Compounds of drugs with an albumin binding moiety

Abstract

The present application relates to compounds or pharmaceutically acceptable salts thereof, wherein the compounds comprise at least one polymeric moiety, to which at least two drug moieties are covalently and reversibly conjugated, which drug moieties are conjugated to an albumin binding moiety. The application also relates to pharmaceutical compositions comprising at least one such compound and their medical uses.

Description

[0001] Compounds of drugs with an albumin binding moiety

[0002] The present application relates to compounds or pharmaceutically acceptable salts thereof, wherein the compounds comprise at least one polymeric moiety, to which at least two drug moieties are covalently and reversibly conjugated, which drug moieties are conjugated to an albumin binding moiety. The application also relates to pharmaceutical composition comprising at least one such compound and their medical uses.

[0003] Whereas some classes of therapeutic proteins, including antibodies, have long inherent half- lives, many other molecules, particularly protein or peptide hormones are often susceptible to enzymatic degradation, renal clearance and / or rapid receptor-mediated clearance, which leads to a short plasma elimination half-life. Furthermore, due to the challenges associated with oral delivery, most peptide- or protein-based drugs require parenteral administration, which combined with a short half-life necessitates frequent injections, resulting in discomfort and inconvenience for the patient. This may negatively impact adherence and, ultimately, limit treatment efficacy and outcomes.

[0004] Injecting lipidated peptides has been demonstrated to have slower absorption from the subcutaneous tissue compared to the non-derivatized peptide as well as longer circulatory half- life due to reversible binding to albumin. The half-life of endogenous albumin in the circulation is approximately 3 weeks. This long half-life can be attributed both to its large molecular size, which minimizes renal clearance, as well as to recycling via the neonatal Fc receptor (FcRn). In the circulation, the large molecular size protects the bound peptide from renal clearance and reduces the rate of distribution to the extravascular compartment.

[0005] The slower absorption is thought to be due to a reduced rate of diffusion in the tissue by a mechanism involving interaction of the fatty acid side chain with cell membranes and / or proteins such as albumin present at the injection site. The rate of diffusion in the tissue following injection and the passage over the capillary wall would expectedly be reduced due to the large molecular size of the albumin-peptide complex. Molecules with a molecular size greater than approximately 16 kDa are preferentially alternatively be absorbed via a lymphatic route compared to direct absorption into blood across the capillary wall. Thus, slower absorption and reversible albumin binding has enabled extension of dosing intervals for drugs, such as peptide drugs, to up to a week. However, an even further extension of the dosing intervals would be desirable.

[0006] It is an object of the present invention to overcome the shortcomings of current therapies at least partially.

[0007] This object is achieved with a compound or a pharmaceutically acceptable salt thereof, wherein the compound comprises at least one polymeric moiety, to which at least two moieties of formula (I) are conjugated and / or to which at least one moiety of formula (T) is conjugated, wherein formula (I) and (T) are wherein each -L2- is independently a spacer moiety or is absent; each -L1- is independently a linker moiety that is covalently and reversibly conjugated to -D-; each -L1- is independently a linker moiety that is covalently and reversibly conjugated to -D-; each -D- is independently a drug moiety; each -AB is independently an albumin-binding moiety; and each a is independently 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.

[0008] Applicant discovered that the compounds of the present invention are capable of further extending half-life and dosing frequency. It was surprisingly found that a compound of two or more drugs comprising an albumin binding moiety may coordinate more than one albumin molecule, resulting in a large molecular size of the albumin-drug complex.

[0009] This results in compounds exhibiting a further increased albumin binding and slowed absorption of the macromolecular drug-albumin complex. Such compounds also demonstrate a reduced absorption from the site of administration, such as from subcutaneous tissue, compared to administration of the corresponding unconjugated drugs. Consequently, such compounds have a prolonged half-life compared to the corresponding unconjugated drugs.

[0010] Within the present invention the terms are used having the meaning as follows.

[0011] As used herein, the term “GLP-1 receptor agonist” refers to agonists of the GLP-1 receptor (GLP1R) and optionally in addition agonists of one or more other receptors, such as for example a receptor for gastric inhibitory polypeptide (GIPR), a receptor for glucagon (GCGR), a receptor for amylin, a receptor for peptide YY (PYYR) or a receptor for glucagon-like peptide-2 (GLP2R). An “agonist” of a receptor, such as an agonist of the GLP-1 receptor, is a chemical compound that activates such receptor to produce a biological response. If a GLP-1 receptor agonist is in addition to being a GLP1R agonist also an agonist of one receptor other than GLP1R, such as an agonist of GIPR, GCGR, an amylin receptor, a PYYR or GLP2R, such GLP-1 receptor agonist is also referred to as being a “dual GLP-1 receptor agonist” or short “dual agonist”. Likewise, if a GLP-1 receptor agonist is in addition to being a GLP1R agonist also an agonist of two other receptors, which may be selected from the group consisting of GIPR, GCGR, an amylin receptor, a PYYR or GLP2R, such GLP-1 receptor agonist is also referred to as being a “triple GLP-1 receptor agonist” or short “triple agonist”.

[0012] As used herein, the term “peptide” as used herein refers to a chain of at least 2 and up to and including 50 amino acid monomer moieties, which may also be referred to as “amino acid residues”, linked by peptide (amide) linkages. The amino acid monomers may be selected from the group consisting of proteinogenic amino acids and non-proteinogenic amino acids and may be D- or L-amino acids. The term “peptide” also includes peptidomimetics, such as peptoids, beta-peptides, cyclic peptides and depsipeptides and covers such peptidomimetic chains with up to and including 50 monomer moieties. The cyclic peptides may be mono-, bi-, tri- or tetracyclic peptides. The term “peptide” also includes lasso peptides.

[0013] As used herein, the term “protein” refers to a chain of more than 50 amino acid monomer moieties, which may also be referred to as “amino acid residues”, linked by peptide linkages, in which preferably no more than 12000 amino acid monomers are linked by peptide linkages, such as no more than 10000 amino acid monomer moieties, no more than 8000 amino acid monomer moieties, no more than 5000 amino acid monomer moieties or no more than 2000 amino acid monomer moieties. As used herein, the term “small molecule drug” refers to drugs that are organic compounds with a molecular weight of less than 1000 Da, such as less than 900 Da or less than 800 Da. It is understood that nucleobase-based drug moieties, such as adenine or guanine analogues, may also be a type of small molecule drugs.

[0014] As used herein, the terms “medium molecule drug” or “medium size molecule drug” refer to drugs that are organic compounds which are not peptides and which are not proteins and have a molecular weight ranging from and including 1 kDa to 7.5 kDa.

[0015] As used herein, the term “oligonucleotide” refers to double- or single-stranded RNA and DNA with preferably 2 to 1000 nucleotides and any modifications thereof. Modifications include, for example, those which provide other chemical groups that incorporate additional charge, polarizability, hydrogen bonding, electrostatic interaction, and fluxionality to the nucleic acid ligand bases or to the nucleic acid ligand as a whole. Such modifications include for example, to 2’-position sugar modifications, 5-position pyrimidine modifications, 8-position purine modifications, modifications at exocyclic amines, substitution of 4-thiouridines, substitution of 5-bromo or 5 -iodo-uracil; backbone modifications, methylations, unusual base-pairing combinations such as the isobases isocytidine and isoguanidine. Modifications can also include 3’ and 5’ modifications such as capping and change of stereochemistry. The term also includes aptamers.

[0016] As used herein, the term “peptide nucleic acids” refers to organic polymers having a peptidic backbone, i.e., a backbone in which the monomers are connected to each other through peptide linkages, to which nucleobases such as adenine, cytosine, guanine, thymine and uracil, are attached. In certain embodiments, the peptide backbone comprises N-(2-aminoethyl)-glycine.

[0017] As used herein, the term "random coil" relates to any conformation of a polymeric molecule, including proteins, in which the individual monomeric elements that form said polymeric structure are essentially randomly oriented towards the adjacent monomeric elements while still being chemically bound to said adjacent monomeric elements. In particular, a polypeptide or protein having random coil conformation substantially lacks a defined secondary and tertiary structure. The nature of polypeptide random coils and their methods of experimental identification are known to the person skilled in the art. In particular, the lack of secondary and tertiary structure of a protein may be determined by circular dichroism (CD) measurements. CD spectroscopy represents a light absorption spectroscopy method in which the difference in absorbance of right- 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 a wavelength between approximately 190 and 250 nm. At these wavelengths the different secondary structures commonly found in conformations each give rise to a characteristic shape and magnitude of the CD spectrum. Accordingly, by using CD spectrometry the skilled artisan is readily capable of determining whether an amino acid polymer adopts random coil conformation at physiological conditions.

[0018] When determining whether a peptide or protein adopts random coil conformation under experimental conditions using the methods as described herein, the biophysical parameters such as temperature, pH, osmolarity and protein content may be different to the physiological conditions normally found in vivo. Temperatures between 1 °C and 42 °C or preferably 4 °C to 25 °C may be considered useful to test and / or verify the biophysical properties and biological activity of a peptide or protein under physiological conditions in vitro.

[0019] Several buffers, in particular in experimental settings (for example in the determination of protein structures, in particular in circular dichroism (CD) measurements and other methods that allow the person skilled in the art to determine the structural properties of a protein / polypeptide or peptide stretch) or in buffers, solvents and / or excipients for pharmaceutical compositions, are considered to represent "physiological solutions" or "physiological conditions" in vitro. Examples of such buffers are, e.g. phosphate-buffered saline (PBS: 115 mM NaCl, 4 mM KH2PO4, 16 mM Na2HPO4pH 7.4), Tris buffers, acetate buffers, citrate buffers or similar buffers such as those used in the appended examples. Generally, the pH of a buffer representing physiological conditions should lie in a range from 6.5 to 8.5, preferably in a range from 7.0 to 8.0, most preferably in a range from 7.2 to 7.7 and the osmolarity should lie in a range from 10 to 1000 mmol / kg H2O, more preferably in a range from 50 to 500 mmol / kg H2O and most preferably in a range from 200 to 350 mmol / kg H2O. Optionally, the protein content of a buffer representing physiological conditions may lie in a range from 0 to 100 g / 1, neglecting the protein with biological activity itself, whereby typical stabilizing proteins may be used, for example human or bovine serum albumin. Other established biophysical methods for determining random coil conformation include nuclear magnetic resonance (NMR) spectroscopy, absorption spectrometry, infrared and Raman spectroscopy, measurement of the hydrodynamic volume via size exclusion chromatography, analytical ultracentrifugation and dynamic / static light scattering as well as measurements of the frictional coefficient or intrinsic viscosity.

[0020] As used herein the term “physiological conditions” refers to aqueous buffer at pH 7.4, 37°C.

[0021] As used herein the term “pharmaceutical composition” refers to a composition containing one or more active ingredients, such as for example at least one compound of the present invention, and one or more excipients, as well as any product which results, directly or indirectly, from combination, complexation or aggregation of any two or more of the ingredients of the composition, or from dissociation of one or more of the ingredients, or from other types of reactions or interactions of one or more of the ingredients. Accordingly, a pharmaceutical composition of the present invention encompasses any composition made by admixing one or more compound of the present invention and one or more pharmaceutically acceptable excipient.

[0022] As used herein, the term "excipient" refers to a diluent, adjuvant, or vehicle with which the therapeutic, such as a drug or prodrug, is administered. Such pharmaceutical excipient may be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, including but not limited to peanut oil, soybean oil, mineral oil, sesame oil and the like. Water is an example for an excipient when the pharmaceutical composition is administered orally. Saline and aqueous dextrose are examples of excipients when the pharmaceutical composition is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions are in certain embodiments employed as liquid excipients for injectable solutions. Suitable pharmaceutical excipients include starch, glucose, lactose, sucrose, mannitol, trehalose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. The pharmaceutical composition, if desired, can also contain minor amounts of wetting or emulsifying agents, pH buffering agents, like, for example, acetate, succinate, tris, carbonate, phosphate, HEPES (4-(2-hydroxyethyl)-l -piperazineethanesulfonic acid), MES (2-(A-morpholino)ethanesulfonic acid), or can contain detergents, like Tween, poloxamers, poloxamines, CHAPS, Igepal, or amino acids like, for example, glycine, lysine, or histidine. These pharmaceutical compositions can take the form of solutions, suspensions, emulsions, tablets, pills, capsules, powders, or sustained-release formulations. The pharmaceutical composition may be formulated as a suppository, with traditional binders and excipients such as triglycerides. Oral formulation can include standard excipients such as pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, etc. Such compositions will contain a therapeutically effective amount of the drug or drug moiety, together with a suitable amount of excipient so as to provide the form for proper administration to the patient. The formulation should suit the mode of administration.

[0023] As used herein the term “liquid composition” refers to a mixture comprising a water-soluble compound and one or more solvents, such as water.

[0024] The term “suspension composition” relates to a mixture comprising at least one water-insoluble compound and one or more solvents, such as water.

[0025] As used herein, the term “dry composition” means that a pharmaceutical composition is provided in a dry form. Suitable methods for drying are spray-drying and lyophilization, i.e., freeze-drying. Such dry composition has a residual water content of a maximum of 10%, such as less than 5% or less than 2%, determined according to Karl Fischer. In certain embodiments such dry pharmaceutical composition is dried by lyophilization.

[0026] The term “drug” as used herein refers to a substance used in the treatment, cure, prevention, or diagnosis of a disease or used to otherwise enhance physical or mental well-being. If a drug is conjugated to another moiety, the moiety of the resulting product that originated from the drug is referred to as “drug moiety”.

[0027] As used herein the term “prodrug” refers to a covalent conjugate in which a drug moiety is reversibly and covalently connected to a specialized protective group through a reversible linker moiety, also referred to as “reversible prodrug linker moiety” or “reversible linker moiety”, which is conjugated through a reversible linkage to the drug moiety and wherein the specialized protective group alters or eliminates undesirable properties in the parent molecule. This also includes the enhancement of desirable properties in the drug and the suppression of undesirable properties. The specialized non-toxic protective group is referred to as “carrier”. A prodrug releases the reversibly and covalently bound drug moiety in the form of its corresponding drug. In other words, a prodrug is a compound comprising a drug moiety which is covalently and reversibly conjugated to a carrier moiety via a reversible linker moiety, which covalent and reversible conjugation of the carrier to the reversible linker moiety is either directly or through a spacer. Such compound releases the formerly conjugated drug moiety in the form of a free unmodified drug.

[0028] A “reversible linkage” is a linkage that is degradable, i.e., cleavable, in the absence of enzymes under physiological conditions (aqueous buffer at pH 7.4, 37°C) with a half-life ranging from 1 hour to three months. A “stable linkage” is a linkage having a half-life under physiological conditions (aqueous buffer at pH 7.4, 37°C) in the absence of enzymes of more than three months.

[0029] As used herein, the terms “traceless prodrug linker” or “traceless linker” means a reversible prodrug linker, i.e., a linker moiety reversibly and covalently connecting a drug moiety with a carrier, which upon cleavage releases the drug in its free form. As used herein, the term “free form” of a drug means the drug in its unmodified, pharmacologically active form.

[0030] As used herein, the term “reagent” means a chemical compound which comprises at least one functional group for reaction with the functional group of another chemical compound or drug. It is understood that a drug comprising a functional group, such as a primary or secondary amine or hydroxyl functional group, is also a reagent.

[0031] As used herein, the term “moiety” means a part of a molecule, which lacks one or more atom(s) compared to the corresponding reagent. If, for example, a reagent of the formula “H-X-H” reacts with another reagent and becomes part of the reaction product, the corresponding moiety of the reaction product has the structure “H-X-” or “-X-”, whereas each indicates attachment to another moiety. Accordingly, a drug moiety is released from a prodrug as a drug.

[0032] If a chemical structure of a group of atoms is provided, which group of atoms is attached to at least one other moiety, said chemical structure may be attached to the at least one other moiety in either orientation, unless explicitly stated otherwise. For example, a moiety “-C(O)N(R1)-” may be attached to two moieties either as “-C(O)N(R1)-” or as “-N(R1)C(O)-”. Similarly, a moiety may be attached to two moieties either as or as

[0033] As used herein, the term “functional group” means a group of atoms which can react with other groups of atoms. Functional groups are for example selected from the group consisting of carboxylic acid, primary or secondary amine, maleimide, thiol, sulfonic acid, carbonate, carbamate, hydroxyl, aldehyde, ketone, hydrazine, isocyanate, isothiocyanate, phosphoric acid, phosphonic acid, haloacetyl, alkyl halide, acryloyl, aryl fluoride, hydroxylamine, disulfide, sulfonamides, sulfuric acid, vinyl sulfone, vinyl ketone, diazoalkane, oxirane and aziridine.

[0034] As used herein, the term “pharmaceutically acceptable salt(s) thereof’ refers to salts that retain the biological effectiveness or properties of the compound and that typically are not biologically or otherwise undesirable. In certain embodiments, the compound is capable of forming acid / or base salts by virtue of the presence of amino and / or carboxylic functional groups or groups similar thereto. Pharmaceutically acceptable acid addition salts can be formed with inorganic acids and organic acids, e.g., acetate, aspartate, benzoate, besylate, bromide / hydrobromide, bicarbonate / carbonate, bisulfate / sulfate, camphorsulfonate, chloride / hydrochloride, chlortheophyllinate, citrate, ethanedi sulfonate, fumarate, gluceptate, gluconate, glucuronate, hippurate, hydroiodide / iodide, isethionate, 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 salts. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Organic acids from which salts can be derived include, for example, 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, sulfosalicylic acid, and the like. Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases. Inorganic bases from which salts can be derived include, for example, ammonium salts and metals from columns I to XII of the periodic table. In certain embodiments, the salts are derived from sodium, potassium, ammonium, calcium, magnesium, iron, silver, zinc, and copper; particularly suitable salts include ammonium, potassium, sodium, calcium and magnesium salts. Organic bases from which salts can be derived include, for example, primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, basic ion exchange resins, and the like. Certain organic amines include isopropylamine, benzathine, cholinate, diethanolamine, diethylamine, lysine, meglumine, piperazine, or tromethamine. The pharmaceutically acceptable salts can be synthesized from a parent compound, a basic or acidic moiety, by conventional chemical methods.

[0035] The term "pharmaceutically acceptable" means a substance that does not cause harm when administered to a patient and in certain embodiments means approved by a regulatory agency, such as the EMA (Europe) and / or the FDA (US) and / or any other national regulatory agency for use in animals, in particular for use in humans.

[0036] As used herein the terms “about” or “approx.” in combination with a numerical value is used to indicate a range ranging from and including the numerical value plus and minus no more than 10% of said numerical value. For example, the phrases “about 200” or “approx. 200” is used to mean a range ranging from and including 200 + / - 10%, i.e. ranging from and including 180 to 220. It is understood that a percentage given as “about 20%” or “approx. 20%” does not mean “20% + / - 10%”, i.e. ranging from and including 10 to 30%, but “about 20%” or “approx. 20%” means ranging from and including 18 to 22%, i.e. plus and minus 10% of the numerical value which is 20.

[0037] As used herein, the term “polymer” means a molecule comprising repeating structural units, i.e., the monomers, connected by chemical bonds in a linear, circular, branched, crosslinked or dendrimeric way or a combination thereof, which may be of synthetic or biological origin or a combination of both. It is understood that a polymer may also comprise one or more other chemical groups and / or moieties, such as, for example, one or more functional groups. In certain embodiments a soluble polymer has a molecular weight of at least 0.5 kDa, e.g., a molecular weight of at least 1 kDa, a molecular weight of at least 2 kDa, a molecular weight of at least 3 kDa or a molecular weight of at least 5 kDa. If the polymer is soluble, it in certain embodiments has a molecular weight of at most 1000 kDa, such as at most 750 kDa, such as at most 500 kDa, such as at most 300 kDa, such as at most 200 kDa, or such as at most 100 kDa. It is understood that for water-insoluble polymers, such as hydrogels, no meaningful molecular weight ranges can be provided. It is understood that also a peptide or protein is a polymer in which the amino acids are the repeating structural units, even though the side chains of each amino acid may be different.

[0038] As used herein, the term “polymeric” means a reagent or a moiety comprising one or more polymers or polymer moieties. A polymeric reagent or moiety may optionally also comprise one or more other moiety / moieties, which are in certain embodiments selected from the group consisting of:

[0039] • C1-50alkyl, C2-50 alkenyl, C2-50 alkynyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11 -membered heterobicyclyl, phenyl, naphthyl, indenyl, indanyl, and tetralinyl; and

[0040] • linkages selected from the group comprising wherein dashed lines indicate attachment to the remainder of the moiety or reagent, and

[0041] -R and -Raare independently of each other 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. The person skilled in the art understands that the polymerization products obtained from a polymerization reaction do not all have the same molecular weight, but rather exhibit a molecular weight distribution. Consequently, the molecular weight ranges, molecular weights, ranges of numbers of monomers in a polymer and numbers of monomers in a polymer as used herein, refer to the number average molecular weight and number average of monomers, i.e., to the arithmetic mean of the molecular weight of the polymer or polymeric moiety and the arithmetic mean of the number of monomers of the polymer or polymeric moiety.

[0042] Accordingly, in a polymeric moiety comprising “x” monomer units any integer given for “x” therefore corresponds to the arithmetic mean number of monomers. Any range of integers given for “x” provides the range of integers in which the arithmetic mean numbers of monomers lie. An integer for “x” given as “about x” means that the arithmetic mean numbers of monomers lie in a range of integers of x + / - 10%, in certain embodiments x + / - 8%, in certain embodiments x + / - 5% and in certain embodiments x + / - 2%.

[0043] As used herein, the term “number average molecular weight” means the ordinary arithmetic mean of the molecular weights of the individual polymers.

[0044] As used herein the term “water-soluble” with reference to the compound of the present invention means that at least 1 g of the compound may be dissolved in one liter of water at 20°C to form a homogeneous solution. Accordingly, the term “water-insoluble” with reference to the compound means that less than 1 g of the compound may be dissolved in one liter of water at 20°C to form a homogeneous solution.

[0045] As used herein, the term “PEG-based” in relation to a moiety or reagent means that said moiety or reagent comprises PEG. In certain embodiments a PEG-based moiety or reagent comprises at least 10% (w / w) PEG, such as at least 20% (w / w) PEG, such as at least 30% (w / w) PEG, such as at least 40% (w / w) PEG, such as at least 50% (w / w), such as at least 60 (w / w) PEG, such as at least 70% (w / w) PEG, such as at least 80% (w / w) PEG, such as at least 90% (w / w) PEG, such as at least 95%. The remaining weight percentage of the PEG-based moiety or reagent are other moieties that in certain embodiments are selected from the following moieties and linkages: C1-50alkyl, C2-50 alkenyl, C2-50 alkynyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11 -membered heterobicyclyl, phenyl, naphthyl, indenyl, indanyl, and tetralinyl; and linkages selected from the group comprising wherein dashed lines indicate attachment to the remainder of the moiety or reagent, and

[0046] -R and -Raare independently of each other 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 “substituted” as used herein means that one or more -H atom(s) of a molecule or moiety are replaced by a different atom or a group of atoms, which are referred to as “substituent”.

[0048] In certain embodiments the one or more further optional substituents are independently of each other selected from the group consisting of halogen, -CN, -COORxl, -ORxl, -C(O)Rxl, -C(O)N(RxlRxla), -S(O)2N(RxlRxla), -S(O)N(RxlRxla), -S(O)2Rxl, -S(O)Rxl,

[0049] -N(Rxl)S(O)2N(RxlaRxlb), -SRX1, -N(RxlRxla), -NO2, -OC(O)Rxl, -N(Rxl)C(O)Rxla, -N(Rxl)S(O)2Rxla, -N(Rxl)S(O)Rxla, -N(Rxl)C(O)ORxla, -N(Rxl)C(O)N(RxlaRxlb),

[0050] -OC(O)N(RxlRxla), -T0, C1-50alkyl, C2-50 alkenyl, and C2-50 alkynyl; wherein -T0, C1-50alkyl, C2-50 alkenyl, and C2-50 alkynyl are optionally substituted with one or more -Rx2, which are the same or different and wherein C1-50alkyl, C2-50 alkenyl, and C2-50 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T0-, -C(O)O-, -O-, -C(O)-, -C(O)N(Rx3)-, -S(O)2N(RX3)-, -S(O)N(RX3)-, -S(O)2-, -S(O)-, -N(Rx3)S(O)2N(Rx3a)-, -S-, -N(Rx3)-, -OC(ORx3)(Rx3a)-, -N(Rx3)C(O)N(Rx3a)-, and -OC(O)N(Rx3)-;

[0051] -Rxl, -Rxxla, -Rxlbare independently of each other selected from the group consisting of -H, -T0, Ci-50 alkyl, C2-50alkenyl, and C2-50alkynyl; wherein -T0, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally substituted with one or more -Rx2, which are the same or different and wherein C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T0-, -C(O)O-, -O-, -C(O)-, -C(O)N(Rx3)-, -S(O)2N(RX3)-, -S(O)N(RX3)-; -S(O)2-, -S(O)-, -N(Rx3)S(O)2N(Rx3a)-, -S-, -N(Rx3)-, -OC(ORx3)(Rx3a)-, -N(Rx3)C(O)N(Rx3a)-, and -OC(O)N(Rx3)-; each T0is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, and 8- to 11-membered heterobicyclyl; wherein each T0is independently optionally substituted with one or more -Rx2, which are the same or different; each -Rx2is independently selected from the group consisting of halogen, -CN, oxo (=0), -COORx4, -ORx4, -C(O)Rx4, -C(O)N(Rx4Rx4a), -S(O)2N(Rx4Rx4a), -S(O)N(Rx4Rx4a), -S(O)2RX4, -S(O)RX4, -N(Rx4)S(O)2N(Rx4aRx4b), -SRx4, -N(Rx4Rx4a), -NO2, -OC(O)Rx4, -N(Rx4)C(O)Rx4a, -N(Rx4)S(O)2Rx4a, -N(Rx4)S(O)Rx4a, -N(Rx4)C(O)ORx4a, -N(Rx4)C(O)N(Rx4aRx4b), -OC(O)N(Rx4Rx4a), and C1-6alkyl; wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different; each -Rx3, -Rx3a, -Rx4, -Rx4a, -Rx4bis independently selected from the group consisting of -H and C1-6alkyl; wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different.

[0052] In certain embodiments the one or more further optional substituents are independently of each other selected from the group consisting of halogen, -CN, -COORxl, -ORxl, -C(O)Rxl, -C(O)N(RxlRxla), -S(O)2N(RxlRxla), -S(O)N(RxlRxla), -S(O)2Rxl, -S(O)Rxl,

[0053] -N(Rxl)S(O)2N(RxlaRxlb), -SRxl, -N(RxlRxla), -NO2, -OC(O)Rxl, -N(Rxl)C(O)Rxla, -N(Rxl)S(O)2Rxla, -N(Rxl)S(O)Rxla, -N(Rxl)C(O)ORxla, -N(Rxl)C(O)N(RxlaRxlb),

[0054] -OC(O)N(RxlRxla), -T0, C1-10alkyl, C2-10alkenyl, and C2-10alkynyl; wherein -T0, C1-10alkyl, C2-10alkenyl, and C2-10alkynyl are optionally substituted with one or more -Rx2, which are the same or different and wherein C1-10alkyl, C2-10alkenyl, and C2-10alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T0-, -C(O)O-, -O-, -C(O)-, -C(O)N(Rx3)-, -S(O)2N(RX3)-, -S(O)N(RX3)-, -S(O)2-, -S(O)-, -N(Rx3)S(O)2N(Rx3a)-, -S-, -N(Rx3)-, -OC(ORx3)(Rx3a)-, -N(Rx3)C(O)N(Rx3a)-, and -OC(O)N(Rx3)-; each -Rxl, -Rxla, -Rxlb, -Rx3, -Rx3ais independently selected from the group consisting of -H, halogen, C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl; each T0is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, and 8- to 11-membered heterobicyclyl; wherein each T0is independently optionally substituted with one or more -Rx2, which are the same or different; each -Rx2is independently selected from the group consisting of halogen, -CN, oxo (=0), -C00Rx4, -0Rx4, -C(0)Rx4, -C(O)N(Rx4Rx4a), -S(O)2N(Rx4Rx4a), -S(O)N(Rx4Rx4a), -S(O)2RX4, -S(O)RX4, -N(Rx4)S(O)2N(Rx4aRx4b), -SRx4, -N(Rx4Rx4a), -N02, -0C(0)Rx4, -N(Rx4)C(O)Rx4a, -N(Rx4)S(O)2Rx4a, -N(Rx4)S(O)Rx4a, -N(Rx4)C(O)ORx4a, -N(Rx4)C(O)N(Rx4aRx4b), -OC(O)N(Rx4Rx4a), and C1-6alkyl; wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different; each -Rx4, -Rx4a, -Rx4bis independently selected from the group consisting of -H, halogen, C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl;

[0055] In certain embodiments the one or more further optional substituents are independently of each other selected from the group consisting of halogen, -CN, -C00Rxl, -0Rxl, -C(0)Rxl, -C(0)N(RxlRxla), -S(0)2N(RxlRxla), -S(0)N(RxlRxla), -S(O)2Rxl, -S(O)Rxl,

[0056] -N(Rxl)S(0)2N(RxlaRxlb), -SRX1, -N(RxlRxla), -N02, -0C(0)Rxl, -N(Rxl)C(0)Rxla, -N(Rxl)S(0)2Rxla, -N(Rxl)S(0)Rxla, -N(Rxl)C(0)0Rxla, -N(Rxl)C(0)N(RxlaRxlb),

[0057] -0C(0)N(RxlRxla), -T0, C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl; wherein -T0, C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl are optionally substituted with one or more -Rx2, which are the same or different and wherein C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T0-, -C(0)0-, -0-, -C(0)-, -C(0)N(Rx3)-, -S(O)2N(RX3)-, -S(0)N(RX3)-, -S(0)2-, -S(0)-, -N(Rx3)S(O)2N(Rx3a)-, -S-, -N(Rx3)-, -OC(ORx3)(Rx3a)-, -N(Rx3)C(O)N(Rx3a)-, and -0C(0)N(Rx3)-; each -Rxl, -Rxla, -Rxlb, -Rx2, -Rx3, -Rx3ais independently selected from the group consisting of -H, halogen, C1-6alkyl, C2-6 alkenyl, and C2-6 alkynyl; each T0is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, and 8- to 11-membered heterobicyclyl; wherein each T0is independently optionally substituted with one or more -Rx2, which are the same or different. In certain embodiments a maximum of 6 -H atoms of an optionally substituted molecule are independently replaced by a substituent, e.g. 5 -H atoms are independently replaced by a substituent, 4 -H atoms are independently replaced by a substituent, 3 -H atoms are independently replaced by a substituent, 2 -H atoms are independently replaced by a substituent, or 1 -H atom is replaced by a substituent.

[0058] The term “interrupted” means that a moiety is inserted between two carbon atoms or - if the insertion is at one of the moiety’s ends - between a carbon or heteroatom and a hydrogen atom, in certain embodiments between a carbon and a hydrogen atom.

[0059] As used herein, the term “monocyclic or bicyclic aryl” means an aromatic hydrocarbon ring system which may be monocyclic or bicyclic, wherein the monocyclic aryl ring consists of at least 5 ring carbon atoms and may comprise up to 10 ring carbon atoms and wherein the bicylic aryl ring consists of at least 8 ring carbon atoms and may comprise up to 12 ring carbon atoms. Each hydrogen atom of a monocyclic or bicyclic aryl may be replaced by a substituent as defined below.

[0060] As used herein, the term “monocyclic or bicyclic heteroaryl” means a monocyclic aromatic ring system that may comprise 2 to 6 ring carbon atoms and 1 to 3 ring heteroatoms or a bicyclic aromatic ring system that may comprise 3 to 9 ring carbon atoms and 1 to 5 ring heteroatoms, such as nitrogen, oxygen and sulfur. Examples for monocyclic or bicyclic heteroaryl groups include, but are not limited to, benzofuranyl, benzothiophenyl, furanyl, imidazolyl, indolyl, azaindolyl, azabenzimidazolyl, benzoxazolyl, benzthiazolyl, benzthiadiazolyl, benzotriazolyl, tetrazinyl, tetrazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinolinyl, quinazolinyl, quinoxalinyl, triazolyl, thiazolyl and thiophenyl. Each hydrogen atom of a monocyclic or bicyclic heteroaryl may be replaced by a substituent as defined below.

[0061] As used herein, the term “cleavable triggering moiety (-Tr)” refers to a moiety that may undergo chemical or enzymatic cleavage under physiological conditions (aqueous buffer at pH 7.4, 37°C), wherein upon cleavage of said cleavable triggering moiety a compound will release at least two drug moieties comprising an albumin-binding moiety. As used herein, the term “C1-4alkyl” alone or in combination means a straight-chain or branched alkyl moiety having 1 to 4 carbon atoms. If present at the end of a molecule, examples of straight-chain or branched C1-4alkyl are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl. When two moieties of a molecule are linked by the C1-4alkyl, then examples for such C1-4alkyl groups are -CH2-, -CH2-CH2-, -CH(CH3)-,

[0062] -CH2-CH2-CH2-, -CH(C2H5)-, -C(CH3)2-. Each hydrogen of a C1-4alkyl carbon may optionally be replaced by a substituent as defined above. Optionally, a C1-4alkyl may be interrupted by one or more moieties as defined below.

[0063] As used herein, the term “nucleophile” refers to a reagent or functional group that forms a bond to its reaction partner, i.e., the electrophile by donating both bonding electrons.

[0064] As used herein, the term “C1-4alkyl” alone or in combination means a straight-chain or branched alkyl moiety having 1 to 6 carbon atoms. If present at the end of a molecule, examples of straight-chain and branched C1-4alkyl groups are 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. When two moieties of a molecule are linked by the C1-4alkyl group, then examples for such C1-4alkyl groups are -CH2-, -CH2-CH2-, -CH(CH3)-, -CH2-CH2-CH2-,

[0065] -CH(C2H5)- and -C(CH3)2-. Each hydrogen atom of a C1-4carbon may optionally be replaced by a substituent as defined above. Optionally, a C1-4alkyl may be interrupted by one or more moieties as defined below.

[0066] Accordingly, “C1-40alkyl”, “C1-20 alkyl” or “C1-50alkyl” means an alkyl chain having 1 to 10, 1 to 20 or 1 to 50 carbon atoms, respectively, wherein each hydrogen atom of the C1-10, C1-20 or C1-50carbon may optionally be replaced by a substituent as defined above. Optionally, a C1-10or C1-50alkyl may be interrupted by one or more moieties as defined below.

