Maleimide compounds

Abstract

The present invention relates to compounds, or pharmaceutically acceptable salts, hydrates or solvates thereof, having the structural Formula (1), shown below: wherein m, n, R1, L and PL, and any groups associated therewith, are as defined herein. The present invention also relates to pharmaceutical compositions comprising the maleimide compounds described herein, as well as to the use of said compounds in the treatment of various diseases / disorders.

Description

1 MALEIMIDE COMPOUNDS INTRODUCTION

[0001] The present invention relates to maleimide compounds. More specifically, the present invention relates to maleimide compounds that are suitable for use in the treatment of various diseases / disorders. The present invention also relates to pharmaceutical compositions comprising the maleimide compounds described herein, as well as to the use of said compounds in the treatment of various diseases / disorders. BACKGROUND OF THE INVENTION

[0002] Antibody-drug conjugates (ADCs) are an example of protein / peptide binder-payload conjugates. Other examples of protein / peptide binder-payload conjugates include chelating a radionuclide to a nanobody for use in imaging and radiotherapy. While there are many other examples of protein / peptide binder-payload conjugates, ADCs have recently become of particular interest as they are a promising class of targeted therapeutics which aim to selectively delivery of drugs to malignant cells without undesired toxicity towards healthy tissues. ADCs are composed of both antibodies and drugs. The role of the antibody is to bind to cell-surface antigens overexpressed by cancer cells, enabling the selective delivery of highly cytotoxic payloads to tumour sites.

[0003] One method for the production of ADCs involves conjugating a payload to surface- exposed lysine residues via N-hydroxysuccinimide (NHS) ester motifs. Alternative methods involve conjugating a payload to antibody cysteine residues. Due to the high abundance of reactive cysteine (8) residues in antibodies, modifications at these residues suffer from an inherent lack of site-selectivity and result in highly heterogeneous ADCs which vary in terms of conjugation site and the number of drug molecules attached to each antibody. This can have a deleterious effect on both the safety and efficacy of ADCs.

[0004] Furthermore, antibody binding can be inhibited by protein aggregation. Chemical and physical degradation can lead to structural changes in ADCs, leading to excessive protein aggregation. There are various factors that can cause this, such as frequent freezing / thawing, high protein and salt concentrations, elevated temperature and / or low pH. In addition, most payloads are hydrophobic, and binding the payload at a high drug to antibody ratio (DAR) on the protein surface can lead to excessive protein aggregation, thereby hindering the successful development of ADCs.

[0005] Therefore, there remains a need for an effective class of protein / peptide binder- payload conjugates, in particular ADCs, which mitigate the problems discussed herein. The present invention was devised with the foregoing in mind.2 SUMMARY OF THE INVENTION

[0006] According to a first aspect of the present invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein.

[0007] According to a further aspect of the present invention, there is provided a pharmaceutical composition comprising a compound as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in admixture with a pharmaceutically acceptable diluent or carrier.

[0008] According to a further aspect of the present invention, there is provided a method of treating a disease or disorder in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein, or a pharmaceutical composition, as defined herein.

[0009] According to a further aspect of the present invention, there is provided a method of treating I. a proliferative disorder; II. an infectious disease; III. a chronic disease; IV. a hereditary disease; V. a bone disease; VI. an autoimmune disease; VII. a respiratory disease; or VIII. a neurodegenerative disease, in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein, or a pharmaceutical composition, as defined herein.

[0010] According to a further aspect of the present invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein, or a pharmaceutical composition as defined herein for use in therapy.

[0011] According to a further aspect of the present invention, there is provided a compound or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein, or a pharmaceutical composition as defined herein for use in the treatment of a disease or disorder.

[0012] According to a further aspect of the present invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein, or a pharmaceutical composition as defined herein for use in the treatment of3 I. a proliferative disorder; II. an infectious disease; III. a chronic disease; IV. a hereditary disease; V. a bone disease; VI. an autoimmune disease; VII. a respiratory disease; or VIII. a neurodegenerative disease.

[0013] According to a further aspect of the present invention, there is provided the use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein in the manufacture of a medicament for the treatment of a disease or disorder.

[0014] According to a further aspect of the present invention, there is provided the use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein in the manufacture of a medicament for the treatment of I. a proliferative disorder; II. an infectious disease; III. a chronic disease; IV. a hereditary disease; V. a bone disease; VI. an autoimmune disease; VII. a respiratory disease; or VIII. a neurodegenerative disease.

[0015] According to a further aspect of the present invention, there is provided a process for preparing a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein.

[0016] According to a further aspect of the present invention, there is provided a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, obtainable by, or obtained by, or directly obtained by a process of preparing a compound as defined herein.

[0017] According to a further aspect of the present invention, there are provided novel intermediates as defined herein which are suitable for use in any one of the synthetic methods set out herein.

[0018] According to a further aspect of the present invention, there is provided a method of preparing a protein / peptide-payload conjugate, the method comprising contacting a compound or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein (e.g., a compound of Formula (I)) with one or more proteins and / or peptides, thereby forming a protein / peptide-payload conjugate.4

[0019] According to a further aspect of the present invention, there is provided a protein / peptide-payload conjugate obtainable by, obtained by, or directly obtained by the aforementioned method of preparing a protein / peptide-payload conjugate.

[0020] According to a further aspect of the present invention, there is provided a method of preparing an antibody-payload conjugate, the method comprising contacting a compound or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein (e.g., a compound of Formula (I)), with one or more antibodies, thereby forming an antibody-payload conjugate.

[0021] According to a further aspect of the present invention, there is provided an antibody- payload conjugate obtainable by, obtained by, or directly obtained by the aforementioned method of preparing an antibody-payload conjugate.

[0022] According to a further aspect of the present invention, there is provided a method of preparing an antibody-drug conjugate, the method comprising contacting a compound or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein (e.g., a compound of Formula (I)), with one or more antibodies, thereby forming an antibody-drug conjugate.

[0023] According to a further aspect of the present invention, there is provided an antibody- drug conjugate obtainable by, obtained by, or directly obtained by the aforementioned method of preparing an antibody-drug conjugate.

[0024] According to a further aspect of the present invention, there is provided a method of preparing an affibody-payload conjugate, the method comprising contacting a compound or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein (e.g., a compound of Formula (I)), with one or more affibodies, thereby forming an affibody-payload conjugate.

[0025] According to a further aspect of the present invention, there is provided an affibody- payload conjugate obtainable by, obtained by, or directly obtained by the aforementioned method of preparing an affibody-payload conjugate.

[0026] Features, including optional, suitable, and preferred features in relation to one aspect of the invention may also be features, including optional, suitable and preferred features in relation to any other aspect of the invention. DETAILED DESCRIPTION OF THE INVENTION Definitions5

[0027] Unless otherwise stated, the following terms used in the specification and claims have the following meanings set out below.

[0028] It is to be appreciated that references to “treating” or “treatment” include prophylaxis as well as the alleviation of established symptoms of a condition. “Treating” or “treatment” of a state, disorder or condition therefore includes: (1) preventing or delaying the appearance of clinical symptoms of the state, disorder or condition developing in a human that may be afflicted with or predisposed to the state, disorder or condition but does not yet experience or display clinical or subclinical symptoms of the state, disorder or condition, (2) inhibiting the state, disorder or condition, i.e., arresting, reducing or delaying the development of the disease or a relapse thereof (in case of maintenance treatment) or at least one clinical or subclinical symptom thereof, or (3) relieving or attenuating the disease, i.e., causing regression of the state, disorder or condition or at least one of its clinical or subclinical symptoms.

[0029] A “therapeutically effective amount” means the amount of a compound that, when administered to a mammal for treating a disease, is sufficient to effect such treatment for the disease. The "therapeutically effective amount" will vary depending on the compound, the disease and its severity and the age, weight, etc., of the mammal to be treated.

[0030] In this specification the term “alkyl” includes both straight and branched chain alkyl groups. References to individual alkyl groups such as “propyl” are specific for the straight chain version only and references to individual branched chain alkyl groups such as “isopropyl” are specific for the branched chain version only. For example, “(1-6C)alkyl” includes (1- 4C)alkyl, (1-3C)alkyl, propyl, isopropyl and t butyl.

[0031] The term "(m-nC)" or "(m-nC) group" used alone or as a prefix, refers to any group having m to n carbon atoms.

[0032] An “alkylene” group is an alkyl group that is positioned between and serves to connect two other chemical groups. Thus, “(1-6C)alkylene” means a linear saturated divalent hydrocarbon radical of 1 to 6 carbon atoms or a branched saturated divalent hydrocarbon radical of 3 to 6 carbon atoms, for example, methylene (-CH2-), ethylene (-CH2CH2-), propylene (-CH2CH2CH2-), 2-methylpropylene (-CH2CH(CH3)CH2-), pentylene (- CH2CH2CH2CH2CH2-), and the like.

[0033] The term “alkenyl” refers to straight and branched chain alkyl groups comprising 2 or more carbon atoms, wherein at least one carbon-carbon double bond is present within the group. Examples of alkenyl groups include ethenyl, propenyl and but-2,3-enyl and includes all possible geometric (E / Z) isomers.

[0034] The term “alkynyl” refers to straight and branched chain alkyl groups comprising 2 or6 more carbon atoms, wherein at least one carbon-carbon triple bond is present within the group. Examples of alkynyl groups include acetylenyl and propynyl.

[0035] “(3-10C)cycloalkyl” means a hydrocarbon ring containing from 3 to 10 carbon atoms, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and bicyclo[2.2.1]heptyl.

[0036] The term “alkoxy” refers to O-linked straight and branched chain alkyl groups. Examples of alkoxy groups include methoxy, ethoxy, propoxy and t-butoxy.

[0037] The term “haloalkyl” is used herein to refer to an alkyl group in which one or more hydrogen atoms have been replaced by halogen (e.g., fluorine) atoms. Examples of haloalkyl groups include -CH2F, -CHF2 and -CF3

[0038] The term “halo” or “halogeno” refers to fluoro, chloro, bromo and iodo, suitably fluoro, chloro and bromo, more suitably, fluoro and chloro.

[0039] The term “carbocyclyl”, “carbocyclic” or “carbocycle” means a non-aromatic saturated or partially saturated monocyclic, fused, bridged, or spiro bicyclic carbon-containing ring system(s). Monocyclic carbocyclic rings contain from about 3 to 12 (suitably from 3 to 7) ring atoms. Bicyclic carbocycles contain from 6 to 17 member atoms, suitably 7 to 12 member atoms, in the ring. Bicyclic carbocyclic(s) rings may be fused, spiro, or bridged ring systems. Polycyclic carbocycles contain from 13 to 24 member atoms, suitably 13 to 18 member atoms, in the ring. Polycyclic carbocyclic(s) rings may be fused, spiro, or bridged ring systems. Examples of carbocyclic groups include cyclopropyl, cyclobutyl, cyclohexyl, cyclohexenyl, spiro[3.3]heptanyl and fluorene.

[0040] The term “heterocyclyl”, “heterocyclic” or “heterocycle” means a non-aromatic saturated or partially saturated monocyclic, fused, bridged, or spiro bicyclic heterocyclic ring system(s). Monocyclic heterocyclic rings contain from about 3 to 12 (suitably from 3 to 7) ring atoms, with from 1 to 5 (suitably 1, 2 or 3) heteroatoms selected from nitrogen, oxygen or sulfur in the ring. Bicyclic heterocycles contain from 7 to 17 member atoms, suitably 7 to 12 member atoms, in the ring. Bicyclic heterocyclic(s) rings may be fused, spiro, or bridged ring systems. Examples of heterocyclic groups include cyclic ethers such as oxiranyl, oxetanyl, tetrahydrofuranyl, dioxanyl, and substituted cyclic ethers. Heterocycles containing nitrogen include, for example, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, tetrahydrotriazinyl, tetrahydropyrazolyl, and the like. Typical sulfur containing heterocycles include tetrahydrothienyl, dihydro-1,3-dithiol, tetrahydro-2H-thiopyran, and hexahydrothiepine. Other heterocycles include dihydro oxathiolyl, tetrahydro oxazolyl, tetrahydro-oxadiazolyl, tetrahydrodioxazolyl, tetrahydro oxathiazolyl, hexahydrotriazinyl, tetrahydro oxazinyl, morpholinyl, thiomorpholinyl, tetrahydropyrimidinyl, dioxolinyl, octahydrobenzofuranyl,7 octahydrobenzimidazolyl, and octahydrobenzothiazolyl. For heterocycles containing sulfur, the oxidized sulfur heterocycles containing SO or SO2groups are also included. Examples include the sulfoxide and sulfone forms of tetrahydrothienyl and thiomorpholinyl such as tetrahydrothiene 1,1-dioxide and thiomorpholinyl 1,1-dioxide. Heterocycles may comprise 1 or 2 oxo (=O) or thioxo (=S) substituents. A suitable value for a heterocyclyl group which bears 1 or 2 oxo (=O) or thioxo (=S) substituents is, for example, 2-oxopyrrolidinyl, 2- thioxopyrrolidinyl, 2-oxoimidazolidinyl, 2-thioxoimidazolidinyl, 2-oxopiperidinyl, 2,5- dioxopyrrolidinyl, 2,5-dioxoimidazolidinyl or 2,6-dioxopiperidinyl. Particular heterocyclyl groups are saturated monocyclic 3 to 7 membered heterocyclyls containing 1, 2 or 3 heteroatoms selected from nitrogen, oxygen or sulfur, for example azetidinyl, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, morpholinyl, tetrahydrothienyl, tetrahydrothienyl 1,1-dioxide, thiomorpholinyl, thiomorpholinyl 1,1-dioxide, piperidinyl, homopiperidinyl, piperazinyl or homopiperazinyl. As the skilled person would appreciate, any heterocycle may be linked to another group via any suitable atom, such as via a carbon or nitrogen atom. However, reference herein to piperidino or morpholino refers to a piperidin-1- yl or morpholin-4-yl ring that is linked via the ring nitrogen.

[0041] The phrase “bridged ring systems” will be understood to mean ring systems in which two rings share more than two atoms, see for example Advanced Organic Chemistry, by Jerry March, 4th Edition, Wiley Interscience, pages 131-133, 1992. Examples of bridged heterocyclyl ring systems include, aza-bicyclo[2.2.1]heptane, 2-oxa-5- azabicyclo[2.2.1]heptane, aza-bicyclo[2.2.2]octane, aza-bicyclo[3.2.1]octane and quinuclidine.

[0042] By “spiro bi-cyclic ring systems” we mean that the two ring systems share one common spiro carbon atom, i.e., the heterocyclic ring is linked to a further carbocyclic or heterocyclic ring through a single common spiro carbon atom. Examples of spiro ring systems include 6- azaspiro[3.4]octane, 2-oxa-6-azaspiro[3.4]octane, 2-azaspiro[3.3]heptanes, 2-oxa-6- azaspiro[3.3]heptanes, 7-oxa-2-azaspiro[3.5]nonane, 6-oxa-2-azaspiro[3.4]octane, 2-oxa-7- azaspiro[3.5]nonane and 2-oxa-6-azaspiro[3.5]nonane.

[0043] The term “heteroaryl” or “heteroaromatic” means an aromatic mono , bi , or polycyclic ring incorporating 1 or more (for example 1-4, particularly 1, 2 or 3) heteroatoms selected from nitrogen, oxygen or sulfur. The term heteroaryl includes both monovalent species and divalent species. Examples of heteroaryl groups are monocyclic and bicyclic groups containing from 5 to 12 ring members, and more usually from 5 to 10 ring members. The heteroaryl group can be, for example, a 5- or 6-membered monocyclic ring or a 9- or 10-membered bicyclic ring, for example a bicyclic structure formed from fused 5 and 6 membered rings or two fused 6 membered rings. Each ring may contain up to about 4 heteroatoms typically selected from8 nitrogen, sulfur and oxygen. Typically the heteroaryl ring will contain up to 3 heteroatoms, more usually up to 2, for example 1 heteroatom. In one embodiment, the heteroaryl ring contains at least 1 ring nitrogen atom. The nitrogen atoms in the heteroaryl rings can be basic, as in the case of an imidazole or pyridine, or essentially non-basic as in the case of an indole or pyrrole nitrogen. In general the number of basic nitrogen atoms present in the heteroaryl group, including any amino group substituents of the ring, will be less than 5.

[0044] Examples of heteroaryl include furyl, pyrrolyl, thienyl, oxazolyl, isoxazolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,3,5-triazenyl, benzofuranyl, indolyl, isoindolyl, benzothienyl, benzoxazolyl, benzimidazolyl, benzothiazolyl, benzothiazolyl, indazolyl, purinyl, benzofurazanyl, quinolyl, isoquinolyl, quinazolinyl, quinoxalinyl, cinnolinyl, pteridinyl, naphthyridinyl, carbazolyl, phenazinyl, benzisoquinolinyl, pyridopyrazinyl, thieno[2,3 b]furanyl, 2H-furo[3,2 b]pyranyl, 5H-pyrido[2,3 d]oxazinyl, 1H-pyrazolo[4,3 d]oxazolyl, 4H-imidazo[4,5 d]thiazolyl, pyrazino[2,3 d]pyridazinyl, imidazo[2,1 b]thiazolyl, imidazo[1,2 b][1,2,4]triazinyl. “Heteroaryl” also covers partially aromatic bi- or polycyclic ring systems wherein at least 1 ring is an aromatic ring and 1 or more of the other ring(s) is a non-aromatic, saturated or partially saturated ring, provided at least 1 ring contains 1 or more heteroatoms selected from nitrogen, oxygen or sulfur. Examples of partially aromatic heteroaryl groups include but are not limited to tetrahydroisoquinolinyl, tetrahydroquinolinyl, 2-oxo-1,2,3,4-tetrahydroquinolinyl, dihydrobenzthienyl, dihydrobenzfuranyl, 2,3-dihydro-benzo[1,4]dioxinyl, benzo[1,3]dioxolyl, 2,2-dioxo-1,3-dihydro-2-benzothienyl, 4,5,6,7-tetrahydrobenzofuranyl, indolinyl, 1,2,3,4 tetrahydro 1,8 naphthyridinyl, 1,2,3,4 tetrahydropyrido[2,3 b]pyrazinyl and 3,4 dihydro 2H pyrido[3,2 b][1,4]oxazinyl.

[0045] Examples of 5-membered heteroaryl groups include but are not limited to pyrrolyl, furanyl, thienyl, imidazolyl, furazanyl, oxazolyl, oxadiazolyl, oxatriazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, triazolyl and tetrazolyl groups.

[0046] Examples of 6-membered heteroaryl groups include but are not limited to pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl and triazinyl.

[0047] A bicyclic heteroaryl group may be, for example, a group selected from: a benzene ring fused to a 5- or 6-membered ring containing 1, 2 or 3 ring heteroatoms; a pyridine ring fused to a 5- or 6-membered ring containing 1, 2 or 3 ring heteroatoms; a pyrimidine ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; a pyrrole ring fused to a 5- or 6-membered ring containing 1, 2 or 3 ring heteroatoms; a pyrazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms;9 a pyrazine ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; an imidazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; an oxazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; an isoxazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; a thiazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; an isothiazole ring fused to a 5- or 6-membered ring containing 1 or 2 ring heteroatoms; a thiophene ring fused to a 5- or 6-membered ring containing 1, 2 or 3 ring heteroatoms; a furan ring fused to a 5- or 6-membered ring containing 1, 2 or 3 ring heteroatoms; a cyclohexyl ring fused to a 5- or 6-membered heteroaromatic ring containing 1, 2 or 3 ring heteroatoms; and a cyclopentyl ring fused to a 5- or 6-membered heteroaromatic ring containing 1, 2 or 3 ring heteroatoms.

[0048] Particular examples of bicyclic heteroaryl groups containing a 6-membered ring fused to a 5-membered ring include but are not limited to benzfuranyl, benzthiophenyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzthiazolyl, benzisothiazolyl, isobenzofuranyl, indolyl, isoindolyl, indolizinyl, indolinyl, isoindolinyl, purinyl (e.g., adeninyl, guaninyl), indazolyl, benzodioxolyl and pyrazolopyridinyl groups.

[0049] Particular examples of bicyclic heteroaryl groups containing two fused 6-membered rings include but are not limited to quinolinyl, isoquinolinyl, chromanyl, thiochromanyl, chromenyl, isochromenyl, chromanyl, isochromanyl, benzodioxanyl, quinolizinyl, benzoxazinyl, benzodiazinyl, pyridopyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, phthalazinyl, naphthyridinyl and pteridinyl groups.

[0050] The term “aryl” means a cyclic or polycyclic aromatic ring having from 5 to 24 carbon atoms. Monocyclic aryls suitably contain 6 member atoms. Bicyclic aryls suitably contain 10 member atoms. Polycyclic aryls suitably contain carbocycles contain from 14 to 24 member atoms. Polycyclic aryl rings may be fused, spiro, or bridged ring systems. The term aryl includes both monovalent species and divalent species. Examples of aryl groups include but are not limited to phenyl, biphenyl, naphthyl, phenanthrene, phenalene, tetracene and the like. In a particular embodiment, an aryl is phenyl.

[0051] This specification also makes use of several composite terms to describe groups comprising more than one functionality. Such terms will be understood by a person skilled in the art. For example (3-6C)cycloalkyl(m-nC)alkyl comprises (m-nC)alkyl substituted by (3-10 6C)cycloalkyl.

[0052] The term "optionally substituted" refers to either groups, structures, or molecules that are substituted and those that are not substituted. The term “substituted” suitably means that any one (or more) of the hydrogen radicals in the group / structure / molecule to be substituted (e.g., a hydrogen radical in a CH3group) is substituted by a relevant stipulated group.

[0053] Where optional substituents are chosen from “one or more” groups it is to be understood that this definition includes all substituents being chosen from one of the specified groups or the substituents being chosen from two or more of the specified groups.

[0054] The phrase “compound of the invention” means those compounds which are disclosed herein, both generically and specifically (e.g., compounds of Formula (I), as well as compounds of sub-formulae (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I-IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I- IIId), (I-IIIe), or (I-IIIf)). Compounds of the invention

[0055] In one aspect, the present invention relates to compounds, or pharmaceutically acceptable salts, hydrates or solvates thereof, having the structural Formula (I), shown below:wherein: m is 1, 2 or 3; n is 1, 2 or 3; R1is a group of formula: X1-Y1-X2-Y211 wherein: X1is aryl, carbocycle, (1-6C)alkyl, (2-6C)alkenyl or -(CRaRb)q-S-S-, where Raand Rbare each independently selected from hydrogen or (1-6C)alkyl, and where q is 0, 1, 2, 3 or 4; Y1is absent or is selected from (1-6C)alkyl, (1-6C)hydroxyalkyl, (1-6C)haloalkyl or (1- 6C)alkoxy; X2 is absent or is selected from -S-S-, -O-, -C(O)-, -C(O)-O-, -O-C(O)-, -O-C(O)-NRc-, -C(O)-N(Rc)-, -N(Rc)-C(O)-, -NRc-, -N(Rc)-C(O)-NRc-, -S-C(O)-, -SO2N(Rc)- or - N(Rc)SO2-, where each Rc is independently selected from hydrogen or (1-6C)alkyl; and Y2 is selected from hydrogen, halo, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkoxy-(1- 6C)alkyl, aryl or carbocycle; and wherein any aryl or carbocycle is optionally substituted by one or more substituents independently selected from halo, hydroxy, cyano, amino, nitro, (1-4C)alkyl, (1- 4C)hydroxyalkyl, (1-4C)haloalkyl or (1-4C)alkoxy; L is a linker; and PL is a payload.

