Imino-anthracycline derivatives and methods

Abstract

The present invention provides a novel class of cytotoxic imino-anthracycline derivatives, methods for their preparation, pharmaceutical composition containing them and use thereof in treating certain mammalian tumors. The present invention also provides imino-anthracycline-linker reagents suitable for conjugation with carriers and methods for their preparation.

Description

[0001] NMS-127 IMINO-ANTHRACYCLINE DERIVATIVES AND METHODS FIELD OF THE INVENTION The present invention provides a novel class of cytotoxic imino-anthracycline derivatives, methods for their preparation, pharmaceutical composition containing them and use thereof in treating certain mammalian tumors. The present invention also provides imino-anthracycline-linker reagents suitable for conjugation with carriers and methods for their preparation. BACKGROUND OF THE INVENTION Anthracyclines are antibiotic compounds that exhibit cytotoxic activity. Several studies have indicated that anthracyclines may operate to kill cells by a number of different mechanisms including: 1) intercalation with the DNA of a cell thereby inhibiting DNA-dependent nucleic acid synthesis; 2) production of free radicals which then react with cellular macromolecules to cause damage to the cells, 3) topoisomerase II inhibition by stabilizing an intermediate wherein a DNA strand is cut and covalently linked to the enzyme [ Marinello J, et al., “Anthracyclines as Topoisomerase II Poisons: From Early Studies to New Perspectives”, Int. J. Mol. Sci.2018;19(11):3480] or 4) interactions with the cell membrane [see, e.g., C. Peterson et al., ”Transport and storage of Anthracycline in experimental systems and human leukemia” in Anthracycline Antibiotics In Cancer Therapy (1982), pp.132-146; and N.R. Bachur, “Free Radical Damage” id. pp.97-102]. Because of their cytotoxic activity, anthracyclines have been used in the treatment of numerous cancers such as leukemia, breast carcinoma, lung carcinoma, ovarian adenocarcinoma and sarcomas [see e.g., P.H- Wiernik, in Anthracycline: Current Status And New Developments (1980), p. 11]. Commonly used anthracyclines include doxorubicin, epirubicin, idarubicin and daunomycin. Many new highly cytotoxic anthracycline derivatives have been synthesized. Anthracycline derivatives bearing a substituted morpholino ring linked at the C-3’ position of the sugar moiety have shown promising antitumor activity on experimental murine tumors [see: J. W. Lown, Bioactive Molecules, vol 6, (1988), pp.55-101] and in clinical trials in the treatment of hepatocellular carcinoma [see: C. Sessa, O. Valota, C. Geroni, Cardiovascular Toxicology, vol.7(2), (2007), pp.75-79 ]. Morpholino analogs of doxorubicin and daunorubicin, formed by cyclization on the glycoside amino group, have greater potency (Acton et al (1984) J. Med. Chem.638- 645; WO9802446; US 4464529; US 4672057; US 5304687). 5-imino anthracycline derivatives have been disclosed as antitumor agents in Acton et al (1979) J. Med. Chem.36-39 and in Acton et al (1981) J. Med. Chem.669-673. Despite the efforts in anticancer research, cancer remains a looming and elusive target, therefore there is still a need for new anticancer agents. Although these compounds may be useful in the treatment of neoplasms and other disease states wherein a selected cell population is sought to be eliminated, their therapeutic efficacy is often limited by the dose-dependent toxicity associated with their administration. Limitations in the use of anthracycline derivatives in clinical include inadequate accumulation in the tumor, cardiotoxicity, prolonged time of infusions, resistance of cancer cells overexpressing membrane transporters and dose- limiting side effects such as diarrhea and bone marrow suppression (lnt. J. Nanomedicine, 2007; 2(4): 567-83; Med. Sci. Monit.2000; 6(2); Adriamycin Review, pp 123-131, Mediokon, Belgium: European Press, 1975; Ann Intern Med. m2\ 96(2):133-139). Conjugation of cytotoxic drugs to carriers able to vehicle the drug thus improving tumor targeting or able to modify its pharmacokinetic properties is one of the strategies that has been undertaken to solve the above mentioned issues (Xie et al (2006) Expert. Opin. Biol. Ther.6(3):281-291; Kovtun et al (2006) Cancer Res.66(6):3214-3121. Anthracycline derivative conjugates have been disclosed, for instance, in lnt. Pat. App. W02009 / 099741, in WO2010 / 009124 and in WO2023083716. Different examples of conjugation of cytotoxic drugs with carriers such as proteins, peptides, aptamers, polymers, nanoparticles or small molecules have been reported. The conjugates show better target delivery, improved solubility and in some cases different pharmacokinetic properties, such as increasing half life or local concentration of the drug, thus improving drug performances. For this reason, there is an increasing demand for the development of functionalized cytotoxic agents suitable to be conjugated with different carriers. We now report here a new class of imino-anthracycline drug derivatives endowed with cytotoxic activity, thus useful for inhibiting tumor growth. Anthracycline derivatives conjugates have been reported to undergo deactivacting metabolism in whole blood stability test (Bioconjugate Chem.2018, 29, 1155−1167), while the new class of imino-anthracycline derivatives resulted metabolically stable. We also report functionalized imino-anthracycline-linker reagents which are suitable to be conjugated with carriers such as polyclonal antibodies, proteins, peptide or small molecules. BRIEFDESCRIPTION OF THE DRAWINGSFigure 1 shows the chemical structure of the Conjugate C1 obtained by reaction of compd.8a with cysteine as carrier. Figure 2 shows the HPLC chromatogram of the Conjugate C1 @ 320 nm and its m / z value after 2 hours treatment with lysosome extract in the presence of E64 cysteine protease inhibitor. Figure 3 shows the HPLC chromatogram of the Conjugate C1 @ 320 nm and its m / z values after 2 hours treatment with lysosome extract DEFINITIONS “Imino-anthracycline drug” or “Imino-anthracycline derivative” is a compound of formula (I) endowed with cytotoxic activity. “Imino-anthracycline-linker reagent” (Ia) is a compound comprising an imino-anthracycline drug or imino anthracycline derivative covalently attached to a linker moiety that includes a reactive functional group. Imino-anthracycline drug- linker reagent can be conveniently used to prepare the imino-anthracycline drug conjugates by reaction with a suitable carrier moiety. "Imino-anthracycline drug conjugate" or “imino-anthracycline derivative conjugate” is a compound comprised of an imino-anthracycline derivative covalently attached, through a linker, to a carrier moiety, wherein the carrier moiety includes antibodies, proteins, peptides or small molecules. Imino-anthracycline drug conjugate compounds include antibody-drug conjugate (ADC), peptide-drug conjugate (PDC) and small molecule drug conjugate (SMDC) compounds. “Linker” or "link" is a chemical moiety comprising a covalent bond or a chain of atoms or groups, covalently attached to the “imino-anthracycline drug” or “imino-anthracycline derivative” of formula (I) to form the imino-anthracycline-linker reagent (Ia). The term “antibody” herein is used in the broadest sense and specifically covers monoclonal antibodies, polyclonal antibodies, dimers, multimers, nobodies, multispecific antibodies (e.g., bispecific antibodies), and antibody fragments, so long as they exhibit the desired biological activity (Miller et al (2003) Jour. of Immunology 170:4854-4861). 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, 5thEd., Garland Publishing, New York). A target antigen generally has numerous binding sites, also called epitopes, recognized by CDRs (Complementarity-Determining Regions) on multiple antibodies. 