[0067] As used herein, the term “C2-6 alkenyl” alone or in combination means a straight-chain or branched hydrocarbon moiety comprising at least one carbon-carbon double bond having 2 to 6 carbon atoms. If present at the end of a molecule, examples are -CH=CH2, -CH=CH-CH3, -CH2-CH=CH2, -CH=CHCH2-CH3and -CH=CH-CH=CH2. When two moieties of a molecule are linked by the C2-6 alkenyl group, then an example for such C2-6 alkenyl is -CH=CH-. Each hydrogen atom of a C2-6 alkenyl moiety may optionally be replaced by a substituent as defined above. Optionally, a C2-6 alkenyl may be interrupted by one or more moieties as defined below.

[0068] Accordingly, the term “C2-10alkenyl”, “C2-20 alkenyl” or “C2-50 alkenyl” alone or in combination means a straight-chain or branched hydrocarbon moiety comprising at least one carbon-carbon double bond having 2 to 10, 2 to 20 or 2 to 50 carbon atoms. Each hydrogen atom of a C2-10alkenyl, C2-20 alkenyl or C2-50 alkenyl group may optionally be replaced by a substituent as defined above. Optionally, a C2-10alkenyl, C2-20 alkenyl or C2-50 alkenyl may be interrupted by one or more moieties as defined below.

[0069] As used herein, the term “C2-6 alkynyl” alone or in combination means straight-chain or branched hydrocarbon moiety comprising at least one carbon-carbon triple bond having 2 to 6 carbon atoms. If present at the end of a molecule, examples are -C=CH, -CH2-C≡CH, CH2-CH2-C≡CH and CH2-C≡C-CH3. When two moieties of a molecule are linked by the alkynyl group, then an example is -C=C-. Each hydrogen atom of a C2-6 alkynyl group may optionally be replaced by a substituent as defined above. Optionally, one or more double bond(s) may occur. Optionally, a C2-6 alkynyl may be interrupted by one or more moieties as defined below.

[0070] Accordingly, as used herein, the term “C2-10alkynyl”, “C2-20 alkynyl” and “C2-50 alkynyl” alone or in combination means a straight-chain or branched hydrocarbon moiety comprising at least one carbon-carbon triple bond having 2 to 10, 2 to 20 or 2 to 50 carbon atoms, respectively. Each hydrogen atom of a C2-10alkynyl, C2-20 alkynyl or C2-50 alkynyl group may optionally be replaced by a substituent as defined above. Optionally, one or more double bond(s) may occur. Optionally, a C2-10alkynyl, C2-20 alkynyl or C2-50 alkynyl may be interrupted by one or more moieties as defined below.

[0071] As mentioned above, a C1-4alkyl, C1-6 alkyl, C1-10 alkyl, C1-20 alkyl, C1-50alkyl, C2-6 alkenyl, C2-10alkenyl, C2-20 alkenyl, C2-50 alkenyl, C2-6 alkynyl, C2-10alkynyl, C2-20 alkenyl or C2-50 alkynyl may optionally be interrupted by one or more moieties which in certain embodiments are selected from the group consisting of

[0072] wherein dashed lines indicate attachment to the remainder of the moiety or reagent; and

[0073] -R and -Raare independently of each other 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.

[0074] As used herein, the term "C3-10 cycloalkyl" means a cyclic alkyl chain having 3 to 10 carbon atoms, which may be saturated or unsaturated, e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, cyclononyl or cyclodecyl. Each hydrogen atom of a C3-10 cycloalkyl carbon may be replaced by a substituent as defined above. The term "C3-10 cycloalkyl" also includes bridged bicycles like norbomane or norbornene.

[0075] The term “8- to 30-membered carbopoly cyclyl” or “8- to 30-membered carbopoly cycle” means a cyclic moiety of two or more rings with 8 to 30 ring atoms, where two neighboring rings share at least one ring atom and that may contain up to the maximum number of double bonds (aromatic or non-aromatic ring which is fully, partially or un- saturated). In certain embodiments an 8- to 30-membered carbopoly cyclyl means a cyclic moiety of two, three, four or five rings, in certain embodiments of two, three or four rings.

[0076] As used herein, the term "3- to 10-membered heterocyclyl" or "3- to 10-membered heterocycle" means a ring with 3, 4, 5, 6, 7, 8, 9 or 10 ring atoms that may contain up to the maximum number of double bonds (aromatic or non-aromatic ring which is fully, partially or unsaturated) wherein at least one ring atom up to 4 ring atoms are replaced by a heteroatom selected from the group consisting of sulfur (including -S(O)-, -S(O)2-), oxygen and nitrogen (including =N(0)-) and wherein the ring is linked to the rest of the molecule via a carbon or nitrogen atom. Examples for 3- to 10-membered heterocycles include but are not limited to aziridine, oxirane, thiirane, azirine, oxirene, thiirene, azetidine, oxetane, thietane, furan, thiophene, pyrrole, pyrroline, imidazole, imidazoline, pyrazole, pyrazoline, oxazole, oxazoline, isoxazole, isoxazoline, thiazole, thiazoline, isothiazole, isothiazoline, thiadiazole, thiadiazoline, tetrahydrofiiran, tetrahydrothiophene, pyrrolidine, imidazolidine, pyrazolidine, oxazolidine, isoxazolidine, thiazolidine, isothiazolidine, thiadiazolidine, sulfolane, pyran, dihydropyran, tetrahydropyran, imidazolidine, pyridine, pyridazine, pyrazine, pyrimidine, piperazine, piperidine, morpholine, tetrazole, triazole, triazolidine, tetrazolidine, diazepane, azepine and homopiperazine. Each hydrogen atom of a 3- to 10-membered heterocyclyl or 3- to 10-membered heterocyclic group may be replaced by a substituent as defined below.

[0077] As used herein, the term "8- to 11 -membered heterobicyclyl" or "8- to 11 -membered heterobicycle" means a heterocyclic moiety of two rings with 8 to 11 ring atoms, where at least one ring atom is shared by both rings and that may contain up to the maximum number of double bonds (aromatic or non-aromatic ring which is fully, partially or un-saturated) wherein at least one ring atom up to 6 ring atoms are replaced by a heteroatom selected from the group consisting of sulfur (including -S(O)-, -S(O)2-), oxygen and nitrogen (including =N(O)-) and wherein the ring is linked to the rest of the molecule via a carbon or nitrogen atom. Examples for an 8- to 11 -membered heterobicycle are indole, indoline, benzofuran, benzothiophene, benzoxazole, benzisoxazole, benzothiazole, benzisothiazole, benzimidazole, benzimidazoline, quinoline, quinazoline, dihydroquinazoline, quinoline, dihydroquinoline, tetrahydroquinoline, decahydroquinoline, isoquinoline, decahydroisoquinoline, tetrahydroisoquinoline, dihydroisoquinoline, benzazepine, purine and pteridine. The term 8- to 11-membered heterobicycle also includes spiro structures of two rings like l,4-dioxa-8-azaspiro[4.5]decane or bridged heterocycles like 8-aza-bicyclo[3.2.1]octane. Each hydrogen atom of an 8- to 11- membered heterobicyclyl or 8- to 11-membered heterobicycle carbon may be replaced by a substituent as defined below.

[0078] Similary, the term “8- to 30-membered heteropoly cyclyl” or “8- to 30-membered heteropoly cycle” means a heterocyclic moiety of more than two rings with 8 to 30 ring atoms, in certain embodiments of three, four or five rings, where two neighboring rings share at least one ring atom and that may contain up to the maximum number of double bonds (aromatic or non-aromatic ring which is fully, partially or unsaturated), wherein at least one ring atom up to 10 ring atoms are replaced by a heteroatom selected from the group of sulfur (including -S(O)- and -S(O)2-), oxygen and nitrogen (including =N(O)-) and wherein the ring is linked to the rest of a molecule via a carbon or nitrogen atom.

[0079] It is understood that the phrase “the pair Rx / Ryis joined together with the atom to which they are attached to form a C3-10 cycloalkyl or a 3- to 10-membered heterocyclyl” in relation with a moiety of the structure means that Rxand Ryform the following structure: wherein R is C3-10 cycloalkyl or 3- to 10-membered heterocyclyl.

[0080] It is also understood that the phrase “the pair Rx / Ryis joint together with the atoms to which they are attached to form a ring A” in relation with a moiety of the structure means that Rxand Ryform the following structure:

[0081] As used herein, "halogen" means fluoro, chloro, bromo or iodo. In certain embodiments halogen is fluoro or chloro.

[0082] In general, the term “comprise” or “comprising” also encompasses “consist of’ or “consisting of’. The compounds of the present invention release a compound H-D-AB upon cleavage of the linkage between -L1- and -D-, wherein H- is hydrogen. If a compound of the present invention for example comprises semaglutide in bound form, such as conjugated to -L1- or -L1-, the semaglutide moiety -D-AB may for simplification be referred to herein as semaglutide, even though it strictly speaking would be a “semaglutide moiety”.

[0083] The compounds release the corresponding free drug of the moiety -D-AB, which is H-D-AB, wherein H- is hydrogen.

[0084] In certain embodiments the compound comprises at least one polymeric moiety, to which at least two moieties of formula (I) are conjugated, wherein formula (I) is wherein each -L2- is independently a spacer moiety or is absent; each -L1- is independently a linker moiety that is covalently and reversibly conjugated to -D-; each -D- is independently a drug moiety; each -AB is independently an albumin-binding moiety.

[0085] In certain embodiments the compound comprises at least one polymeric moiety, to which at least one moiety of formula (T) is conjugated, wherein formula (T) is wherein each -L2- is independently a spacer moiety or is absent; each -L1- is independently a linker moiety that is covalently and reversibly conjugated to -D-; each -D- is independently a drug moiety; each -AB is independently an albumin-binding moiety; and each a is independently 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.

[0086] In certain embodiments the compound comprises two moieties of formula (I). In certain embodiments the compound comprises three moieties of formula (I). In certain embodiments the compound comprises four moieties of formula (I). In certain embodiments the compound comprises five moieties of formula (I). In certain embodiments the compound comprises six moieties of formula (I). In certain embodiments the compound comprises seven moieties of formula (I). In certain embodiments the compound comprises eight moieties of formula (I).

[0087] In certain embodiments the at least one polymeric moiety of the compounds of the present invention is a linear polymeric moiety -P-.

[0088] In certain embodiments a moiety of formula (I) or (I’) is conjugated to each of the two ends of such linear moiety -P-.

[0089] In certain embodiments the compound is of formula (I-a) or (I-a’) wherein each -L2- is independently a spacer moiety or is absent; each -L1- is independently a linker moiety that is covalently and reversibly conjugated to -D-; each -L1- is independently a linker moiety that is covalently and reversibly conjugated to -D-; each -D- is independently a drug moiety; each -AB is independently an albumin-binding moiety;

[0090] -P- is a polymeric moiety; and each a is independently 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.

[0091] In certain embodiments the compound is of formula (I-a). In certain embodiments the compound is of formula (I-a’).

[0092] It is understood that a moiety -L1- is conjugated to more than one moiety -D- and that all linkages between -L1- and a moiety -D- are covalent and reversible. In certain embodiments both a of formula (I-a’) are the same integer. In certain embodiments both a of formula (I-a’) are 2. In certain embodiments both a of formula (I-a’) are 3. In certain embodiments both a of formula (I-a’) are 4. In certain embodiments both a of formula (I-a’) are 5. In certain embodiments both a of formula (I-a’) are 6. In certain embodiments both a of formula (I-a’) are 7. In certain embodiments both a of formula (I-a’) are 8. In certain embodiments both a of formula (I-a’) are 9. In certain embodiments both a of formula (I-a’) are 10. In certain embodiments both a of formula (I-a’) are 11. In certain embodiments both a of formula (I-a’) are 12. In certain embodiments both a of formula (I-a’) are 13. In certain embodiments both a of formula (I-a’) are 14. In certain embodiments both a of formula (I-a’) are 15. In certain embodiments both a of formula (I-a’) are 16.

[0093] Optionally, further moieties of formula (I) or (I’) are conjugated to -P- of formula (I-a) or (I- a’).

[0094] In certain embodiments no further moieties of formula (I) or (I’) are conjugated to -P- of formula (I-a) or (I-a’).

[0095] A moiety -P- of formula (I-a) or (I-a’) comprises one or more polymer, such as a polymer selected from the group consisting of poly(2-methacryloyl-oxyethyl phosphoyl cholines), poly(acrylic acids), poly(acrylates), poly(acrylamides), poly(alkoxy) polymers, poly(amides), poly(amidoamines), poly(amino acids), poly(anhydrides), poly(aspartamides), poly(hydroxybutyrate), poly(glycolic acids), polybutylene terephthalates, poly(caprolactones), poly(carbonates), poly(cyanoacrylates), poly(dimethylacrylamides), poly(esters), poly(ethylenes), poly(ethyleneglycols), poly(ethylene oxides), poly(ethylene phosphates), poly(ethyloxazolines), poly(glycolic acids), poly(hydroxyethyl acrylates), poly(hydroxyethyl- oxazolines), poly(2-hydroxyethyl methacrylates), poly(N-(2- hydroxypropyl)methacrylamides), poly(hydroxypropyl methacrylates), poly(hydroxypropyloxazolines), poly(iminocarbonates), poly(lactic acids), poly(lactic-co- glycolic acids), poly(methacrylamides), poly(methacrylates), poly(methyloxazolines), poly(organophosphazenes), poly(ortho esters), poly(oxazolines), polypropylene glycols), poly(siloxanes), poly(urethanes), poly(vinyl alcohols), poly(vinyl amines), poly(vinylmethylethers), poly(vinylpyrrolidones), celluloses, carboxymethyl celluloses, hydroxypropyl methylcelluloses, chitins, chitosans, dextrans, dextrins, gelatins, hyaluronic acids and derivatives, functionalized hyaluronic acids, mannans, pectins, rhamnogalacturonans, starches, hydroxyalkyl starches, hydroxyethyl starches and other carbohydrate-based polymers, xylans, and copolymers thereof.

[0096] In certain embodiments -P- of formula (I-a) or (I-a’) comprises one or more polymer selected from the group consisting of 2-methacryloyl-oxy ethyl phosphoyl cholins, poly(acrylic acids), poly(acrylates), poly(acrylamides), poly(alkyloxy) polymers, poly(amides), poly(amidoamines), poly(amino acids), poly(anhydrides), poly(aspartamides), poly(butyric acids), poly(glycolic acids), polybutylene terephthalates, poly(caprolactones), poly(carbonates), poly(cyanoacrylates), poly(dimethylacrylamides), poly(esters), poly(ethylenes), poly(ethyleneglycols), poly(ethylene oxides), poly(ethyl phosphates), poly(ethyloxazolines), poly(glycolic acids), poly(hydroxyethyl acrylates), poly(hydroxyethyl- oxazolines), poly(hydroxymethacrylates), poly(hydroxypropylmethacrylamides), poly(hydroxypropyl methacrylates), poly(hydroxypropyloxazolines), poly(iminocarbonates), poly(lactic acids), poly(lactic-co-glycolic acids), poly(methacrylamides), poly(methacrylates), poly(methyloxazolines), poly(organophosphazenes), poly(ortho esters), poly(oxazolines), polypropylene glycols), poly(siloxanes), poly(urethanes), poly(vinyl alcohols), poly(vinyl amines), poly(vinylmethylethers), polyvinylpyrrolidones), silicones, celluloses, carbomethyl celluloses, hydroxypropyl methylcelluloses, chitins, chitosans, dextrans, dextrins, gelatins, hyaluronic acids and derivatives, functionalized hyaluronic acids, mannans, pectins, rhamnogalacturonans, starches, hydroxyalkyl starches, hydroxyethyl starches and other carbohydrate-based polymers, xylans, and copolymers thereof.

[0097] In certain embodiments -P- of formula (la) or (I-a’) is a PEG-based or hyaluronic acid-based moiety. In certain embodiments -P- of formula (la) or (I-a’) is a PEG-based moiety. In certain embodiments -P- of formula (la) or (I-a’) is a hyaluronic acid-based moiety.

[0098] In certain embodiments -P- of formula (la) or (I-a’) is of formula (I-ai) wherein dashed lines indicate attachment to -L2-; n is an integer such that the molecular weight of the PEG moiety ranges from about 1 about 20 kDa; -X1- and -X2- are independently of each other selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry1)-, -S(O)2N(Ry1)-, -S(O)N(Ry1)-, -S(O)2-, -S(O)-, -N(Ryl)S(O)2N(Ryla)-, -S-, -N(Ry1)-, -OC(ORyl)(Ryla)-,

[0099] -N(Ryl)C(O)N(Ryla)-, -OC(O)N(Ry1)-, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl; wherein -T-, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally substituted with one or more -Ry2, which are the same or different and wherein C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry3)-,

[0100] -S(O)2N(Ry3)-, -S(O)N(Ry3)-, -S(O)2-, -S(O)-, -N(Ry3)S(O)2N(Ry3a)-, -S-,

[0101] -N(Ry3)-, -OC(ORy3)(Ry3a)-, -N(Ry3)C(O)N(Ry3a)-, and -OC(O)N(Ry3)-;

[0102] -Ryland -Rylaare independently of each other selected from the group consisting of -H, -T, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl; wherein -T, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally substituted with one or more -Ry2, which are the same or different, and wherein C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry4)-, -S(O)2N(Ry4)-, -S(O)N(Ry4)-, -S(O)2-, -S(O)-, -N(Ry4)S(O)2N(Ry4a)-, -S-, -N(Ry4)-, -OC(ORy4)(Ry4a)-, -N(Ry4)C(O)N(Ry4a)-, and -OC(O)N(Ry4)-; each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl, and 8- to 30-membered heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -Ry2, which are the same or different; each -Ry2is independently selected from the group consisting of halogen, -CN, oxo (=0), -C00Ry5, -ORy5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a),

[0103] -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -N O2, -0C(0)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(0)0Ry5a, -N(Ry5)C(O)N(Ry5aRy5b), -OC(O)N(Ry5Ry5a), and C1-6alkyl; wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different; and each -Ry3, -Ry3a, -Ry4, -Ry4a, -Ry5, -Ry5aand -Ry5bis independently selected from the group consisting of -H, and C1-6alkyl, wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different.

[0104] In certain embodiments n of formula (I-ai) ranges from 2 to 22. In certain embodiments -X1- and -X2- of formula (I-ai) are independently of each other selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry1)-, -S(O)2N(Ry1)-, -S(O)N(Ry1)-, -S(O)2-, -S(O)-, -N(Ryl)S(O)2N(Ryla)-, -S-,

[0105] -N(Ry1)-, -OC(ORyl)(Ryla)-, -N(Ryl)C(O)N(Ryla)-, -OC(O)N(Ry1)-, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl; wherein -T-, C1-20 alkyl, C2-20alkenyl, and C2-20alkynyl are optionally substituted with one or more -Ry2, which are the same or different and wherein C1-20 alkyl, C2-20alkenyl, and C2-20alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry3)-, -S(O)2N(Ry3)-, -S(O)N(Ry3)-, -S(O)2-, -S(O)-, -N(Ry3)S(O)2N(Ry3a)-, -S-, -N(Ry3)-, -OC(ORy3)(Ry3a)-, -N(Ry3)C(O)N(Ry3a)-, and -OC(O)N(Ry3)-;

[0106] -Ryland -Rylaare independently of each other selected from the group consisting of -H, -T, C1-10alkyl, C2-10alkenyl, and C2-10alkynyl; wherein -T, C1-10 alkyl, C2-10alkenyl, and C2-10alkynyl are optionally substituted with one or more -Ry2, which are the same or different, and wherein C1-10 alkyl, C2-10alkenyl, and C2-10alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry4)-, -S(O)2N(Ry4)-, -S(O)N(Ry4)-, -S(O)2-, -S(O)-, -N(Ry4)S(O)2N(Ry4a)-, -S-, -N(Ry4)-, -OC(ORy4)(Ry4a)-, -N(Ry4)C(O)N(Ry4a)-, and -OC(O)N(Ry4)-; each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl, and 8- to 30-membered heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -Ry2, which are the same or different;

[0107] -Ry2is selected from the group consisting of halogen, -CN, oxo (=0), -C00Ry5, -0Ry5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -N02, -0C(0)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b), -OC(O)N(Ry5Ry5a), and C1-6alkyl; wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different; and each -Ry3, -Ry3a, -Ry4, -Ry4a, -Ry5, -Ry5aand -Ry5bis independently of each other selected from the group consisting of -H, and C1-6alkyl; wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different. In certain embodiments -X1- and -X2- of formula (I-ai) are independently of each other selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry1)-,

[0108] -S(O)2N(Ryl)-,-S(O)N(Ry1)-, -S(O)2-, -S(O)-, -N(Ryl)S(O)2N(Ryla)-, -S-,

[0109] -N(Ry1)-, -OC(ORyl)(Ryla)-, -N(Ryl)C(O)N(Ryla)-, -OC(O)N(Ry1)-, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl; wherein -T-, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally substituted with one or more -Ry2, which are the same or different and wherein C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry3)-, -S(O)2N(Ry3)-, -S(O)N(Ry3)-, -S(O)2-, -S(O)-, -N(Ry3)S(O)2N(Ry3a)-, -S-, -N(Ry3)-, -OC(ORy3)(Ry3a)-, -N(Ry3)C(O)N(Ry3a)-, and -OC(O)N(Ry3)-;

[0110] -Ryland -Rylaare independently selected from the group consisting of -H, -T, C1-10 alkyl, C2-10alkenyl, and C2-10alkynyl; each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl, and 8- to 30-membered heteropolycyclyl; each -Ry2is independently selected from the group consisting of halogen, and C1-6 alkyl; and each -Ry3, -Ry3a, -Ry4, -Ry4a, -Ry5, -Ry5aand -Ry5bis independently of each other selected from the group consisting of -H, and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different.

[0111] In certain embodiments -P- of formula (I-a) or (I-a’) is of formula (I-ai-i) wherein dashed lines indicate attachment to -L2-; each -XA- is independently selected from the group consisting of

[0112]

[0113] wherein a dashed line indicates attachment to -L2- or the remainder of the moiety of formula (I-ai-i); each -R04, -R04a, -R04band -R04cis independently selected from the group consisting of halogen, -H, -CN, -T0, C1-50alkyl, C2-50 alkenyl, and C2-50 alkynyl; wherein -T0, C1-50alkyl, C2-50 alkenyl, and C2-50 alkynyl are optionally substituted with one or more -R06, which are the same or different, and wherein C1-50alkyl, C2-50 alkenyl, and C2-50 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T0-, -C(O)O-, -O-, -C(O)-, -C(O)N(R07)-, -S(O)2N(R07)-, -S(O)N(R07)-, -S(O)2-, -S(O)-, -N(R07)S(O)2N(R07a)-, -S-,

[0114] -N(R07)-, -OC(OR07)(R07a)-, -N(R07)C(O)N(R07a)-, and -OC(O)N(R07)-; each T0is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, and 8- to 11 -membered heterobicyclyl; wherein each T0is independently optionally substituted with one or more -R06, which are the same or different; and each -R06, -R07and -R07ais independently selected from the group consisting of -H and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different each b is independently 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; each c is independently 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; and n is an integer such that the molecular weight of the PEG moiety ranges from about 1 kDa to about 20 kDa.

[0115] In certain embodiments n of formula (I-ai-i) ranges from 2 to 22, i.e., n is in certain embodiments selected from the group consisting of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 and 22. In general, based on the number of ethylene glycol units the molecular weight of a PEG moiety can be calculated by multiplying the number of ethylene glycol units with 0.044 kDa.

[0116] In certain embodiments both moieties -XA- are identical. In certain embodiments the moieties -XA- are different from each other.

[0117] In certain embodiments a moiety -XA- is selected from the group consisting of formula (x-1), (x-2), (x-3), (x-4), (x-5), (x-6), (x-7), (x-8), (x-9), (x-10), (x-11), (x-12), (x-13), (x-14), (x-15), (x-16), (x-17), (x-18), (x-19), (x-20), (x-21), (x-22) and (x-23). In certain embodiments a moiety -XA- is selected from the group consisting of formula (x-1), (x-2), (x-3), (x-5), (x-6), (x-7), (x-8), (x-12), (x-13), (x-14), (x-15), (x-16), (x-17), (x-18), (x-19), (x-20), (x-21), (x-22) and (x-23). In certain embodiments a moiety -XA- is selected from the group consisting of formula (x-1), (x-2), (x-3), (x-5), (x-6), (x-7), (x-8), (x-12), (x-13), (x-14), (x-15), (x-16), (x- 17), (x-18), (x-19), (x-20) and (x-21). In certain embodiments a moiety -XA- is selected from the group consisting of formula (x-1), (x-2), (x-3), (x-5), (x-12), (x-13), (x-14), (x-15), (x-16), (x-17) and (x-18).

[0118] In certain embodiments -R04of formula is -H. In certain embodiments -R04ais -H. In certain embodiments -R04bis -H. In certain embodiments -R04cis -H.

[0119] In certain embodiments both -XA- are of formula (x-1), in particular of formula (x-E) wherein the dashed line marked with the asterisk indicates attachment to -L2- and the unmarked dashed line indicates attachment to the remainder of -P-. In certain embodiments the dashed line marked with the asterisk indicates attachment to a moiety of formula (x-2) of -L2-. In certain embodiments -P- of formula (I-a) or (I-a’) is of formula (I-aii) wherein dashed lines indicate attachment to -L2-; each b is independently 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; each c is independently an integer selected from the group consisting of 1, 2, 3, 4, 5, 6,

[0120] 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16; and n is used as defined for n of formula (I-ai).

[0121] In certain embodiments -P- of formula (I-a) or (I-a’) is of formula (I-aii’) wherein dashed lines indicate attachment to -L2-; and n is an integer such that the molecular weight of the PEG moiety ranges from about 1 about 20 kDa.

[0122] In certain embodiments -P- of formula (I-a) or (I-a’) is selected from the group consisting of

[0123] wherein dashed lines indicate attachment to -L2-;

[0124] -R04is defined as above; and n is an integer such that the molecular weight of the PEG moiety ranges from about 1 about 20 kDa.

[0125] In certain embodiments -R04of formula (I-aii’-xiii), (I-aii’-xiv), (I-aii’-xv) or (I-aii’-xvi) is -H.

[0126] In certain embodiments n of formulas (I-aii’-i), (I-aii’-ii), (I-aii’-iii), (I-aii’-iv), (I-aii’-v), (I- aii’vi), (I-aii’-vii), (I-aii’-viii), (I-aii’-ix), (I-aii’-x), (I-aii’-xi), (I-aii’-xii), (I-aii’-xiii), (I-aii’- xiv), (I-aii’-xv) and (I to (I-aii’-xvi) ranges from 2 to 22, i.e., n is in certain embodiments selected from the group consisting of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 32 and 22.

[0127] A dashed line in any one of formulas (I-aii’-i), (I-aii’-ii), (I-aii’-iii) and (I-aii’-vi) suitably indicates attachment to -L2- via a moiety of formula (x-2), resulting in a moiety of formula (x- 162’) (x-162’), wherein the dashed line marked with the asterisk indicates attachment to the remainder of -L2- and the unmarked dashed line indicates attachment to the remainder of -P-. A dashed line in any one of formulas (I-aii’-v), (I-aii’-vi), (I-aii’-vii) and (I-aii’-viii) suitably indicates attachment to -L2- via a moiety of formula (x-1), resulting in a moiety of formula (x- 162”) (x-162”), wherein the dashed line marked with the asterisk indicates attachment to the remainder of -L2- and the unmarked dashed line indicates attachment to the remainder of -P-.

[0128] A dashed line in any one of formulas (I-aii”-ix), (I-aii”-x), (I-aii”-xi) and (I-aii ”-xii) suitably indicates attachment to -L2- via a moiety of formula (x-13), resulting in a moiety of formula

[0129] (x-12’) (x-12‘), wherein the dashed line marked with the asterisk indicates attachment to the remainder of -L2- and the unmarked dashed line indicates attachment to the remainder of -P-, with -R04being used as defined in formula (I-ai-i). Suitably, -R04of formula (x-12’) is -H.

[0130] A dashed line in any one of formulas (I-aii ”-xiii), (I-aii”-xiv), (I-aii”-xv) and (I-aii”-xvi) suitably indicates attachment to -L2- via a moiety of formula (x-14), resulting in a moiety of formula (x-12”) (x-12”), wherein the dashed line marked with the asterisk indicates attachment to the remainder of -L2- and the unmarked dashed line indicates attachment to the remainder of -P-, with -R04being used as defined in formula (I-ai-i). Suitably, -R04of formula (x-12”) is -H.

[0131] In certain embodiments n of formula (I-ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is an integer such that the molecular weight of the PEG moiety ranges from 1 to 15 kDa. In certain embodiments n of formula (I-ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is an integer such that the molecular weight of the PEG moiety ranges from 1 to 10 kDa. In certain embodiments n of formula (I-ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is an integer such that the molecular weight of the PEG moiety is about 1 kDa. In certain embodiments n of formula (I-ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is an integer such that the molecular weight of the PEG moiety is about 2 kDa. In certain embodiments n of formula (I- ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is an integer such that the molecular weight of the PEG moiety is about 2.5 kDa. In certain embodiments n of formula (I-ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is an integer such that the molecular weight of the PEG moiety is about 3 kDa. In certain embodiments n of formula (I-ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is an integer such that the molecular weight of the PEG moiety is about 4 kDa. In certain embodiments n of formula (I-ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is an integer such that the molecular weight of the PEG moiety is about 5 kDa. In certain embodiments n of formula (I-ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is an integer such that the molecular weight of the PEG moiety is about 7.5 kDa. In certain embodiments n of formula (I-ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is an integer such that the molecular weight of the PEG moiety is about 10 kDa. In certain embodiments n of formula (I- ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is an integer such that the molecular weight of the PEG moiety is about 15 kDa. In certain embodiments n of formula (I-ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is an integer such that the molecular weight of the PEG moiety is about 20 kDa.

[0132] In general, the conversion of the molecular weight of a PEG moiety to the number of ethylene glycol units, such as n in formula (I-ai), (I-ai-i), (I-aii), (I-aii’), (I-aii’-i), (I-aii’-ii), (I-aii’-iii), (I-aii ’-iv), (I-aii ’-v), (I-aii ’-vi), (I-aii ’-vii), (I-aii ’-viii), (I-aii ’-ix), (I-aii ’-x), (I-aii ’-xi), (I- aii’-xii), (I-aii ’-xiii), (I-aii’-xiv), (I-aii’-xv) and (I-aii’-xvi), can easily be made by dividing the molecular weight of the PEG moiety in kDa by 0.044 (molecular weight of one ethylene glycol unit: 44 Da).

[0133] In certain embodiments n of formula (I-ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is an integer ranging from and including about 22 to about 450. In certain embodiments n of formula (I-ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is about 22. In certain embodiments n of formula (I-ai), (I-ai-i), (I-aii) or (I-aii’) is about 23. In certain embodiments n of formula (I-ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is about 45. In certain embodiments n of formula (I-ai) is about 57. In certain embodiments n of formula (I-ai), (I-ai- i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is about 68. In certain embodiments n of formula (I- ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is about 90. In certain embodiments n of formula (I-ai) is about 113. In certain embodiments n of formula (I-ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is about 170. In certain embodiments n of formula (I-ai), (I-ai-i), (I- aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is about 230. In certain embodiments n of formula (I-ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is about 340. In certain embodiments n of formula (I-ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is about 450.

[0134] In certain embodiments n of formula (I-ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is an integer ranging from and including 2 to 21. In certain embodiments n of formula (I-ai), (I- ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is 2. In certain embodiments n of formula (I-ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is 2. In certain embodiments n of formula (I- ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is 3. In certain embodiments n of formula (I-ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is 4. In certain embodiments n of formula (I-ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is 5. In certain embodiments n of formula (I-ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is 6. In certain embodiments n of formula (I-ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is 7. In certain embodiments n of formula (I-ai), (I-ai-i), (I-aii), (I-aii’) or (I-aii’-i) to (I-aii’-xvi) is 2.

[0135] In certain embodiments -P- of formula (I-a) or (I-a’) is of formula (P-i) wherein dashed lines indicate attachment to -L2-, and n ranges from 50 to 200.

[0136] In certain embodiments -P- of formula (I-a) or (I-a’) is of formula (P-ii) wherein dashed lines indicate attachment to -L2-; and n ranges from 50 to 200. In certain embodiments n of formula (P-i) and (P-ii) ranges 60 to 180, from 70 to 160, from 80 to 160, from 90 to 140, from 95 to 130 or from 100 to 125. In certain embodiments n of formula (P-i) and (P-ii) n is selected such that P has a molecular weight of about 5 kDa.

[0137] In certain embodiments n of formulas (P-i) or (P-ii) ranges from 2 to 22, i.e., n is in certain embodiments 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22.

[0138] In certain embodiments n of formulas (P-i) or (P-ii) ranges from 23 to 49, i.e., n is in certain embodiments 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 or 49.

[0139] In certain embodiments -P- of formula (I-a) or (I-a’) is of formula (I-aiv) wherein the dashed lines indicate attachment to -BP-; each -XA- is independently used as defined in formula (I-ai-i); d, e, f and g are independently an integer selected from the group consisting of 1, 2,3, 4, 5, 6, 7, 8, 9 and 10; each m is independently an integer ranging from 1 to 100; and n is an integer such that the molecular weight of the PEG moiety ranges from about 1 about 20 kDa.

[0140] In certain embodiments d of formula (I-aiv) is an integer ranging from 1 to 8. In certain embodiments d of formula (I-aiv) is an integer ranging from 1 to 6. In certain embodiments d of formula (I-aiv) is 1. In certain embodiments d of formula (I-aiv) is 2. In certain embodiments d of formula (I-aiv) is 3. In certain embodiments d of formula (I-aiv) is 4. In certain embodiments d of formula (I-aiv) is 5. In certain embodiments d of formula (I-aiv) is 6.

[0141] In certain embodiments g of formula (I-aiv) is an integer ranging from 1 to 8. In certain embodiments g of formula (I-aiv) is an integer ranging from 1 to 6. In certain embodiments g of formula (I-aiv) is 1. In certain embodiments g of formula (I-aiv) is 2. In certain embodiments g of formula (I-aiv) is 3. In certain embodiments g of formula (I-aiv) is 4. In certain embodiments g of formula (I-aiv) is 5. In certain embodiments g of formula (I-aiv) is 6.

[0142] In certain embodiments d and g of formula (I-aiv) are the same integer. In certain embodiments both d and g of formula (I-aiv) are 1. In certain embodiments both d and g of formula (I-aiv) are 2. In certain embodiments both d and g of formula (I-aiv) are 3. In certain embodiments both d and g of formula (I-aiv) are 4.

