Cytotoxic compounds

Abstract

The present disclosure provides, inter alia, glycosylated compounds and conjugates thereof useful for treating cancer.

Description

[0001] CYTOTOXIC COMPOUNDS CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No.63 / 387,426, filed December 14, 2022, which is incorporated by reference herein in its entirety. FIELD The disclosure relates to DNA-alkylating units comprising alkylating binding units. In particular it relates to compounds comprising a G-alkylating unit (e.g., PBD, PDD or any other suitable unit) or an A-alkylating unit (e.g., CXI units), and to pharmaceutically acceptable salts thereof, which are useful as medicaments, in particular as anti-proliferative agents. BACKGROUND The pyrrolobenzodiazepines (PBDs) are a group of compounds some of which have been shown to be sequence-selective DNA minor-groove binding agents. The PBDs were originally discovered in Streptomyces species.[1]They are tricyclic in nature, and are comprised of fused 6-7-5–membered rings and can be identified as an anthranilate (A ring), a diazepine (B ring) and a pyrrolidine (C ring)[1c]They are characterized by an electrophilic N10=C11 imine group (as shown below) or the hydrated equivalent, a carbinolamine [NH-CH(OH)], or a carbinolamine alkyl ether ([NH-CH(OR, where R = alkyl)] which can form a covalent bond to a C2-amino group of guanine in DNA to form a DNA adduct[2]. The natural products interact in the minor groove of the DNA helix with excellent fit (i.e., good “isohelicity”) due to a right- handed longitudinal twist induced by a stereogenic C11a-position which has the (S)- configuration[3]. Carbinolamine Imine Carbinolamine alkyl ether Scheme 1: Interconvertible forms of the PBD The DNA adduct has been reported to inhibit a number of biological processes including the binding of transcription factors[4] [5]and the function of enzymes such as endonucleases[6]and RNA polymerase[7]. PBD monomers (e.g., anthramycin) have been shown by footprinting[3], NMR[8], molecular modelling[9]and X-ray crystallography

[0010] to span three base pairs and to have a thermodynamic preference for the sequence 5’-Pu-G-Pu-3’ (where Pu = purine, and G is the reacting guanine)

[0011] and a kinetic preference for the sequence 5’-Py-G-Py-3’ (where Py is pyridine). PBDs are thought to interact with DNA by first locating at a low-energy binding sequence (i.e., a 5’-Pu-G-Pu-3’ triplet) through Van der Waals, hydrogen bonding and electrostatic interactions[4]. Then, once in place, a nucleophilic attack by the exocyclic C2-amino group of the central guanine occurs to form the covalent adduct[4](Fig 2). Once bound, the PBD remains anchored in the DNA minor groove, avoiding DNA repair by causing negligible distortion of the DNA helix

[0010] . The ability of PBDs to form an adduct in the minor groove and for PBD dimers to crosslink DNA enables them to interfere with DNA processing and, hence, their potential for use as antiproliferative agents. WO-A-2017 / 032983, WO-A-2013 / 164592, WO-A-2017 / 223275, WO-A-2021 / 137646, WO-A- 2019 / 126691, WO-A-2019 / 104289, US 10526294, and US 10143695 disclose PBD (6-7-5) and pyridinobenzodiazepine (PDD; 6-7-6) monomers linked to heterocyclic chains via their A- rings, all of which have been shown to act as cytotoxic agents in vitro and as anti-tumour agents in vivo in animal tumour models. Furthermore, the C8’-linked PBD dimer SJG-136

[0012] has completed Phase I clinical trials for leukaemia and ovarian cancer

[0013] and a number of PBD dimer-based antibody-drug conjugates (ADCs) have been devised and some are in various stages of clinical trials. Scheme 2: Chemical structure of SJG-136 In addition to this, the indolinobenzodiazepine-based ADCs IMGN779 and IMGN632

[0014] have both progressed to Phase II and III studies respectively.

[0002] Scheme 3: Chemical structure of IMGN-779 US-A-2019 / 151465 (LegoChem) discloses antibody-drug conjugates (ADCs) wherein a plurality of active agents is conjugated to an antibody through at least one branched linker. WO- A-2020 / 222573 (LegoChem) discloses a tris structured linker. WO-A-2018 / 234636 (Glykos) discloses hydrophilic linkers and conjugates. The natural PBD monomer Sibiromycin

[0015] is one of the most potent naturally-occurring PBDs reported (sub-micromolar cytotoxicity) and has a sibirosamine sugar on the C7 position of the molecule. The potent cytotoxicity is thought to relate to its DNA-binding profile and potential ability to inhibit transcription factor binding

[0016] . Carbohydrate moieties have previously been incorporated into PBD-based monomers developed by Lown and colleagues

[0017] . It was observed that addition of a sugar moiety to certain positions on the polyamide chain enhanced cytotoxicity in some cell-lines. It is known that glucuronide and glucose are cleaved by glycosidases in vivo and they have been incorporated into both amine-containing and phenol-containing linker-payloads of various families as part of the linker construct

[0018] . The incorporation of glucose in this context enhances PK properties of the resultant ADC, and the payload is liberated from the linker payload construct through cleavage of the glucuronide moiety. A glucose moiety has also been incorporated into Auristatin (e.g., monomethyl auristatin E, “MMAE”) -based pro-drugs

[0019] , enhancing efficacy, tolerability and solubility when compared to the parent unsubstituted MMAE molecule. Other sequence-selective DNA minor-groove binding agents are known, including the duocarmycins or CXIs (for example, cyclopropapyrroloindole (CPI), cyclopropabenzindole (CBI) or cyclopropathienoindole (CTI) moieties).1 Many CXI analogues have since been developed, including bisalkylating dimers (A-A inter- strand cross-linkers) consisting of two CXI units, such as bizelesin. Scheme 4: Chemical structure of Bizelesin, a CPI dimer Bizelesin is an example of the seco-CPI (open form, with a chloromethyl functionality), rather than the spiro (closed, cyclopropyl) form, found in CC-1065.5This seco modification was found to be a prodrug of the CPI, and was more stable but had equivalent activity to the CPI dimer U-77809 (the corresponding parent drug form). Prodrug (seco) CXI forms are known to spirocyclise via a Winstein-Baird mechanism (Scheme 5) to the cyclopropane active, spiro form. Scheme 5: Interconvertible forms of the CXI WO-A-2015 / 104373 and WO-A-2015 / 104386 (to Synthon) WO-A-2017 / 012924 (to Nerviano) and WO-A-2003 / 0022806 (to Boger) also disclose CXI moieties. The exceptional potency of PBD (6-7-5) and PDD (6-7-6) compounds and CXI compounds make them attractive candidates for targeted delivery via an Antibody-Drug Conjugate (ADC). The present disclosure seeks to address this need and to overcome problem(s) associated with the prior art. SUMMARY In one aspect, the inventors have surprisingly discovered that carbohydrate (e.g., sugar) moieties can be successfully incorporated on to specific positions of an extended G-alkylator or A- alkylator payload structure, thereby enhancing hydrophilicity of the payload itself. The specific locations selected allow the addition of a sugar group to the molecule, without adversely interfering with the ability of the released agent to kill cancer cells. This is advantageous as substitutions on certain positions of the heterocyclic chain on a payload can alter DNA binding and cytotoxicity. In a non-limiting example, Fig.21 shows non-limiting examples of second generation linker payloads with sugar moieties at specific positions of the G-alkylating compounds. In the case of the subject material, the liberated parent can bind effectively to DNA resulting in potent cytotoxicity. The glycosylated substituent may act as a prodrug moiety that is selectively cleaved at the tumour site, so an ADC containing the glycosylated payload produces potent in vivo efficacy (similar to the unsubstituted parent molecule) but has a substantially increased tolerability profile, thereby widening the therapeutic window substantially. In some embodiments, the compounds and / or conjugates thereof described herein that comprise at least one glycosylated substituent have enhanced or increased hydrophilicity compared to said compounds that do not comprise at least one glycosylated substituent. In some embodiments, the compounds and / or conjugates thereof described herein that comprise at least one glycosylated substituent have enhanced or increased tolerability compared to said compounds that do not comprise at least one glycosylated substituent. When combined, these traits result in highly effective compounds. Thus, the inventors have discovered that the incorporation of sugar moieties into the structure of the G-monoalkylating agent or A- monoalkylating agent provides favourable properties for efficient conjugation, efficacy and tolerability. There is nevertheless a need for improved cytotoxic payloads especially those that may be useful in ADCs. For example, 50 mg / kg is an established single dose ‘platform’ MTD for linker-payload N-(4-((S)-2-((S)-2-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3- methylbutanamido)propanamido)phenyl)-4-(4-(((S)-2-methoxy-12-oxo-6a,7,8,9,10,12- hexahydrobenzo[e]pyrido[1,2-a][1,4]diazepin-3-yl)oxy)butanamido)-1-methyl-1H-pyrrole-2- carboxamide (i.e., control 3) when conjugated to multiple antibodies at DAR 4, and the effective dose is 10 mg / kg with regressions observed at 5 mg / kg. Given the hydrophobic nature of the construct, it is not possible to produce ADCs at higher DARs (which are thought to have better bystander effect than DAR 4) with control 3. . The present disclosure accordingly provides in a first aspect a compound of formula (I): D – Q – B - T (I) or a salt, solvate or tautomer thereof, wherein: D is a source of an alkylating DNA minor groove binding unit; Q is a linker; B is a DNA binding amide-containing chain; and T is an end group, wherein D, B, Q and / or T comprise at least one carbohydrate substituent. Suitably, the carbohydrate substituent may be RS, a univalent saccharide substituent, preferably glycosyl or O-glycosyl. Suitably, D may be the G-alkylator unit G comprising a group of formula (II): (II) wherein: the dotted line indicates the optional presence of a double bond between one or more of C1 and C2, C2 and C3, and C3 and C4; the wavy line indicates the point of attachment to Q; m is 0 or 1; R1, R3and R4are independently selected from H and R29; R2is selected from H, L2-R28,R29, and –LS-RS; or one of R1and R2, R2and R3, or R3and R4, together with the carbon atoms to which they are attached form a 6-membered aryl, or a 5- or 6-membered cyclic, heterocyclic, or heteroaryl ring optionally substituted with 1, 2 or 3 independently selected optional R20groups; R5and R6are selected such that either (i) R5is selected from H, OH and OC1-6alkyl; and R6is selected from H, SO3H, –LS-RS, nitrogen protecting groups, –L2-R28and RA(ii) R5is oxo or H, and R6is H or C1-6alkyl; or (iii) R5and R6together form a double bond; R7and R9are independently selected from H and R20; R8is selected from H, SR24, SCH2Ph, R20, L2-R28, and –LS-RS; RAis selected from (CH2)j-OH, (CH2)j-CO2R26, C(=O)-O-(CH2)k-NR26R27, (CH2)jNR26R27, C(=O)-NH-(CH2)j-NR26R27and C(=O)-NH-(CH2)k-C(=NH)NR26R27; L2is a bond or a linker moiety having 1-200 non-hydrogen atoms selected from C, N, P, O, S or halogen, and optionally incorporates ether, oxo, carboxamidyl, urethanyl, branched, cyclic, unsaturated, heterocyclyl, aryl or heteroaryl moieties; and R28is selected from an azide, alkyne, bisulfone, carbohydrazide, hydrazine, hydroxylamine, iodoacetamide, isothiocyanate, maleimide, phosphine, pyrridopyridazine, semihydrazide, succinimidyl ester, sulfodichlorophenol ester, sulfonyl halide, sulfosuccinimidyl ester, 4- sulfotetrafluorophenyl ester, tetrafluorophenyl ester, thiazole, RA,O-(CH2)k-NR26R26, NHNH2, or is a targeting agent wherein the targeting agent is selected from a protein, a portion of a protein, a peptide, a nucleic acid, or an antibody; each R29is independently selected from R20, R21, =CH2, =CH-(CH2)s-CH3, =CH-(CH2)s-R21, =O, (CH2)s-OR21, (CH2)s-CO2R21, (CH2)s-NR21R24, O-(CH2)t-NR21R24, NH-C(O)-R21, O- (CH2)t-NH-C(O)-R21, O-(CH2)t-C(O)-NH-R21, (CH2)s-SO2R21, O-SO2R21, (CH2)s-C(O)R21and (CH2)s-C(O)NR21R24; each R20is independently selected from F, Cl, Br, (CH2)j-OH, C1-6alkyl, OC1-6alkyl, OCH2Ph, (CH2)j-CO2R26, O-(CH2)k-NR26R27, C(=O)-O-(CH2)k-NR26R27, C(=O)-NR26R27, (CH2)j- NR26R27, NR26NH2, C(=O)-NH-(CH2)j-NR26R27, C(=O)-NH-C6H4-(CH2)j-R26, C(=O)-NH- (CH2)k-C(=NH)NR26R27, –L2-R28, S(O)2-(C1-6alkyl), O-(CH2)k-O-(C1-6alkyl), (CH2)j- S(O)2-NR26R27, C(=NH)-O-(C1-6alkyl), (CH2)k-O-(C1-6alkyl), CN, NCO, Cy, C(O)-NH- (CH2)j-Cy, C(O)-Cy, NH-C(O)-NR26R27and ; each j and s is independently selected from 0, 1, 2, 3, 4, 5 or 6; each k and t is independently selected from 1, 2, 3, 4, 5 or 6; each R21is independently selected from H, C1-12alkyl, C5-6heterocyclyl, C5-9heteroaryl, C6-15heteroarylalkyl, phenyl and C7-12aralkyl groups; wherein the heterocyclyl, heteroaryl, heteroarylalkyl, phenyl and aralkyl groups are optionally substituted with 1, 2 or 3 independently selected optional R20groups; each R24, R26and R27is independently selected from H and C1-12alkyl; each Cy is independently selected from a C5-6heterocyclyl or C5-6heteroaryl group, wherein the heterocyclyl or heteroaryl groups are optionally substituted with 1 or 2 R20groups; LSis a bond, an amino acid, a peptide chain having from 2 to 6 amino acids, an alkylene chain containing from 1 to 12 carbon atoms which may contain one or more carbon-carbon double or triple bonds, a paraformaldehyde chain –(OCH2)1-12-, a polyethylene glycol chain -(OCH2CH2)1-6-, which chains may be interrupted by or optionally incorporates one or more of P, O, S, NH, C5-9heteroarylene, phenylene, heterocyclyl, cycloalkyl, ether, oxo, carboxamidyl, and / or urethanyl moieties wherein the C5-9heteroarylene, phenylene, heterocyclyl, and / or cycloalkyl moieties are optionally substituted, optionally LSis: ; and RSis a univalent saccharide substituent, preferably glycosyl or O-glycosyl. Suitably, D may be the G-alkylator unit G comprising a group of formula (II): (II) wherein: the dotted line indicates the optional presence of a double bond between one or more of C1 and C2, C2 and C3, and C3 and C4; the wavy line indicates the point of attachment to Q; m is 0 or 1; R1, R3and R4are independently selected from H and R29; R2is selected from H, L2-R28,R29, and –LS-RS; or one of R1and R2, R2and R3, or R3and R4, together with the carbon atoms to which they are attached form a 6-membered aryl, or a 5- or 6-membered cyclic, heterocyclic, or heteroaryl ring optionally substituted with 1, 2 or 3 independently selected optional R20groups; R5 and R6 are selected such that either (i) R5 is selected from H, OH and OC1-6 alkyl; and R6 is selected from H, SO3H, –LS-RS, nitrogen protecting groups, –L2-R28and RA(ii) R5is oxo or H, and R6is H or C1-6alkyl; or (iii) R5and R6together form a double bond; R7and R9are independently selected from H and R20; R8is selected from H, SR24, SCH2Ph, R20, L2-R28, and –LS-RS; RAis selected from (CH2)j-OH, (CH2)j-CO2R26, C(=O)-O-(CH2)k-NR26R27, (CH2)jNR26R27, C(=O)-NH-(CH2)j-NR26R27and C(=O)-NH-(CH2)k-C(=NH)NR26R27; L2is a bond or a linker moiety having 1-200 non-hydrogen atoms selected from C, N, P, O, S or halogen, and optionally incorporates ether, oxo, carboxamidyl, urethanyl, branched, cyclic, unsaturated, heterocyclyl, aryl or heteroaryl moieties; and R28 is selected from an azide, alkyne, bisulfone, carbohydrazide, hydrazine, hydroxylamine, iodoacetamide, isothiocyanate, maleimide, phosphine, pyrridopyridazine, semihydrazide, succinimidyl ester, sulfodichlorophenol ester, sulfonyl halide, sulfosuccinimidyl ester, 4- sulfotetrafluorophenyl ester, tetrafluorophenyl ester, thiazole, RA,O-(CH2)k-NR26R26, NHNH2, or is a targeting agent wherein the targeting agent is selected from a protein, a portion of a protein, a peptide, a nucleic acid, or an antibody; each R29is independently selected from R20, R21, =CH2, =CH-(CH2)s-CH3, =CH-(CH2)s-R21, =O, (CH2)s-OR21, (CH2)s-CO2R21, (CH2)s-NR21R24, O-(CH2)t-NR21R24, NH-C(O)-R21, O- (CH2)t-NH-C(O)-R21, O-(CH2)t-C(O)-NH-R21, (CH2)s-SO2R21, O-SO2R21, (CH2)s-C(O)R21and (CH2)s-C(O)NR21R24; each R20is independently selected from F, Cl, Br, (CH2)j-OH, C1-6alkyl, OC1-6alkyl, OCH2Ph, (CH2)j-CO2R26, O-(CH2)k-NR26R27, C(=O)-O-(CH2)k-NR26R27, C(=O)-NR26R27, (CH2)j- NR26R27, NR26NH2, C(=O)-NH-(CH2)j-NR26R27, C(=O)-NH-C6H4-(CH2)j-R26, C(=O)-NH- (CH2)k-C(=NH)NR26R27, –L2-R28, S(O)2-(C1-6alkyl), O-(CH2)k-O-(C1-6alkyl), (CH2)j- S(O)2-NR26R27, C(=NH)-O-(C1-6alkyl), (CH2)k-O-(C1-6alkyl), CN, NCO, Cy, C(O)-NH- (CH2)j-Cy, C(O)-Cy, NH-C(O)-NR26R27and ; each j and s is independently selected from 0, 1, 2, 3, 4, 5 or 6; each k and t is independently selected from 1, 2, 3, 4, 5 or 6; each R21is independently selected from H, C1-12alkyl, C5-6heterocyclyl, C5-9heteroaryl, C6-15heteroarylalkyl, phenyl and C7-12aralkyl groups; wherein the heterocyclyl, heteroaryl, heteroarylalkyl, phenyl and aralkyl groups are optionally substituted with 1, 2 or 3 independently selected optional R20groups; each R24, R26and R27is independently selected from H and C1-12alkyl; each Cy is independently selected from a C5-6heterocyclyl or C5-6heteroaryl group, wherein the heterocyclyl or heteroaryl groups are optionally substituted with 1 or 2 R20groups; LSis a bond, an amino acid, a peptide chain having from 2 to 6 amino acids, an alkylene chain containing from 1 to 12 carbon atoms which may contain one or more carbon-carbon double or triple bonds, a paraformaldehyde chain –(OCH2)1-12-, a polyethylene glycol chain -(OCH2CH2)1-6-, which chains may be interrupted by or optionally incorporates one or more of P, O, S, NH, C5-9heteroarylene, phenylene, heterocyclyl, cycloalkyl, ether, oxo, carboxamidyl, and / or urethanyl moieties wherein the C5-9heteroarylene, phenylene, heterocyclyl, and / or cycloalkyl moieties are optionally substituted, optionally LSis: or ; LCcomprises one or more groups selected from an amino acid, an amino acid derivative, a peptide chain having from 2 to 6 amino acids or amino acid derivatives, an alkylene chain containing from 1 to 12 carbon atoms which may contain one or more carbon- carbon double or triple bonds, a paraformaldehyde chain –(OCH2)1-12-, a polyethylene glycol chain -(OCH2CH2)1-8-, which chains may be interrupted by one or more P, O, S and / or NH groups and / or C5-9heteroarylene and / or phenylene, wherein each C5-9heteroarylene group and / or each phenylene group is optionally substituted; and RSis a univalent saccharide substituent, preferably glycosyl or O-glycosyl. Suitably, G is selected from a group of formula G1 to G8: (G1); (G2);

[0003] 6);

[0004] (G7); and (G8). In some embodiments, D may comprise A, an A-alkylating DNA group of formula (IIIa) or (IIIb): or IIIa (seco form) IIIb (spiro form) wherein: Z1is a leaving group, optionally halide, triflate, or tosylate; X is C-R17, N, N-R17, S or O; the dotted line to X indicates the optional presence of a double bond depending on the nature of X; R17is H, –LS-RS, or R20; R20is independently selected from F, Cl, Br, (CH2)j-OH, C1-6alkyl, OC1-6alkyl, OCH2Ph, (CH2)j-CO2R26, O-(CH2)k-NR26R27, C(=O)-O-(CH2)k-NR26R27, C(=O)-NR26R27, (CH2)j- NR26R27, NR26NH2, C(=O)-NH-(CH2)j-NR26R27, C(=O)-NH-C6H4-(CH2)j-R26, C(=O)-NH- (CH2)k-C(=NH)NR26R27, –L2-R28, S(O)2-(C1-6alkyl), O-(CH2)k-O-(C1-6alkyl), (CH2)j- S(O)2-NR26R27, C(=NH)-O-(C1-6alkyl), (CH2)k-O-(C1-6alkyl), CN, NCO, Cy, C(O)-NH- (CH2)j-Cy, C(O)-Cy, NH-C(O)-NR26R27and ; L2is a bond or a linker moiety having 1-200 non-hydrogen atoms selected from C, N, P, O, S or halogen, and optionally incorporates ether, oxo, carboxamidyl, urethanyl, branched, cyclic, unsaturated, heterocyclyl, aryl or heteroaryl moieties; and R28is selected from an azide, alkyne, bisulfone, carbohydrazide, hydrazine, hydroxylamine, iodoacetamide, isothiocyanate, maleimide, phosphine, pyrridopyridazine, semihydrazide, succinimidyl ester, sulfodichlorophenol ester, sulfonyl halide, sulfosuccinimidyl ester, 4- sulfotetrafluorophenyl ester, tetrafluorophenyl ester, thiazole, RA,O-(CH2)k-NR26R26, NHNH2, or is a targeting agent wherein the targeting agent is selected from a protein, a portion of a protein, a peptide, a nucleic acid, or an antibody; RAis selected from (CH2)j-OH, (CH2)j-CO2R26, C(=O)-O-(CH2)k-NR26R27, (CH2)jNR26R27, C(=O)-NH-(CH2)j-NR26R27and C(=O)-NH-(CH2)k-C(=NH)NR26R27; each R26and R27is independently selected from H and C1-12alkyl; each Cy is independently selected from a C5-6heterocyclyl or C5-6heteroaryl group, wherein the heterocyclyl or heteroaryl groups are optionally substituted with 1 or 2 R20groups; each j independently selected from 0, 1, 2, 3, 4, 5 or 6; each k is independently selected from 1, 2, 3, 4, 5 or 6; z is 0 or 1; R''' is OH or –LS-RS; LSis a bond, an amino acid, a peptide chain having from 2 to 6 amino acids, an alkylene chain containing from 1 to 12 carbon atoms which may contain one or more carbon-carbon double or triple bonds, a paraformaldehyde chain –(OCH2)1-12-, a polyethylene glycol chain -(OCH2CH2)1-6-, which chains may be interrupted by or optionally incorporates one or more of P, O, S, NH, C5-9heteroarylene, phenylene, heterocyclyl, cycloalkyl, ether, oxo, carboxamidyl, and / or urethanyl moieties wherein the C5-9heteroarylene, phenylene, heterocyclyl, and / or cycloalkyl moieties are optionally substituted, optionally LSis: ; and RSis a univalent saccharide substituent, preferably glycosyl or O-glycosyl. Suitably, the compound of formula (I) may be a compound of formula IV: (IV), where the substituents have the definitions indicated above. Suitably, the linker group Q may comprise X1-L-X2, wherein: X1is selected from O, S, NR13, CR13R14, CR13R14O, C(=O), C(=O)NR13, NR13C(=O), O-C(O) and C(O)-O, or is absent; L is selected from an amino acid, a peptide chain having from 2 to 6 amino acids, an alkylene chain containing from 1 to 12 carbon atoms which may contain one or more carbon- carbon double or triple bonds, a paraformaldehyde chain –(OCH2)1-12-, a polyethylene glycol chain -(OCH2CH2)1-6-, which chains may be interrupted by one or more P, O, S and / or NH groups and / or C5-9heteroarylene and / or phenylene, wherein each C5-9heteroarylene group and / or each phenylene group is optionally substituted; X2is selected from O, S, NR15, CR15R16, CR15R16O, C(=O), C(=O)NR15, NR15C(=O), O-C(O) and C(O)-O or is absent; and R13, R14,R15and R16are independently selected from H and C1-6alkyl. Suitably, the DNA binding amide-containing chain B may comprise (A)q, wherein: q is selected from 0, 1, 2, 3, 4, 5 and 6; A is selected from: and ; A1 A2 for each A1 group, one of Y3and Y4is independently selected from N-R30, S and O; and the other of Y3and Y4is CH; and Y5is independently selected from CR30, N, S and COH; for each A2 group, one of Y6and Y7is independently selected from N and CH; and the other of Y6and Y7is CR30; and each R30is independently selected from H, C1-6alkyl, L2-R28and RS. Suitably, the end group T may comprise a group of formula: wherein: p is 0 or 1; RTis selected from –L2-R28, phenyl, and C5-9heteroaryl, wherein the phenyl and C5-9heteroaryl groups are optionally substituted with up to three optional substituent groups selected from OH, C1-6alkyl, OC1-6alkyl, –L2-R28, (CH2)j-CO2R11, O-(CH2)k-NR11R12, (CH2)j- NR11R12, C(=O)-NH-(CH2)k-NR11R12, C(=O)-NH-R24, and C(=O)-NH-(CH2)k- C(=NH)NR11R12, optionally with the proviso that the optionally substituted C5-9heteroaryl is not indolyl; R19is selected from H, C1-6alkyl, L2-R28, RS, and (CH2)t-NR20R21; Y1and Y2are independently N or CR31, wherein at least one of Y1and Y2is CR31; each R31 is independently selected from H, C1-6 alkyl, L2-R28 and RS; and R11, R12, and R24are independently selected from H, –L2-R28, and C1-6alkyl. Non-limiting examples of compounds of the disclosure include: ,

[0005] wherein RSis a univalent saccharide substituent, preferably glycosyl or O-glycosyl. Suitably, the compound may comprise at least one L2-R28group. More suitably, D, T, Q and / or B may be substituted with a L2-R28group. L2may be selected from: (i) , (ii) , (iii) , (iv) , (v) , (vi) , (vii) , (viii) , (ix) , (x) or (xi) ; wherein XAAis an amino acid sequence; and K2is -[CH2CH2O]0-50- or -[CH2]0-12-. In embodiments, XAAmay be L-valyl-L-alanine. Suitably, R28may be maleimide: ; optionally linked to a targeting agent. Suitably, L2-R28may comprise ; ; ; ; ; ; 