[0056] In one aspect, the present invention relates to compounds, or pharmaceutically acceptable salts, hydrates or solvates thereof, having the structural Formula (I), shown below:wherein: m is 1, 2 or 3; n is 1, 2 or 3;12 R1is a group of formula: X1-Y1-X2-Y2wherein: X1is aryl, carbocycle, (1-6C)alkyl, (2-6C)alkenyl or -(CRaRb)q-S-S-, where Raand Rbare each independently selected from hydrogen or (1-6C)alkyl, and where q is 0, 1, 2, 3 or 4; Y1 is absent or is selected from (1-6C)alkyl, (1-6C)hydroxyalkyl, (1-6C)haloalkyl or (1- 6C)alkoxy; X2 is absent or is selected from -S-S-, -O-, -C(O)-, -C(O)-O-, -O-C(O)-, -O-C(O)-NRc-, -C(O)-N(Rc)-, -N(Rc)-C(O)-, -NRc-, -N(Rc)-C(O)-NRc-, -S-C(O)-, -SO2N(Rc)- or - N(Rc)SO2-, where each Rc is independently selected from hydrogen or (1-6C)alkyl; and Y2 is selected from hydrogen, halo, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkoxy-(1- 6C)alkyl, aryl, carbocycle or -[CH2-CH2-O]p-CH2-CH2-OH, wherein p is 1, 2, 3, 4, or 5; and wherein any aryl or carbocycle is optionally substituted by one or more substituents independently selected from halo, hydroxy, cyano, amino, nitro, (1-4C)alkyl, (1- 4C)hydroxyalkyl, (1-4C)haloalkyl or (1-4C)alkoxy; L is a linker; and PL is a payload.

[0057] The inventors have successfully synthesised on-demand stabilised maleimides, as defined by compounds of Formula (I), which allow triggered hydrolysis of the resulting thio- succinimide conjugates. The compounds of Formula (I) allow for the efficient and controlled delivery of a payload (e.g., an active agent such as a cytotoxin) to a target cell.

[0058] The compounds of Formula (I) may bind to one or more proteins and / or peptides, thereby forming protein / peptide-payload conjugates. Accordingly, the present invention provides a method of preparing a protein / peptide-payload conjugate, the method comprising contacting a compound or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein (e.g., a compound of Formula (I)), with one or more proteins and / or peptides, thereby forming a protein / peptide-payload conjugate. The protein / peptide may bind to any portion of the compounds of Formula (I). Suitably, the protein / peptide binds the compounds of Formula (I) through sulfur atoms on the protein / peptide. More suitably, the protein / peptide binds to the compounds of Formula (I) through the maleimide moiety on the compounds of Formula (I). Even more suitably, the protein / peptide binds to the maleimide moiety of the13 compounds of Formula (I) via a thiol linkage (i.e., a covalent bond between a sulfur atom on the protein / peptide and the maleimide moiety of the compounds of Formula (I)). Accordingly, the protein / peptide may comprise a sulfur atom. The present invention also provides a protein / peptide-payload conjugate obtainable by, obtained by, or directly obtained by the aforementioned method of preparing a protein / peptide-payload conjugate. The compounds of Formula (I) may bind to one or more antibodies (e.g., a nanobody such as Anti-HER2 or Anti- PD-L1 (e.g., anti-PD-L1 sdAb)), thereby forming antibody-payload conjugates. Accordingly, the present invention provides a method of preparing an antibody-payload conjugate, the method comprising contacting a compound or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein (e.g., a compound of Formula (I)), with one or more antibodies, thereby forming an antibody-payload conjugate. The antibody may bind to any portion of the compounds of Formula (I). Suitably, the antibody binds the compounds of Formula (I) through sulfur atoms on the antibody. More suitably, the antibody binds to the compounds of Formula (I) through the maleimide moiety on the compounds of Formula (I). Even more suitably, the antibody binds to the maleimide moiety of the compounds of Formula (I) via a thiol linkage (i.e., a covalent bond between a sulfur atom on the antibody and the maleimide moiety of the compounds of Formula (I)). The sulfur atoms on the antibody may be sulfur atoms on cysteine residues on the antibody, such as sulfur atoms from the cysteine residues on the antibody that are involved in the interchain disulfide linkages of the antibody (i.e. sulfur atoms from cysteine residues made available following the reduction of antibody’s interchain disulfide linkages). Accordingly, the antibody may comprise a sulfur atom. The antibody may comprise a cysteine residue. Suitably, the antibody is as defined anywhere herein. More suitably, the antibody is a nanobody. Even more suitably, the antibody is anti- HER2 or anti-PD-L-1 (e.g., anti-PD-L1 sdAb). In some embodiments, the antibody is trastuzumab. The present invention also provides an antibody-payload conjugate obtainable by, obtained by, or directly obtained by the aforementioned method of preparing an antibody- payload conjugate. Suitably, the payload is a drug. The compounds of Formula (I) may bind to one or more antibodies, thereby forming antibody-drug conjugates. Accordingly, the present invention provides a method of preparing an antibody-drug conjugate, the method comprising contacting a compound or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein (e.g., a compound of Formula (I)), with one or more antibodies, thereby forming an antibody-drug conjugate. The antibody may bind to any portion of the compounds of Formula (I). Suitably, the antibody binds the compounds of Formula (I) through sulfur atoms on the antibody. More suitably, the antibody binds to the compounds of Formula (I) through the maleimide moiety on the compounds of Formula (I). Even more suitably, the antibody binds to the maleimide moiety of the compounds of Formula (I) via a thiol linkage (i.e., a covalent bond between a sulfur atom on the antibody and the maleimide moiety of the14 compounds of Formula (I)). The sulfur atoms on the antibody may be sulfur atoms on cysteine residues on the antibody, such as sulfur atoms from the cysteine residues on the antibody that are involved in the interchain disulfide linkages of the antibody (i.e. sulfur atoms from cysteine residues made available following the reduction of antibody’s interchain disulfide linkages). Accordingly, the antibody may comprise a sulfur atom. The antibody may comprise a cysteine residue. Suitably, the antibody is as defined anywhere herein. More suitably, the antibody is a nanobody. Even more suitably, the antibody is anti-HER2 or anti-PD-L-1 (e.g., anti-PD-L1 sdAb). In some embodiments, the antibody is trastuzumab. The present invention also provides an antibody-drug conjugate obtainable by, obtained by, or directly obtained by the aforementioned method of preparing an antibody-drug conjugate. The compounds of Formula (I) may attach to one or more affibodies (e.g., an Anti-HER2 affibody or an Anti-PD-L1 affibody), thereby forming affibody-payload conjugates. Accordingly, the present invention provides a method of preparing an affibody-payload conjugate, the method comprising contacting a compound or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein (e.g., a compound of Formula (I)), with one or more affibodies, thereby forming an affibody-payload conjugate. The affibody may attach to any portion of the compounds of Formula (I). Suitably, the affibody attached the compounds of Formula (I) through sulfur atoms on the affibody. More suitably, the affibody attaches to the compounds of Formula (I) through the maleimide moiety on the compounds of Formula (I). Even more suitably, the affibody attaches to the maleimide moiety of the compounds of Formula (I) via a thiol linkage (i.e., a covalent bond between a sulfur atom on the affibody and the maleimide moiety of the compounds of Formula (I)). The sulfur atoms on the affibody may be sulfur atoms on an unpaired cysteine residue introduced recombinantly into the affibody sequence. Accordingly, the affibody may comprise a sulfur atom. The affibody may comprise a cysteine residue. The affibody may comprise an unpaired cysteine residue introduced recombinantly into the affibody sequence. Suitably, the affibody is anti-HER2 or anti-PD-L-1. The present invention also provides an affibody-payload conjugate obtainable by, obtained by, or directly obtained by the aforementioned method of preparing an affibody-payload conjugate.

[0059] The antibody, which is a protein capable of identifying and binding to a specific antigen, may be a nanobody, a monoclonal antibody, a polyclonal antibody, a dimer, a trimer, a multimer, a multispecific antibody (e.g., a bispecific antibody), a multivalent antibody or an antibody fragment. The antibody may be murine, human, humanized, chimeric, or derived from other species. The antibody may include a full-length immunoglobulin molecule or an immunologically active portion of a full-length immunoglobulin molecule that contains an antigen binding site that immunospecifically binds an antigen of a target of interest or part thereof. The target of interest may be a cancer cell or a cell that produces autoimmune15 antibodies associated with an autoimmune disease. An antibody fragment comprises a portion of a full-length antibody, generally the antigen binding or variable region thereof. Examples of antibody fragments include Fab, Fab', F(ab')2, and scFv fragments; diabodies; linear antibodies; fragments produced by a Fab expression library, anti-idiotypic (anti-Id) antibodies, CDR (complementary determining region), and epitope-binding fragments of any of the above which immunospecifically bind to cancer cell antigens, viral antigens or microbial antigens, single-chain antibody molecules; and multispecific antibodies formed from antibody fragments. A monoclonal antibody is obtained from a population of substantially homogeneous antibodies (i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts). Monoclonal antibodies are highly specific, being directed against a single antigenic site. The monoclonal antibody may be a chimeric antibody, a humanized antibody or a human antibody.

[0060] Particular compounds of Formula (I) include, for example, compounds of the Formula (I), or pharmaceutically acceptable salts, hydrates and / or solvates thereof, wherein, unless otherwise stated, each of m, n, R1, L and PL, and any associated substituent groups, have any of the meanings defined hereinbefore or in any of paragraphs (1) to (73) hereinafter: Integers m and n

[0061] As described herein, the inventors have found that the location of the amine relative to the maleimide moiety is important for maleimide stability. In particular, it has been found that sufficient spacing between amine and the maleimide moiety reduces the hydrolysis promoting effect of the amine, thereby increasing the hydrolytic stability of the maleimide. (1) m is 1 or 2; (2) m is 2 or 3; (3) m is 2; (4) n is 1 or 2; (5) n is 1; (6) n is 2;

[0062] In a particular group of compounds of the invention, the compounds have the structural Formula (I-Ia), (I-Ib) or (I-Ic) shown below:16wherein n, R1, L and PL are as defined herein.17

[0063] In any of the compounds of Formula (I-Ia), (I-Ib) or (I-Ic), n may be 2. In any of the compounds of Formula (I-Ia), (I-Ib) or (I-Ic), n may be 3. Most suitably, in any of the compounds of Formula (I-Ia), (I-Ib) or (I-Ic), n is 1

[0064] In a particular group of compounds of the invention, the compounds have the structural Formula (I-IIa), (I-IIb) or (I-IIc) shown below:(I-IIb)18(I-IIc) wherein m, R1, L and PL are as defined herein.

[0065] In any of the compounds of Formula (I-IIa), (I-IIb) or (I-IIc), m may be 1. In any of the compounds of Formula (I-IIa), (I-IIb) or (I-IIc), m may be 3. Most suitably, in any of the compounds of Formula (I-IIa), (I-IIb) or (I-IIc), m is 2. R1 (7) R1 is a group of formula: X1-Y1-X2-Y2 wherein: X1 is aryl, carbocycle, (1-4C)alkyl, (2-4C)alkenyl or -(CRaRb)q-S-S-, where Ra and Rb are each independently selected from hydrogen or (1-4C)alkyl, and where q is 0, 1, 2, 3 or 4; Y1 is absent or is selected from (1-4C)alkyl, (1-4C)hydroxyalkyl, (1-4C)haloalkyl or (1- 4C)alkoxy; X2 is absent or is selected from -S-S-, -O-, -C(O)-, -C(O)-O-, -O-C(O)-, -O-C(O)-NRc-, -C(O)-N(Rc)-, -N(Rc)-C(O)-, -NRc-, -N(Rc)-C(O)-NRc-, -S-C(O)-, -SO2N(Rc)- or - N(Rc)SO2-, where each Rc is independently selected from hydrogen or (1-4C)alkyl; and Y2 is selected from hydrogen, halo, (1-6C)alkyl, (1-6C)alkoxy, (1-4C)alkoxy-(1- 4C)alkyl, aryl or carbocycle; and19 wherein any aryl or carbocycle is optionally substituted by one or more substituents independently selected from halo, hydroxy, cyano, amino, nitro, (1-2C)alkyl, (1- 2C)hydroxyalkyl, (1-2C)haloalkyl or (1-2C)alkoxy; (7a) R1is a group of formula: X1-Y1-X2-Y2wherein: X1 is aryl, carbocycle, (1-4C)alkyl, (2-4C)alkenyl or -(CRaRb)q-S-S-, where Ra and Rb are each independently selected from hydrogen or (1-4C)alkyl, and where q is 0, 1, 2, 3 or 4; Y1 is absent or is selected from (1-4C)alkyl, (1-4C)hydroxyalkyl, (1-4C)haloalkyl or (1- 4C)alkoxy; X2 is absent or is selected from -S-S-, -O-, -C(O)-, -C(O)-O-, -O-C(O)-, -O-C(O)-NRc-, -C(O)-N(Rc)-, -N(Rc)-C(O)-, -NRc-, -N(Rc)-C(O)-NRc-, -S-C(O)-, -SO2N(Rc)- or - N(Rc)SO2-, where each Rc is independently selected from hydrogen or (1-4C)alkyl; and Y2 is selected from hydrogen, halo, (1-6C)alkyl, (1-6C)alkoxy, (1-4C)alkoxy-(1- 4C)alkyl, aryl, carbocycle or -[CH2-CH2-O]p-CH2-CH2-OH, wherein p is 1, 2, 3, 4, or 5; and wherein any aryl or carbocycle is optionally substituted by one or more substituents independently selected from halo, hydroxy, cyano, amino, nitro, (1-2C)alkyl, (1- 2C)hydroxyalkyl, (1-2C)haloalkyl or (1-2C)alkoxy; (8) R1 is a group of formula: X1-Y1-X2-Y2 wherein: X1 is aryl, carbocycle, (1-4C)alkyl, (2-4C)alkenyl or -(CRaRb)q-S-S-, where Ra and Rb are each independently selected from hydrogen or (1-2C)alkyl, and where q is 0, 1 or 4; Y1is absent or is selected from (1-2C)alkyl, (1-2C)hydroxyalkyl, (1-2C)haloalkyl or (1- 2C)alkoxy; X2 is absent or is selected from -S-S-, -O-, -C(O)-, -C(O)-O-, -O-C(O)-, -O-C(O)-NRc-, -C(O)-N(Rc)-, -N(Rc)-C(O)-, -NRc-, -N(Rc)-C(O)-NRc-, -S-C(O)-, -SO2N(Rc)- or - N(Rc)SO2-, where each Rcis independently selected from hydrogen or (1-2C)alkyl; and20 Y2is selected from hydrogen, halo, (1-4C)alkyl, (1-2C)alkoxy, (1-2C)alkoxy-(1- 2C)alkyl, phenyl or 6- to 13-membered carbocycle; and wherein any aryl or carbocycle is optionally substituted by one, two or three substituents independently selected from halo, hydroxy, cyano, amino, nitro, (1- 2C)alkyl, (1-2C)hydroxyalkyl, (1-2C)haloalkyl or (1-2C)alkoxy; (8a) R1is a group of formula: X1-Y1-X2-Y2 wherein: X1 is aryl, carbocycle, (1-4C)alkyl, (2-4C)alkenyl or -(CRaRb)q-S-S-, where Ra and Rb are each independently selected from hydrogen or (1-2C)alkyl, and where q is 0, 1 or 4; Y1 is absent or is selected from (1-2C)alkyl, (1-2C)hydroxyalkyl, (1-2C)haloalkyl or (1- 2C)alkoxy; X2 is absent or is selected from -S-S-, -O-, -C(O)-, -C(O)-O-, -O-C(O)-, -O-C(O)-NRc-, -C(O)-N(Rc)-, -N(Rc)-C(O)-, -NRc-, -N(Rc)-C(O)-NRc-, -S-C(O)-, -SO2N(Rc)- or - N(Rc)SO2-, where each Rc is independently selected from hydrogen or (1-2C)alkyl; and Y2 is selected from hydrogen, halo, (1-4C)alkyl, (1-2C)alkoxy, (1-2C)alkoxy-(1- 2C)alkyl, phenyl, 6- to 13-membered carbocycle, or -[CH2-CH2-O]p-CH2-CH2-OH, wherein p is 1, 2, 3, or 4; and wherein any aryl or carbocycle is optionally substituted by one, two or three substituents independently selected from halo, hydroxy, cyano, amino, nitro, (1- 2C)alkyl, (1-2C)hydroxyalkyl, (1-2C)haloalkyl or (1-2C)alkoxy; (9) R1 is a group of formula: X1-Y1-X2-Y2 wherein: X1 is phenyl, a polycyclic aromatic hydrocarbon, a 6- to 13-memebred carbocycle (e.g., a polycyclic carbocycle), (1-2C)alkyl or -(CRaRb)q-S-S-, where Raand Rbare each independently selected from hydrogen or (1C)alkyl, and where q is 0, 1 or 4; Y1 is absent or (1-2C)alkyl; X2is absent or is selected from -S-S-, -O-, -C(O)-, -C(O)-O-, -O-C(O)-NRc-, -C(O)- N(Rc)-, -NRc- or -S-C(O)-, where each Rcis hydrogen; and21 Y2is selected from hydrogen, (1-4C)alkyl, (1-2C)alkoxy-(1-2C)alkyl, phenyl or 6- to 9- membered carbocycle; and wherein any aryl or carbocycle is optionally substituted by one, two or three substituents independently selected from halo, hydroxy, amino, nitro, (1C)alkyl, (1C)hydroxyalkyl, (1C)haloalkyl or (1C)alkoxy; (9a) R1is a group of formula: X1-Y1-X2-Y2 wherein: X1 is phenyl, a polycyclic aromatic hydrocarbon, a 6- to 13-memebred carbocycle (e.g., a polycyclic carbocycle), (1-2C)alkyl or -(CRaRb)q-S-S-, where Ra and Rb are each independently selected from hydrogen or (1C)alkyl, and where q is 0, 1 or 4; Y1 is absent or (1-2C)alkyl; X2 is absent or is selected from -S-S-, -O-, -C(O)-, -C(O)-O-, -O-C(O)-NRc-, -C(O)- N(Rc)-, -NRc- or -S-C(O)-, where each Rc is hydrogen; and Y2 is selected from hydrogen, (1-4C)alkyl, (1-2C)alkoxy-(1-2C)alkyl, phenyl, 6- to 9- membered carbocycle, or -[CH2-CH2-O]p-CH2-CH2-OH, wherein p is 2, 3, or 4; and wherein any aryl or carbocycle is optionally substituted by one, two or three substituents independently selected from halo, hydroxy, amino, nitro, (1C)alkyl, (1C)hydroxyalkyl, (1C)haloalkyl or (1C)alkoxy; (10) R1 is a group of formula: X1-Y1-X2-Y2 wherein: X1 is phenyl, fluorene, (1-2C)alkyl or -(CRaRb)q-S-S-, where Ra and Rb are each independently selected from hydrogen or (1C)alkyl, and where q is 0, 1 or 4; Y1 is absent or (2C)alkyl; X2 is absent or is selected from -S-S-, -O-C(O)-NRc- or -S-C(O)-, where each Rc is hydrogen; and Y2 is selected from hydrogen, (1-3C)alkyl or (1C)alkoxy-(2C)alkyl; and wherein phenyl is substituted by one or three substituents independently selected from nitro or (1C)alkoxy; (10a) R1is a group of formula:22 X1-Y1-X2-Y2wherein: X1is phenyl, fluorene, (1-2C)alkyl or -(CRaRb)q-S-S-, where Raand Rbare each independently selected from hydrogen or (1C)alkyl, and where q is 0, 1 or 4; Y1is absent or (2C)alkyl; X2is absent or is selected from -S-S-, -O-C(O)-NRc- or -S-C(O)-, where each Rcis hydrogen; and Y2 is selected from hydrogen, (1-3C)alkyl, (1C)alkoxy-(2C)alkyl or -[CH2-CH2-O]p-CH2- CH2-OH, wherein p is 2 or 3; and wherein phenyl is substituted by one or three substituents independently selected from nitro or (1C)alkoxy; (11) R1 is a group of formula: X1-Y1-X2-Y2 wherein: X1 is phenyl, fluorene, (1C)alkyl or -(CRaRb)q-S-S-, where Ra and Rb are each independently selected from hydrogen or (1C)alkyl, and where q is 0 or 1; Y1 is absent or (2C)alkyl; X2 is absent or is -O-C(O)-NRc- or -S-C(O)-, where each Rc is hydrogen; and Y2 is selected from hydrogen or (1C)alkoxy-(2C)alkyl; and wherein phenyl is substituted by one or three substituents independently selected from nitro or (1C)alkoxy; (11a) R1 is a group of formula: X1-Y1-X2-Y2 wherein: X1 is phenyl, fluorene, (1C)alkyl or -(CRaRb)q-S-S-, where Ra and Rb are each independently selected from hydrogen or (1C)alkyl, and where q is 0 or 1; Y1is absent or (2C)alkyl; X2 is absent or is -S-S-, -O-C(O)-NRc-, or -S-C(O)-, where each Rc is hydrogen; and Y2 is selected from hydrogen, (1C)alkoxy-(2C)alkyl, or-[CH2-CH2-O]p-CH2-CH2-OH, wherein p is 3; and23 wherein phenyl is substituted by one or three substituents independently selected from nitro or (1C)alkoxy; (12) R1is a group selected from:24 wherein denotes the point of attachment; (12a) R1is a group selected from:25wherein denotes the point of attachment; (13) R1is a group selected from:wherein denotes the point of attachment; (13a) R1 is a group selected from:26wherein denotes the point of attachment; (14) R1 is a group selected from:27wherein denotes the point of attachment; (14a) R1 is a group selected from:28 wherein denotes the point of attachment; (15) R1is a group selected from:wherein denotes the point of attachment; (16) R1is:wherein denotes the point of attachment;

[0066] In a particular group of compounds of the invention, the compounds have the structural Formula (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf) shown below:Ĩl-llla)Ĩl-lllc)Ĩl-llle)32(I-IIIf) wherein m, L and PL are as defined herein.

[0067] In any of the compounds of Formula (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), m may be 1. In any of the compounds of Formula (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), m may be 3. Most suitably, in any of the compounds of Formula (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), m is 2. Linker L

[0068] The linker group L may be any suitable linker moiety that links the N atom to PL. The linker group L may be any length, and this may be dependent on the size of the payload PL. For example, the linker group L may be a peptide comprising a plurality of amino acids (e.g., 2-50) linked by peptide bonds. Alternatively, the linker group L may be a polyethylene glycol chain (e.g., PEG10k) comprising 100s of bridging chain atoms. It will be understood that a “bridging atom chain” and “bridging chain atoms” (which are used interchangeably throughout the specification) refers to the minimum number of chain atoms in the linking group L directly linking the N atom to PL. For the purpose of illustration only, a propyl linking group (i.e., -CH2- CH2-CH2-) is a three bridging atom chain. In the context of the linker it will also be understood that the term “alkylene linker” refers to the minimum number of alkylene atoms directly linking the N atom to PL. For the purpose of illustration only, a (3C)alkylene linker will be understood to mean that three carbon atoms directly link the N atom to PL. This does not take into account for any additional optional groups in the linker L, meaning that -CH2-CH2-C(O)NH-CH2- would still be considered as a (3C)alkylene linker. (17) L is a 1-1000 bridging atom chain linking the N atom to PL, wherein the 1-1000 bridging33 atom chain is optionally substituted by one or more group(s) LX; (18) L is a 1-750 bridging atom chain linking the N atom to PL, wherein the 1-750 bridging atom chain is optionally substituted by one or more group(s) LX; (19) L is a 2-500 bridging atom chain linking the N atom to PL, wherein the 2-500 bridging atom chain is optionally substituted by one or more group(s) LX; (20) L is a 5-250 bridging atom chain linking the N atom to PL, wherein the 5-250 bridging atom chain is optionally substituted by one or more group(s) LX; (21) L is a 5-100 bridging atom chain linking the N atom to PL, wherein the 5-100 bridging atom chain is optionally substituted by one or more group(s) LX; (22) L is a 5-50 bridging atom chain linking the N atom to PL, wherein the 5-50 bridging atom chain is optionally substituted by one or more group(s) LX; (23) L is a 5-40 bridging atom chain linking the N atom to PL, wherein the 5-40 bridging atom chain is optionally substituted by one or more group(s) LX; (24) L is a 7-30 bridging atom chain linking the N atom to PL, wherein the 7-30 bridging atom chain is optionally substituted by one or more group(s) LX;

[0069] The linker group L may comprise one or more groups selected from an alkylenediamine moiety, an alkynylene moiety, a polyethylene glycol moiety, an amino acid residue, an arylene-containing moiety, a heteroarylene-containing moiety, a heterocyclyl- containing moiety, a cycloalkyl-containing moiety and combinations thereof. It will be understood that these groups can contribute to the number of bridging chain atoms when they are part of the moiety directly linking the N atom to PL. The alkylenediamine moiety refers to a functional group that contains or is derived from an alkylenediamine moiety, such as, an ethylenediamine. The alkynylene moiety refers to a functional group that comprises one or more alkynylene moieties, such as ethynylene. The polyethylene glycol moiety refers to a functional group that comprises one or more alkylene glycol moieties, such as, one or more ethylene glycol moieties. The amino acid residues refer to both natural and unnatural amino acid residues. The amino acid residue may also comprise two or more amino acids, such as, for example, dipeptide and tripeptide moieties. Suitable amino acid residues include Phe, Lys, Val, Ala, Cit, Leu, Ile, Arg, and Trp residues. The arylene-containing moiety refers to a functional group that comprises one or more arylene groups. Suitably, the arylene will be a 6- membered arylene such as phenylene. The heteroarylene-containing moiety refers to a functional group that comprises one or more heteroarylene groups. The heterocyclyl- containing moiety refers to a functional group that comprises one or more heterocycle groups.34 The cycloalkyl-containing moiety refers to a functional group that comprises one or more cycloalkyl groups. Suitably, the linker group L comprises 1-20 of the aforementioned groups. More suitably, the linker group L comprises 1-15 of the aforementioned groups. Even more suitably, the linker group L comprises 1-10 of the aforementioned groups. Yet even more suitably, the linker group L comprises 1-5 of the aforementioned groups.