[0143] In certain embodiments e of formula (I-aiv) is an integer ranging from 1 to 8. In certain embodiments e of formula (I-aiv) is an integer ranging from 1 to 6. In certain embodiments e of formula (I-aiv) is 1. In certain embodiments e of formula (I-aiv) is 2. In certain embodiments e of formula (I-aiv) is 3. In certain embodiments e of formula (I-aiv) is 4. In certain embodiments e of formula (I-aiv) is 5. In certain embodiments e of formula (I-aiv) is 6.

[0144] In certain embodiments f of formula (I-aiv) is an integer ranging from 1 to 8. In certain embodiments f of formula (I-aiv) is an integer ranging from 1 to 6. In certain embodiments f of formula (I-aiv) is 1. In certain embodiments f of formula (I-aiv) is 2. In certain embodiments f of formula (I-aiv) is 3. In certain embodiments f of formula (I-aiv) is 4. In certain embodiments f of formula (I-aiv) is 5. In certain embodiments f of formula (I-aiv) is 6.

[0145] In certain embodiments e and f of formula (I-aiv) are the same integer. In certain embodiments both e and f of formula (I-aiv) are 1. In certain embodiments both e and f of formula (I-aiv) are 2. In certain embodiments both e and f of formula (I-aiv) are 3. In certain embodiments both e and f of formula (I-aiv) are 4.

[0146] In certain embodiments n of formula (I-aiv) is an integer such that the molecular weight of the PEG moiety ranges from 1 to 15 kDa. In certain embodiments n of formula (I-aiv) is an integer such that the molecular weight of the PEG moiety ranges from 1 to 10 kDa. In certain embodiments n of formula (I-aiv) is an integer such that the molecular weight of the PEG moiety is about 1 kDa. In certain embodiments n of formula (I-aiv) is an integer such that the molecular weight of the PEG moiety is about 2 kDa. In certain embodiments n of formula (I- aiv) is an integer such that the molecular weight of the PEG moiety is about 2.5 kDa. In certain embodiments n of formula (I-aiv) is an integer such that the molecular weight of the PEG moiety is about 3 kDa. In certain embodiments n of formula (I-aiv) is an integer such that the molecular weight of the PEG moiety is about 4 kDa. In certain embodiments n of formula (I- aiv) is an integer such that the molecular weight of the PEG moiety is about 5 kDa. In certain embodiments n of formula (I-aiv) is an integer such that the molecular weight of the PEG moiety is about 7.5 kDa. In certain embodiments n of formula (I-aiv) is an integer such that the molecular weight of the PEG moiety is about 10 kDa. In certain embodiments n of formula (I- aiv) is an integer such that the molecular weight of the PEG moiety is about 15 kDa. In certain embodiments n of formula (I-aiv) is an integer such that the molecular weight of the PEG moiety is about 20 kDa.

[0147] In certain embodiments n of formula (I-aiv) is an integer ranging from and including about 22 to about 450. In certain embodiments n of formula (I-aiv) is about 22. In certain embodiments n of formula (I-aiv) is about 23. In certain embodiments n of formula (I-aiv) is about 45. In certain embodiments n of formula (I-ai) is about 57. In certain embodiments n of formula (I- aiv) is about 68. In certain embodiments n of formula (I-aiv) is about 90. In certain embodiments n of formula (I-ai) is about 113. In certain embodiments n of formula (I-aiv) is about 170. In certain embodiments n of formula (I-aiv) is about 230. In certain embodiments n of formula (I-aiv) is about 340. In certain embodiments n of formula (I-aiv) is about 450.

[0148] In certain embodiments the at least one polymeric moiety is a linear polymeric moiety -P- comprising a first and a second end and the at least two moieties of formula (I) and / or the at least one moiety of formula (I’) is / are conjugated to -P- at sites selected from the group consisting of internal sites, the first end and the second end.

[0149] In certain embodiments the at least one polymeric moiety of the compounds of the present invention comprises a plurality of linearly connected units selected from the group consisting of an unmarked dashed line indicates a point of attachment to an adjacent unit at a dashed line marked with # or to a hydrogen, a dashed line marked with # indicates a point of attachment to an adjacent unit at an unmarked dashed line or to a hydroxyl; a dashed line marked with the asterisk indicates attachment to -L2-; the total number of units Z2in -P- is at least 2; the total number of units Z1and Z2is at least 5;

[0150] -Ra1and -Ra2are each independently selected from the group consisting of hydrogen; Ci-4 alkyl; an alkali metal ion, an ammonium ion, an alkaline earth metal ion, or other suitable counterion;

[0151] -X3- is selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry1)-, -S(O)2N(Ry1)-, -S(O)N(Ry1)-, -S(O)2-, -S(O)-, -N(Ryl)S(O)2N(Ryla)-, -S-, -N(Ry1)-, -OC(ORyl)(Ryla)-, -N(Ryl)C(O)N(Ryla)-, -OC(O)N(Ry1)-, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl; wherein -T-, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally substituted with one or more -Ry2, which are the same or different and wherein C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry3)-, -S(O)2N(Ry3)-, -S(O)N(Ry3)-, -S(O)2-, -S(O)-, -N(Ry3)S(O)2N(Ry3a)-, -S-, -N(Ry3)-, -OC(ORy3)(Ry3a)-, -N(Ry3)C(O)N(Ry3a)-, and -OC(O)N(Ry3)-;

[0152] -Ryland -Rylaare independently of each other selected from the group consisting of -H, -T, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl; wherein -T, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally substituted with one or more -Ry2, which are the same or different, and wherein C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry4)-, -S(O)2N(Ry4)-, -S(O)N(Ry4)-, -S(O)2-, -S(O)-, -N(Ry4)S(O)2N(Ry4a)-, -S-, -N(Ry4)-, -OC(ORy4)(Ry4a)-, -N(Ry4)C(O)N(Ry4a)-, and -OC(O)N(Ry4)-; each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl, and 8- to 30-membered heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -Ry2, which are the same or different; each -Ry2is independently selected from the group consisting of halogen, -CN, oxo (=0), -C00Ry5, -ORy5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -N02, -OC(O)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b), -OC(O)N(Ry5Ry5a), and C1-6alkyl; wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different; and each -Ry3, -Ry3a, -Ry4, -Ry4a, -Ry5, -Ry5aand -Ry5bis independently selected from the group consisting of -H, and C1-6alkyl, wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different.

[0153] In certain embodiments -X3- is selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry1)-, -S(O)2N(Ry1)-, -S(O)N(Ry1)-, -S(O)2-,

[0154] -S(O)-, -N(Ryl)S(O)2N(Ryla)-, -S-, -N(Ry1)-, -OC(ORyl)(Ryla)-, -N(Ryl)C(O)N(Ryla)-, -OC(O)N(Ry1)-, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl; wherein -T-, C1-20 alkyl, C2.2o alkenyl, and C2-20alkynyl are optionally substituted with one or more -Ry2, which are the same or different and wherein C1-20 alkyl, C2-20alkenyl, and C2-20alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry3)-, -S(O)2N(Ry3)-, -S(O)N(Ry3)-, -S(O)2-, -S(O)-, -N(Ry3)S(O)2N(Ry3a)-, -S-, -N(Ry3)-, -OC(ORy3)(Ry3a)-, -N(Ry3)C(O)N(Ry3a)-, and -OC(O)N(Ry3)-;

[0155] -Ryland -Rylaare independently of each other selected from the group consisting of -H, -T, C 1-10 alkyl, C2-10alkenyl, and C2-10alkynyl; wherein -T, C1-10alkyl, C2-10alkenyl, and C2-10alkynyl are optionally substituted with one or more -Ry2, which are the same or different, and wherein C1-10alkyl, C2-10alkenyl, and C2-10alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry4)-, -S(O)2N(Ry4)-, -S(O)N(Ry4)-, -S(O)2-, -S(O)-, -N(Ry4)S(O)2N(Ry4a)-, -S-, -N(Ry4)-, -OC(ORy4)(Ry4a)-, -N(Ry4)C(O)N(Ry4a)-, and -OC(O)N(Ry4)-; each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl, and 8- to 30-membered heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -Ry2, which are the same or different;

[0156] -Ry2is selected from the group consisting of halogen, -CN, oxo (=0), -COORy5, -ORy5, -C(O)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -N02, -OC(O)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)O Ry5a, -N(Ry5)C(O)N(Ry5aRy5b), -OC(O)N(Ry5Ry5a), and C1-6alkyl; wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different; and each -Ry3, -Ry3a, -Ry4, -Ry4a, -Ry5, -Ry5aand -Ry5bis independently of each other selected from the group consisting of -H, and C1-6alkyl; wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different.

[0157] In certain embodiments -X3- is selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry1)-, -S(O)2N(Ryl)-,-S(O)N(Ry1)-, -S(O)2-,

[0158] -S(O)-, -N(Ryl)S(O)2N(Ryla)-, -S-, -N(Ry1)-, -OC(ORyl)(Ryla)-,

[0159] -N(Ryl)C(O)N(Ryla)-, -OC(O)N(Ry1)-, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl; wherein -T-, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally substituted with one or more -Ry2, which are the same or different and wherein C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry3)-,

[0160] -S(O)2N(Ry3)-, -S(O)N(Ry3)-, -S(O)2-, -S(O)-, -N(Ry3)S(O)2N(Ry3a)-, -S-,

[0161] -N(Ry3)-, -OC(ORy3)(Ry3a)-, -N(Ry3)C(O)N(Ry3a)-, and -OC(O)N(Ry3)-;

[0162] -Ryland -Rylaare independently selected from the group consisting of -H, -T, C1-10 alkyl, C2-10alkenyl, and C2-10alkynyl; each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl, and 8- to 30-membered heteropolycyclyl; each -Ry2is independently selected from the group consisting of halogen, and C1-6alkyl; and each -Ry3, -Ry3a, -Ry4, -Ry4a, -Ry5, -Ry5aand -Ry5bis independently of each other selected from the group consisting of -H, and C1-6alkyl; wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different.

[0163] In certain embodiments the total number of units Z1and Z2is such that -P- has a molecular weight ranging from about 1 about 20 kDa. In certain embodiments the total number of units Z1and Z2is such that -P- has a molecular weight ranging from about 1 about 15 kDa. In certain embodiments the total number of units Z1and Z2is such that -P- has a molecular weight of about 1 kDa. In certain embodiments the total number of units Z1and Z2is such that -P- has a molecular weight of about 2 kDa. In certain embodiments the total number of units Z1and Z2is such that -P- has a molecular weight of about 3 kDa. In certain embodiments the total number of units Z1and Z2is such that -P- has a molecular weight of about 4 kDa. In certain embodiments the total number of units Z1and Z2is such that -P- has a molecular weight of about 5 kDa. In certain embodiments the total number of units Z1and Z2is such that -P- has a molecular weight of about 7.5 kDa. In certain embodiments the total number of units Z1and Z2is such that -P- has a molecular weight of about 10 kDa. In certain embodiments the total number of units Z1and Z2is such that -P- has a molecular weight of about 15 kDa. In certain embodiments the total number of units Z1and Z2is such that -P- has a molecular weight of about 20 kDa.

[0164] In certain embodiments -X3- is of formula (I-b) wherein the unmarked dashed line indicates attachment to the carbonyl of Z2; the dashed line marked with the asterisk indicates attachment to -L2-; dl is independently 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; d2 is independently 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.

[0165] In certain embodiments dl of formula (I-b) is 1. In certain embodiments dl of formula (I-b) is 2. In certain embodiments dl of formula (I-b) is 3. In certain embodiments dl of formula (I-b) is 4. In certain embodiments dl of formula (I-b) is 5. In certain embodiments dl of formula (I- b) is 6.

[0166] In certain embodiments d2 of formula (I-b) is 1. In certain embodiments d2 of formula (I-b) is 2. In certain embodiments d2 of formula (I-b) is 3. In certain embodiments d2 of formula (I-b) is 4. In certain embodiments d2 of formula (I-b) is 5. In certain embodiments d2 of formula (I- b) is 6. In certain embodiments -X3- is of formula (I-b’) wherein the unmarked dashed line indicates attachment to the carbonyl of Z2; and the dashed line marked with the asterisk indicates attachment to -L2-.

[0167] In certain embodiments the compound is of formula (I-c) or (I-c’) wherein each -L2- is independently a spacer moiety or is absent; each -L1- is independently a linker moiety that is covalently and reversibly conjugated to -D-; each -L1- is independently a linker moiety that is covalently and reversibly conjugated to -D-; each -D- is independently a drug moiety; each -AB is independently an albumin-binding moiety;

[0168] -P- is a polymeric moiety; each BP is independently a branching point; each a is independently an integer selected from the group consisting of 1, 2, 3, 4, 5, 6,

[0169] 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16; and p and q are independently an integer selected from the group consisting of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16.

[0170] In certain embodiments the compound is of formula (I-c). In certain embodiments the compound is of formula (I-c’). It is understood that a moiety -L1- is conjugated to more than one moiety -D- and that all linkages between -L1- and a moiety -D- are covalent and reversible.

[0171] In certain embodiments both a of formula (I-c’ ) are the same integer. In certain embodiments both a of formula (I-c’) are 2. In certain embodiments both a of formula (I-c’) are 3. In certain embodiments both a of formula (I-c’) are 4. In certain embodiments both a of formula (I-c’) are 5. In certain embodiments both a of formula (I-a’) are 6. In certain embodiments both a of formula (I-c’) are 7. In certain embodiments both a of formula (I-c’) are 8. In certain embodiments both a of formula (I-c’) are 9. In certain embodiments both a of formula (I-c’) are 10. In certain embodiments both a of formula (I-c’) are 11. In certain embodiments both a of formula (I-c’) are 12. In certain embodiments both a of formula (I-c’) are 13. In certain embodiments both a of formula (I-c’) are 14. In certain embodiments both a of formula (I-c’) are 15. In certain embodiments both a of formula (I-c’) are 16.

[0172] In certain embodiments p and q of formula (I-c) or (I-c’) are the same integer. In certain embodiments p and q of formula (I-c) or (I-c’) are a different integer.

[0173] Embodiments for -P- are as described for formula (I-a) and (I-a’) elsewhere herein.

[0174] Each BP of formula (I-c) and (I-c’) is independently a branching point. In certain embodiments both BP are identical. In certain embodiments both BP are different. BP point may be a single atom, such as a nitrogen or carbon atom, or may be a group of atoms, such as a di-, tri- or tetraamino acid. A diamino acid may be selected from the group consisting of lysine, ornithine, 2,3-diaminoproprionic acid and 2,4-diaminobutyric acid, each either in R- and S-configuration.

[0175] In certain embodiments BP of formula (I-c’) comprises a lysine, in particular a lysine in S- configuration. In certain moieties both moieties BP of formula (I-c’) comprise a lysine, in particular a lysine in S-configuration.

[0176] In certain embodiments both moieties BP have the structure of formula (I-c-i) wherein the unmarked dashed lines indicate attachment to -L2-; the dashed line marked with the asterisk indicates attachment to -P-; and each h is independently an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7,

[0177] 8, 9 and 10; and each i is independently an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10.

[0178] In certain embodiments both h of formula (I-c-i) are the same integer. In certain embodiments both h of formula (I-c-i) are 2 and i of formula (I-c-i) is 4. In certain embodiments both h of formula (I-c-i) are 3 and i of formula (I-c-i) is 4. In certain embodiments both h of formula (I- c-i) are 4 and i of formula (I-c-i) is 4.

[0179] In certain embodiments both moieties BP have the structure of formula (I-c-i’) the unmarked dashed lines indicate attachment to -L2-; and the dashed line marked with the asterisk indicates attachment to -P-. In certain embodiments one BP of formula (I-c’) is lysine, in particular lysine in S configuration. In certain embodiments both moeities BP of formula (I-c’) are lysine, in particular lysine in S configuration. In certain embodiments the moiety BP-P-BP is of formula (I-d’)

[0180] (I-d’), wherein the dashed lines indicate attachment to -L2-; each m is independently an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7 and 8; n is an integer ranging from 2 to 200; each o is independently an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7 and 8; and each p is independently an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7 and 8.

[0181] In certain embodiments the moiety BP-P-BP is of formula (I-d) (I-d), wherein the dashed lines indicate attachment to -L2-; each m is independently an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7 and 8; each p is independently an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7 and 8; and n is an integer ranging from 2 to 200.

[0182] In certain embodiments n of formula (I-d) and (I-d’) ranges 60 to 180, from 70 to 160, from 80 to 160, from 90 to 140, from 95 to 130 or from 100 to 125. In certain embodiments n of formula (I-d) and (I-d’) is selected such that P has a molecular weight of about 5 kDa.

[0183] In certain embodiments the moiety BP-P-BP is of formula (I-e)

[0184] (I-e), wherein dashed lines indicate attachment to -L2-; and n is an integer ranging from 2 to 200.

[0185] In certain embodiments n of formula (I-e) ranges 60 to 180, from 70 to 160, from 80 to 160, from 90 to 140, from 95 to 130 or from 100 to 125. In certain embodiments n of formula (I-e) is selected such that P has a molecular weight of about 5 kDa.

[0186] In certain embodiments the at least one polymeric moiety of the compound of the present invention is a multi-arm polymeric moiety. Such multi-arm polymeric moiety comprises at least one branching point. Accordingly, in certain embodiments the compound comprises at least one branching point B, to which at least two moieties of formula (lb) and / or at least one moiety of formula (lb’) are conjugated, wherein formula (lb) and (lb’) are wherein the dashed line indicates attachment to a branching point B;

[0187] -A- is a polymeric moiety each -L2- is independently a spacer moiety or is absent; each -L1- is independently a linker moiety that is covalently and reversibly conjugated to -D-; each -L1- is independently a linker moiety that is covalently and reversibly conjugated to -D-; each -D- is independently a drug moiety; each -AB is independently an albumin-binding moiety; and each a is independently 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.

[0188] In certain embodiments the compound comprises at least one branching point B, to which at least two moieties of formula (lb) are conjugated, wherein formula (lb) is

[0189] -:-A-L2-L1-D-AB(IB)wherein the dashed line indicates attachment to a branching point B;

[0190] -A- is a polymeric moiety each -L2- is independently a spacer moiety or is absent; each -L1- is independently a linker moiety that is covalently and reversibly conjugated to -D-; each -D- is independently a drug moiety; and each -AB is independently an albumin-binding moiety.

[0191] In certain embodiments the compound comprises at least one branching point B, to which at least one moiety of formula (lb’) is conjugated, wherein formula (lb’) is wherein the dashed line indicates attachment to a branching point B;

[0192] -A- is a polymeric moiety each -L2- is independently a spacer moiety or is absent; each -L1- is independently a linker moiety that is covalently and reversibly conjugated to -D-; each -D- is independently a drug moiety; each -AB is independently an albumin-binding moiety; and each a is independently 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.

[0193] The moiety -A- of formula (lb) or (lb’) comprises one or more polymer, such as a polymer selected from the group consisting of 2-methacryloyl-oxy ethyl phosphoyl cholins, poly(acrylic acids), poly(acrylates), poly(acrylamides), poly(alkyloxy) polymers, poly(amides), poly(amidoamines), poly(amino acids), poly(anhydrides), poly(aspartamides), poly(butyric acids), poly(glycolic acids), polybutylene terephthalates, poly(caprolactones), poly(carbonates), poly(cyanoacrylates), poly(dimethylacrylamides), poly(esters), poly(ethylenes), poly(ethyleneglycols), poly(ethylene oxides), poly(ethyl phosphates), poly(ethyloxazolines), poly(glycolic acids), poly(hydroxyethyl acrylates), poly(hydroxyethyl- oxazolines), poly(hydroxymethacrylates), poly(hydroxypropylmethacrylamides), poly(hydroxypropyl methacrylates), poly(hydroxypropyloxazolines), poly(iminocarbonates), poly(lactic acids), poly(lactic-co-glycolic acids), poly(methacrylamides), poly(methacrylates), poly(methyloxazolines), poly(organophosphazenes), poly(ortho esters), poly(oxazolines), polypropylene glycols), poly(siloxanes), poly(urethanes), poly(vinyl alcohols), poly(vinyl amines), poly(vinylmethylethers), polyvinylpyrrolidones), silicones, celluloses, carbomethyl celluloses, hydroxypropyl methylcelluloses, chitins, chitosans, dextrans, dextrins, gelatins, hyaluronic acids and derivatives, functionalized hyaluronic acids, mannans, pectins, rhamnogalacturonans, starches, hydroxyalkyl starches, hydroxyethyl starches and other carbohydrate-based polymers, xylans, and copolymers thereof.

[0194] In certain embodiments -A- of formula (lb) or (lb’) comprises a PEG-based polymer or a hyaluronic acid-based polymer. In certain embodiments -A- of formula (lb) or (lb ’) comprises a PEG-based polymer. In certain embodiments -A- of formula (lb) or (lb’) comprises a hyaluronic acid-based polymer. In certain embodiments -A- of formula (lb) or (lb’) is of formula (I-ba) wherein the unmarked dashed line indicates attachment to the branching point B; the dashed line marked with the asterisk indicates attachment to -L2-; z is an integer selected such that the molecular weight of -A- ranges from about 0.5 kDa to about 10 kDa;

[0195] -X8- is selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry1)-, -S(O)2N(Ry1)-, -S(O)N(Ry1)-, -S(O)2-, -S(O)-, -N(Ryl)S(O)2N(Ryla)-, -S-, -N(Ry1)-, -OC(ORyl)(Ryla)-, -N(Ryl)C(O)N(Ryla)-, -OC(O)N(Ry1)-, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl; wherein -T-, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally substituted with one or more -Ry2, which are the same or different and wherein C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry3)-, -S(O)2N(Ry3)-, -S(O)N(Ry3)-, -S(O)2-, -S(O)-, -N(Ry3)S(O)2N(Ry3a)-, -S-, -N(Ry3)-, -OC(ORy3)(Ry3a)-, -N(Ry3)C(O)N(Ry3a)-, and -OC(O)N(Ry3)-;

[0196] -Ryland -Rylaare independently of each other selected from the group consisting of -H, -T, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl; wherein -T, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally substituted with one or more -Ry2, which are the same or different, and wherein C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry4)-, -S(O)2N(Ry4)-, -S(O)N(Ry4)-, -S(O)2-, -S(O)-, -N(Ry4)S(O)2N(Ry4a)-, -S-, -N(Ry4)-, -OC(ORy4)(Ry4a)-, -N(Ry4)C(O)N(Ry4a)-, and -OC(O)N(Ry4)-; each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl, and 8- to 30-membered heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -Ry2, which are the same or different; each -Ry2is independently selected from the group consisting of halogen, -CN, oxo (=0), -COORy5, -ORy5, -C(O)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -N 02, -OC(O)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b), -OC(O)N(Ry5Ry5a), and C1-6alkyl; wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different; and each -Ry3, -Ry3a, -Ry4, -Ry4a, -Ry5, -Ry5aand -Ry5bis independently selected from the group consisting of -H, and C1-6alkyl, wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different.

[0197] In certain embodiments -X8- is selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry1)-, -S(O)2N(Ry1)-, -S(O)N(Ry1)-, -S(O)2-, -S(O)-,

[0198] -N(Ryl)S(O)2N(Ryla)-, -S-, -N(Ry1)-, -OC(ORyl)(Ryla)-, -N(Ryl)C(O)N(Ryla)-, -OC(O)N(Ry1)-, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl; wherein -T-, C1-20 alkyl, C2.2o alkenyl, and C2-20alkynyl are optionally substituted with one or more -Ry2, which are the same or different and wherein C1-20 alkyl, C2-20alkenyl, and C2-20alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry3)-, -S(O)2N(Ry3)-, -S(O)N(Ry3)-, -S(O)2-, -S(O)-, -N(Ry3)S(O)2N(Ry3a)-, -S-, -N(Ry3)-, -OC(ORy3)(Ry3a)-, -N(Ry3)C(O)N(Ry3a)-, and -OC(O)N(Ry3)-;

[0199] -Ryland -Rylaare independently of each other selected from the group consisting of -H, -T, C 1-10 alkyl, C2-10alkenyl, and C2-10alkynyl; wherein -T, C1-10alkyl, C2-10alkenyl, and C2-10alkynyl are optionally substituted with one or more -Ry2, which are the same or different, and wherein C1-10alkyl, C2-10alkenyl, and C2-10alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry4)-, -S(O)2N(Ry4)-, -S(O)N(Ry4)-, -S(O)2-, -S(O)-, -N(Ry4)S(O)2N(Ry4a)-, -S-, -N(Ry4)-, -OC(ORy4)(Ry4a)-, -N(Ry4)C(O)N(Ry4a)-, and -OC(O)N(Ry4)-; each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl, and 8- to 30-membered heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -Ry2, which are the same or different;

[0200] -Ry2is selected from the group consisting of halogen, -CN, oxo (=0), -COORy5, -ORy5, -C(O)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -NO2, -OC(O)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b), -OC(O)N(Ry5Ry5a), and C1-6alkyl; wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different; and each -Ry3, -Ry3a, -Ry4, -Ry4a, -Ry5, -Ry5aand -Ry5bis independently of each other selected from the group consisting of -H, and C1-6alkyl; wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different.

[0201] In certain embodiments -X8- is selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry1)-, -S(O)2N(Ryl)-,-S(O)N(Ry1)-, -S(O)2-,

[0202] -S(O)-, -N(Ryl)S(O)2N(Ryla)-, -S-, -N(Ry1)-, -OC(ORyl)(Ryla)-,

[0203] -N(Ryl)C(O)N(Ryla)-, -OC(O)N(Ry1)-, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl; wherein -T-, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally substituted with one or more -Ry2, which are the same or different and wherein C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry3)-,

[0204] -S(O)2N(Ry3)-, -S(O)N(Ry3)-, -S(O)2-, -S(O)-, -N(Ry3)S(O)2N(Ry3a)-, -S-,

[0205] -N(Ry3)-, -OC(ORy3)(Ry3a)-, -N(Ry3)C(O)N(Ry3a)-, and -OC(O)N(Ry3)-;

[0206] -Ryland -Rylaare independently selected from the group consisting of -H, -T, C1-10 alkyl, C2-10alkenyl, and C2-10alkynyl; each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl, and 8- to 30-membered heteropolycyclyl; each -Ry2is independently selected from the group consisting of halogen, and C1-6alkyl; and each -Ry3, -Ry3a, -Ry4, -Ry4a, -Ry5, -Ry5aand -Ry5bis independently of each other selected from the group consisting of -H, and C1-6alkyl; wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different.

[0207] In certain embodiments -A- of formula (lb) or (lb’) is of formula (I-bb) or (I-bb’) wherein the unmarked dashed line indicates attachment to the branching point B; the dashed line marked with the asterisk indicates attachment to -L2-; z is an integer selected such that the molecular weight of -A- ranges from about 0.5 kDa to about 10 kDa; zl is selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16; and z2 is selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16.

[0208] In certain embodiments -A- of formula (lb) or (lb’) is of formula (I-bb). In certain embodiments -A- of formula (lb) or (lb’) is of formula (I-bb’).

[0209] In certain embodiments -A- of formula (lb) or (lb’) is of formula (I-bc) or (I-bc’) wherein the unmarked dashed line indicates attachment to the branching point B; the dashed line marked with the asterisk indicates attachment to -L2-; z is an integer selected such that the molecular weight of -A- ranges from about 0.5 kDa to about 10 kDa; zl is selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16; and z2 is selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 16. In certain embodiments -A- of formula (lb) or (lb’) is of formula (I-bc). In certain embodiments -A- of formula (lb) or (lb’) is of formula (I-bc’).

[0210] In certain embodiments zl of formula (I-bb), (I-bb’), (I-bc) or (I-bc’) is 1. In certain embodiments zl of formula (I-bb) , (I-bb’), (I-bc) or (I-bc’) is 2. In certain embodiments zl of formula (I-bb), (I-bb’), (I-bc) or (I-bc’) is 3. In certain embodiments zl of formula (I-bb) , (I- bb’), (I-bc) or (I-bc’) is 4. In certain embodiments zl of formula (I-bb), (I-bb’), (I-bc) or (I-bc) is 5. In certain embodiments zl of formula (I-bb), (I-bb’), (I-bc) or (I-bc’) is 6. In certain embodiments zl of formula (I-bb), (I-bb’), (I-bc) or (I-bc’) is 7. In certain embodiments zl of formula (I-bb), (I-bb’), (I-bc) or (I-bc) is 8. In certain embodiments zl of formula (I-bb), (I- bb’), (I-bc) or (I-bc’) is 9. In certain embodiments zl of formula (I-bb), (I-bb’), (I-bc) or (I- bc’) is 10. In certain embodiments zl of formula (I-bb), (I-bb’), (I-bc) or (I-bc’) is 11. In certain embodiments zl of formula (I-bb), (I-bb’), (I-bc) or (I-bc’) is 12. In certain embodiments zl of formula (I-bb) , (I-bb’), (I-bc) or (I-bc’) is 13. In certain embodiments zl of formula (I-bb), (I-bb’), (I-bc) or (I-bc’) is 14. In certain embodiments zl of formula (I-bb), (I-bb’), (I-bc) or (I- bc’) is 15. In certain embodiments zl of formula (I-bb), (I-bb’), (I-bc) or (I-bc’) is 16.

[0211] In certain embodiments z2 of formula (I-bb), (I-bb’), (I-bc) or (I-bc’) is 1. In certain embodiments z2 of formula (I-bb), (I-bb’), (I-bc) or (I-bc’) is 2. In certain embodiments z2 of formula (I-bb), (I-bb’), (I-bc) or (I-bc’) is 3. In certain embodiments z2 of formula (I-bb), (I- bb’), (I-bc) or (I-bc’) is 4. In certain embodiments z2 of formula (I-bb), (I-bb’), (I-bc) or (I- bc’) is 5. In certain embodiments z2 of formula (I-bb), (I-bb’), (I-bc) or (I-bc’) is 6. In certain embodiments z2 of formula (I-bb), (I-bb’), (I-bc) or (I-bc’) is 7. In certain embodiments z2 of formula (I-bb), (I-bb’), (I-bc) or (I-bc’) is 8. In certain embodiments z2 of formula (I-bb), (I- bb’), (I-bc) or (I-bc’) is 9. In certain embodiments z2 of formula (I-bb), (I-bb’), (I-bc) or (I- bc’) is 10. In certain embodiments z2 of formula (I-bb), (I-bb’), (I-bc) or (I-bc’) is 11. In certain embodiments z2 of formula (I-bb), (I-bb’), (I-bc) or (I-bc’) is 12. In certain embodiments z2 of formula (I-bb), (I-bb’), (I-bc) or (I-bc’) is 13. In certain embodiments z2 of formula (I-bb), (I- bb’), (I-bc) or (I-bc’) is 14. In certain embodiments z2 of formula (I-bb), (I-bb’), (I-bc) or (I- bc’) is 15. In certain embodiments z2 of formula (I-bb), (I-bb’), (I-bc) or (I-bc’) is 16. In certain embodiments zl of formula (I-bb), (I-bb’), (I-bc) or (I-bc’) is 3 and z2 of formula (I- bb), (I-bb’), (I-bc) or (I-bc’) is 2. In certain embodiments zl of formula (I-bb), (I-bb’), (I-bc) or (I-bc’) is 2 and z2 of formula (I-bb), (I-bb’), (I-bc) or (I-bc’) is 2.

[0212] In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is an integer such that the molecular weight of the -A- ranges from and includes about 0.5 kDa to about 10 kDa. In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is an integer such that the molecular weight of the -A- is about 0.5 kDa. In certain embodiments z of formula (I- ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is an integer such that the molecular weight of the -A- is about 1 kDa. In certain embodiments of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is an integer such that the molecular weight of the -A- is about 1.5 kDa. In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is an integer such that the molecular weight of the -A- is about 2 kDa. In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is an integer such that the molecular weight of the -A- is about 2.5 kDa. In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is an integer such that the molecular weight of the -A- is about 3 kDa. In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is an integer such that the molecular weight of the -A- is about 3.5 kDa. In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is an integer such that the molecular weight of the -A- is about 4 kDa. In certain embodiments z of formula (I- ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is an integer such that the molecular weight of the -A- is about 5 kDa. In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is an integer such that the molecular weight of the -A- is about 6 kDa. In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is an integer such that the molecular weight of the -A- is about 7 kDa. In certain embodiments of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I- bc’) is an integer such that the molecular weight of the -A- is about 8 kDa. In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is an integer such that the molecular weight of the -A- is about 9 kDa. In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is an integer such that the molecular weight of the -A- is about 10 kDa.

[0213] In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is an integer ranging from and including about 11 to about 230. In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is an integer ranging from and including about 11 to about 225. In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is about 11. In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is about 12. In certain embodiments z of formula(I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is about 22. In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is about 23. In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is about 34. In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is about 45. In certain embodiments z of formula (I-ba), (I-bb) or (-I-bc) is about 57. In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is about 68. In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is about 79. In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is about 90. In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is about 102. In certain embodiments z of formula (I-ba), (I-bb), (I- bb’), (I-bc) or (I-bc’) is about 113. In certain embodiments z of formula (I-bb) or (I-bc) is about 135. In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is about 160. In certain embodiments z of formula (I-bb) or (I-bc) is about 180. In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is about 205. In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is about 225. In certain embodiments z of formula (I-ba), (I-bb), (I-bb’), (I-bc) or (I-bc’) is about 230.

[0214] In certain embodiments the compound comprises one branching point B, such as a branching point selected from the group consisting of wherein dashed lines indicate attachment to -A- of formula (lb);

[0215] -R1is used as defined for the term “substituent”; and

[0216] -X4-, -X5-, -X6- and -X7- are independently used as defined for -X1- and -X2- of formula (I-ai).

[0217] In certain embodiments -X4-, -X5- and -X6- of formula (I-b 1) and (I-b2) are identical. In certain embodiments -X4-, -X5- and -X6- of formula (I-bl) and (I-b2) are identical and are selected from the group consisting of -CH2-, -CH2CH2- and -CH2CH2CH2-. In certain embodiments the compound comprises one branching point of formula (I-bl). In certain embodiments the compound comprises one branching point of formula (I-b2) . In certain embodiments the compound comprises one branching point of formula (I-b3). In certain embodiments the compound comprises one branching point of formula (I-b3), wherein -X4-, -X5-, -X6- and -X7- are identical. In certain embodiments the compound comprises one branching point of formula (I-b3), wherein -X4-, -X5-, -X6- and -X7- are selected from the group consisting of -CH2-, -CH2CH2- and -CH2CH2CH2-. In certain embodiments the compound comprises one branching point of formula (I-b3), wherein -X4-, -X5-, -X6- and -X7- are -CH2-.