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 specifically 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., IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2) or subclass of immunoglobulin molecule. The immunoglobulins can be derived from any species, including human, murine, or rabbit origin. An “ErbB receptor” is a receptor protein tyrosine kinase which belongs to the ErbB receptor family which are important mediators of cell growth, differentiation and survival. The ErbB receptor family includes four distinct members including epidermal growth factor receptor (EGFR, ErbB1, HER1), HER2 (ErbB2 or p185neu), HER3 (ErbB3) and HER4 (ErbB4 or tyro2). The ErbB receptor will generally comprise an extracellular domain, which may bind an ErbB ligand; a lipophilic transmembrane domain; a conserved intracellular tyrosine kinase domain; and a carboxyl-terminal signaling domain harboring several tyrosine residues which can be phosphorylated. The ErbB receptor may be a “native sequence” ErbB receptor or an “aminoacid sequence variant” thereof. The ErbB receptor may be native sequence human ErbB receptor. Accordingly, a “member of the ErbB receptor family” is EGFR (ErbB1), ErbB2, ErbB3, ErbB4 or any other ErbB receptor currently known or to be identified in the future. ERB3 and ERB4 receptors display increased expression on at least some breast cancer cell lines. Anti-ErbB2 antibodies have been characterized (US 5677171; US 5821337; US 6054297; US 6165464; US 6407213; US 6719971; US 6800738). “Carrier moiety” is derived from polyclonal and monoclonal antibodies, proteins or peptides of natural or synthetic origin. Carrier moieties are suitable for conjugation with imino-anthracycline linker reagents of formula (Ia). Carrier moieties may be derived from polyclonal antibodies raised against tumor associated antigens; or from monoclonal antibodies binding to antigens preferentially or selectively expressed on tumor cell populations; or from natural or recombinant peptides or proteins or growth factors preferentially or selectively binding to tumor cells; or from natural or synthetic polymeric carriers such as polylysine, polyglutamic acid, polyaspartic acid and their analogues and derivatives, or such as dextran or other polymeric carbohydrate analogues and their derivatives; or from synthetic copolymers such as those derived from N-(2-hydroxypropyl)methacrylamide (HPMA) see: J. Kopecek, Macromolecules. H. Benoit & P. Rempp, Ed.: 505-520 (1982) Pergamon Press. Oxford, England; or from poly(aminoacid) copolymers such as poly(GluNa, Ala, Tyr) which are useful as targetable drug-carriers for lung tissue R. Duncan et al., Journal of Bioactive and Compatible Polymers, Vol 4, July 1989. The term payload, as used herein, refers to any chemical structure deriving from chemical or biochemical degradation of the carrier comprising an imino-anthracycline residue endowed with a cytotoxic activity. In one particular embodiment preferred payloads are compound of formula (Ia’). 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 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 invention 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. The monoclonal antibodies herein specifically include “chimeric” antibodies in which a portion of 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. "Antibody fragments" comprise a portion of a full-length antibody, generally the antigen binding or variable region thereof. Examples of antibody fragments include Fab, Fab', F(ab')2, and Fv fragments; diabodies; linear antibodies; fragments produced by a Fab expression library, anti-idiotypic (anti-Id) antibodies, CDR (complementary determining region), and epitope-binding fragments of any of the above which specifically bind to cancer cell antigens, viral antigens or microbial antigens, single-chain antibody molecules; and multispecific antibodies formed from antibody fragments. The term “aminoacid side chain” includes those groups found in: (i) naturally occurring aminoacids such as alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine; (ii) minor aminoacids such as ornithine and citrulline; (iii) unnatural D-aminoacids, beta-aminoacids, synthetic analogs and derivatives of naturally occurring aminoacids; and (iv) all enantiomers, diastereomers, isomerically enriched, isotopically labelled, protected forms, and racemic mixtures thereof. With the term “straight or branched C1-C6alkyl” we intend any of the groups such as, for instance, methyl, ethyl, n- propyl, n-butyl, n-pentyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl. With the term “straight or branched C1-C4 hydroxyalkyl” we intend any of the groups such as, for instance, 2- hydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, 4-hydroxybutyl, 3-hydroxybutyl, 2-hydroxybutyl. With the term “halogen” we intend a fluorine, chlorine, bromine or iodine. With the term “straight or branched C1-C4haloalkyl”, we intend any of the above defined C1-C4alkyl groups which are substituted by one or more than one halogen atom such as, for instance, trifluoromethyl and trifluoroethyl. The term "heterocyclyl" as used herein refers to a saturated or unsaturated non-aromatic 5- to 7- membered carbocyclic ring, wherein 1 to 3 carbon atoms are replaced by heteroatoms selected from nitrogen, oxygen and sulfur, wherein said heteroatoms may be directly connected to each other, nitrogen and sulfur may optionally be oxidized, nitrogen may optionally be quaternized or bring a substituent. Non limiting examples of heterocyclyl groups are, for instance, piperidinyl, piperazinyl, oxazolidinyl, 4-methylpiperazinyl, 4-ethylpiperazinyl, diazepinyl, etc. The term "aryl" as used herein refers to carbocyclic hydrocarbons with from 1 to 2 ring moieties, either fused or linked to each other by single bonds, wherein at least one of the rings is aromatic. Examples of aryl groups according to the invention are, for instance, phenyl, biphenyl, α- or β-naphthyl, dihydronaphthyl, and the like. The term “carbocycle” refers to 3- to 7-membered all-carbon monocyclic ring, which may contain one or more double bonds, but does not have a completely conjugated π-electron system. Examples of carbocycles, without limitation, are cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexanyl, cyclohexenyl and cyclohexadienyl. The term “leaving group” refers to a group that can be substituted by another group in a substitution reaction. Such leaving groups are well-known in the art and examples include, but are not limited to, halides (fluoride, chloride, bromide and iodide), azides, sulfonates (e.g., an optionally substituted C1-C6alkanesulfonate, such as methanesulfonate and trifluoromethanesulfonate, or an optionally substituted C7-C12 alkylbenzenesulfonate, such as p-toluenesulfonate), succinimide-N-oxide, p-nitrophenoxide, pentafluorophenoxide, tetrafluorophenoxide, carboxylates, aminocarboxylates (carbamates) and alkoxycarboxylates (carbonates). For substitutions at saturated carbon, halides and sulfonates are preferred leaving groups. For substitutions at a carbonyl carbon a halide, succinimide-N-oxide, p-nitrophenoxide, pentafluorophenoxide, tetrafluorophenoxide, a carboxylate, or an alkoxycarboxylate (carbonate) may for example be used as a leaving group. The term "leaving group" also refers to a group that is eliminated because of an elimination reaction, e.g., an electronic cascade reaction or a spirocyclization reaction. In this instance, a halide, a sulfonate, an azide, an aminocarboxylate (carbamate) or an alkoxycarboxylate (carbonate) may for example be used as a leaving group. It is known to the person skilled in the art that transformation of a chemical functional group into another may require that one or more reactive centers in the compound containing such functional group may to be protected in order to avoid undesired side reactions. Protection of such reactive centers, and subsequent deprotection at the end of the synthetic transformations, can be accomplished following standard procedures described in the literature (see, for instance, Green, Theodora W. and Wuts, Peter G.M. – Protective Groups in Organic Synthesis, Third Edition, John Wiley & Sons Inc., New York (NY), 1999). Therefore, the term “protecting group” refers to a group used to protect such reactive centers in a chemical synthesis, for example, a hydroxyl group (–OH), an amino group (-NH), a thiol group (-SH), a carbonyl group (-C=O), a carboxylic group (-COOH). Examples of protecting groups are those reported in the literature (see, for instance, ibidem). The term “nitrogen protecting group” refers to a group that with the nitrogen atom form carbamates, amides, cyclic imides, N-alkyl and N-aryl amines. Such protecting groups are well-known in the art (see e.g. ibidem). Non limiting examples of carbamate protecting groups are, for instance, methyl and ethyl carbamate, 9-fluorenylmethyl carbamate (Fmoc), 2,2,2-trichloroethylcarbamate (Troc), t-butyl carbamate (BOC), vinyl carbamate (Voc), allyl carbamate (Alloc), benzyl carbamate (Cbz), p-nitrobenzyl and the like. Non limiting examples of amides are, for instance N- trichloroacetamide, N-trifluoroacetamide (TFA) and the like. Non limiting examples of cyclic imide protecting groups are, for