of formula (X) 1 and -R 2The electron-withdrawing group is optionally substituted pyrrolyl, pyridyl, pyrimidinyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, quinolyl, indolyl, or indenyl. In certain embodiments, -R of formula (X) 1 and -R 2 The electron-withdrawing group is an optionally substituted alkenyl containing 2 to 20 carbon atoms. In certain embodiments, the -R of formula (X) 1 and -R 2 The electron-withdrawing group is an optionally substituted alkynyl containing 2 to 20 carbon atoms. In certain embodiments, the -R of formula (X) 1 and -R 2 The electron-withdrawing group is -COR 3 -SOR 3 , or -SO2R 3 And here, -R 3 -H, optionally substituted alkyl containing 1 to 20 carbon atoms, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -OR 8 or -NR 8 2, and each -R 8 These are either alkyl groups independently substituted with -H or containing 1 to 20 carbon atoms, or both -R groups. 8 The groups, together with the nitrogen atoms to which they are bonded, form a heterocyclic ring. In certain embodiments, the -R of formula (X) 1 and -R 2 The electron-withdrawing group is -SR 9 And here, -R 9 This is an optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, or optionally substituted heteroarylalkyl, which contains 1 to 20 carbon atoms.

[0370] In certain embodiments, -R of formula (X) 1 or -R 2At least one of them is -CN, -SOR 3 or -SO2R 3 In certain embodiments, -R of formula (X) 1 and -R 2 At least one of them is -CN or -SO2R 3 In certain embodiments, -R of formula (X) 1 and -R 2 At least one of them is -CN or -SO2R 3 And, -R 3 This may be a substituted alkyl, may be a substituted aryl, or -NR 8 2. In certain embodiments, -R of formula (X) 1 and -R 2 At least one of them is -CN, -SO2N(CH3)2, -SO2CH3, phenyl substituted with -SO2, phenyl substituted with -SO2 and -Cl, -SO2N(CH2CH2)2O, -SO2CH(CH3)2, -SO2N(CH3)(CH2CH3), or -SO2N(CH2CH2OCH3)2.

[0371] In a particular embodiment, each -R of formula (X) 4 These are independently C1-C3 alkyl groups. In certain embodiments, both -R 4 It is methyl.

[0372] In certain embodiments, -Y- in formula (X) does not exist. In certain embodiments, -Y- in formula (X) is -N(R 6 It is CH2-.

[0373] In certain embodiments, -L 1 - means that n in the formula is 1, -R 1 -CN and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - means that n in the formula is 1, -R 1 is -SO2N(CH3)2, and -R 2 -H and -R4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - means that n in the formula is 1, -R 1 It is SO2CH3, and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - means that n in the formula is 1, -R 1 is -SO2N(CH2CH2)2CHCH3, and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - means that n in the formula is 1, -R 1 However, it is a phenyl compound substituted with -SO2, and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - means that n in the formula is 1, -R 1 However, it is a phenyl substituted with -SO2 and -Cl, and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - means that n in the formula is 1, -R 1 is -SO2N(CH2CH2)2O, and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - means that n in the formula is 1, -R 1 is -SO2CH(CH3)2, and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - means that n in the formula is 1, -R 1 is -SO2N(CH3)(CH2CH3), and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - means that n in the formula is 1, -R1 is -SO2N(CH2CH2OCH3)2, and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - means that n in the formula is 1, -R 1 However, it is a phenyl substituted with -SO2 and -CH3, and -R 2 -H and -R 4 This is the one in equation (X) where -CH3 is present.

[0374] In certain embodiments, -L 1 - is where n in the formula is 2, and -R 1 -CN and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - is where n in the formula is 2, and -R 1 is -SO2N(CH3)2, and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - is where n in the formula is 2, and -R 1 It is SO2CH3, and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - is where n in the formula is 2, and -R 1 is -SO2N(CH2CH2)2CHCH3, and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - is where n in the formula is 2, and -R 1 However, it is a phenyl compound substituted with -SO2, and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - is where n in the formula is 2, and -R 1 However, it is a phenyl substituted with -SO2 and -Cl, and -R2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - is where n in the formula is 2, and -R 1 is -SO2N(CH2CH2)2O, and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - is where n in the formula is 2, and -R 1 is -SO2CH(CH3)2, and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - is where n in the formula is 2, and -R 1 is -SO2N(CH3)(CH2CH3), and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - is where n in the formula is 2, and -R 1 is -SO2N(CH2CH2OCH3)2, and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - is where n in the formula is 2, and -R 1 However, it is a phenyl substituted with -SO2 and -CH3, and -R 2 -H and -R 4 This is the one in equation (X) where -CH3 is present.

[0375] In certain embodiments, -L 1 - is where n in the formula is 3, and -R 1 -CN and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - is where n in the formula is 3, and -R 1 is -SO2N(CH3)2, and -R 2 -H and -R 4It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - is where n in the formula is 3, and -R 1 It is SO2CH3, and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - is where n in the formula is 3, and -R 1 is -SO2N(CH2CH2)2CHCH3, and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - is where n in the formula is 3, and -R 1 However, it is a phenyl compound substituted with -SO2, and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - is where n in the formula is 3, and -R 1 However, it is a phenyl substituted with -SO2 and -Cl, and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - is where n in the formula is 3, and -R 1 is -SO2N(CH2CH2)2O, and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - is where n in the formula is 3, and -R 1 is -SO2CH(CH3)2, and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - is where n in the formula is 3, and -R 1 is -SO2N(CH3)(CH2CH3), and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - is where n in the formula is 3, and -R 1is -SO2N(CH2CH2OCH3)2, and -R 2 -H and -R 4 It is of formula (X), where is -CH3. In a particular embodiment, -L 1 - is where n in the formula is 3, and -R 1 However, it is a phenyl substituted with -SO2 and -CH3, and -R 2 -H and -R 4 This is the one in equation (X) where -CH3 is present.

[0376] The term used exclusively in relation to formula (X) has the following meanings: The term "alkyl" refers to a linear, branched, or cyclic saturated hydrocarbon group having 1 to 20, 1 to 12, 1 to 8, 1 to 6, or 1 to 4 carbon atoms. In certain embodiments, alkyl groups are linear or branched. Examples of linear or branched alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, and n-decyl. In certain embodiments, alkyl groups are cyclic. Examples of cyclic alkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentadienyl, and cyclohexyl.

[0377] The term "alkoxy" refers to an alkyl group bonded to oxygen, such as methoxy, ethoxy, isopropoxy, cyclopropoxy, and cyclobutoxy.

[0378] The term "alkenyl" refers to a non-aromatic unsaturated hydrocarbon having a carbon-carbon double bond and 2-20, 2-12, 2-8, 2-6, or 2-4 carbon atoms.

[0379] The term "alkynyl" refers to a non-aromatic unsaturated hydrocarbon having a carbon-carbon triple bond and 2-20, 2-12, 2-8, 2-6, or 2-4 carbon atoms.

[0380] The term "aryl" refers to an aromatic hydrocarbon group having 6 to 18 carbon atoms, preferably 6 to 10 carbon atoms, such as phenyl, naphthyl, and anthracenyl groups. The term "heteroaryl" refers to an aromatic ring having 3 to 15 carbon atoms, preferably 3 to 7 carbon atoms, including at least one N, O, or S atom, such as pyrrolyl, pyridyl, pyrimidinyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, quinolyl, indolyl, and indenyl groups.

[0381] In certain embodiments, an alkenyl, alkynyl, aryl, or heteroaryl moiety may be coupled to the remainder of the molecule by an alkyl bond. Under these circumstances, the substituent is referred to as an alkenylalkyl, alkynylalkyl, arylalkyl, or heteroarylalkyl, indicating that the alkylene moiety lies between the alkenyl, alkynyl, aryl, or heteroaryl moiety and the molecule to which the alkenyl, alkynyl, aryl, or heteroaryl is coupled.

[0382] The term "halogen" refers to bromo, fluoro, chloro, and iodine.

[0383] The term “heterocyclic ring” or “heterocyclyl” refers to a 3- to 15-membered aromatic or non-aromatic ring containing at least one N, O, or S atom. Examples include piperidinyl, piperazinyl, tetrahydropyranyl, pyrrolidine, and tetrahydrofuranyl, as well as exemplary groups provided for the term “heteroaryl” above. In certain embodiments, the heterocyclic ring or heterocyclyl is non-aromatic. In certain embodiments, the heterocyclic ring or heterocyclyl is aromatic.

[0384] The term "optionally substituted" means that the group may be unsubstituted, or may be substituted with one or more substituents (e.g., 1, 2, 3, 4, or 5) that may be the same or different. Examples of substituents include alkyl, alkenyl, alkynyl, halogen, -CN, and -OR. aa , -SR aa , -NR aa R bb -NO2, -C=NH(OR aa ), -C(O)R aa -OC(O)R aa , -C(O)OR aa -C(O)NR aa R bb -OC(O)NR aa R bb , -NR aa C(O)R bb , -NR aa C(O)OR bb ,-S(O)R aa -S(O)2R aa , -NR aa S(O)R bb -C(O)NR aa S(O)R bb , -NR aa S(O)2R bb -C(O)NR aa S(O)2R bb -S(O)NR aa R bb -S(O)2NR aa R bb , -P(O)(OR aa )(OR bb Examples include heterocyclyl, heteroaryl, or aryl, where alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, heteroaryl, and aryl are each independently -R cc It is sometimes replaced by -R aa and -R bb Each of these is independently either -H, alkyl, alkenyl, alkynyl, heterocyclyl, heteroaryl, or aryl, or -R aa and -R bbThese, together with the nitrogen atom to which they are bonded, form a heterocycline, which is optionally substituted with alkyl, alkenyl, alkynyl, halogen, hydroxyl, alkoxy, or -CN, where each -R cc These are independently alkyl, alkenyl, alkynyl, halogen, heterocyclyl, heteroaryl, aryl, -CN, or -NO2.

[0385] In certain embodiments, -L 1 - has the structure disclosed in formula I of WO2021 / 242756 A1. Therefore, in certain embodiments, part -L 1 - is equation (XIIa): [ka] (In the formula, Unmarked dashed lines indicate connections to -D-. The dashed line with an asterisk indicates -L 2 - indicates binding to -R 2 ,-R 4 and -R 8 These are independently -H or C 1-4 Selected from the group consisting of alkyl groups, -R 3 is C 1-4 Alkyl or -R 3 and -R 4 These, together with the atoms to which they are bonded, form a 5- or 6-membered heterocyclic ring. -R 5 It is NH2, However, -R 4 and -R 3 However, when they combine with the atoms to which they are bonded to form a 5- or 6-membered heterocyclic ring (from), -R 2 is not -H, Here, -L in equation (XIIa) 1 (- is sometimes replaced) It belongs to them.

[0386] In certain embodiments, -R of formula (XIIa) 4 and -R 8 Both are -H.

[0387] In certain embodiments, -R 3 is methyl. In certain embodiments, -R 3 It is -H.

[0388] In certain embodiments, -R 2 It is -H.

[0389] In certain embodiments, part-L 1 - is equation (XIIa-i) [ka] (In the formula, Unmarked dashed lines indicate connections to -D-. The dashed line with an asterisk indicates -L 2 (Indicates a connection to -) It belongs to them.

[0390] In certain embodiments, part-L 1 - is equation (XIIa-ii) [ka] (In the formula, Unmarked dashed lines indicate connections to -D-. The dashed line with an asterisk indicates -L 2 (Indicates a connection to -) It belongs to them.

[0391] In certain embodiments, part-L 1 - is equation (XIIa-iii) [ka] (In the formula, Unmarked dashed lines indicate connections to -D-. The dashed line with an asterisk indicates -L 2(Indicates a connection to -) It belongs to them.

[0392] In certain embodiments, -L 1 - has the structure disclosed in Formula II of WO2022 / 096636 A1. Therefore, in certain embodiments, part -L 1 - is equation (XIIb): [ka] (In the formula, Unmarked dashed lines indicate connections to -D-. The dashed line with an asterisk indicates -L 2 (Indicates a connection to -) It belongs to them.

[0393] In certain embodiments, -L 2 - does not exist.