[0218] In certain embodiments the compound is of formula (I-b4) wherein each -A- is a polymeric moiety; each -L2- is independently a spacer moiety or is absent; each -L1- is independently a linker moiety that is covalently and reversibly conjugated to -D-; each -D- is independently a drug moiety; each -AB is independently an albumin-binding moiety;

[0219] -X4-, -X5-, -X6- and -X7- are independently of each other selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry1)-, -S(O)2N(Ry1)-, -S(O)N(Ry1)-, -S(O)2-, -S(O)-, -N(Ryl)S(O)2N(Ryla)-, -S-,

[0220] -N(Ry1)-, -OC(ORyl)(Ryla)-, -N(Ryl)C(O)N(Ryla)-, -OC(O)N(Ry1)-, C1-50alkyl, C2-50 alkenyl, and C2-50 alkynyl; wherein -T-, C1-50alkyl, C2-50 alkenyl, and C2-50 alkynyl are optionally substituted with one or more -Ry2, which are the same or different and wherein C1-50alkyl, C2-50 alkenyl, and C2-50 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry3)-, -S(O)2N(Ry3)-, -S(O)N(Ry3)-, -S(O)2-, -S(O)-, -N(Ry3)S(O)2N(Ry3a)-, -S-, -N(Ry3)-, -OC(ORy3)(Ry3a)-, -N(Ry3)C(O)N(Ry3a)-, and -OC(O)N(Ry3)-;

[0221] -Ryland -Rylaare independently of each other selected from the group consisting of -H, -T, C1-50alkyl, C2-50 alkenyl, and C2-50 alkynyl; wherein -T, C1-50alkyl, C2-50 alkenyl, and C2-50 alkynyl are optionally substituted with one or more -Ry2, which are the same or different, and wherein C1-50alkyl, C2-50 alkenyl, and C2-50 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry4)-, -S(O)2N(Ry4)-, -S(O)N(Ry4)-, -S(O)2-, -S(O)-, -N(Ry4)S(O)2N(Ry4a)-, -S-, -N(Ry4)-, -OC(ORy4)(Ry4a)-, -N(Ry4)C(O)N(Ry4a)-, and -OC(O)N(Ry4)-; each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl, and 8- to 30-membered heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -Ry2, which are the same or different; each -Ry2is independently selected from the group consisting of halogen, -CN, oxo (=0), -C00Ry5, -0Ry5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a),

[0222] -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -NO2, -0C(0)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a,

[0223] -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b), -OC(O)N(Ry5Ry5a), and C1-6alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; and each -Ry3, -Ry3a, -Ry4, -Ry4a, -Ry5, -Ry5aand -Ry5bis independently selected from the group consisting of -H, and C1-6 alkyl, wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different.

[0224] In certain embodiments -X4-, -X5-, -X6- and -X7- of formula (I-b4) are independently of each other selected from the group consisting of -T-, -C(0)0-, -0-, -C(0)-,

[0225] -C(0)N(Ry1)-, -S(0)2N(Ry1)-, -S(0)N(Ry1)-, -S(0)2-, -S(0)-, -N(Ryl)S(0)2N(Ryla)-, -S-, -N(Ry1)-, -0C(0Ryl)(Ryla)-, -N(Ryl)C(0)N(Ryla)-, -0C(0)N(Ryl)-, C1-50alkyl, C2-50 alkenyl, and C2-50 alkynyl; wherein -T-, C1-20 alkyl, C2-20 alkenyl, and C2-20 alkynyl are optionally substituted with one or more -Ry2, which are the same or different and wherein C1-20 alkyl, C2-20 alkenyl, and C2-20 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(0)0-, -0-, -C(0)-, -C(0)N(Ry3)-, -S(O)2N(Ry3)-, -S(0)N(Ry3)-, -S(0)2-, -S(0)-, -N(Ry3)S(O)2N(Ry3a)-, -S-, -N(Ry3)-, -OC(ORy3)(Ry3a)-, -N(Ry3)C(O)N(Ry3a)-, and -0C(0)N(Ry3)-;

[0226] -Ryland -Rylaare independently of each other selected from the group consisting of -H, -T, C1-10alkyl, C2-10alkenyl, and C2-10alkynyl; wherein -T, C1-10 alkyl, C2-10alkenyl, and C2-10alkynyl are optionally substituted with one or more -Ry2, which are the same or different, and wherein C1-10alkyl, C2-10alkenyl, and C2-10alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry4)-, -S(O)2N(Ry4)-, -S(O)N(Ry4)-, -S(O)2-, -S(O)-, -N(Ry4)S(O)2N(Ry4a)-, -S-, -N(Ry4)-, -OC(ORy4)(Ry4a)-, -N(Ry4)C(O)N(Ry4a)-, and -OC(O)N(Ry4)-; each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl, and 8- to 30-membered heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -Ry2, which are the same or different;

[0227] -Ry2is selected from the group consisting of halogen, -CN, oxo (=0), -C00Ry5, -0Ry5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -N02, -0C(0)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b), -OC(O)N(Ry5Ry5a), and C1-6alkyl; wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different; and each -Ry3, -Ry3a, -Ry4, -Ry4a, -Ry5, -Ry5aand -Ry5bis independently of each other selected from the group consisting of -H, and C1-6alkyl; wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different.

[0228] In certain embodiments -X4-, -X5-, -X6- and -X7- of formula (I-b4) are independently of each other selected from the group consisting of -T-, -C(0)0-, -0-, -C(0)-,

[0229] -C(0)N(Ry1)-, -S(0)2N(Ryl)-,-S(0)N(Ryl)-, -S(0)2-, -S(0)-, -N(Ryl)S(0)2N(Ryla)-, -S-, -N(Ry1)-, -0C(0Ryl)(Ryla)-, -N(Ryl)C(0)N(Ryla)-, -0C(0)N(Ryl)-, C1-50alkyl, C2-50 alkenyl, and C2-50 alkynyl; wherein -T-, C1-50alkyl, C2-50 alkenyl, and C2-50 alkynyl are optionally substituted with one or more -Ry2, which are the same or different and wherein C1-50alkyl, C2-50 alkenyl, and C2-50 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(0)0-, -0-, -C(0)-, -C(0)N(Ry3)-, -S(O)2N(Ry3)-, -S(0)N(Ry3)-, -S(0)2-, -S(0)-, -N(Ry3)S(O)2N(Ry3a)-, -S-, -N(Ry3)-, -OC(ORy3)(Ry3a)-, -N(Ry3)C(O)N(Ry3a)-, and -0C(0)N(Ry3)-;

[0230] -Ryland -Rylaare independently selected from the group consisting of -H, -T, C1-10 alkyl, C2-10alkenyl, and C2-10alkynyl; each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl, and 8- to 30-membered heteropolycyclyl; each -Ry2is independently selected from the group consisting of halogen, and C1-6alkyl; and each -Ry3, -Ry3a, -Ry4, -Ry4a, -Ry5, -Ry5aand -Ry5bis independently of each other selected from the group consisting of -H, and C1-6alkyl; wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different.

[0231] In certain embodiments -X4-, -X5-, -X6- and -X7- of formula (I-b3) and (I-b4) are identical. In certain embodiments -X4-, -X5-, -X6- and -X7- of formula (I-b3) and (I-b4) are identical and are selected from the group consisting of -CH2-, -CH2CH2- and -CH2CH2CH2-. In certain embodiments the moiety is of formula (I-b5) wherein dashed lines indicate attachment to -L2-; and n1, n2, n3 and n4 are independently an inter ranging from and including about 10 to about 300, in certain embodiments from and including about 10 to about 230.

[0232] In certain embodiments the moiety is of formula (I-b6) wherein dashed lines indicate attachment to -L2-; and n1, n2, n3 and n4 are independently an inter ranging from and including about 10 to about

[0233] 230.

[0234] In certain embodiments n1, n2, n3 and n4 of formula (I-b5) or (I-b6) are the same integer. In certain embodiments n1, n2, n3 and n4 of formula (I-b5) or (I-b6) are about 11. In certain embodiments n1, n2, n3 and n4 of formula (I-b5) or (I-b6) are about 12. In certain embodiments n1, n2, n3 and n4 of formula (I-b5) or (I-b6) are about 22. In certain embodiments n1, n2, n3 and n4 of formula (I-b5) or (I-b6) are about 23. . In certain embodiments n1, n2, n3 and n4 of formula (I-b5) or (I-b6) are about 28. In certain embodiments n1, n2, n3 and n4 of formula (I- b5) or (I-b6) are about 29. In certain embodiments n1, n2, n3 and n4 of formula (I-b5) or (I- b6) are about 34. In certain embodiments n1, n2, n3 and n4 of formula (I-b5) or (I-b6) are about 45. In certain embodiments n1, n2, n3 and n4 of formula (I-b5) or (I-b6) are about 56. In certain embodiments n1, n2, n3 and n4 of formula (I-b5) or (I-b6) are about 68. In certain embodiments n1, n2, n3 and n4 of formula (I-b5) or (I-b6) are about 80. In certain embodiments n1, n2, n3 and n4 of formula (I-b5) or (I-b6) are about 90. In certain embodiments n1, n2, n3 and n4 of formula (I-b5) or (I-b6) are about 100. In certain embodiments n1, n2, n3 and n4 of formula (I- b5) or (I-b6) are about 115. In certain embodiments n1, n2, n3 and n4 of formula (I-b5) or (I- b6) are about 135. In certain embodiments n1, n2, n3 and n4 of formula (I-b5) or (I-b6) are about 160. In certain embodiments n1, n2, n3 and n4 of formula (I-b5) or (I-b6) are about 180. In certain embodiments n1, n2, n3 and n4 of formula (I-b5) or (I-b6) are about 200. In certain embodiments n1, n2, n3 and n4 of formula (I-b5) or (I-b6) are about 225. In certain embodiments n1, n2, n3 and n4 of formula (I-b5) or (I-b6) are about 230.

[0235] In certain embodiments the compound comprises more than one branching point B, such as two or more branching points selected from the group consisting of (I-b 1), (I-b2) and (I-b3).

[0236] In certain embodiments -D- is a drug moiety selected from the group consisting of small molecule drug moieties, medium size molecule drug moieties, oligonucleotide drug moieties, peptide nucleic acid drug moieties, peptide drug moieties and protein drug moieties.

[0237] 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 size 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.

[0238] In certain embodiments -D- or -D-AB is a GLP-1 receptor agonist moiety. Accordingly, the compound of the present invention may be a GLP-1 receptor agonist compound.

[0239] In certain embodiments -D- or -D-AB is a mono agonist of the GLP-1 receptor, i.e., only activates the GLP-1 receptor. In certain embodiments -D- or -D-AB is an agonist of the GLP-1 receptor and an agonist of a further receptor, i.e., -D- or -D-AB is a dual GLP-1 receptor agonist. Such further receptor may be selected from the group consisting of the GIP receptor, the GCG receptor, an amylin receptor, a PYY receptor and the GLP-2 receptor.

[0240] In certain embodiments -D- or -D-AB is an agonist of the GLP-1 receptor and of the GIP receptor. In certain embodiments -D- or -D-AB is an agonist of the GLP-1 receptor and of the GCG receptor. In certain embodiments -D- or -D-AB is an agonist of the GLP-1 receptor and of an amylin receptor. In certain embodiments -D- or -D-AB is an agonist of the GLP-1 receptor and of a PYY receptor. In certain embodiments -D- or -D-AB is an agonist of the GLP-1 receptor and of the GLP-2 receptor.

[0241] In certain embodiments -D- or -D-AB is an agonist of the GLP-1 receptor and growth / differentiation factor 15 (GDF15). In certain embodiments -D- or -D-AB is an agonist of the GLP-1 receptor and fibroblast growth factor 21 (FGF21).

[0242] In certain embodiments -D- or -D-AB is an agonist of the GLP-1 receptor and an agonist of two further receptors, i.e., -D- or -D-AB is a triple GLP-1 receptor agonist. These further receptors are in certain embodiments selected from the group consisting of the GIP receptor (GIPR), the GCG receptor (GCGR), an amylin receptor, a PYY receptor (PYYR) and the GLP- 2 receptor (GLP2R).

[0243] In certain embodiments -D- or -D-AB is a triple GLP-1 receptor agonist that activates the GLP- 1 receptor, the GIP receptor and the GCG receptor. In certain embodiments -D- or -D-AB is a triple GLP-1 receptor agonist that activates the GLP-1 receptor, the GIP receptor and an amylin receptor. In certain embodiments -D- or -D-AB is a triple GLP-1 receptor agonist that activates the GLP-1 receptor, the GIP receptor and a PYY receptor. In certain embodiments -D- or -D-AB is a triple GLP- 1 receptor agonist that activates the GLP- 1 receptor, the GIP receptor and the GLP-2 receptor. In certain embodiments -D- or -D-AB is a triple GLP- 1 receptor agonist that activates the GLP-1 receptor, the GCG receptor and an amylin receptor. In certain embodiments -D- or -D-AB is a triple GLP-1 receptor agonist that activates the GLP-

[0244] 1 receptor, the GCG receptor and a PYY receptor. In certain embodiments -D- or -D-AB is a triple GLP- 1 receptor agonist that activates the GLP- 1 receptor, the GCG receptor and the GLP-

[0245] 2 receptor. In certain embodiments -D- or -D-AB is a triple GLP-1 receptor agonist that activates the GLP-1 receptor, an amylin receptor and a PYY receptor. In certain embodiments -D- or -D-AB is a triple GLP-1 receptor agonist that activates the GLP-1 receptor, the amylin receptor and the GLP-2 receptor. In certain embodiments -D- or -D-AB is a triple GLP-1 receptor agonist that activates the GLP-1 receptor, a PYY receptor and the GLP-2 receptor.

[0246] In certain embodiments -D- is a human GLP-1 of SEQ ID NO: 1 : HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG.

[0247] In certain embodiments -D- is human GLP-1 analog of SEQ ID NO: 1, which peptide sequence may comprise 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 may be any combination thereof. Such amino acid change may be at the N-terminus, the C-terminus and / or at an internal site of the GLP-1 of SEQ ID NO: 1. In certain embodiments such human GLP-1 analog has a maximum of 3 amino acid changes compared to SEQ ID NO: 1, i.e., a maximum of three amino acids are added to, deleted from or substituted compared to the sequence of SEQ ID NO: 1.

[0248] In certain embodiments -D- has the sequence HXiEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NO:2), wherein Xi is 2-aminoisobutyric acid (Aib).

[0249] In certain embodiments -D- has the sequence

[0250] HXiEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NO:3), wherein Xi is Aib and the C-terminal glycine, i.e., the glycine at position 31, is amidated as a C -terminal primary amide.

[0251] In certain embodiments -D- is exenatide. Exenatide has the sequence HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS (SEQ ID NO:4).

[0252] In certain embodiments -D- has the sequence

[0253] HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS (SEQ ID NO:5), wherein the C-terminal serine, i.e., the serine at position 39, is amidated as a C-terminal primary amide.

[0254] In certain embodiments -D- is lixisenatide. Lixisenatide has the sequence HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPSKKKKKK (SEQ ID NO:6), wherein the C-terminal lysine, i.e., the lysine at position 44, is amidated as a C-terminal primary amide.

[0255] In certain embodiments -D- has the sequence

[0256] HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPSKKKKKK (SEQ ID NO:7).

[0257] In certain embodiments -D- has the sequence

[0258] HX1EGTFTSDLSKQX2EEEAVRLFIEWLKQGGPSSGAPPPC (SEQ ID NO:8), wherein Xi is D-alanine and X2 is norleucine (Nle).

[0259] In certain embodiments -D- has the sequence

[0260] HX1EGTFTSDLSKQX2EEEAVRLFIEWLKQGGPSSGAPPPC (SEQ ID NO:9), wherein Xi 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.

[0261] In certain embodiments -D- is PEG-loxenatide. PEG-loxenatide has the sequence HX1EGTFTSDLSKQX2EEEAVRLFIEWLKQGGPSSGAPPPC (SEQ ID NO: 10), wherein Xi is D-alanine; X2 is Nle; the cysteine at position 39 is chemically modified through conjugation to the thiol group of the cysteine side-chain with wherein the dashed line indicates attachment to the thiol group of the cysteine side chain of the cysteine at position 39, and each mPEG is methoxypoly(ethylene glycol) with a molecular weight of approx. 20 kDa. In certain embodiments -D- has the sequence

[0262] HX1EGTFTSDLSKQX2EEEAVRLFIEWLKQGGPSSGAPPPC (SEQ ID NO: 11), wherein Xi is D-alanine; X2 is Nle; the cysteine at position 39 is chemically modified through conjugation to the thiol group of the cysteine side-chain with wherein the dashed line indicates attachment to the thiol group of the cysteine side chain of the cysteine at position 39, each mPEG is methoxypoly(ethylene glycol) with a molecular weight of approx. 20 kDa, and the C-terminal cysteine, i.e., the cysteine at position 39, is amidated as a C-terminal primary amide.

[0263] In certain embodiments -D- has the sequence

[0264] HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NO: 12).

[0265] In certain embodiments -D- has the sequence

[0266] HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NO: 13), and the C-terminal glycine, i.e., the glycine at position 31, is amidated as a C-terminal primary amide.

[0267] In certain embodiments -D- has the sequence

[0268] HVEGTFTSDVSSYLEEQAAREFIKWLVRGRG (SEQ ID NO: 14).

[0269] In certain embodiments -D- has the sequence

[0270] HVEGTFTSDVSSYLEEQAAREFIKWLVRGRG (SEQ ID NO: 15), and the C-terminal glycine, i.e., the glycine at position 31, is amidated as a C-terminal primary amide.

[0271] In certain embodiments -D- has the sequence

[0272] HGEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NO: 16). In certain embodiments -D- has the sequence

[0273] HGEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NO: 17), and the C-terminal glycine, i.e., the glycine at position 31, is amidated as a C-terminal primary amide.

[0274] In certain embodiments -D- has the sequence HXiEGTFTSDVSSYLEGQAAKEFIAWLVRGRGL (SEQ ID NO: 18), wherein Xi is Aib.

[0275] In certain embodiments -D- has the sequence

[0276] HXiEGTFTSDVSSYLEGQAAKEFIAWLVRGRGL (SEQ ID NO: 19), wherein Xi is Aib and the C-terminal leucine, i.e., the leucine at position 32, is amidated as a C-terminal primary amide.

[0277] In certain embodiments -D- has the sequence

[0278] YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS (SEQ ID NO:20), wherein Xi 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.

[0279] In certain embodiments -D- has the sequence YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS (SEQ ID NO:21), wherein Xi is Aib and X2 is Aib.

[0280] In certain embodiments -D- has the sequence

[0281] HSQGTFTSDKSEYLDSERARDFVAWLEAGG (SEQ ID NO:22).

[0282] In certain embodiments -D- has the sequence

[0283] HSQGTFTSDKSEYLDSERARDFVAWLEAGG (SEQ ID NO:23), wherein the C-terminal glycine, i.e., the glycine at position 30, is amidated as a C-terminal primary amide.

[0284] In certain embodiments -D- has the sequence HXiQGTFTSDYSKYLDERAAKDFIKWLESA (SEQ ID NO:24), wherein Xi is 1 -amino-cyclobutanecarboxylic acid (Ac4c); and the C-terminal alanine, i.e. the alanine at position 29, is amidated as a C-terminal primary amide.

[0285] In certain embodiments -D- has the sequence HXiQGTFTSDYSKYLDERAAKDFIKWLESA (SEQ ID NO:25), wherein Xi is 1 -amino-cyclobutanecarboxylic acid (Ac4c).

[0286] In certain embodiments -D- has the sequence

[0287] HXiQGTFTSDYSKYLDEKAAKEFIQWLLQT (SEQ ID NO:26), wherein Xi is Aib and the glutamic acid at position 16 and the lysine at position 20 are connected via a lactam bridge.

[0288] In certain embodiments -D- has the sequence

[0289] HXiQGTFTSDYSKYLDEKAAKEFIQWLLQT (SEQ ID NO:27), wherein Xi is Aib, the glutamic acid at position 16 and the lysine at position 20 are connected via a lactam bridge and the C-terminal threonine, i.e., the threonine at position 29, is amidated as a C-terminal primary amide.

[0290] In certain embodiments -D- has the sequence HXiQGTFTSDYSKYLDEKKAKEFVEWLLEGGPSSG (SEQ ID NO:28), wherein Xi is Aib and the C-terminal glycine, i.e., the glycine at position 34, is amidated as a C-terminal primary amide.

[0291] In certain embodiments -D- has the sequence HXiQGTFTSDYSKYLDEKKAKEFVEWLLEGGPSSG (SEQ ID NO:29), wherein Xi is Aib.

[0292] In certain embodiments -D- has the sequence HXiEGSFTSELATILDKQAARDFIAWLIQHKITD (SEQ ID NO:30), wherein Xi is Aib.

[0293] In certain embodiments -D- has the sequence

[0294] HXiEGSFTSELATILDKQAARDFIAWLIQHKITD (SEQ ID NO:31), wherein Xi is Aib and the C-terminal aspartic acid, i.e., the aspartic acid at position 33, is amidated as a C-terminal primary amide.

[0295] In certain embodiments -D- has the sequence

[0296] YX1QGTFTSDYSIX2LDKKAQX3AFIEYLLEGGPSSGAPPPS (SEQ ID NO:32), wherein Xi is Aib, X2 is a-methyl-leucine (aMeL), X3 is Aib; and the C-terminal serine, i.e. the serine at position 39, is amidated as a C-terminal primary amide.

[0297] In certain embodiments -D- has the sequence YX1QGTFTSDYSIX2LDKKAQX3AFIEYLLEGGPSSGAPPPS (SEQ ID NO:33), wherein Xi is Aib, X2 is a-methyl-leucine (aMeL) and X3 is Aib.

[0298] In certain embodiments -D- has the sequence HXiEGTFTSDVSSYLEEEAAKEFIAWLVRGGPSSGAPPPSK (SEQ ID NO:54), wherein Xi is Aib.

[0299] In certain embodiments -D- has the sequence

[0300] HXiEGTFTSDVSSYLEEQAAKEFIAWLVRGGG (SEQ ID NO:55), wherein Xi is Aib.

[0301] In certain embodiments -D- has the sequence

[0302] HXiEGTFTSDVSSYLEEQAAKEFIAWLVRGGGGAQPGAQPGAQPGAQPGAQPGAQP GAQPGAQPGAQPGQKP (SEQ ID NO:56), wherein Xi is Aib.

[0303] In certain embodiments -D- has the sequence

[0304] HXiEGTFTSDVSSYLEEQAAKEFIAWLVRGGGGAQPGAQPGAQPGAQPGAQPGAQP GAQPGAQPGAQPGQKP (SEQ ID NO:56), wherein Xi is Aib.

[0305] In certain embodiments -D- is a drug selected from the group consisting of insulins; amylin and amylin / calcitonin; PYY; GIP; MSH; C5a binders; GDF15; PCSK9 I; immune stimulants; urocortin2; MIC-1; IL-1R antagonists; leptin; gastrin; glucagon; exendin-4; GLP-1; GLP-2; and GIP. In certain embodiments -D- is a drug moiety selected from the group consisting of insulin; insulin analogues; amylin; dual amylin / cal citonin agonists; PYY; GIP; MSH; C5 inhibitors or modulators; GDF15; PCSK9 inhbitors; immune stimulants; urocortin II; MIC-1; IL-1R antagonists; leptin; gastrin; glucagon; oxyntomodulin; neurokinin A; tachykinin / neurokinin receptor 2 (NK2R) agonists; neurokinin receptor (NKR) agonists and GLP-2.

[0306] In certain embodiments -D- is an insulin, such as insulin detemir, insulin degludec and insulin. In certain embodiments -D- is amylin and amylin / calcitonin, such as for example cagrilintide. In certain embodiments -D- is PYY, such as NNC0165-1875. In certain embodiments -D- is GIP. In certain embodiments -D- is MSH. In certain embodiments -D- is a C5a binder, such as zilucoplan. In certain embodiments -D- is GDF15, such as NN LA-GDF15. In certain embodiments -D- is PCSK9 i. In certain embodiments -D- is an immune stimulant, such as romurtide or mifamurtide. In certain embodiments -D- is muramyl dipeptide. In certain embodiments -D- is urocortin2. 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.

[0307] In certain embodiments -D- is selected from the list consisting of growth hormones, such as human growth hormone; FGF21; EGF(a); and coagulations factors.

[0308] In certain embodiments -D- is a growth hormone, such as a human growth hormone, such as somapacitan. In certain embodiments -D- is FGF21, such as NNC0194 0499. In certain embodiments -D- is EGF(a). In certain embodiments -D- is a coagulation factor.

[0309] In certain embodiments -D- is selected from cytotoxic small molecule drugs; chemotherapy small molecule drugs; and immune activating small molecule drugs.

[0310] In certain embodiments -D- is a cytotoxic small molecule drug. In certain embodiments -D- is a chemotherapy small molecule drug. In certain embodiments -D- is and immune activating small molecule drug, such as telratolimod.

[0311] In certain embodiments -D- is paclitaxel. In certain embodiments -D- is doxorubicin. In certain embodiments -D- is 5-FU. In certain embodiments -D- is a PTH moiety.

[0312] In certain embodiments -AB is a fatty acid-based albumin-binding moiety.

[0313] A moiety -AB binds to albumin, such as human albumin, under physiological conditions (aqueous buffer pH 7.4, 37°C).

[0314] A moiety -D- may be conjugated to one moiety -AB. A moiety -D- may be conjugated to more than one moiety -AB. In certain embodiments the linkage between -D- and a moiety -AB is a stable linkage. In case a moiety -D- comprises two moieties -AB, the linkage between -D- and a first moiety -AB may be reversible and the linkage between -D- and a second moiety -AB may be stable. Alternatively, in case a moiety -D- comprises two moieties -AB, the linkage between -D- and both moieties -AB may be stable.

[0315] In certain embodiments -AB is of formula (A): wherein the dashed line indicates attachment to -D-; -F0is of formula (a- 1) wherein the dashed line indicates attachment to -LA-;

[0316] -R° is selected from the group consisting of -CR1RlaRlb, -COOR1,

[0317] -R1, -R1aand -Rlbare selected from the group consisting of -H, methyl, ethyl, propyl and isopropyl; n is an integer ranging from and including 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,

[0318] 18, 19, 20, 21 and 22;

[0319] -LA- is absent or is of formula (a-2) wherein the unmarked dashed line indicates attachment to -LB-; the dashed line marked with the asterisk indicates attachment to -F0;

[0320] -Ra- is selected from the group consisting wherein the dashed line marked with the asterisk indicates attachment to -F0; the unmarked dashed line indicates attachment to the remainder of -LA- ; 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;

[0321] -LB- is absent or is of formula (a-3) wherein the unmarked dashed line indicates attachment to -D-; the dashed line marked with the asterisk indicates attachment to -LA;

[0322] -Rd- is selected from the group consisting of C1-50alkyl, C2-50 alkenyl and C2-50 alkynyl, wherein C1-50alkyl, C2-50 alkenyl, and C2-50 alkynyl may be substituted with one or more -R1, which may be the same or different, and which C1-50alkyl, C2-50 alkenyl or C2-50 alkynyl may be interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-,

[0323] -C(O)N(R2)-, -S(O)2N(R2)-, -S(O)N(R2)-, -S(O)2-, -S(O)-,

[0324] -N(R2)S(O)2N(R2a)-, -S-, -N(R2)-, -OC(OR2)(R2a)-, -N(R2)C(O)N(R2a)-, and -OC(O)N(R2)-; each -T- is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl, and 8- to 30-membered heteropoly cyclyl; wherein each -T- may independently be substituted with one or more -R1, which may be the same or different; each -R1is independently selected from the group consisting of halogen, -CN, oxo (=0), -C00R3, -OR3, -C(0)R3, -C(O)N(R3R3a), -S(O)2N(R3R3a), -S(O)N (R3R3a), -S(O)2R3, -S(O)R3, -N(R3)S(O)2N(R3aR3b), -SR3,-N(R3R3a), -N02, -0C(0)R3, -N(R3)C(O)R3a, -N(R3)S(O)2R3a, -N(R3)S(O)R3a,

[0325] -N(R3)C(O)OR3a, -N(R3)C(O)N(R3aR3b), -OC(O)N(R3R3a), and C1-6alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; each -R2, -R2a, -R3, -R3aand -R3bis independently selected from the group consisting of -H, and C1-6 alkyl, wherein C1-6 alkyl may be substituted with one or more halogen, which may be the same or different; and

[0326] -Re- is selected from the group consisting of -CH2-, not absent, then

[0327] In certain embodiments -LA- is of formula (a-2), i.e., is not absent. In certain embodiments -LA- is absent.

[0328] In certain embodiments wherein the dashed line marked with the asterisk indicates attachment to -F0and the unmarked dashed line indicates attachment to the remainder of -LA-. In certain embodiments -Ra- is wherein the dashed line marked with the asterisk indicates attachment to -F0and the unmarked dashed line indicates attachment to the remainder of -LA-.

[0329] .

[0330] In certain embodiments -R - is In certain embodiments -R - is

[0331] In certain embodiments m of formula (a-2) is 1. In certain embodiments m of formula (a-2) is 2. In certain embodiments m of formula (a-2) is 3. In certain embodiments m of formula (a-2) is 4. In certain embodiments m of formula (a-2) is 5. In certain embodiments m of formula (a- 2) is 6. In certain embodiments m of formula (a-2) is 7. In certain embodiments m of formula (a-2) is 8. In certain embodiments m of formula (a-2) is 9. In certain embodiments m of formula (a-2) is 10.

[0332] In certain embodiments p of formula (a-2) is 1. In certain embodiments p of formula (a-2) is 2.

[0333] In certain embodiments p of formula (a-2) is 3. In certain embodiments p of formula (a-2) is 4.

[0334] In certain embodiments p of formula (a-2) is 5. In certain embodiments p of formula (a-2) is 6.

[0335] In certain embodiments p of formula (a-2) is 7. In certain embodiments p of formula (a-2) is 8.

[0336] In certain embodiments p of formula (a-2) is 9. In certain embodiments p of formula (a-2) is 10.

[0337] In certain embodiments -LB- is of formula (a-3). In certain embodiments -LB- is absent.

[0338] If -LB- is absent, the unmarked dashed line in formula (a-2) indicates attachment to -D-.

[0339] In certain embodiments -Rc- is In certain embodiments -Rc- is

[0340] In certain embodiments -Re- is -CH2-. In certain embodiments -Re- is In certain embodiments -Re- is In certain embodiments both -LA- and -LB- are absent. If both -LA- and -LB- are absent, the dashed line in formula (a-1) indicates attachment to -D-.

[0341] In certain embodiments -F0is selected from the group consisting of

[0342] wherein dashed lines indicate attachment to -LA-.

[0343] If -LA- is absent, the dashed line in formulas (a-4) to (a-39) indicates attachment to -LB-. If both -LA- and -LB- are absent, the dashed line in formulas (a-4) to (a-39) indicates attachment to -D-. In certain embodiments -F0is of formula (a-4). In certain embodiments -F0is of formula (a-5).

[0344] In certain embodiments -F0is of formula (a-6). In certain embodiments -F0is of formula (a-7).

[0345] In certain embodiments -F0is of formula (a-8). In certain embodiments -F0is of formula (a-9).

[0346] In certain embodiments -F0is of formula (a- 10). In certain embodiments -F0is of formula

[0347] (a-11). In certain embodiments -F0is of formula (a-12). In certain embodiments -F0is of formula (a-13). In certain embodiments -F0is of formula (a-14). In certain embodiments -F0is of formula (a- 15). In certain embodiments -F0is of formula (a- 16). In certain embodiments -F0is of formula (a- 17). In certain embodiments -F0is of formula (a- 18). In certain embodiments -F0is of formula (a- 19). In certain embodiments -F0is of formula (a-20). In certain embodiments -F0is of formula (a-21). In certain embodiments -F0is of formula (a-22). In certain embodiments -F0is of formula (a-23). In certain embodiments -F0is of formula (a-24). In certain embodiments -F0is of formula (a-25). In certain embodiments -F0is of formula (a-26). In certain embodiments -F0is of formula (a-27). In certain embodiments -F0is of formula (a-28). In certain embodiments -F0is of formula (a-29). In certain embodiments -F0is of formula (a-30). In certain embodiments -F0is of formula (a-31). In certain embodiments -F0is of formula (a-32). In certain embodiments -F0is of formula (a-33). In certain embodiments -F0is of formula (a-34). In certain embodiments -F0is of formula (a-35). In certain embodiments -F0is of formula (a-36). In certain embodiments -F0is of formula (a- 37). In certain embodiments -F0is of formula (a-38). In certain embodiments -F0is of formula (a-39).

[0348] In certain embodiments -F0is of formula (a-4) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-5) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-6) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-7) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-8) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-9) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a- 10) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-11) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-12) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-13) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-14) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a- 15) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a- 16) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a- 17) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a- 18) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a- 19) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-20) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-21) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-22) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-23) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-24) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-25) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-26) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-27) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-28) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-29) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-30) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-31) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-32) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-33) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-34) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-35) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-36) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-37) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-38) and both -LA- and -LB- are absent. In certain embodiments -F0is of formula (a-39) and both -LA- and -LB- are absent.

[0349] In certain embodiments -LA- is selected from the group consisting of

[0350] wherein a dashed line marked with an asterisk indicates attachment to -F0- and an unmarked dashed line indicates attachment to -LB-. If -LB- is absent an unmarked dashed indicates attachment to -D-.

[0351] In certain embodiments -LA- is of formula (a-40). In certain embodiments -LA- is of formula (a-41). In certain embodiments -LA- is of formula (a-42). In certain embodiments -LA- is of formula (a-43). In certain embodiments -LA- is of formula (a-44). In certain embodiments -LA- is of formula (a-45). In certain embodiments -LA- is of formula (a-46). In certain embodiments -LA- is of formula (a-47). In certain embodiments -LA- is of formula (a- 48). In certain embodiments -LA- is of formula (a-49). In certain embodiments -LA- is of formula (a-50). In certain embodiments -LA- is of formula (a-51). In certain embodiments -LA- is of formula (a-52). In certain embodiments -LA- is of formula (a-53). In certain embodiments -LA- is of formula (a-54). In certain embodiments -LA- is of formula (a- 55). In certain embodiments -LA- is of formula (a-56). In certain embodiments -LA- is of formula (a-57). In certain embodiments -LA- is of formula (a-58). In certain embodiments -LA- is of formula (a-59). In certain embodiments -LA- is of formula (a-60). In certain embodiments -LA- is of formula (a-61). In certain embodiments -LA- is of formula (a- 62). In certain embodiments -LA- is of formula (a-63). In certain embodiments -LA- is of formula (a-64). In certain embodiments -LA- is of formula (a-65). In certain embodiments -LA- is of formula (a-66). In certain embodiments -LA- is of formula (a-67). In certain embodiments -LA- is of formula (a-68). In certain embodiments -LA- is of formula (a- 69). In certain embodiments -LA- is of formula (a-70). In certain embodiments -LA- is of formula (a-71). In certain embodiments -LA- is of formula (a-72). In certain embodiments -LA- is of formula (a-73). In certain embodiments -LA- is of formula (a-74). In certain embodiments -LA- is of formula (a-75). In certain embodiments -LA- is of formula (a- 76). In certain embodiments -LA- is of formula (a-77). In certain embodiments -LA- is of formula (a-78). In certain embodiments -LA- is of formula (a-79). In certain embodiments -LA- is of formula (a-80). In certain embodiments -LA- is of formula (a-81). In certain embodiments -LA- is of formula (a-82).