instance, N-phthalimide, N-dithiasuccinoylimide (Dts) and the like. Non limiting examples of N-alkyl and N-aryl protecting groups are, for instance, N-allylamine, N-benzylamine and the like. The term “hydroxyl protecting group” refers to a group that with the oxygen atom form ethers, esters, cyclic acetals or ketals. Such protecting groups are well-known in the art (see e.g. ibidem). Non limiting examples of ethers protecting groups are, for instance, alkyl ethers and benzyl ethers, such as methoxymethyl ether (MOM-OR), tetrahydropyranyl ether (THP-OR), allyl ether (Allyl-OR), benzyl ether (Bn-OR), triphenylmethyl ether (Tr-OR) and the like, or silyl ethers, such as trimethylsilyl ether (TMS-OR), t-butyldimethylsilyl ether (TBS-OR or TBDMS-OR), t-butyldiphenylsilyl ether (TBDPS-OR) diphenylmethylsilyl ether (DPMS-OR) and the like. Non limiting examples of esters protecting groups are, for instance, trifluoroacetate, benzoate (Bz-OR) and carbonates, such as ethylcarbonate and the like. Non limiting examples of cyclic acetals or ketals protecting groups are, for instance, methylene acetal, ethylidene acetal, methoxymethylene acetal and the like. The term "active ester" refers to a functional group in which the alkoxy group of the ester moiety is a good leaving group. Examples of such alkoxy groups include, but are not limited to, succinimide-N-oxide (NHS esters), p- nitrophenoxide, pentafluorophenoxide, tetrafluorophenoxide, 1-hydroxybenzotriazole and 1-hydroxy-7- azabenzotriazole, and groups with comparable leaving capability. Unsubstituted alkyl-based alkoxy groups such as methoxy, ethoxy, isopropoxy, and t-butoxy do not qualify as good leaving groups and methyl, ethyl, isopropyl, and t- butyl esters are therefore not considered to be active esters. The term “electron withdrawing group” refers to an atom group that draws electron density from neighboring atoms towards itself, usually by resonance or inductive effects. Non limiting examples are halogens, trifluoromethyl group, nitro (NO2) group and nitrile (CN). The term “nucleophiles” refers to molecules that bear a nucleophilic group. The term “nucleophilic group” refers to a species that donates an electron-pair to an electrophilic group to form a chemical bond in a chemical reaction. Examples of such nucleophilic groups include, but are not limited to halogens, amines, nitrites, azides, hydroxyls, alkoxyde anions, carboxylate anions, thiols, thiolates, etc. The term “electrophilic group” refers to a species that accepts an electron-pair from a nucleophilic group to form a chemical bond in a chemical reaction. Examples of such electrophilic groups include, but are not limited to esters, aldehydes, amides, ketones, etc.The term “unnatural D-aminoacid” refers to the D- stereoisomer of the naturally occurring aminoacid (L-stereoisomer). SUMMARY OF THE INVENTION We now report here a new class of imino-anthracycline derivatives endowed with cytotoxic activity, thus useful for inhibiting tumor growth. We also report functionalized imino-anthracycline-linker reagents which are suitable to be conjugated with carriers such as polyclonal antibodies, proteins, peptide or small molecules. Accordingly, a first object of the present invention is an imino-anthracycline derivative of formula (I): OO HO A O wherein: A is a group selected from: Rc Rc , Het a 3- to 8- Cb is 3- to 8- membered carbocycle; Q is nitrogen or CH; Ra, Rb and Rc are independently hydrogen, a straight or branched (C1-C6) alkyl, or -(CH2CH2O)jCH3, wherein: j is an integer from 1 to 8; R1 and R2 are independently hydrogen, a straight or branched (C1-C6) alkyl, halogen or R1 and R2 taken together form a 3- to 6-membered carbocycle; n, n1 and n2 are independently an integer from 0 to 6. Preferred compound of formula (I) are imino-anthracycline derivatives wherein: A is a group selected from (IIa)-(IIg) Rc Rc , Het a 5- to 7- Cb is 5- to 7- membered carbocycle; Q is nitrogen or CH; Ra, Rb and Rc are independently hydrogen, a straight or branched (C1-C6) alkyl or -(CH2CH2O)jCH3wherein: j is an integer from 1 to 4; R1 and R2 are independently hydrogen, a straight or branched (C1-C6) alkyl, halogen or R1 and R2 taken together form a 3- to 6-membered carbocycle and n, n1and n2are independently an integer from 0 to 4. More preferred compound of formula (I) are imino-anthracycline derivatives wherein: A is a group selected from: Ra ,, wherein: Ra, Rb and Rc are independently a straight or branched (C1-C6) alkyl or -(CH2CH2O)jCH3 wherein: j is an integer from 1 to 4. Preferred specific compounds of formula (I), or a pharmaceutically acceptable salt thereof, are the compounds listed below: 2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]piperazine-1-carboxylate (compd.1); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]4-methylpiperazine-1- carboxylate (compd 2); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]1,4-diazepane-1-carboxylate (compd.3); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]4-(methylamino)piperidine-1- carboxylate (compd.4); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]N-methyl-N-(4-piperidyl) carbamate (compd.5); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]N-methyl-N-[2-(methylamino) ethyl]carbamate (compd.6); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]N-[2,2-dimethyl-3-(methylamino) propyl]-N-methyl-carbamate (compd.7); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] 4-(2-hydroxyacetyl)-1,4- diazepane-1-carboxylate(compd.8) and [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] N-[2-[(2-hydroxyacetyl)-methyl- amino]ethyl]-N-methyl-carbamate (compd.9). A second object of the present invention is to provide imino-anthracycline-linker reagents of formula (Ia):O O HO A1 O L wherein: A1 is a group selected from: Rc Rc * * , Het a 3- to 8- Cb is 3- to 8- membered carbocycle; Q is nitrogen or CH; Rb and Rc are independently hydrogen, a straight or branched (C1-C6) alkyl or -(CH2CH2O)jCH3wherein: j is an integer from 1 to 8; R1 and R2 are independently hydrogen, a straight or branched (C1-C6) alkyl, halogen or R1 and R2 taken together form a 3- to 6-membered carbocycle; n, n1and n2are independently an integer from 0 to 6; * is attachment point of the A1 group to the linker L and L is a linker of formula (IV): WPE G RM (IV)wherein: W is independently null or a self immolative system selected from the group consisting of: * * , R3 and R4 are, each independently, hydrogen, halogen, straight or branched (C1-C4) alkyl, straight or branched (C1-C4) hydroxyalkyl, -O(CH2-CH2O)zCH3, or -(CH2-CH2O)zCH3; wherein: z is an integer from 1 to 24; Su is group selected from (VIa)-(VIc): HO C H O H O O O O * is G or RM; PE is independently null, dipeptidic, tripeptidic or tetrapeptidic moiety, consisting of any combination of natural L-aminoacids or unnatural D-aminoacids; G is independently null or selected from the group consisting of (VIIa)-(VIIg): * y y y is an integer from 0 to 24; k is an integer from 0 to 8; * is the attachment point to the RM group; RM is a reactive moiety selected from the group consisting of (VIIIa)-(VIIIj): , R5 R6 are, or or branched (C1-C4) hydroxyalkyl, straight or branched (C1-C4) haloalkyl or, R5 and R6 taken together form a 3- to 6-membered carbocycle; R7 is hydrogen, (C1-C4) alkyl or an electron-withdrawing group selected from the group consisting of NO2 and CN; r is an integer from 0 to 7; m is an integer from 1 to 8; X is a halogen. In the compound of formula (Ia) the self immolative system W tethers in a stable way the moiety A1 to the PE-G-RM residue, or to the G-RM moiety when PE is null or to the RM group when PE and G are both null. Preferred compounds of formula (Ia) are imino-anthracycline-linker reagents wherein: A1 is group selected from:

[0002] *** * , Rc are or or - jCH3 wherein: j is an integer from 1 to 4; and L is a linker of formula (IV) wherein: W is independently null or a self immolative system selected from the group consisting of: * Su HOH N, * Su is group selected from (VIa)-(VIc); PE is a dipeptide, tripeptide or tetrapeptide moiety, consisting of any combination of natural L-aminoacids and unnatural D aminoacids selecting from: glycine, alanine, leucine, valine, citrulline, phenylalanine, glutamic acid and aspartic acid wherein the C-terminal aminoacid residue is linked to W, or to A1 when W is null, and the N-terminal aminoacid residue is linked to G or to RM when G is null. G is null or selected from the group consisting of (VIIa)-(VIIg): wherein: y is an integer from 0 to 12; k is an integer from 0 to 8; RM is selected from a group (VIIIa)-(VIIIj): wherein: R5, R6 and R7 are hydrogen; r is an integer from 0 to 4; m is an integer from 1 to 8; X is chlorine or bromine. More preferred compounds of formula (Ia) are anthracycline-linker reagents wherein: A1 is selected from the group consisting of (IIIa’), (IIIa”), (IIIb’), (IIIc’), (IIIe’’), (IIIe’’’), (IIIf’) and (IIIg’) wherein: Rb and Rc are independently straight (C1-C6) alkyl or -(CH2CH2O)jCH3 wherein: j is an integer from 1 to 4; and L is a linker of formula (IV) wherein: W is independently null or a self immolative system selected from the group consisting of: * Su HOH N, * Su is group selected from (VIa)-(VIc); PE is a dipeptide selected from valine-alanine and valine-citrulline, or a tripeptide selected from phenylalanine- leucine-glycine, glutamic acid-valine-alanine and glutamic acid-valine-citrulline or the tetrapeptide glycine- glycine-phenylalanine-glycine, wherein the C-terminal aminoacid residue is linked to W and the N-terminal aminoacid residue is linked to G or RM when G is null; G is null or selected from the group consisting of (VIIa)-(VIIg): wherein: y is an integer from 0 to 8; k is an integer from 0 to 5; RM is a reactive moiety selected from the group (VIIIa)-(VIIIj): wherein: R5, R6 and R7 are hydrogen, r is an integer from 0 to 4; m is an integer from 1 to 4; X is bromine. Others more preferred compounds of formula (Ia) are imino-anthracycline-linker reagents wherein: A1 is selected from the group consisting of (IIIa’), (IIIa”), (IIIb’), (IIIc’), (IIIe’’), (IIIe’’’), (IIIf’) and (IIIg’) wherein: Rb and Rc are independently straight (C1-C6) alkyl or -(CH2CH2O)jCH3wherein: j is an integer from 1 to 4; and L is a linker (IVa)-(IVh):

[0003] , r is an integer from 0 to 4. Preferred specific compounds of formula (Ia) or a pharmaceutically acceptable salt thereof, are the compounds listed below: O1-[[4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]propanoyl]amino]phenyl] methyl]O4-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl- 5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]piperazine-1,4- dicarboxylate (compd.1a);O1-[[4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1- yl)hexanoylamino]-3-methyl-butanoyl]amino]-5-ureido-pentanoyl]amino] phenyl]methyl]O4-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4- [[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4- dihydro-1H-tetracen-2-yl]ethyl]piperazine-1,4-dicarboxylate (compd.2a); O1-[[4-[[2-[[(2S)-2-[[2-[[2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]acetyl]amino]acetyl]amino]-3-phenyl-propanoyl] amino]acetyl]amino]phenyl]methyl]O4-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4- [[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4- dihydro-1H-tetracen-2-yl]ethyl]piperazine-1,4-dicarboxylate (compd.3a); O4-[[4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-l)hexanoylamino]-3-methyl-butanoyl]amino] propanoyl] amino]phenyl] methyl]O1-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl- 5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]1,4-diazepane-1,4- dicarboxylate (compd.4a); O4-[[4-[[2-[[(2S)-2-[[2-[[2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]acetyl]amino]acetyl]amino]-3-phenyl-propanoyl] amino]acetyl]amino]phenyl]methyl]O1-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4- [[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4- dihydro-1H-tetracen-2-yl]ethyl] 1,4-diazepane-1,4-dicarboxylate (compd.5a); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]4-[[4-[[(2S)-2-[[(2S)-2-[6-(2,5- dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]propanoyl]amino]phenyl]methoxycarbonyl-methyl- amino]piperidine-1-carboxylate (compd.6a); [4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]propanoyl]amino]phenyl]methyl 4-[methyl-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl- 5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethoxy]carbonyl- amino]piperidine-1-carboxylate (compd.7a); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] N-[2-[[4-[[(2S)-2-[[(2S)-2-[6-(2,5- dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]-5-ureido-pentanoyl]amino]phenyl]methoxycarbonyl- methyl-amino]ethyl]-N-methyl-carbamate (compd.8a); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] N-[2-[[4-[[(2S)-2-[[(2S)-2-[6-(2,5- dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]propanoyl]amino]phenyl]methoxycarbonyl-methyl-amino] ethyl]-N-methyl-carbamate (compd.9a); [4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]propanoyl]amino]phenyl]methyl N-[2,2-dimethyl-3-[methyl-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10- methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2- yl]ethoxy]carbonyl-amino]propyl]-N-methyl-carbamate (compd.10a); (4S)-4-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-5-[[(1S)-2-methyl-1-[[(1S)-1-methyl-2-oxo-2-[4-[[4-[2-oxo-2-[(2S,4S)- 2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4- dihydro-1H-tetracen-2-yl]ethoxy]carbonylpiperazine-1-carbonyl]oxymethyl]anilino]ethyl]carbamoyl]propyl]amino]-5-oxo-pentanoic acid (compd.11a); (4S)-4-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-5-[[(1S)-2-methyl-1-[[(1S)-1-methyl-2-[4-[[methyl-[2-[methyl-[2-oxo-2- [(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1- azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethoxy]carbonyl- amino]ethyl]carbamoyl]oxymethyl]anilino]-2-oxo-ethyl]carbamoyl]propyl]amino]-5-oxo-pentanoic acid (compd.12a); (4S)-4-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-5-[[(1S)-2-methyl-1-[[(1S)-1-methyl-2-oxo-2-[4-[[4-[2-oxo-2-[(2S,4S)- 2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo [7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethoxy]carbonyl-1,4-diazepane-1-carbonyl] oxymethyl]anilino]ethyl]carbamoyl]propyl]amino]-5-oxo-pentanoic acid (compd.13a); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] N-[2-[[2-[[[2-[[(2S)-2-[[2-[[2-[6- (2,5-dioxopyrrol-1-yl)hexanoylamino]acetyl]amino]acetyl]amino]-3-phenyl-propanoyl]amino]acetyl]amino]methoxy] acetyl]-methyl-amino]ethyl]-N-methyl-carbamate (compd.14a); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] 4-[2-[[[2-[[(2S)-2-[[2-[[2-[6-(2,5- dioxopyrrol-1-yl)hexanoylamino]acetyl]amino]acetyl]amino]-3-phenyl-propanoyl]amino]acetyl]amino]methoxy]acetyl]- 1,4-diazepane-1-carboxylate (compd.15a); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] N-[2-[[2-[[[(2S)-2-[[(2S)-2-[6-(2,5- dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]propanoyl]amino]methoxy]acetyl]-methyl-amino]ethyl]-N- methyl-carbamate (compd.16a) and [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(1S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] N-[2-[[2-[[[(2S)-2-[[(2S)-2-[6-(2,5- dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]propanoyl]amino]methoxy]acetyl]-ethyl-amino]ethyl]-N- ethyl-carbamate (compd.17a). The imino-anthracycline-linker reagents of formula (Ia) are compounds comprising a reactive functionality (RM moiety) that can react with a carrier moiety thus forming an imino-anthracycline drug conjugate. When the carrier moiety is an antibody (Ab) the conjugate is an antibody-drug conjugate (ADC); when the carrier moiety is a peptide the conjugate is an peptide-drug conjugate (PDC); when the carrier moiety is a small molecule (SM) the conjugate is an small molecule-drug conjugate (SMDC). In an imino-anthracycline drug conjugates of imino-anthracycline-linker reagent of formula (Ia) the bond between A1 and the linker L, or one or more of the covalent bonds between W and PE or between PE and G or between G and PE of the linker itself, may be stable outside a cell, i.e. extracellular, or it may be cleavable by enzymatic activity, hydrolysis, or other metabolic conditions thus releasing an imino-anthracycline payload that is the compound exhibiting cytotoxic activity. It is clear from the people skill in the art that, when a bound is broken the valence of the involved atoms is restored with hydrogen atom or with OH group depending upon the breaking type reaction. Therefore, without limiting the scope of the present invention, when the A1-L bond is broken, the released imino-anthracycline payload is a compound of formula (Ia’): OO HO A1 O wherein: A1 is selected from the group consisting of: Rc Rc , Het, Cb, Rb, Rc, R1, R2, Q, n, n1 and n2 are as defined above. The present invention also provides the use of a compound of formula (Ia) or a pharmaceutically acceptable salt thereof, in the preparation of conjugates. The present invention also provides a compound of formula (Ia) or a pharmaceutically acceptable salt thereof, for use in the preparation of conjugates. The