[0394] In certain embodiments, -L 2 - is especially suitable for -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(R y1 )-,-S(O)2N(R y1 )-,-S(O)N(R y1 )-, -S(O)2-, -S(O)-, -N(R y1 )S(O)2N(R y1a )-, -S-, -N(R y1 )-, -OC(OR y1 )(R y1a )-,-N(R y1 )C(O)N(R y1a )-,-OC(O)N(R y1 )-, C 1-50 Alkyl, C 2-50 Alkenyl and C 2-50 A spacer portion selected from the group consisting of alkynnyls, where -T-, C 1-50 Alkyl, C 2-50 Alkenyl and C 2-50 Alkinyl has one or more -Rs, which may be the same or different. y2 In some cases, it is replaced by C 1-50Alkyl, C 2-50 Alkenyl and C 2-50 Alkinyls include -T-, -C(O)O-, -O-, -C(O)-, and -C(O)N(R) y3 )-,-S(O)2N(R y3 )-,-S(O)N(R y3 )-, -S(O)2-, -S(O)-, -N(R y3 )S(O)2N(R y3a )-, -S-, -N(R y3 )-, -OC(OR y3 )(R y3a )-,-N(R y3 )C(O)N(R y3a )-, and -OC(O)N(R y3 )- may intersect with one or more groups selected from the group consisting of, -R y1 and -R y1a These are -H, -T, and C, which are independent of each other. 1-50 Alkyl, C 2-50 Alkenyl and C 2-50 Selected from the group consisting of alkynyls, where -T, C 1-50 Alkyl, C 2-50 Alkenyl and C 2-50 Alkinyl has one or more -Rs, which may be the same or different. y2 In some cases, it is replaced by C 1-50 Alkyl, C 2-50 Alkenyl and C 2-50 Alkinyls include -T-, -C(O)O-, -O-, -C(O)-, and -C(O)N(R) y4 )-,-S(O)2N(R y4 )-,-S(O)N(R y4 )-, -S(O)2-, -S(O)-, -N(R y4 )S(O)2N(R y4a )-, -S-, -N(R y4 )-, -OC(OR y4 )(R y4a )-,-N(R y4 )C(O)N(R y4a )-, and -OC(O)N(R y4 )- may intersect with one or more groups selected from the group consisting of, Each T independently consists of phenyl, naphthyl, indenyl, indanyl, tetralinyl, and C. 3-10 Selected from the group consisting of cycloalkyls, 3-10 membered heterocyclils, 8-11 membered heterobicyclils, 8-30 membered carbopolycyclils, and 8-30 membered heteropolycyclils, where each T is independently one or more identical or different -R y2 It is sometimes replaced by, Each-R y2 These are, independently, halogen, -CN, oxo (=O), and -COOR. y5 , -OR y5 , -C(O)R y5 ,-C(O)N(R y5 R y5a ), -S(O)2N(R y5 R y5a ), -S(O)N(R y5 R y5a ), -S(O)2R y5 ,-S(O)R y5 , -N(R y5 )S(O)2N(R y5a R y5b ), -SR y5 , -N(R y5 R y5a ), -NO2, -OC(O)R y5 , -N(R y5 )C(O)R y5a , -N(R y5 )S(O)2R y5a , -N(R y5 )S(O)R y5a , -N(R y5 )C(O)OR y5a , -N(R y5 )C(O)N(R y5a R y5b ), -OC(O)N(R y5 R y5a ), and C 1-6 Selected from the group consisting of alkyl groups, where C 1-6 Alkyl is optionally substituted with one or more halogens, either the same or different. Each-R y3 ,-R y3a ,-R y4 ,-R y4a ,-Ry5 ,-R y5a and -R y5b These are independently -H and C 1-6 Selected from the group consisting of alkyl groups, where C 1-6 Alkyl atoms are sometimes substituted with one or more halogens, either the same or different.

[0395] In certain embodiments, -L 2 - stands for -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(R y1 )-,-S(O)2N(R y1 )-,-S(O)N(R y1 )-, -S(O)2-, -S(O)-, -N(R y1 )S(O)2N(R y1a )-, -S-, -N(R y1 )-, -OC(OR y1 )(R y1a )-,-N(R y1 )C(O)N(R y1a )-,-OC(O)N(R y1 )-, C 1-50 Alkyl, C 2-50 Alkenyl and C 2-50 Selected from alkinyl, where -T-, C 1-20 Alkyl, C 2-20 Alkenyl and C 2-20 Alkinyl has one or more -Rs, which may be the same or different. y2 In some cases, it is replaced by C 1-20 Alkyl, C 2-20 Alkenyl and C 2-20 Alkinyls include -T-, -C(O)O-, -O-, -C(O)-, and -C(O)N(R) y3 )-,-S(O)2N(R y3 )-,-S(O)N(R y3 )-, -S(O)2-, -S(O)-, -N(R y3 )S(O)2N(R y3a )-, -S-, -N(R y3 )-, -OC(OR y3 )(R y3a )-,-N(R y3 )C(O)N(R y3a )-, and -OC(O)N(Ry3 )- may intersect with one or more groups selected from the group consisting of, -R y1 and -R y1a These are -H, -T, and C, which are independent of each other. 1-10 Alkyl, C 2-10 Alkenyl and C 2-10 Selected from the group consisting of alkynyls, where -T, C 1-10 Alkyl, C 2-10 Alkenyl and C 2-10 Alkinyl has one or more -Rs, which may be the same or different. y2 In some cases, it is replaced by C 1-10 Alkyl, C 2-10 Alkenyl and C 2-10 Alkinyls include -T-, -C(O)O-, -O-, -C(O)-, and -C(O)N(R) y4 )-,-S(O)2N(R y4 )-,-S(O)N(R y4 )-, -S(O)2-, -S(O)-, -N(R y4 )S(O)2N(R y4a )-, -S-, -N(R y4 )-, -OC(OR y4 )(R y4a )-,-N(R y4 )C(O)N(R y4a )-, and -OC(O)N(R y4 )- may intersect with one or more groups selected from the group consisting of, Each T independently consists of phenyl, naphthyl, indenyl, indanyl, tetralinyl, and C. 3-10 Selected from the group consisting of cycloalkyls, 3-10 membered heterocyclils, 8-11 membered heterobicyclils, 8-30 membered carbopolycyclils, and 8-30 membered heteropolycyclils, where each T is independently one or more identical or different -R y2 It is sometimes replaced by, -R y2 These are halogen, -CN, oxo (=O), and -COOR. y5 , -OR y5 , -C(O)R y5 ,-C(O)N(R y5 Ry5a ), -S(O)2N(R y5 R y5a ), -S(O)N(R y5 R y5a ), -S(O)2R y5 ,-S(O)R y5 , -N(R y5 )S(O)2N(R y5a R y5b ), -SR y5 , -N(R y5 R y5a ), -NO2, -OC(O)R y5 , -N(R y5 )C(O)R y5a , -N(R y5 )S(O)2R y5a , -N(R y5 )S(O)R y5a , -N(R y5 )C(O)OR y5a , -N(R y5 )C(O)N(R y5a R y5b ), -OC(O)N(R y5 R y5a ), and C 1-6 Selected from the group consisting of alkyl groups, where C 1-6 Alkyl is optionally substituted with one or more halogens, either the same or different. Each-R y3 ,-R y3a ,-R y4 ,-R y4a ,-R y5 ,-R y5a and -R y5b These are, independently of each other, -H and C 1-6 Selected from the group consisting of alkyl groups, where C 1-6 Alkyl atoms are sometimes substituted with one or more halogens, either the same or different.

[0396] In certain embodiments, -L 2 - stands for -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(R y1 )-,-S(O)2N(R y1 )-,-S(O)N(R y1 )-, -S(O)2-, -S(O)-, -N(Ry1 )S(O)2N(R y1a )-, -S-, -N(R y1 )-, -OC(OR y1 )(R y1a )-,-N(R y1 )C(O)N(R y1a )-,-OC(O)N(R y1 )-, C 1-50 Alkyl, C 2-50 Alkenyl and C 2-50 Selected from the group consisting of alkynnyls, where -T-, C 1-50 Alkyl, C 2-50 Alkenyl and C 2-50 Alkinyl has one or more -Rs, which may be the same or different. y2 In some cases, it is replaced by C 1-50 Alkyl, C 2-50 Alkenyl and C 2-50 Alkinyls include -T-, -C(O)O-, -O-, -C(O)-, and -C(O)N(R) y3 )-,-S(O)2N(R y3 )-,-S(O)N(R y3 )-, -S(O)2-, -S(O)-, -N(R y3 )S(O)2N(R y3a )-, -S-, -N(R y3 )-, -OC(OR y3 )(R y3a )-,-N(R y3 )C(O)N(R y3a )-, and -OC(O)N(R y3 )- may intersect with one or more groups selected from the group consisting of, -R y1 and -R y1a These are independently -H, -T, and C 1-10 Alkyl, C 2-10 Alkenyl and C 2-10 Selected from the group consisting of alkynnyls, Each T independently consists of phenyl, naphthyl, indenyl, indanyl, tetralinyl, and C. 3-10Selected from the group consisting of cycloalkyls, 3-10 membered heterocyclils, 8-11 membered heterobicyclils, 8-30 membered carbopolycyclils, and 8-30 membered heteropolycyclils, Each-R y2 These are, independently, halogen and C 1-6 Selected from the group consisting of alkyl groups, Each-R y3 ,-R y3a ,-R y4 ,-R y4a ,-R y5 ,-R y5a and -R y5b These are, independently of each other, -H and C 1-6 Selected from the group consisting of alkyl groups, where C 1-6 Alkyl atoms are sometimes substituted with one or more halogens, either the same or different.

[0397] In certain embodiments, -L 2 - are -O-, -S-, -T- and -C(O)N(R y1 )- where one or more elements selected independently of C may interrupt 1-20 It is an alkyl chain, and this C 1-20 The alkyl chain consists of -OH, -T, and -C(O)N(R) y6 R y6a ) is optionally substituted with one or more elements independently selected from, where -R y1 ,-R y6 ,-R y6a H and C are independent of each other. 1-4 Selected from the group consisting of alkyl groups, T is phenyl, naphthyl, indenyl, indanyl, tetralinyl, C 3-10 The group is selected from cycloalkyls, 3-10 member heterocyclils, 8-11 member heterobicyclils, 8-30 member carbopolycyclils, and 8-30 member heteropolycyclils.

[0398] In certain embodiments, -L 2 - has a molecular weight in the range of 14 g / mol to 750 g / mol.

[0399] In certain embodiments, -L 2 - includes the portion selected from the following: [ka] (In the formula, -R and -R a (These are independently selected from the group consisting of -H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-methylbutyl, 2,2-dimethylpropyl, n-hexyl, 2-methylpentyl, 3-methylpentyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, and 3,3-dimethylpropyl).

[0400] In certain embodiments, -L 2 - has a chain length of 1 to 20 atoms. In certain embodiments, -L 2 - has a chain length of 2 to 10 atoms.

[0401] In certain embodiments, -L 2 - has a chain length of at least 35 atoms. In certain embodiments, -L 2 - has a chain length of at least 50 atoms. In certain embodiments, -L 2 - has a chain length of at least 75 atoms. In certain embodiments, -L 2 - has a chain length of at least 100 atoms. In certain embodiments, -L 2 - has a chain length of at least 150 atoms. In certain embodiments, -L 2 - has a chain length of at least 200 atoms. In certain embodiments, -L 2 - has a chain length of at least 250 atoms. In certain embodiments, -L 2 - has a chain length of at least 300 atoms. In certain embodiments, -L 2 - has a chain length of up to 3000 atoms. In certain embodiments, -L 2 - has a chain length of up to 2500 atoms. In certain embodiments, -L2 - has a chain length of up to 2000 atoms. In certain embodiments, -L 2 - has a chain length of up to 1500 atoms. In certain embodiments, -L 2 - has a chain length in the range of 35 to 3000 atoms. In certain embodiments, -L 2 - has a chain length in the range of 50 to 2500 atoms. In certain embodiments, -L 2 - has a chain length in the range of 75 to 2000 atoms. In certain embodiments, -L 2 - has a chain length in the range of 100 to 1500 atoms. In certain embodiments, -L 2 - has a chain length ranging from 125 to 1000 atoms.

[0402] In certain embodiments, -L 2 - is equation (XI) [ka] (In the formula, Dashed lines without a mark are -L 1 - indicates binding to The dashed line with an asterisk is -AB 1 This shows a connection to, h is an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and 16. It belongs to them.

[0403] In certain embodiments, -L 2 - is from formula (XI), where h is 1. In certain embodiments, -L 2 - is from formula (XI), where h is 2. In certain embodiments, -L 2 - is from formula (XI), where h is 3. In certain embodiments, -L 2 - is from formula (XI), where h is 4. In certain embodiments, -L 2 - is from formula (XI), and h is 5. In certain embodiments, -L 2- is from formula (XI), where h is 6. In certain embodiments, -L 2 - is from formula (XI), where h is 7. In certain embodiments, -L 2 - is from formula (XI), and h is 8. In certain embodiments, -L 2 - is from formula (XI), and h is 9. In certain embodiments, -L 2 - is from formula (XI), where h is 10. In certain embodiments, -L 2 - is from formula (XI), where h is 11. In certain embodiments, -L 2 - is from formula (XI), where h is 12. In certain embodiments, -L 2 - is from formula (XI), where h is 13. In certain embodiments, -L 2 - is from formula (XI), where h is 14. In certain embodiments, -L 2 - is from equation (XI), and h is 15.