[0352] In certain embodiments -LB- is selected from the group consisting of

[0353] (a-90),

[0354]

[0355] (a-94), wherein the dashed line marked with the asterisk indicates attachment to -LA-; the unmarked dashed line indicates attachment to -D-; and q is an integer ranging from and including 2 to 50.

[0356] If -LA- is absent, the dashed line marked with the asterisk in formulas (a-83) to (a-94) indicates attachment to -F0.

[0357] In certain embodiments q of formula (a-84) is an integer ranging from and including 3 to 45.

[0358] In certain embodiments q of formula (a-84) is an integer ranging from and including 4 to 40.

[0359] In certain embodiments q of formula (a-84) is an integer ranging from and including 5 to 35.

[0360] In certain embodiments q of formula (a-84) is an integer ranging from and including 6 to 30.

[0361] In certain embodiments q of formula (a-84) is an integer ranging from and including 7 to 25.

[0362] In certain embodiments q of formula (a-84) is an integer ranging from and including 10 to 20. In certain embodiments q of formula (a-84) is 23. In certain embodiments -LB- is of formula (a-83). In certain embodiments -LB- is of formula (a-84). In certain embodiments -LB- is of formula (a-84) with q = 23. In certain embodiments -LB- is of formula (a-85). In certain embodiments -LB- is of formula (a-86). In certain embodiments -LB- is of formula (a-87). In certain embodiments -LB- is of formula (a-88). In certain embodiments -LB- is of formula (a-89). In certain embodiments -LB- is of formula (a-90). In certain embodiments -LB- is of formula (a-91). In certain embodiments -LB- is of formula (a-92). In certain embodiments -LB- is of formula (a-93). In certain embodiments -LB- is of formula (a-94).

[0363] In certain embodiments -AB is of formula (i) wherein the dashed line indicates attachment to -D-; n is an integer ranging from and including 14 to 22; and the stereocenter marked with the asterisk is either in S- or R-configuration.

[0364] In certain embodiments -AB is of formula (i) and n is 14. In certain embodiments -AB is of formula (i) and n is 15. In certain embodiments -AB is of formula (i) and n is 16. In certain embodiments -AB is of formula (i) and n is 17. In certain embodiments -AB is of formula (i) and n is 18. In certain embodiments -AB is of formula (i) and n is 19. In certain embodiments -AB is of formula (i) and n is 20. In certain embodiments -AB is of formula (i) and n is 21. In certain embodiments -AB is of formula (i) and n is 22.

[0365] In certain embodiments -AB is of formula (i) and n is 14 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (i) and n is 15 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (i) and n is 16 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (i) and n is 17 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (i) and n is 18 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (i) and n is 19 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (i) and n is 20 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (i) and n is 21 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (i) and n is 22 and the stereocenter marked with the asterisk is in R-configuration.

[0366] In certain embodiments -AB is of formula (i) and n is 14 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (i) and n is 15 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (i) and n is 16 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (i) and n is 17 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (i) and n is 18 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (i) and n is 19 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (i) and n is 20 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (i) and n is 21 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (i) and n is 22 and the stereocenter marked with the asterisk is in S-configuration.

[0367] In certain embodiments -AB is of formula (i-a): wherein the dashed line indicates attachment to -D-.

[0368] In certain embodiments -AB is of formula (i-b): wherein the dashed line indicates attachment to -D-.

[0369] In certain embodiments -AB is of formula (i-c): wherein the dashed line indicates attachment to -D-.

[0370] In certain embodiments -AB is of formula (i-d): wherein the dashed line indicates attachment to -D-.

[0371] In certain embodiments -AB is of formula (i-e): wherein the dashed line indicates attachment to -D-.

[0372] In certain embodiments -AB is of formula (i-f): wherein the dashed line indicates attachment to -D-.

[0373] In certain embodiments -AB is of formula (ii) wherein the dashed line indicates attachment to -D-; n is an integer ranging from 14 to 22; and the stereocenter marked with the asterisk is either in S- or R-configuration.

[0374] In certain embodiments -AB is of formula (ii) and n is 14. In certain embodiments -AB is of formula (ii) and n is 15. In certain embodiments -AB is of formula (ii) and n is 16. In certain embodiments -AB is of formula (ii) and n is 17. In certain embodiments -AB is of formula (ii) and n is 18. In certain embodiments -AB is of formula (ii) and n is 19. In certain embodiments -AB is of formula (ii) and n is 20. In certain embodiments -AB is of formula (ii) and n is 21. In certain embodiments -AB is of formula (ii) and n is 22.

[0375] In certain embodiments -AB is of formula (ii) and n is 14 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (ii) and n is 15 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (ii) and n is 16 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (ii) and n is 17 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (ii) and n is 18 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (ii) and n is 19 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (ii) and n is 20 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (ii) and n is 21 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (ii) and n is 22 and the stereocenter marked with the asterisk is in R-configuration.

[0376] In certain embodiments -AB is of formula (ii) and n is 14 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (ii) and n is 15 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (ii) and n is 16 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (ii) and n is 17 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (ii) and n is 18 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (ii) and n is 19 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (ii) and n is 20 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (ii) and n is 21 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (ii) and n is 22 and the stereocenter marked with the asterisk is in S-configuration.

[0377] In certain embodiments -AB is of formula (ii-a) : wherein the dashed line indicates attachment to -D-.

[0378] In certain embodiments -AB is of formula (ii-b): wherein the dashed line indicates attachment to -D-.

[0379] In certain embodiments -AB is of formula (ii-c) : wherein the dashed line indicates attachment to -D-.

[0380] In certain embodiments -AB is of formula (ii-d): wherein the dashed line indicates attachment to -D-.

[0381] In certain embodiments -AB is of formula (ii-e) : wherein the dashed line indicates attachment to -D-.

[0382] In certain embodiments -AB is of formula (ii-f): wherein the dashed line indicates attachment to -D-.

[0383] In certain embodiments -AB is of formula (iii) wherein the dashed line indicates attachment to -D-; t is an integer ranging from and including 14 to 22; and the stereocenter marked with the asterisk is either in S- or R-configuration.

[0384] In certain embodiments -AB is of formula (iii) and t is 14. In certain embodiments -AB is of formula (iii) and t is 15. In certain embodiments -AB is of formula (iii) and t is 16. In certain embodiments -AB is of formula (iii) and t is 17. In certain embodiments -AB is of formula (iii) and t is 18. In certain embodiments -AB is of formula (iii) and t is 19. In certain embodiments -AB is of formula (iii) and t is 20. In certain embodiments -AB is of formula (iii) and t is 21. In certain embodiments -AB is of formula (iii) and t is 22.

[0385] In certain embodiments -AB is of formula (iii) and t is 14 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (iii) and t is 15 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (iii) and t is 16 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (iii) and t is 17 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (iii) and t is 18 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (iii) and t is 19 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (iii) and t is 20 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (iii) and t is 21 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (iii) and t is 22 and the stereocenter marked with the asterisk is in R-configuration.

[0386] In certain embodiments -AB is of formula (iii) and t is 14 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (iii) and t is 15 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (iii) and t is 16 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (iii) and t is 17 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (iii) and t is 18 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (iii) and t is 19 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (iii) and t is 20 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (iii) and t is 21 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (iii) and t is 22 and the stereocenter marked with the asterisk is in S-configuration.

[0387] In certain embodiments -AB is of formula (iii-a) wherein the dashed line indicates attachment to -D-.

[0388] In certain embodiments -AB is of formula (iii-b) wherein the dashed line indicates attachment to -D-;

[0389] In certain embodiments -AB is of formula (iii-c) wherein the dashed line indicates attachment to -D-.

[0390] In certain embodiments -AB is of formula (iii-d) wherein the dashed line indicates attachment to -D-.

[0391] In certain embodiments -AB is of formula (iii-e) wherein the dashed line indicates attachment to -D-.

[0392] In certain embodiments -AB is of formula (iii-f) wherein the dashed line indicates attachment to -D-.

[0393] In certain embodiments -AB is of formula (iv) wherein the dashed line indicates attachment to -D-, and u is an integer ranging from and including 14 to 22.

[0394] In certain embodiments -AB is of formula (iv) and u is 14. In certain embodiments -AB is of formula (iv) and u is 15. In certain embodiments -AB is of formula (iv) and u is 16. In certain embodiments -AB is of formula (iv) and u is 17. In certain embodiments -AB is of formula (iv) and u is 18. In certain embodiments -AB is of formula (iv) and u is 19. In certain embodiments -AB is of formula (iv) and u is 20. In certain embodiments -AB is of formula (iv) and u is 21. In certain embodiments -AB is of formula (iv) and u is 22.

[0395] In certain embodiments -AB is of formula (v) wherein the dashed line indicates attachment to -D-; v is an integer ranging from and including 14 to 22; and the stereocenter marked with the asterisk is either in S- or R-configuration. In certain embodiments -AB is of formula (v) and v is 14. In certain embodiments -AB is of formula (v) and v is 15. In certain embodiments -AB is of formula (v) and v is 16. In certain embodiments -AB is of formula (v) and v is 17. In certain embodiments -AB is of formula (v) and v is 18. In certain embodiments -AB is of formula (v) and v is 19. In certain embodiments -AB is of formula (v) and v is 20. In certain embodiments -AB is of formula (v) and v is 21. In certain embodiments -AB is of formula (v) and v is 22.

[0396] In certain embodiments -AB is of formula (v) and v is 14 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (v) and v is 15 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (v) and v is 16 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (v) and v is 17 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (v) and v is 18 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (v) and v is 19 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (v) and v is 20 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (v) and v is 21 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (v) and v is 22 and the stereocenter marked with the asterisk is in R-configuration.

[0397] In certain embodiments -AB is of formula (v) and v is 14 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (v) and v is 15 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (v) and v is 16 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (v) and v is 17 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (v) and v is 18 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (v) and v is 19 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (v) and v is 20 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (v) and v is 21 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (v) and v is 22 and the stereocenter marked with the asterisk is in S-configuration.

[0398] In certain embodiments -AB is of formula (v-a) wherein the dashed line indicates attachment to -D-.

[0399] In certain embodiments -AB is of formula (v-b) wherein the dashed line indicates attachment to -D-;

[0400] In certain embodiments -AB is of formula (v-c) wherein the dashed line indicates attachment to -D-.

[0401] In certain embodiments -AB is of formula (v-d) wherein the dashed line indicates attachment to -D-.

[0402] In certain embodiments -AB is of formula (vi-e) wherein the dashed line indicates attachment to -D-.

[0403] In certain embodiments -AB is of formula (vi-f) wherein the dashed line indicates attachment to -D-.

[0404] In certain embodiments -AB is of formula (vii) wherein the dashed line indicates attachment to -D-; w is an integer ranging from and including 14 to 22; and the stereocenter marked with the asterisk is either in S- or R-configuration.

[0405] In certain embodiments -AB is of formula (vii) and w is 14. In certain embodiments -AB is of formula (vii) and w is 15. In certain embodiments -AB is of formula (vii) and w is 16. In certain embodiments -AB is of formula (vii) and w is 17. In certain embodiments -AB is of formula (vii) and w is 18. In certain embodiments -AB is of formula (vii) and w is 19. In certain embodiments -AB is of formula (vii) and w is 20. In certain embodiments -AB is of formula (vii) and w is 21. In certain embodiments -AB is of formula (vii) and w is 22.

[0406] In certain embodiments -AB is of formula (vii) and w is 14 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (vii) and w is 15 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (vii) and w is 16 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (vii) and w is 17 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (vii) and w is 18 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (vii) and w is 19 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (vii) and w is 20 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (vii) and w is 21 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (vii) and w is 22 and the stereocenter marked with the asterisk is in R-configuration.

[0407] In certain embodiments -AB is of formula (vii) and w is 14 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (vii) and w is 15 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (vii) and w is 16 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (vii) and w is 17 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (vii) and w is 18 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (vii) and w is 19 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (vii) and w is 20 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (vii) and w is 21 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (vii) and w is 22 and the stereocenter marked with the asterisk is in S-configuration.

[0408] In certain embodiments -AB is of formula (vii-a): wherein the dashed line indicates attachment to -D-.

[0409] In certain embodiments -AB is of formula (vii-b): wherein the dashed line indicates attachment to -D-.

[0410] In certain embodiments -AB is of formula (vii-c): wherein the dashed line indicates attachment to -D-.

[0411] In certain embodiments -AB is of formula (vii-d): wherein the dashed line indicates attachment to -D-.

[0412] In certain embodiments -AB is of formula (vii-e): wherein the dashed line indicates attachment to -D-.

[0413] In certain embodiments -AB is of formula (vii-f): wherein the dashed line indicates attachment to -D-.

[0414] In certain embodiments -AB is of formula (viii) wherein the dashed line indicates attachment to -D-; w is an integer ranging from and including 14 to 22; and the stereocenter marked with the asterisk is either in S- or R-configuration.

[0415] In certain embodiments -AB is of formula (viii) and x is 14. In certain embodiments -AB is of formula (viii) and x is 15. In certain embodiments -AB is of formula (viii) and x is 16. In certain embodiments -AB is of formula (viii) and x is 17. In certain embodiments -AB is of formula (viii) and x is 18. In certain embodiments -AB is of formula (viii) and x is 19. In certain embodiments -AB is of formula (viii) and x is 20. In certain embodiments -AB is of formula (viii) and x is 21. In certain embodiments -AB is of formula (viii) and x is 22.

[0416] In certain embodiments -AB is of formula (viii) and x is 14 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (viii) and x is 15 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (viii) and x is 16 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (viii) and x is 17 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (viii) and x is 18 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (viii) and x is 19 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (viii) and x is 20 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (viii) and x is 21 and the stereocenter marked with the asterisk is in R-configuration. In certain embodiments -AB is of formula (viii) and x is 22 and the stereocenter marked with the asterisk is in R-configuration.

[0417] In certain embodiments -AB is of formula (viii) and x is 14 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (viii) and x is 15 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (viii) and x is 16 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (viii) and x is 17 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (viii) and x is 18 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (viii) and x is 19 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (viii) and x is 20 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (viii) and x is 21 and the stereocenter marked with the asterisk is in S-configuration. In certain embodiments -AB is of formula (viii) and x is 22 and the stereocenter marked with the asterisk is in S-configuration.

[0418] In certain embodiments -AB is of formula (viii-a) wherein the dashed line indicates attachment to -D-.

[0419] In certain embodiments -AB is of formula (viii-b) wherein the dashed line indicates attachment to -D-.

[0420] In certain embodiments -AB is of formula (viii-c) wherein the dashed line indicates attachment to -D-.

[0421] In certain embodiments -AB is of formula (viii-d) wherein the dashed line indicates attachment to -D-.

[0422] In certain embodiments -AB is of formula (viii-e) wherein the dashed line indicates attachment to -D-.

[0423] In certain embodiments -AB is of formula (viii-f) wherein the dashed line indicates attachment to -D-.

[0424] In certain embodiments -AB is of formula (ix-i) wherein with Ph being 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.

[0425] In certain embodiments -AB is of formula (ix-i) with a being 1, b being 1, c being 1, d being 1, m being 1, n being 18 and m being 1.

[0426] In certain embodiments -AB is of formula (ix-i) and X1- isand-X2is . In certain embodiments -AB is of formula (ix-i) and X1- isand_X2is In certain embodiments -AB is of formula (ix-i) and X1- is and -X2is . In certain embodiments -AB is of formula (ix-i) and X1- is and-X2is In certain embodiments -AB is of formula (ix-i) and X1- is and -X2is In certain embodiments -AB is of formula (ix-i) and X1- is and -X2is in certain embodiments -AB is of formula (ix-i) and X1- is and-X2is In certain embodiments -AB is of formula (ix-i) and X1- is and_X2 is in certain embodiments -AB is of formula (ix-i) and X1- is and -X2is In certain embodiments -AB is of formula (ix-i) and 2 is and -X is In certain embodiments -AB is of formula (ix-i) and In certain embodiments -AB is of formula (ix-i) and

[0427] In certain embodiments -AB is a peptidic albumin-binding moiety.

[0428] If -D- is a peptide or protein drug moiety, such peptidic moiety -AB may be fused to the N- or C-terminus of -D-, either directly or with a peptidic spacer between -D- and -AB.

[0429] In certain embodiments -AB is selected from the group consisting of WWEQDRDWDFDVFGGGTP (SEQ ID NO:34);

[0430] DICLPRWGCLW (SEQ ID NO: 35), wherein the cysteines at position 3 and 9 are connected via a disulfide bridge;

[0431] RLIEDICLPRWGCLWEDD (SEQ ID NO: 36), wherein the cysteines at position 7 and 13 are connected via a disulfide bridge;

[0432] LAEAI<VLANRELDI<YGVSDFYI<RLINI<AI<TVEGVEALI<LHILAALP (SEQ ID NO:37); IAEAI<EAANAELDSYGVSDFYI<RLIDI<AI<TVEGVEALI<DAILAALP (SEQ ID NO:38); and

[0433] X1EYEX2EYE (SEQ ID NO:39), wherein X1 is fluorescein-(AEEA), X2 is K(palmitate), and AEEA is 2-(2-(2- aminoethoxy)acetyl.

[0434] In certain embodiments -AB is of SEQ ID NO:34. In certain embodiments -AB is of SEQ ID NO:35. In certain embodiments -AB is of SEQ ID NO:36. In certain embodiments -AB is of SEQ ID NO:37. In certain embodiments -AB is of SEQ ID NO:38. In certain embodiments -AB is of SEQ ID NO:39.

[0435] In certain embodiments -AB is of formula (A-a): wherein the dashed line indicates attachment to -D-; -F0and -LA- are used as defined in formula (A), -LB- is a polymeric moiety.

[0436] The moiety -LB- is a polymeric moiety, meaning that it comprises at least one polymer moiety. In certain embodiments the one or more polymer moiety has a molecular weight of at least 450 Da. In certain embodiments the one or more polymer moiety has a molecular weight of at least 1 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of at least 1.5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of at least 2 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of at least 2.5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of at least 3 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of at least 3.5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of at least 4 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of at least 5 kDa. In certain embodiments the one or more polymer moiety has a maximum molecular weight of 160 kDa. In certain embodiments the one or more polymer moiety has a maximum molecular weight of 120 kDa. In certain embodiments the one or more polymer moiety has a maximum molecular weight of 100 kDa. In certain embodiments the one or more polymer moiety has a maximum molecular weight of 80 kDa. In certain embodiments the one or more polymer moiety has a maximum molecular weight of 70 kDa. In certain embodiments the one or more polymer moiety has a maximum molecular weight of 60 kDa. In certain embodiments the one or more polymer moiety has a maximum molecular weight of 50 kDa. In certain embodiments the one or more polymer moiety has a maximum molecular weight of 40 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 450 Da. In certain embodiments the one or more polymer moiety has a molecular weight of about 1 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 1.5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 2 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 2.5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 3 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 3.5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 4 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 4.5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 5.5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 6 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 6.5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 7 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 7.5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 8 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 8.5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 9 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 9.5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 10 kDa. It is understood that if -LB- comprises one polymer moiety the minimum and maximum molecular weights provided above apply to this one polymer moiety and if -LB- comprises more than one polymer moiety the minimum and maximum molecular weights provided above refer to the minimum and maximum molecular weight of all polymer moieties together.

[0437] In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of at least 1.2 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of at least 1.5 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of at least 2 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of at least 2.5 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of at least 3 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of at least 3.5 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of at least 4 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of at least 4.5 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of at least 5 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of no more than 200 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of no more than 175 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of no more than 150 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of no more than 125 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of no more than 100 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of no more than 75 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of no more than 50 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of no more than 45 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of no more than 40 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of no more than 35 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of no more than 30 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of about 1.2 nm. In certain embodiments the one or more polymer moiety of -LB-has a Flory radius of about 1.5 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of about 2 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of about 2.5 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of about 3 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of about 3.5 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of about 4 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of about 4.5 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of about 5 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of about 5.5 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of about 6 nm. In certain embodiments the one or more polymer moiety of -LB-has a Flory radius of about 6.5 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of about 7 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of about 8.5 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of about 9 nm. In certain embodiments the one or more polymer moiety of -LB- has a Flory radius of about 10 nm. It is understood that if -LB- comprises one polymer moiety the Flory radius provided above applies to this one polymer moiety and if -LB- comprises more than one polymer moiety the Flory radius provided above refers to the Flory radius of all polymer moieties together.

[0438] -LB- comprises one or more polymer moiety, such as polymer moiety selected from the group consisting of poly(2-methacryloyl-oxyethyl phosphoyl cholins), poly(acrylic acids), poly(acrylates), poly(acrylamides), poly(alkyloxy) polymers, poly(amides), poly(amidoamines), poly(amino acids), poly(anhydrides), poly(aspartamides), poly(butyric acids), poly(glycolic acids), polybutylene terephthalates, poly(caprolactones), poly(carbonates), poly(cyanoacrylates), poly(dimethylacrylamides), poly(esters), poly(ethylenes), poly(ethyleneglycols), poly(ethylene oxides), poly(ethyl phosphates), poly(ethyloxazolines), poly(glycolic acids), poly(hydroxyethyl acrylates), poly(hydroxyethyl- oxazolines), poly(hydroxymethacrylates), poly(hydroxypropylmethacrylamides), poly(hydroxypropyl methacrylates), poly(hydroxypropyloxazolines), poly(iminocarbonates), poly(lactic acids), poly(lactic-co-glycolic acids), poly(methacrylamides), poly(methacrylates), poly(methyloxazolines), poly(organophosphazenes), poly(ortho esters), poly(oxazolines), polypropylene glycols), poly(siloxanes), poly(urethanes), poly(vinyl alcohols), poly(vinyl amines), poly(vinylmethylethers), polyvinylpyrrolidones), silicones, celluloses, carbomethyl celluloses, hydroxypropyl methylcelluloses, chitins, chitosans, dextrans, dextrins, gelatins, hyaluronic acids and derivatives, functionalized hyaluronic acids, alginate, mannans, pectins, rhamnogalacturonans, starches, hydroxyalkyl starches, hydroxyethyl starches and other carbohydrate-based polymers, xylans, and copolymers thereof.

[0439] In certain embodiments -LB- comprises a PEG-based polymer. In certain embodiments -LB- comprises a hyaluronic acid-based polymer. In certain embodiments -LB- comprises a random coil polymer. In certain embodiments -LB- comprises a poly- sarcosine polymer.

[0440] In certain embodiments -LB- of formula (A-a) is of formula (a-3’) wherein the unmarked dashed line indicates attachment to -D-; the dashed line marked with the asterisk indicates attachment to -LA; -Rc- is

[0441] -Rd- is a polymeric moiety; and

[0442] O

[0443] -Re- is selected from the group consisting of -CH2-,

[0444] If -Rb- of formula (A-a) is then -Rc- of formula (a-3’) is and if -Rb- of formula

[0445] (A-a) is then -Rc- of formula (a-3’) is

[0446] The moiety -Rd- of formula (a-3’) is a polymeric moiety, meaning that it comprises at least one polymer moiety. In certain embodiments the one or more polymer moiety has a molecular weight of at least 450 Da. In certain embodiments the one or more polymer moiety has a molecular weight of at least 1 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of at least 1.5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of at least 2 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of at least 2.5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of at least 3 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of at least 3.5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of at least 4 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of at least 5 kDa. In certain embodiments the one or more polymer moiety has a maximum molecular weight of 160 kDa. In certain embodiments the one or more polymer moiety has a maximum molecular weight of 120 kDa. In certain embodiments the one or more polymer moiety has a maximum molecular weight of 100 kDa. In certain embodiments the one or more polymer moiety has a maximum molecular weight of 80 kDa. In certain embodiments the one or more polymer moiety has a maximum molecular weight of 70 kDa. In certain embodiments the one or more polymer moiety has a maximum molecular weight of 60 kDa. In certain embodiments the one or more polymer moiety has a maximum molecular weight of 50 kDa. In certain embodiments the one or more polymer moiety has a maximum molecular weight of 40 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 450 Da. In certain embodiments the one or more polymer moiety has a molecular weight of about 1 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 1.5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 2 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 2.5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 3 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 3.5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 4 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 4.5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 5.5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 6 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 6.5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 7 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 7.5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 8 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 8.5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 9 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 9.5 kDa. In certain embodiments the one or more polymer moiety has a molecular weight of about 10 kDa. It is understood that if -Rd- of formula (a-3’) comprises one polymer moiety the minimum and maximum molecular weights provided above apply to this one polymer moiety and if -Rd- of formula (a-3’) comprises more than one polymer moiety the minimum and maximum molecular weights provided above refer to the minimum and maximum molecular weight of all polymer moieties together.

[0447] In certain embodiments the one or more polymer moiety of -Rd- of formula (a-3’) has a Flory radius of at least 1.2 nm. In certain embodiments the one or more polymer moiety has a Flory radius of at least 1.5 nm. In certain embodiments the one or more polymer moiety has a Flory radius of at least 2 nm. In certain embodiments the one or more polymer moiety has a Flory radius of at least 2.5 nm. In certain embodiments the one or more polymer moiety has a Flory radius of at least 3 nm. In certain embodiments the one or more polymer moiety has a Flory radius of at least 3.5 nm. In certain embodiments the one or more polymer moiety has a Flory radius of at least 4 nm. In certain embodiments the one or more polymer moiety has a Flory radius of at least 4.5 nm. In certain embodiments the one or more polymer moiety has a Flory radius of at least 5 nm. In certain embodiments the one or more polymer moiety has a Flory radius of no more than 200 nm. In certain embodiments the one or more polymer moiety has a Flory radius of no more than 175 nm. In certain embodiments the one or more polymer moiety has a Flory radius of no more than 150 nm. In certain embodiments the one or more polymer moiety has a Flory radius of no more than 125 nm. In certain embodiments the one or more polymer moiety has a Flory radius of no more than 100 nm. In certain embodiments the one or more polymer moiety has a Flory radius of no more than 75 nm. In certain embodiments the one or more polymer moiety has a Flory radius of no more than 50 nm. In certain embodiments the one or more polymer moiety has a Flory radius of no more than 45 nm. In certain embodiments the one or more polymer moiety has a Flory radius of no more than 40 nm. In certain embodiments the one or more polymer moiety has a Flory radius of no more than 35 nm. In certain embodiments the one or more polymer moiety has a Flory radius of no more than 30 nm. In certain embodiments the one or more polymer moiety has a Flory radius of about 1.2 nm. In certain embodiments the one or more polymer moiety has a Flory radius of about 1.5 nm. In certain embodiments the one or more polymer moiety has a Flory radius of about 2 nm. In certain embodiments the one or more polymer moiety has a Flory radius of about 2.5 nm. In certain embodiments the one or more polymer moiety has a Flory radius of about 3 nm. In certain embodiments the one or more polymer moiety has a Flory radius of about 3.5 nm. In certain embodiments the one or more polymer moiety has a Flory radius of about 4 nm. In certain embodiments the one or more polymer moiety has a Flory radius of about 4.5 nm. In certain embodiments the one or more polymer moiety has a Flory radius of about 5 nm. In certain embodiments the one or more polymer moiety has a Flory radius of about 5.5 nm. In certain embodiments the one or more polymer moiety has a Flory radius of about 6 nm. In certain embodiments the one or more polymer moiety has a Flory radius of about 6.5 nm. In certain embodiments the one or more polymer moiety has a Flory radius of about 7 nm. In certain embodiments the one or more polymer moiety has a Flory radius of about 8.5 nm. In certain embodiments the one or more polymer moiety has a Flory radius of about 9 nm. In certain embodiments the one or more polymer moiety has a Flory radius of about 10 nm. It is understood that if -Rd- of formula (a-3’) comprises one polymer moiety the Flory radius provided above applies to this one polymer moiety and if -Rd- of formula (a-3’) comprises more than one polymer moiety the Flory radius provided above refers to the Flory radius of all polymer moieties together.

[0448] -Rd- of formula (a-3’) comprises one or more polymer moiety, such as polymer moiety selected from the group consisting of poly(2-methacryloyl-oxyethyl phosphoyl cholins), poly(acrylic acids), poly(acrylates), poly(acrylamides), poly(alkyloxy) polymers, poly(amides), poly(amidoamines), poly(amino acids), poly(anhydrides), poly(aspartamides), poly(butyric acids), poly(glycolic acids), polybutylene terephthalates, poly(caprolactones), poly(carbonates), poly(cyanoacrylates), poly(dimethylacrylamides), poly(esters), poly(ethylenes), poly( ethyleneglycols), poly(ethylene oxides), poly(ethyl phosphates), poly(ethyloxazolines), poly(glycolic acids), poly(hydroxyethyl acrylates), poly(hydroxyethyl- oxazolines), poly(hydroxymethacrylates), poly(hydroxypropylmethacrylamides), poly(hydroxypropyl methacrylates), poly(hydroxypropyloxazolines), poly(iminocarbonates), poly(lactic acids), poly(lactic-co-glycolic acids), poly(methacrylamides), poly(methacrylates), poly(methyloxazolines), poly(organophosphazenes), poly(ortho esters), poly(oxazolines), polypropylene glycols), poly(siloxanes), poly(urethanes), poly(vinyl alcohols), poly(vinyl amines), poly(vinylmethylethers), poly(vinyplyrrolidones), silicones, celluloses, carbomethyl celluloses, hydroxypropyl methylcelluloses, chitins, chitosans, dextrans, dextrins, gelatins, hyaluronic acids and derivatives, functionalized hyaluronic acids, alginate, mannans, pectins, rhamnogalacturonans, starches, hydroxyalkyl starches, hydroxyethyl starches and other carbohydrate-based polymers, xylans, and copolymers thereof.

[0449] In certain embodiments -Rd- of formula (a-3’) comprises a PEG-based polymer. In certain embodiments -Rd- of formula (a-3’) comprises a hyaluronic acid-based polymer. In certain embodiments -Rd- of formula (a-3’) comprises a random coil polymer. In certain embodiments -Rd- of formula (a-3’) comprises a poly-sarcosine polymer.

[0450] In certain embodiments the distance between any two moieties -AB 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 moieties -AB may bind to different albumin molecules and / or two or more moieties -AB may bind to one albumin molecule. In general, if a compound has x moieties -AB they may bind to up to x albumin molecules. It is understood that not all moieties -AB of a compound may be bound to an albumin molecule at any given time.

[0451] Binding to two or more different albumin molecules increases the molecular weight of the compound significantly, which has an advantageous effect on circulation half-life.

[0452] In certain embodiments -D- is a protein or peptide drug moiety and -AB is conjugated to a functional group of -D- provided by the N-terminal amine, the C-terminal carboxyl or a side chain of an amino acid residue. In certain embodiments -AB is conjugated to the N-terminal amine functional group of -D-. In certain embodiments -AB is conjugated to the C-terminal carboxyl functional group. In certain embodiments -AB is conjugated to a functional group provided by an amino acid residue of -D-, such as by a lysine, serine, aspartic acid, glutamic acid, arginine, histidine, threonine, glutamine, asparagine, cysteine, proline, tyrosine or tryptophan. In certain embodiments -AB is conjugated to the functional group of the side chain of a lysine of -D-. In certain embodiments -AB is conjugated to the functional group of the side chain of a serine of -D-. In certain embodiments -AB is conjugated to the functional group of the side chain of an aspartic acid of -D-. In certain embodiments -AB is conjugated to the functional group of the side chain of a glutamic acid of -D-. In certain embodiments -AB is conjugated to the functional group of the side chain of an arginine of -D-. In certain embodiments -AB is conjugated to the functional group of the side chain of a histidine of -D-. In certain embodiments -AB is conjugated to the functional group of the side chain of a threonine of -D-. In certain embodiments -AB is conjugated to the functional group of the side chain of a glutamine of -D-. In certain embodiments -AB is conjugated to the functional group of the side chain of an asparagine of -D-. In certain embodiments -AB is conjugated to the functional group of the side chain of a cysteine of -D-. In certain embodiments -AB is conjugated to the functional group of the side chain of a proline of -D-. In certain embodiments -AB is conjugated to the functional group of the side chain of a tyrosine of -D-. In certain embodiments -AB is conjugated to the functional group of the side chain of a tryptophan of -D-.

[0453] In certain embodiments -D-AB is selected from the group consisting of semaglutide, liraglutide, ecnoglutide, GZR18, GL0034, tirzepatide, cotadutide, BI-456906, pemvidutide, mazdutide, dapiglutide and retatrutide.

[0454] In certain embodiments -D-AB is selected from the group consisting of semaglutide, liraglutide, ecnoglutide, GZR18 and GL0034.

[0455] In certain embodiments -D-AB is semaglutide. Semaglutide is a compound of formula HXiEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NO:40), wherein

[0456] Xi is a-aminoisobutyric acid (Aib); and the lysine at position 20 is chemically modified through conjugation to the epsilon-amine group of the lysine side-chain with wherein the dashed line indicates attachment to the epsilon-amine group of the lysine side chain of the lysine at position 20.

[0457] Semaglutide may be prepared using methods known to those skilled in the art, such as those described in W02006 / 097537.

[0458] In certain embodiments -D-AB is liraglutide. Liraglutide is a compound of formula

[0459] HAEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NO:41), wherein the lysine at position 20 is chemically modified through conjugation to the epsilon-amine group of the lysine side chain with wherein the dashed line indicates attachment to the epsilon-amine group of the lysine side chain of the lysine at position 20.

[0460] In certain embodiments -D-AB is ecnoglutide. Ecnoglutide is a compound of formula

[0461] HVEGTFTSDVSSYLEEQAAREFIKWLVRGRG (SEQ ID NO:42), wherein the lysine at position 24 is chemically modified through conjugation to the epsilon-amine group of the lysine side chain with wherein the dashed line indicates attachment to the epsilon-amine group of the lysine side chain of the lysine at position 24.