imino-anthracycline compounds of formula (I), as defined above, can be prepared according to the general synthetic processes described hereafter in Scheme A. Scheme A (IX) Pathway 1 Pathway 2(I) Pathway 1 A compound of formula (I) wherein A is selected from the group consisting of (IIa)–(IIg), wherein at least one Ra, Rb or Rc is hydrogen; Het is a 3- to 8- membered heterocycle; Cb is 3- to 8- membered carbocycle; Q is nitrogen or CH; R1 and R2 are independently hydrogen, a straight or branched (C1-C6) alkyl, halogen or R1 and R2 taken together form a 3- to 6-membered carbocycle and n, n1and n2are independently an integer from 0 to 6, can be prepared as summarized in Scheme B below. Scheme B OO HO OO O H OO A' A' Step 1) reaction of a compound of formula (IX) with a suitable compound of formula (X): wherein A’ is a group selected from the group (IIa)– Rc Rc , (Bpoc), tert- or 4- or (C1-C6) alkyl, -(CH2CH2O)jCH3, or a protecting group orthogonal to Bpoc, Boc or MMT, preferably N-allyloxycarbonyl (Alloc); Het is a 3- to 8- membered heterocycle; Cb is 3- to 8- membered carbocycle; Q is nitrogen or CH; R1 and R2 are independently hydrogen, a straight or branched (C1-C6) alkyl, halogen or R1 and R2 taken together form a 3- to 6- membered carbocycle and n, n1and n2are independently an integer from 0 to 6. Step 2) reaction of the so obtained compound of formula (XI): A' with ammonia in a suitable A' wherein A’ is as defined in step 1. Step 3) removal of the protecting group / s from compound of formula (XII), to give a compound of formula (I) Please note that in compound of formula (I) when A is a group (IIa)-(IIg), wherein Ra is H, then A is equal to A1; namely a group (IIIa)H-(IIIg)H and compound of formula (I) is compound (Ia’). According to step 1) the reaction of a compound of formula (IX) with compound of formula (X) can be accomplished in a variety of ways. This reaction may be carried out in a suitable organic solvent, preferably DCM, acetone or THF, at a temperature ranging from room temperature to 40 C° and for a time varying from about 30 minutes to about 15 days. According to step 2) the reaction of a compound of formula (XI), to introduce imino group, can be performed in a variety of ways and experimental conditions. In particular, the reaction can be carried out with ammonia solution, in an organic solvent, preferably DCM, at room temperature or below, for a time varying from about 30 minutes to about 4 days. According to step 3) removal of the Bpoc, Boc or MMT protecting group from compound of formula (XII) can be accomplished in a variety of ways and experimental conditions, which are widely known in the art (see e.g. Protective Groups in Organic Synthesis; Theodora W. Greeen, Peter G. M. Wuts 4thedition). Preferably the removal is accomplished under acid conditions using hydrogen chloride, acetic acid, trifluoroacetic acid, trichloroacetic acid or dichloroacetic acid in solvents such as tetrahydrofuran or dichloromethane, at room temperature or below. Orthogonal protecting group, if present, can be carried out in a variety of ways and experimental conditions, which are widely known in the art (see e.g. Protective Groups in Organic Synthesis; Theodora W. Greeen, Peter G. M. Wuts 4thedition). When ortogonal protectig group is Alloc, the removal can be accomplished in neutral conditions with catalytic amounts of Pd(PPh3)4 optionally, in the presence of PhSiH3 or Bu3SnH as scavenger for the allyl system Pathway 2 A compound of formula (I) wherein A is selected from the group (IIa)–(IIg), wherein: Ra, Rb and Rc are independently straight or branched (C1-C6) alkyl or -(CH2CH2O)jCH3; Het is a 3- to 8- membered heterocycle; Cb is 3- to 8- membered carbocycle; Q is nitrogen or CH; R1 and R2 are independently hydrogen, a straight or branched (C1-C6) alkyl, halogen or R1 and R2 taken together form a 3- to 6-membered carbocycle and n, n1 and n2 are independently an integer from 0 to 6, can be prepared as summarized in Scheme C below. Scheme CO O OO O O O O O O AOA Step 4) reaction of a compound of formula (IX) with the intermediate of formula (XIII): (XIII) A wherein A is selected from the group consisting of (IIa)–(IIg), wherein Ra, Rb and Rc are independently straight or branched (C1-C6) alkyl or -(CH2CH2O)jCH3; Het is a 3- to 8- membered heterocycle; Cb is 3- to 8- membered carbocycle; Q is nitrogen or CH; R1 and R2 are independently hydrogen, a straight or branched (C1-C6) alkyl, halogen or R1 and R2 taken together form a 3- to 6-membered carbocycle and n, n1and n2are independently an integer from 0 to 6. Step 5) reaction of the so obtained compound of formula (XIV): wherein A is as defined in step 4, compound of formula (I): wherein A is defined above. According to step 4) the reaction of a compound of formula (IX) with a compound of formula (XIII) can be performed as described above under step 1. According to step 5) the reaction of a compound of formula (XIV), to introduce imino group, can be performed as described above under step 2. The compounds of general formula (I) can be further converted in other compounds of the same general formula (I) according to methods well known in the literature, as reported in the experimental section; see e.g. example 5 pages 45-46. Imino-anthracycline-linker reagents compound of formula (Ia), as defined above, can be prepared according to the general synthetic processes described hereafter in Scheme D. Scheme D O OH O O OH O O A1 O A1 L Accordingly, Step 6) reaction of a compound of formula (Ia’): OOH OO A1 wherein A1 is a group of formula

[0004] Rc Rc , : L (XV)wherein LG is a group selected from chlorine, p-Nitrophenol, imidazole, -OH, -O-succiminidyl or -O-acetyl and L is a linker of formula (IV): WPE G RM (IV)wherein W is independently null or a group selected from (Va)-(Vf); PE is independently null or a dipeptidic, tripeptidic or tetrapetidic moiety consisting of any combination of natural L-aminoacids or unnatural D-aminoacids; G is independently null or selected from the group consisting of (VIIa)-(VIIg) and RM is an reactive moiety selected from the group (VIIIa)-(VIIIj), to give a compound (Ia). According to step 6) the reaction of a compound of formula (Ia’) with a compound of formula (XV) can be accomplished in a variety of ways and experimental conditions, which are widely known in the art. When LG is p-Nitrophenol, the reaction can be performed in a suitable organic solvent, preferably DMF or DCM, in the presence of a suitable base, preferably TEA or DIPEA, at a temperature ranging from room temperature to 100 C° and for a time varying from about 1 hour to about 48 hours, when LG is OH, the reaction may be carried out in a suitable organic solvent, preferably DCM, THF or DMF, in presence of coupling agent preferably, HATU, TBTU or EEDQ at a temperature ranging from 0° C to 80 °C and for a time varying from about 30 minutes to about 24 hours, when LG is O-succiminidyl, the reaction can be performed in a suitable organic solvent, preferably DMF, DCM or THF, in the presence of a suitable base, preferably TEA or DIPEA, at a temperature ranging from room temperature to 80 C° and for a time varying from about 1 hour to about 24 hours, when LG is O-acetyl, the reaction can be performed in a suitable organic solvent, preferably DCM, THF, acetone or toluene in the presence of a suitable base, preferably K2CO3, or a suitable acid preferably pyridinium p-toluenesulfonate at a temperature ranging from 0° C to 80 C° and for a time varying from about 1 hour to about 24 hours. The compounds of general formula (IX), (X), (XIII) and (XV) are commercially available or can be prepared with known methods starting from commercially available intermediate through procedure and experimental conditions which are widely known in the art or can be prepared as describe below in the experimental part. The compound of general formula (I) and (Ia), can be prepared according to scheme B, C and D reported above, under experimental conditions reported in the experimental part below. From all of the above it is clear to the skilled person that any compound of formula (I) and (Ia) bearing a functional group which can be further derivatized to another functional group, by working according to methods well known in the art thus leading to other compounds of the formula (I) and (Ia), is intended to be comprised within the scope of the present invention. When preparing the compounds of general formula (I) and (Ia) according to any of the above variants of the process, optional functional groups within the starting