[0404] In certain embodiments, -L 2 - has a molecular weight of at least 450 Da. In certain embodiments, -L 2 - has a molecular weight of at least 1 kDa. In certain embodiments, -L 2 - has a molecular weight of at least 1.5 kDa. In certain embodiments, -L 2 - has a molecular weight of at least 2 kDa. In certain embodiments, -L 2 - has a molecular weight of at least 2.5 kDa. In certain embodiments, -L 2 - has a molecular weight of at least 3 kDa. In certain embodiments, -L 2 - has a molecular weight of at least 3.5 kDa. In certain embodiments, -L 2 - has a molecular weight of at least 4 kDa. In certain embodiments, -L 2 - has a molecular weight of at least 5 kDa. In certain embodiments, -L 2 - has a maximum molecular weight of 160 kDa. In certain embodiments, -L2 - has a maximum molecular weight of 120 kDa. In certain embodiments, -L 2 - has a maximum molecular weight of 100 kDa. In certain embodiments, -L 2 - has a maximum molecular weight of 80 kDa. In certain embodiments, -L 2 - has a maximum molecular weight of 70 kDa. In certain embodiments, -L 2 - has a maximum molecular weight of 60 kDa. In certain embodiments, -L 2 - has a maximum molecular weight of 50 kDa. In certain embodiments, -L 2 - has a maximum molecular weight of 40 kDa. In certain embodiments, -L 2 - has a molecular weight of approximately 450 Da. In certain embodiments, -L 2 - has a molecular weight of approximately 1 kDa. In certain embodiments, -L 2 - has a molecular weight of approximately 1.5 kDa. In certain embodiments, -L 2 - has a molecular weight of approximately 2 kDa. In certain embodiments, -L 2 - has a molecular weight of approximately 2.5 kDa. In certain embodiments, -L 2 - has a molecular weight of approximately 3 kDa. In certain embodiments, -L 2 - has a molecular weight of approximately 3.5 kDa. In certain embodiments, -L 2 - has a molecular weight of approximately 4 kDa. In certain embodiments, -L 2 - has a molecular weight of approximately 4.5 kDa. In certain embodiments, -L 2 - has a molecular weight of approximately 5 kDa. In certain embodiments, -L 2 - has a molecular weight of approximately 5.5 kDa. In certain embodiments, -L 2 - has a molecular weight of approximately 6 kDa. In certain embodiments, -L 2 - has a molecular weight of approximately 6.5 kDa. In certain embodiments, -L 2 - has a molecular weight of approximately 7 kDa. In certain embodiments, -L 2 - has a molecular weight of approximately 7.5 kDa. In certain embodiments, -L2 - has a molecular weight of approximately 8 kDa. In certain embodiments, -L 2 - has a molecular weight of approximately 8.5 kDa. In certain embodiments, -L 2 - has a molecular weight of approximately 9 kDa. In certain embodiments, -L 2 - has a molecular weight of approximately 9.5 kDa. In certain embodiments, -L 2 - has a molecular weight of approximately 10 kDa.

[0405] In certain embodiments, -L 2 - indicates that it contains a polymer portion, which means it contains at least one polymer portion. -L 2 -If - contains one polymer moiety, the minimum and maximum molecular weights provided above apply to this one polymer moiety, -L 2 If - contains two or more polymer moieties, it is understood that the minimum and maximum molecular weights provided above refer to the minimum and maximum molecular weights of all polymer moieties combined.

[0406] In certain embodiments, -L 2 -One or more polymer portions have a flowy radius of at least 1.2 nm. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of at least 1.5 nm. In certain embodiments, -L 2 -One or more polymer portions have a flowy radius of at least 2 nm. In certain embodiments, -L 2 -One or more polymer portions have a flowy radius of at least 2.5 nm. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of at least 3 nm. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of at least 3.5 nm. In certain embodiments, -L 2 -One or more polymer portions have a flory radius of at least 4 nm. In certain embodiments, -L 2-One or more polymer portions have a flowly radius of at least 4.5 nm. In certain embodiments, -L 2 -One or more polymer portions have a flory radius of at least 5 nm. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of 200 nm or less. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of 175 nm or less. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of 150 nm or less. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of 125 nm or less. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of 100 nm or less. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of 75 nm or less. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of 50 nm or less. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of 45 nm or less. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of 40 nm or less. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of 35 nm or less. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of 30 nm or less. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of approximately 1.2 nm. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of about 1.5 nm. In certain embodiments, -L 2 -One or more polymer portions have a flowy radius of about 2 nm. In certain embodiments, -L 2-One or more polymer portions have a flowly radius of approximately 2.5 nm. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of about 3 nm. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of approximately 3.5 nm. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of about 4 nm. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of approximately 4.5 nm. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of about 5 nm. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of approximately 5.5 nm. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of about 6 nm. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of approximately 6.5 nm. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of about 7 nm. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of approximately 8.5 nm. In certain embodiments, -L 2 -One or more polymer portions have a flowly radius of about 9 nm. In certain embodiments, -L 2 -One or more polymer portions have a flory radius of approximately 10 nm. -L 2 -If it contains one polymer portion, the flory radius provided above applies to this one polymer portion, -L 2 If - contains two or more polymer parts, it is understood that the flory radius provided above refers to the flory radius of all combined polymer parts.

[0407] -L 2- is one or more polymer moieties, for example, poly(2-methacryloyl-oxyethyl phosphorylcholine), poly(acrylic acid), poly(acrylate), poly(acrylamide), poly(alkyloxy)polymer, poly(amide), poly(amideamine), poly(amino acid), poly(acid anhydride), poly(aspartamide), poly(butyric acid), poly(glycolic acid), polybutylene terephthalate, poly(caprolactone), poly(carbonate), poly(cyanoacrylate), poly(dimethylacrylamide), poly(ester), poly(ethylene), poly(ethylene glycol), poly(ethylene oxide), poly(ethyl phosphate), poly(ethyl oxazoline), poly(glycolic acid), poly(hydroxyethyl acrylate), poly(hydroxyethyl oxazoline), poly(hydroxymethacrylate), poly(hydroxypropyl methacrylamide), poly(hydroxypropyl methacrylate), poly(hydroxypropyl methacrylate), poly(hydroxypropyl methacrylate) The polymer contains polymer portions selected from the group consisting of oxypropyl oxazoline, poly(iminocarbonate), poly(lactic acid), poly(lactic acid-co-glycolic acid), poly(methacrylamide), poly(methacrylate), poly(methyloxazoline), poly(organophosphazene), poly(orthoester), poly(oxazoline), poly(propylene glycol), poly(siloxane), poly(urethane), poly(vinyl alcohol), poly(vinylamine), poly(vinyl methyl ether), poly(vinylpyrrolidone), silicone, cellulose, carbomethylcellulose, hydroxypropylmethylcellulose, chitin, chitosan, dextran, dextrin, gelatin, hyaluronic acid and derivatives, functionalized hyaluronic acid, alginate, mannan, pectin, rhamnogalacturonan, starch, hydroxyalkyl starch, hydroxyethyl starch and other carbohydrate polymers, xylan, and copolymers thereof.

[0408] In certain embodiments, -L 2 - contains a PEG-based polymer. In certain embodiments, -L 2 - contains a hyaluronic acid-based polymer. In certain embodiments, -L 2- comprises a random coil polymer. In certain embodiments, -L 2 - contains polysarcosine polymer.

[0409] In certain embodiments, -L 2 - is equation (XII) [ka] (In the formula, -X 1 - and -X 2 - is independent of T-, -C(O)O-, -O-, -C(O)-, -C(O)N(R y1 )-,-S(O)2N(R y1 )-,-S(O)N(R y1 )-, -S(O)2-, -S(O)-, -N(R y1 )S(O)2N(R y1a )-, -S-, -N(R y1 )-, -OC(OR y1 )(R y1a )-,-N(R y1 )C(O)N(R y1a )-,-OC(O)N(R y1 )-, C 1-20 Alkyl, C 2-20 Alkenyl and C 2-20 Selected from the group consisting of alkynnyls, where -T-, C 1-20 Alkyl, C 2-20 Alkenyl and C 2-20 Alkinyl has one or more -Rs, which may be the same or different. y2 In some cases, it is replaced by C 1-20 Alkyl, C 2-20 Alkenyl and C 2-20 Alkinyls include -T-, -C(O)O-, -O-, -C(O)-, and -C(O)N(R) y3 )-,-S(O)2N(R y3 )-,-S(O)N(R y3 )-, -S(O)2-, -S(O)-, -N(R y3 )S(O)2N(R y3a )-, -S-, -N(R y3 )-, -OC(OR y3 )(R y3a)-,-N(R y3 )C(O)N(R y3a )-, and -OC(O)N(R y3 )- may intersect with one or more groups selected from the group consisting of, -R y1 and -R y1a These are -H, -T, and C, which are independent of each other. 1-10 Alkyl, C 2-10 Alkenyl and C 2-10 Selected from the group consisting of alkynnyls, where -T-, C 1-10 Alkyl, C 2-10 Alkenyl and C 2-10 Alkinyl has one or more -Rs, which may be the same or different. y2 In some cases, it is replaced by C 1-10 Alkyl, C 2-10 Alkenyl and C 2-10 Alkinyls include -T-, -C(O)O-, -O-, -C(O)-, and -C(O)N(R) y4 )-,-S(O)2N(R y4 )-,-S(O)N(R y4 )-, -S(O)2-, -S(O)-, -N(R y4 )S(O)2N(R y4a )-, -S-, -N(R y4 )-, -OC(OR y4 )(R y4a )-,-N(R y4 )C(O)N(R y4a )-, and -OC(O)N(R y4 )- may intersect with one or more groups selected from the group consisting of, Each T independently consists of phenyl, naphthyl, indenyl, indanyl, tetralinyl, and C. 3-10 Selected from the group consisting of cycloalkyls, 3-10 membered heterocyclils, 8-11 membered heterobicyclils, 8-30 membered carbopolycyclils, and 8-30 membered heteropolycyclils, where each T is independently one or more identical or different -R y2 It is sometimes replaced by, -R y2 These are halogen, -CN, oxo (=O), and -COOR. y5 , -ORy5 , -C(O)R y5 ,-C(O)N(R y5 R y5a ), -S(O)2N(R y5 R y5a ), -S(O)N(R y5 R y5a ), -S(O)2R y5 ,-S(O)R y5 , -N(R y5 )S(O)2N(R y5a R y5b ), -SR y5 , -N(R y5 R y5a ), -NO2, -OC(O)R y5 , -N(R y5 )C(O)R y5a , -N(R y5 )S(O)2R y5a , -N(R y5 )S(O)R y5a , -N(R y5 )C(O)OR y5a , -N(R y5 )C(O)N(R y5a R y5b ), -OC(O)N(R y5 R y5a ), and C 1-6 Selected from the group consisting of alkyl groups, where C 1-6 Alkyl is optionally substituted with one or more halogens, either the same or different. Each-R y3 ,-R y3a ,-R y4 ,-R y4a ,-R y5 ,-R y5a and -R y5b These are, independently of each other, -H and C 1-6 Selected from the group consisting of alkyl groups, where C 1-6 Alkyl is optionally substituted with one or more halogens, either the same or different. -POL- is the polymer portion. It belongs to them.

[0410] In a particular embodiment, -X of formula (XII) 1 - and -X2 - is independently, C 1-20 Alkyl, C 2-20 Alkenyl and C 2-20 Selected from the group consisting of alkynnyls, where -T-, C 1-20 Alkyl, C 2-20 Alkenyl and C 2-20 Alkinyl has one or more -Rs, which may be the same or different. y2 In some cases, it is replaced by C 1-20 Alkyl, C 2-20 Alkenyl and C 2-20 Alkinyls include -T-, -C(O)O-, -O-, -C(O)-, and -C(O)N(R) y3 )-, -S-, -N(R y3 )-, -OC(OR y3 )(R y3a )-,-N(R y3 )C(O)N(R y3a )-, and -OC(O)N(R y3 )- may intersect with one or more groups selected from the group consisting of, Each T independently consists of phenyl, naphthyl, indenyl, indanyl, tetralinyl, and C. 3-10 Selected from the group consisting of cycloalkyls and 3- to 10-membered heterocyclines, where each T is independently one or more identical or different -R groups. y2 It is sometimes replaced by, -R y2 These are halogens, -CN, oxo (=O), and C 1-6 Selected from the group consisting of alkyl groups, where C 1-6 Alkyl is optionally substituted with one or more halogens, either the same or different. Each-R y3 ,-R y3a ,-R y4 ,-R y4a ,-R y5 ,-R y5a and -R y5b These are, independently of each other, -H and C 1-6 Selected from the group consisting of alkyl groups, where C 1-6 Alkyl atoms are sometimes substituted with one or more halogens, either the same or different.

[0411] In a particular embodiment, -POL- in formula (XII) is equivalent to formula (XII-i) [ka] (In the formula, (y is an integer between 2 and 1000) It belongs to them.

[0412] In certain embodiments, y in formula (XII-i) is selected such that the molecular weight of the (XII-i) portion is about 1 kDa. In certain embodiments, y in formula (XII-i) is selected such that the molecular weight of the (XII-i) portion is about 2 kDa. In certain embodiments, y in formula (XII-i) is selected such that the molecular weight of the (XII-i) portion is about 3 kDa. In certain embodiments, y in formula (XII-i) is selected such that the molecular weight of the (XII-i) portion is about 4 kDa. In certain embodiments, y in formula (XII-i) is selected such that the molecular weight of the (XII-i) portion is about 5 kDa. In certain embodiments, y in formula (XII-i) is selected such that the molecular weight of the (XII-i) portion is about 6 kDa. In certain embodiments, y in formula (XII-i) is selected such that the molecular weight of the (XII-i) portion is about 7 kDa. In certain embodiments, y in formula (XII-i) is selected such that the molecular weight of the (XII-i) portion is about 8 kDa. In certain embodiments, y in formula (XII-i) is selected such that the molecular weight of the (XII-i) portion is about 9 kDa. In certain embodiments, y in formula (XII-i) is selected such that the molecular weight of the (XII-i) portion is about 10 kDa. In certain embodiments, y in formula (XII-i) is selected such that the molecular weight of the (XII-i) portion is about 11 kDa. In certain embodiments, y in formula (XII-i) is selected such that the molecular weight of the (XII-i) portion is about 12 kDa. In certain embodiments, y in formula (XII-i) is selected such that the molecular weight of the (XII-i) portion is about 13 kDa. In certain embodiments, y in formula (XII-i) is selected such that the molecular weight of the (XII-i) portion is about 14 kDa. In certain embodiments, y in formula (XII-i) is selected such that the molecular weight of the (XII-i) portion is about 15 kDa. In certain embodiments, y in formula (XII-i) is selected such that the molecular weight of the (XII-i) portion is about 20 kDa. In certain embodiments, y in formula (XII-i) is selected such that the molecular weight of the (XII-i) portion is about 25 kDa.In certain embodiments, y in formula (XII-i) is selected such that the molecular weight of the (XII-i) portion is approximately 30 kDa. In certain embodiments, y in formula (XII-i) is selected such that the molecular weight of the (XII-i) portion is approximately 40 kDa.