[0006] optionally linked to a targeting agent. The compound ac cording to formula (I) may comprise at least one L2-R28group and the targeting agent is linked to the compound through the L2-R28group. In a further aspect, there is provided a compound of formula (I) and salts and solvates thereof for use as a medicament. In a further aspect, there is provided a compound of formula (I) and salts and solvates thereof for use in the treatment of a proliferative disease. In a further aspect, there is provided a compound of formula (I) and salts and solvates thereof for use in a method of therapy. In a further aspect, there is provided a pharmaceutical composition comprising a compound of formula (I) and salts and solvates and a pharmaceutically acceptable excipient, carrier or diluent. In a further aspect, there is provided a compound of formula (I) and salts and solvates thereof for use in the manufacture of a medicament for treating a proliferative disease. ADCs (Antibody-drug Conjugates) may be composed of an antibody, linker and payload. Linker payload complexes usually contain hydrophilic groups (in the form of extended PEG) in order to reduce hydrophobicity and promote efficient conjugation of the structure to the antibody. DNA- interactive agents are usually particularly hydrophobic in nature, leading to significant issues with PK and during the conjugation process. The use of sugar groups in the payload structure itself as masking agents, surprisingly reduces hydrophobicity, enhances PK properties and increases the tolerability of the ADC. This is particularly advantageous because it may result in (a) more efficient conjugation than other classes of payloads, (b) similar cytotoxicity to the unsubstituted form of the payload with significantly improved tolerability and conjugation properties compared to molecules in the prior art, and (c) enhanced PK profile compared to unsubstituted agents. Thus, in a further aspect, a compound of formula (I) and salts and solvates thereof may be linked, either directly or indirectly, to a targeting agent to provide a targeted conjugate. In this aspect, the compound may comprise at least one L2-R28group and the targeting agent is linked to the compound through the L2-R28group. The targeting agent may comprise an antibody, an antibody fragment, a hormone or a hormone fragment. Thus, in a further aspect, the compound of formula (I) and salts and solvates thereof, may be linked, either directly or indirectly, to a targeting agent (e.g., antibody, antibody fragment, hormone, etc.) to provide a targeted conjugate. The target conjugates of the present disclosure may contain one or multiple compounds of formula (I) (or salts and solvates thereof). A variety of target conjugates are known in the art and may be used with a compound of formula (I) and salts and solvates thereof. For example, in a particular aspect the target conjugate is an antibody-drug conjugate, wherein one or more compounds of formula (I) are linked, directly or indirectly, to the antibody. Therefore, the compound of formula (I) and salts and solvates thereof, may be used as a payload on a targeted conjugate. In an aspect, compounds of formula (I), formula (IV), and / or conjugates thereof, comprising at least one carbohydrate substituent have enhanced or increased hydrophilicity compared to compounds of formula (I), formula (IV), and / or conjugates thereof not comprising at least one carbohydrate substituent. In some embodiments, compounds of formula (I) and / or conjugates thereof comprising at least one RShave enhanced or increased hydrophilicity compared to compounds of formula (I) and / or conjugates thereof not comprising at least one RS. In some embodiments, compounds of formula (I), formula (IV), and / or conjugates thereof, comprising at least one RShave enhanced or increased hydrophilicity compared to compounds of formula (I), formula (IV), and / or conjugates thereof not comprising at least one RS. In some embodiments, compounds of formula (I), formula (IV), and / or conjugates thereof, comprising at least one RShave about 1-fold, about 2-fold, about 5-fold, about 10-fold, about 20-fold, about 50-fold, or about 100-fold enhanced or increased hydrophilicity compared to compounds of formula (I), formula (IV), and / or conjugates thereof not comprising at least one RS. In a non-limiting example increased or enhanced hydrophilicity allows for efficient conjugation of the compounds of formula (I) and / or formula (IV) to a targeting agent and / or at a higher DAR (e.g., DAR 8). In some embodiments, compounds of formula (I) with a G- alkylating DNA group of formula (II) or one of G1-G8 as the D moiety, compounds of formula (IV), and / or conjugates thereof, comprising at least one carbohydrate substituent have enhanced or increased hydrophilicity compared to compounds of formula (I) with a G- alkylating DNA group of formula (II) or one of G1-G8 as the D moiety, compounds of formula (IV), and / or conjugates thereof not comprising at least one carbohydrate substituent. In some embodiments, compounds of formula (I) with a G- alkylating DNA group of formula (II) or one of G1-G8 as the D moiety, compounds of formula (IV), and / or conjugates thereof, comprising at least one RShave enhanced or increased hydrophilicity compared to compounds of formula (I) with a G- alkylating DNA group of formula (II) or one of G1-G8 as the D moiety, compounds of formula (IV), and / or conjugates thereof not comprising at least one RS. In some embodiments, compounds of formula (I) with a G- alkylating DNA group of formula (II) or one of G1-G8 as the D moiety, compounds of formula (IV), and / or conjugates thereof, comprising at least one RShave about 1-fold, about 2-fold, about 5-fold, about 10-fold, about 20-fold, about 50-fold, or about 100-fold enhanced or increased hydrophilicity compared to compounds of formula (I) with a G- alkylating DNA group of formula (II) or one of G1-G8 as the D moiety, compounds of formula (IV), and / or conjugates thereof not comprising at least one RS. In a non-limiting example increased or enhanced hydrophilicity allows for efficient conjugation of the compounds of formula (I) with a G- alkylating DNA group of formula (II) or one of G1-G8 as the D moiety and / or compounds of formula (IV) to a targeting agent and / or at a higher DAR (e.g., DAR 8). In some embodiments, compounds of formula (I) with an A-alkylating DNA group of formula (IIIa) or (IIIb) as the D moiety and / or conjugates thereof, comprising at least one carbohydrate substituent have enhanced or increased hydrophilicity compared to compounds of formula (I) with an A-alkylating DNA group of formula (IIIa) or (IIIb) as the D moiety and / or conjugates thereof not comprising at least one carbohydrate substituent. In some embodiments, compounds of formula (I) with an A-alkylating DNA group of formula (IIIa) or (IIIb) as the D moiety and / or conjugates thereof, comprising at least one RShave enhanced or increased hydrophilicity compared to compounds of compounds of formula (I) with an A-alkylating DNA group of formula (IIIa) or (IIIb) as the D moiety and / or conjugates thereof not comprising at least one RS. In some embodiments, compounds of formula (I) with an A-alkylating DNA group of formula (IIIa) or (IIIb) as the D moiety and / or conjugates thereof, comprising at least one RShave about 1-fold, about 2-fold, about 5-fold, about 10-fold, about 20-fold, about 50-fold, or about 100-fold enhanced or increased hydrophilicity compared to compounds of formula (I) with an A- alkylating DNA group of formula (IIIa) or (IIIb) as the D moiety and / or conjugates thereof not comprising at least one RS. In a non-limiting example increased or enhanced hydrophilicity allows for efficient conjugation of the compounds of formula (I) with an A-alkylating DNA group of formula (IIIa) or (IIIb) as the D moiety to a targeting agent and / or at a higher DAR (e.g., DAR 8). In an aspect, compounds of formula (I), formula (IV), and / or conjugates thereof, comprising at least one carbohydrate substituent have enhanced or increased tolerability compared to compounds of formula (I), formula (IV), and / or conjugates thereof not comprising at least one carbohydrate substituent. In some embodiments, compounds of formula (I), formula (IV), and / or conjugates thereof, comprising at least one RShave enhanced or increased tolerability compared to compounds of formula (I), formula (IV), and / or conjugates thereof not comprising at least one RS. In some embodiments, compounds of formula (I) and / or conjugates thereof, comprising at least one RShave enhanced or increased tolerability compared to compounds of formula (I) and / or conjugates thereof not comprising at least one RS. In some embodiments, compounds of formula (I), formula (IV), and / or conjugates thereof, comprising at least one RShave a 2-fold to 10-fold or more increase in tolerability compared to compounds of formula (I), formula (IV), and / or conjugates thereof not comprising at least one RS. In some embodiments, compounds of formula (I) with a G- alkylating DNA group of formula (II) or one of G1-G8 as the D moiety, compounds of formula (IV), and / or conjugates thereof, comprising at least one carbohydrate substituent have enhanced or increased tolerability compared to compounds of formula (I) with a G- alkylating DNA group of formula (II) or one of G1-G8 as the D moiety, compounds of formula (IV), and / or conjugates thereof not comprising at least one carbohydrate substituent. In some embodiments, compounds of formula (I) with a G- alkylating DNA group of formula (II) or one of G1-G8 as the D moiety, compounds of formula (IV), and / or conjugates thereof, comprising at least one RShave enhanced or increased tolerability compared to compounds of formula (I) with a G- alkylating DNA group of formula (II) or one of G1-G8 as the D moiety, compounds of formula (IV), and / or conjugates thereof not comprising at least one RS. In some embodiments, compounds of formula (I) with a G- alkylating DNA group of formula (II) or one of G1-G8 as the D moiety, compounds of formula (IV), and / or conjugates thereof, comprising at least one RShave a 2-fold to 10-fold or more increase in tolerability compared to compounds of formula (I) with a G- alkylating DNA group of formula (II) or one of G1-G8 as the D moiety, compounds of formula (IV), and / or conjugates thereof not comprising at least one RS. In some embodiments, compounds of formula (I) with an A-alkylating DNA group of formula (IIIa) or (IIIb) as the D moiety and / or conjugates thereof, comprising at least one carbohydrate substituent have enhanced or increased tolerability compared to compounds of formula (I) with an A-alkylating DNA group of formula (IIIa) or (IIIb) as the D moiety and / or conjugates thereof not comprising at least one carbohydrate substituent. In some embodiments, compounds of formula (I) with an A-alkylating DNA group of formula (IIIa) or (IIIb) as the D moiety and / or conjugates thereof, comprising at least one RShave enhanced or increased tolerability compared to compounds of formula (I) with an A-alkylating DNA group of formula (IIIa) or (IIIb) as the D moiety and / or conjugates thereof not comprising at least one RS. In some embodiments, compounds of formula (I) with an A-alkylating DNA group of formula (IIIa) or (IIIb) as the D moiety and / or conjugates thereof, comprising at least one RShave a 2-fold to 10-fold or more increase in tolerability compared to compounds of formula (I) with an A-alkylating DNA group of formula (IIIa) or (IIIb) as the D moiety and / or conjugates thereof not comprising at least one RS. In some embodiments, compounds of formula (I) with a G- alkylating DNA group of formula (II) or one of G1-G8 as the D moiety, compounds of formula (IV), and / or conjugates thereof, comprising RS at the R6 position and / or R8 position have enhanced or increased hydrophilicity compared to compounds of formula (I) with a G- alkylating DNA group of formula (II) or one of G1-G8 as the D moiety, compounds of formula (IV), and / or conjugates thereof not comprising RSat the R6position and / or R8position. In some embodiments compounds of formula (I) with a G- alkylating DNA group of formula (II) or one of G1-G8 as the D moiety, compounds of formula (IV), and / or conjugates thereof, comprising RSat the R8position have a 2-fold to 10-fold or more increase in tolerability compared to compounds of formula (I) with a G- alkylating DNA group of formula (II) or one of G1-G8 as the D moiety, compounds of formula (IV), and / or conjugates thereof not comprising RSat the R8position. In some embodiments compounds of formula (I) with a G- alkylating DNA group of formula (II) or one of G1-G8 as the D moiety, compounds of formula (IV), and / or conjugates thereof, comprising RSat the R6position have the same or substantially the same tolerability compared to compounds of formula (I) with a G- alkylating DNA group of formula (II) or one of G1-G8 as the D moiety, compounds of formula (IV), and / or conjugates thereof not comprising RSat the R6position. BRIEF DESCRIPTION OF THE DRAWINGS Embodiments of the present disclosure will now be described further, with reference to the accompanying drawings, in which: Figure 1 illustrates the results of the β-Glucosidase assay at 5 min. Aliquots of 100 µL were taken and analysed by LC-MS at 5 min, 30 min, 1 h, 2 h, 18 h, 36 h, 60 h, 84 h and 132 h. Figure 2 illustrates the results of the β-Glucosidase assay at 30 min. Aliquots of 100 µL were taken and analysed by LC-MS at 5 min, 30 min, 1 h, 2 h, 18 h, 36 h, 60 h, 84 h and 132 h. Figure 3 illustrates the results of the β-Glucosidase assay at 1 h. Aliquots of 100 µL were taken and analysed by LC-MS at 5 min, 30 min, 1 h, 2 h, 18 h, 36 h, 60 h, 84 h and 132 h. Figure 4 illustrates the results of the β-Glucosidase assay at 2 h. Aliquots of 100 µL were taken and analysed by LC-MS at 5 min, 30 min, 1 h, 2 h, 18 h, 36 h, 60 h, 84 h and 132 h. Figure 5 illustrates the results of the β-Glucosidase assay at 18 h. Aliquots of 100 µL were taken and analysed by LC-MS at 5 min, 30 min, 1 h, 2 h, 18 h, 36 h, 60 h, 84 h and 132 h. Figure 6 illustrates the results of the β-Glucosidase assay at 36 h. Aliquots of 100 µL were taken and analysed by LC-MS at 5 min, 30 min, 1 h, 2 h, 18 h, 36 h, 60 h, 84 h and 132 h. Figure 7 illustrates the results of the β-Glucosidase assay at 60 h. Aliquots of 100 µL were taken and analysed by LC-MS at 5 min, 30 min, 1 h, 2 h, 18 h, 36 h, 60 h, 84 h and 132 h. Figure 8 illustrates the results of the β-Glucosidase assay at 84 h. Aliquots of 100 µL were taken and analysed by LC-MS at 5 min, 30 min, 1 h, 2 h, 18 h, 36 h, 60 h, 84 h and 132 h. Figure 9 illustrates the results of the β-Glucosidase assay at 132 h. Aliquots of 100 µL were taken and analysed by LC-MS at 5 min, 30 min, 1 h, 2 h, 18 h, 36 h, 60 h, 84 h and 132 h. Figures 10A- 10F illustrates the results of the β-Galactosidase assay. Aliquots of 100 µL were taken and analysed by LC-MS at 0 min, 5 min, 30 min, 90 min, 4.5 h, 7.5 h and 20 h. Figures 11A- 11D illustrates the results of the β-Glucuronidase assay with (2S,3S,4S,5R,6S)-6- (((S)-3-(4-((5-((4-aminophenyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)amino)-4-oxobutoxy)-12- oxo-6a,7,8,9,10,12-hexahydrobenzo[e]pyrido[1,2-a][1,4]diazepin-2-yl)oxy)-3,4,5- trihydroxytetrahydro-2H-pyran-2-carboxylic acid (88). Aliquots of 100 µL were taken and analysed by LC-MS at 0 min, 5 min, 30 min and 90 min. Figures 12A- 12E illustrates the results of the β-Glucuronidase assay with (2S,3S,4S,5R,6S)-6- (4-((((6aS)-3-(4-((5-((4-aminophenyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)amino)-4- oxobutoxy)-6-hydroxy-2-methoxy-12-oxo-5,6,6a,7,8,9,10,12-octahydrobenzo[e]pyrido[1,2- a][1,4]diazepine-5-carbonyl)oxy)methyl)-2-nitrophenoxy)-3,4,5-trihydroxytetrahydro-2H- pyran-2-carboxylic acid (138). Aliquots of 100 µL were taken and analysed by LC-MS at 0 min, 5 min, 30 min, 90 min, and 150 min. Figures 13A- 13E illustrates the results of the β-Glucuronidase assay with (2S,3S,4S,5R,6S)-6- (4-((((6aS)-3-(4-((5-((4-(5-((4-aminophenyl)carbamoyl)-1-methyl-1H-pyrrol-3- yl)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)amino)-4-oxobutoxy)-6-hydroxy-2-methoxy- 12-oxo-5,6,6a,7,8,9,10,12-octahydrobenzo[e]pyrido[1,2-a][1,4]diazepine-5- carbonyl)oxy)methyl)-2-nitrophenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid (146). Aliquots of 100 µL were taken and analysed by LC-MS at 0 min, 5 min, 30 min, 90 min, and 150 min. Figures 14A- 14E illustrates the results of the β-Glucuronidase assay with (2S,3S,4S,5R,6S)-6- (4-((((5-(3-carboxypropoxy)-4-methoxy-2-((S)-2-((methoxyimino)methyl)piperidine-1- carbonyl)phenyl)carbamoyl)oxy)methyl)-2-nitrophenoxy)-3,4,5-trihydroxytetrahydro-2H- pyran-2-carboxylic acid (150). Aliquots of 100 µL were taken and analysed by LC-MS at 0 min, 5 min, 30 min, 90 min, and 150 min. Figure 15 illustrates the HIC profile of Trastuzumab. Figure 16 illustrates the PLRP trace of Trastuzumab. Heavy (left peak) and light (right peak) chain peaks as indicated. Figure 17 illustrates the HIC profile of Trastuzumab-91. Average DAR calculated as 8. The conjugation process caused no significant aggregation compared to the starting antibody, with 93.1% monomer formed. Figure 18 illustrates the SEC profile of Trastuzumab-91; 93.1% monomer. No free toxin linker could be detected in the ADC sample. Figure 19 is a graph illustrating dose tolerability of Trastuzumab-91 (DAR 8) in non-tumour bearing CD1 mice. Figure 20 is a graph illustrating in vivo efficacy of Trastuzumab-91 (DAR 8) at a single dose of 5 mg / kg. Figure 21 illustrates the protection of the N11-C12-alkylating imine positions or the masking of the C8-positions on G-alkylating PDD-constructs using with sugar-based moieties. Figure 22 is a scheme illustrating PDD-pro-drug compounds before and after cleavage of the sugar group. Figure 23 is a graph illustrating in vivo efficacy of compound 180 at a single dose of 5 mg / kg. DETAILED DESCRIPTION Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this disclosure belongs. All patents and publications referred to herein are incorporated by reference in their entireties. Definitions The following abbreviations are used throughout the specification: Ac acetyl; Alloc allyloxycarbonyl; Boc tert-butyloxycarbonyl; DHP dihydropyran; DMAP 4- dimethylaminopyridine; DMF dimethylformamide; EDCI 1-ethyl-3-(3-dimethylamino- propyl)carbodiimide; Et ethyl; Me methyl; Ph phenyl; Tf trifluoromethanesulfonate; TFA trifluoroacetic acid; THF tetrahydrofuran and THP tetrahydropyranyl. “Substituted”, when used in connection with a chemical substituent or moiety (e.g., an alkyl group), means that one or more hydrogen atoms of the substituent or moiety have been replaced with one or more non-hydrogen atoms or groups, provided that valence requirements are met and that a chemically stable compound results from the substitution. “Optionally substituted” refers to a parent group which may be unsubstituted or which may be substituted with one or more substituents. Suitably, unless otherwise specified, when optional substituents are present, the optional substituted parent group comprises from one to three optional substituents. Where a group may be “optionally substituted with 1, 2 or 3 groups”, this means that the group may be substituted with 0, 1, 2 or 3 of the optional substituents. Suitably, the group is substituted with 1, 2 or 3 of the optional substituents. Where a group is “optionally substituted with one or two optional substituents”, this means that the group may be substituted with 0, 1 or 2 of the optional substituents. Suitably, the group may be optionally substituted with 0 or 1 optional substituents. In some aspects, suitably the group is not optionally substituted. In other aspects, suitably the group is substituted with 1 of the optional substituents. Optional substituents may be selected from C1-8alkyl, C2-7alkenyl, C2-7alkynyl, C1-12alkoxy, C5-20aryl, C3-10cycloalkyl, C3-10cycloalkenyl, C3-10cycloalkynyl, C3-20heterocyclyl, C3-20heteroaryl, acetal, acyl, acylamido, acyloxy, amidino, amido, amino, aminocarbonyloxy, azido, carboxy, cyano, ether, formyl, guanidino, halo, hemiacetal, hemiketal, hydroxamic acid, hydroxyl, imidic acid, imino, ketal, nitro, nitroso, oxo, oxycarbonyl, oxycarboyloxy, sulfamino, sulfamyl, sulfate, sulfhydryl, sulfinamino, sulfinate, sulfino, sulfinyl, sulfinyloxy, sulfo, sulfonamido, sulfonamino, sulfonate, sulfonyl, sulfonyloxy, uredio groups. In some aspects, the optional substituents are 1, 2 or 3 optional substituents independently selected from OH, C1-8alkyl, OC1-12alkyl, and halogen. More suitably, the optional substituents are selected from OH, C1-8alkyl and OC1-12alkyl; more suitably, the optional substituents are selected from C1-8alkyl and OC1-12alkyl. “Independently” or “Independently selected” is used in the context of statement that, for example, “each R', R'', is independently H, C1-8alkyl...” and means that each instance of the functional group, e.g., R', is selected from the listed options independently of any other instance of R' or R'' in the compound. Hence, for example, H may be selected for the first instance of R' in the compound; methyl may be selected for the next instance of R' in the compound; and ethyl may be selected for the first instance of R'' in the compound. “C1-8alkyl”: refers to straight chain and branched saturated hydrocarbon groups, generally having from 1 to 8 carbon atoms; suitably a C1-7alkyl; suitably a C1-6alkyl; suitably a C1-5alkyl; more suitably a C1-4alkyl; more suitably a C1-3alkyl. Examples of alkyl groups include methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, i-butyl, t-butyl, pent-1-yl, pent-2-yl, pent-3-yl, 3- methylbut-1-yl, 3-methylbut-2-yl, 2-methylbut-2-yl, 2,2,2-trimethyleth-1-yl, n-hexyl, n-heptyl, n-octyl and the like. “Alkylene” refers to a divalent radical derived from an alkane which may be a straight chain or branched, as exemplified by –CH2CH2CH2CH2-. The alkylene may have the number of carbons as discussed above for alkyl groups. The term “amino acid” refers to naturally occurring (or “canonical”) α-amino acids and their stereoisomers, unnatural (or “non-canonical”) amino acids and their stereoisomers, and modified or synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally-occurring amino acids. “Stereoisomers” of amino acids refers to mirror image isomers of the amino acids, such as L-amino acids or D-amino acids. For example, a stereoisomer of a naturally-occurring amino acid refers to the mirror image isomer of the naturally-occurring amino acid, i.e., the D-amino acid. Naturally-occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, e.g., hydroxyproline, γ-carboxyglutamate, and O-phosphoserine. Naturally-occurring α-amino acids include, without limitation, they are amino acids selected from alanine (Ala), arginine (Arg), asparagine (Asn), aspartic acid (Asp), cysteine (Cys), glutamine (Gln), glutamic acid (Glu), glycine (Gly), histidine (His), isoleucine (Ile), leucine (Leu), lysine (Lys), methionine (Met), phenylalanine (Phe), proline (Pro), serine (Ser), threonine (Thr), tryptophan (Trp), tyrosine (Tyr), and valine (Val). Stereoisomers of naturally-occurring α-amino acids include, without limitation, D-alanine (D-Ala), D-arginine (D-Arg), D-asparagine (D-Asn), D-aspartic acid (D-Asp), D-cysteine (D-Cys), D-glutamine (D-Gln), D-glutamic acid (D-Glu), D-glycine (D-Gly), D-histidine (D-His), D-isoleucine (D-Ile), D-leucine (D-Leu), D- lysine (D-Lys), D-methionine (D-Met), D-phenylalanine (D-Phe), D-proline (D-Pro), D-serine (D-Ser), D-threonine (Thr), D-tryptophan (D-Trp), D-tyrosine (D-Tyr), and D-valine (D-Val). Unnatural amino acids include, without limitation, amino acid analogs, amino acid mimetics, and synthetic amino acids in either the L- or D-configuration that function in a manner similar to the naturally-occurring amino acids. For example, “amino acid analogs” are unnatural amino acids that have the same basic chemical structure as naturally-occurring amino acids, i.e., an α- carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group, e.g., homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium. Such analogs may have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid. Non-limiting examples of unnatural amino acids include 1-aminocyclopentane-1-carboxylic acid (Acp), 1-aminocyclobutane-1-carboxylic acid (Acb), 1-aminocyclopropane-1-carboxylic acid (Acpc), citrulline (Cit), homocitrulline (HoCit), α-aminohexanedioic acid (Aad), 3-(4- pyridyl)alanine (4-Pal), 3-(3-pyridyl)alanine (3-Pal), propargylglycine (Pra), α-aminoisobutyric acid (Aib), α-aminobutyric acid (Abu), norvaline (Nva), α,β-diaminopropionic acid (Dpr), α,γ- diaminobutyric acid (Dbu), α-tert-butylglycine (Bug), 3,5-dinitrotyrosine (Tyr(3,5-di NO2)), norleucine (Nle), 3-(2-naphthyl)alanine (Nal-2), 3-(1-naphthyl)alanine (Nal-1), cyclohexylalanine (Cha), di-n-propylglycine (Dpg), cyclopropylalanine (Cpa), homoleucine (Hle), homoserine (HoSer), homoarginine (Har), homocysteine (Hcy), methionine sulfoxide (Met(O)), methionine methylsulfonium (Met (S-Me)), α-cyclohexylglycine (Chg), 3-benzo- thienylalanine (Bta), taurine (Tau), hydroxyproline (Hyp), O-benzyl-hydroxyproline (Hyp(Bzl)), homoproline (HoPro), β-homoproline (βHoPro), thiazolidine-4-carboxylic acid (Thz), nipecotic acid (Nip), isonipecotic acid (IsoNip), 3-carboxymethyl-1-phenyl-1,3,8- triazaspiro[4,5]decan-4-one (Cptd), tetrahydro-isoquinoline-3-carboxylic acid (3-Tic), 5H- thiazolo [3,2-a]pyridine-3-carboxylic acid (Btd), 3-aminobenzoic acid (3-Abz), 3-(2- thienyl)alanine (2-Thi), 3-(3-thienyl)alanine (3-Thi), α-aminooctanedioc acid (Asu), diethylglycine (Deg), 4-amino-4-carboxy-1,1-dioxo-tetrahydrothiopyran (Acdt), 1-amino-1-(4- hydroxycyclohexyl) carboxylic acid (Ahch), 1-amino-1-(4-ketocyclohexyl)carboxylic acid (Akch), 4-amino-4-carboxytetrahydropyran (Actp), 3-nitrotyrosine (Tyr(3-NO2)), 1-amino-1- cyclohexane carboxylic acid (Ach), 1-amino-1-(3-piperidinyl)carboxylic acid (3-Apc), 1-amino- 1-(4-piperidinyl)carboxylic acid (4-Apc), 2-amino-3-(4-piperidinyl) propionic acid (4-App), 2- aminoindane-2-carboxylic acid (Aic), 2-amino-2-naphthylacetic acid (Ana), (2S, 5R)-5- phenylpyrrolidine-2-carboxylic acid (Ppca), 4-thiazoylalanine (Tha), 2-aminooctanoic acid (Aoa), 2-aminoheptanoic acid (Aha), ornithine (Orn), azetidine-2-carboxylic acid (Aca), α- amino-3-chloro-4,5-dihydro-5-isoazoleacetic acid (Acdi), thiazolidine-2-carboxylic acid (Thz(2- COOH)), allylglycine (Agl), 4-cyano-2-aminobutyric acid (Cab), 2-pyridylalanine (2-Pal), 2- quinoylalanine (2-Qal), cyclobutylalanine (Cba), a phenylalanine analog, derivatives of lysine, ornithine (Orn) and α,γ-diaminobutyric acid (Dbu), stereoisomers thereof, and combinations thereof (see, e.g., Liu et al., Anal. Biochem., 295:9-16 (2001)). As such, the unnatural α-amino acids are present either as unnatural L-α-amino acids, unnatural D-α-amino acids, or combinations thereof. “Amino acid mimetics” are chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but that function in a manner similar to a naturally- occurring amino acid. Suitable amino acid mimetics include, without limitation, β-amino acids and γ-amino acids. In β-amino acids, the amino group is bonded to the β-carbon atom of the carboxyl group such that there are two carbon atoms between the amino and carboxyl groups. In γ-amino acids, the amino group is bonded to the γ-carbon atom of the carboxyl group such that there are three carbon atoms between the amino and carboxyl groups. Suitable R groups for β- or γ-amino acids include, but are not limited to, side-chains present in naturally-occurring amino acids and unnatural amino acids. “C6-26aralkyl” refers to an arylalkyl group having 6 to 26 carbon atoms and comprising an alkyl group substituted with an aryl group. Suitably the alkyl group is a C1-6 alkyl group and the aryl group is phenyl. Examples of C6-26aralkyl include benzyl and phenethyl. In some cases, the C6-26aralkyl group may be optionally substituted, and an example of an optionally substituted C6-26aralkyl group is 4-methoxylbenzyl. “C5-20Aryl”: refers to fully unsaturated monocyclic, bicyclic and polycyclic aromatic hydrocarbons having at least one aromatic ring and having a specified number of carbon atoms that comprise their ring members (e.g., C5-20aryl refers to an aryl group having from 5 to 20 carbon atoms as ring members). The aryl group may be attached to a parent group or to a substrate at any ring atom and may include one or more non-hydrogen substituents unless such attachment or substitution would violate valence requirements. Suitably, a C6-14aryl is selected from a C6-12aryl, more suitably, a C6-10aryl. Examples of aryl groups include phenyl. “Arylene” refers to a divalent radical derived from an aryl group, e.g., –C6H4- which is the arylene derived from phenyl. “C3-8cycloalkyl” or “3- to 8-membered cycloalkyl” means a closed ring of carbon atoms having 3 to 8 carbon atoms, preferably 3 to 7 carbon atoms, more preferably 3 to 6 carbon atoms and encompasses, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. “C3-8cycloalkylene” or “3- to 8-membered cycloalkylene” refers to a divalent radical derived from a cycloalkyl group, e.g., –C6H10-. “C3-8cycloalkenylene” refers to a divalent radical derived from a cycloalkenyl group, that is a carbocyclic group with one or more C=C, e.g., –C6H8-. Halogen or halo: refers to a group selected from F, Cl, Br, and I. Suitably, the halogen or halo is F or Cl. In some aspects, suitably, the halogen is F. In other aspects, suitably the halogen is Cl. “C5-10heteroaryl” or “5- to 10-membered heteroaryl”: refers to unsaturated monocyclic or bicyclic aromatic groups comprising from 5 to 10 ring atoms, whether carbon or heteroatoms, of which from 1 to 5 are ring heteroatoms. Suitably, any monocyclic heteroaryl ring has from 5 to 6 ring atoms and from 1 to 3 ring heteroatoms. Suitably each ring heteroatom is independently selected from nitrogen, oxygen, and sulfur. The bicyclic rings include fused ring systems and, in particular, include bicyclic groups in which a monocyclic heterocycle comprising 5 ring atoms is fused to a benzene ring. The heteroaryl group may be attached to a parent group or to a substrate at any ring atom and may include one or more non-hydrogen substituents unless such attachment or substitution would violate valence requirements or result in a chemically unstable compound. Examples of monocyclic heteroaryl groups include, but are not limited to, those derived from: N1: pyrrole, pyridine; O1: furan; S1: thiophene; N1O1: oxazole, isoxazole, isoxazine; N2O1: oxadiazole (e.g., 1-oxa-2,3-diazolyl, 1-oxa-2,4-diazolyl, 1-oxa-2,5-diazolyl, 1-oxa-3,4- diazolyl); N3O1: oxatriazole; N1S1: thiazole, isothiazole; N2: imidazole, pyrazole, pyridazine, pyrimidine, pyrazine; N3: triazole, triazine; and, N4: tetrazole. Examples of heteroaryl which comprise fused rings, include, but are not limited to, those derived from: O1: benzofuran, isobenzofuran; N1: indole, isoindole, indolizine, isoindoline; S1: benzothiofuran; N1O1: benzoxazole, benzisoxazole; N1S1: benzothiazole; N2: benzimidazole, indazole; O2: benzodioxole; N2O1: benzofurazan; N2S1: benzothiadiazole; N3: benzotriazole; and N4: purine (e.g., adenine, guanine), pteridine; “heteroarylene” refers to a divalent radical derived from a heteroaryl group (such as those described above) as exemplified by pyridinyl –[C5H3N]-. Heteroarylenes may be monocyclic, bicyclic, or tricyclic ring systems. Representative heteroarylenes, are not limited to, but may be selected from triazolylene, tetrazolylene, oxadiazolylene, pyridylene, furylene, benzofuranylene, thiophenylene, benzothiophenylene, quinolinylene, pyrrolylene, indolylene, oxazolylene, benzoxazolylene, imidazolylene, benzimidazolylene, thiazolylene, benzothiazolylene, isoxazolylene, pyrazolylene, isothiazolylene, pyridazinylene, pyrimidinylene, pyrazinylene, triazinylene, cinnolinylene, phthalazinylene, quinazolinylene, pyrimidylene, azepinylene, oxepinylene, and quinoxalinylene. Heteroarylenes are optionally substituted. “C6-16heteroarylalkyl” refers to an alkyl group substituted with a heteroaryl group. Suitably the alkyl is a C1-6alkyl group and the heteroaryl group is C5-10heteroaryl as defined above. Examples of C6-16 heteroarylalkyl groups include pyrrol-2-ylmethyl, pyrrol-3-ylmethyl, pyrrol- 4-ylmethyl, pyrrol-3-ylethyl, pyrrol-4-ylethyl, imidazol-2-ylmethyl, imidazol-4-ylmethyl, imidazol-4-ylethyl, thiophen-3-ylmethyl, furan-3-ylmethyl, pyridin-2-ylmethyl, pyridin-2- ylethyl, thiazol-2-ylmethyl, thiazol-4-ylmethyl, thiazol-2-ylethyl, pyrimidin-2-ylpropyl, and the like. “C3-20heterocyclyl”: refers to saturated or partially unsaturated monocyclic, bicyclic or polycyclic groups having ring atoms composed of 3 to 20 ring atoms, whether carbon atoms or heteroatoms, of which from 1 to 10 are ring heteroatoms. Suitably, each ring has from 3 to 8 ring atoms and from 1 to 4 ring heteroatoms (e.g., suitably C3-5heterocyclyl refers to a heterocyclyl group having 3 to 5 ring atoms and 1 to 4 heteroatoms as ring members). The ring heteroatoms are independently selected from nitrogen, oxygen, and sulphur. As with bicyclic cycloalkyl groups, bicyclic heterocyclyl groups may include isolated rings, spiro rings, fused rings, and bridged rings. The heterocyclyl group may be attached to a parent group or to a substrate at any ring atom and may include one or more non-hydrogen substituents unless such attachment or substitution would violate valence requirements or result in a chemically unstable compound. Examples of monocyclic heterocyclyl groups include, but are not limited to, those derived from: N1: aziridine, azetidine, pyrrolidine, pyrroline, 2H-pyrrole or 3H-pyrrole, piperidine, dihydropyridine, tetrahydropyridine, azepine; O1: oxirane, oxetane, tetrahydrofuran, dihydrofuran, tetrahydropyran, dihydropyran, pyran, oxepin; S1: thiirane, thietane, tetrahydrothiophene, tetrahydrothiopyran, thiepane; O2: dioxoiane, dioxane, and dioxepane; O3: trioxane; N2: imidazoiidine, pyrazolidine, imidazoline, pyrazoline, piperazine: N1O1: tetrahydrooxazole, dihydrooxazole, tetrahydroisoxazole, dihydroisoxazole, morpholine, tetrahydrooxazine, dihydrooxazine, oxazine; N1S1: thiazoline, thiazolidine, thiomorpholine; N2O1: oxadiazine; O1S1: oxathiole and oxathiane (thioxane); and N1O1S1: oxathiazine. Examples of substituted monocyclic heterocyclyl groups include those derived from saccharides, in cyclic form, for example, furanoses, such as arabinofuranose, lyxofuranose, ribofuranose, and xylofuranse, and pyranoses, such as aliopyranose, altropyranose, glucopyranose, mannopyranose, gulopyranose, idopyranose, galactopyranose, and talopyranose. “Nucleic acid”, refers to a linear polymer of nucleosides (including deoxyribo-nucleosides, ribonucleosides, or analogs thereof) joined by inter-nucleosidic linkages. Nucleic acid may encompass the term “polynucleotide” as well as “oligonucleotide”. The linear polymer may be represented by a sequence of letters, such as “ATGCCTG,” where it will be understood that the nucleotides are in 5' to 3' order from left to right and that “A” denotes deoxyadenosine, “C” denotes deoxycytidine, “G” denotes deoxyguanosine, and “T” denotes deoxythymidine, unless otherwise noted. Another natural nucleotide is “U”, denoting uridine. The letters A, C, G, T and U can be used to refer to the bases themselves, to nucleosides, or to nucleotides comprising the bases, as is standard in the art. In naturally occurring nucleic acids, the inter-nucleoside linkage is typically a phosphodiester bond, and the subunits are referred to as “nucleotides.” Nucleic acids may also include other inter-nucleoside linkages, such as phosphoro-thioate linkages, and the like. Such analogs of nucleotides that do not include a phosphate group are considered to fall within the scope of the term “nucleotide”" as used herein, and nucleic acids comprising one or more inter-nucleoside linkages that are not phosphodiester linkages are still referred to as "polynucleotides”, “oligonucleotides”, etc. Nitrogen protecting groups Nitrogen protecting groups are well known in the art and are groups that block or protect the nitrogen groups from further reaction. Nitrogen protecting groups are exemplified by carbamates, such as methyl or ethyl carbamate, 9-fluorenylmethyloxy-carbonyl (Fmoc), substituted ethyl carbamates, carbamates cleaved by 1,6-beta-elimination, ureas, amides, peptides, alkyl and aryl derivatives. Carbamate protecting groups have the general formula: . In this specification a zig-zag line (or wavy line ) indicates the point of attachment of the shown group (e.g., the protecting group above) to the rest of the compound of formula (I). Suitable nitrogen protecting groups may be selected from acetyl, trifluoroacetyl, t-butyloxy- carbonyl (BOC), benzyloxycarbonyl (Cbz) and 9-fluorenylmethyloxy-carbonyl (Fmoc). A large number of possible carbamate nitrogen protecting groups are listed on pages 706 to 771 of Wuts, P.G.M. and Greene, T.W., Protective Groups in Organic Synthesis, 4thEdition, Wiley- lnterscience, 2007, and in P. Kocienski, Protective Groups, 3rd Edition (2005) which are incorporated herein by reference. Particularly preferred protecting groups include Alloc (allyloxycarbonyl), Troc (2,2,2- Trichloroethyl carbonate), Teoc [2-(Trimethylsilyl)ethoxycarbony], BOC (tert- butyloxycarbonyl), Doc (2,4-dimethylpent-3-yloxycarbonyl), Hoc (cyclohexyloxy-carbonyl), TcBOC (2,2,2-trichloro-tert-butyloxycarbonyl), Fmoc (9-fluorenylmethyloxycarbonyl), 1-Adoc (1-Adamantyloxycarbonyl) and 2-Adoc (2-adamantyloxycarbonyl). Hydroxyl protecting groups Hydroxyl protecting groups are well known in the art, a large number of suitable groups are described on pages 16 to 366 of Wuts, P.G.M. and Greene, T.W., Protective Groups in Organic Synthesis, 4thEdition, Wiley-lnterscience, 2007, and in P. Kocienski, Protective Groups, 3rd Edition (2005) which are incorporated herein by reference. Classes of particular interest include silyl ethers, methyl ethers, alkyl ethers, benzyl ethers, esters, benzoates, carbonates, and sulfonates. Suitable protecting groups include THP (tetrahydropyranyl ether). Hydroxyls may also be protected as N methyl piperazine carbamate, especially the hydroxyl group of a phenol. LS In embodiments, LSis a bond or a linker moiety that is attached or connected to RS. In some embodiments, LSis a bond, an amino acid, a peptide chain having from 2 to 6 amino acids, an alkylene chain containing from 1 to 12 carbon atoms which may contain one or more carbon- carbon double or triple bonds, a paraformaldehyde chain –(OCH2)1-12-, a polyethylene glycol chain -(OCH2CH2)1-6-, which chains may be interrupted by or optionally incorporates one or more of P, O, S, NH, C5-9heteroarylene, phenylene, heterocyclyl, cycloalkyl, ether, oxo, carboxamidyl, and / or urethanyl moieties wherein the C5-9heteroarylene, phenylene, heterocyclyl, and / or cycloalkyl moieties are optionally substituted. In some embodiments, the C5-9heteroarylene, phenylene, heterocyclyl, and / or cycloalkyl moieties are optionally substituted with 1, 2 or 3 independently selected optional R20groups. In some embodiments, LScomprises L2, R28, or L2-R28. In some embodiments, linker Lscomprises one or more groups selected from sulfamino, sulfamyl, sulfate, sulfhydryl, sulfinamino, sulfinate, sulfino, sulfinyl, sulfinyloxy, sulfo, sulfonamido, sulfonamino, sulfonate, sulfonyl, sulfonyloxy, phosphate ester, phosphoramidate, thiophosphate ester, phosphonate, and thiophosphonate. In some embodiments, LScomprises a benzyl carboxylate group. In some embodiments, LScomprises: wherein v is 0, 1, 2, or 3; and each R40is independently selected from -NO2, -SO3R26, -C(=O)-R26, -C(=O)-Cl, -C1-6fluoroalkyl, -C1-6fluoroalkoxy, R20, R28, -[CH2CH2O]1-50-R28, and -NH-XAA-R28, wherein XAAis an amino acid sequence having from 1 to 20 amino acid moieties. In some embodiments, v is 1, 2, or 3; and each R40is independently selected from - NO2, -SO3R26, -C(=O)-R26, -C(=O)-Cl, -C1-6fluoroalkyl, -C1-6fluoroalkoxy, -F, -OH, -NH2, -CN, -NCO, -(CH2)j-CO2R26, -C(=O)-NR26R27, L2-R28, maleimide, , and , wherein XAAis an amino acid sequence having from 1 to 10 amino acid moieties. In some embodiments, LSis: . RSIn some embodiments, the carbohydrate substituent of the compounds of formula (I) is a univalent saccharide substituent, represented by RS. In some embodiments, RSis glycosyl or O- glycosyl. “Saccharide”, refers to a sugar that may be a monosaccharide or disaccharide, and “RS” refers to monosaccharide and / or disaccharide univalent substituents derived from a monosaccharide and / or a disaccharide. The saccharide may suitably be a pentose or hexose or a disaccharides containing a pentose and / or a hexose. Examples of monosaccharides include glucose, fructose, galactose, ribose, ribulose and stereoisomers of these sugars. In this specification, saccharide refers to the sugar in the furanose, acyclic, and / or pyranose forms, and formulae showing sugars in one form are also meant to include the sugar in the other forms unless the context otherwise requires. Saccharides that are univalent substituents may comprise glycosyl groups of the corresponding mono (or di-) saccharide obtainable by removing a hydroxyl group from monosaccharide or disaccharide or by removing a hydrogen from a hydroxyl group of the mono- or di-saccharide. Non-limiting examples of furanoses include arabinofuranose, lyxofuranose, ribofuranose, xylofuranse, etc. Non-limiting examples of pyranoses include aliopyranose, altropyranose, glucopyranose, mannopyranose, gulopyranose, idopyranose, galactopyranose, talopyranose, etc. RTIn embodiments, RTis selected from L2-R28, phenyl, and C5-9heteroaryl, wherein the phenyl and C5-9heteroaryl groups are optionally substituted with up to three optional substituent groups. Hence, any of the phenyl group or the C5-9heteroaryl groups selected for RTmay be optionally substituted with up to three optional substituent groups. Suitably RTis selected from L2-R28, phenyl, pyrrolyl, N-methylpyrrolyl, furanyl, thiophenyl, imidazolyl, N-methylimidazolyl, oxazolyl, thiazolyl, pyridyl, benzofuranyl, benzothiophenyl, benzimidazolyl, N-methylbenzoimidazolyl, benzooxazolyl and benzothiazolyl, wherein the phenyl, pyrrolyl, N-methylpyrrolyl, furanyl, thiophenyl, imidazolyl, N-methylimidazolyl, oxazolyl, thiazolyl, pyridyl, benzofuranyl, benzothiophenyl, benzimidazolyl, N- methylbenzoimidazolyl, benzooxazolyl and benzothiazolyl groups are optionally substituted with up to three optional substituent groups selected from OH, C1-6alkyl, OC1-6alkyl, L2-R28, (CH2)j-CO2R11, O-(CH2)k-NR11R12, (CH2)j-NR11R12, C(=O)-NH-(CH2)k-NR11R12; C(=O)-NH- R24and C(=O)-NH-(CH2)k-C(=NH)NR11R12. Suitably RTis selected from L2-R28, phenyl, pyrrolyl, N-methylpyrrolyl, furanyl, thiophenyl, imidazolyl, N-methylimidazolyl, oxazolyl, thiazolyl, benzofuranyl, benzothiophenyl, benzimidazolyl, N-methylbenzoimidazolyl, benzooxazolyl and benzothiazolyl, wherein the phenyl, pyrrolyl, N-methylpyrrolyl, furanyl, thiophenyl, imidazolyl, N-methylimidazolyl, oxazolyl, thiazolyl, benzofuranyl, benzothiophenyl, benzimidazolyl, N-methylbenzoimidazolyl, benzooxazolyl and benzothiazolyl groups are optionally substituted with one or two optional substituent groups selected from OH, C1-6alkyl, OC1-6alkyl, L2-R28, (CH2)j-CO2R11, O-(CH2)k- NR11R12, (CH2)j-NR11R12, C(=O)-NH-(CH2)k-NR11R12; C(=O)-NH-R24and C(=O)-NH-(CH2)k- C(=NH)NR11R12. Suitably RTis selected from L2-R28, phenyl, N-methylpyrrolyl, thiophenyl, N-methylimidazolyl, oxazolyl, thiazolyl, benzothiophenyl, N-methylbenzoimidazolyl and benzothiazolyl, wherein the phenyl, N-methylpyrrolyl, thiophenyl, N-methylimidazolyl, oxazolyl, thiazolyl, benzothiophenyl, N-methylbenzoimidazolyl and benzothiazolyl groups are optionally substituted with one or two optional substituent groups selected from OH, C1-6alkyl, OC1-6alkyl, L2-R28, (CH2)j-CO2R11O-(CH2)k-NR11R12, (CH2)j-NR11R12, C(=O)-NH-(CH2)k-NR11R12; C(=O)-NH-R24and C(=O)-NH-(CH2)k-C(=NH)NR11R12. Suitably RTis optionally substituted with up to three optional substituent groups selected from OH, C1-6alkyl, OC1-6alkyl, L2-R28, (CH2)j-CO2R11, O-(CH2)k-NH2, (CH2)j-NH2, C(=O)-NH- (CH2)k-NH2; C(=O)-NH-R24and C(=O)-NH-(CH2)k-C(=NH)NH2. Suitably RTis an optionally substituted C(=O)-NH-R24, wherein R24is -C6H4-(CH2)j-R18, and the phenylene group –C6H4- is para substituted. Suitably RTis optionally substituted with up to three optional substituent groups selected from OH, methyl, ethyl, OCH3, OCH2CH3, L2-R28, CO2H, CO2CH3, CO2CH2CH3, O-(CH2)k-NH2and (CH2)j-NH2. Suitably RTis optionally substituted with one or two optional substituent groups. More suitably RTis optionally substituted with one optional substituent group. More suitably RTis selected from: RS, , and ; wherein Z1is selected from NH, N-CH3, N-RS, S and O; Z2is selected from CH and N; Z3is selected from S and O; Z4is selected from CH, CRSand N; R22is selected from –L2-R28, (CH2)jCO2R11, (CH2)jNR11R12and C(=O)-NH-C6H4-(CH2)j-R18; R18is selected from –L2-R28, CO2R11and NR11R12; j is selected from an integer from 0 to 6; R11and R12are independently selected from H, –L2-R28, and C1-6alkyl; and R23is selected from H, RS, –L2-R28, and C1-6alkyl. The wavy line indicates the point of attachment of the above RTgroup to the rest of the compound of formula (I). More suitably RTis selected from: , , and ; wherein Z1is selected from NH, N-CH3, N-RS, S and O; Z2is selected from CH and N; and Z3 is selected from S and O; Z4is selected from CH, RSand N; R11is selected from H, L2-R28, and C1-6alkyl; and R23is selected from H, RS, L2-R28, and C1-6alkyl. L2In embodiments, linker L2is a bond or is a moiety having 1-200 nonhydrogen atoms selected from C, N, P, O, S, or halogen, and optionally incorporates ether, oxo, carboxyl, carboxamide, carboxamidyl, urethanyl, branched, cyclic, unsaturated, amino acid, heterocyclyl, aryl or heteroaryl moieties. In embodiments, linker L2is a bond or comprises one or more groups selected from an amino acid, a peptide chain having from 2 to 100 amino acids, an alkylene chain containing from 1 to 50 carbon atoms which may contain one or more carbon-carbon double or triple bonds, a paraformaldehyde chain –(OCH2)1-50-, and a polyethylene glycol chain -(OCH2CH2)1-50-, which chains may be interrupted by or optionally incorporate one or more of P, O, S, NH, C5-9heteroarylene, phenylene, heterocyclyl, cycloalkyl, ether, oxo, carboxamidyl, and / or urethanyl moieties wherein the C5-9heteroarylene, phenylene, heterocyclyl, and / or cycloalkyl moieties are optionally substituted. In some embodiments, the peptide, alkylene, paraformaldehyde, and polyethylene glycol chains and / or the C5-9heteroarylene, phenylene, heterocyclyl, and cycloalkyl moieties are optionally substituted with 1, 2 or 3 independently selected optional R20groups and / or Ls-Rsgroups. Linker L2may be unbranched or branched, flexible or rigid, short or long and may incorporate any combination of moieties as deemed useful. In some embodiments, at least a portion of the linker L2 may have a polyalkylene oxide polymeric region, which may enhance solubility of the compound of formula (I) or (II). In some embodiments, the linker L2may have a repeating unit of ethylene glycol, and may have a number of repeating ethylene glycol units of about 1 to about 25, or any number therebetween. In some embodiments, L2may include about 3 to about 20, about 4 to about 15, about 5 to about 12 or about 6 to about 10 ethylene glycol units. In some embodiments, at least a portion of Linker L2may include one or more amino acid moieties which may provide enhanced solubility for the compound of formula (I) or (II) or may provide amino acid sequences to enhance target binding, enhance compatibility with a targeting agent, or enhance target binding recognition. In other embodiments, the linker L2may include one or more amino acid moieties that provide a suitable substrate motif for a protease. When a set of amino acid moieties are incorporated into the linker L2that provide a substrate motif specific for a selected protease, the cytotoxic drug compound of formula (I) or (II) may be released from a target bound conjugate to provide localized cytotoxic effects. Such substrate motifs are known in the art and may be incorporated into the linker L2as desired to provide selective release from the target bound conjugate. This selectivity can be based on known presence of a desired protease within the localized delivery region of the conjugate drug. Other polymeric types of moieties may be incorporated in the linker L2, such as polyacids, polysaccharides, or polyamines. Other moieties such as substituted aromatic or heteroaromatic moieties may be used to enhance rigidity or provide synthetically accessible sites on substituents therein for linking to reactive moieties or to the compound of formula (I), group G, Q or T. In some embodiments, linker L2may comprise one or more groups selected from sulfamino, sulfamyl, sulfate, sulfhydryl, sulfinamino, sulfinate, sulfino, sulfinyl, sulfinyloxy, sulfo, sulfonamido, sulfonamino, sulfonate, sulfonyl, sulfonyloxy, phosphate ester, phosphoramidate, thiophosphate ester, phosphonate, and thiophosphonate. For example, the linker L2can include ethylene glycol repeating units, and / or an amino acid sequence. In some embodiments, linker L2includes the formula: -[CH2CH2O]0-50-XAA- wherein XAAis an amino acid sequence. In some embodiments, the linker L2comprises or consists of the formula: or ; wherein RSis a univalent saccharide substituent, preferably glycosyl or O-glycosyl; and LCcomprises one or more groups selected from an amino acid, an amino acid derivative, a peptide chain having from 2 to 6 amino acids or amino acid derivatives, an alkylene chain containing from 1 to 12 carbon atoms which may contain one or more carbon-carbon double or triple bonds, a paraformaldehyde chain –(OCH2)1-12-, a polyethylene glycol chain -(OCH2CH2)1-8-, which chains may be interrupted by one or more P, O, S and / or NH groups and / or C5-9heteroarylene and / or phenylene, wherein each C5-9heteroarylene group and / or each phenylene group is optionally substituted. In embodiments, LCis further conjugated to R28. In some embodiments, the linker L2comprises or consists of the formula: or . In some embodiments, LChas the formula , optionally or . In some embodiments, R28-LCcomprises a maleimide, optionally wherein the maleimide has the formula , optionally or . In some embodiments, LCcomprises a polyethylene glycol chain -(OCH2CH2)1-10-, optionally - (OCH2CH2)8-. In some embodiments, LCis selected from: , , and . In some embodiments, R28-LCis selected from: , , and

[0007] . In some embodiments, R28-L2comprises or consists of the formula: or , wherein R28is selected from an azide, alkyne, bisulfone, carbohydrazide, hydrazine, hydroxylamine, iodoacetamide, isothiocyanate, maleimide, phosphine, pyrridopyridazine, semihydrazide, succinimidyl ester, sulfodichlorophenol ester, sulfonyl halide, sulfosuccinimidyl ester, 4- sulfotetrafluorophenyl ester, tetrafluorophenyl ester, thiazole, RA,O-(CH2)k-NR26R26, NHNH2, or is a targeting agent wherein the targeting agent is selected from a protein, a portion of a protein, a peptide, a nucleic acid, or an antibody; and LChas the formula , wherein X10is a single bond, -HN-[CH2-CH2-O]p-(CH2)1-5-C(O)-, -HN-[CH2-CH2-O]p-(CH2)1-5-C(O)- (CH2)1-5-NHC(O)-[CH2-CH2-O]p-Alk NH-CH-C(O) NH-, or , wherein p is independently at each occurrence an integer from 1-50, and Alk is a C1-C5alkyl; and X20is a single bond, , or . In some embodiments, LChas the formula . In some embodiments, LChas the formula . In some embodiments, p is an integer from 5 to 10, e.g.5, 6, 7, 8, 9, or 10. In some embodiments, p is 8. In some embodiments, X10is -HN-[CH2-CH2-O]p-(CH2)2-C(O)-. In some embodiments, X10is a single bond. In some embodiments, X10 is -HN-[CH2-CH2-O]p-(CH2)2-C(O)-N-. In some embodiments, X10is . In some embodiments, Alk is -CH3. In some embodiments, X20is a single bond. In some embodiments, X20is . In some embodiments, X20is . Any suitable number of ethylene glycol units can be used in the linker L2of the present disclosure. For example, the linker L2can include 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 16, 19, 20, 23, 24, 35, 36, 37, 48, 49, or more ethylene glycol units. In some embodiments, the linker L2can include 8 ethylene glycol units. Several commercially available ethylene glycol groups (polyethylene glycol, PEG) are suitable in the linker L2, such as H2N-PEG8-C(O)OH, having a discrete (“d”) polyethylene glycol having 8 ethylene glycol repeating units. Other discrete PEG units are commercially available and known to one of skill in the art, such as by Advanced ChemTech. In some embodiments, the linker L2includes the formula: -HN-PEG-C(O)-XAA- wherein PEG has 1-50 ethylene glycol units, and XAAis an amino acid sequence. In some embodiments, the linker L2includes the formula: -HN-[CH2-CH2-O]p-(CH2)1-5-C(O)-XAA- wherein p is an integer from 1-50, and XAAis an amino acid sequence. In some embodiments, p is an integer from 5 to 10, e.g.5, 6, 7, 8, 9, or 10. The amino acid portion of the linker L2can include any suitable number of amino acid moieties, as described above. For example, the amino acid sequence XAAcan include from 1 to 100 amino acid moieties, or from 1 to 10 amino acid moieties, or from 1 to 5 amino acid moieties. In some embodiments, XAAis an amino acid sequence comprising 1 to 30 amino acids. In some embodiments, XAAis an amino acid sequence comprising 1 to 25 amino acids, 1 to 20 amino acids, 1 to 15 amino acids, 2 to 15 amino acids, 1 to 10 amino acids, 2 to 10 amino acids, 1 to 9 amino acids, 2 to 9 amino acids, 1 to 8 amino acids, 2 to 8 amino acids, 1 to 7 amino acids, 2 to 7 amino acids, 1 to 6 amino acids, 2 to 6 amino acids, 1 to 5 amino acids, 2 to 5 amino acids, 1 to 4 amino acids, 2 to 4 amino acids, 1 to 3 amino acids, or 2 to 3 amino acids. For example, XAAcan be an amino acid sequence comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or more amino acids. In some embodiments, XAAcan include 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, or more amino acid moieties. In some embodiments, XAAis an amino acid sequence comprising 1 to 10 amino acids. In some embodiments, XAAis an amino acid sequence comprising 2 to 8 amino acids. In some embodiments, XAAis an amino acid sequence comprising 2 to 6 amino acids. In some embodiments, XAAis an amino acid sequence comprising 2 to 4 amino acids. In some embodiments, XAAis an amino acid sequence comprising 4 amino acids. In some embodiments, XAAis an amino acid sequence comprising 3 amino acids. In some embodiments, XAAincludes 2 amino acid moieties. In some embodiments, XAAis Gly-Gly-Phe-Gly. In some embodiments, XAAis Val-Cit. In some embodiments, XAAis Ala-Ala. In some embodiments, XAAis Val-Ala. In some embodiments, XAAis Ala-Ala-Ala. In some embodiments, XAAis Val-Ala-Ala. In some embodiments, the linker L2includes the formula: -HN-PEG8-C(O)-Val-Ala- wherein PEG8has 8 ethylene glycol units. The linker L2can also include a variety of other connecting groups that connect the ethylene glycol portion to the amino acid sequence, or connect the ethylene glycol or amino acid sequence to R28, or the compound of formula (I) or (II). For example, the amino acid sequence can be connected to the compound of formula (I) or (II) via a 4- amino benzyl carboxylate group. In some embodiments, the ethylene glycol portion can be directly linked to R28. In some embodiments, the linker L2 has the formula: . In some embodiments, L2may be selected from: (i) , (ii) , (iii) , (iv) , (v) , (vi) , (vii) , (viii) , (ix) , (x) or (xi) ; wherein XAAis an amino acid sequence; and K2is -[CH2CH2O]0-50- or -[CH2]0-12-. In some embodiments, XAAmay be L-valyl-L-alanine. R28R28is an azide, alkyne, bisulfone, carbohydrazide, hydrazine, hydroxylamine, iodoacetamide, isothiocyanate, maleimide, phosphine, pyrridopyridazine, semihydrazide, succinimidyl ester, sulfodichlorophenol ester, sulfonyl halide, sulfosuccinimidyl ester, 4-sulfotetrafluorophenyl ester, tetrafluorophenyl ester, thiazole, RA,O-(CH2)k-NR26R26, NHNH2, or is a targeting agent wherein the targeting agent is selected from a protein, a portion of a protein, a peptide, a nucleic acid, or an antibody. Hence, R28is a reactive moiety capable of reacting with a targeting agent, or is a targeting agent. Where R28is a reactive moiety, it can react with functional groups such as aldehydes, amines, disulfides, ketones thiols in the targeting agent, or in Staudinger reactions, Pictet-Spengler reactions and / or Click-type chemistry with the targeting agent. For some reactive moieties suitable coupling reagents are used to react the reactive moiety with a targeting agent, e.g., where R28is a carboxylic acid [when RAis(CH2)j-CO2R26] carbodiimide coupling reagents may be used. Suitably, R28 is an azide, alkynes, bisulfone, carbohydrazide, hydroxylamine, iodoacetamide, isothiocyanate, maleimide, phosphine, semihydrazide, succinimidyl ester and sulfonyl halide, RAor is a targeting agent wherein the targeting agent is selected from a protein, a portion of a protein, a peptide, a nucleic acid, or an antibody. In one aspect, suitably, R28is an azide, alkynes, bisulfone, carbohydrazide, hydroxylamine, iodoacetamide, isothiocyanate, maleimide, phosphine, semihydrazide, succinimidyl ester and sulfonyl halide or RA. A number of other chemistries are known for attachment of compounds to antibodies. US 7,595,292 (Brocchini et al.) refers to linkers that form thioesters with the sulfurs in a disulfide bond of an antibody. US 7,985,783 (Carico et al.) refers to the introduction of aldehyde residues into antibodies, which are used to couple compounds to the antibody. In another aspect, R28is a targeting agent wherein the targeting agent is selected from a protein, a portion of a protein, a peptide, a nucleic acid, or an antibody. The targeting agent may bind to a tumor- associated antigen, a cancer-stem-cell associated antigen or a viral antigen. In various embodiments, the targeting agent may bind to a target selected from an acute myeloid leukemia (AML M4) cell, an acute promyelocytic leukemia cell, an acute lymphoblastic leukemia cell, an acute lymphocytic leukemia cell, a chronic lymphocytic leukemia cell, a chronic myeloid leukemia cell, a chronic T-cell lymphocytic leukemia, a myelodysplasia syndromic cell, a multiple myeloma cell, a prostate carcinoma cell, a renal cell adenocarcinoma cell, a pancreatic adenocarcinoma cell, a lung carcinoma cell or a gastric adenocarcinoma cell, a gastric adenocarcinoma cell, a breast cancer cell, a colon cancer cell, a melanoma cell, a thyroid cancer cell, an ovarian cancer cell, a bladder cancer cell, a liver cancer cell, a head and neck cancer cell, an esophageal cancer cell, a Hodgkin lymphoma cell, a non- Hodgkin lymphoma cell, a mesothelioma cell, a neuroblastoma cell, a neuroendocrine tumor cell, a neurofibromatosis type 1 (NF1) cell, a neurofibromatosis type 2 (NF2) or an osteosarcoma cell. In embodiments, R28may be in a preferred embodiment maleimide: ; optionally linked to a targeting agent. L2-R28In embodiments, L2-R28 may act as a linker to link the compound of formula I to a targeting agent. In some preferred embodiments, L2-R28may comprise: ; ; ; ; ;