materials, the reagents or the intermediates thereof, and which could give rise to unwanted side reactions, need to be properly protected according to conventional techniques (see e.g., Protective Groups in Organic Synthesis; Theodora W. Greeen, Peter G. M. Wuts 4thedition). Likewise, the conversion of these latter into the free deprotected compounds may be carried out according to known procedures. The compounds of every general formula can be further transformed in other compounds of the same general formula according to methods well known in the literature, as reported in the experimental section. The final compounds may be isolated and purified using conventional procedures, for example chromatography and / or crystallization and salt formation. The synthesis of a compound of general formula (I) and (Ia), according to the synthetic processes described above, can be conducted in a stepwise manner, whereby each intermediate is isolated and purified if needed by standard purification techniques, like, for example, column chromatography, before carrying out the subsequent reaction. Alternatively, two or more steps of the synthetic sequence can be carried out in a so-called “one-pot” procedure, as known in the art, whereby only the compound resultant from the two or more steps is isolated and purified. If a stereogenic center or another form of an isomeric center is present in a compound of the present invention, all forms of such isomer or isomers, including enantiomers and diastereomers, are intended to be covered herein. Compounds containing a stereogenic center may be used as a racemic mixture, an enantiomerically enriched mixture, or the racemic mixture may be separated using well-known techniques and an individual enantiomer may be used alone. Such separation procedures comprise standard chromatographic techniques, including chromatography using a chiral stationary phase, or crystallization. General methods for separation of compounds containing one or more asymmetric centers are reported, for instance, in Jacques, Jean; Collet, André; Wilen, Samuel H., Enantiomers, Racemates, and Resolutions, John Wiley & Sons Inc., New York (NY), 1981. In cases in which compounds have unsaturated carbon-carbon double bonds, both the cis (Z) and trans (E) isomers are within the scope of this invention. In cases when compounds can exist in tautomeric forms, each form is contemplated as being included within this invention whether existing in equilibrium or predominantly in one form. Pharmaceutically acceptable salts of the compounds of formula (I) and (Ia) include the salts with inorganic or organic acids, e.g. nitric, hydrochloric, hydrobromic, sulfuric, perchloric, phosphoric, acetic, trifluoroacetic, dichloroacetic, propionic, glycolic, lactic, oxalic, fumaric, malonic, malic, maleic, tartaric, citric, benzoic, cinnamic, mandelic, methanesulphonic, isethionic and salicylic acid. Pharmaceutically acceptable salts of the compounds of formula (I) and (Ia) also include the salts with inorganic or organic bases, e.g. alkali or alkaline-earth metals, especially sodium, potassium, calcium, ammonium or magnesium hydroxides, carbonates or bicarbonates, acyclic or cyclic amines. The present invention also provides a method of treating cancer, which comprises administering to a mammal, preferably a human, in need thereof, an effective amount of a compound of formula (I) as defined above. Furthermore the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, as defined above, for use in a method of treating cancer, which comprises administering to a mammal, preferably a human, in need thereof, an effective amount of a compound of formula (I) as defined above. In another aspect the invention provides the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof, as defined above, in the manufacture of a medicament for treating cancer, which comprises administering to a mammal, preferably a human, in need thereof, an effective amount of a compound of formula (I) as defined above. In yet another aspect the invention provides a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, as defined in claim 1, for treating cancer. According to a preferable embodiment of the present invention the cancer is selected from the group consisting of: carcinomas, such as bladder, breast, kidney, liver, colon, lung, including small cell lung cancer, esophagus, gall- bladder, ovary, pancreas, stomach, cervix, prostate, and skin, including squamous cell carcinoma; hematopoietic tumors of lymphoid lineage including leukemia, acute lymphocitic leukemia, acute lymphoblastic leukemia, B-cell lymphoma, angioimmunoblastic T-cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, hairy cell lymphoma and Burkitt's lymphoma; hematopoietic tumors of myeloid lineage, including acute and chronic myelogenous leukemias, myelodysplastic syndrome and promyelocytic leukemia; tumors of mesenchymal origin, including fibrosarcoma and rhabdomyosarcoma; tumors of the central and peripheral nervous system, including glioma, glioblastoma, glioblastoma multiforme, astrocytoma, oligodendroglioma, paraglioma, neuroblastoma, and schwannomas; and other tumors, including melanoma, uveal melanoma, seminoma, teratocarcinoma, osteosarcoma, adrenocortical cancer, xeroderma pigmentosum, keratoxanthoma, thyroid cancers, such as papillary thyroid carcinoma and medullary thyroid carcinoma, Kaposi's sarcoma, chondrosarcoma, and cholangiocarcinoma. The present invention also provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, as defined above, for use as a medicament. The present invention also provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof, as defined above, and at least one pharmaceutically acceptable excipient, carrier or diluent. The present invention also provides a therapeutic combination comprising (a) a compound of formula (I), as defined above and (b) one or more chemotherapeutic agents. Additionally, the invention provides a product comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, as defined above, and one or more chemotherapeutic agents, as a combined preparation for simultaneous, separate or sequential use in anticancer therapy. Moreover, the present invention provides a compound of formula (I), or a pharmaceutically acceptable salt thereof, as defined above, for use in a method of treating a mammal in need thereof in combination with radiation therapy or in combination with chemotherapeutic agents. In one embodiment the chemotherapeutic agents is selected from the group consisting of cytostatic agents, cytotoxic agent and immune checkpoint inhibitors. Cytostatic or cytotoxic agents include, but are not limited to, antibiotic-type agents, alkylating agents, antimetabolite agents, hormonal agents, immunological agents, interferon-type agents, cyclooxygenase inhibitors (e.g. COX-2 inhibitors), matrixmetalloprotease inhibitors, telomerase inhibitors, tyrosine kinase inhibitors, anti-growth factor receptor agents, anti-HER agents, anti-EGFR agents, anti-angiogenesis agents (e.g. angiogenesis inhibitors), farnesyl transferase inhibitors, ras-raf signal transduction pathway inhibitors, cell cycle inhibitors, other cdks inhibitors, tubulin binding agents, topoisomerase I inhibitors, topoisomerase II inhibitors, aromatase inhibitors, inhibitors of kinesins, therapeutic monoclonal antibodies, inhibitors of mTOR, histone deacetylase inhibitors, inhibitors of hypoxic response. Immune checkpoint inhibitors include, but are not limited to, PD-1 and PD-L1 antagonists. If formulated as a fixed dose, such combination products employ the compounds of this invention within the dosage range described below and the other pharmaceutically active agent within the approved dosage range. Compounds of formula (I) may be used sequentially with known anticancer agents when a combination formulation is inappropriate. The compounds of formula (I) of the present invention, suitable for administration to a mammal, e.g. to humans, can be administered by the usual routes and the dosage level depends upon the age, weight, and conditions of the patient and administration route. For example, a suitable dosage adopted for oral administration of a compound of formula (I) may range from about 10 to about 1000 mg per dose, from 1 to 5 times daily. The compounds of the invention can be administered in a variety of dosage forms, e.g. orally, in the form of tablets, capsules, sugar or film coated tablets, liquid solutions or suspensions; rectally in the form of suppositories; parenterally, e.g. intramuscularly, or through