[0070] In some embodiments, the linker group L comprises 1-10 groups selected from an alkylenediamine moiety, an alkynylene moiety, a polyethylene glycol moiety, an amino acid residue, an arylene-containing moiety, a heterocyclyl-containing moiety and combinations thereof. Suitably, the linker group L comprises 1-5 groups selected from an alkylenediamine moiety, an alkynylene moiety, a polyethylene glycol moiety, an amino acid residue, an arylene- containing moiety, a heterocyclyl-containing moiety and combinations thereof. (25) L is a (1-35C) alkylene linker, wherein the alkylene chain optionally further comprises one or more -O-, -C(O)-, -C(O)NRd-, -NRdC(O)-, -C(O)O-, -OC(O), -arylene-, - heterocyclyl- and / or -alkynylene- group(s) within the alkylene chain, where each Rd is independently hydrogen or (1-2C)alkyl and wherein the alkylene chain is optionally substituted by one or more group(s) LX; (26) L is a (2-30C) alkylene linker, wherein the alkylene chain optionally further comprises one or more -O-, -C(O)-, -C(O)NRd-, -NRdC(O)-, -C(O)O-, -OC(O), -arylene-, - heterocyclyl- and / or -alkynylene- group(s) within the alkylene chain, where each Rd is independently hydrogen or (1-2C)alkyl and wherein the alkylene chain is optionally substituted by one or more group(s) LX; (27) L is a (2-30C) alkylene linker, wherein the alkylene chain optionally further comprises one or more -O-, -C(O)-, -C(O)NRd-, -NRdC(O)-, -C(O)O-, -OC(O), -arylene-, - heterocyclyl- and / or -alkynylene- group(s) within the alkylene chain, where each Rd is independently hydrogen or (1-2C)alkyl and wherein the alkylene chain is optionally substituted by one or more group(s) LX; (28) L is a (2-25C) alkylene linker, wherein the alkylene chain optionally further comprises one or more -O-, -C(O)-, -C(O)NRd-, -NRdC(O)-, -C(O)O-, -OC(O), -arylene-, - heterocyclyl- and / or -alkynylene- group(s) within the alkylene chain, where each Rdis independently hydrogen or (1-2C)alkyl and wherein the alkylene chain is optionally substituted by one or more group(s) LX; (29) L is a (2-20C) alkylene linker, wherein the alkylene chain optionally further comprises one or more -O-, -C(O)-, -C(O)NRd-, -NRdC(O)-, -C(O)O-, -OC(O), -arylene-, -35 heterocyclyl- and / or -alkynylene- group(s) within the alkylene chain, where each Rdis independently hydrogen or (1-2C)alkyl and wherein the alkylene chain is optionally substituted by one or more group(s) LX; (30) L is a (2-15C) alkylene linker, wherein the alkylene chain optionally further comprises one or more -O-, -C(O)-, -C(O)NRd-, -NRdC(O)-, -C(O)O-, -OC(O), -arylene-, - heterocyclyl- and / or -alkynylene- group(s) within the alkylene chain, where each Rdis independently hydrogen or (1-2C)alkyl and wherein the alkylene chain is optionally substituted by one or more group(s) LX; (31) L is a (2-15C) alkylene linker, wherein the alkylene chain further comprises one or more -O-, -C(O)-, -C(O)NRd-, -NRdC(O)-, -C(O)O-, -OC(O), -phenylene-, -pyrrolidine-, - piperazine-, -piperidine- and / or -C≡C- group(s) within the alkylene chain, where each Rd is independently hydrogen or (1-2C)alkyl and wherein the alkylene chain is optionally substituted by one or more group(s) LX; (32) L is a (2-15C) alkylene linker, wherein the alkylene chain further comprises one or more -O-, -C(O)-, -C(O)NRd-, -NRdC(O)-, -C(O)O-, -OC(O), -phenylene-, -pyrrolidine-, - piperazine-, -piperidine- and / or -C≡C- groups within the alkylene chain, where each Rd is independently hydrogen or (1C)alkyl and wherein the alkylene chain is optionally substituted by one or more group(s) LX; (33) L is a (2-15C) alkylene linker, wherein the alkylene chain further comprises one to fifteen -O-, -C(O)-, -C(O)NRd-, -NRdC(O)-, -C(O)O-, -OC(O), -phenylene-, -pyrrolidine- , -piperazine-, -piperidine- and / or -C≡C- group(s) within the alkylene chain, where each Rd is independently hydrogen or (1C)alkyl and wherein the alkylene chain is optionally substituted by one or more group(s) LX; (34) L is a (2-15C) alkylene linker, wherein the alkylene chain further comprises one to fifteen -O-, -C(O)-, -C(O)NRd-, -NRdC(O)-, -OC(O), -phenylene-, -pyrrolidine-, - piperazine- and / or -C≡C- group(s) within the alkylene chain, where each Rd is independently hydrogen or (1C)alkyl and wherein the alkylene chain is optionally substituted by one or more group(s) LX; (34a) L is a (2-15C) alkylene linker, wherein the alkylene chain further comprises one to fifteen -O-, -C(O)-, -C(O)NRd-, -NRdC(O)-, -C(O)O-, -OC(O), -phenylene-, -pyrrolidine-, - piperazine- and / or -C≡C- group(s) within the alkylene chain, where each Rdis independently hydrogen or (1C)alkyl and wherein the alkylene chain is optionally substituted by one or more group(s) LX; (35) L is a (2-15C) alkylene linker, wherein the alkylene chain further comprises one to four36 -O- groups, one or two -C(O)- groups, one to four -C(O)NRd- groups, one to three - NRdC(O)- groups, one or two -OC(O) groups, one or two -phenylene- groups, one or two -pyrrolidine- groups, one or two -piperazine- groups and / or one or two -C≡C- groups within the alkylene chain, where each Rdis independently hydrogen or (1C)alkyl and wherein the alkylene chain is optionally substituted by one or more group(s) LX; (35a) L is a (2-15C) alkylene linker, wherein the alkylene chain further comprises one to four -O- groups, one or two -C(O)- groups, one to four -C(O)NRd- groups, one to three -NRdC(O)- groups, one or two -C(O)O- groups, one or two -OC(O) groups, one or two -phenylene- groups, one or two -pyrrolidine- groups, one or two -piperazine- groups and / or one or two -C≡C- groups within the alkylene chain, where each Rd is independently hydrogen or (1C)alkyl and wherein the alkylene chain is optionally substituted by one or more group(s) LX; (36) L is a (2-15C) alkylene linker, wherein the alkylene chain further comprises two to four -O- groups, one or two -C(O)- groups, one to three -C(O)NRd- groups, one or two - NRdC(O)- groups, one -OC(O) group, one -phenylene- group, one -pyrrolidine- group, one -piperazine- group and / or one -C≡C- group(s) within the alkylene chain, where each Rd is independently hydrogen or (1C)alkyl and wherein the alkylene chain is optionally substituted by one or more group(s) LX; (36a) L is a (2-15C) alkylene linker, wherein the alkylene chain further comprises two to four -O- groups, one or two -C(O)- groups, one to three -C(O)NRd- groups, one or two -NRdC(O)- groups, one -C(O)O group, one -OC(O) group, one -phenylene- group, one -pyrrolidine- group, one -piperazine- group and / or one -C≡C- group(s) within the alkylene chain, where each Rd is independently hydrogen or (1C)alkyl and wherein the alkylene chain is optionally substituted by one or more group(s) LX; (37) L is a (2-15C) alkylene linker, wherein the alkylene chain further comprises one to four -O- groups, one or two -C(O)- groups, one to four -C(O)NRd- groups, one to three - NRdC(O)- groups, one or two -OC(O) groups, one or two -phenylene- groups, one or two -pyrrolidine- groups, one or two -piperazine- groups and / or one or two -C≡C- groups within the alkylene chain, where each Rd is independently hydrogen or (1C)alkyl and wherein the alkylene chain is optionally substituted by one, two or three group(s) LX; (37a) L is a (2-15C) alkylene linker, wherein the alkylene chain further comprises one to four -O- groups, one or two -C(O)- groups, one to four -C(O)NRd- groups, one to three -NRdC(O)- groups, one or two -C(O)O groups, one or two -OC(O) groups, one or two -phenylene- groups, one or two -pyrrolidine- groups, one or two -piperazine- groups and / or one or two -C≡C- groups within the alkylene chain, where each Rdis independently hydrogen or (1C)alkyl and wherein37 the alkylene chain is optionally substituted by one, two or three group(s) LX; (38) L is a (2-15C) alkylene linker, wherein the alkylene chain further comprises two to four -O- groups, one or two -C(O)- groups, one to three -C(O)NRd- groups, one or two - NRdC(O)- groups, one -OC(O) group, one -phenylene- group, one -pyrrolidine- group, one -piperazine- group and / or one -C≡C- group(s) within the alkylene chain, where each Rdis independently hydrogen or (1C)alkyl and wherein the alkylene chain is optionally substituted by one or two group(s) LX; (38a) L is a (2-15C) alkylene linker, wherein the alkylene chain further comprises two to four -O- groups, one or two -C(O)- groups, one to three -C(O)NRd- groups, one or two -NRdC(O)- groups, one -C(O)O group, one -OC(O) group, one -phenylene- group, one -pyrrolidine- group, one -piperazine- group and / or one -C≡C- group(s) within the alkylene chain, where each Rd is independently hydrogen or (1C)alkyl and wherein the alkylene chain is optionally substituted by one or two group(s) LX; (39) L is a (2-15C) alkylene linker, wherein the alkylene chain further comprises: (i) three -C(O)NH- groups, one -OC(O) group and one -phenylene- group within the alkylene chain; (ii) two or three -O- groups, one -C(O)- group, one -C(O)NH- group and one - NHC(O)- group within the alkylene chain; (iii) one -C(O)NH group and two -NHC(O)- groups within the alkylene chain; (iv) two or three -O- groups, one -C(O)- group, one -C(O)NH- group and one - NHC(O)- group within the alkylene chain; (v) two or three -O- groups, one -C(O)- group, three -C(O)NH- groups, one - NHC(O)- group, one -OC(O) group, one -phenylene- group and one - pyrrolidine- group within the alkylene chain; (vi) four -O- groups, two -C(O)NH- groups and one -C≡C- group within the alkylene chain; (vii) one -C(O)- group and one -piperazine- group within the alkylene chain; or (viii) four -O- groups, one -C(O)- group and three -C(O)NH- groups within the alkylene chain; and wherein the alkylene chain is optionally substituted by one or two group(s) LX; (39a) L is a (2-15C) alkylene linker, wherein the alkylene chain further comprises: (i) three -C(O)NH- groups, one -OC(O) group and one -phenylene- group within38 the alkylene chain; (ii) two or three -O- groups, one -C(O)- group, one -C(O)NH- group and one - NHC(O)- group within the alkylene chain; (iii) one -C(O)NH group and two -NHC(O)- groups within the alkylene chain; (iv) two or three -O- groups, one -C(O)- group, one -C(O)NH- group and one - NHC(O)- group within the alkylene chain; (v) two or three -O- groups, one -C(O)- group, three -C(O)NH- groups, one - NHC(O)- group, one -OC(O) group, one -phenylene- group and one - pyrrolidine- group within the alkylene chain; (vi) four -O- groups, two -C(O)NH- groups and one -C≡C- group within the alkylene chain; (vii) one -C(O)- group and one -piperazine- group within the alkylene chain; (viii) four -O- groups, one -C(O)- group and three -C(O)NH- groups within the alkylene chain; or (ix) one -C(O)O- group within the alkylene chain; and wherein the alkylene chain is optionally substituted by one or two group(s) LX; (40) L is: (i) a (4C) alkylene linker, wherein the alkylene chain further comprises three - C(O)NH- groups, one -OC(O) group and one -phenylene- group within the alkylene chain, and wherein the alkylene chain is substituted by two groups LX; (ii) a (10C) alkylene linker, wherein the alkylene chain further comprises two -O- groups, one -C(O)- group, one -C(O)NH- group and one -NHC(O)- group within the alkylene chain; (iii) a (12C) alkylene linker, wherein the alkylene chain further comprises three -O- groups, one -C(O)- group, one -C(O)NH- group and one -NHC(O)- group within the alkylene chain; (iv) a (6C) alkylene linker, wherein the alkylene chain further comprises one - C(O)NH group and two -NHC(O)- groups within the alkylene chain, and wherein the alkylene chain is substituted by two groups LX; (v) a (10C) alkylene linker, wherein the alkylene chain further comprises two -O- groups, one -C(O)- group, one -C(O)NH- group and one -NHC(O)- group within the alkylene chain;39 (vi) a (12C) alkylene linker, wherein the alkylene chain further comprises three -O- groups, one -C(O)- group, one -C(O)NH- group and one -NHC(O)- group within the alkylene chain; (vii) a (12C) alkylene linker, wherein the alkylene chain further comprises two -O- groups, one -C(O)- group, three -C(O)NH- groups, one -NHC(O)- group, one - OC(O) group, one -phenylene- group and one -pyrrolidine- group within the alkylene chain; (viii) a (14C) alkylene linker, wherein the alkylene chain further comprises three -O- groups, one -C(O)- group, three -C(O)NH- groups, one -NHC(O)- group, one - OC(O) group, one -phenylene- group and one -pyrrolidine- group within the alkylene chain; (ix) a (13C) alkylene linker, wherein the alkylene chain further comprises four -O- groups, two -C(O)NH- groups and one -C≡C- group within the alkylene chain; (x) a (2C) alkylene linker, wherein the alkylene chain further comprises one -C(O)- group and one -piperazine- group within the alkylene chain; or (xi) a (15C) alkylene linker, wherein the alkylene chain further comprises four -O- groups, one -C(O)- group and three -C(O)NH- groups within the alkylene chain, and wherein the alkylene chain is substituted by one group LX; (40a) L is: (i) a (4C) alkylene linker, wherein the alkylene chain further comprises three - C(O)NH- groups, one -OC(O) group and one -phenylene- group within the alkylene chain, and wherein the alkylene chain is substituted by two groups LX; (ii) a (10C) alkylene linker, wherein the alkylene chain further comprises two -O- groups, one -C(O)- group, one -C(O)NH- group and one -NHC(O)- group within the alkylene chain; (iii) a (12C) alkylene linker, wherein the alkylene chain further comprises three -O- groups, one -C(O)- group, one -C(O)NH- group and one -NHC(O)- group within the alkylene chain; (iv) a (6C) alkylene linker, wherein the alkylene chain further comprises one - C(O)NH group and two -NHC(O)- groups within the alkylene chain, and wherein the alkylene chain is substituted by two groups LX; (v) a (10C) alkylene linker, wherein the alkylene chain further comprises two -O- groups, one -C(O)- group, one -C(O)NH- group and one -NHC(O)- group within40 the alkylene chain; (vi) a (12C) alkylene linker, wherein the alkylene chain further comprises three -O- groups, one -C(O)- group, one -C(O)NH- group and one -NHC(O)- group within the alkylene chain; (vii) a (12C) alkylene linker, wherein the alkylene chain further comprises two -O- groups, one -C(O)- group, three -C(O)NH- groups, one -NHC(O)- group, one - OC(O) group, one -phenylene- group and one -pyrrolidine- group within the alkylene chain; (viii) a (14C) alkylene linker, wherein the alkylene chain further comprises three -O- groups, one -C(O)- group, three -C(O)NH- groups, one -NHC(O)- group, one - OC(O) group, one -phenylene- group and one -pyrrolidine- group within the alkylene chain; (ix) a (13C) alkylene linker, wherein the alkylene chain further comprises four -O- groups, two -C(O)NH- groups and one -C≡C- group within the alkylene chain; (x) a (2C) alkylene linker, wherein the alkylene chain further comprises one -C(O)- group and one -piperazine- group within the alkylene chain; or (xi) a (15C) alkylene linker, wherein the alkylene chain further comprises four -O- groups, one -C(O)- group and three -C(O)NH- groups within the alkylene chain, and wherein the alkylene chain is substituted by one group LX; (xii) a (2C) alkylene linker, wherein the alkylene chain further comprises one - C(O)O- group within the alkylene chain; (41) L is a linker having the formula: -L1-Z1-L2-Z2-L3-Z3-L4-Z4-L5-Z5-L6-Z6- wherein L1 is a (1-4C)alkylene; Z1 is selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; L2is a (1-10C)alkylene, a heterocycle or a group of the formula -[CH2CH2]-[O- CH2CH2]a-, wherein a is 1 to 6; Z2 is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; L3is absent, a (1-10C)alkylene, a (2-10C)alkynylene or a group of the formula - [CH2CH2]-[O-CH2CH2]b-, wherein b is 1 to 6; Z3is absent or is selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O-, -OC(O)-;41 L4is absent or is selected from (1-10C)alkylene, (1-10C)alkylene-arylene or a group of the formula -[CH2CH2]-[O-CH2CH2]c-, wherein c is 1 to 6; Z4is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; L5is absent, a (1-10C)alkylene or a heterocycle; Z5is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; L6is absent, a (1-10C)alkylene or a (1-10C)alkylene-arylene; Z6 is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; wherein each Re is independently hydrogen or (1-2C)alkyl; and wherein any one or more of L1, Z1, L2, Z2, L3, Z3, L4, Z4, L5, Z5, L6 and / or Z6 is optionally substituted by a group LX; (41a) L is a linker having the formula: -L1-Z1-L2-Z2-L3-Z3-L4-Z4-L5-Z5-L6-Z6- wherein L1 is a (1-4C)alkylene; Z1 is selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; L2 is a absent, (1-10C)alkylene, a heterocycle or a group of the formula -[CH2CH2]-[O- CH2CH2]a-, wherein a is 1 to 6; Z2 is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; L3 is absent, a (1-10C)alkylene, a (2-10C)alkynylene or a group of the formula - [CH2CH2]-[O-CH2CH2]b-, wherein b is 1 to 6; Z3 is absent or is selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O-, -OC(O)-; L4 is absent or is selected from (1-10C)alkylene, (1-10C)alkylene-arylene or a group of the formula -[CH2CH2]-[O-CH2CH2]c-, wherein c is 1 to 6; Z4 is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; L5 is absent, a (1-10C)alkylene or a heterocycle; Z5 is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; L6is absent, a (1-10C)alkylene or a (1-10C)alkylene-arylene; Z6 is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; wherein each Re is independently hydrogen or (1-2C)alkyl; and42 wherein any one or more of L1, Z1, L2, Z2, L3, Z3, L4, Z4, L5, Z5, L6and / or Z6is optionally substituted by a group LX; (42) L is a linker having the formula: -L1-Z1-L2-Z2-L3-Z3-L4-Z4-L5-Z5-L6-Z6- wherein L1is a (1-4C)alkylene; Z1 is selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; L2 is a (1-8C)alkylene, a heterocycle or a group of the formula -[CH2CH2]-[O-CH2CH2]a- , wherein a is 1 to 6; Z2 is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; L3 is absent, a (1-8C)alkylene, a (2-8C)alkynylene or a group of the formula -[CH2CH2]- [O-CH2CH2]b-, wherein b is 1 to 6; Z3 is absent or is selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O-, -OC(O)-; L4 is absent or is selected from (1-8C)alkylene, (1-8C)alkylene-arylene or a group of the formula -[CH2CH2]-[O-CH2CH2]c-, wherein c is 1 to 6; Z4 is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; L5 is absent, a (1-8C)alkylene or a heterocycle; Z5 is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; L6 is absent, a (1-8C)alkylene or a (1-8C)alkylene-arylene; Z6 is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; wherein each Re is independently hydrogen or (1-2C)alkyl; and wherein any one or more of L1, Z1, L2, Z2, L3, Z3, L4, Z4, L5, Z5, L6 and / or Z6 is optionally substituted by a group LX; (42a) L is a linker having the formula: -L1-Z1-L2-Z2-L3-Z3-L4-Z4-L5-Z5-L6-Z6- wherein L1is a (1-4C)alkylene; Z1 is selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-;43 L2is absent, a (1-8C)alkylene, a heterocycle or a group of the formula -[CH2CH2]-[O- CH2CH2]a-, wherein a is 1 to 6; Z2is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; L3is absent, a (1-8C)alkylene, a (2-8C)alkynylene or a group of the formula -[CH2CH2]- [O-CH2CH2]b-, wherein b is 1 to 6; Z3is absent or is selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O-, -OC(O)-; L4 is absent or is selected from (1-8C)alkylene, (1-8C)alkylene-arylene or a group of the formula -[CH2CH2]-[O-CH2CH2]c-, wherein c is 1 to 6; Z4 is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; L5 is absent, a (1-8C)alkylene or a heterocycle; Z5 is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; L6 is absent, a (1-8C)alkylene or a (1-8C)alkylene-arylene; Z6 is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; wherein each Re is independently hydrogen or (1-2C)alkyl; and wherein any one or more of L1, Z1, L2, Z2, L3, Z3, L4, Z4, L5, Z5, L6 and / or Z6 is optionally substituted by a group LX; (43) L is a linker having the formula: -L1-Z1-L2-Z2-L3-Z3-L4-Z4-L5-Z5-L6-Z6- wherein L1 is a (1-4C)alkylene; Z1 is selected from -O-, -C(O)-, -C(O)NRe- or -NReC(O)-; L2 is a (1-4C)alkylene, a nitrogen-containing heterocycle or a group of the formula - [CH2CH2]-[O-CH2CH2]a-, wherein a is 1 to 6; Z2 is absent or selected from -O-, -C(O)-, -C(O)NRe- or -NReC(O)-; L3 is absent, a (1-4C)alkylene, a (2-4C)alkynylene or a group of the formula -[CH2CH2]- [O-CH2CH2]b-, wherein b is 1 to 6; Z3is absent or is selected from -O-, -C(O)-, -C(O)NRe- or -NReC(O)-; L4 is absent or is selected from (1-4C)alkylene, (1-4C)alkylene-arylene or a group of the formula -[CH2CH2]-[O-CH2CH2]c-, wherein c is 1 to 6; Z4is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-;44 L5is absent, a (1-4C)alkylene or a nitrogen-containing heterocycle; Z5is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; L6is absent, a (1-4C)alkylene or a (1-4C)alkylene-arylene; Z6is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; wherein each Reis independently hydrogen or (1C)alkyl; and wherein any one or more of L1, Z1, L2, Z2, L3, Z3, L4, Z4, L5, Z5, L6and / or Z6is optionally substituted by a group LX; (43a) L is a linker having the formula: -L1-Z1-L2-Z2-L3-Z3-L4-Z4-L5-Z5-L6-Z6- wherein L1 is a (1-4C)alkylene; Z1 is selected from -O-, -C(O)-, -C(O)O-, -C(O)NRe- or -NReC(O)-; L2 is absent, a (1-4C)alkylene, a nitrogen-containing heterocycle or a group of the formula -[CH2CH2]-[O-CH2CH2]a-, wherein a is 1 to 6; Z2 is absent or selected from -O-, -C(O)-, -C(O)NRe- or -NReC(O)-; L3 is absent, a (1-4C)alkylene, a (2-4C)alkynylene or a group of the formula -[CH2CH2]- [O-CH2CH2]b-, wherein b is 1 to 6; Z3 is absent or is selected from -O-, -C(O)-, -C(O)NRe- or -NReC(O)-; L4 is absent or is selected from (1-4C)alkylene, (1-4C)alkylene-arylene or a group of the formula -[CH2CH2]-[O-CH2CH2]c-, wherein c is 1 to 6; Z4 is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; L5 is absent, a (1-4C)alkylene or a nitrogen-containing heterocycle; Z5 is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; L6 is absent, a (1-4C)alkylene or a (1-4C)alkylene-arylene; Z6 is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; wherein each Re is independently hydrogen or (1C)alkyl; and wherein any one or more of L1, Z1, L2, Z2, L3, Z3, L4, Z4, L5, Z5, L6and / or Z6is optionally substituted by a group LX; (44) L is a linker having the formula:45 -L1-Z1-L2-Z2-L3-Z3-L4-Z4-L5-Z5-L6-Z6- wherein L1is a (1-2C)alkylene; Z1is selected from -C(O)- or -C(O)NRe-; L2is a (1-2C)alkylene, a 6-membered nitrogen-containing heterocycle or a group of the formula -[CH2CH2]-[O-CH2CH2]a-, wherein a is 2 to 4; Z2 is absent or selected from -C(O)NRe- or -NReC(O)-; L3 is absent, a (1-2C)alkylene, a (2-3C)alkynylene or a group of the formula -[CH2CH2]- [O-CH2CH2]b-, wherein b is 2 to 4; Z3 is absent or is selected from -C(O)-, -C(O)NRe- or -NReC(O)-; L4 is absent or is selected from (1-2C)alkylene, (1-2C)alkylene-arylene or a group of the formula -[CH2CH2]-[O-CH2CH2]c-, wherein c is 2 to 4; Z4 is absent or selected from -C(O)- or -OC(O)-; L5 is absent, a (1-2C)alkylene or a 5-memebered nitrogen-containing heterocycle; Z5 is absent or selected from -C(O)NRe- or -OC(O)-; L6 is absent, a (1-2C)alkylene or a (1-2C)alkylene-arylene; Z6 is absent or -OC(O)-; wherein each Re is independently hydrogen or (1C)alkyl; and wherein any one or more of L1, Z1, L2, Z2, L3, Z3, L4, Z4, L5, Z5, L6 and / or Z6 is optionally substituted by a group LX; (44a) L is a linker having the formula: -L1-Z1-L2-Z2-L3-Z3-L4-Z4-L5-Z5-L6-Z6- wherein L1 is a (1-2C)alkylene; Z1 is selected from -C(O)-, -C(O)O- or -C(O)NRe-; L2 is absent, a (1-2C)alkylene, a 6-membered nitrogen-containing heterocycle or a group of the formula -[CH2CH2]-[O-CH2CH2]a-, wherein a is 2 to 4; Z2 is absent or selected from -C(O)NRe- or -NReC(O)-;46 L3is absent, a (1-2C)alkylene, a (2-3C)alkynylene or a group of the formula -[CH2CH2]- [O-CH2CH2]b-, wherein b is 2 to 4; Z3is absent or is selected from -C(O)-, -C(O)NRe- or -NReC(O)-; L4is absent or is selected from (1-2C)alkylene, (1-2C)alkylene-arylene or a group of the formula -[CH2CH2]-[O-CH2CH2]c-, wherein c is 2 to 4; Z4is absent or selected from -C(O)- or -OC(O)-; L5 is absent, a (1-2C)alkylene or a 5-memebered nitrogen-containing heterocycle; Z5 is absent or selected from -C(O)NRe- or -OC(O)-; L6 is absent, a (1-2C)alkylene or a (1-2C)alkylene-arylene; Z6 is absent or -OC(O)-; wherein each Re is independently hydrogen or (1C)alkyl; and wherein any one or more of L1, Z1, L2, Z2, L3, Z3, L4, Z4, L5, Z5, L6 and / or Z6 is optionally substituted by a group LX; (45) L is a linker having the formula: -L1-Z1-L2-Z2-L3-Z3-L4-Z4-L5-Z5-L6-Z6- wherein L1 is a (1-2C)alkylene; Z1 is selected from -C(O)- or -C(O)NRe-; L2 is a (1-2C)alkylene, a 6-membered nitrogen-containing heterocycle or a group of the formula -[CH2CH2]-[O-CH2CH2]a-, wherein a is 2 to 4; Z2 is absent or selected from -C(O)NRe- or -NReC(O)-; L3 is absent, a (1-2C)alkylene, a (2-3C)alkynylene or a group of the formula -[CH2CH2]- [O-CH2CH2]b-, wherein b is 2 to 4; Z3 is absent or is selected from -C(O)-, -C(O)NRe- or -NReC(O)-; L4 is absent or is selected from (1-2C)alkylene, (1-2C)alkylene-arylene or a group of the formula -[CH2CH2]-[O-CH2CH2]c-, wherein c is 2 to 4; Z4is absent or selected from -C(O)- or -OC(O)-; L5 is absent, a (1-2C)alkylene or a 5-memebered nitrogen-containing heterocycle; Z5 is absent or selected from -C(O)NRe- or -OC(O)-;47 L6is absent, a (1-2C)alkylene or a (1-2C)alkylene-arylene; Z6is absent or -OC(O)-; wherein each Reis independently hydrogen or (1C)alkyl; and wherein any one or more of L2, L3or L4is optionally substituted by a group LX; (45a) L is a linker having the formula: -L1-Z1-L2-Z2-L3-Z3-L4-Z4-L5-Z5-L6-Z6- wherein L1 is a (1-2C)alkylene; Z1 is selected from -C(O)-, -C(O)O- or -C(O)NRe-; L2 is absent, a (1-2C)alkylene, a 6-membered nitrogen-containing heterocycle or a group of the formula -[CH2CH2]-[O-CH2CH2]a-, wherein a is 2 to 4; Z2 is absent or selected from -C(O)NRe- or -NReC(O)-; L3 is absent, a (1-2C)alkylene, a (2-3C)alkynylene or a group of the formula -[CH2CH2]- [O-CH2CH2]b-, wherein b is 2 to 4; Z3 is absent or is selected from -C(O)-, -C(O)NRe- or -NReC(O)-; L4 is absent or is selected from (1-2C)alkylene, (1-2C)alkylene-arylene or a group of the formula -[CH2CH2]-[O-CH2CH2]c-, wherein c is 2 to 4; Z4 is absent or selected from -C(O)- or -OC(O)-; L5 is absent, a (1-2C)alkylene or a 5-memebered nitrogen-containing heterocycle; Z5 is absent or selected from -C(O)NRe- or -OC(O)-; L6 is absent, a (1-2C)alkylene or a (1-2C)alkylene-arylene; Z6 is absent or -OC(O)-; wherein each Re is independently hydrogen or (1C)alkyl; and wherein any one or more of L2, L3 or L4 is optionally substituted by a group LX; (46) L is a linker having the formula: -L1-Z1-L2-Z2-L3-Z3-L4-Z4-L5-Z5-L6-Z6- wherein L1 is a (1-2C)alkylene; Z1 is selected from -C(O)- or -C(O)NH-;48 L2is a (1-2C)alkylene, a 6-membered nitrogen-containing heterocycle or a group of the formula -[CH2CH2]-[O-CH2CH2]a-, wherein a is 2 to 4; Z2is absent or selected from -C(O)NH- or -NHC(O)-; L3is absent, a (1-2C)alkylene, a (2-3C)alkynylene or a group of the formula -[CH2CH2]- [O-CH2CH2]b-, wherein b is 2 to 4; Z3is absent or is selected from -C(O)-, -C(O)NH- or -NHC(O)-; L4 is absent or is selected from (1-2C)alkylene, (1-2C)alkylene-arylene or a group of the formula -[CH2CH2]-[O-CH2CH2]c-, wherein c is 2 to 4; Z4 is absent or selected from -C(O)- or -OC(O)-; L5 is absent or a 5-memebered nitrogen-containing heterocycle; Z5 is absent or selected from -C(O)NH- or -OC(O)-; L6 is absent or a (1-2C)alkylene-arylene; Z6 is absent or -OC(O)-; wherein any one or more of L2, L3 or L4 is optionally substituted by a group LX; (46a) L is a linker having the formula: -L1-Z1-L2-Z2-L3-Z3-L4-Z4-L5-Z5-L6-Z6- wherein L1 is a (1-2C)alkylene; Z1 is selected from -C(O)-, -C(O)O- or -C(O)NH-; L2 is absent, a (1-2C)alkylene, a 6-membered nitrogen-containing heterocycle or a group of the formula -[CH2CH2]-[O-CH2CH2]a-, wherein a is 2 to 4; Z2 is absent or selected from -C(O)NH- or -NHC(O)-; L3 is absent, a (1-2C)alkylene, a (2-3C)alkynylene or a group of the formula -[CH2CH2]- [O-CH2CH2]b-, wherein b is 2 to 4; Z3 is absent or is selected from -C(O)-, -C(O)NH- or -NHC(O)-; L4 is absent or is selected from (1-2C)alkylene, (1-2C)alkylene-arylene or a group of the formula -[CH2CH2]-[O-CH2CH2]c-, wherein c is 2 to 4; Z4 is absent or selected from -C(O)- or -OC(O)-; L5 is absent or a 5-memebered nitrogen-containing heterocycle;49 Z5is absent or selected from -C(O)NH- or -OC(O)-; L6is absent or a (1-2C)alkylene-arylene; Z6is absent or -OC(O)-; wherein any one or more of L2, L3or L4is optionally substituted by a group LX; (47) L is a linker having the formula: -L1-Z1-L2-Z2-L3-Z3-L4-Z4-L5-Z5-L6-Z6- wherein L1 is a (1-2C)alkylene; Z1 is selected from -C(O)- or -C(O)NH-; L2 is a (1-2C)alkylene, a piperidine or a group of the formula -[CH2CH2]-[O-CH2CH2]a-, wherein a is 2 to 4; Z2 is absent or selected from -C(O)NH- or -NHC(O)-; L3 is absent, a (1-2C)alkylene, a (3C)alkynylene or a group of the formula -[CH2CH2]- [O-CH2CH2]b-, wherein b is 2 or 3; Z3 is absent or is selected from -C(O)-, -C(O)NH- or -NHC(O)-; L4 is absent or is selected from (1-2C)alkylene, (1C)alkylene-phenylene (i.e., - phenylene-CH2-) or a group of the formula -[CH2CH2]-[O-CH2CH2]c-, wherein c is 2 or 3; Z4 is absent or selected from -C(O)- or -OC(O)-; L5 is absent or pyrrolidine; Z5 is absent or selected from -C(O)NH- or -OC(O)-; L6 is absent or a (1C)alkylene-phenylene (i.e., -phenylene-CH2-); Z6 is absent or -OC(O)-; wherein any one or more of L2, L3 or L4 is optionally substituted by a group LX; (47a) L is a linker having the formula: -L1-Z1-L2-Z2-L3-Z3-L4-Z4-L5-Z5-L6-Z6- wherein L1 is a (1-2C)alkylene; Z1 is selected from -C(O)-, -C(O)O- or -C(O)NH-;50 L2is absent, a (1-2C)alkylene, a piperidine or a group of the formula -[CH2CH2]-[O- CH2CH2]a-, wherein a is 2 to 4; Z2is absent or selected from -C(O)NH- or -NHC(O)-; L3is absent, a (1-2C)alkylene, a (3C)alkynylene or a group of the formula -[CH2CH2]- [O-CH2CH2]b-, wherein b is 2 or 3; Z3is absent or is selected from -C(O)-, -C(O)NH- or -NHC(O)-; L4 is absent or is selected from (1-2C)alkylene, (1C)alkylene-phenylene (i.e., - phenylene-CH2-) or a group of the formula -[CH2CH2]-[O-CH2CH2]c-, wherein c is 2 or 3; Z4 is absent or selected from -C(O)- or -OC(O)-; L5 is absent or pyrrolidine; Z5 is absent or selected from -C(O)NH- or -OC(O)-; L6 is absent or a (1C)alkylene-phenylene (i.e., -phenylene-CH2-); Z6 is absent or -OC(O)-; wherein any one or more of L2, L3 or L4 is optionally substituted by a group LX; (48) L is a linker selected from:51wherein denotes the point of attachment to N, denotes the point of attachment to PL, and LXis as defined any one of paragraphs (49) to (55); (48a) L is a linker selected from:53wherein denotes the point of attachment to N, denotes the point of attachment to PL, and LX is as defined any one of paragraphs (49) to (55); (49) LX is a group having the formula: -LX1-ZX1-LX2 wherein LX1 is a (1-10C)alkylene; ZX1 is absent or is selected from -O-, -C(O)-, -C(O)NRf-, -NRfC(O)-, -NRfC(O)O-, -C(O)O- or - OC(O)-; and LX2 is hydrogen, (1-10C)alkyl or -N(Rf)2; wherein each Rf is independently hydrogen or (1-2C)alkyl; (50) LX is a group having the formula: -LX1-ZX1-LX2 wherein LX1 is a (1-8C)alkylene; ZX1 is absent or is selected from -O-, -C(O)-, -C(O)NRf-, -NRfC(O)-, -NRfC(O)O-, -C(O)O- or - OC(O)-; and LX2 is hydrogen, (1-8C)alkyl or -N(Rf)2; wherein each Rf is independently hydrogen or (1-2C)alkyl; (51) LX is a group having the formula: -LX1-ZX1-LX254 wherein LX1is a (1-6C)alkylene; ZX1is absent or is selected from -C(O)NRf-, -NRfC(O)-, -NRfC(O)O- or -C(O)O-; and LX2is hydrogen, (1-6C)alkyl or -N(Rf)2; wherein each Rfis independently hydrogen or (1-2C)alkyl; (52) LXis a group having the formula: -LX1-ZX1-LX2 wherein LX1 is a (1-4C)alkylene; ZX1 is absent or is selected from -C(O)NRf-, -NRfC(O)- or -NRfC(O)O-; and LX2 is hydrogen, (1-4C)alkyl or -N(Rf)2; wherein each Rf is independently hydrogen or (1C)alkyl; (53) LX is a group having the formula: -LX1-ZX1-LX2 wherein LX1 is a (1-4C)alkylene; ZX1 is absent or is selected from -C(O)NH-, -NHC(O)- or -NHC(O)O-; and LX2 is hydrogen, (1-4C)alkyl or -NH2; (54) LX is a group having the formula: -LX1-ZX1-LX2 wherein LX1 is a (1C)alkylene, a (3C)alkylene or a (4C)alkylene; ZX1 is absent or is selected from -C(O)NH-, -NHC(O)- or -NHC(O)O-; and LX2 is hydrogen, (4C)alkyl or -NH2; (55) LX is -CH(CH3)2, -CH2-CH2-CH2-NHC(O)-NH2, -CH2-C(O)NH2, -CH2-CH2-CH2-CH2-NH2 or -CH2-CH2-CH2-CH2-NH-C(O)O-C(CH3)3; Payload PL55 (56) The payload is a drug, a labelling agent or a targeting moiety; (57) The payload is a drug; (58) The payload is a labelling agent; (59) The payload is a targeting moiety; (60) The payload is a drug and the drug is a cytotoxic payload or a therapeutic compound, peptide or polypeptide; (61) The payload is a drug and the drug is a cytotoxin; (62) The payload is a drug and the drug is a biologically active cytotoxic material; (63) The payload is a drug and the drug is selected from the group consisting of auristatins, mayatansines, tubulysins, calicheamicins, duocarmycins, pyrrolobenzodiazepines (in particular pyrrolobenzodiazepine dimers), camptothecin analogues, anthracyclines, amatoxins, protein toxins, immunotoxins, antibiotics or enzymes; (64) The payload is a drug and the drug is selected from monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF), maytansinoids (DM1 and DM4), tubulysin A, tubulysin B, tubulysin C, tubulysin D, tubulysin E, tubulysin F, tubulysin G, tubulysin H, tubulysin I, Calicheamicin γ1, CC-1065, duocarmycin SA, pyrrolobenzodiazepines derivatives (e.g., SGD-1882, SG-3199, SGD-3650, SGD-1910, SG-3249, SG3584 or SG6838) anthramycin, topotecan, irinotecan, belotecan, trastuzumab deruxtecan, daunorubicin, doxorubicin, idarubicin, mitoxantrone, α-amanitin, β-amanitin, γ- amanitin, ε-amanitin, amanullin, amanullinic acid, amaninamide, amanin, proamanullin, Pseudomonas exotoxin, diphtheria toxin, 4-dimethylamino piperidino- hydroxybenzoxazino rifamycin, β-glucuronidase, exatecan and urease; (65) The payload is a drug and the drug is selected from MMAE, MMAF, pyrrolobenzodiazepines derivatives (e.g., SGD-1882, SG-3199, SGD-3650, SGC- 1910, SG-3249, SG3584 or SG6838) or doxorubicin; (66) The payload is a drug and the drug is selected from MMAE, MMAF, or SG6838; (67) The payload is a labelling agent and the labelling agent is a fluorophore, a biotin tag, a radioisotope or a radioisotope containing moiety; (68) The payload is a labelling agent and the labelling agent is fluorescein isothiocyanate (FITC), phycoerythrin (PE), allophycocyanin (APC), Indocicarbocyanine (Cy5), Indocarbocyanine (Cy3), Alexa Fluor (e.g., 350, 405, 488, 532, 546, 568, 594, 647, 680, 700, 750), DyLight (e.g.405, 488, 550, 650, 680, 755, 800), a positron emission tomography (PET) tracer (e.g., [18F] Fludeoxyglucose (18F) (FDG)-glucose analogue,56 [11C] acetate, [11C] methionine, [11C] choline, copper64Cu dotatate, [18F] EF5, [18F] fluciclovine, [18F] fluorocholine, [18F] fluoroethyl-L-tyrosine, [18F] fluoromisonidazole, [18F] fluorothymidine F-18, [64Cu] Cu-ETS2, [68Ga] DOTA-pseudopeptides, DOTA, DOTA-GA, [68Ga] DOTA-TATE, [68Ga] prostate-specific membrane antigen (PSMA) or NODA-GA); (69) The payload is a labelling agent and the labelling agent is FITC, PE, APC, Cy5, Cy3, Alexa Fluor 350, Alexa Fluor 405, Alexa Fluor 488, Alexa Fluor 532, Alexa Fluor 546, Alexa Fluor 568, Alexa Fluor 594, Alexa Fluor 647, Alexa Fluor 680, Alexa Fluor 700, Alexa Fluor 750, DyLight 405, DyLight 488, DyLight 550, DyLight 650, DyLight 680, DyLight 755, DyLight 800, [18F] Fludeoxyglucose (18F) (FDG)-glucose analogue, [11C] acetate, [11C] methionine, [11C] choline, copper 64Cu dotatate, [18F] EF5, [18F] fluciclovine, [18F] fluorocholine, [18F] fluoroethyl-L-tyrosine, [18F] fluoromisonidazole, [18F] fluorothymidine F-18, [64Cu] Cu-ETS2, [68Ga] DOTA-pseudopeptides, DOTA, DOTA-GA, [68Ga] DOTA-TATE, [68Ga] PSMA or NODA-GA; (70) The payload is a labelling agent and the labelling agent is DOTA-pseudopeptides, DOTA, DOTA-GA, [68Ga] DOTA-TATE or NODA-GA; (71) The payload is a labelling agent and the labelling agent is DOTA, DOTA-GA or NODA- GA; (72) The payload is a targeting moiety and the targeting moiety directs the compounds of Formula (I) to a particular location within the body; (73) The payload is a targeting moiety and the targeting moiety is a carbohydrate (e.g., alpha-D-galacto-hexopyranosyl-(1->3)-2-acetamido-2-deoxy-D-galacto- hexopyranose (Gal-alpha 1,3-GalNAc));