[0413] In certain embodiments, y in formula (XII-i) is 2. In certain embodiments, y in formula (XII-i) is about 22. In certain embodiments, y in formula (XII-i) is about 45. In certain embodiments, y in formula (XII-i) is about 68. In certain embodiments, y in formula (XII-i) is about 91. In certain embodiments, y in formula (XII-i) is about 113. In certain embodiments, y in formula (XII-i) is about 136. In certain embodiments, y in formula (XII-i) is about 160. In certain embodiments, y in formula (XII-i) is about 182. In certain embodiments, y in formula (XII-i) is about 204. In certain embodiments, y in formula (XII-i) is about 227. In certain embodiments, y in formula (XII-i) is about 250. In certain embodiments, y in formula (XII-i) is about 340. In certain embodiments, y in formula (XII-i) is about 455. In certain embodiments, y in formula (XII-i) is about 910.

[0414] In certain embodiments, -L 2 - is equation (XII-ii) [ka] (In the formula, The dashed line with an asterisk indicates -L 1 - indicates binding to Unmarked dashed lines are -AB 1 This shows a connection to, a is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15. b is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15. c is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15. x is in the range of 2 to 1000. -R 1 and -R 2 These are, independently of each other, -H and C 1-6 (Selected from the group consisting of alkyl groups) It belongs to them.

[0415] In certain embodiments, x in formula (XII-ii) is 2. In certain embodiments, x in formula (XII-ii) is about 22. In certain embodiments, x in formula (XII-ii) is about 45. In certain embodiments, x in formula (XII-ii) is about 68. In certain embodiments, x in formula (XII-ii) is about 91. In certain embodiments, x in formula (XII-ii) is about 113. In certain embodiments, x in formula (XII-ii) is about 136. In certain embodiments, x in formula (XII-ii) is about 160. In certain embodiments, x in formula (XII-ii) is about 182. In certain embodiments, x in formula (XII-ii) is about 204. In certain embodiments, x in formula (XII-ii) is about 227. In certain embodiments, x in formula (XII-ii) is about 250. In certain embodiments, x in formula (XII-ii) is about 340. In certain embodiments, x in formula (XII-ii) is about 455. In certain embodiments, x in formula (XII-ii) is about 910.

[0416] In a particular embodiment, a in formula (XII-ii) is 5, b in formula (XII-ii) is 2, c in formula (XII-ii) is 2, and -R in formula (XII-ii) is 5. 1 and -R 2 Both are -H.

[0417] In certain embodiments, the albumin-binding moiety of the compounds disclosed herein binds to one albumin, for example, via different binding domains. Preferably, the albumin-binding moiety of the compounds disclosed herein binds to at least two albumins, for example, two albumins.

[0418] In certain embodiments, -L 1 -L 2 - is selected from the following group: [ka] (In the formula, The dashed line with an asterisk indicates the bond to nitrogen of -D-. Unmarked dashed lines are -AB 1 (Shows a connection to).

[0419] In certain embodiments, -L 1 -L 2 - is of formula (XIa). In certain embodiments, -L 1 -L 2 - is of formula (XIb). In certain embodiments, -L 1 -L 2 - is of formula (XIc). In certain embodiments, -L 1 -L 2 - is of formula (XId). In certain embodiments, -L 1 -L 2 - is of formula (XIe). In certain embodiments, -L 1 -L 2 - is from the expression (XIf).

[0420] In certain embodiments, -L 1 -L 2 - is selected from the following group: [ka] (In the formula, The dashed line with an asterisk indicates the bond to nitrogen of -D-. Unmarked dashed lines are -AB 1 (Shows a connection to).

[0421] In certain embodiments, -L 1 -L 2 - is of formula (Xia'). In certain embodiments, -L 1 -L 2 - is from formula (XIb'). In certain embodiments, -L 1 -L 2 - is of formula (XIc'). In certain embodiments, -L 1 -L 2 - is of formula (XId'). In certain embodiments, -L 1 -L 2 - is of formula (XIe'). In certain embodiments, -L 1 -L 2 - is from the expression (XIf').

[0422] In certain embodiments, -L 1 -L 2 - is selected from the following group: [ka] (In the formula, The dashed line with an asterisk indicates the bond to nitrogen of -D-. Unmarked dashed lines are -AB 1 (Shows a connection to).

[0423] In certain embodiments, -L 1 -L 2 - is of formula (Xia''). In certain embodiments, -L 1 -L 2 - is of formula (XIb''). In certain embodiments, -L 1 -L 2 - is of formula (XIc''). In certain embodiments, -L 1 -L 2- is of formula (XId''). In certain embodiments, -L 1 -L 2 - is of formula (XIe''). In certain embodiments, -L 1 -L 2 - is from the expression (XIf').

[0424] In certain embodiments, -L 1 -L 2 - is selected from the following group: [ka] (In the formula, The dashed line with an asterisk indicates the bond to nitrogen of -D-. Unmarked dashed lines are -AB 1 (Shows a connection to).

[0425] In certain embodiments, -L 1 -L 2 - is of formula (XIg). In certain embodiments, -L 1 -L 2 - is of formula (XIh). In certain embodiments, -L 1 -L 2 - is of formula (XIi). In certain embodiments, -L 1 -L 2 - is of formula (XIj). In certain embodiments, -L 1 -L 2 - is of formula (XIk). In certain embodiments, -L 1 -L 2 - is from equation (XIl).

[0426] In certain embodiments, -L 1 -L 2 - is selected from the following group: [ka] (In the formula, The dashed line with an asterisk indicates the bond to nitrogen of -D-. Unmarked dashed lines are -AB 1 (Shows a connection to).

[0427] In certain embodiments, -L 1 -L 2 - is from formula (XIg'). In certain embodiments, -L 1 -L 2 - is of formula (XIh'). In certain embodiments, -L 1 -L 2 - is of formula (XIi'). In certain embodiments, -L 1 -L 2 - is of formula (XIj'). In certain embodiments, -L 1 -L 2 - is of formula (XIk'). In certain embodiments, -L 1 -L 2 - is from equation (XIl').

[0428] In certain embodiments, -L 1 -L 2 - is selected from the following group: [ka] (In the formula, The dashed line with an asterisk indicates the bond to nitrogen of -D-. Unmarked dashed lines are -AB 1 (Shows a connection to).

[0429] In certain embodiments, -L 1 -L 2 - is of formula (XIg''). In certain embodiments, -L 1 -L 2 - is of formula (XIh''). In certain embodiments, -L 1 -L 2 - is of formula (XIi''). In certain embodiments, -L 1 -L 2- is of formula (XIj''). In certain embodiments, -L 1 -L 2 - is of formula (XIk''). In certain embodiments, -L 1 -L 2 - is from equation (XIl'').

[0430] In certain embodiments, the compound is of formula (XIII) [ka] [In the formula, a is 14, 15, 16, 17, 18, 19, 20, 21, or 22. n is an integer between 2 and 1000. The dashed line indicates a part. [ka] (In the formula, Unmarked dashed lines indicate connections to dashed lines in equation (XIII), (The dashed line with an asterisk indicates a connection to -D-) [Shows a connection to] It belongs to them.

[0431] In a particular embodiment, the compound is of formula (XIII), where a is 18, n is 2, and the dashed line with an asterisk indicates the bond to the N-terminal amine functional group of the semaglutide.

[0432] In a particular embodiment, the compound is of formula (XIII), where a is 16, n is 2, and the dashed line with an asterisk indicates the bond to the N-terminal amine functional group of the semaglutide.

[0433] In certain embodiments, the compound is of formula (XIII), where a is 18, n is approximately 23, and the dashed line with an asterisk indicates the bond to the N-terminal amine functional group of the semaglutide.

[0434] In a particular embodiment, the compound is of formula (XIII), where a is 16, n is approximately 23, and the dashed line with an asterisk indicates the bond to the N-terminal amine functional group of the semaglutide.

[0435] In a particular embodiment, the compound is of formula (XIII), where a is 18, n is approximately 108, and the dashed line with an asterisk indicates the bond to the N-terminal amine functional group of the semaglutide.

[0436] In a particular embodiment, the compound is of formula (XIII), where a is 16, n is approximately 108, and the dashed line with an asterisk indicates the bond to the N-terminal amine functional group of the semaglutide.

[0437] In a particular embodiment, part AB 1 - and -AB 2 The distance between them is such that they can bind to two different albumin binding domains, or to two different binding domains of the same albumin. In certain embodiments, partial AB 1 - and -AB 2 The distance between them is such that they can bind to the binding domains of two different albumins.

[0438] In another embodiment, the present invention relates to a pharmaceutical composition comprising at least one compound of the present invention or a pharmaceutically acceptable salt thereof and at least one excipient.

[0439] In another embodiment, the present invention relates to the compounds of the present invention or pharmaceutically acceptable salts thereof or pharmaceutical compositions of the present invention for use as pharmaceuticals, optionally in combination with one or more additional therapeutically active compounds.

[0440] The present invention also relates to the compounds of the present invention, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions for use as pharmaceuticals.

[0441] The present invention also relates to the compounds of the present invention, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions for use in the manufacture of pharmaceuticals.

[0442] Such medicines include HD-AB 2 It can be used in the treatment or prevention of diseases that can be treated or prevented using this method.

[0443] Another aspect of the present invention is HD-AB, which may be combined with one or more additional therapeutically active compounds. 2 The present invention relates to a compound or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing the compound of the present invention, for use in methods of treating or preventing diseases that can be treated or prevented using a pharmaceutically acceptable salt thereof.

[0444] In another embodiment, the present invention is HD-AB 2 A method for treating a patient having a disease that can be treated or prevented using the present invention, comprising the step of administering to a patient in need a pharmaceutically acceptable amount of the present invention or a pharmaceutically acceptable salt thereof or a pharmaceutical composition, optionally in combination with one or more additional therapeutically active compounds.

[0445] The compounds of the present invention, their pharmaceutically acceptable salts, or pharmaceutical compositions may be administered by topical methods, injections, or infusions, such as intra-articular, peri-articular, intradermal, subcutaneous, intramuscular, intravenous, intraosseous, intraperitoneal, intramedullary, intracapsular, intraorbital, intratympanic, intravesical, intracardiac, transtracheal, subepidermal, subcapsular, intraarachnoid, intraspinal, intraventricular, intrasternal injections and infusions; direct delivery to the brain via implantable devices (e.g., Onmaya reservoirs) enabling delivery of the present invention to brain tissue or cerebral fluid; direct intraventricular injection or infusion; injection or infusion into the brain or brain-related regions; injection into the subchoroidal space; posterior orbital injection and ophthalmic instillation. In certain embodiments, the pharmaceutical is for subcutaneous injection, which can be done using a pen-type syringe or via a syringe.

[0446] -D- or -D-AB 2Compounds in which the GLP-1 receptor agonist moiety is or pharmaceutically acceptable salts thereof, or pharmaceutical compositions comprising such compounds, can be used for the treatment or prevention of diseases selected from the group consisting of (i) all forms of diabetes mellitus, (ii) obesity, (iii) non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), (iv) cardiovascular disease, (v) neurodegenerative disorders, (vi) chronic kidney disease (CKD), (vii) diabetic nephropathy (DKD), (viii) peripheral artery disease (PAD), and / or (ix) heart failure (HF).

[0447] Exemplary cardiovascular diseases may be selected from the group consisting of X syndrome, atherosclerosis, myocardial infarction, coronary heart disease, reperfusion injury, stroke, cerebral ischemia, early heart disease or early cardiovascular disease, left ventricular hypertrophy, coronary artery disease, hypertension, essential hypertension, acute hypertensive emergency, cardiomyopathy, cardiac dysfunction, exercise intolerance, acute and / or chronic heart failure, arrhythmia, dysregulation, syncope, angina pectoris, cardiac bypass and / or stent reocclusion, intermittent claudication (obstructive arteriosclerosis), diastolic dysfunction and / or systolic dysfunction; and hypotension such as hypotension.

[0448] -D- or -D-AB 2 Compounds in which the GLP-1 receptor agonist moiety is or pharmaceutically acceptable salts thereof, or pharmaceutical compositions containing such compounds, may be used in the treatment or prevention of diseases selected from the group consisting of dyslipidemia and / or diseases in which one or more of the following clinical outcomes are the treatment target: reduction of total serum lipids; increase of HDL; reduction of small, high-density LDL; reduction of VLDL; reduction of triglycerides; reduction of cholesterol; reduction of plasma levels of lipoprotein a (Lp(a)) in humans; inhibition of apolipoprotein A (apo(A)) production.

[0449] Exemplary neurodegenerative disorders can be selected from the group consisting of Alzheimer's disease and Parkinson's disease.

[0450] Exemplary forms of HF can be selected from the group consisting of heart failure with reduced ejection fraction (HFrEF), heart failure with mildly reduced ejection fraction (HFmrEF), and heart failure with preserved ejection fraction (HFpEF).