[0008] OH

[0009] optionally linked to a targeting agent. In some other preferred embodiments, L2-R28may comprise:

[0010] , optionally ; , optionally ; or , optionally . X1Suitably X1is selected from O, S, NH, CH2, CH2O, C(=O), C(=O)NR13, NR13C(=O), O-C(O) and C(O)-O; Suitably, X1is selected from O, C(=O), C(=O)NR13and NR13C(=O). More suitably X1is selected from O, C(=O)NH and NHC(=O). More suitably X1is O. X2Suitably X2is selected from O, S, NH, CH2, CH2O, C(=O), C(=O)NR15, NR15C(=O), O-C(O) and C(O)O or is absent. Suitably X2is selected from O, C(=O), C(=O)NR15and NR16C(=O) or is absent. More suitably X2is selected from O, C(=O)NH and NHC(=O). Suitably X2is the same as X1. More suitably X2is O. L In embodiments, L is a linker group. Suitably, any of the peptide chain, alkylene chain, paraformaldehyde chain or polyethylene glycol chain may be interrupted by, or substituted with, one or more hetero-atoms (e.g., P, N or NH, O, and S) and / or one or more C5-9heteroarylene groups (e.g., pyrrolylene, pyrazolylene, pyrazolylene, 1,2,3-triazolylene, pyridinylene) and / or one or more phenylene groups, wherein each C5-9heteroarylene group (e.g., pyrrolylene, pyrazolylene, pyrazolylene, 1,2,3-triazolylene, pyridinylene) and / or each phenylene group is optionally substituted. More suitably, the chains may be interrupted by from one to three hetero-atoms (e.g., P, O, S, NH) and / or from one to three C5-9heteroarylene groups and / or from one to three phenylene groups. In some embodiments, L is an amino acid, a peptide chain having from 2 to 6 amino acids, an alkylene chain containing from 1 to 12 carbon atoms which may contain one or more carbon- carbon double or triple bonds, a paraformaldehyde chain –(OCH2)1-12-, a polyethylene glycol chain -(OCH2CH2)1-6-, which chains may be interrupted by or optionally incorporates one or more of O, S, NH, C5-9heteroarylene, phenylene, heterocyclyl, cycloalkyl, ether, oxo, carboxamidyl, and / or urethanyl moieties wherein the C5-9heteroarylene, phenylene, heterocyclyl, and / or cycloalkyl moieties are optionally substituted. In some embodiments, the peptide, alkylene, paraformaldehyde, and polyethylene glycol chains and / or the C5-9heteroarylene, phenylene, heterocyclyl, and cycloalkyl moieties are optionally substituted with 1, 2 or 3 independently selected optional R20groups and / or Ls-Rsgroups. In some embodiments, L may comprise L2-R28and / or Ls-Rs. In some embodiments, L may comprise L2-R28. In some embodiments, L may comprise Ls-Rs. In some embodiments, linker L may comprise one or more groups selected from sulfamino, sulfamyl, sulfate, sulfhydryl, sulfinamino, sulfinate, sulfino, sulfinyl, sulfinyloxy, sulfo, sulfonamido, sulfonamino, sulfonate, sulfonyl, sulfonyloxy, phosphate ester, phosphoramidate, thiophosphate ester, phosphonate, and thiophosphonate. In some embodiments, linker L and / or L2comprises a moiety that permits branching. In some embodiments, linker L and / or L2comprises the formula: ; or ; wherein RSis a univalent saccharide substituent, preferably glycosyl or O-glycosyl; and LCis selected from an amino acid, an amino acid derivative, a peptide chain having from 2 to 6 amino acids or amino acid derivatives, an alkylene chain containing from 1 to 12 carbon atoms which may contain one or more carbon-carbon double or triple bonds, a paraformaldehyde chain – (OCH2)1-12-, a polyethylene glycol chain –(OCH2CH2)1-8-, which chains may be interrupted by one or more P, O, S and / or NH groups and / or C5-9heteroarylene and / or phenylene, wherein each C5-9heteroarylene group and / or each phenylene group is optionally substituted. Suitably L is selected from a peptide chain having from 2 to 5 amino acids, from 2 to 4 amino acids, from 2 to 3 amino acids; an alkylene chain containing from 1 to 11 carbon atoms, from 1 to 10 carbon atoms, from 1 to 9 carbon atoms, from 1 to 8 carbon atoms, from 1 to 7 carbon atoms, from 1 to 6 carbon atoms, from 1 to 5 carbon atoms, from 1 to 4 carbon atoms, from 1 to 3 carbon atoms, which may contain one or more carbon-carbon double or triple bonds; a paraformaldehyde chain –(OCH2)1-12-, –(OCH2)1-11-, –(OCH2)1-10-, –(OCH2)1-9-, –(OCH2)1-8-, – (OCH2)1-7-, –(OCH2)1-6-, –(OCH2)1-5-, –(OCH2)1-4-, –(OCH2)1-3- a polyethylene glycol chain – (OCH2CH2)1-5-, chain –(OCH2CH2)1-4-, chain –(OCH2CH2)1-3-; which chain may be interrupted by one or more hetero-atoms and / or from one to three C5-9heteroarylene groups and / or from one to three phenylene groups, wherein the C5-9heteroarylene and / or phenylene groups are optionally substituted with 1, 2 or 3 independently selected optional R20groups and / or Ls-Rsgroups. In some embodiments, L comprises one or more C5-9heteroarylene and / or phenylene groups optionally substituted with L2-R28and / or Ls-Rs. In some embodiments, L comprises one or more C5-9heteroarylene and / or phenylene groups optionally substituted with L2-R28. In some embodiments, L comprises one or more C5-9heteroarylene and / or phenylene groups optionally substituted with Ls-Rs. More suitably, L may be selected from an alkylene chain containing from 1 to 12 carbon atoms which may contain one or more carbon-carbon double or triple bonds. More suitably, L may be selected from CH=CH, CH2, CH2CH2, CH2CH2CH2, CH2CH2CH2CH2and CH2CH2CH2CH2CH2. G In some embodiments, the D moiety of formula (I) comprises G, a G- alkylating DNA group of formula (II): (II) wherein: the dotted line indicates the optional presence of a double bond between one or more of C1 and C2, C2 and C3, and C3 and C4; the wavy line indicates the point of attachment to Q; m is 0 or 1; R1, R3and R4are independently selected from H, –LS-RS, and R29; R2is selected from H, L2-R28, R29, and –LS-RS, or one of R1and R2, R2and R3, or R3and R4, together with the carbon atoms to which they are attached form a 6-membered aryl, or a 5- or 6-membered cyclic, heterocyclic, or heteroaryl ring optionally substituted with 1, 2 or 3 independently selected optional –LS-RSand R20groups; R5and R6are selected such that either (i) R5is selected from H, OH, –LS-RS, and OC1-6alkyl; and R6is selected from H, SO3H, –LS-RS, nitrogen protecting groups, –L2-R28and RA; (ii) R5is oxo or H, and R6is H or C1-6alkyl; or (iii) R5and R6together form a double bond; R7and R9are independently selected from H, –LS-RS, and R20; R8is selected from H, SR24, SCH2Ph, R20, L2-R28, and –LS-RS; RAis selected from (CH2)j-OH, (CH2)j-CO2R26, C(=O)-O-(CH2)k-NR26R27, (CH2)jNR26R27, C(=O)-NH-(CH2)j-NR26R27and C(=O)-NH-(CH2)k-C(=NH)NR26R27; L2is a bond or a linker moiety having 1-200 non-hydrogen atoms selected from C, N, O, S or halogen, and optionally incorporates ether, oxo, carboxamidyl, urethanyl, branched, cyclic, unsaturated, heterocyclyl, aryl or heteroaryl moieties; and R28is selected from an azide, alkyne, bisulfone, carbohydrazide, hydrazine, hydroxylamine, iodoacetamide, isothiocyanate, maleimide, phosphine, pyrridopyridazine, semihydrazide, succinimidyl ester, sulfodichlorophenol ester, sulfonyl halide, sulfosuccinimidyl ester, 4- sulfotetrafluorophenyl ester, tetrafluorophenyl ester, thiazole, RA,O-(CH2)k-NR26R26, NHNH2, or is a targeting agent wherein the targeting agent is selected from a protein, a portion of a protein, a peptide, a nucleic acid, or an antibody; each R29 is independently selected from R20, R21, =CH2, =CH-(CH2)s-CH3, =CH-(CH2)s-R21, =O, (CH2)s-OR21, (CH2)s-CO2R21, (CH2)s-NR21R24, O-(CH2)t-NR21R24, NH-C(O)-R21, O- (CH2)t-NH-C(O)-R21, O-(CH2)t-C(O)-NH-R21, (CH2)s-SO2R21, O-SO2R21, (CH2)s-C(O)R21and (CH2)s-C(O)NR21R24; each R20is independently selected from F, Cl, Br, (CH2)j-OH, C1-6alkyl, OC1-6alkyl, OCH2Ph, (CH2)j-CO2R26, O-(CH2)k-NR26R27, C(=O)-O-(CH2)k-NR26R27, C(=O)-NR26R27, (CH2)j- NR26R27, NR26NH2, C(=O)-NH-(CH2)j-NR26R27, C(=O)-NH-C6H4-(CH2)j-R26, C(=O)-NH- (CH2)k-C(=NH)NR26R27, –L2-R28, S(O)2-(C1-6 alkyl), O-(CH2)k-O-(C1-6 alkyl), (CH2)j- S(O)2-NR26R27, C(=NH)-O-(C1-6alkyl), (CH2)k-O-(C1-6alkyl), CN, NCO, Cy, C(O)-NH- (CH2)j-Cy, C(O)-Cy, NH-C(O)-NR26R27and ; each j and s is independently selected from 0, 1, 2, 3, 4, 5 or 6; each k and t is independently selected from 1, 2, 3, 4, 5 or 6; each R21is independently selected from H, C1-12alkyl, C5-6heterocyclyl, C5-9heteroaryl, C6-15heteroarylalkyl, phenyl and C7-12aralkyl groups; wherein the heterocyclyl, heteroaryl, heteroarylalkyl, phenyl and aralkyl groups are optionally substituted with 1, 2 or 3 independently selected optional R20groups; each R24, R26and R27is independently selected from H and C1-12alkyl; each Cy is independently selected from a C5-6heterocyclyl or C5-6heteroaryl group, wherein the heterocyclyl or heteroaryl groups are optionally substituted with 1 or 2 R20groups; LSis a bond, an amino acid, a peptide chain having from 2 to 6 amino acids, an alkylene chain containing from 1 to 12 carbon atoms which may contain one or more carbon-carbon double or triple bonds, a paraformaldehyde chain –(OCH2)1-12-, a polyethylene glycol chain –(OCH2CH2)1-6-, which chains may be interrupted by or optionally incorporates one or more of O, S, NH, C5-9heteroarylene, phenylene, heterocyclyl, cycloalkyl, ether, oxo, carboxamidyl, and / or urethanyl moieties wherein the C5-9heteroarylene, phenylene, heterocyclyl, and / or cycloalkyl moieties are optionally substituted, optionally LSis: ; and RSis a univalent saccharide substituent, preferably glycosyl or O-glycosyl. In some embodiments, LSis or ; wherein LCcomprises one or more groups selected from an amino acid, an amino acid derivative, a peptide chain having from 2 to 6 amino acids or amino acid derivatives, an alkylene chain containing from 1 to 12 carbon atoms which may contain one or more carbon-carbon double or triple bonds, a paraformaldehyde chain –(OCH2)1-12-, a polyethylene glycol chain -(OCH2CH2)1-8-, which chains may be interrupted by one or more P, O, S and / or NH groups and / or C5-9heteroarylene and / or phenylene, wherein each C5-9heteroarylene group and / or each phenylene group is optionally substituted; and RSis a univalent saccharide substituent, preferably glycosyl or O-glycosyl. In some embodiments, in the G moiety of formula (II), at least one of R1, R2, R3, R4, R5, R6, R7, R8, and R9is –LS-RS. In some embodiments, in the G moiety of formula (II), R1is –LS-RS. In some embodiments, in the G moiety of formula (II), R2is RS. In some embodiments, in the G moiety of formula (II), R1is –LS-RS. In some embodiments, in the G moiety of formula (II), R2is RS. In some embodiments, in the G moiety of formula (II), R3is –LS-RS. In some embodiments, in the G moiety of formula (II), R3is RS. In some embodiments, in the G moiety of formula (II), R4is –LS-RS. In some embodiments, in the G moiety of formula (II), R4is RS. In some embodiments, in the G moiety of formula (II), R5is –LS-RS. In some embodiments, in the G moiety of formula (II), R5is RS. In some embodiments, in the G moiety of formula (II), R6is –LS-RS. In some embodiments, in the G moiety of formula (II), R6is RS. In some embodiments, in the G moiety of formula (II), R7is –LS-RS. In some embodiments, in the G moiety of formula (II), R7 is RS. In some embodiments, in the G moiety of formula (II), R8 is – LS-RS. In some embodiments, in the G moiety of formula (II), R8is RS. In some embodiments, in the G moiety of formula (II), R9is –LS-RS. In some embodiments, in the G moiety of formula (II), R9is RS. In some embodiments, the G-alkylator unit G comprises a group of formula (II):

[0011] (II) wherein: the dotted line indicates the optional presence of a double bond between one or more of C1 and C2, C2 and C3, and C3 and C4; the wavy line indicates the point of attachment to Q; m is 0 or 1; R1, R3and R4are independently selected from H and R29; R2is selected from H, L2-R28,R29, and RS, or one of R1and R2, R2and R3, or R3and R4, together with the carbon atoms to which they are attached form a 6-membered aryl, or a 5- or 6-membered cyclic, heterocyclic, or heteroaryl ring optionally substituted with 1, 2 or 3 independently selected optional R20groups; R5and R6are selected such that either (i) R5is selected from H, OH and OC1-6alkyl; and R6is selected from H, SO3H, –LS-RS, nitrogen protecting groups, –L2-R28and RA; (ii) R5is oxo or H, and R6is H or C1-6alkyl; or (iii) R5and R6together form a double bond; R7and R9are independently selected from H and R20; R8is selected from H, SR24, SCH2Ph, R20, L2-R28, and RS; RAis selected from (CH2)j-OH, (CH2)j-CO2R26, C(=O)-O-(CH2)k-NR26R27, (CH2)jNR26R27, C(=O)-NH-(CH2)j-NR26R27and C(=O)-NH-(CH2)k-C(=NH)NR26R27; L2is a bond or a linker moiety having 1-200 non-hydrogen atoms selected from C, N, O, S or halogen, and optionally incorporates ether, oxo, carboxamidyl, urethanyl, branched, cyclic, unsaturated, heterocyclyl, aryl or heteroaryl moieties; and R28is selected from an azide, alkyne, bisulfone, carbohydrazide, hydrazine, hydroxylamine, iodoacetamide, isothiocyanate, maleimide, phosphine, pyrridopyridazine, semihydrazide, succinimidyl ester, sulfodichlorophenol ester, sulfonyl halide, sulfosuccinimidyl ester, 4- sulfotetrafluorophenyl ester, tetrafluorophenyl ester, thiazole, RA,O-(CH2)k-NR26R26, NHNH2, or is a targeting agent wherein the targeting agent is selected from a protein, a portion of a protein, a peptide, a nucleic acid, or an antibody; each R29is independently selected from R20, R21, =CH2, =CH-(CH2)s-CH3, =CH-(CH2)s-R21, =O, (CH2)s-OR21, (CH2)s-CO2R21, (CH2)s-NR21R24, O-(CH2)t-NR21R24, NH-C(O)-R21, O- (CH2)t-NH-C(O)-R21, O-(CH2)t-C(O)-NH-R21, (CH2)s-SO2R21, O-SO2R21, (CH2)s-C(O)R21and (CH2)s-C(O)NR21R24; each R20is independently selected from F, Cl, Br, (CH2)j-OH, C1-6alkyl, OC1-6alkyl, OCH2Ph, (CH2)j-CO2R26, O-(CH2)k-NR26R27, C(=O)-O-(CH2)k-NR26R27, C(=O)-NR26R27, (CH2)j- NR26R27, NR26NH2, C(=O)-NH-(CH2)j-NR26R27, C(=O)-NH-C6H4-(CH2)j-R26, C(=O)-NH- (CH2)k-C(=NH)NR26R27, –L2-R28, S(O)2-(C1-6alkyl), O-(CH2)k-O-(C1-6alkyl), (CH2)j- S(O)2-NR26R27, C(=NH)-O-(C1-6alkyl), (CH2)k-O-(C1-6alkyl), CN, NCO, Cy, C(O)-NH- (CH2)j-Cy, C(O)-Cy, NH-C(O)-NR26R27and ; each j and s is independently selected from 0, 1, 2, 3, 4, 5 or 6; each k and t is independently selected from 1, 2, 3, 4, 5 or 6; each R21is independently selected from H, C1-12alkyl, C5-6heterocyclyl, C5-9heteroaryl, C6-15heteroarylalkyl, phenyl and C7-12aralkyl groups; wherein the heterocyclyl, heteroaryl, heteroarylalkyl, phenyl and aralkyl groups are optionally substituted with 1, 2 or 3 independently selected optional R20groups; each R24, R26and R27is independently selected from H and C1-12alkyl; each Cy is independently selected from a C5-6heterocyclyl or C5-6heteroaryl group, wherein the heterocyclyl or heteroaryl groups are optionally substituted with 1 or 2 R20groups; LSis a bond, an amino acid, a peptide chain having from 2 to 6 amino acids, an alkylene chain containing from 1 to 12 carbon atoms which may contain one or more carbon-carbon double or triple bonds, a paraformaldehyde chain –(OCH2)1-12-, a polyethylene glycol chain–-(OCH2CH2)1-6-, which chains may be interrupted by or optionally incorporates one or more of O, S, NH, C5-9heteroarylene, phenylene, heterocyclyl, cycloalkyl, ether, oxo, carboxamidyl, and / or urethanyl moieties wherein the C5-9heteroarylene, phenylene, heterocyclyl, and / or cycloalkyl moieties are optionally substituted, optionally LSis: ; and RSis a univalent saccharide substituent, preferably glycosyl or O-glycosyl. In some embodiments, in the G moiety of formula (II), at least one of R2, R6, and R8is –LS-RS. In some embodiments, in the G moiety of formula (II), R2is –LS-RS. In some embodiments, in the G moiety of formula (II), R2is RS. In some embodiments, in the G moiety of formula (II), R6is –LS-RS. In some embodiments, in the G moiety of formula (II), R6is RS. In some embodiments, in the G moiety of formula (II), R8is –LS-RS. In some embodiments, in the G moiety of formula (II), R8is RS. In some embodiments, the G-alkylator unit G comprises a group of formula (II-A): (II-A), where the substituents have the definitions indicated above. In some embodiments, G is selected from a group of G1 to G8: (G1); (G2);

[0012] 3); 4);5); 6);

[0013] (G7); and (G8). In some embodiments, G is selected from a group of G1-A to G8-A: (G1-A); (G2-A);

[0014] 5-A); 6-A);

[0015] (G7-A); and (G8-A). In some embodiments, the compounds according to formula (I) may be a compound according to formula (IV): (IV). In some embodiments, in formula (IV), at least one of R2, R5, R6, and R8is –LS-RS. In some embodiments, in formula (IV), R2is –LS-RS. In some embodiments, in formula (IV), R2is RS. In some embodiments, in formula (IV), R5is –LS-RS. In some embodiments, in formula (IV), R5is RS. In some embodiments, in formula (IV), R6is –LS-RS. In some embodiments, in formula (IV), R6is RS. In some embodiments, in formula (IV), R8is –LS-RS. In some embodiments, in formula (IV), R8is RS. In some embodiments, the compounds according to formula (I) may be a compound according to formula (IV-A): (IV-A), where the substituents have the definitions indicated above. In some embodiments, the compound according to formula (I) may be a compound selected from the group consisting of: , , ,

[0016] 

[0017] herein Rs is a univalent saccharide substituent, preferably glycosyl or O-glycosyl. some embodiments, the compound according to formula (I) may be a compound selected m the group consisting of:

[0018] OH

[0019] , , and , wherein RSis a univalent saccharide substituent, preferably glycosyl or O-glycosyl. A In some embodiments, the D moiety of formula (I) comprises A, an A-alkylating DNA group. In this specification, the seco form and spiro form of A groups are used, unless the context otherwise requires, interchangeably. Thus, an A group of a seco form of A includes the spiro form of the A group and a spiro form of the A group includes seco form of the A group. In some embodiments, A is an A-alkylating DNA group of formula (IIIa) or (IIIb): or IIIa (seco form) IIIb (spiro form) wherein: Z1is a leaving group, optionally halide, triflate, or tosylate; X is C-R17, N, N-R17, S or O; the dotted line to X indicates the optional presence of a double bond depending on the nature of X; R17is H, –LS-RS, or R20; z is 0 or 1; ’’’' is OH or –LS-RS; LS is a bond, an amino acid, a peptide chain having from 2 to 6 amino acids, an alkylene chain containing from 1 to 12 carbon atoms which may contain one or more carbon-carbon double or triple bonds, a paraformaldehyde chain –(OCH2)1-12-, a polyethylene glycol chain–-(OCH2CH2)1-6-, which chains may be interrupted by or optionally incorporates one or more of O, S, NH, C5-9heteroarylene, phenylene, heterocyclyl, cycloalkyl, ether, oxo, carboxamidyl, and / or urethanyl moieties wherein the C5-9heteroarylene, phenylene, heterocyclyl, and / or cycloalkyl moieties are optionally substituted, optionally LSis: ; and RSis a univalent saccharide substituent, preferably glycosyl or O-glycosyl. In some embodiments, the A-alkylating DNA group of formula (IIIa) or (IIIb) comprises at least one –LS-RSgroup. In some embodiments, in the A moiety of formula (IIIa), X is C-R17and R17is –LS-RS. In some embodiments, in the A moiety of formula (IIIa), X is C-R17and R17is RS. In some embodiments, in the A moiety of formula (IIIa), X is N-R17and R17is –LS-RS. In some embodiments, in the A moiety of formula (IIIa), X is N-R17and R17is RS. In some embodiments, in the A moiety of formula (IIIa), ’’’' is –LS-RS. In some embodiments, in the A moiety of formula (IIIa), ’’’' is RS. In some embodiments, in the A moiety of formula (IIIb), X is C-R17and R17is –LS-RS. In some embodiments, in the A moiety of formula (IIIb), X is C-R17and R17is RS. In some embodiments, in the A moiety of formula (IIIb), X is N-R17and R17is – LS-RS. In some embodiments, in the A moiety of formula (IIIb), X is N-R17and R17is RS. In some embodiments, the compound according to formula (I) may be a compound selected from the group consisting of: , , , , ,

[0020] herein Rs is a univalent saccharide substituent, preferably glycosyl or O-glycosyl. some embodiments, the compound according to formula (I) may be a compound selected m the group consisting of:

[0021]