intravenous and / or intrathecal and / or intraspinal injection or infusion. The pharmaceutical compositions containing the compounds of the invention are usually prepared following conventional methods and are administered in a suitable pharmaceutical form. For example, the solid oral forms may contain, together with the active compound, diluents, e.g. lactose, dextrose, saccharose, sucrose, cellulose, corn starch or potato starch; lubricants, e.g. silica, talc, stearic acid, magnesium or calcium stearate, and / or polyethylene glycols; binding agents, e.g. starches, arabic gum, gelatine methylcellulose, carboxymethylcellulose or polyvinyl pyrrolidone; disintegrating agents, e.g. starch, alginic acid, alginates or sodium starch glycolate; effervescing mixtures; dyestuffs; sweeteners; wetting agents, such as lecithin, polysorbates, laurylsulphates; and, in general, non-toxic and pharmacologically inactive substances used in pharmaceutical formulations. These pharmaceutical preparations may be manufactured in known manner, for example, by means of mixing, granulating, tableting, sugar-coating, or film-coating processes. The liquid dispersions for oral administration may be, e.g. syrups, emulsions and suspensions. As example the syrups may contain, as a carrier, saccharose or saccharose with glycerin and / or mannitol and sorbitol. The suspensions and the emulsions may contain, as examples of carriers, natural gum, agar, sodium alginate, pectin, methylcellulose, carboxymethylcellulose or polyvinyl alcohol. The suspension or solutions for intramuscular injections may contain, together with the active compound, a pharmaceutically acceptable carrier, e.g. sterile water, olive oil, ethyl oleate, glycols, e.g. propylene glycol and, if desired, a suitable amount of lidocaine hydrochloride. The solutions for intravenous injections or infusions may contain, as a carrier, sterile water or preferably they may be in the form of sterile, aqueous, isotonic, saline solutions or they may contain propylene glycol as a carrier. The suppositories may contain, together with the active compound, a pharmaceutically acceptable carrier, e.g. cocoa butter, polyethylene glycol, a polyoxyethylene sorbitan fatty acid ester surfactant or lecithin. EXPERIMENTAL PART The short forms and abbreviations used herein have the following meaning: g (gram) mg (milligram) mL (millilitre) µL (microliter) mM (millimolar) mmol (millimole) µM (micromolar) MHz (Mega-Hertz) h hour(s) Hz (Hertz) mm (millimetres) ppm (parts per million) cm (centimetres) min (minutes) µm (micron) M (molar) nM (nanomolar) HRMS (high-resolution mass spectra) DTT (dithiothreitol) Rt (retention time) KOtBu (potassium tert-butoxide) rt (room temperature) TEA (triethylamine) TFA (trifluoroacetic acid) Na2SO4 (sodium sulphate) Et2O (Diethyl ether) NaHCO3 (sodium bicarbonate) AcOH (acetic acid) ESI (electrospray ionization) Cs2CO3 (caesium carbonate) K3PO4(potassium phosphate) KOH (potassium hydroxide) p-TsOH (p-toluensulfonic acid) EtOAc (ethyl acetate) LiHMDS (lithium bis(trimethylsilyl)amide) DMA (N,N-dimethylacetamide) DMF (N,N-dimethylformamide) DCM (dichloromethane) DIPEA (N,N-diisopropyl-N-ethylamine) hex (hexane) THF (tetrahydrofuran) DMSO (dimethylsulfoxide) MeOH (methanol) ACN (acetonitrile) EtOH (ethanol) Bn (benzyl) -OMs (mesylate) -OTs (tosylate) HOBT (N-hydroxy-benzotriazole) NMR (Nuclear magnetic resonance) MS (mass spectroscopy) m / z (mass to charge ratio) LC (Liquid chromatography) TLC (thin layer chromatography) ADC (antibody drug conjugate) TCEP (tris(2-carboxyethyl)phosphine) DAR (Drug to Antibody Ratio) PBS (phosphate buffered saline) Bpoc (2-(4-biphenyl)isopropoxycarbonyl) BOC (tert-butoxycarbonyl) Alloc (N-allyloxycarbonyl) Pd(PPh3)4(Tetrakis(triphenylphosphine)palladium) PhSiH3 (Phenylsilane) Bu3SnH (Tributylstannane) TEA (triethylamine) Cys (cysteine) EEDQ (N-Ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) ESI (electrospray ionisation) EDTA (Ethylenediaminetetraacetic acid) ATP (Adenosine triphosphate) RT (room temperature) Da (Dalton) Å (Amstrong) (NaHCO3) Sodium bicarbonate HATU (1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate) SDS-PAGE (sodium dodecyl sulphate–polyacrylamide gel electrophoresis) PLRP LC / MS (Polymeric Reversed Phase Liquid Chromatography / Mass Spectrometry) HPLC-MS (high performance liquid chromatography - mass spectroscopy) TBTU (N,N,N’,N’-tetramethyl-O-(benzotriazol-1-yl)uronium-tetrafluoroborate) RP-HPLC (reverse phase high performance liquid chromatography) EDCI (1-etil-3 (3-dimetilaminopropil) carbodiimide) PREPARATION OF A CONJUGATE As an example, that is not intended to limit the scope of the invention, the preparation of a conjugate between the drug- linker reagent of general formula (Ia), i.e. compd.8a, with a carrier, i.e cysteine, is reported in Figure 1. 6 µL of 1.5 mM solution of the compd.8a in ACN 90% / DMSO 10% were incubated with 4 µL Cys 50 mM and 10 µL of 100mM Tris-HCl pH 7.4 in a total volume of 20 µL aqueous solution, for 2 hr at 25 °C. The obtained Conjugate C1 (m / z = 1474.7 (M+H)+) then was analyzed by HPLC ESI-MS using a reversed phase HPLC method (PLRP-S column 1000A 8uM 150 X 2.1 mm) on a 1100 Agilent HPLC instrument coupled with an Agilent 1946 single quadrupole mass spectrometry detector with an orthogonal ESI source. Release of the payload from a conjugate As an example, that is not intended to limit the scope of the invention, the release of a compound of formula (Ia’), i.e. compd.6 from the Conjugate C1 was performed in presence of cathepsin as reported below. Two aliquots of 5 µL of the conjugate were incubated with 5 µL of 5 mg / mL lysosome extract and 40 µL of 200 mM sodium acetate buffer pH 5.5 / 1 mM EDTA. In one aliquot 1 µL of 1mM E64 cysteine protease inhibitor was added and used as reference (Figure 2). The reaction was incubated for 2 hours at 37 °C with gentle shaking, then the samples were analyzed (Figure 3) by HPLC-MS with UV detection at 320nm and MS detection in the 400-3000 m / z range performed with ESI-ToF MS (Agilent). In these experimental conditions, the payload-linker was partially cleaved by the lysosome enzyme Cathepsin B and subsequently compd.6 was released in solution. In vitro cell proliferation assay The antiproliferative activity of compd.1, 3, 4, 5 and 6 was tested in human cell lines including the breast cancer cell lines NCI-N87, HCC1954, MDA-MB-468 and the colorectal cancer cell line SW620. Exponentially growing cells were seeded in 384-well (Microclear black, Greiner, Frickenhausen, Germany) at a final density ranging from 3,000 to 30,000 cells per cm2in appropriate culture medium + 10% Fetal Calf Serum (FCS, Gibco, Thermo Fisher Scientific). After 24 hours, compound solutions were serially diluted in 100% DMSO and then added to the cell cultures to obtain final compound concentrations in the range 0.001–10 nM. The final DMSO concentration in test wells was adjusted to 0.1% (v / v); control wells were mock-treated and contained the same final concentration of DMSO as test wells. All treatments were performed in duplicate and experiments were repeated three times (N=3). Cell viability was determined after 144 hours by ATP determination in each test well with a luciferase-based detection system (CellTiterGlo, Promega, Madison, WI, USA) following manufacturer’s instructions. The intensity of emitted light (RLU) was measured using an EnVision reader (PerkinElmer, Waltham, MA USA) and expressed as percentage of untreated controls. Inhibitory activity was evaluated comparing treated versus control data using Assay Explorer software (Symix Technologies Inc.). IC50 values were calculated by sigmoidal fitting interpolation using a quadriparametric Hill equation (Graphpad Prism). The mean IC50s (nanomolar, nM) and their standard deviations (StDev) are shown in Table 1. The data indicate that all compounds inhibit the proliferation of all cell lines tested at 144 hours with sub-nanomolar potency. Table 1 NCI-N87 HCC1954 MDA-MB-468 SW620Compd. No N IC50 (nM) StDev N IC50 (nM) StDev N IC50 (nM) StDev N IC50 (nM) StDev6 3 0.093 0.020 3 0.115 0.012 3 0.108 0.045 3 0.516 0.1793 3 0.038 0.017 3 0.047 0.010 3 0.040 0.002 3 0.113 0.0651 3 0.020 0.001 3 0.040 0.009 3 0.027 0.003 3 0.053 0.0194 3 0.021 0.008 3 0.027 0.012 3 0.025 0.009 3 0.086 0.0615 3 0.040 0.002 3 0.047 0.002 3 0.053 0.008 3 0.189 0.164PREPARATION OF COMPOUNDS OF FORMULA (I) AND (Ia) For a reference to any specific compound of formula (I) and (Ia) of the invention, optionally in the form of a pharmaceutically acceptable salts, see the