[0451] -D- or -D-AB 2 Compounds in which the GLP-1 receptor agonist moiety is located, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions containing such compounds, can be used for the treatment of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

[0452] -D- or -D-AB 2 Compounds in which the GLP-1 receptor agonist moiety is or pharmaceutically acceptable salts thereof, or pharmaceutical compositions comprising such compounds, can in certain embodiments be used for the treatment of diseases selected from the group consisting of obesity and eating disorders, where one or more of the following clinical outcomes are the treatment target: reduced food intake, increased energy expenditure, weight loss, appetite suppression, and satiety induction.

[0453] -D- or -D-AB 2Compounds in which the GLP-1 receptor agonist moiety is or pharmaceutically acceptable salts thereof, or pharmaceutical compositions containing such compounds, may also be combined with one or more additional drugs, such as drugs selected from cardiovascular agents, antidiabetic agents, and / or anti-obesity agents. Examples of these pharmacologically active substances include circulatory agents, β-adrenergic receptor blockers, HMG-CoA reductase inhibitors, angiotensin II receptor antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, endothelin antagonists, renin inhibitors, diuretics, aldosterone receptor blockers, endothelin receptor blockers, aldosterone synthase inhibitors, CETP inhibitors, relaxin, PCSK9 inhibitors, BNP and NEP inhibitors, GLP-1 analogs, insulin, sulfonylurea, biguanides, meglitinide, glucosidase inhibitors, glucagon antagonists, DPP-IV inhibitors, and SGLT2 inhibitors. The compounds of the present invention, their pharmaceutically acceptable salts, or pharmaceutical compositions may also be used in combination with cardiac surgery.

[0454] -D-AB 2 The compounds of the present invention, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions, in which the compound is a GLP-1 receptor agonist, may also be administered in combination with a growth hormone, such as human growth hormone. Such human growth hormone may be in the form of an unmodified drug, such as human growth hormone of SEQ ID NO: 58, or as a conjugate or complex containing human growth hormone. Preferably, -D-AB 2 Compounds that are GLP-1 receptor agonists have the following structure: [ka] (In the formula, D is the human growth hormone polypeptide of SEQ ID NO: 58, which is bound to the rest of the molecule via an amine functional group provided by the lysine side chain. (Each p1, p2, p3, and p4 is an integer between 210 and 240, independently.) It is administered to patients in combination with lonapegsomatropin, which has the properties of lonapegsomatropin.

[0455] Sequence ID 58 has the following sequence: FPTIPLSRLFDNAMLRAHRLHQLAFDTYQEFEEAYIPKEQKYSFLQNPQTSLCFSESIPTPSNREETQQKSNLELLRISLLLIQSWLEPVQFLRSVFANSLVYGASDSNVYDLLKDLEEGIQTLMGRLEDGSPRTGQIFKQTYSKFDTNSHNDDALLKNYGLLYCFRKDMDKVETFLRIVQCRSVEGSCGF In such combination therapies, -D-AB 2 Compounds that are GLP-1 receptor agonists can be administered before, simultaneously with, or after the administration of unmodified human growth hormone, a conjugate containing human growth hormone, or a complex containing human growth hormone.

[0456] The compounds of the present invention, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions may be administered once a week, every two weeks, every three weeks, or once a month, for example, by subcutaneous administration.

[0457] In certain embodiments, the compound of the present invention or a pharmaceutically acceptable salt thereof or pharmaceutical composition may be administered once a week, every two weeks, every three weeks, or once a month.

[0458] The present invention can be further described by the following non-limiting items.

[0459] 1. Equation (Ia) or (Ib) [ka] (In the formula, Each -D- is an independent drug portion. Each-AB 1 and -AB 2 This is an independently albumin-binding moiety, Each-L 1- is a linker portion that is independently and covalently and reversibly bonded to -D-. Each-L 2 - is either an independent spacer or does not exist. x is an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, and 25. (y is an integer selected from the group consisting of 2, 3, 4, and 5.) A compound of or a pharmaceutically acceptable salt thereof.

[0460] 2. The compound of item 1 or a pharmaceutically acceptable salt thereof, wherein the compound is of formula (Ia).

[0461] 3. A compound of item 1 or 2, or a pharmaceutically acceptable salt thereof, where x is 1.

[0462] 4. -D- or -D-AB 2 One of the compounds listed in items 1-3, or a pharmaceutically acceptable salt thereof, wherein the GLP-1 receptor agonist moiety is the GLP-1 receptor agonist portion.

[0463] 5. -D-AB 2 One of the compounds listed in items 1-4, or a pharmaceutically acceptable salt thereof, wherein the compound is semaglutide.

[0464] 6. -L 1 - is one of the compounds listed in items 1-5, or a pharmaceutically acceptable salt thereof, of formula (XIIb).

[0465] 7. -L 1 - is one of the compounds listed in items 1-5, or a pharmaceutically acceptable salt thereof, of which is of formula (XIIa).

[0466] 8. -L 1 - is one of the compounds from items 1-5 or 7, or a pharmaceutically acceptable salt thereof, of formula (XIIa-i).

[0467] 9. -L1 - is one of the compounds from items 1-5, 7, or 8, or a pharmaceutically acceptable salt thereof, of formula (XIIa-ii).

[0468] 10. -L 1 - is one of the compounds from items 1-5, 7, or 8, or a pharmaceutically acceptable salt thereof, of formula (XIIa-iii).

[0469] 11. -L 1 - is one of the compounds listed in items 1-5, or a pharmaceutically acceptable salt thereof, which is of formula (II).

[0470] 12. -R in equation (II) 1 and R 1a A compound of item 11 or a pharmaceutically acceptable salt thereof, wherein both atoms are -H.

[0471] 13. -R in equation (II) 1 Since is -H, R in equation (II) 1a A compound of item 11 or a pharmaceutically acceptable salt thereof, wherein the compound is methyl.

[0472] 14. -R in equation (II) 1 and R 1a A compound of item 11 or a pharmaceutically acceptable salt thereof, wherein both are methyl.

[0473] 15. -R in equation (II) 1 and R 1a A compound of item 11 or a pharmaceutically acceptable salt thereof, wherein both atoms are -H.

[0474] 16. Equation (II) -X- is -C(R 7 R 7a ) - one of the compounds listed in items 11-15 or a pharmaceutically acceptable salt thereof.

[0475] 17. Equation (II) -X- is -C(R 4 R 4a ) - one of the compounds listed in items 11-15 or a pharmaceutically acceptable salt thereof.

[0476] 18. Equation (II) -X- is -C(R 4 R 4a )-C(R 5 R 5a ) - one of the compounds listed in items 11-15 or a pharmaceutically acceptable salt thereof.

[0477] 19. -R in equation (II) 7 ga-NR 10 -(C=O)-R 11 The compound of item 16 or a pharmaceutically acceptable salt thereof.

[0478] 20. -R in equation (II) 7 ga-N(R 10 R 10a ) the compound of item 16 or a pharmaceutically acceptable salt thereof.

[0479] 21. -R in equation (II) 10 Compounds of item 19 or 20 or pharmaceutically acceptable salts thereof, wherein the compound is methyl.

[0480] 22. -R in equation (II) 10 A compound of item 19 or 20, or a pharmaceutically acceptable salt thereof, wherein the compound is H.

[0481] 23. -R in equation (II) 10a A compound from any of items 20-22 or a pharmaceutically acceptable salt thereof, wherein the compound is -H.

[0482] 24. -R in equation (II) 10a One of the compounds listed in items 20-22, or a pharmaceutically acceptable salt thereof, wherein the compound is methyl.

[0483] 25. -R in equation (II) 11 However, -L 2 A compound from any one of items 16, 19, or 21-23, or a pharmaceutically acceptable salt thereof, which is a -H substituted with -.

[0484] 26. X in equation (II)1 A compound from any of items 11-25, or a pharmaceutically acceptable salt thereof, wherein C is present.

[0485] 27. Equation (II) = X 3 A compound from any of items 11-26 or a pharmaceutically acceptable salt thereof, wherein the compound is O.

[0486] 28. -X in equation (II) 2 -ga-C(R 8 R 8a )-C(R 9 R 9a ) - one of the compounds listed in items 11-27 or a pharmaceutically acceptable salt thereof.

[0487] 29. -X in equation (II) 2 -ga-C(R 8 R 8a ) - one of the compounds listed in items 11-27 or a pharmaceutically acceptable salt thereof.

[0488] 30. -R in equation (II) 8 and -R 8a A compound of item 28 or 29, or a pharmaceutically acceptable salt thereof, where both atoms are -H.

[0489] 31. -R in equation (II) 9 and -R 9a Compounds of item 28 or 30 or pharmaceutically acceptable salts thereof, where both are -H.

[0490] 32. -R in equation (II) 2 and -R 2a One of the compounds from items 11-31 or a pharmaceutically acceptable salt thereof, where both atoms are -H.

[0491] 33. -R in equation (II) 2 is methyl, and -R of formula (II) 2a A compound from any of items 11-31 or a pharmaceutically acceptable salt thereof, wherein the ion is -H.

[0492] 34. -R in equation (II) 2 and -R 2a One of the compounds from items 11-31, or a pharmaceutically acceptable salt thereof, where both are methyl.

[0493] 35. -R in equation (II) 2 and -R 2a One of the compounds from items 11-34, or a pharmaceutically acceptable salt thereof, where both are methyl.

[0494] 36. -R in equation (II) 2 and -R 2a One of the compounds from items 11-34 or a pharmaceutically acceptable salt thereof, where both atoms are -H.

[0495] 37. -R in equation (II) 2 is methyl, and -R of formula (II) 2a A compound from any of items 11-34 or a pharmaceutically acceptable salt thereof, wherein the compound is -H.

[0496] 38. -L 1 - is one of the compounds listed in items 1-5, or a pharmaceutically acceptable salt thereof, which is of formula (III).

[0497] 39. -L 1 - is one of the compounds listed in items 1-5, or a pharmaceutically acceptable salt thereof, which is of formula (IV).

[0498] 40. -L 1 - is one of the compounds listed in items 1-5, or a pharmaceutically acceptable salt thereof, which is of formula (V).

[0499] 41. -L 1 - is one of the compounds from items 1-5 or a pharmaceutically acceptable salt thereof, wherein - is of formula (VI).

[0500] 42. -L 1 - is one of the compounds listed in items 1-5 or a pharmaceutically acceptable salt thereof, wherein - is of formula (VII).

[0501] 43. -L 1 - is one of the compounds listed in items 1-5, or a pharmaceutically acceptable salt thereof, which is of formula (VIII).

[0502] 44. -L 1 - is one of the compounds listed in items 1-5, or a pharmaceutically acceptable salt thereof, which is of formula (IX).

[0503] 45. -L 1 - is one of the compounds from items 1-5 or a pharmaceutically acceptable salt thereof, wherein - is of formula (X).

[0504] 46. ​​-L 1 One of the compounds from items 1 to 45, or a pharmaceutically acceptable salt thereof, in which - is conjugated to the N-terminal amine functional group of -D-.

[0505] 47. -AB 1 One of the compounds listed in items 1-46, or a pharmaceutically acceptable salt thereof, having the formula (A).

[0506] 48. -F in equation (A) 0 However, formulas (a-4), (a-5), (a-6), (a-7), (a-8), (a-9), (a-10), (a-11), (a-12), (a-13), (a-1 4), (a-15), (a-16), (a-17), (a-18), (a-19), (a-20), (a-21), (a-22), (a-23), (a-24 Compounds of item 47 or pharmaceutically acceptable salts thereof, selected from the group consisting of (a-25), (a-26), (a-27), (a-28), (a-29), (a-30), (a-31), (a-32), (a-33), (a-34), (a-35), (a-36), (a-37), (a-38), and (a-39).

[0507] 49. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, wherein the compound is of formula (a-4).

[0508] 50. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-5).

[0509] 51. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, wherein the compound is of formula (a-6).

[0510] 52. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-7).

[0511] 53. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-8).

[0512] 54. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-9).

[0513] 55. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-10).

[0514] 56. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-11).

[0515] 57. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-12).

[0516] 58. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-13).

[0517] 59. -F in equation (A) 0A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-14).

[0518] 60. -F of equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-15).

[0519] 61. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-16).

[0520] 62. -F of equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-17).

[0521] 63. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-18).

[0522] 64. -F of equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-19).

[0523] 65. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-20).

[0524] 66. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-21).

[0525] 67. -F of equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-22).

[0526] 68. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-23).

[0527] 69. -F of equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-24).

[0528] 70. -F of equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-25).

[0529] 71. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-26).

[0530] 72. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-27).

[0531] 73. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-28).

[0532] 74. -F of equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-29).

[0533] 75. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-30).

[0534] 76. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-31).

[0535] 77. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-32).

[0536] 78. -F of equation (A) 0A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-33).

[0537] 79. -F of equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-34).

[0538] 80. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-35).

[0539] 81. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-36).

[0540] 82. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-37).

[0541] 83. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-38).

[0542] 84. -F in equation (A) 0 A compound of item 47 or 48 or a pharmaceutically acceptable salt thereof, which is of formula (a-39).

[0543] 85. -L in equation (A) A - Not present is any one compound from items 1-84 or a pharmaceutically acceptable salt thereof.