[0022] herein Rs is a univalent saccharide substituent, preferably glycosyl or O-glycosyl. cceptor human framework” for the purposes herein is a framework comprising the amino d sequence of a light chain variable domain (VL) framework or a heavy chain variablemain (VH) framework derived from a human immunoglobulin framework or a humannsensus framework, as defined below. An acceptor human framework“" derived fro”" aman immunoglobulin framework or a human consensus framework may comprise the same ino acid sequence thereof, or it may contain amino acid sequence changes. In some bodiments, the number of amino acid changes are 10 or less, 9 or less, 8 or less, 7 or less, 6 less, 5 or less, 4 or less, 3 or less, or 2 or less In some embodiments the VL acceptor human framework is identical in sequence to the VL human immunoglobulin framework sequence or human consensus framework sequence. “Affinity” refers to the strength of the sum total of noncovalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen). Unless indicated otherwise, as used herein,“"binding affinit”" refers to intrinsic binding affinity which reflects a 1 : 1 interaction between members of a binding pair (e.g., antibody and antigen). The affinity of a molecule X for its partner Y can generally be represented by the dissociation constant (Kd). Affinity can be measured by common methods known in the art, including those described herein. Specific illustrative and exemplary embodiments for measuring binding affinity are described in the following. An “affinity matured” antibody refers to an antibody with one or more alterations in one or more hypervariable regions (HVRs), compared to a parent antibody which does not possess such alterations, such alterations resulting in an improvement in the affinity of the antibody for antigen. The term “antibody” is used herein in the broadest sense and encompasses various antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), and antibody fragments so long as they exhibit the desired antigen-binding activity. An “antibody fragment” refers to a molecule other than an intact antibody that comprises a portion of an intact antibody and that binds the antigen to which the intact antibody binds. Examples of antibody fragments include but are not limited to Fv, Fab, Fa’', Fa’'-SH, F(a’')2; diabodies; linear antibodies; single-chain antibody molecules (e.g., scFv); and multispecific antibodies formed from antibody fragments. The term “chimeric” antibody refers to an antibody in which a portion of the heavy and / or light chain is derived from a particular source or species, while the remainder of the heavy and / or light chain is derived from a different source or species. The “class” of an antibody refers to the type of constant domain or constant region possessed by its heavy chain. There are five major classes of antibodies: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgGi, IgG2, IgG3, IgG4, IgAi, and IgA2. The heavy chain constant domains that correspond to the different classes of immunoglobulins are called α, δ, ε, γ, and μ, respectively. The term “cytotoxic agent” as used herein refers to a substance that inhibits or prevents a cellular function and / or causes cell death or destruction. Cytotoxic agents include, but are not limited to, radioactive isotopes (e.g., At211, I131, I125, Y90, Re186,Re188,Sm153, Bi212, P32, Pb212and radioactive isotopes of Lu); chemotherapeutic agents or drugs (e.g., methotrexate, adriamicin, vinca alkaloids (vincristine, vinblastine, etoposide), doxorubicin, melphalan, mitomycin C, chlorambucil, daunorubicin or other intercalating agents); growth inhibitory agents; enzymes and fragments thereof such as nucleolytic enzymes; antibiotics; toxins such as small molecule toxins or enzymatically active toxins of bacterial, fungal, plant or animal origin, including fragments and / or variants thereof; and the various antitumor or anticancer agents disclosed below. By “co-administering” is meant intravenously administering two (or more) drugs during the same administration, rather than sequential infusions of the two or more drugs. Generally, this will involve combining the two (or more) drugs into the same IV bag prior to co-administration thereof. A drug that is administered “concurrently” with one or more other drugs is administered during the same treatment cycle, on the same day of treatment as the one or more other drugs, and, optionally, at the same time as the one or more other drugs. For instance, for cancer therapies given every 3 weeks, the concurrently administered drugs are each administered on day-1 of a 3-week cycle. A “chemotherapeutic agent” refers to a chemical compound useful in the treatment of cancer. Examples of chemotherapeutic agents include alkylating agents such as thiotepa and cyclosphosphamide (CYTOXAN®); alkyl sulfonates such as busulfan, improsulfan and piposulfan; aziridines such as benzodopa, carboquone, meturedopa, and uredopa; ethylenimines and methylamelamines including altretamine, triethylenemelamine, triethylenephosphoramide, triethylenethiophosphoramide and trimethylomelamine; acetogenins (especially bullatacin and bullatacinone); delta-9-tetrahydrocannabinol (dronabinol, MARINOL®); beta-lapachone; lapachol; colchicines; betulinic acid; a camptothecin (including the synthetic analogue topotecan (HYCAMTIN®), CPT-11 (irinotecan, CAMPTOSAR®), acetylcamptothecin, scopolectin, and 9-aminocamptothecin); bryostatin; callystatin; CC-1065 (including its adozelesin, carzelesin and bizelesin synthetic analogues); podophyllotoxin; podophyllinic acid; teniposide; cryptophycins (particularly cryptophycin 1 and cryptophycin 8); dolastatin; duocarmycin (including the synthetic analogues, KW-2189 and CB1-TM1); eleutherobin; pancratistatin; a sarcodictyin; spongistatin; nitrogen mustards such as chlorambucil, chlornaphazine, chlorophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, phenesterine, prednimustine, trofosfamide, uracil mustard; nitrosoureas such as carmustine, chlorozotocin, fotemustine, lomustine, nimustine, and ranimnustine; antibiotics such as the enediyne antibiotics (e.g., calicheamicin, especially calicheamicin gamma1l and calicheamicin omegal1 (see, e.g., Nicolaou et al., Angew. Chem Intl. Ed. Engl., 33 : 183-186 (1994)); CDP323, an oral alpha-4 integrin inhibitor; dynemicin, including dynemicin A; an esperamicin; as well as neocarzinostatin chromophore and related chromoprotein enediyne antibiotic chromophores), aclacinomysins, actinomycin, authramycin, azaserine, bleomycins, cactinomycin, carabicin, carminomycin, carzinophilin, chromomycins, dactinomycin, daunorubicin, detorubicin, 6-diazo- 5-oxo-L-norleucine, doxorubicin (including ADRIAMYCIN®, morpholino-doxorubicin, cyanomorpholino- doxorubicin, 2-pyrrolino-doxorubicin, doxorubicin HCl liposome injection (DOXIL®), liposomal doxorubicin TLC D-99 (MYOCET®), peglylated liposomal doxorubicin (CAELYX®), and deoxydoxorubicin), epirubicin, esorubicin, idarubicin, marcellomycin, mitomycins such as mitomycin C, mycophenolic acid, nogalamycin, olivomycins, peplomycin, porfiromycin, puromycin, quelamycin, rodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; anti-metabolites such as methotrexate, gemcitabine (GEMZAR®), tegafur (UFTORAL®), capecitabine (XELODA®), an epothilone, and 5- fluorouracil (5-FU); folic acid analogues such as denopterin, methotrexate, pteropterin, trimetrexate; purine analogs such as fludarabine, 6-mercaptopurine, thiamiprine, thioguanine; pyrimidine analogs such as ancitabine,93olubilizede, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, floxuridine; androgens such as calusterone, dromostanolone propionate, epitiostanol, mepitiostane, testolactone; anti-adrenals such as aminoglutethimide, mitotane, trilostane; folic acid replenisher such as frolinic acid; aceglatone; aldophosphamide glycoside; aminolevulinic acid; eniluracil; amsacrine; bestrabucil; bisantrene;93olubilizee; defofamine; demecolcine; diaziquone; elfornithine; elliptinium acetate; an epothilone; etoglucid; gallium nitrate; hydroxyurea; lentinan; lonidainine; maytansinoids such as maytansine and ansamitocins; mitoguazone; mitoxantrone; mopidanmol; nitraerine; pentostatin; phenamet; pirarubicin; losoxantrone; 2- ethylhydrazide; procarbazine; PSK® polysaccharide complex (JHS Natural Products, Eugene, OR); razoxane; rhizoxin; sizofiran; spirogermanium; tenuazonic acid; triaziquone; 2,2’,2’-trichlorotriethylamine; trichothecenes (especially T-2 toxin, verracurin A, roridin A and anguidine); urethan; vindesine (ELDISINE®, FILDESIN®); dacarbazine; mannomustine; mitobronitol; mitolactol; pipobroman; gacytosine; arabinoside (“Ara-”"); thiotepa; taxoid, e.g., paclitaxel (TAXOL®), albumin-engineered nanoparticle formulation of paclitaxel (ABRAXANETM), and docetaxel (TAXOTERE®);93olubilized93l; 6-thioguanine; mercaptopurine; methotrexate; platinum agents such as cisplatin, oxaliplatin (e.g., ELOXATIN®), and carboplatin; vincas, which prevent tubulin polymerization from forming microtubules, including vinblastine (VELBAN®), vincristine (ONCOVIN®), vindesine (ELDISINE®, FILDESIN®), and vinorelbine (NAVELBINE®); etoposide (VP- 16); ifosfamide; mitoxantrone; leucovorin; novantrone; edatrexate; daunomycin; aminopterin; ibandronate; topoisomerase inhibitor RFS 2000; difluoromethyl ornithine (DMFO); retinoids such as retinoic acid, including bexarotene (TARGRETIN®); bisphosphonates such as clodronate (for example, BONEFOS® or OSTAC®), etidronate (DIDROCAL®), NE-58095, zoledronic acid / zoledronate (ZOMETA®), alendronate (FOSAMAX®), pamidronate (AREDIA®), tiludronate (SKELID®), or risedronate (ACTONEL®); troxacitabine (a 1,3- dioxolane nucleoside cytosine analog); antisense oligonucleotides, particularly those that inhibit expression of genes in signalling pathways implicated in aberrant cell proliferation, such as, for example, PKC-alpha, Raf, H-Ras, and epidermal growth factor receptor (EGF- R); vaccines such as THERATOPE® vaccine and gene therapy vaccines, for example, ALLOVECTIN® vaccine, LEUVECTIN® vaccine, and VAXID® vaccine; topoisomerase 1 inhibitor (e.g., LURTOTECAN®); rmRH (e.g., ABARELIX®); BAY439006 (sorafenib; Bayer); SU-11248 (sunitinib, SUTENT®, Pfizer); perifosine, COX-2 inhibitor (e.g., celecoxib or etoricoxib), proteosome inhibitor (e.g., PS341); bortezomib (VELCADE®); CCI-779; tipifarnib (R11577); orafenib, ABT510; Bcl-2 inhibitor such as oblimersen sodium (GENASENSE®); pixantrone; EGFR inhibitors; tyrosine kinase inhibitors; serine-threonine kinase inhibitors such as rapamycin (sirolimus, RAPAMUNE®); farnesyltransferase inhibitors such as lonafarnib (SCH 6636, SARASARTM); and pharmaceutically acceptable salts, acids or derivatives of any of the above; as well as combinations of two or more of the above such as CHOP, an abbreviation for a combined therapy of cyclophosphamide, doxorubicin, vincristine, and prednisolone; and FOLFOX, an abbreviation for a treatment regimen with oxaliplatin (ELOXATINTM) combined with 5-FU and leucovorin. Chemotherapeutic agents as defined herein include “anti-hormonal agents” or “endocrine therapeutics” which act to regulate, reduce, block, or inhibit the effects of hormones that can promote the growth of cancer. They may be hormones themselves, including, but not limited to: anti-estrogens with mixed agonist / antagonist profile, including, tamoxifen (NOLVADEX®), 4- hydroxytamoxifen, toremifene (FARESTON®), idoxifene, droloxifene, raloxifene (EVISTA®), trioxifene, keoxifene, and selective estrogen receptor modulators (SERMs) such as SERM3; pure anti-estrogens without agonist properties, such as fulvestrant (FASLODEX®), and EM800 (such agents may block estrogen receptor (ER) dimerization, inhibit DNA binding, increase ER turnover, and / or suppress ER levels); aromatase inhibitors, including steroidal aromatase inhibitors such as formestane and exemestane (AROMASIN®), and nonsteroidal aromatase inhibitors such as anastrazole (ARFMIDEX®), letrozole (FEMARA®) and aminoglutethimide, and other aromatase inhibitors include vorozole (RIVISOR®), megestrol acetate (MEGASE®), fadrozole, and 4(5)-imidazoles; lutenizing hormone-releaseing hormone agonists, including leuprolide (LUPRON® and ELIGARD®), goserelin, buserelin, and tripterelin; sex steroids, including progestines such as megestrol acetate and medroxyprogesterone acetate, estrogens such as diethylstilbestrol and95olubilin, and androgens / retinoids such as fluoxymesterone, all transretionic acid and fenretinide; onapristone; anti-progesterones; estrogen receptor down- regulators (ERDs); anti-androgens such as flutamide, nilutamide and bicalutamide; and pharmaceutically acceptable salts, acids or derivatives of any of the above; as well as combinations of two or more of the above. “Drug”, “drug substance”, “active pharmaceutical ingredient”, and the like, refer to a compound (e.g., compounds of formula (I), formula (IV), and compounds of other formulae set out herein and compounds specifically named above) that may be used for treating a subject in need of treatment. “Conjugate” refers to compounds or constructs comprising (a) at least one drug compound of formula (I), formula (IV), and compounds of other formulae set out herein and compounds specifically named above, and (b) at least one targeting agent (e.g., a protein, a portion of a protein, a peptide, a nucleic acid, an antibody, an antibody fragment, a hormone, etc.). “Effector functions” refer to those biological activities attributable to the Fc region of an antibody, which vary with the antibody isotype. Examples of antibody effector functions include: Clq binding and complement dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; down regulation of cell surface receptors (e.g., B cell receptor); and B cell activation. The term “epitope” refers to the particular site on an antigen molecule to which an antibody binds. The “epitope 4D5” or “4D5 epitope” or “4D5” is the region in the extracellular domain of HER2 to which the antibody 4D5 (ATCC CRL 10463) and trastuzumab bind. This epitope is close to the transmembrane domain of HER2, and within domain IV of HER2. To screen for antibodies which bind to the 4D5 epitope, a routine cross-blocking assay such as that described in Antibodies, A Laboratory Manual, Cold Spring Harbor Laboratory, Ed Harlow and David Lane (1988), can be performed. Alternatively, epitope mapping can be performed to assess whether the antibody binds to the 4D5 epitope of HER2 (e.g., any one or more residues in the region from about residue 550 to about residue 610, inclusive, of HER2 (SEQ ID NO: 39). The “epitope 2C4” or “2C4 epitope” is the region in the extracellular domain of HER2 to which the antibody 2C4 binds. In order to screen for antibodies which bind to the 2C4 epitope, a routine cross-blocking assay such as that described in Antibodies, A Laboratory Manual, Cold Spring Harbor Laboratory, Ed Harlow and David Lane (1988), can be performed. Alternatively, epitope mapping can be performed to assess whether the antibody binds to the 2C4 epitope of HER2. Epitope 2C4 comprises residues from domain II in the extracellular domain of HER2. The 2C4 antibody and pertuzumab bind to the extracellular domain of HER2 at the junction of domains I, II and III (Franklin et al. Cancer Cell 5:317-328 (2004)). Anti-HER2 murine antibody 7C2 binds to an epitope in domain I of HER2. See, e.g., PCT Publication No. WO 98 / 17797. This epitope is distinct from the epitope bound by trastuzumab, which binds to domain IV of HER2, and the epitope bound by pertuzumab, which binds to domain II of HER2. By binding domain IV, trastuzumab disrupts ligand- independent HER2-HER3 complexes, thereby inhibiting downstream signalling (e.g., PI3K / AKT). In contrast, pertuzumab binding to domain II prevents ligand-driven HER2 interaction with other HER family members (e.g., HER3, HERl or HER4), thus also preventing downstream signal transduction. Binding of mAb 7C2 to domain I does not result in interference of trastuzumab or pertuzumab binding to domains IV and II, respectively, thereby offering the potential of combining a mAb 7C2 ADC with trastuzumab, trastuzumab emtansine (T-DM-1), and / or pertuzumab. Murine antibody 7C2, 7C2.B9, is described in PCT Publication No. WO 98 / 17797. An anti-HER27C2 humanized antibody is disclosed in WO2016 / 040723 Al. “Excipient” refers to any substance that may influence the bioavailability of a drug but is otherwise pharmacologically inactive. The term “Fc region” herein is used to define a C-terminal region of an immunoglobulin heavy chain that contains at least a portion of the constant region. The term includes native sequence Fc regions and variant Fc regions. In one embodiment, a human IgG heavy chain Fc region extends from Cys226, or from Pro230, to the carboxyl-terminus of the heavy chain. However, the C-terminal lysine (Lys447) of the Fc region may or may not be present. Unless otherwise specified herein, numbering of amino acid residues in the Fc region or constant region is according to the EU numbering system, also called the EU index, as described in Kabat et al., Sequences of Proteins of Immunological Interest,5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD, 1991. “Framework” or “FR” refers to variable domain residues other than hypervariable region (HVR) residues. The FR of a variable domain generally consists of four FR domains: FR1, FR2, FR3, and FR4. Accordingly, the HVR and FR sequences generally appear in the following sequence in VH (or VL): FR1-H1(L1)-FR2-H2(L2)-FR3-H3(L3)-FR4. The terms “full length antibody,” “intact antibody,” and “whole antibody” are used herein interchangeably to refer to an antibody having a structure substantially similar to a native antibody structure or having heavy chains that contain an Fc region as defined herein. The terms “host cell,” “host cell line,” and “host cell culture” are used interchangeably and refer to cells into which exogenous nucleic acid has been introduced, including the progeny of such cells. Host cells include “transformants” and “transformed cells,” which include the primary transformed cell and progeny derived therefrom without regard to the number of passages. Progeny may not be completely identical in nucleic acid content to a parent cell, but may contain mutations. Mutant progeny that have the same function or biological activity as screened or selected for in the originally transformed cell are included herein. A “human antibody” is one which possesses an amino acid sequence which corresponds to that of an antibody produced by a human or a human cell or derived from a non-human source that utilizes human antibody repertoires or other human antibody- encoding sequences. This definition of a human antibody specifically excludes a humanized antibody comprising non- human antigen-binding residues. A “human consensus framework” is a framework which represents the most commonly occurring amino acid residues in a selection of human immunoglobulin VL or VH framework sequences. Generally, the selection of human immunoglobulin VL or VH sequences is from a subgroup of variable domain sequences. Generally, the subgroup of sequences is a subgroup as in Kabat et al., Sequences of Proteins of Immunological Interest, Fifth Edition, NIH Publication 91-3242, Bethesda MD (1991), vols.1-3. In one embodiment, for the VL, the subgroup is subgroup kappa I as in Kabat et al., supra. In one embodiment, for the VH, the subgroup is subgroup III as in Kabat et al., supra. A “humanized” antibody refers to a chimeric antibody comprising amino acid residues from non-human HVRs and amino acid residues from human FRs. In certain embodiments, a humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the HVRs (e.g., “complementary determining regions”, CDRs) correspond to those of a non-human antibody, and all or substantially all of the FRs correspond to those of a human antibody. A humanized antibody optionally may comprise at least a portion of an antibody constant region derived from a human antibody. A “humanized form” of an antibody, e.g., a non-human antibody, refers to an antibody that has undergone humanization. The term “hypervariable region” or “HVR,” as used herein, refers to each of the regions of an antibody variable domain which are hypervariable in sequence and / or form structurally defined loops (“hypervariable loops”). Generally, native four-chain antibodies comprise six HVRs; three in the VH (H1, H2, H3), and three in the VL (L1, L2, L3). HVRs generally comprise amino acid residues from the hypervariable loops and / or from CDRs, the latter being of highest sequence variability and / or involved in antigen recognition. Exemplary hypervariable loops occur at amino acid residues 26-32 (L1), 50-52 (L2), 91-96 (L3), 26-32 (H1), 53-55 (H2), and 96-101 (H3). (Chothia and Lesk, J. Mol. Biol.196:901-917 (1987).) Exemplary CDRs (CDR- L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2, and CDR-H3) occur at amino acid residues 24-34 of L1, 50-56 of L2, 89-97 of L3, 31-35B of H1, 50-65 of H2, and 95-102 of H3. (Kabat et al., Sequences of Proteins of Immunological Interest,5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD (1991).) With the exception of CDR1 in VH, CDRs generally comprise the amino acid residues that form the hypervariable loops. CDRs also comprise “specificity determining residues,” or “SDRs,” which are residues that contact antigen. SDRs are contained within regions of the CDRs called abbreviated-CDRs, or a- CDRs. Exemplary a-CDRs (a-CDR-L1, a-CDR-L2, a-CDR-L3, a-CDR-H1, a-CDR-H2, and a-CDR- H3) occur at amino acid residues 31-34 of LI, 50-55 of L2, 89-96 of L3, 31-35B of HI, 50-58 of H2, and 95-102 of H3. (See Almagro and Fransson, Front. Biosci.13 : 1619- 1633 (2008).) Unless otherwise indicated, HVR residues and other residues in the variable domain (e.g., FR residues) are numbered herein according to Kabat et al., supra. An “immunoconjugate” is an antibody conjugated to one or more heterologous molecule(s), including but not limited to a cytotoxic agent. The term “immunosuppressive agent” as used herein for adjunct therapy refers to substances that act to suppress or mask the immune system of the mammal being treated herein. This would include substances that suppress cytokine production, downregulate or suppress self-antigen expression, or mask the MHC antigens. Examples of such agents include 2-amino-6-aryl-5- substituted pyrimidines (see U.S. Pat. No.4,65,077); non-steroidal anti-inflammatory drugs (NSAIDs); ganciclovir, tacrolimus, glucocorticoids such as cortisol or aldosterone, anti- inflammatory agents such as a cyclooxygenase inhibitor, a 5- lipoxygenase inhibitor, or a leukotriene receptor antagonist; purine antagonists such as azathioprine or mycophenolate mofetil (MMF); alkylating agents such as cyclophosphamide;98olubilized98ie; danazol; dapsone; glutaraldehyde (which masks the MHC antigens, as described in U.S. Pat. No. 4,120,649); anti-idiotypic antibodies for MHC antigens and MHC fragments; cyclosporin A; steroids such as corticosteroids or glucocorticosteroids or glucocorticoid analogues, e.g., prednisone, methylprednisolone, including SOLU-MEDROL® methylprednisolone sodium succinate, and dexamethasone; dihydrofolate reductase inhibitors such as methotrexate (oral or subcutaneous); anti-malarial agents such as chloroquine and hydroxychloroquine; sulfasalazine; leflunomide; cytokine or cytokine receptor antibodies including anti-interferon-alpha, -beta, or - gamma antibodies, anti-tumor necrosis factor(TNF)-alpha antibodies (infliximab (REMICADE®) or adalimumab), anti-TNF-alpha immunoadhesin (etanercept), anti-TNF-beta antibodies, anti-interleukin-2 (IL-2) antibodies and anti-IL-2 receptor antibodies, and anti- interleukin-6 (IL-6) receptor antibodies and antagonists (such as ACTEMRA™ (tocilizumab)); anti-LFA-1 antibodies, including anti-CD11a and anti-CD18 antibodies; anti-L3T4 antibodies; heterologous anti-lymphocyte globulin; pan-T antibodies, preferably anti-CD3 or anti- CD4 / CD4a antibodies; soluble peptide containing a LFA-3 binding domain (WO 90 / 08187); streptokinase; transforming growth factor-beta (TGF-beta); streptodornase; RNA or DNA from the host; FK506; RS-61443; chlorambucil; deoxyspergualin; rapamycin; T-cell receptor (Cohen et al, U.S. Pat. No.5,114,721); T-cell receptor fragments (Offner et al, Science, 251 : 430-432 (1991); WO 90 / 11294; Ianeway, Nature, 341 : 482 (1989); and WO 91 / 01133); BAFF antagonists such as BAFF antibodies and BR3 antibodies and zTNF4 antagonists (for review, see Mackay and Mackay, Trends Immunol, 23 : 113-5 (2002) and see also definition below); biologic agents that interfere with T cell helper signals, such as anti- CD40 receptor or anti- CD40 ligand (CD 154), including blocking antibodies to CD40-CD40 ligand (e.g., Durie et al, Science, 261 : 1328-30 (1993); Mohan et al, J. Immunol, 154: 1470- 80 (1995)) and CTLA4-Ig (Finck et al, Science, 265: 1225-7 (1994)); and T-cell receptor antibodies (EP 340,109) such as T10B9. Some preferred immunosuppressive agents herein include cyclophosphamide, chlorambucil, azathioprine, leflunomide, MMF, or methotrexate. An “isolated antibody” is one which has been separated from a component of its natural environment. In some embodiments, an antibody is purified to greater than 95% or 99% purity as determined by, for example, electrophoretic (e.g., SDS-PAGE, isoelectric focusing (IEF), capillary electrophoresis) or chromatographic (e.g., ion exchange or reverse phase HPLC). For review of methods for assessment of antibody purity, see, e.g., Flatman et al., J. Chromatogr. B 848:79-87 (2007). An “isolated nucleic acid" refers to a nucleic acid molecule that has been separated from a component of its natural environment. An isolated nucleic acid includes a nucleic acid molecule contained in cells that ordinarily contain the nucleic acid molecule, but the nucleic acid molecule is present extrachromosomally or at a chromosomal location that is different from its natural chromosomal location. “Isolated nucleic acid encoding an antibody” refers to one or more nucleic acid molecules encoding antibody heavy and light chains (or fragments thereof), including such nucleic acid molecule(s) in a single vector or separate vectors, and such nucleic acid molecule(s) present at one or more locations in a host cell. The term “human epidermal growth factor receptor 2” (HER2),” as used herein, refers to any native, mature HER2 which results from processing of a HER2 precursor protein in a cell. The term generally is taken to mean a protein involved in normal cell growth. Human epidermal growth factor receptor 2 may be made in larger than normal amounts by some types of cancer cells, including breast, ovarian, bladder, pancreatic, and stomach cancers. This may cause cancer cells to grow more quickly and spread to other parts of the body. The term as used herein includes HER2 from any vertebrate source, including mammals such as primates (e.g., humans and cynomolgus monkeys) and rodents (e.g., mice and rats), unless otherwise indicated. The term also includes naturally occurring variants of HER2, e.g., splice variants or allelic variants. The amino acid sequence of an exemplary human HER2 precursor protein, with signal sequence (with signal sequence, amino acids 1-22) is shown in SEQ ID NO: 64. The amino acid sequence of an exemplary mature human HER2 is amino acids 23-1255 of SEQ ID NO: 64. The term “HER2 -positive cell” refers to a cell that expresses HER2 on its surface. The term “monoclonal antibody” as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical and / or bind the same epitope, except for possible variant antibodies, e.g., containing naturally occurring mutations or arising during production of a monoclonal antibody preparation, such variants generally being present in minor amounts. In contrast to polyclonal antibody preparations, which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody of a monoclonal antibody preparation is directed against a single determinant on an antigen. Thus, the modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method. For example, the monoclonal antibodies to be used in accordance with the present disclosure may be made by a variety of techniques, including but not limited to the hybridoma method, recombinant DNA methods, phage- display methods, and methods utilizing transgenic animals containing all or part of the human immunoglobulin loci, such methods and other exemplary methods for making monoclonal antibodies being described herein. A “naked antibody” refers to an antibody that is not conjugated to a heterologous moiety (e.g., a cytotoxic moiety) or radiolabel. The naked antibody may be present in a pharmaceutical formulation. “Native antibodies” refer to naturally occurring immunoglobulin molecules with varying structures. For example, native IgG antibodies are heterotetrameric glycoproteins of about 150,000 daltons, composed of two identical light chains and two identical heavy chains that are disulfide-bonded. From N- to C-terminus, each heavy chain has a variable region (VH), also called a variable heavy domain or a heavy chain variable domain, followed by three constant domains (CHI, CH2, and CH3). Similarly, from N- to C-terminus, each light chain has a variable region (VL), also called a variable light domain or a light chain variable domain, followed by a constant light (CL) domain. The light chain of an antibody may be assigned to one of two types, called kappa (κ) and lambda (λ), based on the amino acid sequence of its constant domain. “Percent (%) amino acid sequence identity” with respect to a reference polypeptide sequence is defined as the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the reference polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. Those skilled in the art can determine appropriate parameters for aligning sequences, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared. For purposes herein, however, % amino acid sequence identity values are generated using the sequence comparison computer program ALIGN-2. The ALIGN-2 sequence comparison computer program was authored by Genentech, Inc., and the source code has been filed with userdocumentation in the U.S. Copyright Office, Washington D.C., 20559, where it is registered under U.S. Copyright Registration No. TXU510087. The ALIGN-2 programme is publicly available from Genentech, Inc., South San Francisco, California, or may be compiled from the source code. The ALIGN-2 program should be compiled for use on a UNIX operating system, including digital UNIX V4.0D. All sequence comparison parameters are set by the ALIGN-2 program and do not vary. In situations where ALIGN-2 is employed for amino acid sequence comparisons, the % amino acid sequence identity of a given amino acid sequence A to, with, or against a given amino acid sequence B (which can alternatively be phrased as a given amino acid sequence A that has or comprises a certain % amino acid sequence identity to, with, or against a given amino acid sequence B) is calculated as follows: 100 times the fraction X / Y where X is the number of amino acid residues scored as identical matches by the sequence alignment program ALIGN-2 in that program’s alignment of A and B, and where Y is the total number of amino acid residues in B. It will be appreciated that where the length of amino acid sequence A is not equal to the length of amino acid sequence B, the % amino acid sequence identity of A to B will not equal the % amino acid sequence identity of B to A. Unless specifically stated otherwise, all % amino acid sequence identity values used herein are obtained as described in the immediately preceding paragraph using the ALIGN-2 computer program. The term “PD-1 axis binding antagonist” refers to a molecule that inhibits the interaction of a PD-1 axis binding partner with either one or more of its binding partner, so as to remove T-cell dysfunction resulting from signalling on the PD-1 signalling axis–- with a result being to restore or enhance T-cell function (e.g., proliferation, cytokine production, target cell killing). As used herein, a PD-1 axis binding antagonist includes a PD-1 binding antagonist, a PD-L1 binding antagonist and a PD-L2 binding antagonist. The term "PD-1 binding antagonis”" refers to a molecule that decreases, blocks, inhibits, abrogates or interferes with signal transduction resulting from the interaction of PD- 1 with one or more of its binding partners, such as PD-L1, PD-L2. In some embodiments, the PD-1 binding antagonist is a molecule that inhibits the binding of PD-1 to one or more of its binding partners. In a specific aspect, the PD-1 binding antagonist inhibits the binding of PD-1 to PD-L1 and / or PD-L2. For example, PD-1 binding antagonists include anti-PD-1 antibodies, antigen binding fragments thereof, immunoadhesins, fusion proteins, oligopeptides and other molecules that decrease, block, inhibit, abrogate or interfere with signal transduction resulting from the interaction of PD-1 with PD-L1 and / or PD-L2. In one embodiment, a PD-1 binding antagonist reduces the negative co-stimulatory signal mediated by or through cell surface proteins expressed on T lymphocytes mediated signalling through PD-1 so as render a dysfunctional T- cell less dysfunctional (e.g., enhancing effector responses to antigen recognition). In some embodiments, the PD-1 binding antagonist is an anti-PD-1 antibody. In a specific aspect, a PD-1 binding antagonist is MDX-1106 (nivolumab) described herein. In another specific aspect, a PD-1 binding antagonist is MK- 3475 (lambrolizumab) described herein. In another specific aspect, a PD-1 binding antagonist is CT-011 (pidilizumab) described herein. In another specific aspect, a PD-1 binding antagonist is AMP-224 described herein. The term “PD-L1 binding antagonist” refers to a molecule that decreases, blocks, inhibits, abrogates or interferes with signal transduction resulting from the interaction of PD- L1 with either one or more of its binding partners, such as PD-1, B7-1. In some embodiments, a PD-L1 binding antagonist is a molecule that inhibits the binding of PD-L1 to its binding partners. In a specific aspect, the PD-L1 binding antagonist inhibits binding of PD-L1 to PD-1 and / or B7-1. In some embodiments, the PD-L1 binding antagonists include anti-PD-L1 antibodies, antigen binding fragments thereof, immunoadhesins, fusion proteins, oligopeptides and other molecules that decrease, block, inhibit, abrogate or interfere with signal transduction resulting from the interaction of PD-L1 with one or more of its binding partners, such as PD-1, B7-1. In one embodiment, a PD-L1 binding antagonist reduces the negative co-stimulatory signal mediated by or through cell surface proteins expressed on T lymphocytes mediated signalling through PD-L1 so as to render a dysfunctional T-cell less dysfunctional (e.g., enhancing effector responses to antigen recognition). In some embodiments, a PD-L1 binding antagonist is an anti- PD-L1 antibody. In a specific aspect, an anti-PD-L1 antibody is YW243.55. S70 described herein. In another specific aspect, an anti- PD-L1 antibody is MDX-1105 described herein. In still another specific aspect, an anti-PD- L1 antibody is MPDL3280A described herein. In still another specific aspect, an anti-PD-L1 antibody is MEDI4736 described herein. The term “PD-L2 binding antagonist” refers to a molecule that decreases, blocks, inhibits, abrogates or interferes with signal transduction resulting from the interaction of PD- L2 with either one or more of its binding partners, such as PD-1. In some embodiments, a PD-L2 binding antagonist is a molecule that inhibits the binding of PD-L2 to one or more of its binding partners. In a specific aspect, the PD-L2 binding antagonist inhibits binding of PD-L2 to PD-1. In some embodiments, the PD-L2 antagonists include anti-PD-L2 antibodies, antigen binding fragments thereof, immunoadhesins, fusion proteins, oligopeptides and other molecules that decrease, block, inhibit, abrogate or interfere with signal transduction resulting from the interaction of PD-L2 with either one or more of its binding partners, such as PD-1. In one embodiment, a PD-L2 binding antagonist reduces the negative co-stimulatory signal mediated by or through cell surface proteins expressed on T lymphocytes mediated signalling through PD-L2 so as render a dysfunctional T-cell less dysfunctional (e.g., enhancing effector responses to antigen recognition). In some embodiments, a PD-L2 binding antagonist is an immunoadhesin. A “fixed” or “flat” dose of a therapeutic agent herein refers to a dose that is administered to a human patient without regard for the weight (WT) or body surface area (BSA) of the patient. The fixed or flat dose is therefore not provided as a mg / kg dose or a mg / m2dose, but rather as an absolute amount of the therapeutic agent. A “loading” dose herein generally comprises an initial dose of a therapeutic agent administered to a patient, and is followed by one or more maintenance dose(s) thereof. Generally, a single loading dose is administered, but multiple loading doses are contemplated herein. Usually, the amount of loading dose(s) administered exceeds the amount of the maintenance dose(s) administered and / or the loading dose(s) are administered more frequently than the maintenance dose(s), so as to achieve the desired steady-state concentration of the therapeutic agent earlier than can be achieved with the maintenance dose(s). A “maintenance” dose herein refers to one or more doses of a therapeutic agent administered to the patient over a treatment period. Usually, the maintenance doses are administered at spaced treatment intervals, such as approximately every week, approximately every 2 weeks, approximately every 3 weeks, or approximately every 4 weeks, preferably every 3 weeks. “Infusion” or “infusing” refers to the introduction of a drug-containing solution into the body through a vein for therapeutic purposes. Generally, this is achieved via an intravenous (IV) bag. An “intravenous bag” or “IV bag” is a bag that can hold a solution which can be administered via the vein of a patient. In one embodiment, the solution is a saline solution (e.g., about 0.9% or about 0.45% NaCl). Optionally, the IV bag is formed from polyolefin or polyvinal chloride. The term “variable region” or “variable domain” refers to the domain of an antibody heavy or light chain that is involved in binding the antibody to antigen. The variable domains of the heavy chain and light chain (VH and VL, respectively) of a native antibody generally have similar structures, with each domain comprising four conserved framework regions (FRs) and three hypervariable regions (HVRs). (See, e.g., Kindt et al. Kuby Immunology, 6thed., W.H. Freeman and Co., page 91 (2007).) A single VH or VL domain may be sufficient to confer antigen-binding specificity. Furthermore, antibodies that bind a particular antigen may be isolated using a VH or VL domain from an antibody that binds the antigen to screen a library of complementary VL or VH domains, respectively. See, e.g., Portolano et al., J. Immunol. 150:880-887 (1993 ); Clarkson et al., Nature 352:624-628 (1991). The term “vector,” as used herein, refers to a nucleic acid molecule capable ofpropagating another nucleic acid to which it is linked. The term includes the vector as a self- replicating nucleic acid structure as well as the vector incorporated into the genome of a host cell into which it has been introduced. Certain vectors are capable of directing the expression of nucleic acids to which they are operatively linked. Such vectors are referred to herein as “expression vectors.” A “free cysteine amino acid” refers to a cysteine amino acid residue which has been engineered into a parent antibody, has a thiol functional group (-SH), and is not paired as an intramolecular or intermolecular disulfide bridge. The term “or pharmaceutically acceptable salts, solvates, tautomers, stereoisomers or mixtures thereof” means that pharmaceutically acceptable salt, solvate, tautomeric, stereoisomeric forms of the shown structure are also included. Mixtures thereof means that mixture of these forms may be present, for example, the compounds of the disclosure may include both a tautomeric form and a pharmaceutically acceptable salt. “Pharmaceutically acceptable” substances refers to those substances which are within the scope of sound medical judgment suitable for use in contact with the tissues of subjects without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit-to- risk ratio, and effective for their intended use. “Pharmaceutical composition” refers to the combination of one or more drug substances and one or more excipients. As used herein, “solvate” refers to a complex of variable stoichiometry formed by a solute (e.g., formulas (1)-(1) (A), (B), (C), (D), or any other compound herein or a salt thereof) and a solvent. Pharmaceutically acceptable solvates may be formed for crystalline compounds wherein solvent molecules are incorporated into the crystalline lattice during crystallization. The incorporated solvent molecules can be water molecules or non-aqueous molecules, such as but not limited to, ethanol, isopropanol, dimethyl sulfoxide, acetic acid, ethanolamine, and ethyl acetate molecules. The term “subject” as used herein refers to a human or non-human mammal. Examples of non- human mammals include livestock animals such as sheep, horses, cows, pigs, goats, rabbits and deer; and companion animals such as cats, dogs, rodents, and horses. “Therapeutically effective amount” of a drug refers to the quantity of the drug or composition that is effective in treating a subject and thus producing the desired therapeutic, ameliorative, inhibitory, or preventative effect. The therapeutically effective amount may depend on the weight and age of the subject and the route of administration, among other things. “Tolerability” refers to a level of toxicities associated with a therapy or therapeutic regimen, which can be reasonably tolerated by patients, without discontinuing the therapy due to the toxicities. Non-limiting examples of tolerability include maximum tolerated dose (MTD). “Treating” refers to reversing, alleviating, inhibiting the progress of, or preventing a disorder, disease or condition to which such term applies, or to reversing, alleviating, inhibiting the progress of, or preventing one or more symptoms of such disorder, disease or condition. “Treatment” refers to the act of “treating”, as defined immediately above. As used herein the term “comprising” means “including at least in part of” and is meant to be inclusive or open ended. When interpreting each statement in this specification that includes the term “comprising”, features, elements and / or steps other than that or those prefaced by the term may also be present. Related terms such as “comprise” and “comprises” are to be interpreted in the same manner. The term “consisting essentially of” limits the scope of a claim to the specified materials or steps “and those that do not materially affect the basic and novel characteristic(s)” of the present disclosure. When the phrase “consisting essentially of” appears in a clause of the body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause. The term “consisting of” excludes any element, step, or ingredient not specified in the claim; “consisting of” defined as “closing the claim to the inclusion of materials other than those recited except for impurities ordinarily associated therewith. When the phrase “consists of” appears in a clause of the body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause; other elements are not excluded from the claim as a whole. It should be understood that while various embodiments in the specification are presented using “comprising” language, under various circumstances, a related embodiment is also described using “consisting essentially of” or “consisting of” language. Applications The disclosure finds application in the treatment of proliferative diseases. In certain aspects a method of treating a proliferative disease is provided, the method comprising administering to a subject a therapeutically effective amount of a compound of the formula (I) and salts and solvates thereof or a composition comprising a compound of formula (I) and salts and solvates thereof. In certain aspects a method of treating a proliferative disease is provided, the method comprising administering to a subject a therapeutically effective amount of a targeted conjugate comprising a compound of the formula (I) and salts and solvates thereof. In certain aspects a method of treating a proliferative disease is provided, the method comprising administering to a subject a therapeutically effective amount of an antibody-drug conjugate comprising a compound of the formula (I) and salts and solvates thereof. The term “proliferative disease” refers to an unwanted or uncontrolled cellular proliferation of excessive or abnormal cells which is undesired, such as, neoplastic or hyperplastic growth, whether in vitro or in vivo. Examples of proliferative conditions include, but are not limited to, benign, pre-malignant, and malignant cellular proliferation, including but not limited to, neoplasms and tumours (e.g., histocytoma, glioma, astrocyoma, osteoma), cancers (e.g., lung cancer, small cell lung cancer, hepatocellular cancer, gastric or stomach cancer including gastrointestinal cancer, bowel cancer, colon cancer, hepatoma, breast cancer, glioblastoma, cervical cancer, ovarian cancer, oesophageal [or esophageal] cancer, oral cancer, prostate cancer, testicular cancer, liver cancer, rectal cancer, colorectal cancer, endometrial or uterine carcinoma, uterine cancer, salivary gland carcinoma, kidney or renal cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma, anal carcinoma, penile carcinoma, head and neck cancer, bladder cancer, pancreas cancer, brain cancer, sarcoma, osteosarcoma, Kaposi’s sarcoma, melanoma), leukemias, psoriasis, bone diseases, fibroproliferative disorders (e.g., of connective tissues), and atherosclerosis. Suitably the proliferative disease is selected from bladder cancer, bone cancer, bowel cancer, brain cancer, breast cancer, cervical cancer, colon cancer, head and neck cancer, leukemia, liver cancer, lung cancer, lymphoma, melanoma, oesophageal cancer, oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, rectal cancer, renal cancer, retinoblastoma, sarcoma, skin cancer, stomach cancer, testicular cancer, thyroid cancer and uterine cancer. Any type of cell may be treated, including but not limited to, bone, eye, head and neck, lung, gastrointestinal (including, e.g., mouth, oesophagus, bowel, colon), breast (mammary), cervix, ovarian, uterus, prostate, liver (hepatic), kidney (renal), bladder, pancreas, brain, and skin. A skilled person is readily able to determine whether or not a candidate compound treats a proliferative condition for any particular cell type. Suitably subjects are human, livestock animals and companion animals. In a further aspect, the compound of formula (I) and salts and solvates thereof, may be linked, either directly or indirectly, to a targeting agent (e.g., antibody, antibody fragment, hormone, etc.) to provide a targeted conjugate. The target conjugates of the present disclosure may contain one or multiple compounds of formula (I) (or salts and solvates thereof). A variety of target conjugates are known in the art and may be used with a compound of formula (I) and salts and solvates thereof. For example, in a particular aspect, the target conjugate is an antibody-drug conjugate, wherein one or more compounds of formula (I) are linked, directly or indirectly, to the antibody. Therefore, the compound of formula (I) and salts and solvates thereof, may be used as a payload on a targeted conjugate. Suitably, a compound of formula (I) and salts and solvates thereof, for use as a drug in targeted conjugate is prepared by attaching a compound of formula (I) and salts and solvates thereof to a targeting agent, either directly or via an optional linker group. Suitably, the compound of formula (I) and salts and solvates thereof, is attached to a targeting agent via a linker group. Suitably, the targeted conjugate is for use in the treatment of a disease, more specifically of a proliferative disease. Suitably, the drug may be attached by any suitable functional group that it contains to the targeting agent either directly or via a linker group. Typically, the drug contains, or can be modified to contain, one or more functional groups such as amine, hydroxyl or carboxylic acid groups for attaching the drug to the targeting agent either directly or via a linker group. In some aspects, one or more atoms or groups of the compound of formula (I) may be eliminated during the attachment of the drug to the antibody. In some aspects, the targeting agent binds to a cell surface receptor or a tumor-associated antigen. In some aspects, the targeting agent is an antibody. In some aspects, the targeting agent is a hormone. In some aspects, the targeting agent is a protein. In some aspects, the targeting agent is a polypeptide. In some aspects, the targeting agent is a small molecule (for example, folic acid). The compounds of formula (I) find application as payloads for antibodies or antibody fragments. The compounds of formula (I) readily allow conjugation to antibodies or antibody fragments or other targeting agent via, for example, a linker group. Linker Group A linker is a bifunctional compound which can be used to link a drug and a targeting moiety (e.g., an antibody) to form a targeted drug conjugate (e.g., an antibody-drug conjugate) or targeting conjugate. Such conjugates are useful in the treatment of disease as a drug (e.g., a cytotoxic agent) may be delivered to a cell through recognition of an antigen. In one aspect, a second section of the linker group is introduced which has a second reactive site (e.g., an electrophilic group) that is reactive to an opposing group (e.g., a nucleophilic group) present on a targeting agent such as an antibody. Useful nucleophilic groups on an antibody include, but are not limited to, sulfhydryl, hydroxyl and amino groups. In this instance, the heteroatom of the nucleophilic group of an antibody is reactive to an electrophilic group on a linker group and forms a covalent bond to that linker group. The electrophilic group then provides a site of attachment for the linker-payload or linker-drug, and can include the disulfide bridges of the antibody (i.e., a stochastic conjugation) or a residue containing an electrophilic group (either synthetic or naturally-occurring) introduced to the antibody to allow efficient conjugation (i.e., site-specific conjugation). In another aspect, a linker group has a reactive site which has a nucleophilic group that is reactive to an electrophilic group present on an antibody. Electrophilic groups on an antibody include, but are not limited to, aldehyde and ketone carbonyl groups. The heteroatom of a nucleophilic group of a linker group can react with an electrophilic group on an antibody and form a covalent bond to the antibody. Nucleophilic groups in this respect may include, but are not limited to, hydrazide, oxime, amino, hydrazine, thiosemicarbazone, hydrazine carboxylate, and arylhydrazide. The electrophilic group on an antibody provides a convenient site for attachment to a linker group. For a more comprehensive list of linking technologies, please see Jain, N.; Smith, S. W.; Ghone, S.; Tomczuk, B., Current ADC Linker Chemistry. Pharmaceutical Research 2015, 32 (11), 3526-3540. Linkers can either be cleavable or non-cleavable, with cleavable linkers normally represented by combinations of amino acids. The list of cleavable linkers includes, but is not limited to, valine- citruline, valine-alanine and any combination of two to eight amino acids. A self-immolative unit (e.g., a PAB spacer) can be included to assist with clean cleavage, and optionally hydrophilic groups (e.g., PEG) can be added to increase hydrophilicity of the construct. In some aspects, more suitably, the linker group comprises a self-immolative unit. A range of self- immolative units are known in the art