[0071] The drug, labelling agent or targeting moiety comprises a functional group that can be linked to the linker. Such a group may include, for example, an amino group, an imine group or a hydroxy group.

[0072] Suitably, m is as defined in numbered paragraph (1). Suitably m is as defined in numbered paragraph (2). Most suitably m is as defined in numbered paragraph (3).

[0073] Suitably, n is as defined in numbered paragraph (4). Suitably, n is as defined in numbered paragraph (5). Most suitably, n is as defined in numbered paragraph (6).

[0074] Suitably, R1is as defined in numbered paragraph (7). Suitably, R1is as defined in numbered paragraph (7a). Suitably, R1is as defined in numbered paragraph (8). Suitably, R157 is as defined in numbered paragraph (8a). Suitably, R1is as defined in numbered paragraph (9). Suitably, R1is as defined in numbered paragraph (9a). Suitably, R1is as defined in numbered paragraph (10). Suitably, R1is as defined in numbered paragraph (10a). Suitably, R1is as defined in numbered paragraph (11). Suitably, R1is as defined in numbered paragraph (11a). Suitably, R1is as defined in numbered paragraph (12). Suitably, R1is as defined in numbered paragraph (12a). Suitably, R1is as defined in numbered paragraph (13). Suitably, R1 is as defined in numbered paragraph (13a). Suitably, R1 is as defined in numbered paragraph (14). Suitably, R1 is as defined in numbered paragraph (14a). Suitably, R1 is as defined in numbered paragraph (15). Suitably, R1 is as defined in numbered paragraph (16).

[0075] Suitably, L is as defined in numbered paragraph (17). Suitably, L is as defined in numbered paragraph (18). Suitably, L is as defined in numbered paragraph (19). Suitably, L is as defined in numbered paragraph (20). Suitably, L is as defined in numbered paragraph (21). Suitably, L is as defined in numbered paragraph (22). Suitably, L is as defined in numbered paragraph (23). Suitably, L is as defined in numbered paragraph (24). Suitably, L is as defined in numbered paragraph (25). Suitably, L is as defined in numbered paragraph (26). Suitably, L is as defined in numbered paragraph (27). Suitably, L is as defined in numbered paragraph (28). Suitably, L is as defined in numbered paragraph (29). Suitably, L is as defined in numbered paragraph (30). Suitably, L is as defined in numbered paragraph (31). Suitably, L is as defined in numbered paragraph (32). Suitably, L is as defined in numbered paragraph (33). Suitably, L is as defined in numbered paragraph (34). Suitably, L is as defined in numbered paragraph (34a). Suitably, L is as defined in numbered paragraph (35). Suitably, L is as defined in numbered paragraph (35a). Suitably, L is as defined in numbered paragraph (36). Suitably, L is as defined in numbered paragraph (36a). Suitably, L is as defined in numbered paragraph (37). Suitably, L is as defined in numbered paragraph (37a). Suitably, L is as defined in numbered paragraph (38). Suitably, L is as defined in numbered paragraph (38). Suitably, L is as defined in numbered paragraph (38a). Suitably, L is as defined in numbered paragraph (39). Suitably, L is as defined in numbered paragraph (39a). Suitably, L is as defined in numbered paragraph (40). Suitably, L is as defined in numbered paragraph (40a). Suitably, L is as defined in numbered paragraph (41). Suitably, L is as defined in numbered paragraph (41a). Suitably, L is as defined in numbered paragraph (42). Suitably, L is as defined in numbered paragraph (42a). Suitably, L is as defined in numbered paragraph (43). Suitably, L is as defined in numbered paragraph (43a). Suitably, L is as defined in numbered paragraph (44). Suitably, L is as defined in numbered paragraph (44a). Suitably, L is as defined in numbered paragraph (45). Suitably, L is as defined in numbered paragraph (45a). Suitably, L is as defined in numbered paragraph (46). Suitably, L is as defined in numbered paragraph (46a). Suitably, L is as defined in numbered paragraph58 (47). Suitably, L is as defined in numbered paragraph (47a). Suitably, L is as defined in numbered paragraph (48). Suitably, L is as defined in numbered paragraph (48a).

[0076] Suitably, LXis as defined in numbered paragraph (49). Suitably, LXis as defined in numbered paragraph (50). Suitably, LXis as defined in numbered paragraph (51). Suitably, LXis as defined in numbered paragraph (52). Suitably, LXis as defined in numbered paragraph (53). Suitably, LXis as defined in numbered paragraph (54). Suitably, LXis as defined in numbered paragraph (55).

[0077] Suitably, PL is as defined in numbered paragraph (56).