[0544] 86. -L in equation (A) A- is the formula (a-40), (a-41), (a-42), (a-43), (a-44), (a-45), (a-46), (a-47), (a-48), (a-49), (a-50), (a-51) , (a-52), (a-53), (a-54), (a-55), (a-56), (a-57), (a-58), (a-59), (a-60), (a-61), (a-62), (a-63), (a- One compound from items 47 to 84, or a pharmaceutically acceptable salt thereof, selected from the group consisting of (a-65), (a-66), (a-67), (a-68), (a-69), (a-70), (a-71), (a-72), (a-73), (a-74), (a-75), (a-76), (a-77), (a-78), (a-79), (a-80), (a-81), and (a-82).

[0545] 87. -L in equation (A) A - is a compound or a pharmaceutically acceptable salt thereof from any one of items 47-84 or 86, wherein - is of formula (a-40).

[0546] 88. -L in equation (A) A - is a compound or a pharmaceutically acceptable salt thereof from any one of items 47-84 or 86, which is of formula (a-41).

[0547] 89. -L in equation (A) A - is a compound or a pharmaceutically acceptable salt thereof from any one of items 47-84 or 86, which is of formula (a-42).

[0548] 90. -L in equation (A) A - is a compound or a pharmaceutically acceptable salt thereof from any one of items 47-84 or 86, which is of formula (a-43).

[0549] 91. -L in equation (A) A - is a compound or a pharmaceutically acceptable salt thereof from any one of items 47-84 or 86, wherein - is of formula (a-44).

[0550] 92. -L in equation (A) A- is a compound or a pharmaceutically acceptable salt thereof from any one of items 47-84 or 86, wherein - is of formula (a-45).

[0551] 93. -L in equation (A) A - is a compound or a pharmaceutically acceptable salt thereof from any one of items 47-84 or 86, wherein - is of formula (a-46).

[0552] 94. -L in equation (A) A - is a compound or a pharmaceutically acceptable salt thereof from any one of items 47-84 or 86, wherein - is of formula (a-47).

[0553] 95. -L in equation (A) A - is a compound or a pharmaceutically acceptable salt thereof from any one of items 47-84 or 86, wherein - is of formula (a-48).

[0554] 96. -L in equation (A) A - is a compound or a pharmaceutically acceptable salt thereof from any one of items 47-84 or 86, which is of formula (a-49).

[0555] 97. -L in equation (A) A - is one of the compounds from items 47-84 or 86, or a pharmaceutically acceptable salt thereof, which is of formula (a-50).

[0556] 98. -L in equation (A) A - is one of the compounds from items 47-84 or 86, or a pharmaceutically acceptable salt thereof, which is of formula (a-51).

[0557] 99. -L in equation (A) A - is a compound or a pharmaceutically acceptable salt thereof from any one of items 47-84 or 86, which is of formula (a-52).

[0558] 100. -L in equation (A) A - is a compound or a pharmaceutically acceptable salt thereof from any one of items 47-84 or 86, which is of formula (a-53).

[0559] 101. -L in equation (A) A - is one of the compounds in items 47-84 or 86, or a pharmaceutically acceptable salt thereof, which is of formula (a-54).

[0560] 102. -L in equation (A) A - is one of the compounds from items 47-84 or 86, or a pharmaceutically acceptable salt thereof, which is of formula (a-55).

[0561] 103. -L in equation (A) A - is a compound from any one of items 47-84 or 86, or a pharmaceutically acceptable salt thereof, of formula (a-56).

[0562] 104. -L in equation (A) A - is one of the compounds from items 47-84 or 86, or a pharmaceutically acceptable salt thereof, which is of formula (a-57).

[0563] 105. -L in equation (A) A - is one of the compounds from items 47-84 or 86, or a pharmaceutically acceptable salt thereof, which is of formula (a-58).

[0564] 106. -L in equation (A) A - is one of the compounds from items 47-84 or 86, or a pharmaceutically acceptable salt thereof, which is of formula (a-59).

[0565] 107. -L in equation (A) A - is one of the compounds from items 47-84 or 86, or a pharmaceutically acceptable salt thereof, which is of formula (a-60).

[0566] 108. -L in equation (A) A - is one of the compounds from items 47-84 or 86, or a pharmaceutically acceptable salt thereof, which is of formula (a-61).

[0567] 109. -L in equation (A) A- is a compound from any one of items 47-84 or 86, or a pharmaceutically acceptable salt thereof, of formula (a-62).

[0568] 110. -L in equation (A) A - is a compound or a pharmaceutically acceptable salt thereof from any one of items 47-84 or 86, which is of formula (a-63).

[0569] 111. -L in equation (A) A - is a compound or a pharmaceutically acceptable salt thereof from any one of items 47-84 or 86, which is of formula (a-64).

[0570] 112. -L in equation (A) A - is one of the compounds from items 47-84 or 86, or a pharmaceutically acceptable salt thereof, which is of formula (a-65).

[0571] 113. -L in equation (A) A - is a compound from any one of items 47-84 or 86, or a pharmaceutically acceptable salt thereof, of formula (a-66).

[0572] 114. -L in equation (A) A - is one of the compounds from items 47-84 or 86, or a pharmaceutically acceptable salt thereof, which is of formula (a-67).

[0573] 115. -L in equation (A) A - is one of the compounds from items 47-84 or 86, or a pharmaceutically acceptable salt thereof, which is of formula (a-68).

[0574] 116. -L in equation (A) A - is one of the compounds from items 47-84 or 86, or a pharmaceutically acceptable salt thereof, which is of formula (a-69).

[0575] 117. -L in equation (A) A - is one of the compounds from items 47-84 or 86, or a pharmaceutically acceptable salt thereof, which is of formula (a-70).

[0576] 118. -L in equation (A) A - is a compound or a pharmaceutically acceptable salt thereof from any one of items 47-84 or 86, which is of formula (a-71).

[0577] 119. -L in equation (A) A - is a compound or a pharmaceutically acceptable salt thereof from any one of items 47-84 or 86, which is of formula (a-72).

[0578] 120. -L in equation (A) A - is a compound or a pharmaceutically acceptable salt thereof from any one of items 47-84 or 86, which is of formula (a-73).

[0579] 121. -L in equation (A) A - is one of the compounds from items 47-84 or 86, or a pharmaceutically acceptable salt thereof, which is of formula (a-74).

[0580] 122. -L in equation (A) A - is one of the compounds from items 47-84 or 86, or a pharmaceutically acceptable salt thereof, which is of formula (a-75).

[0581] 123. -L in equation (A) A - is a compound or a pharmaceutically acceptable salt thereof from any one of items 47-84 or 86, which is of formula (a-76).

[0582] 124. -L in equation (A) A - is one of the compounds from items 47-84 or 86, or a pharmaceutically acceptable salt thereof, which is of formula (a-77).

[0583] 125. -L in equation (A) A - is one of the compounds from items 47-84 or 86, or a pharmaceutically acceptable salt thereof, which is of formula (a-78).

[0584] 126. -L in equation (A) A- is one of the compounds from items 47-84 or 86, or a pharmaceutically acceptable salt thereof, which is of formula (a-79).

[0585] 127. -L in equation (A) A - is a compound or a pharmaceutically acceptable salt thereof from any one of items 47-84 or 86, which is of formula (a-80).

[0586] 128. -L in equation (A) A - is a compound or a pharmaceutically acceptable salt thereof from any one of items 47-84 or 86, which is of formula (a-81).

[0587] 129. -L in equation (A) A - is a compound from any one of items 47-84 or 86, or a pharmaceutically acceptable salt thereof, of formula (a-82).

[0588] 130. -L in equation (A) B - One of the compounds from items 47-129 or a pharmaceutically acceptable salt thereof, if none of the above are present.

[0589] 131. -L in equation (A) B - is one compound from items 47 to 129 or a pharmaceutically acceptable salt thereof, selected from the group consisting of formulas (a-83), (a-84), (a-85), (a-86), (a-87), (a-88), (a-89), (a-90), (a-91), (a-92), (a-93), and (a-94).

[0590] 132. -L in equation (A) B - is one of the compounds from items 47-129 or 131, or a pharmaceutically acceptable salt thereof, which is of formula (a-83).

[0591] 133. -L in equation (A) B - is one of the compounds from items 47-129 or 131, or a pharmaceutically acceptable salt thereof, which is of formula (a-84).

[0592] 134. The compound of item 133 or a pharmaceutically acceptable salt thereof, wherein q in formula (a-84) is an integer between 3 and 45.

[0593] 135. Compounds of item 133 or 134 or pharmaceutically acceptable salts thereof, wherein q in formula (a-84) is an integer between 4 and 40.

[0594] 136. One compound from items 133-135 or a pharmaceutically acceptable salt thereof, in which q in formula (a-84) is an integer (inter) between 5 and 35.

[0595] 137. One compound from items 133-136 or a pharmaceutically acceptable salt thereof, in which q in formula (a-84) is an integer between 6 and 30.

[0596] 138. One compound from items 133-137 or a pharmaceutically acceptable salt thereof, in which q in formula (a-84) is an integer between 7 and 25.

[0597] 139. One compound from items 133-138 or a pharmaceutically acceptable salt thereof, in which q in formula (a-84) is an integer between 10 and 20.

[0598] 140. One compound from items 133-138 or a pharmaceutically acceptable salt thereof, in which q in formula (a-84) is 23.

[0599] 141. -L in equation (A) B - is one of the compounds from items 47-129 or 131, or a pharmaceutically acceptable salt thereof, which is of formula (a-85).

[0600] 142. -L in equation (A) B - is one of the compounds from items 47-129 or 131, or a pharmaceutically acceptable salt thereof, which is of formula (a-86).

[0601] 143. -L in equation (A) B- is one of the compounds from items 47-129 or 131, or a pharmaceutically acceptable salt thereof, which is of formula (a-87).

[0602] 144. -L in equation (A) B - is one of the compounds from items 47-129 or 131, or a pharmaceutically acceptable salt thereof, which is of formula (a-88).

[0603] 145. -L in equation (A) B - is one of the compounds from items 47-129 or 131, or a pharmaceutically acceptable salt thereof, which is of formula (a-89).

[0604] 146. -L in equation (A) B - is one of the compounds from items 47-129 or 131, or a pharmaceutically acceptable salt thereof, of formula (a-90).

[0605] 147. -L in equation (A) B - is one of the compounds from items 47-129 or 131, or a pharmaceutically acceptable salt thereof, of formula (a-91).

[0606] 148. -L in equation (A) B - is one of the compounds from items 47-129 or 131, or a pharmaceutically acceptable salt thereof, of formula (a-92).

[0607] 149. -L in equation (A) B - is one of the compounds from items 47-129 or 131, or a pharmaceutically acceptable salt thereof, which is of formula (a-93).

[0608] 150. -L in equation (A) B - is one of the compounds from items 47-129 or 131, or a pharmaceutically acceptable salt thereof, which is of formula (a-84).

[0609] 151. -AB 1 A compound from any of items 1-47 or a pharmaceutically acceptable salt thereof, wherein the compound is of formula (i).

[0610] 152. The compound of item 151 or a pharmaceutically acceptable salt thereof, wherein n in formula (i) is 14.

[0611] 153. The compound of item 151 or a pharmaceutically acceptable salt thereof, wherein n in formula (i) is 15.

[0612] 154. The compound of item 151 or a pharmaceutically acceptable salt thereof, wherein n in formula (i) is 16.

[0613] 155. The compound of item 151 or a pharmaceutically acceptable salt thereof, wherein n in formula (i) is 17.

[0614] 156. The compound of item 151 or a pharmaceutically acceptable salt thereof, wherein n in formula (i) is 18.

[0615] 157. The compound of item 151 or a pharmaceutically acceptable salt thereof, wherein n in formula (i) is 19.

[0616] 158. The compound of item 151 or a pharmaceutically acceptable salt thereof, wherein n in formula (i) is 20.

[0617] 159. The compound of item 151 or a pharmaceutically acceptable salt thereof, wherein n in formula (i) is 21.

[0618] 160. The compound of item 151 or a pharmaceutically acceptable salt thereof, wherein n in formula (i) is 22.

[0619] 161. Any one compound from items 151-160, or a pharmaceutically acceptable salt thereof, in which the stereocenter marked with an asterisk is in the R configuration.

[0620] 162. Any one compound from items 151-160, or a pharmaceutically acceptable salt thereof, in which the stereocenter marked with an asterisk is in the S configuration.

[0621] 163. -AB 1 However, the formula [ka] (In the formula, the dashed line represents -L) 2 (Indicates a connection to -) A compound from any of items 1-46 or a pharmaceutically acceptable salt thereof.

[0622] 164. -AB 1 However, the formula [ka] (In the formula, the dashed line represents -L) 2 (Indicates a connection to -) A compound from any of items 1-46 or a pharmaceutically acceptable salt thereof.

[0623] 165. -L 2 -A compound from any one of items 1 to 164 or a pharmaceutically acceptable salt thereof having a chain length of at least 35 atoms.

[0624] 166. -L 2 - A compound from any one of items 1 to 165 or a pharmaceutically acceptable salt thereof having a chain length of at least 50 atoms.

[0625] 167. -L 2 - A compound from any one of items 1 to 166 or a pharmaceutically acceptable salt thereof having a chain length of at least 75 atoms.

[0626] 168. -L 2 - A compound from any one of items 1 to 167 or a pharmaceutically acceptable salt thereof, having a chain length of at least 100 atoms.

[0627] 169. -L 2 - A compound from any one of items 1 to 168 or a pharmaceutically acceptable salt thereof having a chain length of at least 150 atoms.

[0628] 170. -L 2- A compound from any one of items 1 to 169 or a pharmaceutically acceptable salt thereof having a chain length of at least 200 atoms.