[0030] and have been described in, for example, US Patent No.7,754,681, European Patent Publication No.0624377. A variety of suitable linker groups are known in the art and may be used as described herein. For example, the maleimide methodology is routinely used as a method to attach antibodies to drug compounds by providing a linker attached to the drug with a terminal maleimide group. In addition, methodologies using diarylcyclooctyne moieties (such as, but not limited to, DBCO, dibenzylcyclooctyne) are known in the art. Diarylcyclooctynes react with stable azides to provide attachment via the formation of stable triazoles. Diarylcyclooctynes are thermostable with very narrow and specific reactivity toward azides, resulting in almost quantitative yields of stable triazoles. Furthermore, the reaction does not require a cytotoxic Cu(I) catalyst (that is toxic to most organisms) and thus, prevents its use in many biological systems. Still further, alkoxyamine methodologies are also alternatives in the art. For site-specific conjugation of the drug to the antibody, the antibodies may comprise a “tag” (which may be proprietary) that will react with a diarylcyclooctyne (for example DBCO), an alkyoxyamine and / or maleimide group to attach the antibody to the drug. The tag in some instances may be a mutated amino acid. Suitably linker groups incorporating the various groups described above are available in the art. Suitably the linker group is L2-R28as disclosed herein. Antibody Drug Conjugates Antibody therapy has been established for the targeted treatment of patients with cancer, immunological and angiogenic disorders (Carter, P. (2006) Nature Reviews Immunology 6:343- 357). The use of antibody-drug conjugates (ADC), i.e., immunoconjugates, for the local delivery of cytotoxic or cytostatic agents, i.e., drugs to kill or inhibit tumor cells in the treatment of cancer, targets delivery of the drug moiety to tumors, and intracellular accumulation therein, whereas systemic administration of these unconjugated drug agents may result in unacceptable levels of toxicity to normal cells (Xie et al (2006) Expert. Opin. Biol. Ther.6(3):281 -291 ; Kovtun ef a / (2006) Cancer Res.66(6):3214-3121 ; Law et al (2006) CancerRes.66(4):2328- 2337; Wu et al (2005) Nature Biotech.23(9): 1137-1145; Lambert J. (2005) Current Opin. in Pharmacol.5:543-549; Hamann P. (2005) Expert Opin. Ther. Patents 15(9): 1087-1103; Payne, G. (2003) Cancer Cell 3:207-212; Trail ef a / (2003) Cancer Immunol. Immunother.52:328-337; Syrigos and Epenetos (1999) Anticancer Research 19:605-614). Maximal efficacy with minimal toxicity is sought thereby. Efforts to design and refine ADCs have focused on the selectivity of monoclonal antibodies (mAbs) as well as drug mechanism of action, drug-linking, drug / antibody ratio (loading), and drug-releasing properties (Junutula, et al., 2008b Nature Biotech., 26(8):925-932; Doman et al., (2009) Blood 114(13):2721 -2729; US 7521541 ; US 7723485; WO2009 / 052249; McDonagh (2006) Protein Eng. Design & Sel. 19(7 ): 299-307; Doronina et al., (2006) Bioconj. Chem.17:114-124; Erickson et al., (2006) CancerRes.66(8 ): 1- 8; et al., (2005) Clin. CancerRes.1 :843-852; Jeffrey et al., (2005) J. Med. Chem.48:1344-1358; Hamblett et al., (2004) Clin. Cancer Res.10:7063- 7070). In some aspects, the present disclosure relates to a compound of formula (I) and salts and solvates thereof, for use as a drug in an antibody-drug conjugate. In some aspects, the present disclosure relates to an antibody-drug conjugate comprising a compound of formula (I) and salts and solvates thereof. Suitably, a compound of formula (I) and salts and solvates thereof, for use as a drug in an antibody-drug conjugate is prepared by attaching a compound of formula (I) and salts and solvates thereof to an antibody, either directly or via an optional linker group. Suitably, the compound of formula (I) and salts and solvates thereof, is attached to an antibody or antibody fragment thereof via a linker group. Suitably, the antibody-drug conjugate is for use in for treatment of a disease, more specifically of a proliferative disease. Suitably, the drug may be attached by any suitable functional group that it contains to the antibody either directly or via a linker group. Typically, the drug contains, or can be modified to contain, one or more functional groups such as amine, hydroxyl or carboxylic acid groups for attaching the drug to the antibody either directly or via a linker group. In some aspects, the antibody of the antibody drug conjugate is an antibody fragment, such as, but not limited to a single chain antibody. In some aspects, one or more atoms or groups of the compound of formula (I) may be eliminated during the attachment of the drug to the antibody. In some aspects, the antibody binds to a cell surface receptor or a tumor-associated antigen. In some aspects, the present disclosure relates to the use of a compound of formula (I) and salts and solvates thereof, as a drug in an antibody-drug conjugate. Suitably, the use of a compound of formula (I) and salts and solvates thereof, as a drug in an antibody-drug conjugate is accomplished by attaching a compound of formula (I) and salts and solvates thereof to an antibody, either directly or via an optional linker group. Suitably, the compound of formula (I) and salts and solvates thereof, is attached to an antibody via a linker group. Suitably, the antibody-drug conjugate is for use in for treatment of a disease, more specifically of a proliferative disease. Suitably, the drug may be attached by any suitable functional group that it contains to the antibody either directly or via a linker group. Typically, the drug contains, or can be modified to contain, one or more functional groups such as amine, hydroxyl or carboxylic acid groups for attaching the drug to the antibody either directly or via a linker group. In some aspects, the antibody of the antibody drug conjugate is an antibody fragment, such as, but not limited to a single chain antibody. In some aspects, one or more atoms or groups of the compound of formula (I) may be eliminated during the attachment of the drug to the antibody. In some aspects, the antibody binds to a cell surface receptor or a tumor- associated antigen. In some embodiments, ADCs may be produced or generated having (a) an antibody, or antigen- binding fragment thereof (e.g. an antibody, or antigen-binding fragment thereof) and (b) a compound of formula (I) or formula (IV) (i.e., the drug). The drug-to-antibody ratio (DAR) or drug loading indicates the number of drug molecules and / or moieties (i.e., compounds of formula (I) or formula (IV), or moieties thereof) that are conjugated per antibody. In some embodiments, the number of linker-drug moieties attached to an antibody can be any number suitable for development of an ADC. In some embodiments, the number of compounds of formula (I) or formula (IV), or moieties thereof, per antibody ranges from about 1 to about 10. In some embodiments, the number of compounds of formula (I) or formula (IV), or moieties thereof, per antibody is about 10. In some embodiments, the number of compounds of formula (I) or formula (IV), or moieties thereof, per antibody is about 9. In some embodiments, the number of compounds of formula (I) or formula (IV), or moieties thereof, per antibody is about 8. In some embodiments, the number of compounds of formula (I) or formula (IV), or moieties thereof, per antibody is about 7. In some embodiments, the number of compounds of formula (I) or formula (IV), or moieties thereof, per antibody is about 6. In some embodiments, the number of compounds of formula (I) or formula (IV), or moieties thereof, per antibody is about 5. In some embodiments, the number of compounds of formula (I) or formula (IV), or moieties thereof, per antibody is about 4. In some embodiments, the number of compounds of formula (I) or formula (IV), or moieties thereof, per antibody is about 3. In some embodiments, the number of compounds of formula (I) or formula (IV), or moieties thereof, per antibody is about 2. In some embodiments, the number of compounds of formula (I) or formula (IV), or moieties thereof, per antibody is about 1. In some embodiments, the number of compounds of formula (I) or formula (IV), or moieties thereof, per antibody is greater than 4, such as 5, 6, 7, 8, 9, 10, 11, 12 or greater than 12 linker-drug moieties per antibody. Antibody and antibody fragments The term “antibody” specifically covers monoclonal antibodies, polyclonal antibodies, dimers, multimers, multispecific antibodies (e.g., bispecific antibodies), intact antibodies and antibody fragments, so long as they exhibit the desired biological activity, for example, the ability to bind a desired antigen on a target cell or tissue. Antibodies may be murine, human, humanized, chimeric, or derived from other species. An antibody is a protein generated by the immune system that is capable of recognizing and binding to a specific antigen. (Janeway, C, Travers, P., Walport, M., Shlomchik (2001) Immuno Biology,5th Ed., Garland Publishing, New York). A target antigen generally has numerous binding sites, also called epitopes, recognized by CDRs on the antibody. Each antibody that specifically binds to a different epitope has a different structure. Thus, one antigen may have more than one corresponding antibody. An antibody includes a full-length immunoglobulin molecule or an immunologically active portion of a full- length immunoglobulin molecule, i.e., a molecule that contains an antigen binding site that immunospecifically binds an antigen of a target of interest or part thereof, such targets including but not limited to, cancer cell or cells that produce autoimmune antibodies associated with an autoimmune disease. The immunoglobulin can be of any type (e.g., IgG, IgE, IgM, IgD, and IgA), class (e.g., lgG1 , lgG2, lgG3, lgG4, lgA1 and lgA2) or subclass, or allotype (e.g., human G1 m1 , G1 m2, G1 m3, non-G1 m1 [that, is any allotype other than G1 m1], G1 m17, G2m23, G3m21 , G3m28, G3m11 , G3m5, G3m13, G3m14, G3m10, G3m15, G3m16, G3m6, G3m24, G3m26, G3m27, A2m1 , A2m2, Km1 , Km2 and Km3) of immunoglobulin molecule. The immunoglobulins can be derived from any species, including human, murine, or rabbit origin. As used herein, “binds an epitope” is used to mean the antibody binds an epitope with a higher affinity than a non-specific partner such as Bovine Serum Albumin (BSA, Genbank accession no. CAA76847, version no. CAA76847.1 Gl:3336842, record update date: Jan 7, 201102:30 PM). In some embodiments the antibody binds an epitope with an association constant (Ka) at least 2, 3, 4, 5, 10, 20, 50, 100, 200, 500, 1000, 2000, 5000, 104, 105or 106-fold higher than the antibody's association constant for BSA, when measured at physiological conditions. The term “antibody fragment” refers to a portion of a full-length antibody, for example, the antigen binding or variable region thereof. Examples of antibody fragments include Fab, Fa’', F(a’')2, and scFv fragments; diabodies; linear antibodies; fragments produced by a Fab expression library, anti-idiotypic (anti-Id) antibodies, CDR (complementary determining region), single-chain antibody molecules; and multi-specific antibodies formed from antibody fragments and epitope-binding fragments of any of the above which immunospecifically bind to target antigens, such as, for example, cancer cell antigens, viral antigens or microbial antigens. The term “monoclonal antibody” as used herein refers to an antibody 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. Furthermore, in contrast to polyclonal antibody preparations which include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant or epitope on the antigen. In addition to their specificity, the monoclonal antibodies are advantageous in that they may be synthesized uncontaminated by other antibodies. The modifier “monoclonal” indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method. For example, the monoclonal antibodies to be used in accordance with the present disclosure may be made by the hybridoma method first described by Kohler et al (1975) Nature 256:495, or may be made by recombinant DNA methods (see, US 4816567). The monoclonal antibodies may also be isolated from phage antibody libraries using the techniques described in Clackson et al (1991 ) Nature, 352:624-628; Marks et al (1991) J. Mol. Biol., 222:581-597 or from transgenic mice carrying a fully human immunoglobulin system (Lonberg (2008) Curr. Opinion 20(4):450- 459). The antibodies, including monoclonal antibodies, herein specifically include “chimeric” antibodies in which a portion of the antibody structure, for example the heavy and / or light chain, is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they exhibit the desired biological activity (US 4816567; and Morrison et al (1984) Proc. Natl. Acad. Sci. USA, 81 :6851 -6855). Chimeric antibodies include “primatized” antibodies comprising variable domain antigen-binding sequences derived from a non-human primate (e.g., Old World Monkey or Ape) and human constant region sequences. An “intact antibody” herein is one comprising VL and VH domains, as well as a light chain constant domain (CL) and heavy chain constant domains, CH1, CH2 and CH3. The constant domains may be native sequence constant domains (e.g., human native sequence constant domains) or amino acid sequence variant thereof. The intact antibody may have one or more “effector functions” which refer to those biological activities attributable to the Fc region (a native sequence Fc region or amino acid sequence variant Fc region) of an antibody. Examples of antibody effector functions include C1 q binding; complement dependent cytotoxicity; Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; and down regulation of cell surface receptors such as B cell receptor and BCR. The antibodies disclosed herein may be modified. For example, to make them less immunogenic to a human subject. This may be achieved using any of a number of techniques familiar to the person skilled in the art, such as humanisation. Suitably, each targeting agent is independently a protein, a portion of a protein, a polypeptide, a nucleic acid, an antibody or an antibody fragment. More suitably, each targeting agent is independently an antibody or an antibody fragment. More suitably, each targeting agent is an antibody. Suitably, the targeting agent may be any of the antibody or antibody fragments disclosed herein. Suitably, the targeting agent is an anti-CD22 antibodies, anti-Ly6E antibodies, anti-HER2 antibodies, anti-MUC16 antibodies, anti-STEAP-1 antibodies, anti-NaPi2b antibodies, anti- CD79b antibodies, antibody fragments , chimeric and humanized antibodies, human antibodies, library-derived antibodies, multispecific antibodies, antibody variants, substitution, insertion, and deletion variants, glycosylation variants, Fc region variants, cysteine engineered antibody variants, or antibody derivatives as disclosed herein. In various embodiments, the targeting agent may bind to a target selected from an acute myeloid leukemia (AML M4) cell, an acute promyelocytic leukemia cell, an acute lymphoblastic leukemia cell, an acute lymphocytic leukemia cell, a chronic lymphocytic leukemia cell, a chronic myeloid leukemia cell, a chronic T-cell lymphocytic leukemia, a myelodysplasia syndromic cell, a multiple myeloma cell, a prostate carcinoma cell, a renal cell adenocarcinoma cell, a pancreatic adenocarcinoma cell, a lung carcinoma cell or a gastric adenocarcinoma cell, a gastric adenocarcinoma cell, a breast cancer cell, a colon cancer cell, a melanoma cell, a thyroid cancer cell, an ovarian cancer cell, a bladder cancer cell, a liver cancer cell, a head and neck cancer cell, an esophageal cancer cell, a hodgkin lymphoma cell, a non- hodgkin lymphoma cell, a mesothelioma cell, a neuroblastoma cell, a neuroendocrine tumor cell, a neurofibromatosis type 1 (NF1) cell, a neurofibromatosis type 2 (NF2) or an osteosarcoma cell. In some embodiments, the targeting agent binds to a tumor-associated antigen. Examples of tumor-associated antigens include, but are not limited to, 5 alpha reductase, alpha- fetoprotein, AM-1, APC, April, BAGE, beta catenin, Bcl12, bcr-abl, CA-125, CASP-8 / FLICE, Cathepins, CD19, CD20, CD21, CD23, CD22, CD33 CD35, CD44, CD45, CD46, CD5, CD52, CD55, CD59, CDC27, CDK4, CEA, c-myc, Cox-2, DCC, DcR3, E6. / E7, CGFR, EMBP, Dna78, farnesyl transferase, FGF8b, FGF8a, FLK-1 / KDR, folate receptor, G250, GAGE family, gastrin 17, gastrin releasing hormone, GD2 / GD3 / GM2, GnRH, GnTV, GP1, gp100 / Pmel17, gp- 100-in4, gp15, gp75 / TRP-1, hCG, heparance, Her2 / neu, HMTV, Hsp70, hTERT, IGFR1, IL- 13R, iNOS, Ki67, KIAA0205, K-ras. , H-ras, N-ras, KSA, LKLR-FUT, MAGE family, mammaglobin, MAP17, melan-A / MART-1, mesothelin, MIC A / B, MT-MMP, mucin, NY- ESO-1, osteonectin, p15, P170 / MDR1, p53, p97 / melanotransferrin, PAI-1, PDGF, uPA, PRAME, probasin, progenipoietin, RAG, PSA, PSA. -1, Rb, RCAS1, SART-1, SSX-family, STAT3, STn, TAG-72, TGF-alpha, TGF-beta, thymosin-beta-15, TNF-alpha, TYRP-, TYRP-2, tyrosinase, VEGF, ZAG, p16INK4, and glutathione-S-transferase. Administration & Dose Compounds of formula (I), formula (IV), and compounds of other formulae set out herein (i.e., compounds of formula (I) with a G- alkylating DNA group of formula (II) or one of G1-G8 as the D moiety, and compounds of formula (I) with an A-alkylating DNA group of formula (IIIa) or (IIIb) as the D moiety) and / or conjugates thereof, may be administered alone or in combination with one or another or with one or more pharmacologically active compounds which are different from the compounds of formula (I) ), formula (IV), and compounds of other formulae set out herein (i.e., compounds of formula (I) with a G- alkylating DNA group of formula (II) or one of G1-G8 as the D moiety, and compounds of formula (I) with an A- alkylating DNA group of formula (IIIa) or (IIIb) as the D moiety) and / or conjugates thereof. Compounds of the disclosure may suitably be combined with various components to produce compositions of the disclosure. Suitably the compositions are combined with a pharmaceutically acceptable carrier or diluent to produce a pharmaceutical composition (which may be for human or animal use). Suitable carriers and diluents include isotonic saline solutions, for example phosphate-buffered saline. Useful pharmaceutical compositions and methods for their preparation may be found in standard pharmaceutical texts. See, for example, Handbook for Pharmaceutical Additives,3rd Edition (eds. M. Ash and I. Ash), 2007 (Synapse Information Resources, Inc., Endicott, New York, USA) and Remington: The Science and Practice of Pharmacy, 21st Edition (ed. D. B. Troy) 2006 (Lippincott, Williams and Wilkins, Philadelphia, USA) which are incorporated herein by reference. The compounds of the disclosure may be administered by any suitable route. Suitably the compounds of the disclosure will normally be administered orally or by any parenteral route, in the form of pharmaceutical preparations comprising the active ingredient, optionally in the form of a non-toxic organic, or inorganic, acid, or base, addition salt, in a pharmaceutically acceptable dosage form. The compounds of the disclosure, their pharmaceutically acceptable salts, and pharmaceutically acceptable solvates of either entity can be administered alone but will generally be administered in admixture with a suitable pharmaceutical excipient diluent or carrier selected with regard to the intended route of administration and standard pharmaceutical practice. For example, the compounds of the disclosure or salts or solvates thereof can be administered orally, buccally or sublingually in the form of tablets, capsules (including soft gel capsules), ovules, elixirs, solutions or suspensions, which may contain flavouring or colouring agents, for immediate-, delayed-, modified-, sustained-, controlled-release or pulsatile delivery applications. The compounds of the disclosure may also be administered via fast dispersing or fast dissolving dosages forms. Such tablets may contain excipients such as microcrystalline cellulose, lactose, sodium citrate, calcium carbonate, dibasic calcium phosphate and glycine, disintegrants such as starch (preferably corn, potato or tapioca starch), sodium starch glycollate, croscarmellose sodium and certain complex silicates, and granulation binders such as polyvinylpyrrolidone, hydroxypropylmethyl cellulose (HPMC), hydroxypropylcellulose (HPC), sucrose, gelatin and acacia. Additionally, lubricating agents such as magnesium stearate, stearic acid, glyceryl behenate and talc may be included. Solid compositions of a similar type may also be employed as fillers in gelatin capsules. Preferred excipients in this regard include lactose, starch, a cellulose, milk sugar or high molecular weight polyethylene glycols. For aqueous suspensions and / or elixirs, the compounds of the disclosure may be combined with various sweetening or flavouring agents, colouring matter or dyes, with emulsifying and / or suspending agents and with diluents such as water, ethanol, propylene glycol and glycerin, and combinations thereof. Modified release and pulsatile release dosage forms may contain excipients such as those detailed for immediate release dosage forms together with additional excipients that act as release rate modifiers, these being coated on and / or included in the body of the device. Release rate modifiers include, but are not exclusively limited to, hydroxypropylmethyl cellulose, methyl cellulose, sodium carboxymethylcellulose, ethyl cellulose, cellulose acetate, polyethylene oxide, Xanthan gum, Carbomer, ammonio methacrylate copolymer, hydrogenated castor oil, carnauba wax, paraffin wax, cellulose acetate phthalate, hydroxypropylmethyl cellulose phthalate, methacrylic acid copolymer and mixtures thereof. Modified release and pulsatile release dosage forms may contain one or a combination of release rate modifying excipients. Release rate modifying excipients maybe present both within the dosage form i.e., within the matrix, and / or on the dosage form i.e., upon the surface or coating. Fast dispersing or dissolving dosage formulations (FDDFs) may contain the following ingredients: aspartame, acesulfame potassium, citric acid, croscarmellose sodium, crospovidone, diascorbic acid, ethyl acrylate, ethyl cellulose, gelatin, hydroxypropylmethyl cellulose, magnesium stearate, mannitol, methyl methacrylate, mint flavouring, polyethylene glycol, fumed silica, silicon dioxide, sodium starch glycolate, sodium stearyl fumarate, sorbitol, xylitol. The compounds of the disclosure can also be administered parenterally, for example, intravenously, intra-arterially, or they may be administered by infusion techniques. For such parenteral administration they are best used in the form of a sterile aqueous solution which may contain other substances, for example, enough salts or glucose to make the solution isotonic with blood. The aqueous solutions should be suitably buffered (preferably to a pH of from 3 to 9), if necessary. The preparation of suitable parenteral formulations under sterile conditions is readily accomplished by standard pharmaceutical techniques well-known to those skilled in the art. Suitably formulation of the disclosure is optimised for the route of administration e.g., oral, intravenously, etc. Administration may be in one dose, continuously or intermittently (e.g., in divided doses at appropriate intervals) during the course of treatment. Methods of determining the most effective means and dosage are well known to a skilled person and will vary with the formulation used for therapy, the purpose of the therapy, the target cell(s) being treated, and the subject being treated. Single or multiple administrations can be carried out with the dose level and the dose regimen being selected by the treating physician, veterinarian, or clinician. Depending upon the disorder and patient to be treated, as well as the route of administration, the compositions may be administered at varying doses. For example, a typical dosage for an adult human may be 100 ng to 25 mg (suitably about 1 micro g to about 10 mg) per kg body weight of the subject per day. Suitably guidance may be taken from studies in test animals when estimating an initial dose for human subjects. For example when a particular dose is identified for mice, suitably an initial test dose for humans may be approx.0.5x to 2x the mg / Kg value given to mice. Other Forms Unless otherwise specified, included in the above are the well-known ionic, salt, solvate, and protected forms of these substituents. For example, a reference to carboxylic acid (-RCOOH) also includes the anionic (carboxylate) form (-RCOO-), a salt or solvate thereof, as well as conventional protected forms. Similarly, a reference to an amino group includes the protonated form (-RN+HR1R2), a salt or solvate of the amino group, for example, a hydrochloride salt, as well as conventional protected forms of an amino group. Similarly, a reference to a hydroxyl group also includes the anionic form (-O-), a salt or solvate thereof, as well as conventional protected forms. Isomers, Salts and Solvates Certain compounds may exist in one or more particular geometric, optical, enantiomeric,diasteriomeric, epimeric, atropic, mesomeric stereoisomeric, tautomeric, conformational, or anomeric forms, including but not limited to, cis- and trans-forms; E- and Z- forms; c-, t-, and r- forms; endo- and exo-forms; R-, S-, and meso-forms; D- and L-forms; d- and l- forms; (+) and (-) forms; keto-, enol-, and enolate-forms; syn- and anti-forms; synclinal- and anticlinal-forms; alpha- and beta-forms; axial and equatorial forms; boat-, chair-, twist-, envelope-, and halfchair-forms; and combinations thereof, hereinafter collectively referred to as “isomers” (or “isomeric forms”). Note that, except as discussed below for tautomeric forms, specifically excluded from the term “isomers”, as used herein, are structural (or constitutional) isomers (i.e., isomers which differ in the connections between atoms rather than merely by the position of atoms in space). For example, a reference to a methoxy group, -OCH3, is not to be construed as a reference to its structural isomer, a hydroxymethyl group, -CH2OH. A reference to a class of structures may well include structurally isomeric forms falling within that class (e.g., C1-7alkyl includes n-propyl and iso-propyl; butyl includes n-, iso-, sec-, and tert- butyl; methoxyphenyl includes ortho-, meta-, and para-methoxyphenyl). The above exclusion does not apply to tautomeric forms, for example, keto-, enol-, and enolate- forms, as in, for example, the following tautomeric pairs: keto / enol, imine / enamine, amide / imino alcohol, amidine / amidine, nitroso / oxime, thioketone / enethiol, N- nitroso / hyroxyazo, and nitro / aci-nitro. Note that specifically included in the term “isomer” are compounds with 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; O may be in any isotopic form, including16O and18O; and the like. Unless otherwise specified, a reference to a particular compound includes all such isomeric forms, including (wholly or partially) racemic and other mixtures thereof. Methods for the preparation (e.g., asymmetric synthesis) and separation (e.g., fractional118olubilized118ionn and chromatographic means) of such isomeric forms are either known in the art or are readily obtained by adapting the methods taught herein, or known methods, in a known manner. Unless otherwise specified, a reference to a particular compound also includes ionic, salt, solvate, and protected forms of thereof, for example, as discussed below. In some embodiments, the compound of formula (I) and salts and solvates thereof, comprises pharmaceutically acceptable salts of the compounds of formula (I). Compounds of Formula (I), which include compounds specifically named above, may form pharmaceutically acceptable complexes, salts, solvates and hydrates. These salts include nontoxic acid addition salts (including di-acids) and base salts. If the compound is cationic, or has a functional group which may be cationic (e.g., -NH2may be -NH3+), then an acid addition salt may be formed with a suitable anion. Examples of suitable inorganic anions include, but are not limited to, those derived from the following inorganic acids hydrochloric acid, nitric acid, nitrous acid, phosphoric acid, sulfuric acid, sulphurous acid, hydrobromic acid, hydroiodic acid, hydrofluoric acid, phosphoric acid and phosphorous acids. Examples of suitable organic anions include, but are not limited to, those derived from the following organic acids: 2-acetyoxybenzoic, acetic, ascorbic, aspartic, benzoic, camphorsulfonic, cinnamic, citric, edetic, ethanedisulfonic, ethanesulfonic, fumaric, glucheptonic, gluconic, glutamic, glycolic, hydroxymaleic, hydroxynaphthalene carboxylic, isethionic, lactic, lactobionic, lauric, maleic, malic, methanesulfonic, mucic, oleic, oxalic, palmitic, pamoic, pantothenic, phenylacetic, phenylsulfonic, propionic, pyruvic, salicylic, stearic, succinic, sulfanilic, tartaric, toluenesulfonic, and valeric. Examples of suitable polymeric organic anions include, but are not limited to, those derived from the following polymeric acids: tannic acid, carboxymethyl cellulose. Such salts include acetate, adipate, aspartate, benzoate, besylate, bicarbonate, carbonate, bisulfate, sulfate, borate, camsylate, citrate, cyclamate, edisylate, esylate, formate, fumarate, gluceptate, gluconate, glucuronate, hexafluorophosphate, hibenzate, hydrochloride / chloride, hydrobromide / bromide, hydroiodide / iodide, isethionate, lactate, malate, maleate, malonate, mesylate, methylsulfonate, naphthylate, 2-napsylate, nicotinate, nitrate, orotate, oxalate, palmitate, pamoate, phosphate, hydrogen phosphate, dihydrogen phosphate, pyroglutamate, saccharate, stearate, succinate, tannate, tartrate, tosylate, trifluoroacetate and xinofoate salts. For example, if the compound is anionic, or has a functional group which may be anionic (e.g., - RCOOH may be –RCOO-), then a base salt may be formed with a suitable cation. Examples of suitable inorganic cations include, but are not limited to, metal cations, such as an alkali or alkaline earth metal cation, ammonium and substituted ammonium cations, as well as amines. Examples of suitable metal cations include sodium (Na+) potassium (K+), magnesium (Mg2+), calcium (Ca2+), zinc (Zn2+), and aluminum (Al3+). Examples of suitable organic cations include, but are not limited to, ammonium ion (i.e., NH4+) and substituted ammonium ions (e.g., NH3R+, NH2R2+, NHR3+, NR4+). Examples of some suitable substituted ammonium ions are those derived from: ethylamine, diethylamine, dicyclohexylamine, triethylamine, butylamine, ethylenediamine, ethanolamine, diethanolamine, piperazine, benzylamine, phenylbenzylamine, choline, meglumine, and tromethamine, as well as amino acids, such as lysine and arginine. An example of a common quaternary ammonium ion is N(CH3)4+. Examples of suitable amines include arginine, N,’'-dibenzylethylene-diamine, chloroprocaine, choline, diethylamine, diethanolamine, dicyclohexylamine, ethylenediamine, glycine, lysine, N-methylglucamine, olamine, 2-amino-2-hydroxymethyl-propane-1,3-diol, and procaine. For a discussion of useful acid addition and base salts, see S. M. Berge et al., J. Pharm. Sci. (1977) 66:1-19; see also Stahl and Wermuth, Handbook of Pharmaceutical Salts: Properties, Selection, and Use (2011) Pharmaceutically acceptable salts may be prepared using various methods. For example, one may react a compound of Formula 1 with an appropriate acid or base to give the desired salt. One may also react a precursor of the compound of Formula I with an acid or base to remove an acid- or base-labile protecting group or to open a lactone or lactam group of the precursor. Additionally, one may convert a salt of the compound of Formula 1 to another salt through treatment with an appropriate acid or base or through contact with an ion exchange resin. Following reaction, one may then isolate the salt by filtration if it precipitates from solution, or by evaporation to recover the salt. The degree of ionization of the salt may vary from completely ionized to almost non-ionized. It may be convenient or desirable to prepare, purify, and / or handle a corresponding solvate of the active compound. The term “solvate” describes a molecular complex comprising the compound and one or more pharmaceutically acceptable solvent molecules (e.g., EtOH). The term “hydrate” is a solvate in which the solvent is water. Pharmaceutically acceptable solvates include those in which the solvent may be isotopically substituted (e.g., D2O, acetone-d6, DMSO-d6). A currently accepted classification system for solvates and hydrates of organic compounds is one that distinguishes between isolated site, channel, and metal-ion coordinated solvates and hydrates. See, e.g., K. R. Morris (H. G. Brittain ed.) Polymorphism in Pharmaceutical Solids (1995). Isolated site solvates and hydrates are ones in which the solvent (e.g., water) molecules are isolated from direct contact with each other by intervening molecules of the organic compound. In channel solvates, the solvent molecules lie in lattice channels where they are next to other solvent molecules. In metal-ion coordinated solvates, the solvent molecules are bonded to the metal ion. When the solvent or water is tightly bound, the complex will have a well-defined stoichiometry independent of humidity. When, however, the solvent or water is weakly bound, as in channel solvates and in hygroscopic compounds, the water or solvent content will depend on humidity and drying conditions. In such cases, non-stoichiometry will typically be observed. Further particular and preferred aspects are set out in the accompanying independent and dependent claims. Features of the dependent claims may be combined with features of the independent claims as appropriate, and in combinations other than those explicitly set out in the claims. SYNTHETIC STRATEGIES The compounds of Formula (I) may be prepared using the techniques described below. Some of the schemes and examples may omit details of common reactions, including oxidations, reductions, and so on, separation techniques (extraction, evaporation, precipitation, chromatography, filtration, trituration, crystallization, and the like), and analytical procedures, which are known to persons of ordinary skill in the art of organic chemistry. The details of such reactions and techniques can be found in a number of treatises, including Richard Larock, Comprehensive Organic Transformations, A Guide to Functional Group Preparations,2nd Ed (2010), and the multi-volume series edited by Michael B. Smith and others, Compendium of Organic Synthetic Methods (1974 et seq.). Starting materials and reagents may be obtained from commercial sources or may be prepared using literature methods. Some of the reaction schemes may omit minor products resulting from chemical transformations (e.g., an alcohol from the hydrolysis of an ester, CO2from the decarboxylation of a diacid, etc.). In addition, in some instances, reaction intermediates may be used in subsequent steps without isolation or purification (i.e., in situ). In some of the reaction schemes and examples below, certain compounds can be prepared using protecting groups, which prevent undesirable chemical reaction at otherwise reactive sites. Protecting groups may also be used to enhance solubility or otherwise modify physical properties of a compound. For a discussion of protecting group strategies, a description of materials and methods for installing and removing protecting groups, and a compilation of useful protecting groups for common functional groups, including amines, carboxylic acids, alcohols, ketones, aldehydes, and so on, see T. W. Greene and P. G. Wuts, Protecting Groups in Organic Chemistry,4th Edition, (2006) and P. Kocienski, Protective Groups,3rd Edition (2005). Generally, the chemical transformations described throughout the specification may be carried out using substantially stoichiometric amounts of reactants, though certain reactions may benefit from using an excess of one or more of the reactants. Additionally, many of the reactions disclosed throughout the specification may be carried out at about room temperature (RT) and ambient pressure, but depending on reaction kinetics, yields, and so on, some reactions may be run at elevated pressures or employ higher temperatures (e.g., reflux conditions) or lower temperatures (e.g., -78°C. to 0°C.). Any reference in the disclosure to a stoichiometric range, a temperature range, a pH range, etc., whether or not expressly using the word "range," also includes the indicated endpoints. Many of the chemical transformations may also employ one or more compatible solvents, which may influence the reaction rate and yield. Depending on the nature of the reactants, the one or more solvents may be polar protic solvents (including water), polar aprotic solvents, non-polar solvents, or some combination. Representative solvents include saturated aliphatic hydrocarbons (e.g., n-pentane, n-hexane, n-heptane, n-octane); aromatic hydrocarbons (e.g., benzene, toluene, xylenes); halogenated hydrocarbons (e.g., methylene chloride, chloroform, carbon tetrachloride); aliphatic alcohols (e.g., methanol, ethanol, propan-1-ol, propan-2-ol, butan-1-ol, 2-methyl-propan-1-ol, butan-2-ol, 2-methyl-propan-2-ol, pentan-1-ol, 3-methyl- butan-1-ol, hexan-1-ol, 2-methoxy-ethanol, 2-ethoxy-ethanol, 2-butoxy-ethanol, 2-(2-methoxy- ethoxy)-ethanol, 2-(2-ethoxy-ethoxy)-ethanol, 2-(2-butoxy-ethoxy)-ethanol); ethers (e.g., diethyl ether, di-isopropyl ether, dibutyl ether, 1,2-dimethoxy-ethane, 1,2-diethoxy-ethane, 1- methoxy-2-(2-methoxy-ethoxy)-ethane, 1-ethoxy-2-(2-ethoxy-ethoxy)-ethane, tetrahydrofuran, 1,4-dioxane); ketones (e.g., acetone, methyl ethyl ketone); esters (methyl acetate, ethyl acetate); nitrogen-containing solvents (e.g., formamide, N,N-dimethylformamide, acetonitrile, N-methyl- pyrrolidone, pyridine, quinoline, nitrobenzene); sulfur-containing solvents (e.g., carbon disulfide, dimethyl sulfoxide, tetrahydro-thiophene-1,1,-dioxide); and phosphorus-containing solvents (e.g.,HMPA, hexamethylphosphoramide). One synthetic strategy to add a monosaccharide unit to compounds of formula I may involve (stereochemistry not shown): Glucose-based N11-carbamate With the monosaccharide unit linked either to primary alcohol (right) or secondary alcohol (left: any of the four groups); or Glucuronide-based

[0023] Either a carbamate (left; any of the alcohol groups) or directly bound amide (right). In some aspects, the present disclosure relates to a compound of formula (I) and salts and solvates thereof, for use in preparing a drug in an antibody-drug conjugate. Suitably, a compound of formula (I) and salts and solvates thereof, may be used directly to prepare an antibody-drug conjugate when a compound of formula (I) and salts and solvates thereof, contains one or more functional groups (such as amine, hydroxyl or carboxylic acid groups) for attaching the drug to the antibody either directly or via a linker group. Suitably, a compound of formula (I) and salts and solvates thereof, may be used in preparing an antibody-drug conjugate by being modified to contain one or more functional groups (such as amine, hydroxyl or carboxylic acid groups) for attaching the drug to the antibody either directly or via a linker group. Suitably, a compound of formula (I) and salts and solvates thereof, may be used in preparing an antibody-drug conjugate by being modified to contain one or more antibody linker groups, wherein the antibody is attached to the drug through the one or more antibody linker groups. Therefore, the present disclosure provides for compounds of formula (I) further comprising one or more antibody linker group. Suitably, a compound of the formula (I) may contain 1, 2, or 3 antibody linker groups. Suitably, a compound of the formula (I) may contain 1 or 2 antibody linker groups. Suitably, a compound of the formula (I) may contain 1 antibody linker group. In some aspects, one or more atoms or groups of the compound of formula (I) may be eliminated during the attachment of the drug to the antibody or the attachment of the antibody linker to the drug or the modification of the drug to contain one or more functional groups (such as amine, hydroxyl or carboxylic acid groups) for attaching the drug to the antibody either directly or via an antibody linker group. A variety of suitable antibody linker groups are known in the art and may be used as described herein. For example, the maleimide methodology is routinely used as a method to attach antibodies to drug compounds by providing an antibody linker attached to the drug with a terminal succinimide group (forming a succinimide-antibody complex). In addition, methodologies using diarylcyclooctyne moeities (such as, but not limited to, DBCO, dibenzylcyclooctyne) are also alternatives used in the art. Diarylcyclooctynes react with azides to provide attachment via the formation of stable triazoles. Diarylcyclooctynes are thermostable with very narrow and specific reactivity toward azides, resulting in almost quantitative yields of stable triazoles. Furthermore, the reaction does not require a cytotoxic Cu(I) catalyst (that is toxic to most organisms) and thus, prevents its use in many biological systems. Still further, alkoxyamine methodologies are also alternatives used in the art. For site-specific conjugation of the drug to an antibody, the antibodies may comprise a “tag” (which may be proprietary) that will react with a dairylcyclooctyne (for example, DBCO), an alkyloxyamine and / or maleimide group to attach the antibody to the drug. The tag in some instances may be a mutated amino acid. Suitable antibody linker groups incorporating the various groups described above are available in the art. The disclosure will be further described in the following embodiments, which do not limit the scope of the disclosure describe in the claims. Embodiment 1. A compound of formula (I): D – Q – B - T (I) or a salt, solvate or tautomer thereof, wherein: D is a source of an alkylating DNA minor groove binding unit; Q is a linker; B is an DNA binding amide-containing chain; and T is an end group, wherein D, B, Q and / or T comprise at least one carbohydrate substituent. Embodiment 2. The compound of Embodiment 1, wherein the carbohydrate substituent is a univalent saccharide substituent represented by the term RS, preferably RSis glycosyl or O- glycosyl.

[0024] Embodiment 3. The compound of Embodiment 1 or 2, wherein D comprises G, a G- alkylating DNA group of formula (II): (II) wherein: the dotted line indicates the optional presence of a double bond between one or more of C1 and C2, C2 and C3, and C3 and C4; the wavy line indicates the point of attachment to Q; m is 0 or 1; R1, R3and R4are independently selected from H and R29; R2is selected from H, L2-R28,R29, and –LS-RS, or one of R1and R2, R2and R3, or R3and R4, together with the carbon atoms to which they are attached form a 6-membered aryl, or a 5- or 6-membered cyclic, heterocyclic, or heteroaryl ring optionally substituted with 1, 2 or 3 independently selected optional R20groups; R5and R6are selected such that either (i) R5is selected from H, OH and OC1-6alkyl; and R6is selected from H, SO3H, –LS-RS, nitrogen protecting groups, –L2-R28and RA; (ii) R5is oxo or H, and R6is H or C1-6alkyl; or (iii) R5and R6together form a double bond; R7and R9are independently selected from H and R20; R8is selected from H, SR24, SCH2Ph, R20, L2-R28, and –LS-RS; RAis selected from (CH2)j-OH, (CH2)j-CO2R26, C(=O)-O-(CH2)k-NR26R27, (CH2)jNR26R27, C(=O)-NH-(CH2)j-NR26R27and C(=O)-NH-(CH2)k-C(=NH)NR26R27; L2is a bond or a linker moiety having 1-200 non-hydrogen atoms selected from C, N, P, O, S or halogen, and optionally incorporates ether, oxo, carboxamidyl, urethanyl, branched, cyclic, unsaturated, heterocyclyl, aryl or heteroaryl moieties; and R28is selected from an azide, alkyne, bisulfone, carbohydrazide, hydrazine, hydroxylamine, iodoacetamide, isothiocyanate, maleimide, phosphine, pyrridopyridazine, semihydrazide, succinimidyl ester, sulfodichlorophenol ester, sulfonyl halide, sulfosuccinimidyl ester, 4- sulfotetrafluorophenyl ester, tetrafluorophenyl ester, thiazole, RA,O-(CH2)k-NR26R26, NHNH2, or is a targeting agent wherein the targeting agent is selected from a protein, a portion of a protein, a peptide, a nucleic acid, or an antibody; each R29is independently selected from R20, R21, =CH2, =CH-(CH2)s-CH3, =CH-(CH2)s-R21, =O, (CH2)s-OR21, (CH2)s-CO2R21, (CH2)s-NR21R24, O-(CH2)t-NR21R24, NH-C(O)-R21, O- (CH2)t-NH-C(O)-R21, O-(CH2)t-C(O)-NH-R21, (CH2)s-SO2R21, O-SO2R21, (CH2)s-C(O)R21and (CH2)s-C(O)NR21R24; each R20is independently selected from F, Cl, Br, (CH2)j-OH, C1-6alkyl, OC1-6alkyl, OCH2Ph, (CH2)j-CO2R26, O-(CH2)k-NR26R27, C(=O)-O-(CH2)k-NR26R27, C(=O)-NR26R27, (CH2)j- NR26R27, NR26NH2, C(=O)-NH-(CH2)j-NR26R27, C(=O)-NH-C6H4-(CH2)j-R26, C(=O)-NH- (CH2)k-C(=NH)NR26R27, –L2-R28, S(O)2-(C1-6alkyl), O-(CH2)k-O-(C1-6alkyl), (CH2)j- S(O)2-NR26R27, C(=NH)-O-(C1-6alkyl), (CH2)k-O-(C1-6alkyl), CN, NCO, Cy, C(O)-NH- (CH2)j-Cy, C(O)-Cy, NH-C(O)-NR26R27and ; each j and s is independently selected from 0, 1, 2, 3, 4, 5 or 6; each k and t is independently selected from 1, 2, 3, 4, 5 or 6; each R21is independently selected from H, C1-12alkyl, C5-6heterocyclyl, C5-9heteroaryl, C6-15heteroarylalkyl, phenyl and C7-12aralkyl groups; wherein the heterocyclyl, heteroaryl, heteroarylalkyl, phenyl and aralkyl groups are optionally substituted with 1, 2 or 3 independently selected optional R20groups; each R24, R26and R27is independently selected from H and C1-12alkyl; each Cy is independently selected from a C5-6heterocyclyl or C5-6heteroaryl group, wherein the heterocyclyl or heteroaryl groups are optionally substituted with 1 or 2 R20groups; LSis a bond, an amino acid, a peptide chain having from 2 to 6 amino acids, an alkylene chain containing from 1 to 12 carbon atoms which may contain one or more carbon-carbon double or triple bonds, a paraformaldehyde chain –(OCH2)1-12-, a polyethylene glycol chain -(OCH2CH2)1-6-, which chains may be interrupted by or optionally incorporates one or more of P, O, S, NH, C5-9heteroarylene, phenylene, heterocyclyl, cycloalkyl, ether, oxo, carboxamidyl, and / or urethanyl moieties wherein the C5-9heteroarylene, phenylene, heterocyclyl, and / or cycloalkyl moieties are optionally substituted, optionally LSis: or ; LCcomprises one or more groups selected from an amino acid, an amino acid derivative, a peptide chain having from 2 to 6 amino acids or amino acid derivatives, an alkylene chain containing from 1 to 12 carbon atoms which may contain one or more carbon-carbon double or triple bonds, a paraformaldehyde chain –(OCH2)1-12-, a polyethylene glycol chain -(OCH2CH2)1-8-, which chains may be interrupted by one or more P, O, S and / or NH groups and / or C5-9heteroarylene and / or phenylene, wherein each C5-9heteroarylene group and / or each phenylene group is optionally substituted; and RS is a univalent saccharide substituent, preferably glycosyl or O-glycosyl. Embodiment 4. The compound of Embodiment 3, wherein G is selected from a group of formula G1 to G8. Embodiment 5. The compound of Embodiment 1 or 2, wherein D comprises A, an A-alkylating DNA group of formula (IIIa) or (IIIb). Embodiment 6. The compound of Embodiment 3 or 4, wherein each of R1, R3,R7, and R9are H. Embodiment 7. The compound of Embodiment 3 or 4, wherein the compound is of formula IV. Embodiment 8. The compound of any one of Embodiments 1-7, wherein Q comprises X1-L-X2, wherein: X1is selected from O, S, NR13, CR13R14, CR13R14O, C(=O), C(=O)NR13, NR13C(=O), O-C(O) and C(O)-O, or is absent; L is selected from an amino acid, a peptide chain having from 2 to 6 amino acids, an alkylene chain containing from 1 to 12 carbon atoms which may contain one or more carbon- carbon double or triple bonds, a paraformaldehyde chain –(OCH2)1-12-, a polyethylene gly–ol chain -(OCH2CH2)1-6-, which chains may be interrupted by one or more P, O, S and / or NH groups and / or C5-9heteroarylene and / or phenylene, wherein each C5-9heteroarylene group and / or each phenylene group is optionally substituted; X2is selected from O, S, NR15, CR15R16, CR15R16O, C(=O), C(=O)NR15, NR15C(=O), O-C(O) and C(O)-O or is absent; and R13, R14,R15and R16are independently selected from H and C1-6alkyl. Embodiment 9. The compound of any one of Embodiments 1-8, wherein B comprises (A)q, wherein: q is selected from 0, 1, 2, 3, 4, 5 and 6; A is selected from: and ; A1 A2 for each A1 group one of Y3and Y4is independently selected from N-R30, S and O; and the other of Y3and Y4is CH; and Y5is independently selected from CR30, N, S and COH; for each A2 group one of Y6 and Y7 is independently selected from N and CH; and the other of Y6and Y7is CR30; and each R30is independently selected from H, C1-6alkyl, L2-R28and RS. Embodiment 10. The compound of any one of Embodiments 1-9, wherein T comprises a group of formula: wherein: p is 0 or 1; RTis selected from –L2-R28, phenyl, and C5-9heteroaryl, wherein the phenyl and C5-9heteroaryl groups are optionally substituted with up to three optional substituent groups selected from OH, C1-6alkyl, OC1-6alkyl, –L2-R28, (CH2)j-CO2R11, O-(CH2)k-NR11R12, (CH2)j- NR11R12, C(=O)-NH-(CH2)k-NR11R12, C(=O)-NH-R24, and C(=O)-NH-(CH2)k- C(=NH)NR11R12, optionally with the proviso that the optionally substituted C5-9 heteroaryl is not indolyl; R19is selected from H, C1-6alkyl, L2-R28, RS, and (CH2)t-NR20R21; Y1and Y2are independently N or CR31, wherein at least one of Y1and Y2is CR31; each R31is independently selected from H, C1-6alkyl, L2-R28and RS; and R11, R12, and R24are independently selected from H, –L2-R28, and C1-6alkyl. Embodiment 11. A compound of formula (I) and salts and solvates thereof as claimed in any one of the preceding claims, wherein the compound is selected from compounds of formulae: , herein Rs is a univalent saccharide substituent, preferably glycosyl or O-glycosyl.mbodiment 12. The compound of any one of Embodiments 1-11, or a pharmaceuticallyceptable salt thereof, wherein the compound comprises at least one L2-R28 group.mbodiment 13. The compound of Embodiment 12, or a pharmaceutically acceptable salt reof, wherein D, T, Q and / or B is substituted with a L2-R28 group. mbodiment 14. The compound of Embodiment 12 or 13, or a pharmaceutically acceptable salt reof, wherein L2is selected from: (i) , (ii) , (iii) , (iv) , (v) , (vi) , (vii) , (viii) , (ix) , (x) or (xi) ; wherein XAAis an amino acid sequence;– K2is -[CH2CH2O–0-50- or -[CH2]0-12-. Embodiment 15. The compound of any one of Embodiments 3-14, or a pharmaceutically acceptable salt thereof, wherein LSis: , wherein LCcomprises one or more groups selected from an amino acid, an amino acid derivative, a peptide chain having from 2 to 6 amino acids or amino acid derivatives, an alkylene chain containing from 1 to 12 carbon atoms which may contain one or more carbon- carbon double or triple bonds, a paraformaldehyde chain –(OCH2)1-12-, a polyethylene glycol chain -(OCH2CH2)1-8-, which chains may be interrupted by one or more P, O, S and / or NH groups and / or C5-9heteroarylene and / or phenylene, wherein each C5-9heteroarylene group and / or each phenylene group is optionally substituted. Embodiment 16. The compound of Embodiment 15, wherein LCcomprises , optionally or . Embodiment 17. The compound of Embodiment 15 or 16, wherein LCcomprises a a polyethylene glycol chain -(OCH2CH2)1-8-, optionally -(OCH2CH2)8-. Embodiment 18. The compound of any one of Embodiments 15-17, wherein R28-Lc is selected from:

[0025] Embodiment 19. The compound of any one of Embodiments 12-18, or a pharmaceutically acceptable salt thereof, wherein XAA is L-valyl-L-alanine.

[0026] Embodiment 20. The compound of any one of Embodiments 12-19, or a pharmaceutically acceptable salt thereof, wherein R28is maleimide: optionally linked to a targeting agent.

[0027] Embodiment 21. The compound of any one of Embodiments 12-20, or a pharmaceutically acceptable salt thereof, wherein L2-R28 comprises

[0028] 

[0029]

[0030] tionally linked to a targeting agent. mbodiment 22. The compound of formula (I) and salts and solvates thereof of any one of mbodiments 21 to 17, linked, either directly or indirectly, to a targeting agent to provide a geted conjugate. mbodiment 23. The compound of formula (I) and salts and solvates thereof of Embodiment wherein the compound comprises at least one L2-R28 group and the targeting agent is linked the compound through the L2-R28 group. mbodiment 24. The compound as claimed in any one of Embodiments 20 to 23, wherein the geting agent comprises an antibody, an antibody fragment, a hormone or a hormone gment. mbodiment 25. A compound of formula (I) and salts and solvates thereof according to any one Embodiments 1 to 24 for use as a medicament. mbodiment 26. A compound of formula (I) and salts and solvates thereof according to any one Embodiment 1 to 24 for use in the treatment of a proliferative disease. mbodiment 27. The compound of formula (I) and salts and solvates thereof according to mbodiment 26 for use in the treatment of a proliferative disease, wherein the proliferative disease is selected from bladder cancer, bone cancer, bowel cancer, brain cancer, breast cancer, cervical cancer, colon cancer, head and neck cancer, leukemia, liver cancer, lung cancer, lymphoma, melanoma, oesophageal cancer, oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, rectal cancer, renal cancer, retinoblastoma, sarcoma, skin cancer, stomach cancer, testicular cancer, thyroid cancer and uterine cancer. Embodiment 28. A pharmaceutical composition comprising a compound of formula (I) and salts and solvates thereof of any one of Embodiments 1 to 24 and a pharmaceutically acceptable excipient, carrier or diluent. Embodiment 29. Use of a compound of formula (I) and salts and solvates thereof according to any one of Embodiments 1 to 28 in the manufacture of a medicament for treating a proliferative disease. Embodiment 30. A method of treatment of a patient suffering from a proliferative disease, comprising administering to said patient a therapeutically effective amount of a compound of any one of Embodiments 1 to 24 or a pharmaceutical composition of Embodiment 28. Embodiment 31. The method of Embodiment 30, wherein the proliferative disease is selected from bladder cancer, bone cancer, bowel cancer, brain cancer, breast cancer, cervical cancer, colon cancer, head and neck cancer, leukemia, liver cancer, lung cancer, lymphoma, melanoma, oesophageal cancer, oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, rectal cancer, renal cancer, retinoblastoma, sarcoma, skin cancer, stomach cancer, testicular cancer, thyroid cancer and uterine cancer. Embodiment 32. An antibody-drug conjugate comprising a compound of formula (I) and salts and solvates thereof according to any one of Embodiment 1 to 24 Further particular and preferred aspects are set out in the accompanying independent and dependent claims. Features of the dependent claims may be combined with features of the independent claims as appropriate, and in combinations other than those explicitly set out in the claims. EXAMPLES Example 1: Synthesis of A-alkylator compounds, PDD-C8 subsituted compounds, PDD- N11 substituted compounds, and control compounds General synthetic methods. All reagents and solvents were purchased from standard commercial suppliers and used as purchased. Anhydrous reactions were carried out under an inert atmosphere of argon using anhydrous solvents which were used as purchased, without further drying. Thin Layer Chromatography (TLC) was performed on silica gel aluminium plates (Merck 60, F254), and flash column chromatography was carried out using a Biotage Isolera One (automated flash chromatography system), whilst monitoring by TLC (UV, 254 nm). All Nuclear Magnetic Resonance (NMR) spectra were obtained at room temperature using a Bruker 600 MHz Ultrashield with Cryoprobe (Bruker Avance NEO console with Cryoplatform) or a Varian Mercury Vx Agilent 400 MHz spectrometer, for which chemical shifts are expressed in ppm relative to the solvent and coupling constants are expressed in Hz. Microwave reactions were carried out on a Biotage Initiator+ microwave synthesizer. High Resolution Mass Spectrometry (HRMS) was performed on a Thermo Scientific-Exactive HCD Orbitrap Mass Spectrometer. Yields refer to isolated material (homogeneous by TLC and NMR) unless otherwise stated and names are assigned according to IUPAC nomenclature. Liquid Chromatography Mass Spectrometry (LCMS) analysis Methods A-C were performed on a Waters Alliance 2695 with water (A) and acetonitrile (B) comprising the mobile phases. Formic acid (0.1%) was added to both acetonitrile and water to ensure acidic conditions throughout the analysis. Function type: Diode array (535 scans). Column type: Monolithic C18 50 X 4.60 mm. Mass spectrometry data were collected using a Waters Micromass ZQ instrument coupled to the HPLC with a Waters 2996 PDA. Waters Micromass ZQ parameters used were: Capillary (kV), 3.38; Cone (V), 35; Extractor (V), 3.0; Source temperature (°C), 100; De-solvation Temperature (°C), 200; Cone flow rate (L / h), 50; De-solvation flow rate (L / h), 250. Gradient conditions are described as follows. Method A (10 min): from 95% A / 5% B to 50% B over 3 min. Then from 50% B to 80% B over 2 min. Then from 80% B to 95% B over 1.5 min and held constant for 1.5 min. This was then reduced to 5% B over 0.2 min and maintained to 5% B for 1.8 min. The flow rate was 0.5 mL / min, 200 μL was split via a zero dead volume T piece which passed into the mass spectrometer. The wavelength range of the UV detector was 220-400 nm. Method B (5 min): from 95% A / 5% B to 90% B over 3 min. Then from 90% B to 95% B over 0.5 min and held constant for 1 min. This was then reduced to 5% B over 0.5 min. The flow rate was 1.0 mL / min, 100 μL was split via a zero dead volume T piece which passed into the mass spectrometer. The wavelength range of the UV detector was 220-500 nm. Method C (5 min): from 95% A / 5% B, which was increased to 90% B over 3 min and to 95% B over a further 0.5 min. The gradient was then held at 95% B for 1 min and then returned to 5% B over 0.5 min. The total duration of the run was 5 minutes and the solvent flow rate was 1 mL / min, 100 μL was split via a zero dead volume T piece which passed into the mass spectrometer. The wavelength range of the UV detector was 220-500 nm. Liquid Chromatography Mass Spectrometry (LCMS) analysis Methods D-G were performed on a Shimadzu LC-20AD series, Binary Pump, Diode Array Detector. Column type: Agilent Poroshell 120 EC-C18, 2.7 μm, 4.6×50 mm. Mobile phase: A: 0.05% formic acid in water (v / v); B: 0.05% formic acid in acetonitrile (v / v). Flow Rate: 1 mL / min at 25 °C. Detector: 214 nm, 254 nm. Gradient stop time: 5 min. MS: 2020, Quadrupole LC / MS, Ion Source: API-ESI, TIC: 100-1300 m / z, Drying gas flow: 15 L / min, Nebulizer pressure: 1.5 L / min, Drying gas temperature: 250 °C, Vcap: 4500V. Sample preparation: samples were dissolved in methanol at 1-10 μg / mL, then filtered through a 0.22 μm filter membrane. Injection volume: 1-10 μL. Gradient conditions are described as follows. Method D (5 min): 20% A / 80% B for 0.5 min, which was increased to 100% B over 3.5 min, then held at 100% B for 0.5 min. This was then returned to 20% A / 80% B for 0.5 min. Method E (5 min): 50% A / 50% B for 0.5 min, which was increased to 100% B over 3.5 min, then held at 100% B for 0.5 min. This was then returned to 50% A / 50% B for 0.5 min. Method F (5 min): 85% A / 15% B for 0.5 min, which was increased to 100% B over 3.5 min, then held at 100% B for 0.5 min. This was then returned to 85% A / 15% B for 0.5 min. Method G (5 min): 97% A / 3% B for 0.5 min, which was increased to 30% A / 70% B over 3.5 min, then to 100% B over 0.5 min. This was then returned to 97% A / 3% B for 0.5 min. Optical rotations were measured on an SGWzz-1 automatic Polarimeter (Shanghai Shen Guang Instrument Co., Ltd.) or Bellingham-Stanley ADP 440+ Polarimeter. Reverse phase Preparative HPLC was carried out on a Shimadzu LC with CTC IFC, using a Phenomenex Gemini NX 5m, C18, 110 Å, 150 x 50 mm column, eluting with mobile phase: A) water (0.1% TFA), B) acetonitrile, at a flow of 50 mL / min.