[0078] Suitably, PL is as defined in numbered paragraph (57). In such embodiments, PL is suitably as defined in numbered paragraph (60). Suitably, PL is as defined in numbered paragraph (61). Suitably, PL is as defined in numbered paragraph (62). Suitably, PL is as defined in numbered paragraph (63). Suitably, PL is as defined in numbered paragraph (64). Suitably, PL is as defined in numbered paragraph (65). Suitably, PL is as defined in numbered paragraph (66).

[0079] Suitably, PL is as defined in numbered paragraph (58). In such embodiments, PL is suitably as defined in numbered paragraph (67). Suitably, PL is as defined in numbered paragraph (68). Suitably, PL is as defined in numbered paragraph (69). Suitably, PL is as defined in numbered paragraph (70). Suitably, PL is as defined in numbered paragraph (71).

[0080] Suitably, PL is as defined in numbered paragraph (59). In such embodiments, PL is suitably as defined in numbered paragraph (72). Suitably, PL is as defined in numbered paragraph (73).

[0081] In a particular group of compounds of the invention, the compounds have the structural Formula (I-Ia) defined herein.

[0082] In a particular group of compounds of the invention, the compounds have the structural Formula (I-Ib) defined herein.

[0083] In a particular group of compounds of the invention, the compounds have the structural Formula (I-Ic) defined herein.

[0084] In a particular group of compounds of the invention, the compounds have the structural Formula (I-IIa) defined herein.

[0085] In a particular group of compounds of the invention, the compounds have the structural Formula (I-IIb) defined herein.

[0086] In a particular group of compounds of the invention, the compounds have the structural Formula (I-IIc) defined herein.59

[0087] In a particular group of compounds of the invention, the compounds have the structural Formula (I-IIIa) defined herein.

[0088] In a particular group of compounds of the invention, the compounds have the structural Formula (I-IIIb) defined herein.

[0089] In a particular group of compounds of the invention, the compounds have the structural Formula (I-IIIc) defined herein.

[0090] In a particular group of compounds of the invention, the compounds have the structural Formula (I-IIId) defined herein.

[0091] In a particular group of compounds of the invention, the compounds have the structural Formula (I-IIIe) defined herein.

[0092] In a particular group of compounds of the invention, the compounds have the structural Formula (I-IIIf) defined herein.

[0093] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I-IIb), (I- IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0094] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I-IIb), (I- IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).60

[0095] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I-IIb), (I- IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1is as defined in numbered paragraph (8); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0096] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I-IIb), (I- IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (8a); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0097] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I-IIb), (I- IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (9); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0098] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I-IIb), (I- IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present:61 m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1is as defined in numbered paragraph (9a); L is as defined in numbered paragraph (17); LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0099] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I-IIb), (I- IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (10); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0100] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (10a); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0101] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6);62 R1is as defined in numbered paragraph (11); L is as defined in numbered paragraph (17); LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0102] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (11a); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0103] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (12); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0104] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (12a); L is as defined in numbered paragraph (17);63 LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0105] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (13); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0106] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (13a); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0107] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (14); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).64

[0108] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1is as defined in numbered paragraph (14a); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0109] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (15); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0110] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (16); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0111] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present:65 m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1is as defined in numbered paragraph (7); L is as defined in numbered paragraph (19); LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0112] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (19); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0113] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (21); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0114] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6);66 R1is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (21); LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0115] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (24); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0116] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (24); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56). In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I-IIb), (I-IIc), (I- IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (25);67 LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0117] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (25); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0118] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (27); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0119] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (27); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).68

[0120] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1is as defined in numbered paragraph (7); L is as defined in numbered paragraph (29); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0121] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (29); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0122] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (31); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0123] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present:69 m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (31); LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0124] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (33); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0125] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (33); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0126] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6);70 R1is as defined in numbered paragraph (7); L is as defined in numbered paragraph (35); LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0127] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (35a); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0128] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (37); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0129] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (37a);71 LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0130] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (39); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0131] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (39a); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0132] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (40); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).72

[0133] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (40a); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0134] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (41); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0135] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (41a); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0136] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present:73 m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1is as defined in numbered paragraph (7); L is as defined in numbered paragraph (42); LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0137] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (42a); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0138] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (43); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0139] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6);74 R1is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (43a); LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0140] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (44); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0141] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (44a); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0142] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (45);75 LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0143] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (45a); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0144] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (46); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0145] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (46a); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).76

[0146] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1is as defined in numbered paragraph (7); L is as defined in numbered paragraph (47); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0147] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (47a); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0148] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (48); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0149] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present:77 m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (48a); LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0150] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in any one of numbered paragraphs (19)-(48); LX is as defined in numbered paragraph (50); and PL is as defined in numbered paragraph (56).

[0151] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in any one of numbered paragraphs (19)-(48a); LX is as defined in numbered paragraph (50); and PL is as defined in numbered paragraph (56).

[0152] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6);78 R1is as defined in numbered paragraph (7); L is as defined in any one of numbered paragraphs (19)-(48); LXis as defined in numbered paragraph (51); and PL is as defined in numbered paragraph (56).

[0153] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in any one of numbered paragraphs (19)-(48a); LX is as defined in numbered paragraph (51); and PL is as defined in numbered paragraph (56).

[0154] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in any one of numbered paragraphs (19)-(48); LX is as defined in numbered paragraph (52); and PL is as defined in numbered paragraph (56).

[0155] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in any one of numbered paragraphs (19)-(48a);79 LXis as defined in numbered paragraph (52); and PL is as defined in numbered paragraph (56).

[0156] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in any one of numbered paragraphs (19)-(48); LX is as defined in numbered paragraph (53); and PL is as defined in numbered paragraph (56).

[0157] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in any one of numbered paragraphs (19)-(48a); LX is as defined in numbered paragraph (53); and PL is as defined in numbered paragraph (56).

[0158] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in any one of numbered paragraphs (19)-(48); LX is as defined in numbered paragraph (54); and PL is as defined in numbered paragraph (56).80

[0159] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1is as defined in numbered paragraph (7a); L is as defined in any one of numbered paragraphs (19)-(48a); LX is as defined in numbered paragraph (54); and PL is as defined in numbered paragraph (56).

[0160] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in any one of numbered paragraphs (19)-(48); LX is as defined in numbered paragraph (55); and PL is as defined in numbered paragraph (56).

[0161] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in any one of numbered paragraphs (19)-(48a); LX is as defined in numbered paragraph (55); and PL is as defined in numbered paragraph (56).

[0162] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present:81 m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1is as defined in numbered paragraph (7); L is as defined in numbered paragraph (17); LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (60).

[0163] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (60).

[0164] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (61).

[0165] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6);82 R1is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (17); LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (61).

[0166] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (62).

[0167] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (62).

[0168] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (17);83 LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (63).

[0169] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (63).

[0170] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (64).

[0171] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (64).84

[0172] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1is as defined in numbered paragraph (7); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (65).

[0173] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (65).

[0174] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (66).

[0175] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present:85 m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (17); LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (66).

[0176] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (67).

[0177] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (67).

[0178] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6);86 R1is as defined in numbered paragraph (7); L is as defined in numbered paragraph (17); LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (68).

[0179] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (68).

[0180] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (69).

[0181] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (17);87 LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (69).

[0182] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (70).

[0183] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (70).

[0184] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (71).88

[0185] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (71).

[0186] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (72).

[0187] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (72).

[0188] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present:89 m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1is as defined in numbered paragraph (7); L is as defined in numbered paragraph (17); LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (73).

[0189] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (7a); L is as defined in numbered paragraph (17); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (73).

[0190] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (8); L is as defined in numbered paragraph (24); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0191] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6);90 R1is as defined in numbered paragraph (8a); L is as defined in numbered paragraph (24); LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0192] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (9); L is as defined in numbered paragraph (25); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0193] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (9a); L is as defined in numbered paragraph (25); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0194] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (10); L is as defined in numbered paragraph (29);91 LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0195] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (10a); L is as defined in numbered paragraph (29); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0196] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (11); L is as defined in numbered paragraph (35); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0197] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (11a); L is as defined in numbered paragraph (35a); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).92

[0198] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1is as defined in numbered paragraph (12); L is as defined in numbered paragraph (39); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0199] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (12a); L is as defined in numbered paragraph (39a); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0200] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (13); L is as defined in numbered paragraph (40); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0201] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present:93 m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1is as defined in numbered paragraph (13a); L is as defined in numbered paragraph (40a); LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0202] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (14); L is as defined in numbered paragraph (42); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0203] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (14a); L is as defined in numbered paragraph (42a); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0204] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6);94 R1is as defined in numbered paragraph (15); L is as defined in numbered paragraph (45); LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0205] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (15); L is as defined in numbered paragraph (45a); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0206] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (16); L is as defined in numbered paragraph (48); LX is as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0207] In an embodiment of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I- IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, where present: m is as defined in numbered paragraph (3); n is as defined in numbered paragraph (6); R1 is as defined in numbered paragraph (16); L is as defined in numbered paragraph (48a);95 LXis as defined in numbered paragraph (49); and PL is as defined in numbered paragraph (56).

[0208] In any of the aforementioned embodiments of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I-IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, m can be as defined in numbered paragraph (1). Suitably, m is as defined in numbered paragraph (2). Most suitably, m is as defined in numbered paragraph (3).

[0209] In any of the aforementioned embodiments of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I-IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, n can be as defined in numbered paragraph (4). Suitably, n is as defined in numbered paragraph (5). Most suitably, n is as defined in numbered paragraph (6).

[0210] In any of the aforementioned embodiments of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I-IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, R1 can be as defined in numbered paragraph (7). Suitably, R1 is as defined in numbered paragraph (7a). Suitably, R1 is as defined in numbered paragraph (8). Suitably, R1 is as defined in numbered paragraph (8a). Suitably, R1 is as defined in numbered paragraph (9). Suitably, R1 is as defined in numbered paragraph (9a). Suitably, R1 is as defined in numbered paragraph (10). Suitably, R1 is as defined in numbered paragraph (10a). Suitably, R1 is as defined in numbered paragraph (11). Suitably, R1 is as defined in numbered paragraph (11a). Suitably, R1 is as defined in numbered paragraph (12). Suitably, R1 is as defined in numbered paragraph (12a). Suitably, R1 is as defined in numbered paragraph (13). Suitably, R1 is as defined in numbered paragraph (13a). Suitably, R1 is as defined in numbered paragraph (14). Suitably, R1 is as defined in numbered paragraph (14a). Suitably, R1 is as defined in numbered paragraph (15). Suitably, R1 is as defined in numbered paragraph (16).

[0211] In any of the aforementioned embodiments of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I-IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, L can be as defined in numbered paragraph (17). Suitably, L is as defined in numbered paragraph (18). Suitably, L is as defined in numbered paragraph (19). Suitably, L is as defined in numbered paragraph (20). Suitably, L is as defined in numbered paragraph (21). Suitably, L is as defined in numbered paragraph (22). Suitably, L is as defined in numbered paragraph (23). Suitably, L is as defined in numbered paragraph (24). Suitably, L is as defined in numbered paragraph (25). Suitably, L is as defined in numbered paragraph (26). Suitably, L is as defined in numbered paragraph96 (27). Suitably, L is as defined in numbered paragraph (28). Suitably, L is as defined in numbered paragraph (29). Suitably, L is as defined in numbered paragraph (30). Suitably, L is as defined in numbered paragraph (31). Suitably, L is as defined in numbered paragraph (32). Suitably, L is as defined in numbered paragraph (33). Suitably, L is as defined in numbered paragraph (34). Suitably, L is as defined in numbered paragraph (34a). Suitably, L is as defined in numbered paragraph (35). Suitably, L is as defined in numbered paragraph (35a). Suitably, L is as defined in numbered paragraph (36). Suitably, L is as defined in numbered paragraph (36a). Suitably, L is as defined in numbered paragraph (37). Suitably, L is as defined in numbered paragraph (37a). Suitably, L is as defined in numbered paragraph (38). Suitably, L is as defined in numbered paragraph (38). Suitably, L is as defined in numbered paragraph (38a). Suitably, L is as defined in numbered paragraph (39). Suitably, L is as defined in numbered paragraph (39a). Suitably, L is as defined in numbered paragraph (40). Suitably, L is as defined in numbered paragraph (40a). Suitably, L is as defined in numbered paragraph (41). Suitably, L is as defined in numbered paragraph (41a). Suitably, L is as defined in numbered paragraph (42). Suitably, L is as defined in numbered paragraph (42a). Suitably, L is as defined in numbered paragraph (43). Suitably, L is as defined in numbered paragraph (43a). Suitably, L is as defined in numbered paragraph (44). Suitably, L is as defined in numbered paragraph (44a). Suitably, L is as defined in numbered paragraph (45). Suitably, L is as defined in numbered paragraph (45a). Suitably, L is as defined in numbered paragraph (46). Suitably, L is as defined in numbered paragraph (46a). Suitably, L is as defined in numbered paragraph (47). Suitably, L is as defined in numbered paragraph (47a). Suitably, L is as defined in numbered paragraph (48). Suitably, L is as defined in numbered paragraph (48a).

[0212] In any of the aforementioned embodiments of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I-IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, LX can be as defined in numbered paragraph (49). Suitably, LXis as defined in numbered paragraph (50). Suitably, LXis as defined in numbered paragraph (51). Suitably, LX is as defined in numbered paragraph (52). Suitably, LX is as defined in numbered paragraph (53). Suitably, LX is as defined in numbered paragraph (54). Suitably, LXis as defined in numbered paragraph (55).

[0213] In any of the aforementioned embodiments of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I-IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, PL can be as defined in numbered paragraph (57). Suitably, PL is as defined in numbered paragraph (60). Suitably, PL is as defined in numbered paragraph (61). Suitably, PL is as defined in numbered paragraph (62). Suitably, PL is as defined in numbered paragraph (63). Suitably, PL is as97 defined in numbered paragraph (64). Suitably, PL is as defined in numbered paragraph (65). Suitably, PL is as defined in numbered paragraph (66).

[0214] In any of the aforementioned embodiments of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I-IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, PL can be as defined in numbered paragraph (58). Suitably, PL is as defined in numbered paragraph (67). Suitably, PL is as defined in numbered paragraph (68). Suitably, PL is as defined in numbered paragraph (69). Suitably, PL is as defined in numbered paragraph (70). Suitably, PL is as defined in numbered paragraph (71).

[0215] In any of the aforementioned embodiments of the compounds of Formula (I), (I-Ia), (I-Ib), (I-Ic), (I-IIa), (I-IIb), (I-IIc), (I-IIIa), (I-IIIb), (I-IIIc), (I-IIId), (I-IIIe), or (I-IIIf), or a pharmaceutically acceptable salt, hydrate or solvate thereof, PL can be as defined in numbered paragraph (59). Suitably, PL is as defined in numbered paragraph (72). Suitably, PL is as defined in numbered paragraph (73).

[0216] Particular compounds of the present invention include any of the compounds exemplified in the present application, or a pharmaceutically acceptable salt , solvate or hydrate thereof, and, in particular, any of the following:101.

[0217] Particular compounds of the present invention include any of the compounds exemplified in the present application, or a pharmaceutically acceptable salt , solvate or hydrate thereof, and, in particular, any of the following:105.

[0218] Any of the aforementioned compounds of Formula (I) may bind to one or more proteins and / or peptides, thereby forming a protein / peptide-payload conjugate, as defined herein. Accordingly, the present invention provides a method of preparing a protein / peptide- payload conjugate, the method comprising contacting a compound or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein (e.g., a compound of Formula (I)), with one or more proteins and / or peptides, thereby forming a protein / peptide-payload conjugate. The protein / peptide may be as defined anywhere herein. Any of the aforementioned compounds of Formula (I) may bind to one or more antibodies, thereby forming antibody-payload conjugates, as defined herein. Accordingly, the present invention provides a method of preparing an antibody-payload conjugate, the method comprising contacting a compound or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein (e.g., a compound of Formula (I)), with one or more antibodies, thereby forming an antibody-payload conjugate. The antibodies may each independently be as defined anywhere herein. For example, each antibody may independently be selected from a nanobody, a monoclonal antibody, a polyclonal antibody, a dimer, a trimer, a multimer, a multispecific antibody (e.g., a bispecific antibody), a multivalent antibody or an antibody fragment, as defined herein. Suitably, each antibody is a nanobody. Even more suitably, each antibody is independently selected from anti-HER2 or anti-PD-L-1 (e.g., anti-PD-L1 sdAb). In some embodiments, the antibody is trastuzumab. Any of the aforementioned compounds of Formula (I) may bind to one or more antibodies, thereby forming antibody-drug conjugates, as defined herein. Accordingly, the present invention provides a method of preparing an antibody- drug conjugate, the method comprising contacting a compound or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein (e.g., a compound of Formula (I)), with one or more antibodies, thereby forming an antibody-drug conjugate. The antibodies may each independently be as defined anywhere herein. For example, each antibody may independently be selected from a nanobody, a monoclonal antibody, a polyclonal antibody, a106 dimer, a trimer, a multimer, a multispecific antibody (e.g., a bispecific antibody), a multivalent antibody or an antibody fragment, as defined herein. Suitably, each antibody is a nanobody. Even more suitably, each antibody is independently selected from anti-HER2 or anti-PD-L-1 (e.g., anti-PD-L1 sdAb). In some embodiments, the antibody is trastuzumab. Any of the aforementioned compounds of Formula (I) may attach to one or more affibodies, thereby forming affibody-payload conjugates, as defined herein. Accordingly, the present invention provides a method of preparing an affibody-payload conjugate, the method comprising contacting a compound or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein (e.g., a compound of Formula (I)), with one or more affibodies, thereby forming an affibody-payload conjugate. The affibodies may each independently be as defined anywhere herein. For example, each affibody may independently be selected from an from anti-HER2 affibody or an anti-PD-L-1 affibody. Salts, isomers and prodrugs

[0219] A suitable pharmaceutically acceptable salt of a compound of the invention is, for example, an acid-addition salt of a compound of the invention which is sufficiently basic, for example, an acid-addition salt with, for example, an inorganic or organic acid, for example hydrochloric, hydrobromic, sulfuric, phosphoric, trifluoroacetic, formic, citric methane sulfonate or maleic acid. In addition, a suitable pharmaceutically acceptable salt of a compound of the invention which is sufficiently acidic is an alkali metal salt, for example a sodium or potassium salt, an alkaline earth metal salt, for example a calcium or magnesium salt, an ammonium salt or a salt with an organic base which affords a pharmaceutically acceptable cation, for example a salt with methylamine, dimethylamine, trimethylamine, piperidine, morpholine or tris-(2-hydroxyethyl)amine.

[0220] Compounds that have the same molecular formula but differ in the nature or sequence of bonding of their atoms or the arrangement of their atoms in space are termed “isomers”. Isomers that differ in the arrangement of their atoms in space are termed “stereoisomers”. Stereoisomers that are not mirror images of one another are termed “diastereomers” and those that are non-superimposable mirror images of each other are termed “enantiomers”. When a compound has an asymmetric centre, for example, it is bonded to four different groups, a pair of enantiomers is possible. An enantiomer can be characterised by the absolute configuration of its asymmetric centre and is described by the R- and S-sequencing rules of Cahn and Prelog, or by the manner in which the molecule rotates the plane of polarised light and designated as dextrorotatory or levorotatory (i.e., as (+) or (-)-isomers respectively). A chiral compound can exist as either individual enantiomer or as a107 mixture thereof. A mixture containing equal proportions of the enantiomers is called a “racemic mixture”.

[0221] The compounds of this invention may possess one or more asymmetric centres; such compounds can therefore be produced as individual (R)- or (S)-stereoisomers or as mixtures thereof. Unless indicated otherwise, the description or naming of a particular compound in the specification and claims is intended to include both individual enantiomers and mixtures, racemic or otherwise, thereof. The methods for the determination of stereochemistry and the separation of stereoisomers are well-known in the art (see discussion in Chapter 4 of “Advanced Organic Chemistry”, 4th edition J. March, John Wiley and Sons, New York, 2001), for example by synthesis from optically active starting materials or by resolution of a racemic form. Some of the compounds of the invention may have geometric isomeric centres (E- and Z- isomers).

[0222] It is to be understood that the present invention encompasses all optical, diastereoisomers and geometric isomers and mixtures thereof that possess antiproliferative activity.

[0223] The present invention also encompasses compounds of the invention as defined herein which comprise one or more isotopic substitutions. For example, H may be in any isotopic form, including1H,2H(D), and3H (T); C may be in any isotopic form, including12C,13C, and14C; and O may be in any isotopic form, including16O and18O; and the like.

[0224] It is also to be understood that certain compounds of the Formula (I) may exist in solvated as well as unsolvated forms such as, for example, hydrated forms. It is to be understood that the invention encompasses all such solvated forms that possess antiproliferative activity.

[0225] It is also to be understood that certain compounds of the Formula (I) may exhibit polymorphism, and that the invention encompasses all such forms that possess antiproliferative activity.

[0226] Compounds of the Formula (I) may exist in a number of different tautomeric forms and references to compounds of the Formula (I) include all such forms. For the avoidance of doubt, where a compound can exist in one of several tautomeric forms, and only one is specifically described or shown, all others are nevertheless embraced by Formula (I). Examples of tautomeric forms include keto-, enol-, and enolate-forms, as in, for example, the following tautomeric pairs: keto / enol (illustrated below), imine / enamine, amide / imino alcohol, amidine / amidine, nitroso / oxime, thioketone / enethiol, and nitro / aci-nitro.108keto enol enolate

[0227] Compounds of the Formula (I) containing an amine function may also form N- oxides. A reference herein to a compound of the Formula (I) that contains an amine function also includes the N-oxide. Where a compound contains several amine functions, one or more than one nitrogen atom may be oxidised to form an N-oxide. Particular examples of N-oxides are the N-oxides of a tertiary amine or a nitrogen atom of a nitrogen-containing heterocycle. N-Oxides can be formed by treatment of the corresponding amine with an oxidizing agent such as hydrogen peroxide or a per-acid (e.g., a peroxycarboxylic acid), see for example Advanced Organic Chemistry, by Jerry March, 4th Edition, Wiley Interscience, pages. More particularly, N-oxides can be made by the procedure of L. W. Deady (Syn. Comm.1977, 7, 509-514) in which the amine compound is reacted with m-chloroperoxybenzoic acid (mCPBA), for example, in an inert solvent such as dichloromethane.

[0228] The compounds of Formula (I) may be administered in the form of a pro-drug which is broken down in the human or animal body to release a compound of the invention. A pro-drug may be used to alter the physical properties and / or the pharmacokinetic properties of a compound of the invention. A pro-drug can be formed when the compound of the invention contains a suitable group or substituent to which a property-modifying group can be attached. Examples of pro-drugs include in vivo cleavable ester derivatives that may be formed at a carboxy group or a hydroxy group in a compound of the Formula (I) and in-vivo cleavable amide derivatives that may be formed at a carboxy group or an amino group in a compound of the Formula (I).

[0229] Accordingly, the present invention includes those compounds of the Formula (I) as defined hereinbefore, when made available by organic synthesis and when made available within the human or animal body by way of cleavage of a pro-drug thereof. Accordingly, the present invention includes those compounds of the Formula (I) that are produced by organic synthetic means and also such compounds that are produced in the human or animal body by way of metabolism of a precursor compound, that is a compound of the Formula (I) may be a synthetically-produced compound or a metabolically-produced compound.

[0230] A suitable pharmaceutically acceptable pro-drug of a compound of the Formula (I) is one that is based on reasonable medical judgement as being suitable for administration to the human or animal body without undesirable pharmacological activities and without undue toxicity.109

[0231] Various forms of pro-drug have been described, for example in the following documents :- a) Methods in Enzymology, Vol. 42, p. 309-396, edited by K. Widder, et al. (Academic Press, 1985); b) Design of Pro-drugs, edited by H. Bundgaard, (Elsevier, 1985); c) A Textbook of Drug Design and Development, edited by Krogsgaard-Larsen and H. Bundgaard, Chapter 5 “Design and Application of Pro-drugs”, by H. Bundgaard p. 113-191 (1991); d) H. Bundgaard, Advanced Drug Delivery Reviews, 8, 1-38 (1992); e) H. Bundgaard, et al., Journal of Pharmaceutical Sciences, 77, 285 (1988); f) N. Kakeya, et al., Chem. Pharm. Bull., 32, 692 (1984); g) T. Higuchi and V. Stella, “Pro-Drugs as Novel Delivery Systems”, A.C.S. Symposium Series, Volume 14; and h) E. Roche (editor), “Bioreversible Carriers in Drug Design”, Pergamon Press, 1987.