[0629] 171. -L 2 - A compound from any one of items 1 to 170 or a pharmaceutically acceptable salt thereof having a chain length of at least 250 atoms.

[0630] 172. -L 2 - A compound from any one of items 1 to 171 or a pharmaceutically acceptable salt thereof having a chain length of at least 300 atoms.

[0631] 173. -L 2 -A compound from any one of items 1 to 172 or a pharmaceutically acceptable salt thereof having a chain length of up to 3000 atoms.

[0632] 174. -L 2 -A compound from any one of items 1 to 173 or a pharmaceutically acceptable salt thereof having a chain length of up to 2500 atoms.

[0633] 175. -L 2 -A compound from any one of items 1 to 174 or a pharmaceutically acceptable salt thereof having a chain length of up to 2000 atoms.

[0634] 176. -L 2 -A compound from any one of items 1 to 175 or a pharmaceutically acceptable salt thereof having a chain length of up to 1500 atoms.

[0635] 177. -L 2 - A compound from any one of items 1 to 165 or a pharmaceutically acceptable salt thereof having a chain length of 35 to 3000 atoms.

[0636] 178. -L 2 - A compound from any one of items 1-165 or 34, or a pharmaceutically acceptable salt thereof, having a chain length of 50-2500 atoms.

[0637] 179. -L 2 - A compound of any one of items 1-165, 177, or 178, or a pharmaceutically acceptable salt thereof, having a chain length of 75-2000 atoms.

[0638] 180. -L 2 - A compound from any one of items 1-165 or 177-179, or a pharmaceutically acceptable salt thereof, having a chain length of 100-1500 atoms.

[0639] 181. -L 2 - A compound or pharmaceutically acceptable salt thereof of any one of items 1-165 or 177-180, having a chain length of 125-1000 atoms.

[0640] 182. -L 2 -A compound from any one of items 1 to 164 or a pharmaceutically acceptable salt thereof having a molecular weight of at least 450 Da.

[0641] 183. -L 2 -A compound from any one of items 1-164 or 182, or a pharmaceutically acceptable salt thereof, having a molecular weight of at least 1 kDa.

[0642] 184. -L 2 - One of the compounds from items 1-164, 182, or 183, or a pharmaceutically acceptable salt thereof, having a molecular weight of at least 1.5 kDa.

[0643] 185. -L 2 - One of the compounds from items 1-164 or 182-184, or a pharmaceutically acceptable salt thereof, having a molecular weight of at least 2 kDa.

[0644] 186. -L 2 - One of the compounds from items 1-164 or 182-185, or a pharmaceutically acceptable salt thereof, having a molecular weight of at least 2.5 kDa.

[0645] 187. -L 2- One of the compounds from items 1-164 or 182-186, or a pharmaceutically acceptable salt thereof, having a molecular weight of at least 3 kDa.

[0646] 188. -L 2 - One of the compounds from items 1-164 or 182-187, or a pharmaceutically acceptable salt thereof, having a molecular weight of at least 3.5 kDa.

[0647] 189. -L 2 - One of the compounds from items 1-164 or 182-188, or a pharmaceutically acceptable salt thereof, having a molecular weight of at least 4 kDa.

[0648] 190. -L 2 - One of the compounds from items 1-164 or 182-189, or a pharmaceutically acceptable salt thereof, having a molecular weight of at least 4.5 kDa.

[0649] 191. -L 2 - One of the compounds from items 1-164 or 182-190, or a pharmaceutically acceptable salt thereof, having a molecular weight of at least 5 kDa.

[0650] 192. -L 2 - One of the compounds from items 1-164 or 182-191, or a pharmaceutically acceptable salt thereof, having a molecular weight of up to 160 kDa.

[0651] 193. -L 2 - One of the compounds from items 1-164 or 182-192, or a pharmaceutically acceptable salt thereof, having a molecular weight of up to 120 kDa.

[0652] 194. -L 2 - One of the compounds from items 1-164 or 182-193, or a pharmaceutically acceptable salt thereof, having a molecular weight of up to 100 kDa.

[0653] 195. -L 2- One of the compounds from items 1-164 or 182-194, or a pharmaceutically acceptable salt thereof, having a molecular weight of up to 80 kDa.

[0654] 196. -L 2 - One of the compounds from items 1-164 or 182-195, or a pharmaceutically acceptable salt thereof, having a molecular weight of up to 70 kDa.

[0655] 197. -L 2 - One of the compounds from items 1-164 or 182-196, or a pharmaceutically acceptable salt thereof, having a molecular weight of up to 60 kDa.

[0656] 198. -L 2 - One of the compounds from items 1-164 or 182-197, or a pharmaceutically acceptable salt thereof, having a molecular weight of up to 50 kDa.

[0657] 199. -L 2 - One of the compounds from items 1-164 or 182-198, or a pharmaceutically acceptable salt thereof, having a molecular weight of up to 40 kDa.

[0658] 200. -L 2 -A compound from item 1 to 164 or a pharmaceutically acceptable salt thereof having a molecular weight of approximately 450 Da.

[0659] 201. -L 2 -A compound from item 1 to 164 or a pharmaceutically acceptable salt thereof having a molecular weight of approximately 1 kDa.

[0660] 202. -L 2 -A compound from item 1 to 164 or a pharmaceutically acceptable salt thereof having a molecular weight of approximately 1.5 kDa.

[0661] 203. -L 2 -A compound from item 1 to 164 or a pharmaceutically acceptable salt thereof having a molecular weight of approximately 2 kDa.

[0662] 204. -L 2 -A compound from item 1 to 164 or a pharmaceutically acceptable salt thereof having a molecular weight of approximately 2.5 kDa.

[0663] 205. -L 2 -A compound from item 1 to 164 or a pharmaceutically acceptable salt thereof having a molecular weight of approximately 3 kDa.

[0664] 206. -L 2 -A compound from item 1 to 164 or a pharmaceutically acceptable salt thereof having a molecular weight of approximately 3.5 kDa.

[0665] 207. -L 2 -A compound from item 1 to 164 or a pharmaceutically acceptable salt thereof having a molecular weight of approximately 4 kDa.

[0666] 208. -L 2 - One of the compounds from items 1 to 164 or a pharmaceutically acceptable salt thereof, having a molecular weight of approximately 4.5 kDa.

[0667] 209. -L 2 -A compound from item 1 to 164 or a pharmaceutically acceptable salt thereof having a molecular weight of approximately 5 kDa.

[0668] 210. -L 2 -A compound from item 1 to 164 or a pharmaceutically acceptable salt thereof having a molecular weight of approximately 5.5 kDa.

[0669] 211. -L 2 -A compound from item 1 to 164 or a pharmaceutically acceptable salt thereof having a molecular weight of approximately 6 kDa.

[0670] 212. -L 2 - One of the compounds from items 1 to 164 or a pharmaceutically acceptable salt thereof, having a molecular weight of approximately 6.5 kDa.

[0671] 213. -L2 -A compound from item 1 to 164 or a pharmaceutically acceptable salt thereof having a molecular weight of approximately 7 kDa.

[0672] 214. -L 2 - One of the compounds from items 1 to 164 or a pharmaceutically acceptable salt thereof, having a molecular weight of approximately 7.5 kDa.

[0673] 215. -L 2 -A compound from item 1 to 164 or a pharmaceutically acceptable salt thereof having a molecular weight of approximately 8 kDa.

[0674] 216. -L 2 -A compound from item 1 to 164 or a pharmaceutically acceptable salt thereof having a molecular weight of approximately 8.5 kDa.

[0675] 217. -L 2 -A compound from item 1 to 164 or a pharmaceutically acceptable salt thereof having a molecular weight of approximately 9 kDa.

[0676] 218. -L 2 - One of the compounds from items 1 to 164 or a pharmaceutically acceptable salt thereof, having a molecular weight of approximately 9.5 kDa.

[0677] 219. -L 2 -A compound from item 1 to 164 or a pharmaceutically acceptable salt thereof having a molecular weight of approximately 10 kDa.

[0678] 220. -L 2 -A compound from any one of items 1-219 or a pharmaceutically acceptable salt thereof, which contains a polymer portion.

[0679] 221. A compound of item 220 or a pharmaceutically acceptable salt thereof, wherein the polymer part comprises one or more polymer parts.

[0680] 222. One or more polymer moieties are poly(2-methacryloyl-oxyethyl phosphorylcholine), poly(acrylic acid), poly(acrylate), poly(acrylamide), poly(alkyloxy)polymer, poly(amide), poly(amideamine), poly(amino acid), poly(acid anhydride), poly(aspartamide), poly(butyric acid), poly(glycolic acid), polybutylene terephthalate, poly(caprolactone), poly(carbonate), poly(cyanoacrylate), poly(dimethylacrylamide), poly(ester), poly(ethylene), poly(ethylene glycol), poly(ethylene oxide), poly(ethyl phosphate), poly(ethyl oxazoline), poly(glycolic acid), poly(hydroxyethyl acrylate), poly(hydroxyethyl oxazoline), poly(hydroxymethacrylate), poly(hydroxypropyl methacrylamide), poly(hydroxypropyl methacrylate), poly(hydroxypropyl oxazoline) Compounds of item 221 or pharmaceutically acceptable salts thereof, selected from the group consisting of phosphorus, poly(iminocarbonate), poly(lactic acid), poly(lactic acid-co-glycolic acid), poly(methacrylamide), poly(methacrylate), poly(methyloxazoline), poly(organophosphazene), poly(orthoester), poly(oxazoline), poly(propylene glycol), poly(siloxane), poly(urethane), poly(vinyl alcohol), poly(vinylamine), poly(vinyl methyl ether), poly(vinylpyrrolidone), silicone, cellulose, carbomethylcellulose, hydroxypropylmethylcellulose, chitin, chitosan, dextran, dextrin, gelatin, hyaluronic acid and derivatives, functionalized hyaluronic acid, alginate, mannan, pectin, rhamnogalacturonan, starch, hydroxyalkyl starch, hydroxyethyl starch and other carbohydrate polymers, xylan, and copolymers thereof.

[0681] 223. Compounds of item 221 or 222, or pharmaceutically acceptable salts thereof, wherein one or more polymer portions are PEG-based polymers.

[0682] 224. Compounds of item 221 or 222 or pharmaceutically acceptable salts thereof, wherein one or more polymer portions are hyaluronic acid-based polymers.

[0683] 225. Compounds of item 221 or 222, or pharmaceutically acceptable salts thereof, wherein one or more polymer portions comprise random coil peptides or protein polymers.

[0684] 226. Compounds of item 221 or 222 or pharmaceutically acceptable salts thereof, wherein one or more polymer portions are polysarcosine-based polymers.

[0685] 227. -L 2 - One of the compounds from items 220-226 or a pharmaceutically acceptable salt thereof, having a Florey radius of at least 1.2 nm.

[0686] 228. -L 2 - One of the compounds from items 220-227 or a pharmaceutically acceptable salt thereof, having a Florey radius of at least 1.5 nm.

[0687] 229. -L 2 - One of the compounds from items 220-228 or a pharmaceutically acceptable salt thereof, having a Florey radius of at least 2 nm.

[0688] 230. -L 2 - One of the compounds from item 220-86229 or a pharmaceutically acceptable salt thereof having a Florey radius of at least 2.5 nm.

[0689] 231. -L 2 - One of the compounds from items 220-230 or a pharmaceutically acceptable salt thereof, having a Florey radius of at least 3 nm.

[0690] 232. -L 2 - One of the compounds from items 220-231 or a pharmaceutically acceptable salt thereof having a Florey radius of at least 3.5 nm.

[0691] 233. -L 2 - One of the compounds from items 220-232 or a pharmaceutically acceptable salt thereof having a Florey radius of at least 4 nm.

[0692] 234. -L 2 - One of the compounds from items 220-233 or a pharmaceutically acceptable salt thereof, having a Florey radius of at least 4.5 nm.

[0693] 235. -L 2 - One of the compounds from items 220-234 or a pharmaceutically acceptable salt thereof having a Florey radius of at least 5 nm.

[0694] 236. -L 2 - One of the compounds from items 220-235 or a pharmaceutically acceptable salt thereof having a Florey radius of 200 nm or less.

[0695] 237. -L 2 - One of the compounds from items 220-236 or a pharmaceutically acceptable salt thereof having a Florey radius of 175 nm or less.

[0696] 238. -L 2 - One of the compounds from items 220-237 or a pharmaceutically acceptable salt thereof having a Florey radius of 150 nm or less.

[0697] 239. -L 2 - One of the compounds from items 220-238 or a pharmaceutically acceptable salt thereof having a Florey radius of 125 nm or less.

[0698] 240. -L 2 - One of the compounds from items 220-239 or a pharmaceutically acceptable salt thereof having a Florey radius of 100 nm or less.

[0699] 241. -L 2- One of the compounds from item 220-240 or a pharmaceutically acceptable salt thereof having a Florey radius of 75 nm or less.

[0700] 242. -L 2 - One of the compounds from items 220-241 or a pharmaceutically acceptable salt thereof having a Florey radius of 50 nm or less.

[0701] 243. -L 2 - One of the compounds from items 220-242 or a pharmaceutically acceptable salt thereof having a Florey radius of 45 nm or less.

[0702] 244. -L 2 - One of the compounds from items 220-243 or a pharmaceutically acceptable salt thereof having a Florey radius of 40 nm or less.

[0703] 245. -L 2 - One of the compounds from items 220-244 or a pharmaceutically acceptable salt thereof having a Florey radius of 35 nm or less.