[0031]

[0032]

[0033] Example 1A: Synthesis of compound (10). Scheme 5. Synthesis of compound (10). 3-(Methoxycarbonyl)-4-phenylbut-3-enoic acid (1) A solution of benzaldehyde (100 g, 942 mmol) and dimethyl succinate (206 g, 1.41 mol) in tert- butanol (500 mL) was added to a refluxing solution of potassium tert-butoxide (158 g, 1.41 mol) in tert-butanol (1.5 L) over 1 h. The mixture was then stirred for a further 30 min before being allowed to cool to room temperature. After concentrating in vacuo, the resulting residue was diluted with water (500 mL) and extracted with ethyl acetate (500 mL). The aqueous phase was then acidified to pH = 4-5 with an aqueous solution of hydrochloric acid (6 M), then extracted with ethyl acetate (1 L). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo to give the title compound (300 g, impure) as a yellow oil which was used in the subsequent step without further purification. MS (ES+): m / z = 221 (M+H)+; LCMS (Method F): tR = 3.23 min. Methyl 4-hydroxy-2-naphthoate (2) A solution of 3-(methoxycarbonyl)-4-phenylbut-3-enoic acid (1) (300 g) and trifluoroacetic anhydride (99.3 mL, 714 mmol) in tetrahydrofuran (1.5 L) was stirred at 70 °C for 5 h, after which, consumption of starting material was confirmed by TLC. The reaction mixture was then concentrated in vacuo, adjusted to pH = 8-9 with an aqueous solution of sodium hydroxide (1 M) and extracted with ethyl acetate (1 L). The organic phase was then dried over sodium sulfate and concentrated in vacuo. Recrystallisation from ethyl acetate / petroleum spirit, 40-60 °C (10%) gave the title compound (100 g, 53%) as a yellow solid. MS (ES+): m / z = 202 (M+H)+; LCMS (Method F): tR= 3.55 min. Methyl 4-(benzyloxy)-2-naphthoate (3) A solution of methyl 4-hydroxy-2-naphthoate (2) (200 g, 990 mmol), benzyl bromide (203 g, 1.19 mol) and caesium carbonate (386 g, 1.19 mol) in N,N-dimethylformamide (800 mL) was stirred at 90 °C for 16 h, after which TLC confirmed consumption of starting material. The mixture was diluted in ethyl acetate (1.5 L), washed with water (1 L x 2), then brine (500 mL), dried over sodium sulfate and concentrated in vacuo to give the title compound (250 g, 86%) as a white solid, which was used in the subsequent step without further purification. 4-(Benzyloxy)-2-naphthoic acid (4) A solution of methyl 4-(benzyloxy)-2-naphthoate (3) (250 g, 856 mmol) in toluene (500 mL) was charged with an aqueous solution of sodium hydroxide (12 M, 300 mL) and heated to 100 °C for 16 h, after which TLC confirmed the consumption of starting material. The organic phase was separated and concentrated in vacuo. The residue was then taken up into ethyl acetate (1.5 L) and acidified to pH = 2 with an aqueous solution of hydrochloric acid (6 M). The organic phase was separated, dried over sodium sulfate and concentrated in vacuo. Recrystallization from ethyl acetate / petroleum spirit, 40-60 °C (10%) gave the title compound (90 g, 32%) as a white solid. MS (ES+): m / z = 279 (M+H)+; LCMS (Method F): tR= 4.09 min. tert-Butyl (4-(benzyloxy)naphthalen-2-yl)carbamate (5) A solution of 4-(benzyloxy)-2-naphthoic acid (4) (50.0 g, 180 mmol), diphenyl phosphoryl azide (41.5 mL, 234 mmol) and triethylamine (28.9 mL, 270 mmol) in toluene (300 mL) was stirred at room temperature for 1 h, after which TLC showed consumption of starting material. tert-Butanol (200 mL) was added and the resulting mixture was stirred at 90 °C for 17 h. This was then diluted with ethyl acetate (1.5 L) and water (500 mL). The organic phase was separated, dried over sodium sulfate, filtered and concentrated in vacuo. Recrystallization from ethyl acetate / petroleum spirit, 40-60 °C (10%) gave the title compound (35 g, 56%) as a pink solid. MS (ES+): m / z = 350 (M+H)+; LCMS (Method F): tR= 4.67 min. tert-Butyl (4-(benzyloxy)-1-iodonaphthalen-2-yl)carbamate (6) A mixture of tert-butyl (4-(benzyloxy)naphthalen-2-yl)carbamate (5) (55.0 g, 157 mmol), iodic acid (5.50 g, 31.5 mmol) and iodine (16.0 g, 63 mmol) in methanol (400 mL) and water (100 mL) was stirred at 80 °C for 5 h, after which TLC showed consumption of starting material. The mixture was diluted with water (1.0 L) and filtered. The resulting cake was washed with methanol (200 mL) and concentrated in vacuo to give the title compound (72 g, 96%) as a brown solid. MS (ES+): m / z = 476 (M+H)+; LCMS (Method E): tR= 4.91 min. tert-Buty®)-(4-(benzyloxy)-1-iodonaphthalen-2-yl)(oxiran-2-ylmethyl)carbamate (7) A solution of tert-butyl (4-(benzyloxy)-1-iodonaphthalen-2-yl)carbamate (6) (52 g, 109 mmol) in N,N-dimethylformamide (500 mL) was charged with sodium hydride (60% dispersion in mineral oil, 17 g, 425 mmol) and stirred at room temperature for 30 min, after which (S)-oxiran- 2-ylmethyl 3-nitrobenzenesulfonate (51 g, 197 mmol) was added and the resulting mixture stirred for a further 3 h. TLC confirmed consumption of starting material. The reaction mixture was poured cautiously onto ice-water (500 mL) and extracted with ethyl acetate (1.0 L). The organic phase was separated, and washed with water (500 mL) and brine (300 mL), then dried over sodium sulfate and concentrated in vacuo to give the title compound (55 g, 95%) as a white solid.1H NMR (400 MHz, CDCl3) δ 8.33-8.32 (m, 1H), 8.41-8.20 (m, 1H), 7.59-7.48 (m, 4H), 7.45-7.33 (m, 3H), 6.94-6.83 (m, 1H), 5.28 (s, 2H), 4.15-4.09 (m, 1H), 3.50-3.42 (m, 1H), 3.14- 3.13 (m, 1H), 2.82-2.60 (m, 1H), 2.41 (ddd, J=12.4, 4.8, 2.8 Hz, 1H), 1.33-1.31 (m, 9H). tert-Butyl(S)-5-(benzyloxy)-1-(hydroxymethyl)-1,2-dihydro-3H-benzo[e]indole-3- carboxylate (8) Zinc chloride (1 M in tetrahydrofuran, 28 mL) was diluted in anhydrous tetrahydrofuran (40 mL) and cooled to 0 °C, under an inert atmosphere of argon. A solution of methyl lithium (1.6 M in diethyl ether, 70.6 mL) was then added to the cooled mixture, dropwise, and stirred for 30 min, before cooling further to -78 °C. (Trimethylsilyl)isothiocyanate (4 mL, 28.2 mmol) was added dropwise to the reaction mixture at -78 °C, before warming to 0 °C for 30 min and then again cooling to -78 °C. A solution of tert-buI (R)-(4-(benzyloxy)-1-iodonaphthalen-2- yl)(oxiran-2-ylmethyl)carbamate (7) (10 g, 18.8 mmol) in tetrahydrofuran (20 mL) was added dropwise to the reaction mixture at -78 °C for 30 min, then warmed to 0 °C for 1 h, followed by room temperature for 30 min. After quenching with a saturated aqueous solution of ammonium chloride, the mixture was extracted with dichloromethane (500 mL x 3) and the combined organics were washed with brine (100 mL), dried over sodium sulfate and concentrated in vacuo to give the title compound (10 g, impure), which was used in the subsequent step without further purification.1H NMR (400 MHz, CDCl3) δ 8.29 (d, J=8.4 Hz, 1H), 7.90 (s, 1H), 7.71 (d, J=8.2 Hz, 1H), 7.55 (d, J=6.8 Hz, 2H), 7.51-7.40 (m, 3H), 7.36-7.32 (m, 2H), 5.27 (s, 2H), 4.22 (d, J=11.4 Hz, 1H), 4.13 (t, J=10.0 Hz, 1H), 4.01-3.95 (m, 1H), 3.85 (bs, 1H), 3.81-3.73 (m, 1H), 1.60 (s, 9H); MS (ES+): m / z = 406 (M+H)+; LCMS (Method F): tR= 4.69 min. tert-Butyl(S)-5-(benzyloxy)-1-(chloromethyl)-1,2-dihydro-3H-benzo[e]indole-3-carboxylate (9) A solution of tert-butyl (S)-5-(benzyloxy)-1-(hydroxymethyl)-1,2-dihydro-3H-benzo[e]indole- 3-carboxylate (8) (10.0 g, 12.4 mmol), carbon tetrachloride (30 mL) and triphenylphosphine (3.90 g, 14.8 mmol) in dichloromethane (50 mL) was stirred at room temperature for 2 h, after which, TLC showed consumption of starting material. The reaction mixture was then concentrated in vacuo. Purification by flash column chromatography (silica), eluting with ethyl acetate / petroleum spirit, 40-60 °C (10%), followed by recrystallisation from dichloromethane / petroleum spirit, 40-60 °C (90%) gave the title compound (1.47 g, 28%) as a white solid. [^]D23= –14.5o(c 0.470, CH2Cl2);1H NMR (400 MHz, CDCl3) δ 8.29 (d, J=8.4 Hz, 1H), 7.86 (s, 1H), 7.65 (d, J=8.4 Hz, 1H), 7.58-7.30 (m, 7H), 5.27 (s, 2H), 4.27-4.24 (m, 1H), 4.13 (t, J=10.6 Hz, 1H), 4.01-3.87 (m, 2H), 3.44 (t, J=10.4 Hz, 1H), 1.61 (s, 9H); MS (ES+): m / z = 424 (M+H)+; LCMS (Method D): tR= 4.27 min. (S)-1-(Chloromethyl)-2,3-dihydro-1H-benzo[e]indol-5-ol hydrochloride (10) A solution of tert-butyl (S)-5-(benzyloxy)-1-(chloromethyl)-1,2-dihydro-3H-benzo[e]indole-3- carboxylate (9) (100 mg, 0.236 mmol) in anhydrous dichloromethane (3 mL) was charged with boron trichloride (1 M solution in dichloromethane, 708 µL, 0.708 mmol), in a dropwise manner via syringe, at room temperature and stirred under an inert atmosphere of argon. The resulting orange solution was stirred for 5 min before being quenched by cautious addition of methanol (5 mL), then concentrated in vacuo. The residue was charged again with methanol (5 mL) and re-concentrated in vacuo. Diethyl ether (5 mL) was then charged and the residue concentrated in vacuo once again. The residue was then subjected to high vacuum for 30 min to give the title compound (55 mg, impure) as a pale green crystalline solid (unstable), which was used immediately in the subsequent step (amide coupling) without further purification. MS (ES+): m / z = 234 (M+H)+; LCMS (Method C): tR= 2.62 min. Example 1B: Synthesis of compound (16). Scheme 6. Synthesis of compound (16). Methyl 4-bromo-1-methyl-1H-pyrrole-2-carboxylate (12) Sodium hydride (60% dispersion in mineral oil, 300 mg, 613 mmol) was diluted in N,N- dimethylformamide (10 mL) and stirred at 0°C. A solution of methyl 4-bromo-1H-pyrrole-2- carboxylate (11) (1.00 g, 4.90 mmol) was added over 10 min at 0°C. The resulting mixture was stirred at the same temperature for 30 min. Methyl iodide (1.04 g, 7.40 mmol) was then added to the reaction mixture, in a dropwise manner. After being stirred for 18 h at room temperature, the mixture was poured into water, and then extracted with ethyl acetate (20 mL x 2). The combined organic extracts were dried over magnesium sulfate and concentrated in vacuo. Purification by flash column chromatography (silica), eluting with ethyl acetate / petroleum spirit, 40-60 °C (20%) gave the title compound (0.96 g, 90%) as a white solid.1H NMR (400 MHz, CDCl3) δ 6.90 (s, 1H), 6.77 (s, 1H), 3.90 (s, 3H), 3.81 (s, 3H). Methyl4-(4-((tert-butoxycarbonyl)amino)phenyl)-1-methyl-1H-pyrrole-2-carboxylate (13) A solution of methyl 4-bromo-1-methyl-1H-pyrrole-2-carboxylate (12) (1.12 g, 5.14 mmol) and tert-butyl (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate (1.97 g, 6.16 mmol) in toluene, water and propan-2-ol (10 mL) was charged with potassium carbonate (2.14 g, 15.5 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.36 g, 0.31 mmol). The resulting mixture was then heated to 110 °C for 16 h, and subsequently cooled to room temperature before diluting into water (20 mL). The mixture was partitioned between ethyl acetate and brine, and the organic layer was then dried over sodium sulfate, filtered and concentrated in vacuo. Purification by flash column chromatography (silica), eluting with ethyl acetate / petroleum spirit, 40-60 °C (33%) gave the title compound (0.87 g, 51%) as a pale white solid.1H NMR (400 MHz, CDCl3) δ 7.42-7.37 (m, 2H), 7.36-7.32 (m, 2H), 7.16 (d, J=2.0 Hz, 1H), 7.02 (d, J=2.0 Hz, 1H), 6.56 (s, 1H), 3.94 (s, 3H), 3.83 (s, 3H), 1.45 (s, 9H);13C NMR (100 MHz, CDCl3) δ 161.7, 136.5, 129.4, 127.1, 125.9, 125.5, 123.6, 119.0, 115.6, 114.6, 60.4, 51.1, 36.9, 28.3; MS (ES+): m / z = 331 (M+H)+; LCMS (Method B): tR= 4.22 min. Methyl 4-(4-aminophenyl)-1-methyl-1H-pyrrole-2-carboxylate (14) A solution of methyl 4-(4-((tert-butoxycarbonyl)amino)phenyl)-1-methyl-1H-pyrrole-2- carboxylate (13) (4.8 g, 14.5 mmol) in 1,4-dioxane (20 mL) was charged with HCl (4 M in 1,4- dioxane, 20 mL) at room temperature. The resulting mixture was stirred at room temperature for 3 h, after which, TLC showed completion of reaction. The reaction was quenched with a saturated aqueous solution of sodium hydrogen carbonate and extracted with ethyl acetate (20 mL x 2). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. Purification by flash column chromatography (silica), eluting with ethyl acetate / petroleum spirit, 40-60 °C (25%) gave the title compound (3.1 g, 92%) as a light yellow solid.1H NMR (400 MHz, DMSO-d6) δ 7.36 (s, 1H), 7.21 (d, J=8.0 Hz, 2H), 7.03 (s, 1H), 6.54 (d, J=8.0 Hz, 2H), 5.00 (s, 2H), 3.85 (s, 3H), 3.74 (s, 3H); MS (ES+): m / z = 231 (M+H)+; LCMS (Method F): tR= 2.14 min. Methyl 4-(4-(4-((tert-butoxycarbonyl)amino)-1-methyl-1H-pyrrole-2- carboxamido)phenyl)-1-methyl-1H-pyrrole-2-carboxylate (15) A solution of methyl 4-(4-aminophenyl)-1-methyl-1H-pyrrole-2-carboxylate (14) (2.18 g, 9.47 mmol) and 4-((tert-butoxycarbonyl)amino)-1-methyl-1H-pyrrole-2-carboxylic acid (2.73 g, 11.4 mmol) in N,N-dimethylformamide (20 mL) was charged with 4-dimethylaminopyridine (2.89 g, 23.7 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (3.63 g, 18.9 mmol). The resulted mixture was stirred at room temperature for 16 h, then quenched with a saturated aqueous solution of sodium hydrogen carbonate, and extracted with ethyl acetate (20 mL x 2). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. Purification by flash column chromatography (silica), eluting with methanol / dichloromethane (2%) gave the title compound (3.61 g, 84%) as a light yellow solid.1H NMR (400 MHz, CDCl3) δ 8.01 (s, 1H), 7.71 (s, 1H), 7.54-7.49 (m, 2H), 7.44-7.40 (m, 2H), 7.17 (d, J=2.0 Hz, 1H), 7.03 (d, J=2.0 Hz, 1H), 6.85 (s, 1H), 6.63 (s, 1H), 3.94 (s, 3H), 3.88 (s, 3H), 3.83 (s, 3H), 1.50 (s, 9H);13C NMR (100 MHz, CDCl3) δ 161.7, 159.5, 136.0, 130.4, 126.0, 125.5, 123.5, 123.4, 121.8, 120.3, 118.6, 114.6, 110.0, 103.7, 51.1, 36.9, 36.7, 28.4; MS (ES+): m / z = 453 (M+H)+; LCMS (Method F): tR= 3.85 min. Methyl 4-(4-(4-amino-1-methyl-1H-pyrrole-2-carboxamido)phenyl)-1-methyl-1H-pyrrole- 2-carboxylate (16) A solution of methyl 4-(4-(4-((tert-butoxycarbonyl)amino)-1-methyl-1H-pyrrole-2- carboxamido)phenyl)-1-methyl-1H-pyrrole-2-carboxylate (15) (2.42 g, 5.35 mmol) in 1,4- dioxane (20 mL) was charged with HCl (4 M in 1,4-dioxane, 20 mL) at room temperature. The resulting mixture was stirred at room temperature for 3 h, after which TLC revealed consumption of starting material. The reaction was quenched with a saturated aqueous solution of sodium hydrogen carbonate and extracted with ethyl acetate (20 mL x 2). The combined organic extracts was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was triturated with dichloromethane / diethyl ether (1:8) (30 mL) to afford the title compound (1.71 g, 90%) as a light-yellow solid.1H NMR (400 MHz, DMSO-d6) δ 9.52 (s, 1H), 7.67 (d, J=8.0 Hz, 2H), 7.55 (s, 1H), 7.49 (d, J=8.0 Hz, 2H), 7.19 (s, 1H), 6.46 (s, 1H), 6.32 (s, 1H), 3.88 (br, 5H), 3.76 (s, 3H), 3.73 (s, 3H); MS (ES+): m / z = 353 (M+H)+; LCMS (Method F): tR= 2.41 min. Example 1C: Synthesis of compound (18). Scheme 7. Synthesis of compound (18). 6-((5-((4-(5-(Methoxycarbonyl)-1-methyl-1H-pyrrol-3-yl)phenyl)carbamoyl)-1-methyl-1H- pyrrol-3-yl)amino)-6-oxohexanoic acid (17) A solution of adipic acid (38 mg, 0.26 mmol) in dichloromethane (0.5 mL) was charged with triethylamine (151 µL, 1.08 mmol) and HATU (103 mg, 0.27 mmol) and stirred for 5 min before the addition of methyl 4-(4-(4-amino-1-methyl-1H-pyrrole-2-carboxamido)phenyl)-1- methyl-1H-pyrrole-2-carboxylate (16) (100 mg, 0.26 mmol). The resulting mixture was stirred for 18 h, then charged with water (10 mL), and extracted with ethyl acetate (20 mL x 2). The aqueous layer was then acidified to pH = 6 with cautious addition of hydrochloric acid (1 M, aqueous), and extracted with ethyl acetate (20 mL x 2). The combined organic extracts were dried over magnesium sulfate and concentrated in vacuo. The resulting residue was used in the subsequent step with no further purification. MS (ES+): m / z = 480 (M+H)+; LCMS (Method A): tR= 6.33 min. Methyl (S)-4-(4-(4-(6-(1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benzo[e]indol-3-yl)-6- oxohexanamido)-1-methyl-1H-pyrrole-2-carboxamido)phenyl)-1-methyl-1H-pyrrole-2- carboxylate (18) A solution of 6-((5-((4-(5-(methoxycarbonyl)-1-methyl-1H-pyrrol-3-yl)phenyl)carbamoyl)-1- methyl-1H-pyrrol-3-yl)amino)-6-oxohexanoic acid (17) (34 mg, 0.071 mmol) in N,N- dimethylacetamide (1 mL) was charged to (S)-1-(chloromethyl)-2,3-dihydro-1H-benzo[e]indol- 5-ol hydrochloride (10) (32 mg, 0.12 mmol), followed by N-(3-dimethylaminopropyl)-N′- ethylcarbodiimide hydrochloride (68 mg, 0.36 mmol) and the resulting mixture stirred at room temperature for 16 h. Further N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (68 mg, 0.36 mmol) was then added, and the mixture heated to 35 °C, with stirring, for 3 h. The mixture was then diluted into ethyl acetate (20 mL), extracted with cold brine (20 mL x 2), dried over magnesium sulfate, and concentrated in vacuo. Purification by flash column chromatography (silica), eluting with ethyl acetate / petroleum spirit, 40-60 °C (0% to 100%), gave the title compound (4.1 mg, 8%) as a white solid.1H NMR (400 MHz, DMSO-d6) δ 10.32 (s, 1H), 9.82 (s, 1H), 9.77 (s, 1H), 8.06 (d, J=8.5 Hz, 1H), 7.96 (s, 1H), 7.76 (d, J=8.3 Hz, 1H), 7.66 (d, J=8.5 Hz, 2H), 7.54 (s, 1H), 7.49 (d, J=8.3 Hz, 2H), 7.46 (d, J=8.2 Hz, 1H), 7.32-7.25 (m, 1H), 7.20 (s, 1H), 7.18 (s, 1H), 6.94 (s, 1H), 4.31 (t, J=10.2 Hz, 1H), 4.14 (m, 2H), 3.96 (m, 1H), 3.87 (s, 3H), 3.81 (s, 3H), 3.79-3.76 (m, 1H), 3.75 (s, 3H), 2.60-2.51 (m, 2H), 2.28 (m, 2H), 1.71-1.58 (m, 4H); MS (ES+): m / z = 697 (M+H)+; LCMS (Method A): tR= 7.80 min. Example 1D: Synthesis of compound (22). Scheme 8. Synthesis of compound (22).