[0462] In certain embodiments -D-AB is GZR18. GZR18 is a compound of formula HGEGTFTSDVSSYLEGQAAKEFIAWLVRGRG (SEQ ID NO:43), wherein the lysine at position 20 is chemically modified through conjugation to the epsilon-amine group of the lysine side-chain with wherein the dashed line indicates attachment to the epsilon amine group of the lysine side chain of the lysine at position 20. In certain embodiments -D-AB is GL0034. GL0034 is also known as utreglutide and is a compound of formula

[0463] HXiEGTFTSDVSSYLEGQAAKEFIAWLVRGRGL (SEQ ID NO:44), wherein

[0464] Xi is Aib; and the lysine at position 20 is chemically modified through conjugation to the epsilon-amine group of the lysine side-chain with wherein the dashed line indicates attachment to the epsilon amine group of the lysine side chain of the lysine at position 20.

[0465] In certain embodiments -D- or -D-AB is a dual GLP-1 receptor agonist selected from the group consisting of tirzepatide, cotadutide, BI-456906, pemvidutide and mazdutide.

[0466] In certain embodiments -D-AB is a dual GLP-1 receptor agonist that activates the GLP-1 receptor and the GIP receptor. An example for such dual GLP-1 receptor agonist is tirzepatide. In certain embodiments -D-AB is tirzepatide. Tirzepatide is a compound of formula

[0467] YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS (SEQ ID NO:45), wherein

[0468] Xi is Aib;

[0469] X2 is Aib; the lysine at position 20 is chemically modified through conjugation to the epsilon-amine group of the lysine side-chain with ([2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(YGlu)i-CO- (CH2)18-CO2H; and the C-terminal serine, i.e. the serine at position 39, is amidated as a C-terminal primary amide.

[0470] The moiety ([2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(YGlu)i-CO-(CH2)is-CO2H has the following structure wherein the dashed line indicates attachment to -D-.

[0471] In certain embodiments -D-AB is a dual GLP-1 receptor agonist that activates the GLP-1 receptor and the glucagon receptor selected from the group consisting of cotadutide, BI- 456906, pemvidutide and mazdutide.

[0472] In certain embodiments -D-AB is cotadutide. Cotadutide is a compound of formula HSQGTFTSDKSEYLDSERARDFVAWLEAGG (SEQ ID NO:46), wherein the lysine at position 10 is chemically modified through conjugation to the epsilon- amine group of the lysine side-chain with y-Glu-palmitoyl.

[0473] The moiety y-Glu-palmitoyl has the following structure: wherein the dashed line indicates attachment to -D-.

[0474] In certain embodiments -D-AB is BI-456906. BI-456906 is also known as survodutide and is a compound of formula

[0475] HXiQGTFTSDYSKYLDERAAKDFIKWLESA (SEQ ID NO:47), wherein

[0476] Xi is 1 -amino-cyclobutanecarboxylic acid (Ac4c); the lysine at position 24 is chemically modified through conjugation to the epsilon-amine group of the lysine side-chain with [17-carboxy-heptadecanoyl]-isoGlu-GSGSGG; and the C-terminal alanine, i.e. the alanine at position 29, is ami dated as a C-terminal primary amide.

[0477] The moiety [17-carboxy-heptadecanoyl]-isoGlu-GSGSGG has the following structure: wherein the dashed line indicates attachment to -D-.

[0478] In certain embodiments -D-AB is pemvidutide. Pemvidutide is a compound of formula HXiQGTFTSDYSKYLDEKAAKEFIQWLLQT (SEQ ID NO:48), wherein

[0479] Xi is Aib; the glutamic acid at position 16 and the lysine at position 20 are connected via a lactam bridge; the lysine at position 17 is chemically modified through conjugation to the epsilon-amine group of the lysine side-chain with glucuronic acid C-18, which is a moiety of formula wherein the dashed line indicates attachment to the epsilon-amine group of the lysine at position 17; and the C-terminal threonine, i.e. the threonine at position 29, is amidated as a C-terminal primary amide

[0480] In certain embodiments -D-AB is mazdutide. Mazdutide is a compound of formula HXiQGTFTSDYSKYLDEKKAKEFVEWLLEGGPSSG (SEQ ID NO:49), wherein

[0481] X1 is Aib, the lysine at position 20 is chemically modified by conjugation of the epsilon-amine group of the lysine side chain with ([2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(y-Glu)-CO- (CH2)18-CO2H; and the C-terminal glycine, i.e. the glycine at position 34, is amidated. The moiety ([2-(2-amino-ethoxy)-ethoxy]-acetyl)2-(Y-Glu)-CO-(CH2)i8-CO2H has the following structure: wherein the dashed line indicates attachment to -D-.

[0482] In certain embodiments -D-AB is a dual GLP-1 receptor agonist that activates the GLP-1 receptor and the GLP-2 receptor, such as dapiglutide. Dapiglutide is a compound of formula

[0483] HXiEGSFTSELATILDKQAARDFIAWLIQHKITD (SEQ ID NO:50), wherein

[0484] Xi is Aib; and the lysine in position 16 is chemically modified by conjugation of the epsilon-amino- group of the lysine side chain with [17-carboxy-heptadecanoyl]-isoGlu.

[0485] The moiety [17-carboxy-heptadecanoyl]-isoGlu has the following structure: wherein the dashed line indicates attachment to -D-.

[0486] In certain embodiments -D-AB is retatrutide, which is a triple GLP-1 receptor agonist that activates the GLP-1 receptor, the GIP receptor and the GCG receptor. Retatrutide is a compound of formula

[0487] YX1QGTFTSDYSIX2LDKKAQX3AFIEYLLEGGPSSGAPPPS (SEQ ID N0:51), wherein

[0488] X1 is Aib;

[0489] X2 is a-methyl-leucine (aMeL);

[0490] X3 is Aib; the lysine at position 17 is chemically modified by conjugation of the epsilon-amine group of the lysine side chain with (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(yGlu)-CO- (CH2)18-CO2H; and the C-terminal serine, i.e. the serine at position 39, is amidated.

[0491] Retatrutide can also be described as Y-Aib-QGTFTSDYSI-aMeL-LDKK ((2-[2-(2-amino- ethoxy)-ethoxy]-acetyl)-(YGlu)-CO-(CH2)18-CO2H) AQ-Aib-AFIEYLLEGGPSSGAPPPS- NH2(SEQ ID NO:51).

[0492] The moiety (2-[2-(2-amino-ethoxy)-ethoxy]-acetyl)-(yGlu)-CO-(CH2)18-CO2H has the following structure:

[0493] In certain embodiments -D-AB is noiiglutide, also known as SHR20004.

[0494] In certain embodiments -D-AB is ZT002.

[0495] In certain embodiments -D-AB is selected from the group consisting of semaglutide, liraglutide, ecnoglutide, GZR18, GL0034, tirzepatide, cotadutide, BI-456906, pemvidutide, mazdutide, dapiglutide and retatrutide.

[0496] In certain embodiments -D-AB is of formula (b-1) wherein and with Ph being phenyl.

[0497] The moiety -D- of formula (b-1) has the sequence of SEQ ID NO:57

[0498] YX1EGTFTSDYSIX2LDKIAQKAFVQWLIAGGPSSGAPPPS, with Xi and X2 being Aib.

[0499] The compounds of formula (b-1) are disclosed in WO2022159395 and W02023 / 044290, the content of which is herewith incorporated by reference in its entirety.

[0500] In certain embodiments -D-AB is of formula (b-1) and X1- is and -X2is In certain embodiments D-AB is of formula (b-1) and X1- isand_^2 Incertainembodiments D-AB is of formula (b-1) and X1- is and -X2is . In certain embodiments D-AB is of formula (b-1) and X1- is and -X2is Incertainembodiments D-AB is of formula (b-1) and X1- is and -X2is Incertainembodiments D-AB is of formula (b-1) and is and -X2is in certain embodiments D-AB is of formula (b-1) and X1- is and_X2is Incertainembodiments D-AB is of formula (b-1) and X1- isand_x2isin certain embodiments D-AB is of formula (b-1) and X>- is and is In certain embodiments D-AB is of formula

[0501] (b-1) and X - is and -X is In certain embodiments D-AB is of formula (b-1) and X1- is and -X2is In certain embodiments D-AB is

[0502] , o of formula (b-1) and X1- i and -X2is

[0503] In certain embodiments -D-AB is a compound of formula k(YE-(miniPEG)2-YE-COCi6H32CO2H)(N-Me)GSVSEIQLMHNLGKHLNSMERVEW LRKKLQDVHK(YE-(miniPEG)2-YE-COCi6H32CO2H)-OH (SEQ ID NO:52), wherein k is d-Lys; yE is the 1-isomer of gamma, glutamic acid; miniPEG is COCH2OCH2CH2OCH2CH2NH;

[0504] COC16H32CO2H is C18 diacid;

[0505] (N-Me)G is sarcosine;

[0506] K is 1-isomer of lysine; and

[0507] -OH designates the C-terminal amino acid has a terminal carboxylic acid.

[0508] In certain embodiments -D-AB is a compound of formula k(YE-(miniPEG)2-YE-COCi6H32CO2H)(N-Me)GSVSEIQLMHNLGKHLNSMERVEW LRKKLQDVHK(YE-(miniPEG)2-YE-COC16H32CO2H)-OH (SEQ ID NO:53), wherein k is d-Lys; yE is the 1-isomer of gamma, glutamic acid;

[0509] (miniPEG)2is COCH2OCH2CH2OCH2CH2NH;

[0510] COC16H32CO2H is C18 diacid;

[0511] (N-Me)G is sarcosine;

[0512] K is 1-isomer of lysine; and

[0513] -OH designates the C-terminal amino acid has a terminal carboxylic acid. If -D- is a peptide or protein drug moiety, -L1- is either conjugated to a functional group of a side chain of an amino acid residue of -D-, to the N-terminal amine functional group or to the C -terminal carboxyl functional group of -D- or to a nitrogen atom in the backbone chain of -D-.

[0514] If -D- is a peptide or protein drug moiety, -L1- is in certain embodiments conjugated to a functional group of -D- selected from the group consisting of carboxylic acid, primary amine, secondary amine, maleimide, thiol, sulfonic acid, carbonate, carbamate, hydroxyl, aldehyde, ketone, hydrazine, isocyanate, isothiocyanate, phosphoric acid, phosphonic acid, haloacetyl, alkyl halide, acryloyl, aryl fluoride, hydroxylamine, sulfate, disulfide, vinyl sulfone, vinyl ketone, diazoalkane, oxirane, guanidine and aziridine. If -D- is a peptide or protein drug moiety, -L1- is in certain embodiments conjugated to a functional group of -D- selected from the group consisting of hydroxyl, primary amine, secondary amine and guanidine. If -D- is a peptide or protein drug moiety, -L1- is in certain embodiments conjugated to a functional group of -D- selected from the group consisting of primary amine and secondary amine. If -D- is a peptide or protein drug moiety, -L1- is in certain embodiments conjugated to a primary amine of -D-.

[0515] If -D- is a peptide or protein drug moiety, -L1- may be conjugated to a functional group of the side chain of an amino acid residue of -D-, which may be a proteinogenic amino acid residue or a non-proteinogenic amino acid residue.

[0516] If -D- is a peptide or protein drug moiety, -L1- is in certain embodiments conjugated to a functional group of the side chain of a proteinogenic amino acid residue of -D-. In certain embodiments such amino acid residue is selected from the group consisting of histidine, lysine, tryptophan, serine, threonine, tyrosine, aspartic acid, glutamic acid and arginine. In certain embodiments such amino acid residue is selected from the group consisting of lysine, aspartic acid, arginine and serine. In certain embodiments such amino acid residue is selected from the group consisting of lysine, arginine and serine.

[0517] If -D- is a peptide or protein drug moiety, -L1- is in certain embodiments conjugated to a functional group of a lysine residue of -D-. If -D- is a peptide or protein drug moiety, -L1- is in certain embodiments conjugated to a functional group of a histidine residue of -D-. If -D- is a peptide or protein drug moiety, -L1- is in certain embodiments conjugated to a functional group of a tryptophan residue of -D-. If -D- is a peptide or protein drug moiety, -L1- is in certain embodiments conjugated to a functional group of a serine residue of -D-. If -D- is a peptide or protein drug moiety, -L1- is in certain embodiments conjugated to a functional group of a threonine residue of -D-. If -D- is a peptide or protein drug moiety, -L1- is in certain embodiments conjugated to a functional group of a tyrosine residue of -D-. If -D- is a peptide or protein drug moiety, -L1- is in certain embodiments conjugated to a functional group of an aspartic acid residue of -D-. If -D- is a peptide or protein drug moiety, -L1- is in certain embodiments conjugated to a functional group of a glutamic acid residue of -D-. If -D- is a peptide or protein drug moiety, -L1- is in certain embodiments conjugated to a functional group of an arginine residue of -D-.

[0518] If -D- is a peptide or protein drug moiety, -L1- is in certain embodiments conjugated to a functional group of the side chain of a non-proteinogenic amino acid residue of -D-.

[0519] It is understood that not every peptide or protein drug moiety -D- may comprise all of these amino acid residues.

[0520] If -D- is a peptide or protein drug moiety, -L1- is in certain embodiments conjugated to the N- terminal amine functional group of -D-.

[0521] If -D- is a peptide or protein drug moiety, -L1- is in certain embodiments conjugated to the C- terminal functional group of -D-.

[0522] The moiety -L1- may be connected to -D- through any type of linkage, provided that it is reversible. In certain embodiments -L1- is connected to -D- through a linkage selected from the group consisting of amide, ester, carbamate, acetal, aminal, imine, oxime, hydrazone, disulfide and acylguanidine. In certain embodiments -L1- is connected to -D- through a linkage selected from the group consisting of amide, ester, carbamate and acylguanidin. It is understood that some of these linkages per se are not reversible, but that in the present invention neighboring groups present in -L1- render these linkages reversible.

[0523] In certain embodiments -L1- is connected to -D- through an amide linkage. In certain embodiments -L1- is connected to -D- through a carbamate linkage. In certain embodiments -L1- is connected to -D- through an ester linkage. In certain embodiments -L1- is connected to -D- through an acylguanidine linkage.

[0524] The moiety -L1- is a reversible prodrug linker from which the drug, i.e., H-D-AB, is released in its free form, i.e. it is a traceless prodrug linker. It is understood that the “H-“ in “H-D-AB” is a hydrogen. Suitable prodrug linkers are known in the art, such as for example the reversible prodrug linker moieties disclosed in WO 2005 / 099768 A2, WO 2006 / 136586 A2, WO 2011 / 089216 Al and WO 2013 / 024053 Al, which are incorporated by reference herewith.

[0525] In certain embodiments -L1- is disclosed in WO 2009 / 095479 A2. Accordingly, in certain embodiments the moiety -L1- is of formula (II): wherein the dashed line indicates attachment to a nitrogen, hydroxyl or thiol of -D-;

[0526] -X- is selected from the group consisting of -C(R4R4a)-; -N(R4)-; -O-; -C(R4R4a)- C(R5R5a)-; -C(R5R5a)-C(R4R4a)-; -C(R4R4a)-N(R6)-; -N(R6)-C(R4R4a)-;

[0527] C(R4R4a)-O-; -O-C(R4R4a)-; and -C(R7R7a)-;

[0528] X1is selected from the group consisting of C; and S(O);

[0529] -X2- is selected from the group consisting of -C(R8R8a)-; and -C(R8R8a)-C(R9R9a)-;

[0530] =X3is selected from the group consisting of =0; =S; and =N-CN;

[0531] -R1, -R1a, -R2, -R2a, -R4, -R4a, -R5, -R5a, -R6, -R8, -R8a, -R9, and -R9aare independently selected from the group consisting of -H; and C1-6alkyl;

[0532] -R3, and -R3aare independently selected from the group consisting of -H; and C1-6alkyl, provided that in case one of -R3, -R3aor both are other than -H they are connected to N to which they are attached through an SP3-hybridized carbon atom;

[0533] -R7is selected from the group consisting of -N(R10R10a); and -NR10-(C=O)-R11;

[0534] -R7a, -R10, -R10a, and -R11are independently of each other selected from the group consisting of -H; and C1-6alkyl; optionally, one or more of the pairs -R1a / -R4a, -R1a / -R5a, -R1a / -R7a, -R4a / -R5a, and -R8a / -R9aform a chemical bond; optionally, one or more of the pairs -R1 / -R13, -R2 / -R2a, -R4 / -R4a, -R5 / -R5a, -R8 / -R8a, and -R9 / -R9aare joined together with the atom to which they are attached to form a C3- 10 cycloalkyl; or 3- to 10-membered heterocyclyl; optionally, one or more of the pairs -R1 / -R4, -R1 / -R5, -R1 / -R6, -R' / -R7:I, -R4 / -R5, -R4 / -R6, -R8 / -R9, and -R2 / -R3are joined together with the atoms to which they are attached to form a ring A; optionally, R3 / R3aare joined together with the nitrogen atom to which they are attached to form a 3- to 10-membered heterocycle;

[0535] A is selected from the group consisting of phenyl; naphthyl; indenyl; indanyl; tetralinyl; C3-10 cycloalkyl; 3- to 10-membered heterocyclyl; and 8- to 11-membered heterobicyclyl; and wherein -L1- is substituted with at least one -L2- and wherein -L1- is optionally further substituted, provided that the hydrogen marked with the asterisk in formula (II) is not replaced by -L2- or a substituent.

[0536] In certain embodiments -L1- of formula (II) is substituted with one moiety -L2-.

[0537] In certain embodiments -L1- of formula (II) is not further substituted.

[0538] It is understood that if -R3 / -R3aof formula (II) are joined together with the nitrogen atom to which they are attached to form a 3 - to 10-membered heterocycle, only such 3- to 10-membered heterocycles may be formed in which the atoms directly attached to the nitrogen are SP3- hybridized carbon atoms. In other words, such 3- to 10-membered heterocycle formed by -R3 / -R3atogether with the nitrogen atom to which they are attached has the following structure: wherein the dashed line indicates attachment to the rest of -L1-; the ring comprises 3 to 10 atoms comprising at least one nitrogen; and

[0539] R#and R##represent an sp3-hydridized carbon atom.

[0540] It is also understood that the 3- to 10-membered heterocycle may be further substituted. Exemplary embodiments of suitable 3- to 10-membered heterocycles formed by -R3 / -R3aof formula (II) together with the nitrogen atom to which they are attached are the following: wherein dashed lines indicate attachment to the rest of the molecule; and

[0541] -R is selected from the group consisting of -H and C1-6alkyl.

[0542] -L1- of formula (II) may optionally be further substituted. In general, any substituent may be used as far as the cleavage principle is not affected, i.e., the hydrogen marked with the asterisk in formula (II) is not replaced and the nitrogen of the moiety of formula (II) remains part of a primary, secondary or tertiary amine, i.e., -R3and -R3aare independently of each other -H or are connected to -N< through an sp3-hybridized carbon atom.

[0543] In one embodiment -R1or -R1aof formula (II) is substituted with -L2-. In another embodiment -R2or -R2aof formula (II) is substituted with -L2-. In another embodiment -R3or -R3aof formula (II) is substituted with -L2-. In another embodiment -R4of formula (II) is substituted with -L2-. In another embodiment -R5or -R5aof formula (II) is substituted with -L2-. In another embodiment -R6of formula (II) is substituted with -L2-. In another embodiment -R7or -R7aof formula (II) is substituted with -L2-. In another embodiment -R8or -R8aof formula (II) is substituted with -L2-. In another embodiment -R9or -R9aof formula (II) is substituted with -L2-. In another embodiment -R10is substituted with -L2-. In another embodiment -R11is substituted with -L2-. In certain embodiments -R3of formula (II) is substituted with -L2-.

[0544] In certain embodiments -X- of formula (II) is selected from the group consisting of -C(R4R4a)-, -N(R4)- and -C(R7R7a)-. In certain embodiments -X- of formula (II) is -C(R4R4a)-. In certain embodiments -X- of formula (II) is -C(R7R7a)-. In certain embodiments -R7of formula (II) is -NR10-(C=O)-R11.

[0545] In certain embodiments -R7aof formula (II) is selected from -H, methyl and ethyl. In certain embodiments -R7aof formula (II) is -H.

[0546] In certain embodiments -R10is selected from -H, methyl and ethyl. In certain embodiments -R10is methyl.

[0547] In certain embodiments -R11is selected from -H, methyl and ethyl. In certain embodiments -R11is -H. In certain embodiments -R11is substituted with -L2-.

[0548] In certain embodiments -X- of formula (II) is -N(R4)-.

[0549] In certain embodiments -R4is selected from the group consisting of -H, methyl and ethyl. In certain embodiments -R4is -H.

[0550] In certain embodiments X1of formula (II) is C.

[0551] In certain embodiments =X3of formula (II) is =0.

[0552] In certain embodiments -X2- of formula (II) is -C(R8R8a)-.

[0553] In certain embodiments -R8and -R8aof formula (II) are independently selected from the group consisting of -H, methyl and ethyl. In certain embodiments at least one of -R8and -R8aof formula (II) is -H. In certain embodiments both -R8and -R8aof formula (II) are -H.

[0554] In certain embodiments -R1and -R1aof formula (II) are independently selected from the group consisting of -H, methyl and ethyl.

[0555] In certain embodiments at least one of -R1and -R1aof formula (II) is -H. In certain embodiments -R1and -R1aof formula (II) are -H. In certain embodiments at least one of -R1and -R1aof formula (II) is methyl. In certain embodiments both -R1and -R1aof formula (II) are methyl.

[0556] In certain embodiments -R2and -R2aof formula (II) are independently selected from the group consisting of -H, methyl and ethyl. In certain embodiments at least one of -R2and -R2aof formula (II) is -H. In certain embodiments both -R2and -R2aof formula (II) are H.

[0557] In certain embodiments -R3and -R3aof formula (II) are independently selected from the group consisting of -H, methyl, ethyl, propyl and butyl.

[0558] In certain embodiments at least one of -R3and -R3aof formula (II) is methyl. In certain embodiments -R3of formula (II) is methyl and -R3aof formula (II) is -H.

[0559] In certain embodiments -R3and -R3aof formula (II) are both -H.

[0560] In certain embodiments -D- is connected to -L1- through a nitrogen by forming an amide bond.

[0561] In certain embodiments -L1- is of formula (II), wherein X is -C(R7R7a)-; X1is C; -X2- is -C(R8R8a)-C(R9R9a)-; =X3is =0; -R1and -R1aare -H; -R2and -R2aare -H; -R3and -R3aare methyl; -R7is -N(R10R10a); -R7ais -H; -R8, -R8a, -R9and -R9aare -H; and -R10is methyl and -R10ais -H.

[0562] In certain embodiments -L1- is of formula (Ila) wherein the dashed line marked with the asterisk indicates attachment to a nitrogen of -D-; and the unmarked dashed line indicates attachment to -L2-.

[0563] In certain embodiments -L1- is of formula (Ila-a) wherein the dashed line marked with the asterisk indicates attachment to a nitrogen of -D-; and the unmarked dashed line indicates attachment to -L2-.

[0564] In certain embodiments -L1- is of formula (Ila-b) wherein the dashed line marked with the asterisk indicates attachment to a nitrogen of -D-; and the unmarked dashed line indicates attachment to -L2-.

[0565] The moiety of formula (Ila), (Ila-a) and (Ila-b) is connected to -D- via an amide bond formed by a nitrogen of an amine functional group and the carbonyl to the left of the dashed line marked with the asterisk.

[0566] In certain embodiments -L1- is of formula (II), wherein X is -C(R7R7a)-; X1is C; -X2- is -C(R8R8a)-C(R9R9a)-; =X3is =0; -R1and -R1aare -H; -R2and -R2aare -H; -R3and -R3aare methyl; -R7is -NR10-(C=O)-R11; -R7ais -H; -R8, -R8a, -R9and -R9aare -H; and -R10is methyl and -R11is -H.

[0567] In certain embodiments -L1- is of formula (II), wherein X is -C(R7R7a)-; X1is C; -X2- is -C(R8R8a)-C(R9R9a)-; =X3is =0; -R1and -R1aare -H; -R2and -R2aare -H; -R3and -R3aare methyl; -R7is -NR10-(C=O)-R11; -R7ais -H; -R8, -R8a, -R9and -R9aare -H; and -R10is -H and -R11is -H.

[0568] In certain embodiments -L1- is of formula (Ilab) wherein the dashed line marked with the asterisk indicates attachment to a nitrogen of -D-; and the unmarked dashed line indicates attachment to -L2-.

[0569] In certain embodiments -L1- is of formula (Ilab-a) wherein the dashed line marked with the asterisk indicates attachment to a nitrogen of -D-; and the unmarked dashed line indicates attachment to -L2-.

[0570] In certain embodiments -L1- is of formula (Ilab-b) wherein the dashed line marked with the asterisk indicates attachment to a nitrogen of -D-; and the unmarked dashed line indicates attachment to -L2-.

[0571] The moiety of formula (Ilab), (Ilab-a) and (Ilab-b) is connected to -D- via an amide bond formed by a nitrogen of an amine functional group and the carbonyl to the left of the dashed line marked with the asterisk.

[0572] In certain embodiments -L1- is disclosed in W02016 / 020373A1. Accordingly, in certain embodiments the moiety -L1- is of formula (III): wherein the dashed line indicates attachment to a primary or secondary amine or hydroxyl of -D- through an amide or ester linkage, respectively;

[0573] -R1, -R1a, -R2, -R2a, -R3and -R3aare independently of each other selected from the group consisting of -H, -C(R8R8aR8b), -C(=O)R8, -C≡N, -C(=NR8)R8a,

[0574] -CR8(=CR8aR8b), -C≡CR8and -T;

[0575] -R4, -R5and -R5aare independently of each other selected from the group consisting of -H, -C(R9R9aR9b) and -T; al and a2 are independently of each other 0 or 1; each -R6, -R6a, -R7, -R7a, -R8, -R8a, -R8b, -R9, -R9a, and -R9bare independently of each other selected from the group consisting of -H, halogen, -CN, -COOR10, -OR10, -C(O)R10, -C(O)N(R10R10a), -S(O)2N(R10R10a), -S(O) N(R10R10a), -S(O)2R10, -S(O)R10, -N(R10)S(O)2N(R10aR10b), -SR10, -N(R10R10a), -NO2, -OC(O)R10, -N(R10)C(O)R10a, -N(R10)S(O)2R10a, -N(R10)S(O)R10a,

[0576] -N(R10)C(O)OR10a, -N(R10)C(O)N(R10aR10b),-OC(O)N(R10R10a), -T, C1-20 alkyl, C2-20alkenyl, and C2-20alkynyl; wherein -T, C1-20 alkyl, C2-20alkenyl, and C2-20alkynyl are optionally substituted with one or more -R11, which are the same or different and wherein C1-20 alkyl, C2-20alkenyl, and C2-20alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(R12)-, -S(O)2N(R12)-, -S(O)N(R12)-,

[0577] -S(O)2-, -S(O)-, -N(R12)S(O)2N(R12a)-,-S-,

[0578] -N(R12)-, -OC(OR12)(R12a)-, -N(R12)C(O)N(R12a)-, and -OC(O)N(R12)-; each -R10, -R10a, and -R10bis independently selected from the group consisting of -H, -T, C1-20 alkyl, C2-20alkenyl, and C2-20alkynyl; wherein -T, C1-20 alkyl, C2-20alkenyl, and C2-20alkynyl are optionally substituted with one or more -R11, which are the same or different and wherein C1-20 alkyl, C2-20alkenyl, and C2-20alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(R12)-, -S(O)2N(R12)-, -S(O)N(R12)-, -S(O)2-, -S(0)-, -N(R12)S(O)2N(R12a)-, -S-, -N(R12)-, -OC(OR12)(R12a)-, -N(R12)C(O)N(R12a)-, and -OC(O)N(R12)-; each T is independently of each other selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, and 8- to 11-membered heterobicyclyl; wherein each T is independently optionally substituted with one or more -R11, which are the same or different; each -R11is independently of each other selected from halogen, -CN, oxo (=0), -C00R13, -OR13, -C(0)R13, -C(O)N(R13R13a), -S(O)2N(R13R13a),

[0579] -S(O)N(R13R13a), -S(O)2R13, -S(O)R13, -N(R13)S(O)2N(R13aR13b), -SR13,

[0580] -N(R13R13a), -N02, -0C(0)R13, -N(R13)C(O)R13a, -N(R13)S(O)2R13a,

[0581] -N(R13)S(O)R13a, -N(R13)C(O)OR13a, -N(R13)C(O)N(R13aR13b),

[0582] -OC(O)N(R13R13a), and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; each -R12, -R12a, -R13, -R13a, and -R13bis independently selected from the group consisting of -H, and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; optionally, one or more of the pairs -R' / -R1a, -R2 / -R2a, -R3 / -R3a, -R6 / -R6a, and -R7 / -R7aare joined together with the atom to which they are attached to form a C3-10 cycloalkyl or a 3- to 10-membered heterocyclyl; optionally, one or more of the pairs -R1 / -R2, -R1 / -R3, -R1 / -R4, -R1 / -R5, -R1 / -R6, -R1 / -R7, -R2 / -R3, -R2 / -R4, -R2 / -R5, -R2 / -R6, -R2 / -R7, -R3 / -R4, -R3 / -R5, -R3 / -R6, -R3 / -R7, -R4 / -R5, -R4 / -R6, -R4 / -R7, -R5 / -R6, -R5 / -R7, and -R6 / -R7are joint together with the atoms to which they are attached to form a ring A;

[0583] A is selected from the group consisting of phenyl; naphthyl; indenyl; indanyl; tetralinyl; C3-10 cycloalkyl; 3- to 10-membered heterocyclyl; and 8- to 11-membered heterobicyclyl; wherein -L1- is substituted with at least one -L2- and wherein -L1- is optionally further substituted.

[0584] The optional further substituents of -L1- of formula (III) are in certain embodiments as described above.

[0585] In certain embodiments -L1- of formula (III) is substituted with one moiety -L2-. In certain embodiments -L1- of formula (III) is not further substituted.

[0586] In certain embodiments -L1- is as disclosed in EP1536334B1, W02009 / 009712A1, W02008 / 034122A1, WO2009 / 143412A2, WO2011 / 082368A2, and US8618124B2, which are herewith incorporated by reference in their entirety.

[0587] In certain embodiments -L1- is as disclosed in US8946405B2 and US8754190B2, which are herewith incorporated by reference in their entirety. Accordingly, in certain embodiments -L1- is of formula (IV): wherein the dashed line indicates attachment to -D- and wherein attachment is through a functional group of -D- selected from the group consisting of -OH, -SH and -NH2; m is 0 or 1; at least one or both of -R1and -R2is / are independently of each other selected from the group consisting of -CN, -NO2, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted alkenyl, optionally substituted alkynyl, -C(O)R3, -S(O)R3, -S(O)2R3, and -SR4, one and only one of -R1and -R2is selected from the group consisting of -H, optionally substituted alkyl, optionally substituted arylalkyl, and optionally substituted heteroarylalkyl;

[0588] -R3is selected from the group consisting of -H, optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -OR9and -N(R9)2;

[0589] -R4is selected from the group consisting of optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; each -R5is 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; -R9is selected from the group consisting of -H and optionally substituted alkyl;

[0590] -Y- is absent and -X- is -O- or -S-; or

[0591] -Y- is -N(Q)CH2- and -X- is -O-;

[0592] Q is selected from the group consisting of optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl and optionally substituted heteroarylalkyl; optionally, -R1and -R2may be joined to form a 3 to 8-membered ring; and optionally, both -R9together with the nitrogen to which they are attached form a heterocyclic ring; wherein -L1- is substituted with at least one -L2- and wherein -L1- is optionally further substituted.

[0593] Only in the context of formula (IV) the terms used have the following meaning:

[0594] The term “alkyl” as used herein includes linear, branched or cyclic saturated hydrocarbon groups of 1 to 8 carbons, or in certain embodiments 1 to 6 or 1 to 4 carbon atoms.

[0595] The term “alkoxy” includes alkyl groups bonded to oxygen, including methoxy, ethoxy, isopropoxy, cyclopropoxy, cyclobutoxy, and similar.

[0596] The term “alkenyl” includes non-aromatic unsaturated hydrocarbons with carbon-carbon double bonds.

[0597] The term “alkynyl” includes non-aromatic unsaturated hydrocarbons with carbon-carbon triple bonds.

[0598] The term “aryl” includes aromatic hydrocarbon groups of 6 to 18 carbons, such as 6 to 10 carbons, including groups such as phenyl, naphthyl, and anthracenyl. The term “heteroaryl” includes aromatic rings comprising 3 to 15 carbons containing at least one N, O or S atom, such as 3 to 7 carbons containing at least one N, O or S atom, including groups such as pyrrolyl, pyridyl, pyrimidinyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, quinolyl, indolyl, indenyl, and similar. In some instance, alkenyl, alkynyl, aryl or heteroaryl moieties may be coupled to the remainder of the molecule through an alkylene linkage. Under those circumstances, the substituent will be referred to as alkenylalkyl, alkynylalkyl, arylalkyl or heteroarylalkyl, indicating that an alkylene moiety is between the alkenyl, alkynyl, aryl or heteroaryl moiety and the molecule to which the alkenyl, alkynyl, aryl or heteroaryl is coupled.

[0599] The term “halogen” includes bromo, fluoro, chloro and iodo.

[0600] The term “heterocyclic ring” refers to a 4 to 8 membered aromatic or non-aromatic ring comprising 3 to 7 carbon atoms and at least one N, O, or S atom. Examples are piperidinyl, piperazinyl, tetrahydropyranyl, pyrrolidine, and tetrahydrofiiranyl, as well as the exemplary groups provided for the term “heteroaryl” above.

[0601] When a ring system is optionally substituted, suitable substituents are selected from the group consisting of alkyl, alkenyl, alkynyl, or an additional ring, each optionally further substituted. Optional substituents on any group, including the above, include halo, nitro, cyano, -OR, -SR, -NR2, -OCOR, -NRCOR, -COOR, -CONR2, -SOR, -SO2R, -SONR2, -SO2N R2, wherein each R is independently alkyl, alkenyl, alkynyl, aryl or heteroaryl, or two R groups taken together with the atoms to which they are attached form a ring.

[0602] In certain embodiments -L1- of formula (IV) is substituted with one moiety -L2-.

[0603] In certain embodiments -L1- of formula (IV) is not further substituted.