[0704] 246. -L 2 - One of the compounds from items 220-245 or a pharmaceutically acceptable salt thereof having a Florey radius of 30 nm or less.

[0705] 247. -L 2 - One of the compounds from items 220-226 or a pharmaceutically acceptable salt thereof, having a Florey radius of approximately 1.2 nm.

[0706] 248. -L 2 - One of the compounds from items 220-227 or a pharmaceutically acceptable salt thereof, having a Florey radius of approximately 1.5 nm.

[0707] 249. -L 2 - One of the compounds from items 220-227 or a pharmaceutically acceptable salt thereof, having a Florey radius of approximately 2 nm.

[0708] 250. -L 2 - One of the compounds from items 220-227 or a pharmaceutically acceptable salt thereof, having a Florey radius of approximately 2.5 nm.

[0709] 251. -L 2 - One of the compounds from items 220-227 or a pharmaceutically acceptable salt thereof, having a Florey radius of approximately 3 nm.

[0710] 252. -L 2 - One of the compounds from items 220-227 or a pharmaceutically acceptable salt thereof, having a Florey radius of approximately 3.5 nm.

[0711] 253. -L 2 - One of the compounds from items 220-227 or a pharmaceutically acceptable salt thereof, having a Florey radius of approximately 4 nm.

[0712] 254. -L 2 - One of the compounds from items 220-227 or a pharmaceutically acceptable salt thereof, having a Florey radius of approximately 4.5 nm.

[0713] 255. -L 2 - One of the compounds from items 220-227 or a pharmaceutically acceptable salt thereof, having a Florey radius of approximately 5 nm.

[0714] 256. -L 2 - One of the compounds from items 220-227 or a ...

Claims

1. Formula (Ia) or (Ib) 【Chemistry 1】 (In the formula, Each -D- is an independent drug portion. Each-AB 1 and -AB 2 This is an independently albumin-binding moiety, Each-L 1 - is a linker portion that is independently and covalently and reversibly bonded to -D-. Each-L 2 - is either an independent spacer or does not exist. x is an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, and 25. (y is an integer selected from the group consisting of 2, 3, 4, and 5.) A compound of or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1, which is of formula (Ia) having x=1.

3. -AB 1 and / or -AB 2 The compound according to claim 1 or 2, wherein the albumin-binding moiety is independently based on a fatty acid.

4. -AB 1 and / or -AB 2 However, independently, equation (A): 【Chemistry 2】 [In the formula, The dashed lines each indicate a bond to -L 2 - or -D-, -F 0 is equation (a-1) 【Transformation 3】 (In the formula, The dashed line is -L A - indicates binding to -R 0 -CR 1 R 1a R 1b ,-COOR 1 , 【Chemistry 4】 Selected from the group consisting of, -R 1 ,-R 1a and -R 1b It is selected from the group consisting of -H, methyl, ethyl, propyl and isopropyl, n is an integer between 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, and 22. It is, -L A - is either nonexistent or expression (a-2) 【Transformation 5】 (In the formula, Dashed lines without a mark are -L B - indicates binding to The dashed line with an asterisk indicates -F 0 This shows a connection to, -R a -teeth, 【Transformation 6】 (In the formula, The dashed line with an asterisk indicates -F 0 This shows a connection to, Dashed lines without a mark are -L A (Indicates connection to the remainder) Selected from the group consisting of, -R b -teeth, 【Transformation 7】 And, m is an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10. p is an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10. It is, -L B - is either nonexistent or expression (a-3) 【Transformation 8】 (In the formula, Dashed lines without a mark are -L 2 - or -D- indicates binding to D-, The dashed line with an asterisk indicates -L A This shows a connection to, -R c -teeth, 【Chemistry 9】 And, -R d - is C 1-50 Alkyl, C 2-50 Alkenyl or C 2-50 Selected from the group consisting of alkynnyl, C 1-50 Alkyl, C 2-50 Alkenyl and C 2-50 Alkinyl can have one or more -Rs, which may be the same or different. 1 It can be replaced with C 1-50 Alkyl, C 2-50 Alkenyl or C 2-50 Alkinyls include -T-, -C(O)O-, -O-, -C(O)-, and -C(O)N(R) 2 )-,-S(O) 2 N(R 2 )-,-S(O)N(R 2 )-,-S(O) 2 -, -S(O)-, -N(R 2 )S(O) 2 N(R 2a )-, -S-, -N(R 2 )-, -OC(OR 2 )(R 2a )-,-N(R 2 )C(O)N(R 2a )-, and -OC(O)N(R 2 )- may have one or more groups selected from the group consisting of these groups, Each -T- is independently phenyl, naphthyl, indenyl, indanyl, tetralinyl, C 3-10 Selected from the group consisting of cycloalkyls, 3-10 membered heterocyclils, 8-11 membered heterobicyclils, 8-30 membered carbopolycyclils, and 8-30 membered heteropolycyclils, each -T- independently has one or more -R which may be the same or different. 1 It can be replaced with Each -R 1 is, independently, halogen, -CN, oxo(=O), -COOR 3 , -OR 3 , -C(O)R 3 , -C(O)N(R 3 R 3a ), -S(O) 2 N(R 3 R 3a ), -S(O)N(R 3 R 3a ), -S(O) 2 R 3 , -S(O)R 3 , -N(R 3 )S(O) 2 N(R 3a R 3b ), -SR 3 , -N(R 3 R 3a ), -NO 2 , -OC(O)R 3 , -N(R 3 )C(O)R 3a , -N(R 3 )S(O) 2 R 3a , -N(R 3 )S(O)R 3a , -N(R 3 )C(O)OR 3a , -N(R 3 )C(O)N(R 3a R 3b ), -OC(O)N(R 3 R 3a ), and C 1-6 alkyl selected from the group consisting of C 1-6 alkyl is optionally substituted with one or more of the same or different halogens, each -R 2 -R 2a -R 3 -R 3a and -R 3b are each independently selected from the group consisting of -H and C 1-6 alkyl, and the C 1-6 alkyl can be substituted with one or more halogens which can be the same or different -R e - is, -CH 2 -, 【Chemistry 10】 (Selected from the group consisting of) [It belongs to] A compound according to any one of claims 1 to 3, wherein the compound is as described above.

5. -AB 1 and / or -AB 2 The compound according to any one of claims 1 to 4, wherein the compound is independently a peptidoalbumin-binding moiety.

6. -L 1 -But equation (II): 【Chemistry 11】 (In the formula, The dashed line indicates the bond of -D- to nitrogen, hydroxyl, or thiol. -X- is -C(R 4 R 4a )-,-N(R 4 )-, -O-, -C(R 4 R 4a )-C(R 5 R 5a )-,-C(R 5 R 5a )-C(R 4 R 4a )-,-C(R 4 R 4a )-N(R 6 )-,-N(R 6 )-C(R 4 R 4a )-,-C(R 4 R 4a )-O-, -OC(R 4 R 4a )-, and -C(R 7 R 7a Selected from the group consisting of )-, X 1 It is selected from the group consisting of C and S(O), -X 2 - is -C(R 8 R 8a )-, and -C(R 8 R 8a )-C(R 9 R 9a Selected from the group consisting of )-, =X 3 It is selected from the group consisting of =O, =S, and =N-CN, -R 1 ,-R 1a ,-R 2 ,-R 2a ,-R 4 ,-R 4a ,-R 5 ,-R 5a ,-R 6 ,-R 8 ,-R 8a ,-R 9 , and -R 9a These are independently -H and C 1-6 Selected from the group consisting of alkyl groups, -R 3 , and -R 3a These are independently -H and C 1-6 Selected from the group consisting of alkyl, except -R 3 ,-R 3a If one or both of them are not -H, then they are SP to the N to which they are bonded. 3 Bonded by hybrid carbon atoms, -R 7 is -N(R 10 R 10a ), and -NR 10 -(C=O)-R 11 Selected from the group consisting of, -R 7a ,-R 10 ,-R 10a , and -R 11 These are, independently of each other, -H and C 1-6 Selected from the group consisting of alkyl groups, Depending on the circumstances, Pair-R 1a / -R 4a ,-R 1a / -R 5a ,-R 1a / -R 7a ,-R 4a / -R 5a , and -R 8a / -R 9a One or more of them form a chemical bond, Depending on the circumstances, Pair-R 1 / -R 1a ,-R 2 / -R 2a ,-R 4 / -R 4a ,-R 5 / -R 5a ,-R 8 / -R 8a , and -R 9 / -R 9a One or more of them, together with the atom they are bonded to, C 3-10 Forming a cycloalkyl or 3-10 membered heterocycline, Depending on the circumstances, Pair-R 1 / -R 4 ,-R 1 / -R 5 ,-R 1 / -R 6 ,-R 1 / -R 7a ,-R 4 / -R 5 ,-R 4 / -R 6 ,-R 8 / -R 9 , and -R 2 / -R 3 One or more of these, together with the atoms to which they are bonded, form ring A. Depending on the case, R 3 / R 3a These, together with the nitrogen atoms to which they are bonded, form a heterocycle of 3 to 10 members. A is phenyl, naphthyl, indenyl, indanyl, tetralinyl, C 3-10 Selected from the group consisting of cycloalkyls, 3- to 10-membered heterocyclines, and 8- to 11-membered heterobicyclines, -L 1 - is at least one -L 2 - is replaced by -L 1 - is sometimes further substituted, except that the hydrogen with an asterisk in formula (II) is -L 2 -or not substituted by a substituent) A compound according to any one of claims 1 to 5.

7. -L 1 -However, equation (IIa): 【Chemistry 12】 (In the formula, The dashed line with an asterisk indicates the bond to nitrogen of -D-. Dashed lines without a mark are -L 2 (Indicates a connection to -) The compound according to any one of claims 1 to 6.

8. -L 2 -But, equation (XII-ii) 【Chemistry 13】 (In the formula, The dashed line with an asterisk indicates -L 1 - indicates binding to Unmarked dashed lines are -AB 1 This shows a connection to, a is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15. b is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15. c is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15. x is in the range of 2 to 1000. -R 1 and -R 2 These are, independently of each other, -H and C 1-6 (Selected from the group consisting of alkyl groups) The compound according to any one of claims 1 to 7.

9. In the equation, a is 5, b is 2, c is 2, and -R 1 and -R 2 The compound according to claim 8, wherein both are -H.

10. The compound according to claim 8 or 9, wherein x is approximately 10⁸.

11. The compound according to claim 8 or 9, wherein x is approximately 23.

12. -D- or -D-AB 2 The compound according to any one of claims 1 to 11, wherein the GLP-1 receptor agonist moiety is the compound according to any one of claims 1 to 11.

13. -D-AB 2 The compound according to any one of claims 1 to 11, selected from the group consisting of semaglutide, liraglutide, echnoglutide, GZR18, GL0034, tylzepatide, cotadutide, BI-456906, pembidutide, mazdutide, dapiglutide, and letatoltide.

14. -D-AB 2 The compound according to any one of claims 1 to 13, wherein is semaglutide.

15. -D- is converted to -L via the N-terminal amine functional group. 1 -The compound according to any one of claims 12 to 14, which is conjugated to -.

16. -AB 1 However, equation (XIX) 【Chemistry 14】 (In the formula, The dashed line is -L 2 - indicates binding to (a is 14, 15, 16, 17, 18, 19, 20, 21, or 22) The compound according to any one of claims 1 to 15.

17. The compound according to claim 16, wherein a is 18.

18. A pharmaceutical composition comprising at least one compound and at least one excipient as described in any one of claims 1 to 17.

19. A compound according to any one of claims 1 to 17 or a pharmaceutical composition according to claim 18, for use as a pharmaceutical.

20. HD-AB 2 A compound according to any one of claims 1 to 17 or a pharmaceutical composition according to claim 18, for use in the treatment of diseases that can be treated using the compound or the compound according to claim 18.

21. A pharmaceutical composition comprising any one of claims 12 to 17 or at least one such compound for use in the treatment of a disease selected from the group consisting of (i) all forms of diabetes mellitus, (ii) obesity, (iii) non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), (iv) cardiovascular disease, (v) neurodegenerative disorders, (vi) chronic kidney disease (CKD), (vii) diabetic nephropathy (DKD), (viii) peripheral artery disease (PAD), and / or (ix) heart failure (HF).

22. A pharmaceutical composition comprising a compound according to any one of claims 12 to 17 or at least one such compound, for use in the treatment of a disease selected from the group consisting of diseases in which one or more of the following clinical outcomes are targeted for treatment: dyslipidemia; elevated HDL; decreased small, high-density LDL; decreased VLDL; decreased triglycerides; decreased cholesterol; decreased plasma levels of lipoprotein a (Lp(a)) in humans; or inhibition of apolipoprotein A (apo(A)) production.

23. A pharmaceutical composition comprising the compound described in any one of claims 12 to 17 or at least one such compound, for use in the treatment of a disease selected from the group consisting of Alzheimer's disease and Parkinson's disease.

24. A pharmaceutical composition comprising the compound according to any one of claims 12 to 17 or at least one such compound, for use in the treatment of one or more additional drugs selected from the group consisting of cardiovascular agents, antidiabetic agents, and anti-obesity agents.

25. The compound or a pharmaceutically acceptable salt or pharmaceutical composition thereof for use according to claim 22 or 23, wherein the compound or a pharmaceutically acceptable salt thereof or pharmaceutical composition thereof is administered in combination with a growth hormone.

26. A compound for use according to claim 27, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition, wherein the growth hormone is lonapegsomatropin.

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