[0232] A suitable pharmaceutically acceptable pro-drug of a compound of the Formula (I) that possesses a carboxy group is, for example, an in vivo cleavable ester thereof. An in vivo cleavable ester of a compound of the Formula (I) containing a carboxy group is, for example, a pharmaceutically acceptable ester which is cleaved in the human or animal body to produce the parent acid. Suitable pharmaceutically acceptable esters for carboxy include (1-6C)alkyl esters such as methyl, ethyl and tert-butyl, (1-6C)alkoxymethyl esters such as methoxymethyl esters, (1-6C)alkanoyloxymethyl esters such as pivaloyloxymethyl esters, 3- phthalidyl esters, (3-8C)cycloalkylcarbonyloxy-(1-6C)alkyl esters such as cyclopentylcarbonyloxymethyl and 1-cyclohexylcarbonyloxyethyl esters, 2-oxo-1,3- dioxolenylmethyl esters such as 5-methyl-2-oxo-1,3-dioxolen-4-ylmethyl esters and (1- 6C)alkoxycarbonyloxy-(1-6C)alkyl esters such as methoxycarbonyloxymethyl and 1- methoxycarbonyloxyethyl esters.

[0233] A suitable pharmaceutically acceptable pro-drug of a compound of the Formula (I) that possesses a hydroxy group is, for example, an in vivo cleavable ester or ether thereof. An in vivo cleavable ester or ether of a compound of the Formula (I) containing a hydroxy group is, for example, a pharmaceutically acceptable ester or ether which is cleaved in the human or animal body to produce the parent hydroxy compound. Suitable pharmaceutically acceptable ester forming groups for a hydroxy group include inorganic esters such as phosphate esters (including phosphoramidic cyclic esters). Further suitable pharmaceutically110 acceptable ester forming groups for a hydroxy group include (1-10C)alkanoyl groups such as acetyl, benzoyl, phenylacetyl and substituted benzoyl and phenylacetyl groups, (1- 10C)alkoxycarbonyl groups such as ethoxycarbonyl, N,N-(1-6C)2carbamoyl, 2- dialkylaminoacetyl and 2-carboxyacetyl groups. Examples of ring substituents on the phenylacetyl and benzoyl groups include aminomethyl, N-alkylaminomethyl, N,N- dialkylaminomethyl, morpholinomethyl, piperazin-1-ylmethyl and 4-(1-4C)alkylpiperazin-1- ylmethyl. Suitable pharmaceutically acceptable ether forming groups for a hydroxy group include ^-acyloxyalkyl groups such as acetoxymethyl and pivaloyloxymethyl groups.

[0234] A suitable pharmaceutically acceptable pro-drug of a compound of the Formula (I) that possesses a carboxy group is, for example, an in vivo cleavable amide thereof, for example an amide formed with an amine such as ammonia, a (1-4C)alkylamine such as methylamine, a [(1-4C)alkyl]2amine such as dimethylamine, N-ethyl-N-methylamine or diethylamine, a (1-4C)alkoxy-(2-4C)alkylamine such as 2-methoxyethylamine, a phenyl-(1- 4C)alkylamine such as benzylamine and amino acids such as glycine or an ester thereof.

[0235] A suitable pharmaceutically acceptable pro-drug of a compound of the Formula (I) that possesses an amino group is, for example, an in vivo cleavable amide derivative thereof. Suitable pharmaceutically acceptable amides from an amino group include, for example an amide formed with (1-10C)alkanoyl groups such as an acetyl, benzoyl, phenylacetyl and substituted benzoyl and phenylacetyl groups. Examples of ring substituents on the phenylacetyl and benzoyl groups include aminomethyl, N-alkylaminomethyl, N,N- dialkylaminomethyl, morpholinomethyl, piperazin-1-ylmethyl and 4-(1-4C)alkyl)piperazin-1- ylmethyl.

[0236] The in vivo effects of a compound of the Formula (I) may be exerted in part by one or more metabolites that are formed within the human or animal body after administration of a compound of the Formula (I). As stated hereinbefore, the in vivo effects of a compound of the Formula (I) may also be exerted by way of metabolism of a precursor compound (a pro- drug).

[0237] Though the present invention may relate to any compound or particular group of compounds defined herein by way of optional, preferred or suitable features or otherwise in terms of particular embodiments, the present invention may also relate to any compound or particular group of compounds that specifically excludes said optional, preferred or suitable features or particular embodiments.

[0238] Suitably, the present invention excludes any individual compounds not possessing the biological activity defined herein.111 Synthesis

[0239] The compounds of the present invention can be prepared by any suitable technique known in the art. Particular processes for the preparation of these compounds are described further in the accompanying examples.

[0240] In the description of the synthetic methods described herein and in any referenced synthetic methods that are used to prepare the starting materials, it is to be understood that all proposed reaction conditions, including choice of solvent, reaction atmosphere, reaction temperature, duration of the experiment and workup procedures, can be selected by a person skilled in the art.

[0241] It is understood by one skilled in the art of organic synthesis that the functionality present on various portions of the molecule must be compatible with the reagents and reaction conditions utilised.

[0242] It will be appreciated that during the synthesis of the compounds of the invention in the processes defined herein, or during the synthesis of certain starting materials, it may be desirable to protect certain substituent groups to prevent their undesired reaction. The skilled chemist will appreciate when such protection is required, and how such protecting groups may be put in place, and later removed.

[0243] For examples of protecting groups see one of the many general texts on the subject, for example, ‘Protective Groups in Organic Synthesis’ by Theodora Green (publisher: John Wiley & Sons). Protecting groups may be removed by any convenient method described in the literature or known to the skilled chemist as appropriate for the removal of the protecting group in question, such methods being chosen so as to effect removal of the protecting group with the minimum disturbance of groups elsewhere in the molecule.

[0244] Thus, if reactants include, for example, groups such as amino, carboxy or hydroxy it may be desirable to protect the group in some of the reactions mentioned herein.

[0245] By way of example, a suitable protecting group for an amino or alkylamino group is, for example, an acyl group, for example an alkanoyl group such as acetyl, an alkoxycarbonyl group, for example a methoxycarbonyl, ethoxycarbonyl or t-butoxycarbonyl group, an arylmethoxycarbonyl group, for example benzyloxycarbonyl, or an aroyl group, for example benzoyl. The deprotection conditions for the above protecting groups necessarily vary with the choice of protecting group. Thus, for example, an acyl group such as an alkanoyl or alkoxycarbonyl group or an aroyl group may be removed by, for example, hydrolysis with a suitable base such as an alkali metal hydroxide, for example lithium or sodium hydroxide. Alternatively an acyl group such as a tert-butoxycarbonyl group may be removed, for example,112 by treatment with a suitable acid as hydrochloric, sulfuric or phosphoric acid or trifluoroacetic acid and an arylmethoxycarbonyl group such as a benzyloxycarbonyl group may be removed, for example, by hydrogenation over a catalyst such as palladium-on-carbon, or by treatment with a Lewis acid for example boron tris(trifluoroacetate). A suitable alternative protecting group for a primary amino group is, for example, a phthaloyl group which may be removed by treatment with an alkylamine, for example dimethylaminopropylamine, or with hydrazine.

[0246] A suitable protecting group for a hydroxy group is, for example, an acyl group, for example an alkanoyl group such as acetyl, an aroyl group, for example benzoyl, or an arylmethyl group, for example benzyl. The deprotection conditions for the above protecting groups will necessarily vary with the choice of protecting group. Thus, for example, an acyl group such as an alkanoyl or an aroyl group may be removed, for example, by hydrolysis with a suitable base such as an alkali metal hydroxide, for example lithium, sodium hydroxide or ammonia. Alternatively an arylmethyl group such as a benzyl group may be removed, for example, by hydrogenation over a catalyst such as palladium-on-carbon.

[0247] A suitable protecting group for a carboxy group is, for example, an esterifying group, for example a methyl or an ethyl group which may be removed, for example, by hydrolysis with a base such as sodium hydroxide, or for example a t-butyl group which may be removed, for example, by treatment with an acid, for example an organic acid such as trifluoroacetic acid, or for example a benzyl group which may be removed, for example, by hydrogenation over a catalyst such as palladium-on-carbon.

[0248] Resins may also be used as a protecting group.

[0249] Once a compound of Formula (I) has been synthesised by any one of the processes defined herein, the processes may then further comprise the additional steps of: (i) removing any protecting groups present; (ii) converting the compound Formula (I) into another compound of Formula (I); (iii) forming a pharmaceutically acceptable salt, hydrate or solvate thereof; and / or (iv) forming a prodrug thereof.

[0250] An example of (ii) above is when a compound of Formula (I) is synthesised and then one or more of the groups may be further reacted to change the nature of the group and provide an alternative compound of Formula (I).

[0251] The resultant compounds of Formula (I) can be isolated and purified using techniques well known in the art.

[0252] The compounds of Formula (I) may be synthesised by the general synthetic113 routes shown in the Examples section below, specific examples of which are described in more detail in the Examples. Biological Activity

[0253] The biological assays described in the Examples section herein may be used to measure the pharmacological effects of the compounds of the present invention.

[0254] Although the pharmacological properties of the compounds of Formula (I) vary with structural change, as expected, the compounds of the invention were found to be active in the assays described in the Examples section. Pharmaceutical Compositions

[0255] According to a further aspect of the present invention, there is provided a pharmaceutical composition comprising a compound of the invention as defined herein, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in admixture with a pharmaceutically acceptable diluent or carrier.

[0256] The compositions of the invention may be in a form suitable for oral use (for example as tablets, lozenges, hard or soft capsules, aqueous or oily suspensions, emulsions, dispersible powders or granules, syrups or elixirs), for topical use (for example as creams, ointments, gels, or aqueous or oily solutions or suspensions), for administration by inhalation (for example as a finely divided powder or a liquid aerosol), for administration by insufflation (for example as a finely divided powder) or for parenteral administration (for example as a sterile aqueous or oily solution for intravenous, subcutaneous, intramuscular, intraperitoneal or intramuscular dosing or as a suppository for rectal dosing).

[0257] The compositions of the invention may be obtained by conventional procedures using conventional pharmaceutical excipients, well known in the art. Thus, compositions intended for oral use may contain, for example, one or more colouring, sweetening, flavouring and / or preservative agents.

[0258] An effective amount of a compound of the present invention for use in therapy is an amount sufficient to treat or prevent a proliferative condition referred to herein, slow its progression and / or reduce the symptoms associated with the condition.

[0259] The amount of active ingredient that is combined with one or more excipients to produce a single dosage form will necessarily vary depending upon the individual treated and the particular route of administration. For example, a formulation intended for oral114 administration to humans will generally contain, for example, from 0.5 mg to 0.5 g of active agent (more suitably from 0.5 to 100 mg, for example from 1 to 30 mg) compounded with an appropriate and convenient amount of excipients which may vary from about 5 to about 98 percent by weight of the total composition.

[0260] The size of the dose for therapeutic or prophylactic purposes of a compound of the Formula (I) will naturally vary according to the nature and severity of the conditions, the age and sex of the animal or patient and the route of administration, according to well-known principles of medicine.

[0261] In using a compound of the invention for therapeutic or prophylactic purposes it will generally be administered so that a daily dose in the range, for example, 0.1 mg / kg to 75 mg / kg body weight is received, given if required in divided doses. In general lower doses will be administered when a parenteral route is employed. Thus, for example, for intravenous or intraperitoneal administration, a dose in the range, for example, 0.1 mg / kg to 30 mg / kg body weight will generally be used. Similarly, for administration by inhalation, a dose in the range, for example, 0.05 mg / kg to 25 mg / kg body weight will be used. Oral administration may also be suitable, particularly in tablet form. Typically, unit dosage forms will contain about 0.5 mg to 0.5 g of a compound of this invention. Therapeutic Uses and Applications

[0262] The functionality of the compounds of the present invention means that they are suitable in a myriad of applications. The compounds of the invention are suitable for binding to at least one protein and / or peptide, thereby forming protein / peptide-payload conjugates. The compounds of the invention are suitable for binding to at least one antibody (e.g., a nanobody such as Anti-HER2 or Anti-PD-L1 (e.g., anti-PD-L1 sdAb)), thereby forming antibody-payload conjugates. In some embodiments, the antibody is trastuzumab. The compounds of the invention are suitable for binding to at least one antibody, thereby forming antibody-drug conjugates. In some embodiments, the antibody is trastuzumab. The compounds of the invention are also suitable for attaching to at least one affibody (e.g., an Anti-HER2 affibody or an Anti-PD-L1 affibody), thereby forming affibody-payload conjugates.

[0263] The present invention provides a method of treating a disease or disorder in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein, or a pharmaceutical composition, as defined herein. Suitably, the disease or disorder is a proliferative disorder (e.g., cancer), an infectious disease (e.g., human immunodeficiency virus or pneumonia), a chronic disease (e.g.,115 diabetes, asthma or rheumatoid arthritis), a hereditary disease (e.g., Hemophilia A), a bone disease (e.g., osteoporosis or osteoarthritis), an autoimmune disease (e.g., psoriasis or Sjögren's syndrome), a respiratory disease (e.g., idiopathic pulmonary fibrosis) or a neurodegenerative disease (e.g., Alzheimer’s disease).

[0264] The present invention provides a method of treating a proliferative disorder in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein, or a pharmaceutical composition, as defined herein.

[0265] The present invention provides a method of treating an infectious disease in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein, or a pharmaceutical composition, as defined herein.

[0266] The present invention provides a method of treating a chronic disease in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein, or a pharmaceutical composition, as defined herein.

[0267] The present invention provides a method of treating a hereditary disease in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein, or a pharmaceutical composition, as defined herein.

[0268] The present invention provides a method of treating a bone disease in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein, or a pharmaceutical composition, as defined herein.

[0269] The present invention provides a method of treating an autoimmune disease in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein, or a pharmaceutical composition, as defined herein.

[0270] The present invention provides a method of treating a respiratory disease in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt,116 hydrate or solvate thereof, as defined herein, or a pharmaceutical composition, as defined herein.

[0271] The present invention provides a method of treating a neurodegenerative disease in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein, or a pharmaceutical composition, as defined herein.

[0272] The present invention provides a method of inhibiting cell proliferation, in vitro or in vivo, said method comprising contacting a cell with an effective amount of a compound or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein, or a pharmaceutical composition as defined herein.

[0273] Suitably, the present invention provides a method of treating cancer in a patient in need of such treatment, said method comprising administering to said patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein, or a pharmaceutical composition, as defined herein.

[0274] The present invention provides a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein, or a pharmaceutical composition as defined herein for use in therapy.

[0275] The present invention provides a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein, or a pharmaceutical composition as defined herein for use in the treatment of a disease or disorder.

[0276] The present invention provides a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein, or a pharmaceutical composition as defined herein for use in the treatment of a proliferative disorder.

[0277] The present invention provides a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein, or a pharmaceutical composition as defined herein for use in the treatment of an infectious disease.

[0278] The present invention provides a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein, or a pharmaceutical composition as defined herein for use in the treatment of a chronic disease.

[0279] The present invention provides a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein, or a pharmaceutical composition as defined herein for use in the treatment of a hereditary disease.

[0280] The present invention provides a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein, or a pharmaceutical composition as defined herein for use in the treatment of a bone disease.117

[0281] The present invention provides a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein, or a pharmaceutical composition as defined herein for use in the treatment of an autoimmune disease.

[0282] The present invention provides a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein, or a pharmaceutical composition as defined herein for use in the treatment of a respiratory disease.

[0283] The present invention provides a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein, or a pharmaceutical composition as defined herein for use in the treatment of a neurodegenerative disease.

[0284] Suitably, the present invention provides a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein, or a pharmaceutical composition as defined herein for use in the treatment of cancer.

[0285] The present invention provides the use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein in the manufacture of a medicament for the treatment of a disease or disorder.

[0286] The present invention provides the use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein in the manufacture of a medicament for the treatment of a proliferative disorder.

[0287] The present invention provides the use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein in the manufacture of a medicament for the treatment of an infectious disease.

[0288] The present invention provides the use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein in the manufacture of a medicament for the treatment of a chronic disease.

[0289] The present invention provides the use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein in the manufacture of a medicament for the treatment of a hereditary disease.

[0290] The present invention provides the use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein in the manufacture of a medicament for the treatment of a bone disease.

[0291] The present invention provides the use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein in the manufacture of a medicament for the treatment of an autoimmune disease.

[0292] The present invention provides the use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein in the manufacture of a medicament for the treatment of a respiratory disease.118

[0293] The present invention provides the use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein in the manufacture of a medicament for the treatment of a neurodegenerative disease.

[0294] Suitably, the present invention provides the use of a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as defined herein in the manufacture of a medicament for the treatment of cancer.

[0295] In the above-outlined aspects of the invention, the proliferative disorder is suitably cancer, and the cancer is suitably a human cancer. Any suitable cancer may be targeted (e.g., adenoid cystic carcinoma, gastrointestinal adenocarcinoma, adenocarcinoma of the stomach or gastroesophageal junction, adrenal gland tumor, solid tumors, malignant ascites, glioblastoma, amyloidosis, anal cancer, appendix cancer, astrocytoma, ataxia- telangiectasia, BeckwithWiedemann Syndrome, bile duct cancer (cholangiocarcinoma), Birt- Hogg-Dubé Syndrome, bladder cancer, bone cancer, brain stem glioma, brain tumor, breast cancer, Carney Complex, central nervous system tumors, cervical cancer, colorectal cancer, Cowden Syndrome, craniopharyngioma, desmoplastic infantile ganglioglioma, ependymoma, esophageal cancer, esophageal squamous cell carcinoma, Ewing sarcoma, eye cancer, eyelid cancer, familial adenomatous polyposis, familial GIST, familial malignant melanoma, familial non-VHL clear cell renal cell carcinoma, familial pancreatic cancer, gallbladder cancer, gastrointestinal stromal tumor – GIST, germ cell tumor, gestational trophoblastic disease, head and neck cancer, hereditary breast and ovarian cancer, gastric cancer, hereditary diffuse gastric cancer, hereditary leiomyomatosis and renal cell cancer, hereditary mixed polyposis syndrome, hereditary pancreatitis, hereditary papillary renal carcinoma, juvenile polyposis syndrome, kidney cancer, lacrimal gland tumor, laryngeal and hypopharyngeal cancer, leukemia (acute lymphoblastic leukamia (ALL), acute myeloid leukemia (AML), B-cell prolymphocytic leukemia, hairy cell leukemia, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), chronic T-cell lymphocytic leukemia, eosinophilic leukemia), LiFraumeni Syndrome, liver cancer, lung cancer (non-small cell lung cancer, small cell lung cancer), Lymphoma (Hodgkin, non-Hodgkin), Lynch Syndrome, mastocytosis, medulloblastoma, melanoma, meningioma, mesothelioma, multiple endocrine neoplasia Type 1 & 2, multiple myeloma, MUTYH (or MYH)-associated polyposis, myelodysplastic syndromes (MDS), nasal cavity and paranasal sinus Cancer, nasopharyngeal Cancer, neuroblastoma, neuroendocrine tumors (e.g., of the gastrointestinal tract, lung or pancreas), neurofibromatosis Type 1 & 2, nevoid basal cell carcinoma syndrome, oral and oropharyngeal cancer, osteosarcoma, ovarian / fallopian tube / peritoneal cancer, pancreatic cancer, parathyroid cancer, penile cancer, PeutzJeghers Syndrome, pheochromocytoma, paraganglioma, pituitary gland tumor, pleuropulmonary blastoma, prostate cancer, retinoblastoma,119 rhabdomyosarcoma, salivary gland cancer, sarcoma (e.g., Kaposi or soft tissue), skin cancer, small bowel cancer, stomach cancer, testicular cancer, thymoma and thymic carcinoma, thyroid cancer, tuberous sclerosis complex, uterine cancer, vaginal cancer, Von Hippel-Lindau syndrome, vulvar cancer, Waldenstrom’s macroglobulinemia, Werner syndrome, Wilms Tumor and xeroderma pigmentosum). Particular cancers of interest include haematological cancers such as lymphomas (including B-cell lymphoma, diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), Burkitt lymphoma (BL) and angioimmunoblastic T-cell lymphoma (AITL)), haematological malignancies, solid malignancies, leukaemias (including acute lymphoblastic leukaemia (ALL) and chronic myeloid leukaemia (CML)), multiple myeloma, breast cancer, non-small cell lung cancer (NSCLC), colorectal cancer, endometrial cancer, gastro-oesophageal cancer, neuroendocrine cancers, osteosarcomas, prostate cancer, pancreatic cancer, small intestine cancer, bladder cancer, rectal cancer, cholangiocarcinoma, CNS cancer, thyroid cancer, head and neck cancer, oesophageal cancer, and ovarian cancer.

[0296] In the above-outlined aspects of the invention, the infectious disease may be Acute Flaccid Myelitis (AFM), Alpha-gal Syndrome (AGS), Anaplasmosis, Anthrax, Avian Influenza, Babesiosis, Botulism, Brucellosis, Campylobacteriosis, Carbapenem-resistant Infection, Chancroid, Chikungunya Virus Infection (Chikungunya), Chlamydia, Ciguatera (Harmful Algae Blooms (HABs)), Clostridium Difficile Infection, Clostridium Perfringens (Epsilon Toxin), Coccidioidomycosis fungal infection (Valley fever), COVID-19 (Coronavirus Disease 2019), Creutzfeldt-Jacob Disease, transmissible spongiform encephalopathy (CJD), Cryptosporidiosis (Crypto), Cyclosporiasis, Dengue, 1,2,3,4 (Dengue Fever), Diphtheria, E. coli infection, Eastern Equine Encephalitis (EEE), Ebola Hemorrhagic Fever (Ebola), Ehrlichiosis, Encephalitis, Arboviral or parainfectious, Enterovirus Infection, Non-Polio (Non- Polio Enterovirus), Enterovirus Infection, D68 (EV-D68), Giardiasis (Giardia), Glanders, Gonococcal Infection (Gonorrhea), Granuloma inguinale, Haemophilus Influenza disease, Type B (Hib or H-flu), Hantavirus Pulmonary Syndrome (HPS), Hemolytic Uremic Syndrome (HUS), Hepatitis A (Hep A), Hepatitis B (Hep B), Hepatitis C (Hep C / HCV), Hepatitis D (Hep D), Hepatitis E (Hep E), Herpes, Herpes Zoster, zoster VZV (Shingles), Histoplasmosis infection (Histoplasmosis), Human Immunodeficiency Virus / AIDS (HIV / AIDS), Human Papillomavirus (HPV), Influenza (Flu), Lead Poisoning, Legionellosis (Legionnaires Disease), Leprosy (Hansens Disease), Leptospirosis, Listeriosis (Listeria), Lyme Disease, Lymphogranuloma venereum infection (LGV), Malaria, Measles, Melioidosis, Meningitis, Viral (Meningitis, viral), Meningococcal Disease , Bacterial (Meningitis, bacterial), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Monkeypox Virus (Mpox), Multisystem Inflammatory Syndrome in Children (MIS-C), Mumps, Norovirus, Paralytic Shellfish Poisoning120 (Paralytic Shellfish Poisoning, Ciguatera), Pediculosis (Lice, Head and Body Lice), Pelvic Inflammatory Disease (PID), Pertussis (Whooping Cough), Plague; Bubonic, Septicemic, Pneumonic (Plague), Pneumococcal Disease (Pneumonia), Poliomyelitis (Polio), Powassan, Psittacosis (Parrot Fever), Pthiriasis (Crabs; Pubic Lice Infestation), Pustular Rash diseases (Small pox, monkeypox, cowpox), Q-Fever, Rabies, Respiratory Syncytial Virus (RSV), Ricin Poisoning, Rickettsiosis (Rocky Mountain Spotted Fever), Rubella, Including congenital (German Measles), Salmonellosis gastroenteritis (Salmonella), Scabies Infestation (Scabies), Scombroid, Septic Shock (Sepsis), Severe Acute Respiratory Syndrome (SARS), Shigellosis gastroenteritis (Shigella), Smallpox, Staphyloccal Infection, Methicillin-resistant (MRSA), Staphylococcal Food Poisoning, Enterotoxin - B Poisoning (Staph Food Poisoning), Staphylococcal Infection, Vancomycin Intermediate (VISA), Staphylococcal Infection, Vancomycin Resistant (VRSA), Streptococcal Disease, Group A (Group A Strep), Streptococcal Disease, Group B (Strep-B), Streptococcal Toxic-Shock Syndrome, STSS, Toxic Shock (STSS, TSS), Syphilis , primary, secondary, early latent, late latent, congenital, Tetanus Infection, tetani (Lock Jaw), Trichomoniasis (Trichomonas infection), Trichonosis Infection (Trichinosis), Tuberculosis (Latent), Tuberculosis, Mycobacteriosis, Tularemia (Rabbit fever), Typhoid Fever, Group D, Typhus, Vaginosis, bacterial (Yeast Infection), Vaping-Associated Lung Injury (e-Cigarette Associated Lung Injury), Varicella (Chickenpox), Vibrio cholerae (Cholera), Vibriosis (Vibrio), Viral Hemorrhagic Fever (Ebola, Lassa, Marburg), West Nile Virus, Yellow Fever, Yersenia (Yersinia) or Zika Virus Infection (Zika).