[0604] In certain embodiments -L1- is as disclosed in WO2013 / 036857A1, which is herewith incorporated by reference in its entirety. Accordingly, in certain embodiments -L1- is of formula (V): wherein the dashed line indicates attachment to -D- through an amine functional group of -D-; -R1is selected from the group consisting of optionally substituted C1-C6linear, branched, or cyclic alkyl; optionally substituted aryl; optionally substituted heteroaryl; alkoxy; and -NR52;

[0605] -R2is selected from the group consisting of -H; optionally substituted C1-C6alkyl; optionally substituted aryl; and optionally substituted heteroaryl;

[0606] -R3is selected from the group consisting of -H; optionally substituted C1-C6alkyl; optionally substituted aryl; and optionally substituted heteroaryl;

[0607] -R4is selected from the group consisting of -H; optionally substituted C1-C6alkyl; optionally substituted aryl; and optionally substituted heteroaryl; each -R5is independently of each other selected from the group consisting of -H; optionally substituted C1-C6alkyl; optionally substituted aryl; and optionally substituted heteroaryl; or when taken together two -R5can be cycloalkyl or cycloheteroalkyl; wherein -L1- is substituted with at least one -L2- and wherein -L1- is optionally further substituted.

[0608] Only in the context of formula (V) the terms used have the following meaning:

[0609] “Alkyl”, “alkenyl”, and “alkynyl” include linear, branched or cyclic hydrocarbon groups of 1- 8 carbons or 1-6 carbons or 1-4 carbons wherein alkyl is a saturated hydrocarbon, alkenyl includes one or more carbon-carbon double bonds and alkynyl includes one or more carboncarbon triple bonds. Unless otherwise specified these contain 1-6 C.

[0610] “Aryl” includes aromatic hydrocarbon groups of 6-18 carbons, such as 6-10 carbons, including groups such as phenyl, naphthyl, and anthracene “Heteroaryl” includes aromatic rings comprising 3-15 carbons containing at least one N, O or S atom, such as 3-7 carbons containing at least one N, O or S atom, including groups such as pyrrolyl, pyridyl, pyrimidinyl, imidazolyl, oxazolyl, isoxazolyl, thiszolyl, isothiazolyl, quinolyl, indolyl, indenyl, and similar.

[0611] The term “substituted” means an alkyl, alkenyl, alkynyl, aryl, or heteroaryl group comprising one or more substituent groups in place of one or more hydrogen atoms. Substituents may generally be selected from halogen including F, Cl, Br, and I; lower alkyl including linear, branched, and cyclic; lower haloalkyl including fluoroalkyl, chloroalkyl, bromoalkyl, and iodoalkyl; OH; lower alkoxy including linear, branched, and cyclic; SH; lower alkylthio including linear, branched and cyclic; amino, alkylamino, dialkylamino, silyl including alkylsilyl, alkoxysilyl, and arylsilyl; nitro; cyano; carbonyl; carboxylic acid, carboxylic ester, carboxylic amide, aminocarbonyl; aminoacyl; carbamate; urea; thiocarbamate; thiourea; ketone; sulfone; sulfonamide; aryl including phenyl, naphthyl, and anthracenyl; heteroaryl including 5-member heteroaryls including as pyrrole, imidazole, furan, thiophene, oxazole, thiazole, isoxazole, isothiazole, thiadiazole, triazole, oxadiazole, and tetrazole, 6-member heteroaryls including pyridine, pyrimidine, pyrazine, and fused heteroaryls including benzofuran, benzothiophene, benzoxazole, benzimidazole, indole, benzothiazole, benzisoxazole, and benzisothiazole.

[0612] In certain embodiments -L1- of formula (V) is substituted with one moiety -L2-.

[0613] In certain embodiments -L1- of formula (V) is not further substituted.

[0614] In certain embodiments -L1- is as disclosed in US7585837B2, which is herewith incorporated by reference in its entirety. Accordingly, in certain embodiments -L1- is of formula (VI): wherein the dashed line indicates attachment to -D- through an amine functional group of -D;

[0615] R1and R2are independently selected from the group consisting of hydrogen, alkyl, alkoxy, alkoxyalkyl, aryl, alkaryl, aralkyl, halogen, nitro, -SO3H, -SO2NHR5, amino, ammonium, carboxyl, PO3H2, and OPO3H2;

[0616] R3, R4, and R5are independently selected from the group consisting of hydrogen, alkyl, and aryl; wherein -L1- is substituted with at least one -L2- and wherein -L1- is optionally further substituted. Suitable substituents for formulas (VI) are alkyl (such as C1-6alkyl), alkenyl (such as C2-6 alkenyl), alkynyl (such as C2-6 alkynyl), aryl (such as phenyl), heteroalkyl, heteroalkenyl, heteroalkynyl, heteroaryl (such as aromatic 4 to 7 membered heterocycle) or halogen moieties.

[0617] Only in the context of formula (VI) the terms used have the following meaning:

[0618] The terms “alkyl”, “alkoxy”, “alkoxyalkyl”, “aryl”, “alkaryl” and “aralkyl” mean alkyl radicals of 1-8, such as 1-4 carbon atoms, e.g. methyl, ethyl, propyl, isopropyl and butyl, and aryl radicals of 6-10 carbon atoms, e.g. phenyl and naphthyl. The term “halogen” includes bromo, fluoro, chloro and iodo.

[0619] In certain embodiments -L1- of formula (VI) is substituted with one moiety -L2-.

[0620] In certain embodiments -L1- of formula (VI) is not further substituted.

[0621] A further preferred embodiment for -L1- is disclosed in W02002 / 089789A1, which is herewith incorporated by reference in its entirety. Accordingly, a preferred moiety -L1- is of formula (VII):

[0622] (VII), wherein the dashed line indicates attachment to -D- through an amine functional group of -D-;

[0623] Li is a bifunctional linking group,

[0624] Yi and Y2 are independently O, S or NR7;

[0625] R2, R3, R4, R5, R6and R7are independently selected from the group consisting of hydrogen, C1-6 alkyls, C3-12 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls, substituted C1-6 heteroalkyls, C1-6 alkoxy, phenoxy, and C1-6 heteroalkoxy; Ar is a moiety which when included in formula (VII) forms a multi substituted aromatic hydrocarbon or a multi- substituted heterocyclic group;

[0626] X is a chemical bond or a moiety that is actively transported into a target cell, a hydrophobic moiety, or a combination thereof, y is 0 or 1; wherein -L1- is substituted with at least one -L2- and wherein -L1- is optionally further substituted.

[0627] Only in the context of formula (VII) the terms used have the following meaning:

[0628] The term “alkyl” shall be understood to include, e.g., straight, branched, substituted C1-12 alkyls, including alkoxy, C3-8 cycloalkyls or substituted cycloalkyls, etc.

[0629] The term “substituted” shall be understood to include adding or replacing one or more atoms contained within a functional group or compounds with one or more different atoms.

[0630] Substituted alkyls include carboxyalkyls, aminoalkyls, dialkylaminos, hydroxyalkyls and mercaptoalkyls; substituted cycloalkyls include moieties such as 4-chlorocyclohexyl; aryls include moieties such as napthyl; substituted aryls include moieties such as 3 -bromo-phenyl; aralkyls include moieties such as toluyl; heteroalkyls include moieties such as ethylthiophene; substituted heteroalkyls include moieties such as 3 -methoxythiophone; alkoxy includes moieties such as methoxy; and phenoxy includes moieties such as 3 -nitrophenoxy. Halo- shall be understood to include fluoro, chloro, iodo and bromo.

[0631] In certain embodiments -L1- of formula (VII) is substituted with one moiety -L2-.

[0632] In certain embodiments -L1- of formula (VII) is not further substituted.

[0633] In certain embodiments -L1- comprises a substructure of formula (VIII) wherein the dashed line marked with the asterisk indicates attachment to a nitrogen of -D- through an amide bond; the unmarked dashed lines indicate attachment to the remainder of -L1-; and wherein -L1- is substituted with at least one -L2- and wherein -L1- is optionally further substituted.

[0634] In certain embodiments -L1- of formula (VIII) is substituted with one moiety -L2-.

[0635] In certain embodiments -L1- of formula (VIII) is not further substituted.

[0636] In certain embodiments -L1- comprises a substructure of formula (IX) wherein the dashed line marked with the asterisk indicates attachment to a nitrogen of -D- through a carbamate bond; the unmarked dashed lines indicate attachment to the remainder of -L1-; and wherein -L1- is substituted with at least one -L2- and wherein -L1- is optionally further substituted.

[0637] In certain embodiments -L1- of formula (IX) is substituted with one moiety -L2-.

[0638] In certain embodiments -L1- of formula (IX) is not further substituted.

[0639] In certain embodiments -L1- has a structure as disclosed in W02020 / 206358 Al. Accordingly, in certain embodiments the moiety -L1- is of formula (X): wherein the unmarked dashed line indicates attachment to -D-; the dashed line marked with the asterisk indicates attachment to -L2-; n is an integer selected from the group consisting of 0, 1, 2, 3, 4, 5 and 6;

[0640] -R1and -R2are independently an electron- withdrawing group, alkyl, or -H, and wherein at least one of -R1or -R2is an electron-withdrawing group; each -R4is independently C1-C3 alkyl or the two -R4are taken together with the carbon atom to which they are attached to form a 3- to 6-membered ring; and

[0641] -Y- is absent when -D- is a drug moiety connected through an amine, or -Y- is -N(R6)CH2- when -D- is a drug moiety connected through a phenol, alcohol, thiol, thiophenol, imidazole, or non-basic amine; wherein -R6is optionally substituted C1-C6alkyl, optionally substituted aryl, or optionally substituted heteroaryl.

[0642] In certain embodiments n of formula (X) is an integer selected from 1, 2, 3, 4, 5 and 6. In certain embodiments n of formula (X) is an integer selected from 1, 2 and 3. In certain embodiments n of formula (X) is an integer from 0, 1, 2 and 3. In certain embodiments n of formula (X) is 1. In certain embodiments n of formula (X) is 2. In certain embodiments n of formula (X) is 3.

[0643] In certain embodiments the electron-withdrawing group of -R1and -R2of formula (X) is selected from the group consisting of -CN; -NO2; optionally substituted aryl; optionally substituted heteroaryl; optionally substituted alkenyl; optionally substituted alkynyl; -COR3, -SOR3, or -SO2R3, wherein -R3is -H, optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, -OR8or -NR82, wherein each -R8is independently -H or optionally substituted alkyl, or both -R8groups are taken together with the nitrogen to which they are attached to form a heterocyclic ring; or -SR9, wherein -R9is optionally substituted alkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, or optionally substituted heteroarylalkyl. In certain embodiments the electron-withdrawing group of -R1and -R2of formula (X) is -CN. In certain embodiments the electron-withdrawing group of -R1and -R2of formula (X) is -NO2. In certain embodiments the electron-withdrawing group of -R1and -R2of formula (X) is optionally substituted aryl comprising 6 to 10 carbons. In certain embodiments the electronwithdrawing group of -R1and -R2of formula (X) is optionally substituted phenyl, naphthyl, or anthracenyl. In certain embodiments the electron- withdrawing group of -R1and -R2of formula (X) is optionally substituted heteroaryl comprising 3 to 7 carbons and comprising at least one N, O, or S atom. In certain embodiments the electron-withdrawing group of -R1and -R2of formula (X) is optionally substituted pyrrolyl, pyridyl, pyrimidinyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, quinolyl, indolyl, or indenyl. In certain embodiments the electron- withdrawing group of -R1and -R2of formula (X) is optionally substituted alkenyl containing 2 to 20 carbon atoms. In certain embodiments the electron-withdrawing group of -R1and -R2of formula (X) is optionally substituted alkynyl comprising 2 to 20 carbon atoms. In certain embodiments the electron-withdrawing group of -R1and -R2of formula (X) is -COR3, -SOR3, or -SO2R3, wherein -R3is -H, optionally substituted alkyl comprising 1 to 20 carbon atoms, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, optionally substituted heteroaryl alkyl, -OR8or -NR82, wherein each -R8is independently -H or optionally substituted alkyl comprising 1 to 20 carbon atoms, or both -R8groups are taken together with the nitrogen to which they are attached to form a heterocyclic ring. In certain embodiments the electron-withdrawing group of -R1and -R2of formula (X) is -SR9, wherein -R9is optionally substituted alkyl comprising 1 to 20 carbon atoms, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, or optionally substituted heteroarylalkyl.

[0644] In certain embodiments at least one of -R1or -R2of formula (X) is -CN, -SOR3or -SO2R3. In certain embodiments at least one of -R1and -R2of formula (X) is -CN or -SO2R3. In certain embodiments at least one of -R1and -R2of formula (X) is -CN or -SO2R3, wherein -R3is optionally substituted alkyl, optionally substituted aryl, or -NR82. In certain embodiments at least one of -R1and -R2of formula (X) is -CN, -SO2N(CH3)2, -SO2CH3, phenyl substituted with -SO2, phenyl substituted with -SO2 and -Cl, -SO2N(CH CH )2O, -SO2CH(CH3)2, -SO2N(CH3)(CH2CH3), or -SO2N(CH2CH2OCH3)2. In certain embodiments each -R4of formula (X) is independently C1-C3 alkyl. In certain embodiments both -R4are methyl.

[0645] In certain embodiments -Y- of formula (X) is absent. In certain embodiments -Y- of formula (X) is -N(R6)CH2-.

[0646] In certain embodiments -L1- is of formula (X), wherein n is 1, -R1is -CN, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 1, -R1is -SO2N(CH3)2, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 1, -R1is SO2CH3, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 1, -R1is -SO2N(CH2CH2)2CHCH3, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 1, -R1is phenyl substituted with -SO2, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 1, -R1is phenyl substituted with -SO2 and -Cl, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 1, -R1is -SO2N(CH2CH2)2O, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 1, -R1is -SO2CH(CH3)2, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 1, -R1is -SO2N(CH3)(CH2CH3), -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 1, -R1is -SO2N(CH2CH2OCH3)2, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 1, -R1is phenyl substituted with-SO2 and -CH3, -R2is -H, and -R4is -CH3.

[0647] In certain embodiments -L1- is of formula (X), wherein n is 2, -R1is -CN, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 2, -R1is -SO2N(CH3)2, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 2, -R1is SO2CH3, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 2, -R1is -SO2N(CH2CH2)2CHCH3, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 2, -R1is phenyl substituted with -SO2, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 2, -R1is phenyl substituted with -SO2 and -Cl, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 2, -R1is -SO2N(CH2CH2)2O, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 2, -R1is -SO2CH(CH3)2, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 2, -R1is -SO2N(CH3)(CH2CH3), -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 2, -R1is -SO2N(CH2CH2OCH3)2, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 2, -R1is phenyl substituted with -SO2 and -CH3, -R2is -H, and -R4is -CH3.

[0648] In certain embodiments -L1- is of formula (X), wherein n is 3, -R1is -CN, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 3, -R1is -SO2N(CH3)2, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 3, -R1is SO2CH3, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 3, -R1is -SO2N(CH2CH2)2CHCH3, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 3, -R1is phenyl substituted with -SO2, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 3, -R1is phenyl substituted with -SO2 and -Cl, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 3, -R1is -SO2N(CH2CH2)2O, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 3, -R1is -SO2CH(CH3)2, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 3, -R1is -SO2N(CH3)(CH2CH3), -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 3, -R1is -SO2N(CH2CH2OCH3)2, -R2is -H, and -R4is -CH3. In certain embodiments -L1- is of formula (X), wherein n is 3, -R1is phenyl substituted with -SO2 and -CH3, -R2is -H, and -R4is -CH3.

[0649] Only in the context of formula (X) the terms used have the following meaning:

[0650] The term "alkyl" refers to linear, branched, or cyclic saturated hydrocarbon groups of 1 to 20, 1 to 12, 1 to 8, 1 to 6, or 1 to 4 carbon atoms. In certain embodiments an alkyl is 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 an alkyl is cyclic. Examples of cyclic alkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentadienyl, and cyclohexyl.

[0651] The term "alkoxy" refers to alkyl groups bonded to oxygen, including methoxy, ethoxy, isopropoxy, cyclopropoxy, and cyclobutoxy.

[0652] The term "alkenyl" refers to non-aromatic unsaturated hydrocarbons with carbon-carbon double bonds and 2 to 20, 2 to 12, 2 to 8, 2 to 6, or 2 to 4 carbon atoms. The term "alkynyl" refers to non-aromatic unsaturated hydrocarbons with carbon-carbon triple bonds and 2 to 20, 2 to 12, 2 to 8, 2 to 6, or 2 to 4 carbon atoms.

[0653] The term "aryl" refers to aromatic hydrocarbon groups of 6 to 18 carbons, preferably 6 to 10 carbons, including groups such as phenyl, naphthyl, and anthracenyl. The term "heteroaryl" refers to aromatic rings comprising 3 to 15 carbons comprising at least one N, O or S atom, preferably 3 to 7 carbons comprising at least one N, O or S atom, including groups such as pyrrolyl, pyridyl, pyrimidinyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, quinolyl, indolyl, and indenyl.

[0654] In certain embodiments alkenyl, alkynyl, aryl or heteroaryl moieties may be coupled to the remainder of the molecule through an alkyl linkage. Under those circumstances, the substituent will be referred to as alkenylalkyl, alkynylalkyl, arylalkyl or heteroarylalkyl, indicating that an alkylene moiety is between the alkenyl, alkynyl, aryl or heteroaryl moiety and the molecule to which the alkenyl, alkynyl, aryl or heteroaryl is coupled.

[0655] The term "halogen" or "halo" refers to bromo, fluoro, chloro and iodo.

[0656] The term "heterocyclic ring" or "heterocyclyl" refers to a 3- to 15-membered aromatic or non- aromatic ring comprising at least one N, O, or S atom. Examples include piperidinyl, piperazinyl, tetrahydropyranyl, pyrrolidine, and tetrahydrofiiranyl, as well as the exemplary groups provided for the term "heteroaryl" above. In certain embodiments a heterocyclic ring or heterocyclyl is non-aromatic. In certain embodiments a heterocyclic ring or heterocyclyl is aromatic.

[0657] The term "optionally substituted" refers to a group may be unsubstituted or substituted by one or more (e.g., 1, 2, 3, 4 or 5) of the substituents which may be the same or different. Examples of substituents include alkyl, alkenyl, alkynyl, halogen, -CN, -ORaa, -SRaa, -NRaaRbb, -NO2, -C=NH(ORaa), -C(O)Raa, -OC(O)Raa, -C(O)ORaa, -C(O)NRaaRbb, -OC(O)NRaaRbb, -NRaaC(O)Rbb, -NRaaC(O)ORbb, -S(O)Raa, -S(O)2Raa, -NRaaS(O)Rbb, -C(O)NRaaS(O)Rbb, -NRaaS(O)2Rbb, -C(O)NRaaS(O)2Rbb, -S(O)NRaaRbb, -S(O)2NRaaRbb, -P(O)(ORaa)(ORbb), heterocyclyl, heteroaryl, or aryl, wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, heteroaryl, and aryl are each independently optionally substituted by -Rcc, wherein -Raaand -Rbbare each independently -H, alkyl, alkenyl, alkynyl, heterocyclyl, heteroaryl, or aryl, or -Raaand -Rbbare taken together with the nitrogen atom to which they attach to form a heterocyclyl, which is optionally substituted by alkyl, alkenyl, alkynyl, halogen, hydroxyl, alkoxy, or -CN, and wherein: each -Rccis independently alkyl, alkenyl, alkynyl, halogen, heterocyclyl, heteroaryl, aryl, -CN, or -NO2.

[0658] In certain embodiments -L1- has a structure as disclosed in formula I of WO2021 / 242756 Al. Accordingly, in certain embodiments the moiety -L1- is of formula (Xlla): wherein the unmarked dashed line indicates attachment to -D-; the dashed line marked with the asterisk indicates attachment to -L2-;

[0659] -R2, -R4and -R8are independently selected from the group consisting of -H or C 1-4 alkyl; -R3is C1-4 alkyl or -R3and -R4together with the atoms to which they are attached form a 5- or 6-membered heterocyclic ring;

[0660] -R5is -NH2; with the proviso that when -R4and -R3together with the atoms to which they are attached from a 5- or 6-membered heterocyclic ring -R2is not -H; and wherein the -L1- of formula (Xlla) is optionally substituted.

[0661] In certain embodiments both -R4and -R8of formula (Xlla) are -H.

[0662] In certain embodiments -R3is methyl. In certain embodiments -R3is -H.

[0663] In certain embodiments -R2is -H.

[0664] In certain embodiments -L1- is of formula (Xlla-i) the unmarked dashed line indicates attachment to -D-; and the dashed line marked with the asterisk indicates attachment to -L2-.

[0665] In certain embodiments -L1- is of formula (Xlla-ii) the unmarked dashed line indicates attachment to -D-; and the dashed line marked with the asterisk indicates attachment to -L2-.

[0666] In certain embodiments -L1- is of formula (Xlla-iii) the unmarked dashed line indicates attachment to -D-; and the dashed line marked with the asterisk indicates attachment to -L2-.

[0667] In certain embodiments -L1- has a structure as disclosed in formula II of WO2022 / 096636 Al.

[0668] Accordingly, in certain embodiments the moiety -L1- is of formula (Xllb): wherein the unmarked dashed line indicates attachment to -D-; and the dashed line marked with the asterisk indicates attachment to -L2-.

[0669] In certain embodiments -L2- is absent.

[0670] In certain embodiments -L2- is a spacer moiety, in particular selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(0)N(Ry1)-, -S(O)2N(Ry1)-, -S(O)N(Ry1)-, -S(O)2-, -S(O)-, -N(Ryl)S(0)2N(Ryla)-, -S-, -N(Ry1)-, -0C(0Ryl)(Ryla)-,

[0671] -N(Ryl)C(0)N(Ryla)-, -0C(0)N(Ryl)-, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl; wherein -T-, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally substituted with one or more -Ry2, which are the same or different and wherein C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry3)-, -S(O)2N(Ry3)-, -S(O)N(Ry3)-, -S(O)2-, -S(O)-, -N(Ry3)S(O)2N(Ry3a)-, -S-, -N(Ry3)-, -OC(ORy3)(Ry3a)-, -N(Ry3)C(O)N(Ry3a)-, and -OC(O)N(Ry3)-;

[0672] -Ryland -Rylaare independently of each other selected from the group consisting of -H, -T, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl; wherein -T, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally substituted with one or more -Ry2, which are the same or different, and wherein C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry4)-, -S(O)2N(Ry4)-, -S(O)N(Ry4)-, -S(O)2-, -S(O)-, -N(Ry4)S(O)2N(Ry4a)-, -S-, -N(Ry4)-, -OC(ORy4)(Ry4a)-, -N(Ry4)C(O)N(Ry4a)-, and -OC(O)N(Ry4)-; each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl, and 8- to 30-membered heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -Ry2, which are the same or different; each -Ry2is independently selected from the group consisting of halogen, -CN, oxo (=0), -C00Ry5, -0Ry5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -N02, -0C(0)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b), -OC(O)N(Ry5Ry5a), and C1-6alkyl; wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different; and each -Ry3, -Ry3a, -Ry4, -Ry4a, -Ry5, -Ry5aand -Ry5bis independently selected from the group consisting of -H, and C1-6alkyl, wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different.

[0673] In certain embodiments -L2- is selected from -T-, -C(0)0-, -0-, -C(0)-, -C(0)N(Ry1)-, -S(0)2N(Ry1)-, -S(0)N(Ry1)-, -S(0)2-, -S(0)-, -N(Ryl)S(0)2N(Ryla)-, -S-, -N(Ry1)-, -0C(0Ryl)(Ryla)-, -N(Ryl)C(0)N(Ryla)-, -0C(0)N(Ryl)-, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl; wherein -T-, C1-20 alkyl, C2-20alkenyl, and C2-20alkynyl are optionally substituted with one or more -Ry2, which are the same or different and wherein C1-20 alkyl, C2-20alkenyl, and C2-20alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(0)0-, -0-, -C(0)-, -C(0)N(Ry3)-, -S(O)2N(Ry3)-, -S(0)N(Ry3)-, -S(0)2-, -S(0)-, -N(Ry3)S(O)2N(Ry3a)-, -S-, -N(Ry3)-, -OC(ORy3)(Ry3a)-, -N(Ry3)C(O)N(Ry3a)-, and -OC(O)N(Ry3)-;

[0674] -Ryland -Rylaare independently of each other selected from the group consisting of -H, -T, C1-10alkyl, C2-10alkenyl, and C2-10alkynyl; wherein -T, C1-10alkyl, C2-10alkenyl, and C2-10alkynyl are optionally substituted with one or more -Ry2, which are the same or different, and wherein C1-10alkyl, C2-10alkenyl, and C2-10alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry4)-, -S(O)2N(Ry4)-, -S(O)N(Ry4)-, -S(O)2-, -S(O)-, -N(Ry4)S(O)2N(Ry4a)-, -S-, -N(Ry4)-, -OC(ORy4)(Ry4a)-, -N(Ry4)C(O)N(Ry4a)-, and -OC(O)N(Ry4)-; each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl, and 8- to 30-membered heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -Ry2, which are the same or different;

[0675] -Ry2is selected from the group consisting of halogen, -CN, oxo (=0), -C00Ry5, -0Ry5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5, -N(Ry5Ry5a), -N02, -0C(0)Ry5, -N(Ry5) C(0)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b), -OC(O)N(Ry5Ry5a), and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; and each -Ry3, -Ry3a, -Ry4, -Ry4a, -Ry5, -Ry5aand -Ry5bis independently of each other selected from the group consisting of -H, and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different.

[0676] In certain embodiments -L2- is selected from the group consisting of -T-, -C(0)0-, -0-, -C(0)-, -C(0)N(Ry1)-, -S(0)2N(Ry1)-, -S(0)N(Ry1)-, -S(0)2-, -S(0)-,

[0677] -N(Ryl)S(0)2N(Ryla)-, -S-, -N(Ry1)-, -0C(0Ryl)(Ryla)-, -N(Ryl)C(0)N(Ryla)-, -0C(0)N(Ryl)-, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl; wherein -T-, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally substituted with one or more -Ry2, which are the same or different and wherein C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(0)0-, -0-, -C(0)-, -C(0)N(Ry3)-, -S(O)2N(Ry3)-, -S(0)N(Ry3)-, -S(0)2-, -S(0)-, -N(Ry3)S(O)2N(Ry3a)-, -S-, -N(Ry3)-, -OC(ORy3)(Ry3a)-, -N(Ry3)C(O)N(Ry3a)-, and -0C(0)N(Ry3)-; -Ryland -Rylaare independently selected from the group consisting of -H, -T, C1-10alkyl, C2-10alkenyl, and C2-10alkynyl; each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopoly cyclyl, and 8- to 30-membered heteropoly cyclyl; each -Ry2is independently selected from the group consisting of halogen, and C1-6 alkyl; and each -Ry3, -Ry3a, -Ry4, -Ry4a, -Ry5, -Ry5aand -Ry5bis independently of each other selected from the group consisting of -H, and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different.

[0678] In certain embodiments -L2- is a C1-20 alkyl chain, which is optionally interrupted by one or more groups independently selected from -O-, -S-, -T- and -C(O)N(Ry1)-; and which C1-20 alkyl chain is optionally substituted with one or more groups independently selected from -OH, -T and -C(O)N(Ry6Ry6a); wherein -Ryl, -Ry6, -Ry6aare independently selected from the group consisting of H and C1-4alkyl and wherein T is selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopolycyclyl, and 8- to 30-membered heteropoly cyclyl.

[0679] In certain embodiments -L2- has a molecular weight in the range of from 14 g / mol to 750 g / mol.

[0680] In certain embodiments -L2- comprises a moiety selected from

[0681] wherein

[0682] -R and -Raare independently of each other 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.

[0683] In certain embodiments -L2- has a chain length of 1 to 20 atoms. In certain embodiments -L2- has a chain length of 2 to 10 atoms.

[0684] In certain embodiments -L2- has a chain length of at least 35 atoms. In certain embodiments -L2- has a chain length of at least 50 atoms. In certain embodiments -L2- has a chain length of at least 75 atoms. In certain embodiments -L2- has a chain length of at least 100 atoms. In certain embodiments -L2- has a chain length of at least 150 atoms. In certain embodiments -L2- has a chain length of at least 200 atoms. In certain embodiments -L2- has a chain length of at least 250 atoms. In certain embodiments -L2- has a chain length of at least 300 atoms. In certain embodiments -L2- has a chain length of at most 3000 atoms. In certain embodiments -L2- has a chain length of at most 2500 atoms. In certain embodiments -L2- has a chain length of at most 2000 atoms. In certain embodiments -L2- has a chain length of at most 1500 atoms. In certain embodiments -L2- has a chain length ranging from 35 to 3000 atoms. In certain embodiments -L2- has a chain length ranging from 50 to 2500 atoms. In certain embodiments -L2- has a chain length ranging from 75 to 2000 atoms. In certain embodiments -L2- has a chain length ranging from 100 to 1500 atoms. In certain embodiments -L2- has a chain length ranging from 125 to 1000 atoms.

[0685] In certain embodiments -L2- is of formula (XI) wherein the unmarked dashed line indicates attachment to -L1-; the dashed line marked with the asterisk indicates attachment to the at least one polymeric moiety; h is an integer selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13.

[0686] 14, 15 and 16.

[0687] In certain embodiments -L2- is of formula (XI) and h is 1. In certain embodiments -L2- is of formula (XI) and h is 2. In certain embodiments -L2- is of formula (XI) and h is 3. In certain embodiments -L2- is of formula (XI) and h is 4. In certain embodiments -L2- is of formula (XI) and h is 5. In certain embodiments -L2- is of formula (XI) and h is 6. In certain embodiments -L2- is of formula (XI) and h is 7. In certain embodiments -L2- is of formula (XI) and h is 8. In certain embodiments -L2- is of formula (XI) and h is 9. In certain embodiments -L2- is of formula (XI) and h is 10. In certain embodiments -L2- is of formula (XI) and h is 11. In certain embodiments -L2- is of formula (XI) and h is 12. In certain embodiments -L2- is of formula (XI) and h is 13. In certain embodiments -L2- is of formula (XI) and h is 14. In certain embodiments -L2- is of formula (XI) and h is 15. In certain embodiments -L2- has a molecular weight of at least 450 Da. In certain embodiments -L2- has a molecular weight of at least 1 kDa. In certain embodiments -L2- has a molecular weight of at least 1.5 kDa. In certain embodiments -L2- has a molecular weight of at least 2 kDa. In certain embodiments -L2- has a molecular weight of at least 2.5 kDa. In certain embodiments -L2- has a molecular weight of at least 3 kDa. In certain embodiments -L2- has a molecular weight of at least 3.5 kDa. In certain embodiments -L2- has a molecular weight of at least 4 kDa. In certain embodiments -L2- has a molecular weight of at least 5 kDa. In certain embodiments -L2- has a maximum molecular weight of 160 kDa. In certain embodiments -L2- has a maximum molecular weight of 120 kDa. In certain embodiments -L2- has a maximum molecular weight of 100 kDa. In certain embodiments -L2- has a maximum molecular weight of 80 kDa. In certain embodiments -L2- has a maximum molecular weight of 70 kDa. In certain embodiments -L2- has a maximum molecular weight of 60 kDa. In certain embodiments -L2- has a maximum molecular weight of 50 kDa. In certain embodiments -L2- has a maximum molecular weight of 40 kDa. In certain embodiments -L2- has a molecular weight of about 450 Da. In certain embodiments -L2- has a molecular weight of about 1 kDa. In certain embodiments -L2- has a molecular weight of about

[0688] 1.5 kDa. In certain embodiments -L2- has a molecular weight of about 2 kDa. In certain embodiments -L2- has a molecular weight of about 2.5 kDa. In certain embodiments -L2- has a molecular weight of about 3 kDa. In certain embodiments -L2- has a molecular weight of about

[0689] 3.5 kDa. In certain embodiments -L2- has a molecular weight of about 4 kDa. In certain embodiments -L2- has a molecular weight of about 4.5 kDa. In certain embodiments -L2- has a molecular weight of about 5 kDa. In certain embodiments -L2- has a molecular weight of about

[0690] 5.5 kDa. In certain embodiments -L2- has a molecular weight of about 6 kDa. In certain embodiments -L2- has a molecular weight of about 6.5 kDa. In certain embodiments -L2- has a molecular weight of about 7 kDa. In certain embodiments -L2- has a molecular weight of about

[0691] 7.5 kDa. In certain embodiments -L2- has a molecular weight of about 8 kDa. In certain embodiments -L2- has a molecular weight of about 8.5 kDa. In certain embodiments -L2- has a molecular weight of about 9 kDa. In certain embodiments -L2- has a molecular weight of about

[0692] 9.5 kDa. In certain embodiments -L2- has a molecular weight of about 10 kDa.

[0693] In certain embodiments -L2- comprises a polymeric moiety, meaning that it comprises at least one polymer moiety. It is understood that if -L2- comprises one polymer moiety the minimum and maximum molecular weights provided above apply to this one polymer moiety and if -L2- comprises more than one polymer moiety the minimum and maximum molecular weights provided above refer to the minimum and maximum molecular weight of all polymer moieties together.

[0694] In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of at least 1.2 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of at least 1.5 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of at least 2 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of at least 2.5 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of at least 3 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of at least 3.5 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of at least 4 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of at least 4.5 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of at least 5 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of no more than 200 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of no more than 175 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of no more than 150 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of no more than 125 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of no more than 100 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of no more than 75 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of no more than 50 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of no more than 45 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of no more than 40 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of no more than 35 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of no more than 30 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of about 1.2 nm. In certain embodiments the one or more polymer moiety of -L2-has a Flory radius of about 1.5 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of about 2 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of about 2.5 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of about 3 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of about 3.5 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of about 4 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of about 4.5 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of about 5 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of about 5.5 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of about 6 nm. In certain embodiments the one or more polymer moiety of -L2-has a Flory radius of about 6.5 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of about 7 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of about 8.5 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of about 9 nm. In certain embodiments the one or more polymer moiety of -L2- has a Flory radius of about 10 nm. It is understood that if -L2- comprises one polymer moiety the Flory radius provided above applies to this one polymer moiety and if -L2- comprises more than one polymer moiety the Flory radius provided above refers to the Flory radius of all polymer moieties together.