[0034] Methyl 4-(4-(4-amino-1-methyl-1H-pyrrole-2-carboxamido)phenyl)-1-methyl-1H-pyrrole- 2-carboxylate hydrochloride (19) A solution of methyl 4-(4-(4-((tert-butoxycarbonyl)amino)-1-methyl-1H-pyrrole-2- carboxamido)phenyl)-1-methyl-1H-pyrrole-2-carboxylate (15) (1.0 g, 2.2 mmol) in 1,4-dioxane (15 mL) was charged with HCl (4 M in 1,4-dioxane, 15 mL) and stirred at room temperature for 6 h. Upon completion, the reaction mixture was concentrated in vacuo, diethyl ether was then added (15 mL) and the residue re-concentrated in vacuo to give the title compound as a beige solid, which was used directly in the next step without further purification.1H NMR (400 MHz, DMSO-d6) δ 10.11 (br, 2H), 9.98 (s, 1H), 7.69 (d, J=8.0 Hz, 2H), 7.58 (s, 1H), 7.53 (d, J=8.0 Hz, 2H), 7.21 (s, 1H), 7.20 (s, 1H), 7.11 (s, 1H), 3.89 (br, 6H), 3.76 (s, 3H); MS (ES+): m / z = 353 (M+H)+; LCMS (Method A): tR= 5.38 min. Methyl 4-(4-(4-(5-(tert-butoxy)-5-oxopentanamido)-1-methyl-1H-pyrrole-2- carboxamido)phenyl)-1-methyl-1H-pyrrole-2-carboxylate (20) A solution of pentanedioic acid mono-tert-butyl ester (125 mg, 0.67 mmol) in dichloromethane (1 mL) was charged with triethylamine (378 µL, 2.56 mmol) and HATU (258 mg, 0.67 mmol) and stirred at room temperature for 30 min. Methyl 4-(4-(4-amino-1-methyl-1H-pyrrole-2- carboxamido)phenyl)-1-methyl-1H-pyrrole-2-carboxylate hydrochloride (19) (250 mg, 0.64 mmol) was then added and the reaction mixture allowed to stir at room temperature for 16 h. Upon completion, the mixture was concentrated in vacuo. Flash column chromatography (silica), eluting with ethyl acetate / petroleum ether (from 30% to 80%) afforded the title compound (187 mg, 56%) as an off-white solid. MS (ES+): m / z = 523 (M+H)+; LCMS (Method A): tR= 7.62 min. 5-((5-((4-(5-(Methoxycarbonyl)-1-methyl-1H-pyrrol-3-yl)phenyl)carbamoyl)-1-methyl-1H- pyrrol-3-yl)amino)-5-oxopentanoic acid (21) Methyl 4-(4-(4-(5-(tert-butoxy)-5-oxopentanamido)-1-methyl-1H-pyrrole-2- carboxamido)phenyl)-1-methyl-1H-pyrrole-2-carboxylate (20) (170 mg, 0.33 mmol) was dissolved in HCl (1 M in 1,4-dioxane, 4 mL) and allowed to stir at room temperature for 16 h. Upon completion, the reaction mixture was charged with a saturated aqueous solution of sodium hydrogen carbonate (10 mL) and extracted with ethyl acetate (15 mL x 2). The combined organic layers were then dried over magnesium sulfate and concentrated in vacuo to give the title compound as a yellow solid, which was used in the next step without further purification. MS (ES+): m / z = 467 (M+H)+; LCMS (Method A): tR= 6.47 min. Methyl (S)-4-(4-(4-(5-(1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benzo[e]indol-3-yl)-5- oxopentanamido)-1-methyl-1H-pyrrole-2-carboxamido)phenyl)-1-methyl-1H-pyrrole-2- carboxylate (22) A solution of 5-((5-((4-(5-(methoxycarbonyl)-1-methyl-1H-pyrrol-3-yl)phenyl)carbamoyl)-1- methyl-1H-pyrrol-3-yl)amino)-5-oxopentanoic acid (21) (94 mg, 0.20 mmol) in N,N- dimethylacetamide (1 mL) was added to (S)-1-(chloromethyl)-2,3-dihydro-1H-benzo[e]indol-5- ol hydrochloride (10) (54 mg, 0.20 mmol) and N-(3-dimethylaminopropyl)-N′- ethylcarbodiimide hydrochloride (153 mg, 0.80 mmol). The reaction mixture was then stirred at room temperature for 16 h. Upon completion, the mixture was diluted into ethyl acetate and washed with cold brine (20 mL x 2), dried over magnesium sulfate and concentrated in vacuo. Flash column chromatography (silica), eluting with ethyl acetate / petroleum ether (from 60% to 100%), afforded the title compound (24 mg, 18%) as a white solid.1H NMR (400 MHz, DMSO-d6) δ 10.34 (br, 1H), 9.85 (br, 1H), 9.78 (br, 1H), 8.06 (d, J=8.2 Hz, 1H), 7.99 (s, 1H), 7.76 (d, J=8.6 Hz, 1H), 7.67 (d, J=8.2 Hz, 2H), 7.49 (m, 4H), 7.30 (t, J=8.0 Hz, 1H), 7.21 (s, 1H), 7.18 (s, 1H), 6.95 (s, 1H), 4.33-4.28 (m, 1H), 4.14-4.12 (m, 1H), 3.98-3.96 (m, 1H), 3.87 (s, 3H), 3.81 (s, 3H), 3.80-3.78 (m, 1H), 3.75 (s, 3H), 2.61-2.51 (m, 2H), 2.36 (t, J=7.4 Hz, 2H), 1.19 (t, J=7.4 Hz, 2H); MS (ES+): m / z = 682 (M+H)+; LCMS (Method A): tR= 7.67 min. Example 1E: Synthesis of compound (24). Scheme 9. Synthesis of compound (24). 4-((5-((4-(5-(Methoxycarbonyl)-1-methyl-1H-pyrrol-3-yl)phenyl)carbamoyl)-1-methyl-1H- pyrrol-3-yl)amino)-4-oxobutanoic acid (23) A solution of succinic acid (42 mg, 0.38 mmol) in dichloromethane (1 mL) was charged with triethylamine (225 µL, 1.56 mmol) and HATU (148 mg, 0.67 mmol) and stirred at room temperature for 30 min. Methyl 4-(4-(4-amino-1-methyl-1H-pyrrole-2-carboxamido)phenyl)-1- methyl-1H-pyrrole-2-carboxylate (16) (150 mg, 0.38 mmol) was then added and the reaction mixture allowed to stir at room temperature for 16 h. Upon completion, the mixture was concentrated in vacuo, and the residue used directly in the next step without further purification. MS (ES+): m / z = 453 (M+H)+; LCMS (Method A): tR= 6.45 min. Methyl (S)-4-(4-(4-(4-(1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benzo[e]indol-3-yl)-4- oxobutanamido)-1-methyl-1H-pyrrole-2-carboxamido)phenyl)-1-methyl-1H-pyrrole-2- carboxylate (24) A solution of 4-((5-((4-(5-(methoxycarbonyl)-1-methyl-1H-pyrrol-3-yl)phenyl)carbamoyl)-1- methyl-1H-pyrrol-3-yl)amino)-4-oxobutanoic acid (23) (170 mg, 0.38 mmol) in N,N- dimethylacetamide (1 mL) was added to (S)-1-(chloromethyl)-2,3-dihydro-1H-benzo[e]indol-5- ol hydrochloride (10) (101 mg, 0.38 mmol) and N-(3-dimethylaminopropyl)-N′- ethylcarbodiimide hydrochloride (288 mg, 1.50 mmol) and the resulting mixture stirred at room temperature for 16 h. The mixture was subsequently diluted into ethyl acetate and washed with cold brine (20 mL x 2), then dried over magnesium sulfate and concentrated in vacuo. Flash column chromatography (silica), eluting with ethyl acetate / petroleum ether (from 70% to 100%), afforded the title compound (13 mg, 5%) as a white solid.1H NMR (400 MHz, DMSO- d6) δ 10.31 (br, 1H), 9.93 (br, 1H), 9.77 (br, 1H), 8.06 (d, J=8.2 Hz, 1H), 7.94 (s, 1H), 7.77 (d, J=8.6 Hz, 1H), 7.67 (d, J=8.6 Hz, 2H), 7.53 (s, 1H), 7.50-7.46 (m, 3H), 7.30 (t, J=7.6 Hz, 1H), 7.19-7.18 (m, 2H), 6.97 (s, 1H), 4.36 (t, J=10.0 Hz, 1H), 4.21-4.16 (m, 2H), 4.01-3.98 (m, 1H), 3.87 (s, 3H), 3.81 (s, 3H), 3,79 (s, 1H), 3.75 (s, 3H), 2.84-2.77 (m, 2H), 2.63-2.60 (m, 2H); MS (ES+): m / z = 669 (M+H)+; LCMS (Method A): tR = 7.75 min. Example 1F: Synthesis of compound (29). Scheme 10. Synthesis of compound (29). Ethyl 6-aminoimidazo[1,2-a]pyridine-2-carboxylate (25) A slurry of ethyl 6-nitroimidazo[1,2-a]pyridine-2-carboxylate (1.00 g, 4.25 mmol) in methanol (10 mL) was cooled to 0 °C and cautiously charged with hydrochloric acid (12 M, 3.5 mL). Zinc powder (1.11 g, 17.0 mmol) was then added, portion-wise, at the same temperature, resulting in a clear solution which was stirred at 5 °C for 30 min, before warming to room temperature, whereupon it was stirred for a further 30 min. The green slurry was then quenched by slow addition of ammonia (7 N in methanol, 10 mL), giving a beige solid (pH = 10). The solid was filtered under reduced pressure, and the resulting cake washed with methanol (20 mL x 2). The filtrate was then concentrated in vacuo, and the residue suspended in cold chloroform (35 mL). Water (15 mL) was then charged, followed by ammonia (35%, aqueous, 15 mL), to give a brown slurry, which was stirred until clear. The layers were separated, and the aqueous layer extracted with chloroform (20 mL). The combined organic extracts were washed with brine (10 mL), dried over magnesium sulfate, and concentrated in vacuo to give the title compound (367 mg, 42%) as a green solid, which was used in the next step without further purification.1H NMR (400 MHz, DMSO-d6) δ 8.30 (s, 1H), 7.65 (d, J=1.3 Hz, 1H), 7.35 (d, J=9.6 Hz, 1H), 6.93 (dd, J=9.6, 2.1 Hz, 1H), 5.08 (s, 2H), 4.24 (q, J=7.1 Hz, 2H), 1.27 (t, J=7.1 Hz, 3H); MS (ES+): m / z = 206 (M+H)+; LCMS (Method A): tR= 3.83 min. Ethyl6-(4-(methoxymethoxy)benzamido)imidazo[1,2-a]pyridine-2-carboxylate (26) A solution of 4-(methoxymethoxy)benzoic acid (216 mg, 1.18 mmol) in N,N-dimethylacetamide (1 mL) was charged with N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (272 mg, 1.42 mmol) and stirred at room temperature for 2 min. A pre-sonicated solution of ethyl 6- aminoimidazo[1,2-a]pyridine-2-carboxylate (25) (243 mg, 1.18 mmol) in N,N- dimethylacetamide (1.5 mL) was then added, and the resulting mixture stirred for 16 h at room temperature. Subsequently, after diluting into ethyl acetate (10 mL), the mixture was washed with cold brine (10 mL x 2), dried over magnesium sulfate and concentrated in vacuo to give the title compound (284 mg, 65%) as a green oil, which was used in the next step without any further purification. MS (ES+): m / z = 370 (M+H)+; LCMS (Method A): tR= 5.83 min. 6-(4-(Methoxymethoxy)benzamido)imidazo[1,2-a]pyridine-2-carboxylic acid (27) A solution of ethyl 6-(4-(methoxymethoxy)benzamido)imidazo[1,2-a]pyridine-2-carboxylate (26) (284 mg, 0.77 mmol) in tetrahydrofuran (2 mL) was charged with potassium hydroxide (1 M, aqueous, 2.3 mL) at room temperature and stirred for 1 h. The red / brown solution was then quenched by cautious addition of a saturated aqueous solution of citric acid, until pH = 6. The resulting yellow precipitate was filtered under reduced pressure and washed with ethyl acetate and water. Strong vacuum was then applied to the filtered solid for 30 min, affording the title compound (235 mg, 90%) as a cream solid, which was used in the next step without any further purification. MS (ES+): m / z = 342 (M+H)+; LCMS (Method A): tR = 4.88 min. (S)-N-(2-(1-(Chloromethyl)-5-hydroxy-2,3-dihydro-1H-benzo[e]indole-3- carbonyl)imidazo165olubilipyridin-6-yl)-4-(methoxymethoxy)benzamide (28) A slurry of 6-(4-(methoxymethoxy)benzamido)imidazo[1,2-a]pyridine-2-carboxylic acid (27) (80 mg, 0.23 mmol) in N,N-dimethylacetamide (1 mL) was charged to (S)-1-(chloromethyl)-2,3- dihydro-1H-benzo[e]indol-5-ol hydrochloride (10) (66 mg, 0.24 mmol), followed by N-(3- dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (137 mg, 0.71 mmol), and the resulting mixture stirred for 16 h. The mixture was subsequently diluted into ethyl acetate (10 mL), washed with cold brine (10 mL x 2), dried over magnesium sulfate and concentrated in vacuo. Purification was enacted by flash column chromatography (silica), eluting with ethyl acetate / petroleum ether (from 0% to 100%), afforded the title compound (50 mg, 38%) as a cream solid.1H NMR (400 MHz, DMSO-d6) δ 10.40 (s, 1H), 10.29 (s, 1H), 9.44-9.40 (m, 1H), 8.63 (s, 1H), 8.10 (d, J=8.2 Hz, 1H), 8.03 (br, 1H), 7.98 (d, J=9.3 Hz, 2H), 7.81 (d, J=8.4 Hz, 1H), 7.70 (d, J=9.7 Hz, 1H), 7.56 (dd, J=9.8, 2.0 Hz, 1H), 7.53-7.47 (m, 1H), 7.37-7.31 (m, 1H), 7.16 (d, J=9.3 Hz, 2H), 5.29 (s, 2H), 4.95 (d, J=11.4 Hz, 1H), 4.75 (dd, J=13.5, 6.9 Hz, 1H), 4.20-4.14 (m, 1H), 3.98 (dd, J=11.1, 3.0 Hz, 1H), 3.78 (dd, J=11.0, 7.8 Hz, 1H), 3.39 (s, 3H); MS (ES+): m / z = 557 (M+H)+; LCMS (Method A): tR= 6.70 min. (S)-N-(2-(1-(Chloromethyl)-5-hydroxy-2,3-dihydro-1H-benzo[e]indole-3- carbonyl)imidazo165olubilipyridin-6-yl)-4-hydroxybenzamide (29) (S)-N-(2-(1-(Chloromethyl)-5-hydroxy-2,3-dihydro-1H-benzo[e]indole-3-carbonyl)imidazo[1,2- a]pyridin-6-yl)-4-(methoxymethoxy)benzamide (28) (45 mg, 0.081 mmol) was charged with HCl (4 M in 1,4-dioxane, 2 mL) and the resulting green slurry stirred at room temperature for 10 min, whereupon it was charged with an excess of cold diethyl ether. After concentrating in vacuo, the mustard residue was purified by flash column chromatography (silica), eluting with methanol / ethyl acetate (from 0% to 55%) to give the title compound (5.47 mg, 13%) as a cream solid.1H NMR (400 MHz, DMSO-d6) δ 10.20 (s, 1H), 9.42 (s, 1H), 8.63 (s, 1H), 8.10 (d, J=8.4 Hz, 1H), 8.03 (br, 1H), 7.89 (d, J=8.2 Hz, 2H), 7.81 (d, J=8.1 Hz, 1H), 7.69 (d, J=9.7 Hz, 1H), 7.57 (dd, J=9.8, 1.2 Hz, 1H), 7.53-7.47 (m, 1H), 7.37-7.31 (m, 1H), 6.89 (d, J=8.1 Hz, 2H), 4.94 (d, J=11.3 Hz, 1H), 4.74 (t, J=10.5 Hz, 1H), 4.20-4.14 (m, 1H), 4.01-3.94 (m, 1H), 3.78 (dd, J=11.2, 7.9 Hz, 1H); MS (ES+): m / z = 513 (M+H)+; LCMS (Method A): tR= 6.17 min. Example 1G: Synthesis of compound (37). Scheme 11. Synthesis of compound (37). 4-(4-(4-((tert-Butoxycarbonyl)amino)-1-methyl-1H-pyrrole-2-carboxamido)phenyl)-1- methyl-1H-pyrrole-2-carboxylic acid (30) A solution of methyl 4-(4-(4-((tert-butoxycarbonyl)amino)-1-methyl-1H-pyrrole-2- carboxamido)phenyl)-1-methyl-1H-pyrrole-2-carboxylate (15) (5.00 g, 11.0 mmol) in tetrahydrofuran (15 mL), methanol (5 mL) and water (5 mL) was charged with lithium hydroxide (1.30 g, 54.2 mmol) and stirred at 30 °C for 16 h. The resulting mixture was then partially concentrated in vacuo (to remove methanol and tetrahydrofuran), affording a viscous emulsion, which was then diluted into ethyl acetate (250 mL) and acetone (10 mL). After acidifying to pH 5, with an aqueous solution of citric acid (1 M), the aqueous layer was separated and then extracted with ethyl acetate (250 mL), and the combined organic extracts were then dried over magnesium sulfate, filtered and concentrated in vacuo. The resulting beige solid residue was then triturated in diethyl ether / hexane (1:1) with rapid stirring, then filtered under reduced pressure, and then dried under strong vacuum, to give the title compound (3.3 g, 69%) as a cream solid.1H NMR (400 MHz, DMSO-d6) δ 12.23 (s, 1H), 9.75 (s, 1H), 9.11 (s, 1H), 7.70 (d, J=8.7 Hz, 2H), 7.53-7.44 (m, 3H), 7.13 (d, J=2.2 Hz, 1H), 6.99-6.90 (m, 2H), 3.87 (s, 3H), 3.81 (s, 3H), 1.46 (s, 9H); MS (ES+): m / z = 439 (M+H)+; LCMS (Method A): tR= 7.02 min. tert-Butyl (5-((4-(5-((4-aminophenyl)carbamoyl)-1-methyl-1H-pyrrol-3- yl)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamate (31) A solution of 4-(4-(4-((tert-butoxycarbonyl)amino)-1-methyl-1H-pyrrole-2- carboxamido)phenyl)-1-methyl-1H-pyrrole-2-carboxylic acid (30) (3.30 g, 7.53 mmol) in N,N- dimethylformamide (15 mL) was charged with triethylamine (4.40 mL, 31.6 mmol) and HATU (3.00 g, 7.90 mmol) and the resulting mixture was stirred for 10 min at room temperature, before adding 1,4-diaminobenzene (814 mg, 7.53 mmol), and stirring for 16 h. The reaction mixture was then diluted into ethyl acetate (250 mL) and washed with cold brine (100 mL) and an aqueous solution of sodium hydrogen carbonate (100 mL). The organic phase was then dried over magnesium sulfate, filtered, and concentrated in vacuo. Trituration from diethyl ether / hexane (1:1), with rapid stirring, followed by filtration under reduced pressure, and then drying under strong vacuum, gave the title compound (4 g, quant.) as a mustard solid.1H NMR (600 MHz, DMSO-d6) δ 9.75 (s, 1H), 9.47 (s, 1H), 9.11 (s, 1H), 7.70 (d, J=8.6 Hz, 2H), 7.47 (d, J=8.6 Hz, 2H), 7.38 (d, J=1.8 Hz, 1H), 7.33 (d, J=9.0 Hz, 2H), 7.29 (d, J=1.8 Hz, 1H), 6.93 (br, 2H), 6.53 (d, J=9.0 Hz, 2H), 4.86 (br, 2H), 3.89 (s, 3H), 3.81 (s, 3H), 1.46 (s, 9H); MS (ES+): m / z = 529 (M+H)+; LCMS (Method A): tR= 6.25 min. tert-Butyl (5-((4-(5-((4-(((allyloxy)carbonyl)amino)phenyl)carbamoyl)-1-methyl-1H-pyrrol- 3-yl)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamate (32) A solution of tert-butyl (5-((4-(5-((4-aminophenyl)carbamoyl)-1-methyl-1H-pyrrol-3- yl)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamate (31) (4.00 g, 7.57 mmol) in N,N- dimethylacetamide (15 mL) was cooled to 0 °C and charged with pyridine (1.40 mL, 17.4 mmol), followed by dropwise addition of allyl chloroformate (885 µL, 8.32 mmol). After stirring at 0 °C for 30 min, the reaction mixture was precipitated from diethyl ether, then filtered under reduced pressure. The resulting solid was taken up into hot methanol, then filtered again, under reduced pressure, to give the title compound (3.46 g, 75%) as a fine yellow solid.1H NMR (400 MHz, DMSO-d6) δ 9.78 (s, 2H), 9.66 (s, 1H), 9.14 (s, 1H), 7.73 (d, J=8.6 Hz, 2H), 7.65 (d, J=8.9 Hz, 2H), 7.50 (d, J=8.6 Hz, 2H), 7.46-7.39 (m, 4H), 6.96 (s, 2H), 6.01 (ddd, J=22.5, 10.6, 5.4 Hz, 1H), 5.38 (dd, J=17.2, 1.6 Hz, 1H), 5.26 (d, J=10.5 Hz, 1H), 4.63 (d, J=5.4 Hz, 2H), 3.92 (s, 3H), 3.84 (s, 3H), 1.49 (s, 9H); MS (ES+): m / z = 613 (M+H)+; LCMS (Method A): tR= 7.75 min. 5-((4-(5-((4-(((Allyloxy)carbonyl)amino)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3- yl)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3-aminium 2,2,2-trifluoroacetate (33) A solution of tert-butyl (5-((4-(5-((4-(((allyloxy)carbonyl)amino)phenyl)carbamoyl)-1-methyl- 1H-pyrrol-3-yl)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamate (32) (3.00 g, 4.90 mmol) in dichloromethane (10 mL) and trifluoroacetic acid (1.9 mL, 24.5 mmol) was stirred at room temperature for 16 h. The reaction mixture was then precipitated from diethyl ether and concentrated in vacuo. Diethyl ether (200 mL) was then added, and the mixture concentrated in vacuo once again. Strong vacuum was then applied to the residue for 1 h, to give the title compound (3.07 g, quant.) as a beige solid.1H NMR (400 MHz, DMSO-d6) δ 10.04 (s, 2H), 9.98 (s, 1H), 9.81 (s, 1H), 9.66 (s, 1H), 7.73 (d, J=8.6 Hz, 2H), 7.66 (d, J=8.9 Hz, 2H), 7.53 (d, J=8.9 Hz, 2H), 7.47 (s, 1H), 7.43 (d, J=7.3 Hz, 3H), 7.18 (s, 1H), 7.12 (s, 1H), 6.01 (ddd, J=22.4, 10.6, 5.4 Hz, 1H), 5.38 (d, J=17.3 Hz, 1H), 5.26 (d, J=10.5 Hz, 1H), 4.63 (d, J=5.3 Hz, 2H), 3.92 (s, 6H); MS (ES+): m / z = 513 (M+H)+; LCMS (Method A): tR= 5.62 min. tert-Butyl 5-((5-((4-(5-((4-(((allyloxy)carbonyl)amino)phenyl)carbamoyl)-1-methyl-1H- pyrrol-3-yl)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)amino)-5-oxopentanoate (34) A solution of 5-(tert-butoxy)-5-oxopentanoic acid (922 mg, 4.90 mmol) in N,N- dimethylformamide (5 mL) was charged with triethylamine (2.9 mL, 20.6 mmol) and HATU (1.95 g, 5.14 mmol) and the resulting mixture stirred for 10 min at room temperature. To this, a solution of 5-((4-(5-((4-(((allyloxy)carbonyl)amino)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3- yl)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3-aminium 2,2,2-trifluoroacetate (33) (3.07 g, 4.90 mmol) in N,N-dimethylformamide (5 mL) was then added, and the resulting mixture stirred at room temperature for 16 h. Precipitation was instigated by addition of a saturated aqueous solution of sodium hydrogen carbonate. After filtration under reduced pressure, the resulting solid was taken up into hot methanol and again filtered under reduced pressure to give the title compound (2.26 g, 67%) as a cream solid.1H NMR (600 MHz, DMSO-d6) δ 9.81 (s, 1H), 9.79 (s, 1H), 9.76 (s, 1H), 9.63 (br, 1H), 7.71 (d, J=8.6 Hz, 2H), 7.63 (d, J=8.9 Hz, 2H), 7.49 (d, J=8.6 Hz, 2H), 7.45-7.35 (m, 4H), 7.20 (d, J=1.7 Hz, 1H), 6.96 (d, J=1.8 Hz, 1H), 5.99 (ddd, J=22.6, 10.7, 5.4 Hz, 1H), 5.36 (dd, J=17.2, 1.6 Hz, 1H), 5.24 (dd, J=10.5, 1.4 Hz, 1H), 4.60 (d, J=5.4 Hz, 2H), 3.90 (s, 3H), 3.83 (s, 3H), 2.27 (t, J=7.4 Hz, 2H), 2.24 (t, J=7.4 Hz, 2H), 1.78 (p, J=7.5 Hz, 2H), 1.41 (s, 9H);13C NMR (150 MHz, DMSO-d6) δ 172.4, 169.4, 160.1, 160.0, 153.7, 137.6, 134.9, 134.6, 133.9, 130.0, 126.7, 125.7, 124.9, 123.2, 122.5, 122.4, 121.0, 120.9, 119.3, 118.0, 110.7, 105.3, 80.0, 65.0, 36.9, 36.6, 35.0, 34.6, 28.3, 21.3; MS (ES+): m / z = 683 (M+H)+; LCMS (Method A): tR= 7.70 min. 5-((5-((4-(5-((4-(((Allyloxy)carbonyl)amino)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3- yl)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)amino)-5-oxopentanoic acid (35) A slurry of tert-butyl 5-((5-((4-(5-((4-(((allyloxy)carbonyl)amino)phenyl)carbamoyl)-1-methyl- 1H-pyrrol-3-yl)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)amino)-5-oxopentanoate (34) (2.26 g, 3.31 mmol) in dichloromethane (7 mL) was charged with trifluoroacetic acid (3 mL), resulting in an amber / brown solution, which was stirred at room temperature for 16 h. Further trifluoroacetic acid (3 mL) was then charged, and the mixture stirred for a further 2 h. Once the reaction was judged to be complete by TLC and LCMS, the mixture was cooled to 0 °C and diethyl ether (excess) added, and the resulting precipitate filtered under reduced pressure. The precipitate was dried under strong vacuum, to afford the title compound (1.68 g, 81%) as a beige solid. MS (ES+): m / z = 627 (M+H)+; LCMS (Method A): tR= 6.75 min. Allyl (S)-(4-(4-(4-(4-(5-(1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benzo[e]indol-3-yl)-5- oxopentanamido)-1-methyl-1H-pyrrole-2-carboxamido)phenyl)-1-methyl-1H-pyrrole-2- carboxamido)phenyl)carbamate (36) A slurry containing 5-((5-((4-(5-((4-(((allyloxy)carbonyl)amino)phenyl)carbamoyl)-1-methyl- 1H-pyrrol-3-yl)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)amino)-5-oxopentanoic acid (35) (1.68 g, 2.68 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (2.05 g, 10.7 mmol) in N,N-dimethylacetamide (5 mL) was sonicated for 10 min, then added to (S)-1- (chloromethyl)-2,3-dihydro-1H-benzo[e]indol-5-ol hydrochloride (10) (765 mg, 2.83 mmol), and the resulting mixture stirred for 16 h at room temperature. Further (S)-1-(chloromethyl)-2,3- dihydro-1H-benzo[e]indol-5-ol hydrochloride (10) (765 mg, 2.83 mmol) and N-(3- dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (2.05 g, 10.7 mmol) were added to the reaction mixture, which was then stirred for a further 16 h, at room temperature. Precipitation was effected by addition of cold water (excess). After filtration under reduced pressure, the solid residue was washed with water, and then dried under strong vacuum, to give the title compound (impure, 3.0 g) as a grey / green solid, which was used in the subsequent step without further intermediate purification.1H NMR (600 MHz, DMSO-d6) δ 10.40 (s, 1H), 9.98 (s, 1H), 9.84 (s, 2H), 9.65 (s, 1H), 8.08 (d, J=8.4 Hz, 1H), 8.01 (s, 1H), 7.77 (d, J=8.3 Hz, 1H), 7.72 (d, J=8.5 Hz, 2H), 7.65 (d, J=8.5 Hz, 2H), 7.49 (d, J=8.6 Hz, 3H), 7.44 (s, 2H), 7.40 (d, J=8.5 Hz, 2H), 7.33-7.29 (m, 1H), 7.23 (s, 1H), 7.00 (s, 1H), 5.98 (ddd, J=22.6, 10.7, 5.4 Hz, 1H), 5.36 (dd, J=17.2, 1.5 Hz, 1H), 5.24 (d, J=10.4 Hz, 1H), 4.60 (d, J=5.4 Hz, 2H), 4.32 (t, J=10.4 Hz, 1H), 4.14 (d, J=8.8 Hz, 2H), 3.98 (d, J=8.5 Hz, 1H), 3.90 (s, 3H), 3.83 (s, 3H), 3.81- 3.77 (m, 1H), 2.39 (dd, J=8.9, 4.7 Hz, 3H), 1.94 (dt, J=13.4, 12.1 Hz, 3H); MS (ES+): m / z = 842 (M+H)+; LCMS (Method A): tR= 7.82 min. (S)-N-(4-Aminophenyl)-4-(4-(4-(5-(1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H- benzo[e]indol-3-yl)-5-oxopentanamido)-1-methyl-1H-pyrrole-2-carboxamido)phenyl)-1- methyl-1H-pyrrole-2-carboxamide (37) A solution of allyl (S)-(4-(4-(4-(4-(5-(1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H- benzo[e]indol-3-yl)-5-oxopentanamido)-1-methyl-1H-pyrrole-2-carboxamido)phenyl)-1- methyl-1H-pyrrole-2-carboxamido)phenyl)carbamate (36) (30 mg, 0.036 mmol) in dichloromethane (1 mL) was charged with boron trichloride (1 M solution in dichloromethane, 400 µL) and the resulting mixture aged at room temperature, under argon, for 4 days. The reaction was quenched by addition of methanol (10 mL), and then concentrated in vacuo. Purification by flash column chromatography (silica), eluting with methanol / dichloromethane (12%) gave the title compound (6 mg, 22%) as a grey solid.1H NMR (600 MHz, DMSO-d6) δ 10.35 (s, 1H), 9.88-9.81 (m, 1H), 9.77 (s, 1H), 9.48 (s, 1H), 8.08 (d, J=8.2 Hz, 1H), 8.00 (s, 1H), 7.78 (d, J=8.4 Hz, 1H), 7.70 (d, J=8.7 Hz, 2H), 7.48 (dd, J=11.4, 4.4 Hz, 2H), 7.39 (d, J=1.8 Hz, 1H), 7.35-7.31 (m, 2H), 7.29 (t, J=5.3 Hz, 1H), 7.24-7.19 (m, 2H), 6.99-6.93 (m, 2H), 6.55-6.50 (m, 2H), 4.87 (br, 2H), 4.32 (t, J=10.4 Hz, 1H), 4.15 (d, J=11.3 Hz, 2H), 4.02-3.95 (m, 1H), 3.89 (s, 3H), 3.83 (s, 3H), 3.79 (dd, J=11.0, 7.9 Hz, 1H), 2.42-2.25 (m, 6H);13C NMR (150 MHz, DMSO-d6) δ 179.2, 173.5, 169.8, 169.4, 160.0, 145.3, 137.5, 130.1, 128.7, 127.7, 127.2, 126.7, 126.0, 125.1, 124.8, 123.6, 123.2, 123.1, 123.0, 122.6, 122.4, 122.3, 121.0, 119.3, 114.2, 110.1, 105.3, 53.1, 52.5, 51.7, 36.8, 36.6, 35.0, 33.1, 21.1; MS (ES+): m / z = 758 (M+H)+; LCMS (Method A): tR= 6.93 min. Example 1H: Synthesis of compound (39). Scheme 12. Synthesis of compound (39). 2-(3-(2-((5-((4-(5-(Methoxycarbonyl)-1-methyl-1H-pyrrol-3-yl)phenyl)carbamoyl)-1- methyl-1H-pyrrol-3-yl)amino)-2-oxoethyl)phenyl)acetic acid (38) A solution of 2-2-(1,3-phenylene)diacetic acid (171 mg, 0.88 mmol) in N,N-dimethylacetamide (1 mL) was charged with methyl 4-(4-(4-amino-1-methyl-1H-pyrrole-2-carboxamido)phenyl)- 1-methyl-1H-pyrrole-2-carboxylate (16) (150 mg, 0.43 mmol) and N-(3-dimethylaminopropyl)- N′-ethylcarbodiimide hydrochloride (186 mg, 0.97 mmol), and stirred at room temperature for 16 h. The reaction mixture was then diluted into ethyl acetate (100 mL) and washed with cold brine (2 x 50 mL). After drying over magnesium sulfate and concentrating in vacuo, the residue was purified by flash column chromatography (silica), eluting with methanol / ethyl acetate (10%), to give the title compound (86 mg, 38%) as a yellow oil. MS (ES+): m / z = 529 (M+H)+; LCMS (Method A): tR= 6.88 min. Methyl (S)-4-(4-(4-(2-(3-(2-(1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benzo[e]indol-3- yl)-2-oxoethyl)phenyl)acetamido)-1-methyl-1H-pyrrole-2-carboxamido)phenyl)-1-methyl- 1H-pyrrole-2-carboxylate (39) A solution of 2-(3-(2-((5-((4-(5-(methoxycarbonyl)-1-methyl-1H-pyrrol-3- yl)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)amino)-2-oxoethyl)phenyl)acetic acid (38) (86 mg, 0.16 mmol) in N,N-dimethylacetamide (1 mL) was charged with (S)-1-(chloromethyl)-2,3- dihydro-1H-benzo[e]indol-5-ol hydrochloride (10) (43 mg, 0.16 mmol) and N-(3- dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (123 mg, 0.64 mmol) and stirred at room temperature for 16 h. The reaction mixture was then diluted into ethyl acetate (100 mL) and washed with cold brine (2 x 50 mL). After drying over magnesium sulfate and concentrating in vacuo, the residue was purified by flash column chromatography (silica), eluting with ethyl acetate / petroleum spirit, 40-60 °C (from 50% to 100%), to give the title compound (12 mg, 10%) as an off-white solid.1H NMR (600 MHz, DMSO-d6) δ 10.36 (s, 1H), 10.09 (s, 1H), 9.78 (s, 1H), 8.08 (d, J=8.3 Hz, 1H), 7.96 (s, 1H), 7.77 (d, J=8.4 Hz, 1H), 7.68 (d, J=8.7 Hz, 2H), 7.55 (d, J=1.8 Hz, 1H), 7.50 (d, J=8.7 Hz, 2H), 7.48 (d, J=7.5 Hz, 1H), 7.34- 7.29 (m, 2H), 7.28 (d, J=1.8 Hz, 1H), 7.25-7.21 (m, 1H), 7.21-7.17 (m, 3H), 6.97 (d, J=1.8 Hz, 1H), 4.35 (t, J=9.9 Hz, 1H), 4.28 (dd, J=10.7, 1.8 Hz, 1H), 4.13 (t, J=8.3 Hz, 1H), 3.98-3.92 (m, 1H), 3.91-3.87 (m, 4H), 3.81 (s, 3H), 3.77 (s, 3H), 3.73 (dd, J=11.0, 8.1 Hz, 1H), 3.59 (s, 2H);13C NMR (150 MHz, DMSO-d6) δ 169.5, 167.9, 162.8, 161.3, 160.0, 154.8, 142.4, 137.8, 136.8, 135.5, 130.4, 129.4, 128.7, 128.1, 127.7, 127.5, 125.1, 123.6, 123.3, 123.2, 123.1, 122.7, 122.5, 122.2, 120.8, 119.3, 114.5, 114.3, 105.4, 100.3, 53.4, 51.5, 48.1, 43.1, 42.8, 41.3, 38.7, 37.0, 36.6; MS (ES+): m / z = 744 (M+H)+; LCMS (Method A): tR= 8.02 min. Example 1I: Synthesis of compound (42). Scheme 13. Synthesis of compound (42). (S)-7-(1-(Chloromethyl)-5-hydroxy-1,2-dihydro-3H-benzo[e]indol-3-yl)-7-oxoheptanoic acid (41) A solution of pimelic acid (135 mg, 0.50 mmol) in N,N-dimethylacetamide (1 mL) was charged with (S)-1-(chloromethyl)-2,3-dihydro-1H-benzo[e]indol-5-ol hydrochloride (10) (160 mg, 1.00 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (211 mg, 1.10 mmol) and the resulting mixture was stirred at room temperature for 16 h. After diluting into ethyl acetate (100 mL), and washing with cold brine (2 x 50 mL), the organic phase was dried over magnesium sulfate and concentrated in vacuo. Flash column chromatography (silica), eluting with ethyl acetate / petroleum spirit, 40-60 °C (from 50% to 100%) afforded the title compound (138 mg, 59%) as an off-white solid. MS (ES+): m / z = 376 (M+H)+; LCMS (Method A): tR= 6.98 min. Methyl (S)-4-(4-(4-(7-(1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benzo[e]indol-3-yl)-7- oxoheptanamido)-1-methyl-1H-pyrrole-2-carboxamido)phenyl)-1-methyl-1H-pyrrole-2- carboxylate (42) A solution of (S)-7-(1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benzo[e]indol-3-yl)-7- oxoheptanoic acid (41) (133 mg, 0.29 mmol) in N,N-dimethylacetamide (1 mL) was charged with methyl 4-(4-(4-amino-1-methyl-1H-pyrrole-2-carboxamido)phenyl)-1-methyl-1H-pyrrole- 2-carboxylate hydrochloride (19) (113 mg, 0.29 mmol) and N-(3-dimethylaminopropyl)-N′- ethylcarbodiimide hydrochloride (222 mg, 1.16 mmol) and the resulting mixture was stirred at room temperature for 16 h. After diluting into ethyl acetate (100 mL) and washing with cold brine (2 x 50 mL), the organic phase was dried over magnesium sulfate and concentrated in vacuo. Flash column chromatography (silica), eluting with ethyl acetate / petroleum spirit, 40-60 °C (from 75% to 100%) afforded the title compound (13 mg, 6%) as a white solid.1H NMR (600 MHz, DMSO-d6) δ 10.32 (s, 1H), 9.79 (d, J=8.9 Hz, 2H), 8.07 (d, J=8.3 Hz, 1H), 7.99 (s, 1H), 7.77 (d, J=8.4 Hz, 1H), 7.68 (d, J=8.7 Hz, 2H), 7.55 (d, J=1.9 Hz, 1H), 7.51 (d, J=8.6 Hz, 2H), 7.49-7.46 (m, 1H), 7.31 (t, J=7.7 Hz, 1H), 7.20 (dd, J=7.5, 1.9 Hz, 2H), 6.95 (d, J=1.8 Hz, 1H), 4.33 (t, J=10.0 Hz, 1H), 4.15 (d, J=10.5 Hz, 2H), 3.98 (dd, J=10.4, 2.2 Hz, 1H), 3.89 (s, 3H), 3.82 (s, 3H), 3.81-3.77 (m, 1H), 3.77 (s, 3H), 2.59-2.52 (m, 1H), 2.46 (dd, J=16.1, 7.8 Hz, 1H), 2.27 (t, J=7.4 Hz, 2H), 1.63 (dd, J=13.3, 5.9 Hz, 4H), 1.44-1.35 (m, 2H); MS (ES+): m / z = 710 (M+H)+; LCMS (Method A): tR = 7.88 min. Example 1J: Synthesis of compound (43). Scheme 14. Synthesis of compound (43). Methyl(S)-4-(4-(4-(5-(5-hydroxy-1-methyl-1,2-dihydro-3H-benzo[e]indol-3-yl)-5- oxopentanamido)-1-methyl-1H-pyrrole-2-carboxamido)phenyl)-1-methyl-1H-pyrrole-2- carboxylate (43) A solution of methyl (S)-4-(4-(4-(5-(1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H- benzo[e]indol-3-yl)-5-oxopentanamido)-1-methyl-1H-pyrrole-2-carboxamido)phenyl)-1- methyl-1H-pyrrole-2-carboxylate (22) (10 mg, 0.015 mmol) in tetrahydrofuran (1 mL) was charged with ammonium formate (7.4 mg, 0.117 mmol) and palladium on charcoal (10 wt.%) (10 mg), and the resulting mixture heated to 65 °C for 3 h, under argon. After cooling to room temperature, the mixture was filtered over celite and the resulting cake washed with ethyl acetate and water. The phases were separated and the organic layer washed with brine and concentrated in vacuo, to give the title compound (7.7 mg, 81%) as a white solid.1H NMR (600 MHz, DMSO-d6) δ 10.16 (s, 1H), 9.85 (s, 1H), 9.79 (s, 1H), 8.07 (d, J=8.3 Hz, 1H), 7.99 (s, 1H), 7.72 (dd, J=8.6, 4.9 Hz, 1H), 7.70-7.66 (m, 2H), 7.56 (t, J=6.0 Hz, 1H), 7.51 (d, J=8.7 Hz, 2H), 7.45 (dd, J=11.2, 4.0 Hz, 1H), 7.29 (t, J=7.5 Hz, 1H), 7.22 (d, J=1.7 Hz, 1H), 7.19 (t, J=3.6 Hz, 1H), 6.96 (d, J=1.8 Hz, 1H), 4.32-4.25 (m, 1H), 3.89 (s, 3H), 3.83 (s, 3H), 3.77 (br, 4H), 2.37 (t, J=7.5 Hz, 2H), 1.92 (dt, J=14.6, 7.3 Hz, 2H), 1.29 (t, J=6.9 Hz, 3H), 1.24 (br, 3H);13C NMR (150 MHz, DMSO-d6) δ 171.1, 169.8, 161.3, 160.1, 153.7, 140.7, 137.8, 130.2, 129.4, 127.5, 127.2, 125.1, 123.5, 123.3, 123.2, 122.9, 122.7, 122.6, 122.2, 120.9, 120.3, 119.3, 114.3, 105.3, 100.4, 56.9, 51.5, 37.0, 36.6, 35.3, 34.9, 33.3, 30.9, 21.9, 21.0; MS (ES+): m / z = 648 (M+H)+; LCMS (Method A): tR= 7.60 min. Example 1K: Synthesis of compound (51). Scheme 15. Synthesis of compound (51). Methyl4-(((allyloxy)carbonyl)amino)-1-methyl-1H-pyrrole-2-carboxylate (45) A solution of methyl 4-amino-1-methyl-1H-pyrrole-2-carboxylate hydrochloride (44) (2.9 g, 15.2 mmol) in dichloromethane (30 mL) was cooled to 0 °C and charged with pyridine (2.8 mL, 35.0 mmol), followed by allyl chloroformate (1.8 mL, 16.7 mmol). The resulting mixture was stirred for 35 min before diluting into dichloromethane (30 mL) and then washing with a saturated aqueous solution of copper sulfate (2 x 50 mL), brine (2 x 50 mL), and a saturated aqueous solution of sodium hydrogen carbonate (50 mL). The organic phase was then dried over magnesium sulfate, filtered, and concentrated in vacuo, to give the title compound (3.4 g, 94%) as a yellow solid.1H NMR (600 MHz, DMSO-d6) δ 9.45 (s, 1H), 7.09 (s, 1H), 6.66 (s, 1H), 6.08-5.85 (m, 1H), 5.35-5.29 (m, 1H), 5.21 (ddd, J=10.5, 2.9, 1.4 Hz, 1H), 4.57 (dd, J=16.7, 3.4 Hz, 2H), 3.80 (s, 3H), 3.71 (s, 3H);13C NMR (150 MHz, DMSO-d6) δ 161.2, 153.6, 133.9, 123.2, 119.8, 119.4, 117.8, 108.0, 65.0, 51.4, 36.6; MS (ES+): m / z = 239 (M+H)+; LCMS (Method A): tR= 6.32 min. 4-(((Allyloxy)carbonyl)amino)-1-methyl-1H-pyrrole-2-carboxylic acid (46) A solution of methyl 4-(((allyloxy)carbonyl)amino)-1-methyl-1H-pyrrole-2-carboxylate (45) (3.4 g, 14.3 mmol) in tetrahydrofuran (30 mL) was charged with an aqueous solution of sodium hydroxide (1 M) (140 mL) and the resulting mixture was stirred rapidly, at room temperature, for 48 h. The reaction was monitored by LCMS and when complete, was quenched by addition of an aqueous solution of citric acid (1 M) until the pH was adjusted to 3-4. This was then extracted with ethyl acetate (2 x 100 mL). The combined organic extracts were then washed with brine (2 x 100 mL) and water (100 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting residue was rinsed with dichloromethane and filtered, to give the title compound (1.97 g.62%) as a yellow solid.1H NMR (600 MHz, DMSO-d6) δ 12.29 (br, 1H), 9.40 (s, 1H), 7.03 (s, 1H), 6.61 (s, 1H), 5.95 (ddd, J=22.5, 10.6, 5.4 Hz, 1H), 5.32 (dd, J=17.2, 1.1 Hz, 1H), 5.21 (dt, J=11.8, 1.3 Hz, 1H), 4.55 (d, J=5.1 Hz, 2H), 3.78 (s, 3H);13C NMR (150 MHz, DMSO-d6) δ 162.3, 153.6, 134.0, 122.9, 120.4, 119.3, 117.8, 108.1, 65.0, 36.6; MS (ES+): m / z = 225 (M+H)+; LCMS (Method A): tR= 5.33 min. Allyl (5-((4-((tert-butoxycarbonyl)amino)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3- yl)carbamate (47) A solution of 4-(((allyloxy)carbonyl)amino)-1-methyl-1H-pyrrole-2-carboxylic acid (46) (1.97 g, 8.79 mmol) in N,N-dimethylacetamide (18 mL) was charged with N-(3- dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (5.05 g, 26.4 mmol) and tert-butyl (4-aminophenyl)carbamate (2.20 g, 10.6 mmol) and the resulting mixture was stirred at room temperature for 18 h. This was then diluted into ethyl acetate (100 mL) and washed with brine (3 x 50 mL). The organic phase was then dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting residue was precipitated from dichloromethane and diethyl ether to give the title compound (3.26 g, 90%) as a cream solid.1H NMR (600 MHz, DMSO- d6) δ 9.68 (s, 1H), 9.44 (s, 1H), 9.22 (s, 1H), 7.56 (d, J=9.0 Hz, 2H), 7.36 (d, J=8.5 Hz, 2H), 6.96 (s, 1H), 6.88 (s, 1H), 6.01-5.92 (m, 1H), 5.33 (d, J=17.2 Hz, 1H), 5.22 (dd, J=10.5, 1.4 Hz, 1H), 4.57 (d, J=5.2 Hz, 2H), 3.81 (s, 3H), 1.47 (s, 9H);13C NMR (150 MHz, DMSO-d6) δ 160.0, 153.8, 153.3, 135.3, 134.2, 134.1, 123.5, 122.4, 121.1, 118.7, 118.1, 117.8, 105.0, 79.3, 65.0, 36.6, 28.6; MS (ES+): m / z = 415 (M+H)+; LCMS (Method A): tR= 7.17 min. tert-Butyl (4-(4-amino-1-methyl-1H-pyrrole-2-carboxamido)phenyl)carbamate (48) A slurry of allyl (5-((4-((tert-butoxycarbonyl)amino)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3- yl)carbamate (47) (500 mg, 1.21 mmol) in dichloromethane (5 mL) was charged with tetrakis(triphenylphosphine)palladium(0) (14 mg, 0.012 mmol) and pyrrolidine (121 µL, 1.45 mmol) and the resulting mixture was then sonicated until an amber solution formed, which was stirred at room temperature for 45 min. After filtering through celite and washing with dichloromethane, the mixture was concentrated in vacuo, then purified by flash column chromatography (silica), eluting with ethyl acetate / petroleum spirit, 40-60 °C (from 0% to 100%) affording the title compound (261 mg, 65%) as a beige solid.1H NMR (600 MHz, DMSO-d6) δ 9.41 (s, 1H), 9.20 (s, 1H), 7.56-7.53 (m, 2H), 7.34 (d, J=8.5 Hz, 2H), 6.43 (d, J=2.1 Hz, 1H), 6.30 (d, J=2.1 Hz, 1H), 3.72 (s, 3H), 2.74 (s, 2H), 1.47 (s, 9H);13C NMR (150 MHz, DMSO-d6) δ 160.1, 153.3, 135.0, 134.5, 132.2, 123.1, 120.9, 118.7, 116.6, 115.3, 79.2, 36.2, 28.6; MS (ES+): m / z = 331 (M+H)+; LCMS (Method A): tR= 5.32 min. 5-((5-((4-((tert-Butoxycarbonyl)amino)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3- yl)amino)-5-oxopentanoic acid (49) – method 1 tert-Butyl (4-(4-amino-1-methyl-1H-pyrrole-2-carboxamido)phenyl)carbamate (48) (244 mg, 0.74 mmol) was treated with glutaric anhydride (93 mg, 0.81 mmol), 4-dimethylaminopyridine (9 mg, 0.074 mmol) and pyridine (2.5 mL). The reaction was stood at room temperature for 1 h, whereupon it was concentrated in vacuo. The residue was then diluted into ethyl acetate (30 mL), and washed sequentially with a saturated aqueous solution of ammonium chloride (5 x 20 mL) and brine (2 x 20 mL), before drying over anhydrous magnesium sulfate and concentrating in vacuo, to give the title compound (180 mg, 55%) as an off-white solid.1H NMR (600 MHz, DMSO-d6) δ 12.04 (s, 1H), 9.81 (s, 1H), 9.70 (s, 1H), 9.23 (s, 1H), 7.57-7.55 (m, 2H), 7.37 (d, J=8.7 Hz, 2H), 7.19 (d, J=1.8 Hz, 1H), 6.92 (d, J=1.9 Hz, 1H), 3.82 (s, 3H), 2.30-2.23 (m, 4H), 1.80 (p, J=7.4 Hz, 2H), 1.47 (s, 9H);13C NMR (150 MHz, DMSO-d6) δ 174.6, 169.5, 160.0, 153.3, 135.3, 134.2, 124.4, 123.2, 122.5, 121.1, 119.1, 105.1, 79.3, 36.6, 35.1, 33.5, 28.6, 21.2; MS (ES+): m / z = 445 (M+H)+; LCMS (Method A): tR= 6.28 min. 5-((5-((4-((tert-Butoxycarbonyl)amino)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3- yl)amino)-5-oxopentanoic acid (49) – method 2 A solution of glutaric acid (1.07 g, 8.11 mmol) in dichloromethane (4 mL) was charged with triethylamine (2.3 mL, 16.2 mmol) and HATU (1.54 g, 4.06 mmol), and stirred for 5 min, before the addition of tert-butyl (4-(4-amino-1-methyl-1H-pyrrole-2- carboxamido)phenyl)carbamate (48) (1.34 g, 4.06 mmol). The reaction mixture was then stirred at room temperature for 18 h, whereupon it was concentrated in vacuo. Purification by flash column chromatography (silica), eluting with ethyl acetate / petroleum spirit, 40-60 °C (0% to 100%), followed by methanol / ethyl acetate (0% to 100%) gave the title compound as a brown solid, which was used in the next step without any further purification. MS (ES+): m / z = 445 (M+H)+; LCMS (Method A): tR= 6.38 min. tert-Butyl (S)-(4-(4-(5-(1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benzo[e]indol-3-yl)-5- oxopentanamido)-1-methyl-1H-pyrrole-2-carboxamido)phenyl)carbamate (50) A solution of 5-((5-((4-((tert-butoxycarbonyl)amino)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3- yl)amino)-5-oxopentanoic acid (49) (1.8 g, 4.05 mmol) in N,N-dimethylacetamide (8 mL) was charged to (S)-1-(chloromethyl)-2,3-dihydro-1H-benzo[e]indol-5-ol hydrochloride (10) (1.4 g, 5.19 mmol), followed by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (3.96 g, 20.7 mmol) and the resulting green slurry was sonicated, then stirred at room temperature for 48 h. The mixture was then diluted into ethyl acetate (100 mL) and methanol (10 mL), and extracted with brine (50 mL x 3), dried over magnesium sulfate, and concentrated in vacuo. Purification by flash column chromatography (silica), eluting with ethyl acetate / petroleum spirit, 40-60 °C (0% to 100%), gave the title compound (792 mg, 30% over two steps) as a rust- brown solid.1H NMR (600 MHz, CDCl3) δ 9.85 (s, 1H), 8.47 (s, 1H), 8.24 (d, J=8.3 Hz, 1H), 8.17-8.09 (m, 2H), 7.84 (s, 1H), 7.57 (d, J=8.2 Hz, 1H), 7.44 (d, J=8.2 Hz, 2H), 7.30 (d, J=8.1 Hz, 2H), 7.09 (s, 1H), 6.63 (br, 1H), 4.23-4.11 (m, 2H), 3.97-3.82 (m, 2H), 3.81 (s, 3H), 3.45- 3.33 (m, 1H), 2.70-2.54 (m, 4H), 2.51-2.44 (m, 2H), 1.50 (s, 9H); MS (ES+): m / z = 660 (M+H)+; LCMS (Method A): tR= 7.55 min. (S)-N-(4-Aminophenyl)-4-(5-(1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benzo[e]indol-3- yl)-5-oxopentanamido)-1-methyl-1H-pyrrole-2-carboxamide (51) A solution of tert-butyl (S)-(4-(4-(5-(1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H- benzo[e]indol-3-yl)-5-oxopentanamido)-1-methyl-1H-pyrrole-2-carboxamido)phenyl)carbamate (50) (10 mg, 0.015 mmol) in dichloromethane (1 mL) was charged with trifluoroacetic acid (1 mL) and the resulting mixture was stirred at room temperature for 1 min. After precipitating by addition of diethyl ether, the mixture was concentrated in vacuo, then purified by flash column chromatography (silica), eluting with ethyl acetate / petroleum spirit, 40-60 °C (0% to 100%), followed by methanol / ethyl acetate (0% to 100%), to give the title compound (1.2 mg, 14%) as a white solid.1H NMR (600 MHz, MeOD) δ 8.55 (s, 1H), 8.17 (d, J=8.3 Hz, 1H), 7.93 (s, 1H), 7.73 (d, J=8.4 Hz, 1H), 7.49 (t, J=7.6 Hz, 1H), 7.34-7.31 (m, 1H), 7.28-7.26 (m, 2H), 7.16 (s, 1H), 6.82 (s, 1H), 6.73-6.71 (m, 2H), 4.56 (br, 2H), 4.33-4.30 (m, 2H), 4.14-4.09 (m, 1H), 4.12 (dd, J=18.8, 8.5 Hz, 1H), 3.84 (s, 3H), 3.64 (dd, J=11.2, 8.7 Hz, 1H), 2.75-2.68 (m, 1H), 2.65- 2.58 (m, 1H), 2.48 (dd, J=9.4, 5.1 Hz, 2H), 2.12 (t, J=7.0 Hz, 2H); MS (ES+): m / z = 560 (M+H)+; LCMS (Method A): tR= 5.98 min.