[0297] In the above-outlined aspects of the invention, the chronic disease may be ALS (Lou Gehrig's Disease), Alzheimer's Disease and other Dementias, arthritis, asthma, Chronic Obstructive Pulmonary Disease (COPD), Crohn's Disease, Ulcerative Colitis, Other Inflammatory Bowel Diseases, Irritable Bowel Syndrome, Cystic Fibrosis, Diabetes, Eating Disorders, Heart Disease, Obesity, Oral Health, Osteoporosis, Reflex Sympathetic Dystrophy (RSD) Syndrome, Sudden Cardiac Arrest (SCA) in Youth or Tobacco Use and Related Conditions.

[0298] In the above-outlined aspects of the invention, the hereditary disease may be Albinism, Angelman syndrome, Ankylosing spondylitis, Apert syndrome, Charcot-Marie-Tooth disease, Congenital adrenal hyperplasia, Cystic fibrosis, Down syndrome, Duchenne muscular dystrophy, Ehlers-Danlos syndrome, Fabry disease, Fragile X syndrome, Haemochromatosis, Haemophilia, Huntington’s disease, Klinefelter (XXY) syndrome, Marfan syndrome, Neurofibromatosis, Noonan syndrome, Prader-Willi syndrome, Rett syndrome, Tay-Sachs disease, Thalassaemia, Tourette syndrome, Turner syndrome, Von Willebrand disease or Williams syndrome.

[0299] In the above-outlined aspects of the invention, the bone disease may be121 Avascular Necrosis (AVN, Osteonecrosis), Benign Bone Tumor, Bone Lesions, Osteoarthritis, Osteogenesis Imperfecta / Brittle Bone Disease, Osteolysis, Osteoporosis, Osteosarcoma (Bone Cancer), Metastatic Bone Disease, Paget’s disease or Ricketts.

[0300] In the above-outlined aspects of the invention, the autoimmune disease may be rheumatoid arthritis, autoimmune demyelinative diseases (e.g., multiple sclerosis, allergic encephalomyelitis), psoriatic arthritis, endocrine ophthalmopathy, uveoretinitis, systemic lupus erythematosus, myasthenia gravis, Graves’ disease, glomerulonephritis, autoimmune hepatological disorder, inflammatory bowel disease (e.g., Crohn’s disease), anaphylaxis, allergic reaction, Sjögren’s syndrome, type I diabetes mellitus, primary biliary cirrhosis, Wegener’s granulomatosis, fibromyalgia, polymyositis, dermatomyositis, multiple endocrine failure, Schmidt’s syndrome, autoimmune uveitis, Addison’s disease, adrenalitis, thyroiditis, Hashimoto’s thyroiditis, autoimmune thyroid disease, pernicious anemia, gastric atrophy, chronic hepatitis, lupoid hepatitis, atherosclerosis, subacute cutaneous lupus erythematosus, hypoparathyroidism, Dressler’s syndrome, autoimmune thrombocytopenia, idiopathic thrombocytopenic purpura, hemolytic anemia, pemphigus vulgaris, pemphigus, dermatitis herpetiformis, alopecia arcata, pemphigoid, scleroderma, progressive systemic sclerosis, CREST syndrome (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia), male and female autoimmune infertility, ankylosing spondolytis, ulcerative colitis, mixed connective tissue disease, polyarteritis nedosa, systemic necrotizing vasculitis, atopic dermatitis, atopic rhinitis, Goodpasture’s syndrome, Chagas’ disease, sarcoidosis, rheumatic fever, asthma, recurrent abortion, anti-phospholipid syndrome, farmer’s lung, erythema multiforme, post cardiotomy syndrome, Cushing’s syndrome, autoimmune chronic active hepatitis, bird-fancier’s lung, toxic epidermal necrolysis, Alport’s syndrome, alveolitis, allergic alveolitis, fibrosing alveolitis, interstitial lung disease, erythema nodosum, pyoderma gangrenosum, transfusion reaction, Takayasu’s arteritis, polymyalgia rheumatica, temporal arteritis, schistosomiasis, giant cell arteritis, ascariasis, aspergillosis, Sampter’s syndrome, eczema, lymphomatoid granulomatosis, Behcet’s disease, Caplan’s syndrome, Kawasaki’s disease, dengue, encephalomyelitis, endocarditis, endomyocardial fibrosis, endophthalmitis, erythema elevatum et diutinum, psoriasis, erythroblastosis fetalis, eosinophilic faciitis, Shulman’s syndrome, Felty’s syndrome, filariasis, cyclitis, chronic cyclitis, heterochronic cyclitis, Fuch’s cyclitis, IgA nephropathy, Henoch- Schonlein purpura, graft versus host disease, transplantation rejection, cardiomyopathy, Eaton-Lambert syndrome, relapsing polychondritis, cryoglobulinemia, Waldenstrom’s macroglobulemia, Evan’s syndrome, and autoimmune gonadal failure. The autoimmune disease may be a disorder of B lymphocytes (e.g., systemic lupus erythematosus, Goodpasture’s syndrome, rheumatoid arthritis, and type I diabetes), Th1-lymphocytes (e.g.,122 rheumatoid arthritis, multiple sclerosis, psoriasis, Sjögren’s syndrome, Hashimoto’s thyroiditis, Graves’ disease, primary biliary cirrhosis, Wegener’s granulomatosis, tuberculosis, or graft versus host disease), or Th2-lymphocytes (e.g., atopic dermatitis, systemic lupus erythematosus, atopic asthma, rhinoconjunctivitis, allergic rhinitis, Omenn’s syndrome, systemic sclerosis, or chronic graft versus host disease). Generally, disorders involving dendritic cells involve disorders of Th1-lymphocytes or Th2-lymphocytes. The autoimmune disorder may be a T cell-mediated immunological disorder.

[0301] In the above-outlined aspects of the invention, the respiratory disease may be Asbestosis, Asthma, Bronchiectasis, Bronchitis, Chronic cough, Chronic obstructive pulmonary disease (COPD), Common cold, COVID-19, Croup, Cystic fibrosis, Hantavirus pulmonary syndrome, Influenza (flu), Interstitial lung disease (ILD), Long COVID, Lung cancer, Pertussis (whooping cough), Pleurisy, Pneumonia, Pulmonary embolism, Pulmonary fibrosis, Pulmonary hypertension, Pulmonary sarcoidosis, Respiratory syncytial virus (RSV), Sleep apnea, Sudden infant death syndrome (SIDS) or Tuberculosis.

[0302] In the above-outlined aspects of the invention, the neurodegenerative disease may be Alzheimer’s disease and other dementias, Parkinson’s disease (PD) and Parkinsonism, Prion disease, Synucleinopathies, Motor neurone diseases, Huntington’s disease, Spinocerebellar ataxia or Spinal muscular atrophy.

[0303] The present invention also provides a method of imaging a sample, the method comprising contacting a compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof as defined herein, with a biological sample and imaging the sample to determine the presence and / or quantity of a substance in the biological sample.123 EXAMPLES – part A

[0305] The following examples are provided solely to illustrate the present invention and are not intended to limit the scope of the invention, as described herein. Figures Figure 1. Compounds of the present invention. Figure 2. A number of precursors for compounds of the present invention. Figure 3. Synthesis of photo maleimide-Peg2-D-Lys(Boc)-Peg2-MMAF (1). Figure 4. Total absorbance chromatogram of pure stable maleimide-Peg2-D-Lys(Boc)-Peg2- MMAF (1). Figure 5. ESI-MS of stable maleimide-Peg2-D-Lys(Boc)-Peg2-MMAF (1) Figure 6. Conjugation scheme of maleimide-Peg2-D-Lys(Boc)-Peg2-MMAF (1). Figure 7. Synthesis of maleimide-DOTA (2). Figure 8. Total absorbance chromatogram of pure stable maleimide-DOTA (2). Figure 9. ESI-MS of stable maleimide-DOTA (2). Figure 10. Conjugation scheme of maleimide-DOTA (2). Figure 11. LC-MS data for Anti-HER2 Nb unmodified. Figure 12. LC-MS data for Anti-HER2 Nb–(1) conjugate (pre-immolation). Figure 13. LC-MS data for Anti-HER2 Nb–(1) conjugate (post-immolation / hydrolysis purified). Figure 14. LC-MS data for Anti-PD-L1 NB unmodified. Figure 15. LC-MS data for Anti-PD-L1 Nb–(1) conjugate (pre-immolation). Figure 16. LC-MS data for Anti-PD-L1 Nb–(1) conjugate (post-immolation / hydrolysis purified). Figure 17. LC-MS data for Anti-PD-L1 Nb–(2) conjugate (pre-immolation). Figure 18. LC-MS data for Anti-PD-L1 Nb–(2) conjugate (post-immolation / hydrolysis purified). Synthetic procedures for the preparation of small molecules Stable maleimide-Peg2-D-Lys-Peg2-MMAF (1)

[0306] NH2-Peg2-D-Lys(Boc)-Peg2-MMAF-OH (Intermediate I) was assembled on a solid support in a 25 µmol scale from H-(L)-Phe-2CT resin, (46 mg, 0.54 mmol g−1) following124 a stepwise Fmoc / tBu strategy. Coupling reactions were carried out manually on a 5 mL reactor using the following protocols. Swelling: The resin was swelled for 20 min in DCM. Fmoc removal: The resin was treated with a solution of 20 % piperidine in DMF (2 × 10 min), then washed with DCM (3 × 1 min) and DMF (2 × 1 min). Activation / Coupling: Fmoc protected amino acid (4.0 equivalents) and HATU (3.9 equivalents) were dissolved in DMF (1 mL), then DIPEA (10 equivalents) was added. The mixture was pre-activated for 3 min, added to the resin, and stirred at room temperature for 30 min. The resin was washed with DCM (3 × 1 min) and DMF (2 × 1 min). Final cleavage: The resin was treated with the cocktail DCM / HFIP (3:1). The solvents from the cleavage cocktail were then evaporated under a constant flow of nitrogen, redissolved in 500 µL DMSO and used in the next synthetic step without further purification and assuming full conversion to the desired product.

[0307] Stable maleimide I (14 mg, 1.1 Eq, 30 μmol) and HATU (10 mg, 1 Eq, 27 μmol) were dissolved in 500 µL DMSO. N-methylmorpholine (28 mg, 30 μL, 10 Eq, 0.27 mmol) was added and the reaction stirred for 5 minutes at room temperature. The mixture was then added to a stock solution of Intermediate I (35 mg, 1 Eq, 27 μmol) in 500 µL DMSO. After 2h reaction full conversion to the desired product was corroborated by LC-MS analysis. The crude was purified by preparative HPLC and 7.1 mg (17% overall yield) of the desired compound 1 was isolated in a form of an amorphous white solid. ESI-MS calculated for [C83H131N12O26]+1711.9, found 1712.2. The reaction scheme is shown in Figure 3. Stable maleimide-DOTA (2)

[0308] Stable maleimide II (150 mg, 1 Eq, 304 μmol) and HATU (127 mg, 1.1 Eq, 334 μmol) were dissolved in 2 mL DMSO and N-methylmorpholine (61.5 mg, 67 μL, 2 Eq, 608 μmol) was added. After 3 minutes stirring at room temperature, a solution of tert-butyl piperazine-1-carboxylate (62.3 mg, 1.1 Eq, 334 μmol) in 1 mL DMSO was added. LC-MS was checked after 10 minutes and no trace of the starting material was observed. Preparative HPLC was performed to isolate Intermediate II (64 mg, 32% yield) as a colourless oil and employed in the next synthetic step. ESI-MS calculated for [C27H44N5O10S2]+662.3, found 662.6.

[0309] Intermediate II (36 mg, 1 Eq, 54 μmol) was dissolved in 0.7 mL DCM and 0.3 mL TFA and stirred at R.T for 15 min. Solvent was blown off under nitrogen overnight. Reaction mixture was dissolved in DMSO and N-methylmorpholine (55 mg, 60 μL, 10 Eq, 0.54 mmol) was added. After 3 minutes stirring at RT, NHS-DOTA (62 mg, 1.6 mL, 50 mmolar, 1.5 Eq, 82 μmol) in DMSO was added and when no further conversion was observed via LC-MS, the crude reaction was purified by preparative HPLC. Stable maleimide-DOTA 5 was isolated as a colourless oil 10.3 mgs (20% yield over one step). ESI-MS calculated for [C38H62N9O15S2]+125 948.4, found 948.8. The reaction scheme is shown in Figure 7. Preparation of nanobody conjugates with molecules (1) and (2) Anti-HER2 Nb–(1) conjugate

[0310] To a solution of HER2 targeting nanobody1(100 µL, 48 µM, PBS pH 7.4) expressed and purified from E. coli, TCEP (1.2 µL, 10 mM in MQ water, 2.5 equivalents) was added and incubated for 30 minutes at 25 °C to reduce intermolecular disulfides. To this, a solution of 1 (2.4 µL, 10 mM in DMSO, 5 equivalents) was added and incubated for 10 minutes at 25 °C. After full conversion was confirmed by LC-MS, the conjugate was irradiated for 3 minutes with a 30 W LED at 365 nm to unmask the secondary amine and induce hydrolytic stabilisation of the thio-succinimide. Excess small molecule was removed and the samples buffer exchanged into PBS (pH 7.4) by 5× UF / DF using Amicon® spin columns (10 kDa MWCO) (Yield: 80 µL, 30 µM, 51%). Anti-PD-L1 Nb–(1) conjugate

[0311] To a solution of PD-L1 targeting nanobody2(100 µL, 74 µM, PBS pH 7.4) expressed and purified from E. coli, TCEP (1.85 µL, 10 mM in MQ water, 2.5 equivalents) was added and incubated for 30 minutes at 25 °C to reduce intermolecular disulfides. To this, a solution of 1 (3.7 µL, 10 mM in DMSO, 5 equivalents) was added and incubated for 10 minutes at 25 °C. After full conversion was confirmed by LC-MS, the conjugate was irradiated for 3 minutes with a 30 W LED at 365 nm to unmask the secondary amine and induce hydrolytic stabilisation of the thio-succinimide. Excess small molecule was removed and the samples buffer exchanged into PBS (pH 7.4) by 5× UF / DF using Amicon® spin columns (10 kDa MWCO) (Yield: 80 µL, 41 µM, 44%). Anti-PD-L1 Nb–(2) conjugate

[0312] To a solution of PD-L1 targeting nanobody2(100 µL, 74 µM, PBS pH 7.4) expressed and purified from E. coli, TCEP (3.7 µL, 10 mM in MQ water, 5 equivalents) was added and incubated for 30 minutes at 25 ˚ C to reduce intermolecular disulfides. To this, a solution of 2 (7.4 µL, 10 mM in DMSO, 10 equivalents) was added and incubated for 10 minutes at 25 °C. Upon complete conjugation, as determined by LC-MS, TCEP (11.1 µL, 10 mM in MQ water, 15 equivalents) was added along with Tris-HCl pH 8.5 (13.5 µL, 500 mM) to achieve a final Tris-HCl concentration of 50 mM. The reaction was incubated at 37 °C for 1 hour until complete immolation and hydrolysis of the thio-succinimide was achieved. Excess small molecule was removed and the samples buffer exchanged into PBS (pH 7.4) by 5× UF / DF using Amicon® spin columns (10 kDa MWCO) (Yield: 95 µL, 45 µM, 58%).126 EXAMPLES – part B

[0313] The following further examples are provided solely to illustrate the present invention and are not intended to limit the scope of the invention, as described herein. Figures Figure 19. synthesis of maleimide ValCit-MMAE (6). Figure 20. molecular structure of maleimide ValCit-MMAE (6). Figure 21. proposed mechanism for triggered hydrolysis of conjugates of (6). Figure 22. photolysis-triggered maleimide hydrolysis of stable maleimide-ValCit-PAB-Payload conjugates. Figure 23. LC-MS data for Anti-HER2 Nb2 (unmodified). Figure 24. LC-MS data for Anti-HER2 Nb2–(6) conjugate (pre-immolation). Figure 25. LC-MS data for Anti-HER2 Nb2–(6) conjugate (immolated). Figure 26. LC-MS data for Anti-HER2 Nb2–(2) conjugate (pre-immolation). Figure 27. LC-MS data for Anti-HER2 Nb2–(2) conjugate (immolated). Figure 28. LC-MS data for Anti-HER2 affibody (unmodified). Figure 29. LC-MS data for Anti-HER2 affibody–(6) conjugate (pre-immolation). Figure 30. LC-MS data for Anti-HER2 affibody–(6) conjugate (immolated). Figure 31. LC-MS data for Anti-PD-L1 sdAb–(6) conjugate (pre-immolation). Figure 32. LC-MS data for Anti-PD-L1 sdAb–(6) conjugate (immolated). Figure 33. LC-MS data for trastuzumab (unmodified). Figure 34. LC-MS data for trastuzumab-(6) DAR8 (pre-immolation). Figure 35. LC-MS data for trastuzumab-(6) DAR8 (immolated). Figure 36.1H NMR spectrum of compound A2, 500 MHz, CDCl3. Figure 37. total absorbance chromatogram of pure compound A3. Figure 38. total absorbance chromatogram of crude compound A4. Figure 39. total absorbance chromatogram of pure compound A5. Figure 40.1H NMR spectrum of compound A5, 500 MHz CDCl3.127 Figure 41.13C NMR spectrum of compound A5, 125 MHz CDCl3. Figure 42. total absorbance chromatogram of compound A6, 125 MHz CDCl3. Figure 43. Deconvoluted LC-MS spectrum of anti-PDL1 sdAb. Figure 44. Deconvoluted LC-MS spectrum of conjugate anti-PDL1 sdAb -A6 (Calculated mass: 16882 Da). Figure 45. Deconvoluted LC-MS spectrum of conjugate anti-PDL1 sdAb -A6 after 15 min of TCEP reduction (Calculated masses: reduced: 16673 Da; immolated: 16508 Da; hydrolysed: 16526 Da). Figure 46. Deconvoluted LC-MS spectrum of conjugate anti-PDL1 sdAb -A6 after 30 min of TCEP reduction (Calculated masses: reduced: 16673 Da; immolated: 16508 Da; hydrolysed: 16526 Da). Figure 47. Deconvoluted LC-MS spectrum of conjugate anti-PDL1 sdAb -A6 after 1 h of TCEP reduction (Calculated masses: reduced: 16673 Da; immolated: 16508 Da; hydrolysed: 16526 Da). Figure 48. Deconvoluted LC-MS spectrum of conjugate anti-PDL1 sdAb -A6 after 2 h of TCEP reduction (Calculated masses: reduced: 16673 Da; immolated: 16508 Da; hydrolysed: 16526 Da). Synthetic procedure for the preparation of stable maleimide ValCit-MMAE (6)

[0314] Stable maleimide I (14 mg, 1.1 Eq, 30 μmol) and HATU (10 mg, 1 Eq, 27 μmol) were dissolved in 500 µL DMSO. N-methylmorpholine (28 mg, 30 μL, 10 Eq, 0.27 mmol) was added and the reaction stirred for 5 minutes at room temperature. The mixture was then added to a stock solution of Val-Cit-PAB-MMAE (30 mg, 1 Eq, 27 μmol) in 500 µL DMSO. After 2h reaction full conversion to the desired product was corroborated by LC-MS analysis. The crude was purified by preparative HPLC and 15.1 mg (36% overall yield) of the desired compound (6) was isolated in a form of an amorphous white solid. ESI-MS calculated for [C77H114N13O21]2+778.41, found 779.3. The synthesis of (6) is shown in Figure 19. Preparation of protein conjugates with molecules (2) and (6) Anti-HER2 Nb2–(6) conjugate

[0315] To a solution of HER2 targeting nanobody (100 µL, 457 µM, PBS pH 7.4 + 1mM TCEP) expressed and purified from E. coli, Azido-PEG3-azide (11 µL, 100 mM in MQ128 water, 24 equivalents) was added and incubated for 30 minutes at 37 °C. To this, DMF (17µL) and a solution of (6) (9.1 µL, 10 mM in DMF, 2 equivalents) were added and the mixture was incubated for 10 minutes at 25 °C. After full conversion was confirmed by LC-MS, the conjugate was irradiated for 3 minutes with a 30 W LED at 365 nm to unmask the secondary amine and induce hydrolytic stabilisation of the thio-succinimide. Excess small molecule was removed and the samples buffer exchanged into PBS (pH 7.4) by 5× UF / DF using Amicon® spin columns (10 kDa MWCO). Anti-HER2 Nb2–(2) conjugate

[0316] To a solution of HER2 targeting nanobody (100 µL, 457 µM, PBS pH 7.4 + 1mM TCEP) expressed and purified from E. coli, Azido-PEG3-azide (5 µL, 100 mM in MQ water, 11 equivalents) was added and incubated for 30 minutes at 37 °C. To this, a solution of (2) (9.1 µL, 10 mM in DMSO, 2 equivalents) was added and incubated for 10 minutes at 25 °C. Upon complete conjugation, as determined by LC-MS, TCEP (34.2 µL, 200 mM Tris-HCl pH 8.5 in MQ water, 15 equivalents) was added. The reaction was incubated at 37 °C for 2 hours until complete immolation and hydrolysis of the thio-succinimide was achieved. Excess small molecule was removed and the samples buffer exchanged into PBS (pH 7.4) by 5× UF / DF using Amicon® spin columns (10 kDa MWCO) (Yield: 95 µL, 45 µM, 58%). Anti-HER2 affibody Nb–(6) conjugate

[0317] To a solution of HER2 targeting affibody (200 µL, 200 µM, PBS pH 7.4 + 0.5 mM TCEP) expressed and purified from E. coli, Azido-PEG3-azide (5 µL, 100 mM in MQ water, 12.5 equivalents) was added and incubated for 30 minutes at 37 °C. To this, DMF (36 µL) and a solution of (6) (8 µL, 10 mM in DMF, 2 equivalents) were added and the mixture was incubated for 10 minutes at 25 °C. After full conversion was confirmed by LC-MS, the conjugate was irradiated for 3 minutes with a 30 W LED at 365 nm to unmask the secondary amine and induce hydrolytic stabilisation of the thio-succinimide. Anti-PD-L1 sdAb–(6) conjugate

[0318] To a solution of PD-L1 targeting sdAb (90 µL, 74 µM, PBS pH 7.4) expressed and purified from E. coli, TCEP (1.67 µL, 10 mM in MQ water, 2.5 equivalents) was added and incubated for 30 minutes at 25 °C to reduce intermolecular disulfides. To this, a solution of (6) (3.3 µL, 10 mM in DMSO, 5 equivalents) was added and incubated for 10 minutes at 25 °C. After full conversion was confirmed by LC-MS, the conjugate was irradiated for 3 minutes with a 30 W LED at 365 nm to unmask the secondary amine and induce hydrolytic stabilisation of the thio-succinimide. Excess small molecule was removed and the samples buffer exchanged into PBS (pH 7.4) by 5× UF / DF using Amicon® spin columns (10 kDa MWCO) (Yield: 80 µL, 41 µM, 44%).129 Trastuzumab–(6) conjugate (DAR8)

[0319] To a solution of HER2 targeting Trastuzumab antibody (100 µL, 25 mg / mL, 167 µM), TCEP (8.4 µL, 20 mM in MQ water, 10 equivalents) was added and incubated for 60 minutes at 37 °C. Following, azido-PEG3-azide (8.4 µL, 100 mM in MQ water, 50 equivalents) was added and incubated for 30 minutes at 37 °C. To this, DMF (6.5 µL) and a solution of (6) (16.7 µL, 10 mM in DMF, 10 equivalents) were added and the mixture was incubated for 30 minutes at 25 °C. After conversion to DAR8 was confirmed by LC-MS, the conjugate was irradiated for 3 minutes with a 30 W LED at 365 nm to unmask the secondary amine and induce hydrolytic stabilisation of the thio-succinimide. Protein sequences

[0320] anti HER2 Nb2 (SEQ ID NO: 1) EVQLQESGGGLVQPGGSLRLSCAASGFIFSNDAMTWVRQAPGKGLEWVSSINWSGTHTN YADSVKGRFTISRDNAKRTLYLQMNSLKDEDTALYYCVTGYGVTKTPTGQGTQVTVSSEAA AKEACAKGSENLYFQGHHHHHH Calculated molecular weight: 15394 Da Theoretical extinction coefficient: 25565 M−1cm−1.