[0695] -L2- comprises one or more polymer moiety, such as polymer moiety selected from the group consisting of poly(2-methacryloyl-oxyethyl phosphoyl cholins), poly(acrylic acids), poly(acrylates), poly(acrylamides), poly(alkyloxy) polymers, poly(amides), poly(amidoamines), poly(amino acids), poly(anhydrides), poly(aspartamides), poly(butyric acids), poly(glycolic acids), polybutylene terephthalates, poly(caprolactones), poly(carbonates), poly(cyanoacrylates), poly(dimethylacrylamides), poly(esters), poly(ethylenes), poly(ethyleneglycols), poly(ethylene oxides), poly(ethyl phosphates), poly(ethyloxazolines), poly(glycolic acids), poly(hydroxyethyl acrylates), poly(hydroxyethyl- oxazolines), poly(hydroxymethacrylates), poly(hydroxypropylmethacrylamides), poly(hydroxypropyl methacrylates), poly(hydroxypropyloxazolines), poly(iminocarbonates), poly(lactic acids), poly(lactic-co-glycolic acids), poly(methacrylamides), poly(methacrylates), poly(methyloxazolines), poly(organophosphazenes), poly(ortho esters), poly(oxazolines), polypropylene glycols), poly(siloxanes), poly(urethanes), poly(vinyl alcohols), poly(vinyl amines), poly(vinylmethylethers), polyvinylpyrrolidones), silicones, celluloses, carbomethyl celluloses, hydroxypropyl methylcelluloses, chitins, chitosans, dextrans, dextrins, gelatins, hyaluronic acids and derivatives, functionalized hyaluronic acids, alginate, mannans, pectins, rhamnogalacturonans, starches, hydroxyalkyl starches, hydroxyethyl starches and other carbohydrate-based polymers, xylans, and copolymers thereof. In certain embodiments -L2- comprises a PEG-based polymer. In certain embodiments -L2- comprises a hyaluronic acid-based polymer. In certain embodiments -L2- comprises a random coil polymer. In certain embodiments -L2- comprises a poly-sarcosine polymer.

[0696] In certain embodiments the albumin-binding moieties of a compound disclosed herein bind to one albumin, such as via different binding domains. Suitably, the albumin-binding moieties of a compound disclosed herein bind to at least two albumins, such as to two albumins.

[0697] In certain embodiments -L1-L2- is selected from the group consisting wherein the dashed line marked with the asterisk indicates attachment to a nitrogen of -D-; and the unmarked dashed line indicates attachment to the at least one polymeric moiety. In certain embodiments -L1-L2- is of formula (Xia). In certain embodiments -L1-L2- is of formula (Xlb). In certain embodiments -L1-L2- is of formula (XIc). In certain embodiments -L1-L2- is of formula (Xld). In certain embodiments -L1-L2- is of formula (Xie). In certain embodiments -L1-L2- is of formula (Xlf).

[0698] In certain embodiments -L1-L2- is selected from the group consisting wherein the dashed line marked with the asterisk indicates attachment to a nitrogen of -D-; and the unmarked dashed line indicates attachment to the at least one polymeric moiety.

[0699] In certain embodiments -L1-L2- is of formula (Xia’). In certain embodiments -L1-L2- is of formula (Xlb’). In certain embodiments -L1-L2- is of formula (XIc’). In certain embodiments -L1-L2- is of formula (Xld’). In certain embodiments -L1-L2- is of formula (Xie’).

[0700] In certain embodiments -L1-L2- is of formula (Xlf).

[0701] In certain embodiments -L1-L2- is selected from the group consisting wherein the dashed line marked with the asterisk indicates attachment to a nitrogen of -D-; and the unmarked dashed line indicates attachment to the at least one polymeric moiety.

[0702] In certain embodiments -L1-L2- is of formula (Xia”). In certain embodiments -L1-L2- is of formula (Xlb”). In certain embodiments -L1-L2- is of formula (XIc”). In certain embodiments -L1-L2- is of formula (Xld”). In certain embodiments -L1-L2- is of formula (Xie”). In certain embodiments -L1-L2- is of formula (Xlf). In certain embodiments -L1-L2- is selected from the group consisting wherein the dashed line marked with the asterisk indicates attachment to a nitrogen of -D-; and the unmarked dashed line indicates attachment to the at least one polymeric moiety. In certain embodiments -L1-L2- is of formula (Xlg). In certain embodiments -L1-L2- is of formula (Xlh). In certain embodiments -L1-L2- is of formula (Xli). In certain embodiments -L1-L2- is of formula (Xlj). In certain embodiments -L1-L2- is of formula (Xlk). In certain embodiments -L1-L2- is of formula (XII). In certain embodiments -L1-L2- is selected from the group consisting wherein the dashed line marked with the asterisk indicates attachment to a nitrogen of -D-; and the unmarked dashed line indicates attachment to the at least one polymeric moiety.

[0703] In certain embodiments -L1-L2- is of formula (Xlg’). In certain embodiments -L1-L2- is of formula (Xlh’). In certain embodiments -L1-L2- is of formula (Xli’). In certain embodiments -L1-L2- is of formula (Xlj ’). In certain embodiments -L1-L2- is of formula (Xlk’). In certain embodiments -L1-L2- is of formula (XII’).

[0704] In certain embodiments -L1-L2- is selected from the group consisting

[0705] wherein the dashed line marked with the asterisk indicates attachment to a nitrogen of -D-; and the unmarked dashed line indicates attachment to the at least one polymeric moiety.

[0706] In certain embodiments -L1-L2- is of formula (Xlg”). In certain embodiments -L1-L2- is of formula (Xlh”). In certain embodiments -L1-L2- is of formula (Xli”). In certain embodiments -L1-L2- is of formula (Xlj”). In certain embodiments -L1-L2- is of formula (Xlk”). In certain embodiments -L1-L2- is of formula (XII”). In certain embodiments -L1- is a multi-release linker, i.e., a linker from which more than one drug is released. An exemplary class of such multi-release linker is described in the following sections.

[0707] In certain embodiments -L1- is of formula (2a) wherein

[0708] -Tr is a cleavable triggering moiety;

[0709] -Y3- is independently selected from the group consisting of -O-, -S- and -N(R6)-; z is selected from the group consisting of 2 and 3; y is selected from the group consisting of 0, 1, 2, 3, 4 and 5;

[0710] -Ar- is a ring selected from the group consisting of monocyclic or bicyclic aryl and heteroaryl, provided that -Ar- is connected to -Y3- and -R1via carbon atoms; wherein said monocyclic or bicyclic aryl and heteroaryl are optionally substituted with -R°, which are the same or different; each -R0is independently selected from the group consisting of -C(O)OH, -halogen, -NO2, -CN, C1-30 alkyl, C2-30 alkenyl and C2-30 alkynyl; wherein C1-30 alkyl, C2-30 alkenyl and C2-30 alkynyl are optionally substituted with one or more -R4, which are the same or different; and wherein C1-30 alkyl, C2-30 alkenyl and C2-30 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(R5)-, -S(O)2N(R5)-, -S(O)N(R5)-, -S(O)2-, -S(O)-, -N(R5)S(O)2N(R5a)-, -S-, -N(R5)-, -OC(OR5)(R5a)-, -N(R5)C(O)N(R5a)- and -OC(O)N(R5)-; each -R1is independently selected from the group consisting of wherein an unmarked dashed line indicates attachment to -Ar-; a dashed lined marked with an asterisk indicates attachment to -D-; the total number of moieties -D- in the compound ranges from 2 to 6; each -Yi- is independently selected from the group consisting of -O- and -S-; each =¥2 is independently selected from the group consisting of =0 and =S;

[0711] -Y4- is , wherein the dashed line marked with the asterisk indicates attachment to -Ar- and the unmarked dashed lines indicate attachment to -Yi-; each -R2is independently selected from the group consisting of -H, -C(0)0H, -halogen, -NO2, -CN, C1-30 alkyl, C2-30 alkenyl and

[0712] C2-30 alkynyl; wherein C1-30 alkyl, C2-30 alkenyl and C2-30 alkynyl are optionally substituted with one or more -R4, which are the same or different; and wherein C1-30 alkyl, C2-30 alkenyl and C2-30 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(0)N(R5)-, -S(O)2N(R5)-, -S(O)N(R5)-, -S(O)2-, -S(O)-, -N(R5)S(O)2N(R5a)-, -S-, -N(R5)-, -OC(OR5)(R5a)-, -N(R5)C(O)N(R5a)- and -0C(0)N(R5)-; each -R3a, -R3b, -R3c, -R3dare independently selected from the group consisting of -H, -C(0)0H, -F, -NO2, -CN, C1-30 alkyl, C2-30 alkenyl and C2-30 alkynyl; wherein C1-30 alkyl, C2-30 alkenyl and C2-30 alkynyl are optionally substituted with one or more -R4, which are the same or different; and wherein C1-30 alkyl, C2-30 alkenyl and C2-30 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(0)N(R5)-, -S(O)2N(R5)-, -S(O)N(R5)-, -S(O)2-, -S(O)-, -N(R5)S(O)2N(R5a)-, -S-, -N(R5)-, -OC(OR5)(R5a)-, -N(R5)C(O)N(R5a)- and -0C(0)N(R5)-; each -T- is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl and 8- to 11-membered heterobicyclyl, wherein each -T- is independently optionally substituted with one or more -R4, which are the same or different;

[0713] -R4is selected from the group consisting of -NO2, -OCH3, -CN, -N(R5)(R5a), -OH, -C(0)0H and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; -R5and -R5aare independently selected from the group consisting of -H and C1-6alkyl; wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different; each -R6is independently selected from the group consisting of -H and C1-6alkyl; and wherein -L1- is substituted with one moiety -L2-.

[0714] In certain embodiments all -R1of formula (2a) are of formula (a).

[0715] In certain embodiments all -R1of formula (2a) are of formula (b).

[0716] In certain embodiments z of formula (2a) is 2. In certain embodiments z of formula (2a) is 3.

[0717] In certain embodiments z of formula (2a) is 2 and both -R1are of formula (a). In certain embodiments z of formula (2a) is 2 and both -R1are of formula (b). In certain embodiments z is of formula (2a) is 2 and one -R1is of formula (a) and one -R1is of formula (b).

[0718] In certain embodiments z of formula (2a) is 3 and all -R1are of formula (a). In certain embodiments z of formula (2a) is 3 and all -R1are of formula (b). In certain embodiments z of formula (2a) is 3 and one -R1is of formula (a) and two -R1are of formula (b). In certain embodiments z of formula (2a) is 3 and two -R1are of formula (a) and one -R1is of formula (b).

[0719] In certain embodiments y of formula (2a) is 0. In certain embodiments y of formula (2a) is 1. In certain embodiments y of formula (2a) is 2. In certain embodiments y of formula (2a) is 3. In certain embodiments y of formula (2a) is 4. In certain embodiments y of formula (2a) is 5.

[0720] In certain embodiments z of formula (2a) is 2, both -R1of formula (2a) are of formula (a) and y of formula (2a) is 0. In certain embodiments z of formula (2a) is 3, all -R1of formula (2a) are of formula (a) and y of formula (2a) is 0. In certain embodiments z of formula (2a) is 3, two - R1are of formula (a), one -R1of formula (2a) is of formula (b) and y of formula (2a) is 0.

[0721] In certain embodiments -Yi- of formula (2a) is -O-. In certain embodiments -Yi- of formula (2a) is -S-. In certain embodiments =¥2 of formula (2a) is =0. In certain embodiments =¥2 of formula

[0722] (2a) is =S.

[0723] In certain embodiments -Y3- of formula (2a) is -0-. In certain embodiments -Y3- of formula (2a) is -S-. In certain embodiments -Y3- of formula (2a) is -N(R6)-, wherein -R6is as described elsewhere within the section covering the exemplary multi-release linker.

[0724] In certain embodiments -Tr of formula (2a) is selected from the group consisting of a peptidyl moiety; wherein the dashed line marked with an asterisk indicates attachment to -Y3-;

[0725] -Nu is a nucleophile;

[0726] -Y§- is selected from the group consisting of -O-, -C(R10)(R10a)-, -N(R6)- and -S-;

[0727] =Yo is selected from the group consisting of =0, =S and =N(R5);

[0728] -E- and -R are independently selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl and -Q-; wherein C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl are optionally substituted with one or more -R11, which are the same or different; and wherein C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -Q-, -C(O)O-, -O-, -C(O)-, -C(0)N(R12)-, -S(O)2N(R12)-, -S(O)N(R12)-, -S(O)2-, -S(O)-, -N(R12)S(O)2N(R12a)-, -S-, -N(R12)-, -OC(OR12)R12a-, -N(R12)C(O)N(R12a)- and -0C(0)N(R12)-; -Mod is selected from the group consisting of CF3PI1SO2-, CIPI1SO2-, PI1SO2-, MePhSO2-, MeOPhSO2-, 2,4,6-Me3PhSO2-, MeSO2-, O(CH2CH2)2N-SO2-, CN- and Et2NSO2-;

[0729] -R6is selected from the group consisting of -H and C1-6 alkyl;

[0730] -R5, -R6, -R7, -R8, -R9, -R10, -R10aare independently selected from the group consisting of -H, C1-20 alkyl, C2-20 alkenyl, C2-20 alkynyl and -Q; wherein C1-20 alkyl, C2-20 alkenyl and C2-20 alkynyl are optionally substituted with one or more -R11, which are the same or different; and wherein C1-20 alkyl, C2-20 alkenyl and C2-20 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -Q-, -C(O)O-, -O-, -C(O)-, -C(O)N(R12)-, -S(O)2N(R12)-, -S(O)N(R12)-, -S(O)2-, -S(O)-, -N(R12)S(O)2N(R12a)-, -S-, -N(R12)-, -OC(OR12)R12a-, -N(R12)C(O)N(R12a)- and -OC(O)N(R12)-; each Q is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl and 8- to 11- membered heterobicyclyl, wherein each Q is independently optionally substituted with one or more -R11, which are the same or different; and

[0731] -R11is selected from the group consisting of C1-6 alkyl and -N3, wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; and -R12and -R12aare independently selected from the group consisting of -H and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different.

[0732] -Nu of formula (2aa) is a nucleophile that may be selected from the group consisting of primary, secondary, or tertiary amine and amide. In certain embodiments -Nu of formula (2aa) is selected from the group consisting of secondary and tertiary amine. In certain embodiments -Nu of formula (2aa) is a primary amine. In certain embodiments -Nu of formula (2aa) is a secondary amine. In certain embodiments -Nu of formula (2aa) is a tertiary amine. In certain embodiments -Nu of formula (2aa) is an amide.

[0733] In certain embodiments -Y§- of formula (2aa) is selected from the group consisting of -O-, -C(R10)(R10a)- and-N(R6)-, wherein -R10, -R10aand -R6. In certain embodiments -Y§- of formula (2aa) is -O-. In certain embodiments -Y§- of formula (2aa) is -C(R10)(R10a)-, wherein -R10, -R10aare independently selected from the group consisting of -H, C1-20 alkyl, C2-20 alkenyl, C2-20 alkynyl and -Q; wherein C1-20 alkyl, C2-20 alkenyl and C2-20 alkynyl are optionally substituted with one or more -R11, which are the same or different; and wherein C1-20 alkyl, C2-20 alkenyl and C2-20 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -Q-, -C(O)O-,-O-, -C(O)-, -C(O)N(R12)-, -S(O)2N(R12)-, -S(O)N(R12)-,

[0734] -S(O)2-, -S(O)-, -N(R12)S(O)2N(R12a)-, -S-, -N(R12)-, -OC(OR12)R12a-, -N(R12)C(O)N(R12a)- and -OC(O)N(R12)-; each Q is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl and 8- to 11-membered heterobicyclyl, wherein each Q is independently optionally substituted with one or more -R11, which are the same or different; and

[0735] -R11is selected from the group consisting of C1-6 alkyl and -N3, wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; and

[0736] -R12and -R12aare independently selected from the group consisting of -H and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different

[0737] In certain embodiments -Y§- of formula (2aa) is -N(R6)-, wherein -R6is selected from the group consisting of -H and C1-6 alkyl.

[0738] In certain embodiments =Yo of formula (2aa) is selected from the group consisting of =0 and =S. In certain embodiments =Yo of formula (2aa) is =0. In certain embodiments =Yo of formula (2aa) is =S.

[0739] In certain embodiments =Yo of formula (2aa) is =N(R5), wherein -R5is selected from the group consisting of -H, C1-20 alkyl, C2-20 alkenyl, C2-20 alkynyl and -Q; wherein C1-20 alkyl, C2- 20 alkenyl and C2-20 alkynyl are optionally substituted with one or more -R11, which are the same or different; and wherein C1-20 alkyl, C2-20 alkenyl and C2-20 alkynyl are optionally interrupted by one or more groups selected from the group consisting of -Q-, -C(0)0-,-0-, -C(0)-, -C(0)N(R12)-, -S(O)2N(R12)-, -S(O)N(R12)-, -S(0)2-, -S(0)-, -N(R12)S(O)2N(R12a)-, -S-, -N(R12)-, -OC(OR12)R12a-, -N(R12)C(O)N(R12a)- and -0C(0)N(R12)-; each Q is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl and 8- to 11-membered heterobicyclyl, wherein each Q is independently optionally substituted with one or more -R11, which are the same or different; and

[0740] -R11is selected from the group consisting of C1-6alkyl and -N3, wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; and

[0741] -R12and -R12aare independently selected from the group consisting of -H and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different

[0742] In certain embodiments -E- of formula (2aa) is selected from the group consisting of C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl. In certain embodiments -E- of formula (2aa) is C1-6 alkyl. In certain embodiments -E- of formula (2aa) is C2-6 alkenyl. In certain embodiments -E- of formula (2aa) is C2-6 alkynyl. In certain embodiments -E- of formula (2aa) is -Q-, which in certain embodiments is selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl and 8- to 11-membered heterobicyclyl. In certain embodiments Q is phenyl. In certain embodiments Q is naphthyl. In certain embodiments Q is indenyl. In certain embodiments Q is indanyl. In certain embodiments Q is tetralinyl. In certain embodiments Q is C3-10 cycloalkyl. In certain embodiments Q is 3- to 10-membered heterocyclyl. In certain embodiments Q is 8- to 11-membered heterobicyclyl. In certain embodiments Q is substituted with one or more -R11. In certain embodiments Q is not substituted with -R11.

[0743] In certain embodiments -R5of formula (2aa) is selected from the group consisting of -H, C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl. In certain embodiments -R5of formula (2aa) is selected from the group consisting of -H and C1-6 alkyl. In certain embodiments -R5of formula (2aa) is -H. In certain embodiments -R5of formula (2aa) is C1-6 alkyl.

[0744] In certain embodiments -R6, -R7, -R8, -R9, -R10, -R10aas used in the various embodiments for Tr are independently selected from the group consisting of -H, C1-10 alkyl, C2-10alkenyl, C2-10alkynyl and -Q, wherein -Q is as defined elsewhere within the section covering the exemplary multi-release linker.

[0745] In certain embodiments -R7and -R9as used in the various embodiments for Tr are independently selected from the group consisting of -H and C1-6 alkyl. In certain embodiments both -R7and -R9are -H. In certain embodiments -R7is -H. In certain embodiments -R7is C1-6alkyl. In certain embodiments -R9is -H. In certain embodiments -R9is C1-6alkyl.

[0746] In certain embodiments -R10and -R10aof formula (2aa) are independently selected from the group consisting of -H and C1-6alkyl. In certain embodiments both -R10and -R10aof formula (2aa) are -H. In certain embodiments -R10of formula (2aa) is -H. In certain embodiments -R10of formula (2aa) is C1-6alkyl. In certain embodiments -R10aof formula (2aa) is -H. In certain embodiments -R10aof formula (2aa) is C1-6alkyl.

[0747] In certain embodiments -Tr of formula (2a) is of formula (2aa) wherein the dashed line marked with an asterisk indicates attachment to -Y3-; and

[0748] -Nu, -E-, -Y§- and =Yo are as defined elsewhere within the section covering the exemplary multi-release linker herein.

[0749] It is understood that in this instance the release of the drug is not triggered by an enzyme, and that the drug is released in its unmodified, pharmacologically active form in the absence of an enzyme.

[0750] In certain embodiments -Tr of formula (2a) is wherein and the dashed line marked with an asterisk indicates attachment to -Y3-; and

[0751] -R6is as defined elsewhere within the section covering the exemplary multi-release linker herein. In certain embodiments -R6is w...

Claims

Claims1. A compound or a pharmaceutically acceptable salt thereof, wherein the compound comprises at least one polymeric moiety, to which at least two moieties of formula (I) are conjugated and / or to which at least one moiety of formula (I’) is conjugated, wherein formula (I) and (I’) arewherein each -L2- is independently a spacer moiety or is absent; each -L1- is independently a linker moiety that is covalently and reversibly conjugated to -D-; each -L1- is independently a linker moiety that is covalently and reversibly conjugated to -D-; each -D- is independently a drug moiety; each -AB is independently an albumin-binding moiety; and each a 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.

2. The compound or a pharmaceutically acceptable salt thereof of claim 1, wherein the at least one polymeric moiety of the compounds of the present invention is a linear polymeric moiety -P-.

3. The compound or a pharmaceutically acceptable salt thereof of claim 1 or 2, wherein the compound is of formula (I-A) or (I-A')wherein each -L2- is independently a spacer moiety or is absent; each -L1- is independently a linker moiety that is covalently and reversibly conjugated to -D-;each -L1- is independently a linker moiety that is covalently and reversibly conjugated to -D-; each -D- is independently a drug moiety; each -AB is independently an albumin-binding moiety;-P- is a polymeric moiety; and each a is independently 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.

4. The compound or a pharmaceutically acceptable salt thereof of claim 1, wherein the at least one polymeric moiety of the compound of the present invention is a multi-arm polymeric moiety.

5. The compound or a pharmaceutically acceptable salt thereof of claim 1 or 4, wherein the compound comprises at least one branching point B, to which at least two moieties of formula (lb) and / or at least one moiety of formula (lb’) are conjugated, wherein formula (lb) and (lb ’) arewherein the dashed line indicates attachment to a branching point B;-A- is a polymeric moiety each -L2- is independently a spacer moiety or is absent; each -L1- is independently a linker moiety that is covalently and reversibly conjugated to -D-; each -L1- is independently a linker moiety that is covalently and reversibly conjugated to -D-; each -D- is independently a drug moiety; each -AB is independently an albumin-binding moiety; and each a is independently 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.

6. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1, 4 or 5, wherein the compound is of formula (I-b4)wherein-X4-, -X5-, -X6- are independently of each other selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry1)-, -S(O)2N(Ry1)-, -S(O)N(Ry1)-, -S(O)2-, -S(O)-, -N(Ryl)S(O)2N(Ryla)-, -S-, -N(Ry1)-, -OC(ORyl)(Ryla)-,-N(Ryl)C(O)N(Ryla)-, -OC(O)N(Ry1)-, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl; wherein -T-, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally substituted with one or more -Ry2, which are the same or different and wherein C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry3)-, -S(O)2N(Ry3)-, -S(O)N(Ry3)-, -S(O)2-, -S(O)-, -N(Ry3)S(O)2N(Ry3a)-, -S-, -N(Ry3)-, -OC(ORy3)(Ry3a)-, -N(Ry3)C(O)N(Ry3a)-, and -OC(O)N(Ry3)-;-Ryland -Rylaare independently of each other selected from the group consisting of -H, -T, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl; wherein -T, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally substituted with one or more -Ry2, which are the same or different, and wherein C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry4)-, -S(O)2N(Ry4)-, -S(O)N(Ry4)-, -S(O)2-, -S(O)-, -N(Ry4)S(O)2N(Ry4a)-, -S-,-N(Ry4)-, -OC(ORy4)(Ry4a)-, -N(Ry4)C(O)N(Ry4a)-, and -OC(O)N(Ry4)-; each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopolycyclyl, and 8- to 30- membered heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -Ry2, which are the same or different; each -Ry2is independently selected from the group consisting of halogen, -CN, oxo (=0), -C00Ry5, -ORy5, -C(0)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5,-N(Ry5Ry5a), -NO2, -0C(0)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a,-N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a, -N(Ry5)C(O)N(Ry5aRy5b), -OC(O)N(Ry5Ry5a), and C1-6 alkyl; wherein C1-6 alkyl is optionally substituted with one or more halogen, which are the same or different; andeach -Ry3, -Ry3a, -Ry4, -Ry4a, -Ry5, -Ry5aand -Ry5bis independently selected from the group consisting of -H, and C1-6alkyl, wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different; each -A- is a polymeric moiety; each -L2- is independently a spacer moiety or is absent; each -L1- is independently a linker moiety that is covalently and reversibly conjugated to -D-; each -D- is independently a drug moiety; and each -AB is independently an albumin-binding moiety.

7. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1 to6, wherein -L1- is of formula (II):wherein the dashed line indicates attachment to a nitrogen, hydroxyl or thiol of -D-; -X- is selected from the group consisting of -C(R4R4a)-; -N(R4)-; -O-; -C(R4R4a)- C(R5R5a)-; -C(R5R5a)-C(R4R4a)-; -C(R4R4a)-N(R6)-; -N(R6)-C(R4R4a)-;C(R4R4a)-O-; -O-C(R4R4a)-; and -C(R7R7a)-;X1is selected from the group consisting of C; and S(O);-X2- is selected from the group consisting of -C(R8R8a)-; and -C(R8R8a)-C(R9R9a)-;=X3is selected from the group consisting of =0; =S; and =N-CN;-R1, -R1a, -R2, -R2a, -R4, -R4a, -R5, -R5a, -R6, -R8, -R8a, -R9, and -R9aare independently selected from the group consisting of -H; and C1-6alkyl;-R3, and -R3aare independently selected from the group consisting of -H; and C1-6alkyl, provided that in case one of -R3, -R3aor both are other than -H they are connected to N to which they are attached through an SP3-hybridized carbon atom; -R7is selected from the group consisting of -N(R10R10a); and -NR10-(C=O)-R11;-R7a, -R10, -R10a, and -R11are independently of each other selected from the group consisting of -H; and C1-6alkyl; optionally, one or more of the pairs -R1a / -R4a, -R1a / -R5a, -R1a / -R7a, -R4a / -R5a, and -R8a / -R9aform a chemical bond;optionally, one or more of the pairs -R' / -R1a, -R2 / -R2a, -R4 / -R4a, -R5 / -R5a, -R8 / -R8a, and -R9 / -R9aare joined together with the atom to which they are attached to form a C3-10 cycloalkyl; or 3- to 10-membered heterocyclyl; optionally, one or more of the pairs -R1 / -R4, -R1 / -R5, -R1 / -R6, -R' / -R7a, -R4 / -R5, -R4 / -R6, -R8 / -R9, and -R2 / -R3are joined together with the atoms to which they are attached to form a ring A; optionally, R3 / R3aare joined together with the nitrogen atom to which they are attached to form a 3- to 10-membered heterocycle;A is selected from the group consisting of phenyl; naphthyl; indenyl; indanyl; tetralinyl; C3-10 cycloalkyl; 3- to 10-membered heterocyclyl; and 8- to 11-membered heterobicyclyl; and wherein -L1- is substituted with at least one -L2- and wherein -L1- is optionally further substituted, provided that the hydrogen marked with the asterisk in formula (II) is not replaced by -L2- or a substituent.

8. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1 to7, wherein -L1- is of formula (Ila)wherein the dashed line marked with the asterisk indicates attachment to a nitrogen of -D-; and the unmarked dashed line indicates attachment to -L2-.

9. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1 to7, wherein -L1- is of formula (Ilab)whereinthe dashed line marked with the asterisk indicates attachment to a nitrogen of -D-; and the unmarked dashed line indicates attachment to -L2-.

10. The compound of any of claims 1 to 9, wherein -L2- is a spacer moiety selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry1)-,-S(O)2N(Ry1)-, -S(O)N(Ry1)-, -S(O)2-, -S(O)-, -N(Ryl)S(O)2N(Ryla)-, -S-, -N(Ry1)-, -OC(ORyl)(Ryla)-, -N(Ryl)C(O)N(Ryla)-, -OC(O)N(Ry1)-, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl; wherein -T-, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally substituted with one or more -Ry2, which are the same or different and wherein C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry3)-, -S(O)2N(Ry3)-, -S(O)N(Ry3)-, -S(O)2-,-S(O)-, -N(Ry3)S(O)2N(Ry3a)-, -S-,-N(Ry3)-, -OC(ORy3)(Ry3a)-, -N(Ry3)C(O)N(Ry3a)-, and -OC(O)N(Ry3)-;-Ryland -Rylaare independently of each other selected from the group consisting of -H, -T, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl; wherein -T, C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally substituted with one or more -Ry2, which are the same or different, and wherein C1-50alkyl, C2-50alkenyl, and C2-50alkynyl are optionally interrupted by one or more groups selected from the group consisting of -T-, -C(O)O-, -O-, -C(O)-, -C(O)N(Ry4)-, -S(O)2N(Ry4)-, -S(O)N(Ry4)-, -S(O)2-, -S(O)-, -N(Ry4)S(O)2N(Ry4a)-, -S-,-N(Ry4)-, -OC(ORy4)(Ry4a)-, -N(Ry4)C(O)N(Ry4a)-, and -OC(O)N(Ry4)-; each T is independently selected from the group consisting of phenyl, naphthyl, indenyl, indanyl, tetralinyl, C3-10 cycloalkyl, 3- to 10-membered heterocyclyl, 8- to 11-membered heterobicyclyl, 8-to 30-membered carbopolycyclyl, and 8- to 30- membered heteropoly cyclyl; wherein each T is independently optionally substituted with one or more -Ry2, which are the same or different; each -Ry2is independently selected from the group consisting of halogen, -CN, oxo (=0), -COORy5, -ORy5, -C(O)Ry5, -C(O)N(Ry5Ry5a), -S(O)2N(Ry5Ry5a), -S(O)N(Ry5Ry5a), -S(O)2Ry5, -S(O)Ry5, -N(Ry5)S(O)2N(Ry5aRy5b), -SRy5,-N(Ry5Ry5a), -NO2, -OC(O)Ry5, -N(Ry5)C(O)Ry5a, -N(Ry5)S(O)2Ry5a, -N(Ry5)S(O)Ry5a, -N(Ry5)C(O)ORy5a,-N(Ry5)C(O)N(Ry5aRy5b), -OC(O)N(Ry5Ry5a),and C1-6alkyl; wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different; and each -Ry3, -Ry3a, -Ry4, -Ry4a, -Ry5, -Ry5aand -Ry5bis independently selected from the group consisting of -H, and C1-6alkyl, wherein C1-6alkyl is optionally substituted with one or more halogen, which are the same or different.

11. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1 to10, wherein L2- is of formula (XI)wherein the unmarked dashed line indicates attachment to -L1-; the dashed line marked with the asterisk indicates attachment to the at least one polymeric moiety; 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.

12. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1 to11, wherein -D-AB is a GLP-1 receptor agonist moiety.

13. The compound or a pharmaceutically acceptable salt thereof of claim 12, wherein the GLP-1 receptor agonist moiety is selected from the group consisting of semaglutide, liraglutide, ecnoglutide, GZR18, GL0034, tirzepatide, cotadutide, BL456906, pemvidutide, mazdutide, dapiglutide and retatrutide.

14. The compound or a pharmaceutically acceptable salt thereof of any claim 12 or 13, wherein -D-AB is semaglutide.

15. The compound or a pharmaceutically acceptable salt therof of any one of claims 1 or 4 to 14, wherein the compound is of formula (2c”)wherein the dashed line indicates attachment to the N-terminal amine functional group of semaglutide; and n1, n2, n3 and n4 are independently an integer ranging from about 11 to about 115.

16. The compound or a pharmaceutically acceptable salt therof of any one of claims 1 or 4 to 15, wherein the compound is of formula (2c’)wherein the dashed line indicates attachment to the N-terminal amine functional group of semaglutide; and n1, n2, n3 and n4 are independently an integer ranging from about 11 to about 115.

17. The compound or a pharmaceutically acceptable salt thereof of claim 15 or 16, wherein n1, n2, n3 and n4 are independently an integer of about 28.

18. The compound or a pharmaceutically acceptable salt thereof of claim 15 or 16, wherein n1, n2, n3 and n4 are independently an integer of about 56.

19. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1, 2 or 7 to 14, wherein the compound is of formula (2g’)wherein n is independently an integer ranging from about 22 to about 230; dashed lines indicate attachment to a moietythe unmarked dashed line indicates attachment to an unmarked dashed line of formula (2g’); and the dashed line marked with the asterisk indicates attachment to the N-terminal amine functional group of semaglutide.

20. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1, 2 or 7 to 14, wherein the compound is of formula (2g)wherein n is independently an integer ranging from about 22 to about 230; dashed lines indicate attachment to a moietywherein the unmarked dashed line indicates attachment to an unmarked dashed line of formula (2g); and the dashed line marked with the asterisk indicates attachment to the N-terminal amine functional group of semaglutide.

21. The compound or a pharmaceutically acceptable salt thereof of claim 19 or 20, wherein n is about 112.

22. A pharmaceutical composition comprising one or more of the compounds or a pharmaceutically acceptable salt thereof of any one of claims 1 to 21.

23. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1 to 21 or the pharmaceutical composition of claim 22 for the manufacture of a medicament.

24. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1 to 21 or the pharmaceutical composition of claim 22 for use in a treatment of a disease that can be treated with -D-AB.

25. The compound or a pharmaceutically acceptable salt thereof of any one of claims 12 to 21 or a pharmaceutically composition comprising one or more compounds of any one of claims 12 to 21 for use in the treatment of a disease selected from the group consisting of (i) all forms of diabetes, (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 kidney disease (DKD), (viii) peripheral arterial disease (PAD), and / or (ix) heart failure (HF).

26. The compound or a pharmaceutically acceptable salt thereof of any one of claims 12 to 21 or a pharmaceutically composition comprising one or more compounds of any one of claims 12 to 21 for use in the treatment of a disease selected from the group consisting of syndrome X, atherosclerosis, myocardial infarction, coronary heart disease, reperfusion injury, stroke, cerebral ischemia, an early cardiac or early cardiovascular disease, left ventricular hypertrophy, coronary artery disease, hypertension, essential hypertension, acute hypertensive emergency, cardiomyopathy, heart insufficiency, exercise intolerance, acute and / or chronic heart failure, arrhythmia, cardiac dysrhythmia, syncopy, angina pectoris, cardiac bypass and / or stent reocclusion, intermittent claudication (atheroschlerosis oblitterens), diastolic dysfunction, and / or systolic dysfunction; and reduction of blood pressure, such as reduction of systolic blood pressure.

27. The compound or a pharmaceutically acceptable salt thereof or the pharmaceutical composition for use of claim 25 or 26, wherein the compound or a pharmaceutically acceptable salt thereof or the pharmaceutical composition are administered in combination with a growth hormone.

28. The compound or a pharmaceutically acceptable salt thereof or the pharmaceutical composition for use of claim 27, wherein the growth hormone is lonapegsomatropin.

Images