[0035] Example 1L: Synthesis of compound (56). Scheme 16. Synthesis of compound (56). tert-Butyl (S)-1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benzo[e]indole-3-carboxylate (52) A solution of tert-butyl (S)-5-(benzyloxy)-1-(chloromethyl)-1,2-dihydro-3H-benzo[e]indole-3- carboxylate (9) (1.6 g, 3.78 mmol) in dichloromethane (15 mL) and methanol (15 mL) was charged with palladium on charcoal (10 wt.%) (160 mg) and Pearlman’s catalyst (160 mg), and the resulting mixture was stirred at room temperature, under an atmosphere of hydrogen (1 atm), overnight. The mixture was then filtered and concentrated in vacuo. Purification by flash column chromatography (silica), eluting with ethyl acetate / petroleum spirit, 40-60 °C (3%) gave the title compound (1.3 g, 96%) as a white solid.1H NMR (400 MHz, DMSO-d6) δ 10.34 (s, 1H), 8.07 (d, J=8.4 Hz, 1H), 7.74 (d, J=8.4 Hz, 1H), 7.47 (ddd, J=8.4, 6.8, 1.4 Hz, 1H), 7.31- 7.24 (m, 1H), 4.14-3.93 (m, 4H), 3.76 (d, J=9.2 Hz, 1H), 1.54 (s, 9H); MS (ES+): m / z = 334 (M+H)+; LCMS (Method F): tR= 4.37 min. (2R,3S,4S,5R,6S)-2-(Acetoxymethyl)-6-(((S)-1-(chloromethyl)-2,3-dihydro-1H- benzo[e]indol-5-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate (53) A solution of tert-butyl (S)-1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benzo[e]indole-3- carboxylate (52) (100 mg, 0.300 mmol) in dichloromethane (5 mL) was charged with 2,3,4,6- tetra-O-acetyl-α-D-galactopyranosyl trichloroacetimidate (184 mg, 0.375 mmol) and 4 Å molecular sieves (700 mg), and the resulting mixture stirred at room temperature for 1 h. After cooling to -20 °C, boron trifluoride diethyl etherate (170 mg, 1.20 mmol) was added, and the resulting mixture was stirred for 3 h. Quenching was enacted by the addition of water (50 mL), and the mixture was then extracted with ethyl acetate (100 mL x 2). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. Purification by preparative thin layer chromatography (silica), eluting with ethyl acetate / petroleum spirit, 40-60 °C (50%), gave the title compound (80 mg, 85%) as a brown oil. 1H NMR (400 MHz, CDCl3) δ 7.98 (d, J=8.4 Hz, 1H), 7.58 (d, J=8.4 Hz, 1H), 7.45 (s, 1H), 7.23 (s, 1H), 6.65 (s, 1H), 5.68 (dd, J=10.6, 8.0 Hz, 1H), 5.49 (d, J=3.6 Hz, 1H), 5.12 (d, J=8.2 Hz, 2H), 4.33-4.24 (m, 1H), 4.16-4.09 (m, 3H), 3.96 (t, J=9.4 Hz, 1H), 3.90-3.77 (m, 3H), 3.51 (s, 1H), 2.08-2.00 (m, 12H); MS (ES+): m / z = 564 (M+H)+; LCMS (Method F): tR= 1.92 min. (2R,3S,4S,5R,6S)-2-(Acetoxymethyl)-6-(((S)-3-(5-((5-((4-((tert- butoxycarbonyl)amino)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)amino)-5- oxopentanoyl)-1-(chloromethyl)-2,3-dihydro-1H-benzo[e]indol-5-yl)oxy)tetrahydro-2H- pyran-3,4,5-triyl triacetate (54) A solution of (2R,3S,4S,5R,6S)-2-(Acetoxymethyl)-6-(((S)-1-(chloromethyl)-2,3-dihydro-1H- benzo[e]indol-5-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate (53) (50 mg, 0.089 mmol) in N,N-dimethylacetamide (3 mL) was charged with 5-((5-((4-((tert- butoxycarbonyl)amino)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)amino)-5-oxopentanoic acid (49) (26 mg, 0.059 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (34 mg, 0.178 mmol), and the resulting mixture was stirred at room temperature for 5 h. After diluting into water (50 mL), the mixture was extracted with ethyl acetate (50 mL x 2), and the combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. Purification by preparative thin layer chromatography (silica), eluting with methanol / dichloromethane (5%), gave the title compound (15 mg, 17%) as a brown oil.1H NMR (400 MHz, DMSO-d6) δ 9.84 (s, 1H), 9.70 (s, 1H), 9.23 (s, 1H), 8.32 (s, 1H), 7.97-7.82 (m, 2H), 7.69-7.51 (m, 3H), 7.46-7.32 (m, 3H), 7.23-7.18 (m, 1H), 6.96-6.91 (m, 1H), 5.62-5.51 (m, 1H), 5.48-5.37 (m, 3H), 4.60-4.48 (m, 1H), 4.46-4.29 (m, 1H), 4.28-3.97 (m, 5H), 3.93-3.86 (m, 1H), 3.82 (s, 4H), 2.69-2.57 (m, 2H), 2.42-2.32 (m, 2H), 2.18 (s, 3H), 2.08 (s, 3H), 2.04-2.00 (m, 3H), 1.99-1.89 (m, 5H), 1.47 (s, 9H); MS (ES+): m / z = 990 (M+H)+; LCMS (Method F): tR = 2.03 min. (2R,3S,4S,5R,6S)-2-(Acetoxymethyl)-6-(((S)-3-(5-((5-((4-aminophenyl)carbamoyl)-1- methyl-1H-pyrrol-3-yl)amino)-5-oxopentanoyl)-1-(chloromethyl)-2,3-dihydro-1H- benzo[e]indol-5-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate (55) A solution of (2R,3S,4S,5R,6S)-2-(Acetoxymethyl)-6-(((S)-3-(5-((5-((4-((tert- butoxycarbonyl)amino)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)amino)-5-oxopentanoyl)-1- (chloromethyl)-2,3-dihydro-1H-benzo[e]indol-5-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate (54) (15 mg, 0.015 mmol) in dichloromethane (2 mL) was charged with trifluoroacetic acid (0.5 mL) and the resulting mixture was stirred at room temperature for 3 h, before concentrating in vacuo. The title compound was employed in the subsequent step without further purification. MS (ES+): m / z = 890 (M+H)+; LCMS (Method F): tR= 3.34 min. N-(4-Aminophenyl)-4-(5-((S)-1-(chloromethyl)-5-(((2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6- (hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-1,2-dihydro-3H-benzo[e]indol-3-yl)-5- oxopentanamido)-1-methyl-1H-pyrrole-2-carboxamide (56) A solution of (2R,3S,4S,5R,6S)-2-(Acetoxymethyl)-6-(((S)-3-(5-((5-((4- aminophenyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)amino)-5-oxopentanoyl)-1-(chloromethyl)- 2,3-dihydro-1H-benzo[e]indol-5-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate (55) (15 mg, 0.017 mmol) in acetonitrile (0.5 mL) was cooled to 0 °C and charged with lithium hydroxide (2 mg, 0.083 mmol) and water (0.1 mL). The resulting mixture was stirred at room temperature for 3 h, then purified by reverse phase chromatography (55% acetonitrile in water), to give the title compound (1 mg, 8%) as a brown oil.1H NMR (400 MHz, DMSO-d6) δ 8.29 (d, J=8.2 Hz, 3H), 7.85 (d, J=8.4 Hz, 1H), 7.53 (d, J=7.8 Hz, 1H), 7.38 (t, J=7.8 Hz, 1H), 7.28 (d, J=8.6 Hz, 1H), 7.18 (s, 1H), 5.74 (s, 4H), 4.92 (d, J=8.8 Hz, 1H), 4.37 (s, 8H), 3.81 (d, J=14.8 Hz, 14H), 2.33 (s, 6H); MS (ES+): m / z = 722 (M+H)+; LCMS (Method F): tR= 0.64 min. Example 1M: Synthesis of compound (60). Scheme 17. Synthesis of compound (60). (2R,3S,4S,5R,6S)-2-(Acetoxymethyl)-6-(((S)-3-(5-((5-((4-((S)-2-((S)-2-((tert- butoxycarbonyl)amino)-3-methylbutanamido)propanamido)phenyl)carbamoyl)-1-methyl- 1H-pyrrol-3-yl)amino)-5-oxopentanoyl)-1-(chloromethyl)-2,3-dihydro-1H-benzo[e]indol-5- yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate (57) A solution of (2R,3S,4S,5R,6S)-2-(acetoxymethyl)-6-(((S)-3-(5-((5-((4- aminophenyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)amino)-5-oxopentanoyl)-1-(chloromethyl)- 2,3-dihydro-1H-benzo[e]indol-5-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate (55) (386 mg, 0.433 mmol), (tert-butoxycarbonyl)-L-valyl-L-alanine (137 mg, 0.476 mmol) and HATU (247 mg, 0.650 mmol) in N,N-dimethylformamide (10 mL) was charged with N,N- diisopropylethylamine (280 mg, 2.17 mmol) and the resulting mixture was stirred at room temperature for 16 h. The mixture was then diluted into water (100 mL) and extracted with ethyl acetate (50 mL x 3). The combined organic extracts were then washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. Purification by flash column chromatography (silica), eluting with dichloromethane:methanol (1:0 to 30:1) to give the title compound (200 mg, 40%) as a yellow solid.1H NMR (400 MHz, DMSO-d6) δ 9.92-9.67 (m, 2H), 8.32 (s, 1H), 8.28-8.00 (m, 1H), 7.96-7.86 (m, 2H), 7.68-7.39 (m, 6H), 7.26-7.19 (m, 1H), 7.00-6.93 (m, 1H), 6.88-6.70 (m, 1H), 5.59-5.54 (m, 1H), 5.46-5.38 (m, 3H), 4.60-4.52 (m, 1H), 4.48-4.31 (m, 2H), 4.28-4.15 (m, 3H), 4.13-3.97 (m, 2H), 3.93-3.74 (m, 5H), 2.70-2.57 (m, 1H), 2.42-2.32 (m, 2H), 2.26-1.86 (m, 17H), 1.43-1.33 (m, 9H), 1.33-1.27 (m, 3H), 0.89-0.81 (m, 6H); MS (ES+): m / z = 1160 (M+H)+; LCMS (Method F): tR= 4.17 min. (2R,3S,4S,5R,6S)-2-(Acetoxymethyl)-6-(((S)-3-(5-((5-((4-((S)-2-((S)-2-amino-3- methylbutanamido)propanamido)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)amino)-5- oxopentanoyl)-1-(chloromethyl)-2,3-dihydro-1H-benzo[e]indol-5-yl)oxy)tetrahydro-2H- pyran-3,4,5-triyl triacetate (58) A solution of (2R,3S,4S,5R,6S)-2-(acetoxymethyl)-6-(((S)-3-(5-((5-((4-((S)-2-((S)-2-((tert- butoxycarbonyl)amino)-3-methylbutanamido)propanamido)phenyl)carbamoyl)-1-methyl-1H- pyrrol-3-yl)amino)-5-oxopentanoyl)-1-(chloromethyl)-2,3-dihydro-1H-benzo[e]indol-5- yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate (57) (200 mg, 0.172 mmol) in dichloromethane (4 mL) was charged with trifluoroacetic acid (1 mL) and stirred at room temperature for 3 h. The resulting mixture was then concentrated in vacuo and the residue used immediately in the subsequent step without further purification. MS (ES+): m / z = 1060 (M+H)+; LCMS (Method F): tR= 1.77 min. N-(4-((S)-2-((S)-2-Amino-3-methylbutanamido)propanamido)phenyl)-4-(5-((S)-1- (chloromethyl)-5-(((2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H- pyran-2-yl)oxy)-1,2-dihydro-3H-benzo[e]indol-3-yl)-5-oxopentanamido)-1-methyl-1H- pyrrole-2-carboxamide (59) A solution of (2R,3S,4S,5R,6S)-2-(Acetoxymethyl)-6-(((S)-3-(5-((5-((4-((S)-2-((S)-2-amino-3- methylbutanamido)propanamido)phenyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)amino)-5- oxopentanoyl)-1-(chloromethyl)-2,3-dihydro-1H-benzo[e]indol-5-yl)oxy)tetrahydro-2H-pyran- 3,4,5-triyl triacetate (58) (183 mg, 0.172 mmol) in acetonitrile (2 mL) and water (2 mL) was cooled to 0 °C and charge with lithium hydroxide (41 mg, 1.73 mmol). The resulting mixture was stirred at this temperature for 2 h, before freeze drying, to afford the unpurified title compound (230 mg, crude), which was used in the subsequent step without further purification. MS (ES+): m / z = 892 (M+H)+; LCMS (Method F): tR= 0.88 min. 4-(5-((S)-1-(Chloromethyl)-5-(((2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6- (hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-1,2-dihydro-3H-benzo[e]indol-3-yl)-5- oxopentanamido)-N-(4-((S)-2-((S)-2-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1- yl)hexanamido)-3-methylbutanamido)propanamido)phenyl)-1-methyl-1H-pyrrole-2- carboxamide (60) A solution of N-(4-((S)-2-((S)-2-Amino-3-methylbutanamido)propanamido)phenyl)-4-(5-((S)-1- (chloromethyl)-5-(((2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran- 2-yl)oxy)-1,2-dihydro-3H-benzo[e]indol-3-yl)-5-oxopentanamido)-1-methyl-1H-pyrrole-2- carboxamide (59) (70 mg, 0.078 mmol) and sodium hydrogen carbonate (13 mg, 0.156 mmol) in tetrahydrofuran (2 mL) and water (2 mL) was charged with 6-maleimidohexanoic acid N- hydroxysuccinimide ester (121 mg, 0.392 mmol) and the resulting mixture was stirred for 16 h at room temperature. Purification by preparative HPLC, gave the title compound (12.5 mg, 15%) as a white solid.1H NMR (400 MHz, DMSO-d6) δ 9.88-9.80 (m, 1H), 9.77-9.66 (m, 1H), 8.46-8.07 (m, 3H), 7.99-7.78 (m, 2H), 7.66-7.48 (m, 5H), 7.42-7.35 (m, 1H), 7.25-7.19 (m, 1H), 7.04-6.89 (m, 3H), 4.97-4.85 (m, 1H), 4.72-4.52 (m, 1H), 4.44-4.31 (m, 2H), 4.29-3.95 (m, 4H), 3.91-3.72 (m, 6H), 3.67-3.43 (m, 4H), 3.41-3.32 (m, 6H), 2.65-2.54 (m, 2H), 2.42-2.35 (m, 2H), 2.24-2.07 (m, 2H), 2.01-1.86 (m, 3H), 1.54-1.41 (m, 4H), 1.30 (d, J=7.4 Hz, 3H), 1.23-1.13 (m, 2H), 0.93-0.79 (m, 6H); MS (ES+): m / z = 1085 (M+H)+; LCMS (Method F): tR= 3.06 min. Example 1N: Synthesis of compound (72). Scheme 18. Synthesis of compound (72). Methyl 4-(2-(benzyloxy)-4-formylphenoxy)butanoate (62) A mixture of 3-(benzyloxy)-4-hydroxybenzaldehyde (61) (10.0 g, 44.0 mmol), methyl 4- bromobutanoate (8.3 mL, 65.0 mmol) and potassium carbonate (12.6 g, 88.0 mmol) in acetone (100 mL) was heated to 40 ˚C for 18 h. The reaction mixture was diluted with water (500 mL) and extracted with ethyl acetate (2 x 300 mL). The organic layer was concentrated in vacuo. The resulting residue was purified by column chromatography (silica), eluting with acetone / dichloromethane (from 0% to 30%) to give the title compound (13.8 g, 96%) as a yellow oil.1H NMR (400 MHz, CDCl3) δ 9.82 (s, 1H), 7.49 – 7.42 (m, 4H), 7.38 (t, J = 7.3 Hz, 2H), 7.35 – 7.29 (m, 1H), 7.00 (d, J = 8.0 Hz, 1H), 5.17 (s, 2H), 4.16 (t, J = 6.2 Hz, 2H), 3.68 (s, 3H), 2.57 (t, J = 7.2 Hz, 2H), 2.24 – 2.15 (m, 2H);13C NMR (100 MHz, CDCl3) δ 190.9, 173.5, 154.6, 149.0, 136.7, 130.2, 128.7, 128.1, 127.3, 126.9, 112.2, 71.0, 67.9, 51.8, 30.3, 24.5; MS (ES+): m / z = 329 (M+H)+; LCMS (Method B): tR= 4.00 min. Methyl 4-(2-(benzyloxy)-4-formyl-5-nitrophenoxy)butanoate (63) A solution of methyl 4-(2-(benzyloxy)-4-formylphenoxy)butanoate (62) (7.20 g, 21.9 mmol) in trifluoroacetic acid (30 mL) at 0 °C was added to a stirring solution of potassium nitrate (2.7 g, 26.3 mmol) in trifluoroacetic acid (30 mL), dropwise. The resulting mixture was stirred at room temperature for 30 min and then quenched with a saturated aqueous solution of sodium hydrogen carbonate (100 mL) and extracted with ethyl acetate (2 x 80 mL). The organic layer was concentrated in vacuo. The resulting residue was purified by column chromatography (silica), eluting with ethyl acetate / petroleum spirit, 40-60 °C (from 0% to 50%) to give the title compound (5.60 g, 68%) as a yellow solid.1H NMR (400 MHz, CDCl3) δ 10.41 (s, 1H), 7.62 (s, 1H), 7.48 (s, 1H), 7.44 – 7.35 (m, 5H), 5.26 (s, 2H), 4.22 (t, J = 6.2 Hz, 2H), 3.69 (s, 3H), 2.57 (t, J = 7.1 Hz, 2H), 2.26 – 2.19 (m, 2H);13C NMR (100 MHz, CDCl3) δ 187.6, 173.2, 152.5, 152.1, 143.9, 135.3, 128.7, 128.4, 127.3, 125.3, 111.6, 108.5, 71.1, 68.6, 51.7, 30.1, 24.1; MS (ES+): m / z = 374 (M+H)+; LCMS (Method B): tR= 4.15 min. Methyl 4-(4-formyl-2-hydroxy-5-nitrophenoxy)butanoate (64) A solution of methyl 4-(2-(benzyloxy)-4-formyl-5-nitrophenoxy)butanoate (63) (5.50 g, 14.7 mmol) in trifluoroacetic acid (30 mL) was heated to 80 °C for 30 min. It was then cooled to room temperature and quenched with a saturated aqueous solution of sodium hydrogen carbonate (30 mL). The aqueous mixture was extracted with ethyl acetate and the organic layer was concentrated in vacuo. The resulting residue was purified by column chromatography (silica), eluting with ethyl acetate / petroleum spirit, 40-60 °C (from 0% to 50%), to give the title compound (2.10 g, 50%) as a brown solid.1H NMR (400 MHz, CDCl3) δ 10.41 (s, 1H), 7.62 (s, 1H), 7.45 (s, 1H), 6.75 (br. s, 1H), 4.27 (t, J = 6.0 Hz, 2H), 3.73 (s, 3H), 2.60 – 2.55 (m, 2H), 2.29 – 2.22 (m, 2H);13C NMR (100 MHz, CD3OD) δ 189.5, 175.4, 152.5, 115.1, 112.3, 110.9, 109.9, 101.4, 69.5, 52.1, 31.2, 25.4; MS (ES-): m / z = 282 (M-H)-; LCMS (Method B): tR= 3.47 min. Methyl 4-(4-formyl-5-nitro-2-((2-(trimethylsilyl)ethoxy)methoxy)phenoxy)butanoate (65) A mixture of methyl 4-(4-formyl-2-hydroxy-5-nitrophenoxy)butanoate (64) (2.10 g, 7.40 mmol), 2-(trimethylsilyl)ethoxymethyl chloride (1.50 g, 8.90 mmol) and potassium carbonate (2.60 g, 18.5 mmol) in acetone (30 mL) was stirred at room temperature for 2 h. The reaction mixture was diluted with water (150 mL) and extracted with ethyl acetate (2 x 60 mL). The organic layer was concentrated in vacuo. The resulting residue was purified by column chromatography (silica), eluting with ethyl acetate / petroleum spirit, 40-60 °C (from 0% to 50%) to give the title compound (2.50 g, 82%) as a brown oil.1H NMR (400 MHz, CDCl3) δ 10.36 (s, 1H), 7.65 (s, 1H), 7.64 (s, 1H), 5.41 (s, 2H), 4.26 (t, J = 6.2 Hz, 2H), 3.85 – 3.80 (m, 2H), 3.71 (s, 3H), 2.60 (t, J = 7.1 Hz, 2H), 2.24 (p, J = 6.6 Hz, 2H), 1.00 – 0.96 (m, 2H), 0.02 (s, 9H) ;13C NMR (100 MHz, CDCl3) δ 187.2, 172.9, 152.1, 150.9, 144.2, 125.1, 114.0, 108.4, 93.4, 68.4, 67.1, 51.5, 30.0, 24.0, 17.8, -1.6; MS (ES-): m / z = 412 (M-H)-; LCMS (Method B): tR= 4.50 min. 4-(4-Methoxy-4-oxobutoxy)-2-nitro-5-((2-(trimethylsilyl)ethoxy)methoxy)benzoic acid (66) A solution of sodium chlorite (1.30 g, 14.9 mmol) and sodium monophosphate (1.00 g, 8.40 mmol) in water (30 mL) was added to a mixture of methyl 4-(4-formyl-5-nitro-2-((2- (trimethylsilyl)ethoxy)methoxy)phenoxy)butanoate (65) (2.50 g, 6.00 mmol). Hydrogen peroxide (50% in water, 2.8 mL) was then added dropwise, and the resulting solution was stirred at 40 °C for 1 h. The reaction mixture was quenched with a saturated aqueous solution of sodium metabisulfite (60 mL) and acidified with acetic acid (1.5 mL). The aqueous mixture was extracted with ethyl acetate (2 x 60 mL) and the organic layer was concentrated in vacuo. The resulting residue was purified by column chromatography (silica), eluting with ethyl acetate / petroleum spirit, 40-60 °C (from 0% to 50%) to give the title compound (2.40 g, 93%) as a brown oil.1H NMR (400 MHz, CD3OD) δ 7.42 (s, 1H), 7.41 (s, 1H), 5.30 (s, 2H), 4.08 (t, J = 6.6 Hz, 2H), 3.78 – 3.74 (m, 2H), 3.61 (s, 3H), 2.49 (t, J = 8.1 Hz, 2H), 2.09 – 2.03 (m, 2H), 0.91 – 0.86 (m, 2H), -0.07 (s, 9H);13C NMR (100 MHz, CD3OD) δ 175.0, 167.8, 151.9, 150.7, 144.2, 121.8, 117.0, 109.6, 94.8, 69.6, 67.9, 52.2, 31.1, 25.3, 18.7, -1.3; MS (ES-): m / z = 428 (M-H)-; LCMS (Method B): tR= 4.08 min. Methyl (S)-4-(4-(2-(hydroxymethyl)piperidine-1-carbonyl)-5-nitro-2-((2- (trimethylsilyl)ethoxy)methoxy)phenoxy)butanoate (67) A solution of 4-(4-methoxy-4-oxobutoxy)-2-nitro-5-((2-(trimethylsilyl)ethoxy)methoxy)benzoic acid (66) (2.40 g, 5.60 mmol) in anhydrous dichloromethane (30 mL) was charged with HATU (2.60 g, 6.70 mmol) and anhydrous triethylamine (1.5 mL, 11.2 mmol). The reaction mixture was stirred at room temperature for 5 min. (S)-Piperidin-2-ylmethanol (711 mg, 6.20 mmol) was then added and the resulting mixture was stirred at room temperature for 17 h. The reaction mixture was diluted with ethyl acetate (90 mL) and washed with brine (90 mL). The organic layer was concentrated in vacuo. The resulting residue was purified by column chromatography (silica), eluting with ethyl acetate / petroleum spirit, 40-60 °C (from 0% to 100%) to give the title compound (2.60 g, 88%) as a brown oil.1H NMR (400 MHz, DMSO-d6) δ 7.71 (s, 1H), 7.15 (s, 1H), 5.40 (s, 2H), 4.80 (t, J = 5.6 Hz, 1H), 4.18 – 4.09 (m, 2H), 3.76 – 3.70 (m, 2H), 3.60 (s, 3H), 3.57 – 3.39 (m, 2H), 3.34 – 2.70 (m, 3H), 2.50 – 2.46 (m, 2H), 2.07 – 1.97 (m, 2H), 1.85 – 1.28 (m, 6H), 0.92 – 0.84 (m, 2H), -0.04 (d, J = 3.6 Hz, 9H);13C NMR (100 MHz, CDCl3) δ 173.2, 168.0, 152.3, 148.6, 138.2, 127.2, 112.6, 108.7, 93.5, 68.2, 67.1, 60.3, 53.5, 51.6, 51.1, 43.4, 37.3, 30.1, 24.1, 18.0, -1.5; MS (ES-): m / z = 527 (M+H)+; LCMS (Method B): tR= 4.10 min. Methyl (S)-4-(5-amino-4-(2-(hydroxymethyl)piperidine-1-carbonyl)-2-((2- (trimethylsilyl)ethoxy)methoxy)phenoxy)butanoate (68) A solution of ammonium chloride (15.8 g, 297 mmol) in water (25 mL) was added to a mixture of methyl (S)-4-(4-(2-(hydroxymethyl)piperidine-1-carbonyl)-5-nitro-2-((2- (trimethylsilyl)ethoxy)methoxy)phenoxy)butanoate (67) (2.60 g, 4.90 mmol) in acetone (30 mL) and tetrahydrofuran (30 mL), and charged with zinc powder (65.4 g, 148 mmol). The resulting mixture was stirred at room temperature for 30 min and then filtered through celite. The cake was washed with ethyl acetate. The filtrate was concentrated in vacuo and the resulting residue was purified by column chromatography (silica), eluting with methanol / dichloromethane (from 0% to 10%) to give the title compound (2.40 g, 98%) as an orange viscous oil.1H NMR (400 MHz, CDCl3) 6.99 - 6.68 (m, 2 H), 5.20 (s, 2 H), 5.05 (br. s., 1 H), 3.97 (br. s., 3 H), 3.63 (dd, J = 5.9, 7.8 Hz, 3 H), 3.57 (br. s., 3 H)– 3.52 - 3.15 (m, 3 H), 2.42 (br. s., 2 H), 2.03 (br. s., 2 H)– 1.82 - 1.33 (m, 6 H)– 0.89 - 0.76 (m, 2 H), -0.09 (br. s., 9 H);13C NMR (100 MHz, CDCl3) δ 173.8, 173.6, 171.8, 152.9, 141.1, 125.5, 112.1, 108.2, 94.2, 77.2, 68.0, 66.5, 57.8, 53.6, 51.8, 51.3, 30.6, 30.3, 29.2, 25.6, 24.3, 18.1, -1.4; MS (ES-): m / z = 497 (M+H)+; LCMS (Method B): tR= 3.85 min. Methyl (S)-4-(5-(((allyloxy)carbonyl)amino)-4-(2-(hydroxymethyl)piperidine-1-carbonyl)- 2-((2-(trimethylsilyl)ethoxy)methoxy)phenoxy)butanoate (69) A solution of methyl (S)-4-(5-amino-4-(2-(hydroxymethyl)piperidine-1-carbonyl)-2-((2- (trimethylsilyl)ethoxy)methoxy)phenoxy)butanoate (68) (2.40 g, 4.80 mmol) and pyridine (973 µL, 12.1 mmol) in anhydrous dichloromethane (20 mL) was cooled to -10 °C and charged dropwise with a solution of allylchloroformate (468 µL, 4.30 mmol) in anhydrous dichloromethane (10 mL). The reaction mixture was stirred at room temperature for 40 min. The reaction mixture was sequentially washed with a saturated aqueous solution of copper (II) sulfate (20 mL), water (20 mL) and a saturated aqueous solution of sodium hydrogen carbonate (20 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting residue was purified by column chromatography (silica), eluting with ethyl acetate / petroleum spirit, 40-60 °C (from 0% to 100%) to give the title compound (2.10 g, 75%) as a brown viscous oil.1H NMR (400 MHz, CDCl3) δ 8.44 (s, 1H), 7.70 (s, 1H), 7.03 (s, 1H), 5.90 (ddt, J = 15.9, 10.7, 5.5 Hz, 1H), 5.31 (d, J = 17.2 Hz, 1H), 5.21 – 5.11 (m, 3H), 4.58 (d, J = 5.5 Hz, 2H), 4.05 (t, J = 6.8 Hz, 3H), 3.86 (s, 1H), 3.74 (t, J = 8.5 Hz, 2H), 3.66 – 3.51 (m, 5H), 3.40 – 3.21 (m, 1H), 3.11 – 2.82 (m, 1H), 2.49 (t, J = 7.4 Hz, 2H), 2.15 – 2.08 (m, 2H), 1.66 – 1.44 (m, 6H), 0.93 – 0.86 (m, 2H), -0.03 (s, 9H);13C NMR (100 MHz, CDCl3) δ 173.5, 171.2, 170.7, 153.8, 150.7, 132.6, 117.8, 116.3, 106.0, 94.1, 67.7, 66.4, 65.7, 60.4, 57.8, 51.7, 30.6, 25.6, 24.4, 21.1, 19.8, 18.1, 14.2, -1.4; MS (ES-): m / z = 581 (M+H)+; LCMS (Method B): tR= 4.27 min. Allyl 6-hydroxy-3-(4-methoxy-4-oxobutoxy)-12-o...

Claims

CLAIMS 1. A compound of formula (I): D – Q – B - T (I) or a salt, solvate or tautomer thereof, wherein: D is a source of an alkylating DNA minor groove binding unit; Q is a linker; B is an DNA binding amide-containing chain; and T is an end group, wherein D, B, Q and / or T comprise at least one carbohydrate substituent.

2. The compound as claimed in claim 1, wherein the carbohydrate substituent is a univalent saccharide substituent represented by the term RS, preferably RSis glycosyl or O- glycosyl.

3. The compound as claimed in claim 1 or claim 2, wherein D comprises G, a G- alkylating DNA group of formula (II): (II) wherein: the dotted line indicates the optional presence of a double bond between one or more of C1 and C2, C2 and C3, and C3 and C4; the wavy line indicates the point of attachment to Q; m is 0 or 1; R1, R3and R4are independently selected from H and R29; R2is selected from H, L2-R28,R29, and –LS-RS, or one of R1and R2, R2and R3, or R3and R4, together with the carbon atoms to which they are attached form a 6-membered aryl, or a 5- or 6-membered cyclic,heterocyclic, or heteroaryl ring optionally substituted with 1, 2 or 3 independently selected optional R20groups; R5and R6are selected such that either (i) R5is selected from H, OH and OC1-6alkyl; and R6is selected from H, SO3H, –LS-RS, nitrogen protecting groups, –L2-R28 and RA; (ii) R5 is oxo or H, and R6is H or C1-6alkyl; or (iii) R5and R6together form a double bond; R7and R9are independently selected from H and R20; R8is selected from H, SR24, SCH2Ph, R20, L2-R28, and –LS-RS; RAis selected from (CH2)j-OH, (CH2)j-CO2R26, C(=O)-O-(CH2)k-NR26R27, (CH2)jNR26R27, C(=O)-NH-(CH2)j-NR26R27and C(=O)-NH-(CH2)k-C(=NH)NR26R27; L2is a bond or a linker moiety having 1-200 non-hydrogen atoms selected from C, N, P, O, S or halogen, and optionally incorporates ether, oxo, carboxamidyl, urethanyl, branched, cyclic, unsaturated, heterocyclyl, aryl or heteroaryl moieties; and R28is selected from an azide, alkyne, bisulfone, carbohydrazide, hydrazine, hydroxylamine, iodoacetamide, isothiocyanate, maleimide, phosphine, pyrridopyridazine, semihydrazide, succinimidyl ester, sulfodichlorophenol ester, sulfonyl halide, sulfosuccinimidyl ester, 4- sulfotetrafluorophenyl ester, tetrafluorophenyl ester, thiazole, RA,O-(CH2)k-NR26R26, NHNH2, or is a targeting agent wherein the targeting agent is selected from a protein, a portion of a protein, a peptide, a nucleic acid, or an antibody; each R29is independently selected from R20, R21, =CH2, =CH-(CH2)s-CH3, =CH-(CH2)s-R21, =O, (CH2)s-OR21, (CH2)s-CO2R21, (CH2)s-NR21R24, O-(CH2)t-NR21R24, NH-C(O)-R21, O- (CH2)t-NH-C(O)-R21, O-(CH2)t-C(O)-NH-R21, (CH2)s-SO2R21, O-SO2R21, (CH2)s-C(O)R21and (CH2)s-C(O)NR21R24; each R20is independently selected from F, Cl, Br, (CH2)j-OH, C1-6alkyl, OC1-6alkyl, OCH2Ph, (CH2)j-CO2R26, O-(CH2)k-NR26R27, C(=O)-O-(CH2)k-NR26R27, C(=O)-NR26R27, (CH2)j- NR26R27, NR26NH2, C(=O)-NH-(CH2)j-NR26R27, C(=O)-NH-C6H4-(CH2)j-R26, C(=O)-NH- (CH2)k-C(=NH)NR26R27, –L2-R28, S(O)2-(C1-6alkyl), O-(CH2)k-O-(C1-6alkyl), (CH2)j- S(O)2-NR26R27, C(=NH)-O-(C1-6alkyl), (CH2)k-O-(C1-6alkyl), CN, NCO, Cy, C(O)-NH- (CH2)j-Cy, C(O)-Cy, NH-C(O)-NR26R27and ; each j and s is independently selected from 0, 1, 2, 3, 4, 5 or 6; each k and t is independently selected from 1, 2, 3, 4, 5 or 6; each R21is independently selected from H, C1-12alkyl, C5-6heterocyclyl, C5-9heteroaryl, C6-15heteroarylalkyl, phenyl and C7-12aralkyl groups; wherein the heterocyclyl, heteroaryl, heteroarylalkyl, phenyl and aralkyl groups are optionally substituted with 1, 2 or 3 independently selected optional R20groups;each R24, R26and R27is independently selected from H and C1-12alkyl; each Cy is independently selected from a C5-6heterocyclyl or C5-6heteroaryl group, wherein the heterocyclyl or heteroaryl groups are optionally substituted with 1 or 2 R20groups; LS is a bond, an amino acid, a peptide chain having from 2 to 6 amino acids, an alkylene chain containing from 1 to 12 carbon atoms which may contain one or more carbon-carbon double or triple bonds, a paraformaldehyde chain –(OCH2)1-12-, a polyethylene glycol chain -(OCH2CH2)1-6-, which chains may be interrupted by or optionally incorporates one or more of P, O, S, NH, C5-9heteroarylene, phenylene, heterocyclyl, cycloalkyl, ether, oxo, carboxamidyl, and / or urethanyl moieties wherein the C5-9heteroarylene, phenylene, heterocyclyl, and / or cycloalkyl moieties are optionally substituted, optionally LSis:LCcomprises one or more groups selected from an amino acid, an amino acid derivative, a peptide chain having from 2 to 6 amino acids or amino acid derivatives, an alkylene chain containing from 1 to 12 carbon atoms which may contain one or more carbon-carbon double or triple bonds, a paraformaldehyde chain –(OCH2)1-12-, a polyethylene glycol chain -(OCH2CH2)1-8-, which chains may be interrupted by one or more P, O, S and / or NH groups and / or C5-9heteroarylene and / or phenylene, wherein each C5-9heteroarylene group and / or each phenylene group is optionally substituted; and RSis a univalent saccharide substituent, preferably glycosyl or O-glycosyl.

4. The compound as claimed in claim 3, wherein G is selected from a group of formula G1 to G8: (G1);(G2); G3); G4);G5);5. e co poud as ca ed ca o ca , wherein D comprises A, an A- alkylating DNA group of formula (IIIa) or (IIIb): or IIIa (seco form) IIIb (spiro form) wherein: Z1 is a leaving group, optionally halide, triflate, or tosylate;X is C-R17, N, N-R17, S or O; the dotted line to X indicates the optional presence of a double bond depending on the nature of X; R17is H, –LS-RS, or R20; R20 is independently selected from F, Cl, Br, (CH2)j-OH, C1-6 alkyl, OC1-6 alkyl, OCH2Ph, (CH2)j-CO2R26, O-(CH2)k-NR26R27, C(=O)-O-(CH2)k-NR26R27, C(=O)-NR26R27, (CH2)j- NR26R27, NR26NH2, C(=O)-NH-(CH2)j-NR26R27, C(=O)-NH-C6H4-(CH2)j-R26, C(=O)-NH- (CH2)k-C(=NH)NR26R27, –L2-R28, S(O)2-(C1-6alkyl), O-(CH2)k-O-(C1-6alkyl), (CH2)j- S(O)2-NR26R27, C(=NH)-O-(C1-6alkyl), (CH2)k-O-(C1-6alkyl), CN, NCO, Cy, C(O)-NH- (CH2)j-Cy, C(O)-Cy, NH-C(O)-NR26R27and ; L2is a bond or a linker moiety having 1-200 non-hydrogen atoms selected from C, N, P, O, S or halogen, and optionally incorporates ether, oxo, carboxamidyl, urethanyl, branched, cyclic, unsaturated, heterocyclyl, aryl or heteroaryl moieties; and R28is selected from an azide, alkyne, bisulfone, carbohydrazide, hydrazine, hydroxylamine, iodoacetamide, isothiocyanate, maleimide, phosphine, pyrridopyridazine, semihydrazide, succinimidyl ester, sulfodichlorophenol ester, sulfonyl halide, sulfosuccinimidyl ester, 4- sulfotetrafluorophenyl ester, tetrafluorophenyl ester, thiazole, RA,O-(CH2)k-NR26R26, NHNH2, or is a targeting agent wherein the targeting agent is selected from a protein, a portion of a protein, a peptide, a nucleic acid, or an antibody; RAis selected from (CH2)j-OH, (CH2)j-CO2R26, C(=O)-O-(CH2)k-NR26R27, (CH2)jNR26R27, C(=O)-NH-(CH2)j-NR26R27and C(=O)-NH-(CH2)k-C(=NH)NR26R27; each R26and R27is independently selected from H and C1-12alkyl; each Cy is independently selected from a C5-6heterocyclyl or C5-6heteroaryl group, wherein the heterocyclyl or heteroaryl groups are optionally substituted with 1 or 2 R20groups; each j independently selected from 0, 1, 2, 3, 4, 5 or 6; each k is independently selected from 1, 2, 3, 4, 5 or 6; z is ’’’r 1; R''' is OH or –LS-RS; LSis a bond, an amino acid, a peptide chain having from 2 to 6 amino acids, an alkylene chain containing from 1 to 12 carbon atoms which may contain one or more carbon-carbon double or triple bonds, a paraformaldehyde chain –(OCH2)1-12-, a polyethylene glycol chain -(OCH2CH2)1-6-, which chains may be interrupted by or optionally incorporates one or more of P, O, S, NH, C5-9heteroarylene, phenylene, heterocyclyl, cycloalkyl, ether, oxo, carboxamidyl, and / or urethanyl moieties wherein the C5-9heteroarylene, phenylene, heterocyclyl, and / or cycloalkyl moieties are optionally substituted, optionally LSis:; and RSis a univalent saccharide substituent, preferably glycosyl or O-glycosyl.

6. The compound as claimed in either claim 3 or claim 4, wherein each of R1, R3,R7, and R9are H.

7. The compound as claimed in either claim 3 or claim 4, wherein the compound is of formula IV: (IV).

8. The compound as claimed in any one of the previous claims, wherein Q comprises X1- L-X2, wherein: X1is selected from O, S, NR13, CR13R14, CR13R14O, C(=O), C(=O)NR13, NR13C(=O), O-C(O) and C(O)-O, or is absent; L is selected from an amino acid, a peptide chain having from 2 to 6 amino acids, an alkylene chain containing from 1 to 12 carbon atoms which may contain one or more carbon- carbon double or triple bonds, a paraformaldehyde chain –(OCH2)1-12-, a polyethylene gly–ol chain -(OCH2CH2)1-6-, which chains may be interrupted by one or more P, O, S and / or NH groups and / or C5-9heteroarylene and / or phenylene, wherein each C5-9heteroarylene group and / or each phenylene group is optionally substituted; X2is selected from O, S, NR15, CR15R16, CR15R16O, C(=O), C(=O)NR15, NR15C(=O), O-C(O) and C(O)-O or is absent; and R13, R14,R15and R16are independently selected from H and C1-6alkyl.

9. The compound as claimed in any one of the preceding claims, wherein B comprises (A)q, wherein: q is selected from 0, 1, 2, 3, 4, 5 and 6;A is selected from: and ; A1 A2 for each A1 group one of Y3and Y4is independently selected from N-R30, S and O; and the other of Y3and Y4is CH; and Y5is independently selected from CR30, N, S and COH; for each A2 group one of Y6and Y7is independently selected from N and CH; and the other of Y6and Y7is CR30; and each R30is independently selected from H, C1-6alkyl, L2-R28and RS.

10. The compound as claimed in any one of the preceding claims, wherein T comprises a group of formula: wherein:p is 0 or 1; RTis selected from –L2-R28, phenyl, and C5-9heteroaryl, wherein the phenyl and C5-9heteroaryl groups are optionally substituted with up to three optional substituent groups selected from OH, C1-6alkyl, OC1-6alkyl, –L2-R28, (CH2)j-CO2R11, O-(CH2)k-NR11R12, (CH2)j- NR11R12, C(=O)-NH-(CH2)k-NR11R12, C(=O)-NH-R24, and C(=O)-NH-(CH2)k- C(=NH)NR11R12, optionally with the proviso that the optionally substituted C5-9heteroaryl is not indolyl; R19is selected from H, C1-6alkyl, L2-R28, RS, and (CH2)t-NR20R21; Y1and Y2are independently N or CR31, wherein at least one of Y1and Y2is CR31; each R31is independently selected from H, C1-6alkyl, L2-R28and RS; and R11, R12, and R24are independently selected from H, –L2-R28, and C1-6alkyl.

11. The compound of formula (I) and salts and solvates thereof as claimed in any one of the preceding claims, wherein the compound is selected from compounds of formulae:OH , andOH herein Rs is a univalent saccharide substituent, preferably glycosyl or O-glycosyl. The compound of any one of claims 1 to 11, or a pharmaceutically acceptable salt reof, wherein the compound comprises at least one L2-R28 group. The compound of claim 12, or a pharmaceutically acceptable salt thereof, wherein D, T, and / or B is substituted with a L2-R28 group. The compound of claim 12 or claim 13, or a pharmaceutically acceptable salt thereof,herein L2is selected from: herein XAA is an amino acid sequence;- K2is -[CH2CH2O-0-50- or -[CH2]o-i2-. The compound of any one of claims 3-14, or a pharmaceutically acceptable salt thereof,herein Ls is:herein Lc comprises one or more groups selected from an amino acid, an amino acidrivative, a peptide chain having from 2 to 6 amino acids or amino acid derivatives, an ylene chain containing from 1 to 12 carbon atoms which may contain one or more carbon¬rbon double or triple bonds, a paraformaldehyde chain -(OCH2)I-I2-, a polyethylene glycolain -(OCH2CH2)I-8-, which chains may be interrupted by one or more P, O, S and / or NHoups and / or C5-9 heteroarylene and / or phenylene, wherein each C5-9 heteroarylene group and / orch phenylene group is optionally substituted.The compound of claim 15, wherein Lc comprises , optionally o The compound of claim 15 or 16, wherein Lc comprises a a polyethylene glycol chain -CH2CH2)I-8-, optionally -(OCH2CH2)8-. The compound of any one of claims 15-17, wherein R28-Lc is selected from: The compound of any one of claims 12 to 18, or a pharmaceutically acceptable salt reof, wherein XAA is L-valyl-L-alanine.The compound of any one of claims 12 to 19, or a pharmaceutically acceptable saltreof, wherein R28 is maleimide: tionally linked to a targeting agent. The compound of any one of claims 12 to 20, or a pharmaceutically acceptable saltreof, wherein L2-R28 comprises, optionallytionally linked to a targeting agent. The compound of formula (I) and salts and solvates thereof of any one of claims 21 to linked, either directly or indirectly, to a targeting agent to provide a targeted conjugate. The compound of formula (I) and salts and solvates thereof of claim 22, wherein thempound comprises at least one L2-R28 group and the targeting agent is linked to thempound through the L2-R28 group. The compound as claimed in any one of claims 20 to 23, wherein the targeting agentmprises an antibody, an antibody fragment, a hormone or a hormone fragment.A compound of formula (I) and salts and solvates thereof according to any one of ims 1 to 24 for use as a medicament. A compound of formula (I) and salts and solvates thereof according to any one of ims 1 to 24 for use in the treatment of a proliferative disease. The compound of formula (I) and salts and solvates thereof according to claim 26 fore in the treatment of a proliferative disease, wherein the proliferative disease is selected fromadder cancer, bone cancer, bowel cancer, brain cancer, breast cancer, cervical cancer, colonncer, head and neck cancer, leukemia, liver cancer, lung cancer, lymphoma, melanoma,sophageal cancer, oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, rectalncer, renal cancer, retinoblastoma, sarcoma, skin cancer, stomach cancer, testicular cancer,yroid cancer and uterine cancer. A pharmaceutical composition comprising a compound of formula (I) and salts and vates thereof of any one of claims 1 to 24 and a pharmaceutically acceptable excipient,rrier or diluent. Use of a compound of formula (I) and salts and solvates thereof according to any one of ims 1 to 28 in the manufacture of a medicament for treating a proliferative disease. A method of treatment of a patient suffering from a proliferative disease, comprisingministering to said patient a therapeutically effective amount of a compound of any one of ims 1 to 24 or a pharmaceutical composition of claim 28. The method of claim 30, wherein the proliferative disease is selected from bladderncer, bone cancer, bowel cancer, brain cancer, breast cancer, cervical cancer, colon cancer,ad and neck cancer, leukemia, liver cancer, lung cancer, lymphoma, melanoma, oesophagealncer, oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, rectal cancer, renalncer, retinoblastoma, sarcoma, skin cancer, stomach cancer, testicular cancer, thyroid cancerd uterine cancer. An antibody -drug conjugate comprising a compound of formula (I) and salts and vates thereof according to any one of claims 1 to 24.

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