[0321] anti HER2 affibody (SEQ ID NO: 2) GHHHHHHGVDNKFNKEMCNAYWEIALLPNLNNQQKRAFIRSLYDDPSQSANLLAEAKKLN DAQAPK Calculated molecular weight: 7589 Da Theoretical extinction coefficient: 8480 M−1cm−1.

[0322] anti-HER2 sdAb (2Rb17c) (SEQ ID NO: 3) EVQLQESGGGLVQPGGSLRLSCAASGFIFSNDAMTWVRQAPGKGLEWVSSINWSGTHTN YADSVKGRFTISRDNAKRTLYLQMNSLKDEDTALYYCVTGYGVTKTPTGQGTQVTVSSDCE GSENLYFQGHHHHHH Calculated molecular weight: 14768 Da Theoretical extinction coefficient: 25565 M−1cm−1. Synthetic procedure for the preparation of maleimide A6130

[0323] Maleimide (2.9 g, 30 mmol) was dissolved in acetonitrile (40 mL), and 2,5- dimethylfuran (9.5 mL, 90 mmol) was added. The mixture was heated at 60 °C with stirring for 6 h. The solvent was removed under reduced pressure to afford a mixture of the exo- and endo-products A1 (5.8 g, quantitative yield).

[0324] 1,2-dibromoethane (5.6 g, 30 mmol) was dissolved in DMF (15 mL) at room temperature and potassium carbonate (21 g, 150 mmol) was added. A solution of the protected maleimide A1 (5.8 g, 30 mmol) in DMF (300 mL) was added dropwise over 30 min at room temperature. The reaction mixture was heated at 50 °C and stirred for an additional 1.5 h. The solvent was removed under reduced pressure at 60 °C and the remaining crude was partitioned between H2O and ethyl acetate (EtOAc). The organic layer was dried over Mg2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography (DCM / acetone 100:2) and isolated as a diastereomeric mixture A2 (1:1) (2.3 g, 26%).

[0325] β-Alanine t-butyl ester hydrochloride (1.09 g, 6 mmol) and A2 (600 mg, 2 mmol) were dissolved in DMF (15 mL) at room temperature, and potassium carbonate (1.38 g, 10 mmol) was added. The reaction mixture was stirred at room temperature for 72 h. The solvent was removed under reduced pressure at 60 °C, and A3 was isolated as a white amorphous solid by preparative reverse-phase HPLC using a linear gradient 5% B(1 min)>13 min>35% B (200 mg, 28%). ESI-MS calculated for [C19H29N2O5]+365.21, found 366.23.131

[0326] A3 (128 mg, 0.35 mmol), 4-nitrophenyl (4-(pyridin-2-yldisulfaneyl)benzyl) carbonate (116 mg, 0.28 mmol), and N-methylmorpholine (386 µL, 3.51 mmol) were suspended in DMSO (480 µL) and the reaction mixture was stirred at room temperature for 5 h. Product A4 was employed in the next step without further purification. ESI-MS calculated for [C32H38N3O7S2]+640.22, found 640.40.

[0327] To A4 (225 mg, 0.35 mmol) dissolved in DMSO (650 µL), 2-(2-(2-(2- mercaptoethoxy)ethoxy)ethoxy)ethan-1-ol (222 mg, 1.06 mmol) was added and the reaction mixture was stirred at room temperature for 2 h. A5 was isolated as a white amorphous solid by preparative reverse-phase HPLC using a linear gradient 5% B(1 min)>15 min>95% B (70 mg, 27%). ESI-MS calculated for [C35H50N2NaO11S2]+761.28, found 761.42.

[0328] A5 (10 mg, 14 µmol) was dissolved in DMSO (0.6 mL, 20 mM) and the mixture was stirred in an open Eppendorf at 90 °C for 2 h to afford the deprotected maleimide A6, which was directly employed in the bioconjugation step. ESI-MS calculated for [C29H42N2NaO10S2]+665.22, found 665.42.

[0329] Anti-PD-L1 sdAb (78 µM, 50 µL) in PBS (pH 7.4) was reduced for 10 min at room temperature using 5 equivalents of TCEP. After checking the completion of the reduction step by LC–MS, the excess of TCEP was quenched by adding azido-PEG-azide (5 uL,10 mM) and incubating the protein at 37 °C for 1 h.5 equivalents of A6 were subsequently added and the reaction mixture was incubated for 10 min at room temperature. After checking the conversion by LC-MS, the reaction mixture was buffer exchanged into PBS (pH 7.4) using a132 ZebaTMspin desalting column to remove excess azido-PEG-azide. The modified protein was reduced using 5 equiv of TCEP, and the conversion towards the reduced, immolated and hydrolysed products was determined after 15 min, 30 min, 1 h, and 2 h.133 REFERENCES 1. Vaneycken, I.; Devoogdt, N.; Van Gassen, N.; Vincke, C.; Xavier, C.; Wernery, U.; Muyldermans, S.; Lahoutte, T.; Caveliers, V. Preclinical Screening of Anti-HER2 Nanobodies for Molecular Imaging of Breast Cancer. The FASEB Journal 2011, 25 (7), 2433–2446.2. Fedorov, A. A.; Fedorov, E. V.; Samanta, D.; Almo, S. C.; Ploegh, H.; Ingram, J.; Dougan, M. RCSB PDB - 5DXW: Crystal structure of mouse PD-L1 nanobody. https: / / www.rcsb.org / structure / 5DXW (accessed 2023-10-25).

Claims

134 CLAIMS 1. A compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, having the structural Formula (I), shown below:wherein: m is 1, 2 or 3; n is 1, 2 or 3; R1is a group of formula: X1-Y1-X2-Y2wherein: X1is aryl, carbocycle, (1-6C)alkyl, (2-6C)alkenyl or -(CRaRb)q-S-S-, where Raand Rbare each independently selected from hydrogen or (1-6C)alkyl, and where q is 0, 1, 2, 3 or 4; Y1is absent or is selected from (1-6C)alkyl, (1-6C)hydroxyalkyl, (1-6C)haloalkyl or (1- 6C)alkoxy; X2is absent or is selected from -S-S-, -O-, -C(O)-, -C(O)-O-, -O-C(O)-, -O-C(O)-NRc-, -C(O)-N(Rc)-, -N(Rc)-C(O)-, -NRc-, -N(Rc)-C(O)-NRc-, -S-C(O)-, -SO2N(Rc)- or - N(Rc)SO2-, where each Rcis independently selected from hydrogen or (1-6C)alkyl; and Y2 is selected from hydrogen, halo, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkoxy-(1- 6C)alkyl, aryl, carbocycle or -[CH2-CH2-O]p-CH2-CH2-OH, wherein p is 1, 2, 3, 4, or 5; and135 wherein any aryl or carbocycle is optionally substituted by one or more substituents independently selected from halo, hydroxy, cyano, amino, nitro, (1-4C)alkyl, (1- 4C)hydroxyalkyl, (1-4C)haloalkyl or (1-4C)alkoxy; L is a linker; and PL is a payload.

2. The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, according to claim 1, wherein m is 2.

3. The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, according to claim 1 or 2, wherein n is 2.

4. The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, according to claim 1, 2 or 3, wherein R1 is a group of formula: X1-Y1-X2-Y2 wherein: X1 is aryl, carbocycle, (1-4C)alkyl, (2-4C)alkenyl or -(CRaRb)q-S-S-, where Ra and Rb are each independently selected from hydrogen or (1-4C)alkyl, and where q is 0, 1, 2, 3 or 4; Y1 is absent or is selected from (1-4C)alkyl, (1-4C)hydroxyalkyl, (1-4C)haloalkyl or (1- 4C)alkoxy; X2 is absent or is selected from -S-S-, -O-, -C(O)-, -C(O)-O-, -O-C(O)-, -O-C(O)-NRc-, -C(O)-N(Rc)-, -N(Rc)-C(O)-, -NRc-, -N(Rc)-C(O)-NRc-, -S-C(O)-, -SO2N(Rc)- or - N(Rc)SO2-, where each Rc is independently selected from hydrogen or (1-4C)alkyl; and Y2 is selected from hydrogen, halo, (1-6C)alkyl, (1-6C)alkoxy, (1-4C)alkoxy-(1- 4C)alkyl, aryl, carbocycle or -[CH2-CH2-O]p-CH2-CH2-OH, wherein p is 1, 2, 3, 4, or 5; and wherein any aryl or carbocycle is optionally substituted by one or more substituents independently selected from halo, hydroxy, cyano, amino, nitro, (1-2C)alkyl, (1- 2C)hydroxyalkyl, (1-2C)haloalkyl or (1-2C)alkoxy.136 5. The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, according to any one of the preceding claims, wherein R1is a group of formula: X1-Y1-X2-Y2wherein: X1is phenyl, a polycyclic aromatic hydrocarbon, a 6- to 13-memebred carbocycle (e.g., a polycyclic carbocycle), (1-2C)alkyl or -(CRaRb)q-S-S-, where Raand Rbare each independently selected from hydrogen or (1C)alkyl, and where q is 0, 1 or 4; Y1 is absent or (1-2C)alkyl; X2 is absent or is selected from -S-S-, -O-, -C(O)-, -C(O)-O-, -O-C(O)-NRc-, -C(O)- N(Rc)-, -NRc- or -S-C(O)-, where each Rc is hydrogen; and Y2 is selected from hydrogen, (1-4C)alkyl, (1-2C)alkoxy-(1-2C)alkyl, phenyl, 6- to 9- membered carbocycle, or -[CH2-CH2-O]p-CH2-CH2-OH, wherein p is 2, 3, or 4; and wherein any aryl or carbocycle is optionally substituted by one, two or three substituents independently selected from halo, hydroxy, amino, nitro, (1C)alkyl, (1C)hydroxyalkyl, (1C)haloalkyl or (1C)alkoxy.

6. The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, according to any one of the preceding claims, wherein R1 is a group of formula: X1-Y1-X2-Y2 wherein: X1 is phenyl, fluorene, (1C)alkyl or -(CRaRb)q-S-S-, where Ra and Rb are each independently selected from hydrogen or (1C)alkyl, and where q is 0 or 1; Y1 is absent or (2C)alkyl; X2 is absent or is -S-S-, -O-C(O)-NRc-, or -S-C(O)-, where each Rc is hydrogen; and Y2 is selected from hydrogen, (1C)alkoxy-(2C)alkyl, or-[CH2-CH2-O]p-CH2-CH2-OH, wherein p is 3; and wherein phenyl is substituted by one or three substituents independently selected from nitro or (1C)alkoxy.

7. The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, according to any one of the preceding claims, wherein R1is a group selected from:138 wherein denotes the point of attachment.

8. The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, according to any one of the preceding claims, wherein R1is a group selected from:wherein denotes the point of attachment.

9. The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, according to any one of the preceding claims, wherein L is a 5-250 bridging atom chain linking the N atom to PL, wherein the 5-250 bridging atom chain is optionally substituted by one or more group(s) LX.

10. The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, according to any one of the preceding claims, wherein L is a (1-35C) alkylene linker, wherein the alkylene chain optionally further comprises one or more -O-, -C(O)-, -C(O)NRd-, -NRdC(O)- , -C(O)O-, -OC(O), -arylene-, -heterocyclyl- and / or -alkynylene- group(s) within the alkylene139 chain, where each Rdis independently hydrogen or (1-2C)alkyl and wherein the alkylene chain is optionally substituted by one or more group(s) LX.

11. The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, according to any one of the preceding claims, wherein L is a (2-15C) alkylene linker, wherein the alkylene chain optionally further comprises one or more -O-, -C(O)-, -C(O)NRd-, -NRdC(O)- , -C(O)O-, -OC(O), -arylene-, -heterocyclyl- and / or -alkynylene- group(s) within the alkylene chain, where each Rd is independently hydrogen or (1-2C)alkyl and wherein the alkylene chain is optionally substituted by one or more group(s) LX.

12. The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, according to any one of the preceding claims, wherein L is a (2-15C) alkylene linker, wherein the alkylene chain further comprises one to four -O- groups, one or two -C(O)- groups, one to four -C(O)NRd- groups, one to three -NRdC(O)- groups, one or two -C(O)O- groups, one or two -OC(O) groups, one or two -phenylene- groups, one or two -pyrrolidine- groups, one or two -piperazine- groups and / or one or two -C≡C- groups within the alkylene chain, where each Rd is independently hydrogen or (1C)alkyl and wherein the alkylene chain is optionally substituted by one or more group(s) LX.

13. The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, according to any one of the preceding claims, wherein L is a (2-15C) alkylene linker, wherein the alkylene chain further comprises: (i) three -C(O)NH- groups, one -OC(O) group and one -phenylene- group within the alkylene chain; (ii) two or three -O- groups, one -C(O)- group, one -C(O)NH- group and one - NHC(O)- group within the alkylene chain; (iii) one -C(O)NH group and two -NHC(O)- groups within the alkylene chain; (iv) two or three -O- groups, one -C(O)- group, one -C(O)NH- group and one - NHC(O)- group within the alkylene chain; (v) two or three -O- groups, one -C(O)- group, three -C(O)NH- groups, one - NHC(O)- group, one -OC(O) group, one -phenylene- group and one - pyrrolidine- group within the alkylene chain; (vi) four -O- groups, two -C(O)NH- groups and one -C≡C- group within the alkylene140 chain; (vii) one -C(O)- group and one -piperazine- group within the alkylene chain; (viii) four -O- groups, one -C(O)- group and three -C(O)NH- groups within the alkylene chain;or (ix) one -C(O)O- group within the alkylene chain; and wherein the alkylene chain is optionally substituted by one or two group(s) LX.

14. The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, according to any one of the preceding claims, wherein L is: (i) a (4C) alkylene linker, wherein the alkylene chain further comprises three - C(O)NH- groups, one -OC(O) group and one -phenylene- group within the alkylene chain, and wherein the alkylene chain is substituted by two groups LX; (ii) a (10C) alkylene linker, wherein the alkylene chain further comprises two -O- groups, one -C(O)- group, one -C(O)NH- group and one -NHC(O)- group within the alkylene chain; (iii) a (12C) alkylene linker, wherein the alkylene chain further comprises three -O- groups, one -C(O)- group, one -C(O)NH- group and one -NHC(O)- group within the alkylene chain; (iv) a (6C) alkylene linker, wherein the alkylene chain further comprises one - C(O)NH group and two -NHC(O)- groups within the alkylene chain, and wherein the alkylene chain is substituted by two groups LX; (v) a (10C) alkylene linker, wherein the alkylene chain further comprises two -O- groups, one -C(O)- group, one -C(O)NH- group and one -NHC(O)- group within the alkylene chain; (vi) a (12C) alkylene linker, wherein the alkylene chain further comprises three -O- groups, one -C(O)- group, one -C(O)NH- group and one -NHC(O)- group within the alkylene chain; (vii) a (12C) alkylene linker, wherein the alkylene chain further comprises two -O- groups, one -C(O)- group, three -C(O)NH- groups, one -NHC(O)- group, one - OC(O) group, one -phenylene- group and one -pyrrolidine- group within the alkylene chain; (viii) a (14C) alkylene linker, wherein the alkylene chain further comprises three -O-141 groups, one -C(O)- group, three -C(O)NH- groups, one -NHC(O)- group, one - OC(O) group, one -phenylene- group and one -pyrrolidine- group within the alkylene chain; (ix) a (13C) alkylene linker, wherein the alkylene chain further comprises four -O- groups, two -C(O)NH- groups and one -C≡C- group within the alkylene chain; (x) a (2C) alkylene linker, wherein the alkylene chain further comprises one -C(O)- group and one -piperazine- group within the alkylene chain; or (xi) a (15C) alkylene linker, wherein the alkylene chain further comprises four -O- groups, one -C(O)- group and three -C(O)NH- groups within the alkylene chain, and wherein the alkylene chain is substituted by one group LX (xii) a (2C) alkylene linker, wherein the alkylene chain further comprises one - C(O)O- group within the alkylene chain.

15. The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, according to any one of the preceding claims, wherein L is a linker having the formula: -L1-Z1-L2-Z2-L3-Z3-L4-Z4-L5-Z5-L6-Z6- wherein L1 is a (1-4C)alkylene; Z1 is selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; L2 is a absent, (1-10C)alkylene, a heterocycle or a group of the formula -[CH2CH2]-[O- CH2CH2]a-, wherein a is 1 to 6; Z2 is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; L3 is absent, a (1-10C)alkylene, a (2-10C)alkynylene or a group of the formula - [CH2CH2]-[O-CH2CH2]b-, wherein b is 1 to 6; Z3 is absent or is selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O-, -OC(O)-; L4 is absent or is selected from (1-10C)alkylene, (1-10C)alkylene-arylene or a group of the formula -[CH2CH2]-[O-CH2CH2]c-, wherein c is 1 to 6; Z4 is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; L5 is absent, a (1-10C)alkylene or a heterocycle; Z5is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; L6is absent, a (1-10C)alkylene or a (1-10C)alkylene-arylene;142 Z6is absent or selected from -O-, -C(O)-, -C(O)NRe-, -NReC(O)-, -C(O)O- or -OC(O)-; wherein each Reis independently hydrogen or (1-2C)alkyl; and wherein any one or more of L1, Z1, L2, Z2, L3, Z3, L4, Z4, L5, Z5, L6and / or Z6is optionally substituted by a group LX.

16. The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, according to any one of the preceding claims, wherein L is a linker having the formula: -L1-Z1-L2-Z2-L3-Z3-L4-Z4-L5-Z5-L6-Z6- wherein L1 is a (1-2C)alkylene; Z1 is selected from -C(O)-, -C(O)O- or -C(O)NRe-; L2 is absent, a (1-2C)alkylene, a 6-membered nitrogen-containing heterocycle or a group of the formula -[CH2CH2]-[O-CH2CH2]a-, wherein a is 2 to 4; Z2 is absent or selected from -C(O)NRe- or -NReC(O)-; L3 is absent, a (1-2C)alkylene, a (2-3C)alkynylene or a group of the formula -[CH2CH2]- [O-CH2CH2]b-, wherein b is 2 to 4; Z3 is absent or is selected from -C(O)-, -C(O)NRe- or -NReC(O)-; L4 is absent or is selected from (1-2C)alkylene, (1-2C)alkylene-arylene or a group of the formula -[CH2CH2]-[O-CH2CH2]c-, wherein c is 2 to 4; Z4 is absent or selected from -C(O)- or -OC(O)-; L5 is absent, a (1-2C)alkylene or a 5-memebered nitrogen-containing heterocycle; Z5 is absent or selected from -C(O)NRe- or -OC(O)-; L6 is absent, a (1-2C)alkylene or a (1-2C)alkylene-arylene; Z6 is absent or -OC(O)-; wherein each Re is independently hydrogen or (1C)alkyl; and wherein any one or more of L2, L3 or L4 is optionally substituted by a group LX.

17. The compound, or a pharmaceutically acceptable, salt, hydrate or solvate thereof, according to any one of the preceding claims, wherein L is a linker selected from:144wherein denotes the point of attachment to N, denotes the point of attachment to PL.

18. The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, according to any one of claims 9-17, wherein LX is a group having the formula: -LX1-ZX1-LX2 wherein LX1 is a (1-10C)alkylene; ZX1is absent or is selected from -O-, -C(O)-, -C(O)NRf-, -NRfC(O)-, -NRfC(O)O-, -C(O)O- or - OC(O)-; and LX2 is hydrogen, (1-10C)alkyl or -N(Rf)2; wherein each Rfis independently hydrogen or (1-2C)alkyl.

19. The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof,145 according to any one of claims 9-18, wherein LXis a group having the formula: -LX1-ZX1-LX2wherein LX1is a (1-4C)alkylene; ZX1is absent or is selected from -C(O)NH-, -NHC(O)- or -NHC(O)O-; and LX2is hydrogen, (1-4C)alkyl or -NH2.

20. The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, according to any one of the preceding claims, wherein the payload is a drug and the drug is selected from the group consisting of auristatins, mayatansines, tubulysins, calicheamicins, duocarmycins, pyrrolobenzodiazepines (in particular pyrrolobenzodiazepine dimers), camptothecin analogues, anthracyclines, amatoxins, protein toxins, immunotoxins, antibiotics or enzymes.

21. The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, according to any one of the preceding claims, wherein the payload is a labelling agent and the labelling agent is a fluorophore, a biotin tag, a radioisotope or a radioisotope containing moiety.

22. The compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, according to any one of the preceding claims, wherein the compound has any one of the following structures:

149.

23. A pharmaceutical composition comprising a compound according to any one of the preceding claims, or a pharmaceutically acceptable salt, hydrate or solvate thereof, in admixture with a pharmaceutically acceptable diluent or carrier.

24. A compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, according to any one of claims 1-22, or a pharmaceutical composition according to claim 23, for use in therapy.150 25. A compound, or a pharmaceutically acceptable salt, hydrate or solvate thereof, according to any one of claims 1-22, or a pharmaceutical composition according to claim 23 for use in the treatment of I. a proliferative disorder; II. an infectious disease; III. a chronic disease; IV. a hereditary disease; V. a bone disease; VI. an autoimmune disease; VII. a respiratory disease; or VIII. a neurodegenerative disease.

26. A method of preparing: (i) a protein / peptide-payload conjugate, the method comprising contacting a compound or a pharmaceutically acceptable salt, hydrate or solvate thereof according to any one of claims 1- 22 with one or more proteins and / or peptides, thereby forming a protein / peptide-payload conjugate; (ii) an antibody-payload conjugate, the method comprising contacting a compound or a pharmaceutically acceptable salt, hydrate or solvate thereof according to any one of claims 1- 22 with one or more antibodies, thereby forming an antibody-payload conjugate; (iii) an antibody-drug conjugate, the method comprising contacting a compound or a pharmaceutically acceptable salt, hydrate or solvate thereof according to any one of claims 1- 22 with one or more antibodies, thereby forming an antibody-drug conjugate; or (iv) an affibody-payload conjugate, the method comprising contacting a compound or a pharmaceutically acceptable salt, hydrate or solvate thereof according to any one of claims 1- 22 with one or more affibodies, thereby forming an affibody-payload conjugate.

27. The method of claim 26, wherein each antibody is independently selected from a nanobody, a monoclonal antibody, a polyclonal antibody, a dimer, a trimer, a multimer, a multispecific antibody (e.g., a bispecific antibody), a multivalent antibody or an antibody fragment.

28. The method of claim 27, wherein each nanobody is independently selected from anti- HER2 or anti-PD-L1 (e.g., anti-PD-L1 sdAb).151 29. The method of claim 26 or 27, wherein each antibody is trastuzumab.

30. A protein / peptide-payload conjugate, an antibody-payload conjugate, an antibody- drug conjugate, or an affibody-payload conjugate obtainable by, obtained by, or directly obtained by the method of preparing a protein / peptide-payload conjugate, an antibody- payload conjugate, an antibody-drug conjugate, or an affibody-payload conjugate of claim 26.

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