experimental section and claims. Referring to the examples that follow, compounds of the present invention were synthesized using the methods described herein, or other methods, which are well known in the art. With the aim at better illustrating the present invention, without posing any limitation to it, the following examples are given. As used herein the symbols and conventions used in the processes, schemes and examples are consistent with those used in the contemporary scientific literature, for example, the Journal of the American Chemical Society or the Journal of Biological Chemistry. Compound names are IUPAC names, generated by using Biovia Draw 2020 (by Dassault Systemes). Unless otherwise noted, all materials, including anhydrous solvent such as DMF, THF, DCM, were obtained from commercial suppliers, of the best grade and used without further purification. All reactions involving air- or moisture- sensitive compounds were performed under nitrogen or argon atmosphere. GENERAL PURIFICATION AND ANALYTICAL METHODS Flash Chromatography was performed on silica gel (Merck grade 9395, 60A). HPLC LCQ method HPLC-MS / UV analyses were performed on a LCQ DecaXP (Thermo, San Jose, US) ion trap instrument, equipped with an electrospray (ESI) ion source. The mass spectrometer is connected to a Surveyor HPLC system (Thermo, San Jose, US) with an UV photodiode array detector (UV detection 215-400 nm). A Waters XSelect CSH C18 column 50x4.6 mm, 3.5 µm particle size was used. Mobile phase A was ammonium acetate 5 mM buffer (pH 4.5 with acetic acid):acetonitrile 95:5, and mobile phase B was ammonium acetate 5 mM buffer (pH 4.5 with acetic acid): acetonitrile 5:95. Gradient from 0 to 100 % B in 7 minutes, hold 100% B 2 minutes. Flow rate 1 mL / min. Injection volume 10 µL. Retention times (HPLC r.t.) are given in minutes. Full scan, mass range from 50 to 1200 amu. Heated capillary temp was 200 °C and Spray voltage value was set at 4kV. Mass are given as m / z ratio. Instrument control, data acquisition and processing were performed by using Xcalibur 1.4 SR1 software (Thermo). UPLC / HRMS High Resolution Mass Spectrometry (HRMS) was performed on a Waters Acquity H-class UPLC equipped with a Waters Acquity PDA detector and with Waters Xevo G2-XS quadrupole time of flight mass spectrometer (qTOF). Reversed phase chromatography was performed on a Waters BEH C18 UPLC column (2.1 x 50mm, particle size1.7µ m) kept at 50°C. Two mobile phases were used: phase A 0.1% formic acid in highly purified water (UPLC-MSgrade) and mobile phase B was 0.1% formic acid in acetonitrile (UPLC-MS grade). The gradient was run from 5% to95% of mobile phase B in 4.86 min, hold 95% B 0.64 minutes. Flow rate 0.5 mL / min. Injection volume 1 µ L. The PDArange was 210–400 nm 4.8 nm resolution. The mass experiment type was MSe (Full scan precursor and fragment ion scanning) and it was conducted in resolution mode. The ESI source operated at 150 °C, 0.8 kV capillary voltage, 25 V cone voltage, 1000 L / h desolvation gas flow at 500 °C and 100 L / h nitrogen cone flow. The collision Energy was 4.00 eV for the Low energy acquisition and was 20.0 to 40.0 eV for the high energy ramp. The range 100-2000 m / z was fixed, and all the experiments were carried out at 0.08s as mass scan time. Leucine Enkephalin was chosen as stable, soluble, and appropriate reference compound for real-time single-point accurate mass error correction.100 pg / µL solution of Leucine Enkephaline was directly introduced in the ESI source during all the acquisition. Preparative HPLC The preparative HPLC equipment consisted of a Shimadzu HPLC system equipped with SCL-8A System Controller, two LC-8A pumps, SPD-6A UV spectrophotometric detector and manual Rheodyne injection system. Data acquisition (analogic signal) and data processing were provided by Empower 2 software. Purification was carried out at 25 °C ata flow rate of 15mL / min using a Waters X-Terra MS RP18 (150 x 30 mm, 10 µ m) column. Mobile phase A was 0.1%TFA in water / acetonitrile (95:5) or, alternatively, Mobile phase A was 0.05% NH3 in water / acetonitrile (95:5) and mobile phase B was H2O / acetonitrile (5:95); the gradient was from 10 to 90% B in 15 minutes then ramp to 100% B in 0.1minutes. Injection volume max 500 µ L.NMR1H-NMR spectra were recorded at a constant temperature of 28 °C on a Varian INOVA 400 spectrometer operating at 400.5 MHz and equipped with a 5 mm1H{15N-31P} z-axis PFG indirect detection probe or on a Varian INOVA 500 spectrometer operating at 499.7 MHz and equipped with a 5 mm1H{13C-15N} triple resonance indirect detection probe or on Bruker 600 Avance III spectrometer operating at 600.13 MHz equipped with a 5 mm broadband inverse detection BBI Z gradient probe. Chemical shifts were referenced with non-deuterated residual solvent signal. Data are reported as follows: chemical shift (δ), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, qt = quintet, br. s = broad singlet,dd = doublet of doublets, ddd = doublet of doublets of doublets, m = multiplet), coupling constants (J, Hz) and number of protons. The synthetic preparation of some compounds of formula (I) of the invention is described in the following examples. The compounds of the present invention, as prepared according to the following examples, were also characterized by1H NMR and / or by HPLC / MS analytical data; HPLC / MS data were collected following any one of methods LCQ or LCT. Example 1 [1-methyl-1-(4-phenylphenyl)ethyl] 4-chlorocarbonylpiperazine-1-carboxylate [1-methyl-1-(4-phenylphenyl)ethyl] 1.0 Eq.) (prepared as reported in WO2023083716) and triethylamine (0.070 g, 0.097 mL, 0.693 mmol, 1.5 Eq.) were dissolved in toluene (8 mL). This solution was cooled in ice bath and then phosgene (solution in toluene 20%, 0.27 g, 0.29 mL, 0.55 mmol, 1.2 Eq.) was added dropwise. After 10 minutes, ice bath was removed. After 20 minutes, HPLC-MS showed complete conversion. The white solid formed during reaction was removed by filtration and filtrate was evaporated to dryness by rotavapor. Crude mixture was loaded to a chromatographic column and eluted with Hexane / AcOEt 8 / 2 to 7 / 3 to give title compound (white solid, 0.157 g, 87% yield). 1H NMR (401MHz, DMSO-d6) δ ppm 1.71 - 1.73 (6 H, m) 3.33 - 3.80 (8 H, m) 7.33 (1 H, d, J=7.10 Hz) 7.39 - 7.46 (4 H, m) 7.58 - 7.64 (4 H, m); MS (ESI) : [M+K]+425.3. Operating in an analogous way, but employing suitable substituted starting material the following compounds were obtained: [1-methyl-1-(4-phenylphenyl)ethyl] 4-chlorocarbonyl-1,4-diazepane-1-carboxylate 1H NMR (401 MHz, DMSO-d6) δ m) 1.81 - 1.97 (1 H, m) 3.38 - 3.89 (8 H, m) 7.31 - 7.51 (5 H, m) 7.56 (4 H, m) MS (ESI) : [M+Na]+423.3.[1-methyl-1-(4-phenylphenyl)ethyl] N-(1- chlorocarbonyl-4-piperidyl)-N-methyl-carbamateMS (ESI) : [M+K]+453.3 [1-methyl-1-(4-phenylphenyl)ethyl] 4-[chlorocarbonyl(methyl)amino]piperidine-1-carboxylate MS (ESI) : [M+Na]+437.1. [1-methyl-1-(4-phenylphenyl)ethyl] N-[2-[chlorocarbonyl(methyl)amino]ethyl]-N-methyl-carbamate 1H NMR (500 MHz, DMSO-d6) δ 3.34 - 3.72 (4 H, m) 7.31 - 7.38 (1 H, m) 7.40 (2 H, br d, J=8.20 Hz) 7.45 - 7.49 (2 H, m) 7.60 (2 H, dd, J=8.32, 2.97 Hz) 7.65 (2 H, br d, J=7.53 Hz) MS (ESI) : [M+Na]+411.2. [1-methyl-1-(4-phenylphenyl)ethyl]N-[3-[chlorocarbonyl(methyl)amino]-2,2-dimethyl-propyl]-N-methyl- carbamate MS (ESI) : [M+Na]+453.3. Example 2 O4-[1-methyl-1-(4-phenylphenyl)ethyl]O1-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-7-methoxy-4- [[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-6,11- dioxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] piperazine-1,4-dicarboxylate A microwave -4-methoxy-7- [[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-8,10-dihydro- 7H-tetracene-5,12-dione (0.03 g, 0.046 mmol, 1.0 Eq.) (commercially available) and anhydrous dichloromethane (2.5 mL). To this solution molecular sieves (4 Å powder, <5 micron, 0.03 g), 4-(dimethylamino)pyridine (0.045 g, 0.374 mmol, 8.0 Eq.) and [1-methyl-1-(4-phenylphenyl)ethyl] 4-chlorocarbonylpiperazine-1-carboxylate (0.054 g, 0.140 mmol, 3.0 Eq.) were added. Reaction was stirred at 40° C for 20 h, then was diluted with DCM and washed with water. Aqueous layer was extracted with DCM twice. Reunited organic phases were anhydrified with Na2SO4and solvent was evaporated to dryness by rotavapor. Crude mixture was dissolved in minimum volume of DCM, added to a chromatographic column and eluted with DCM / Acetone 9 / 1 to give title compound (0.036 g., 77% Yield). H NMR (401 MHz, DMSO-d6) δ ppm 1.20 - 1.28 (3 H, m) 1.63 - 1.72 (2 H, m) 1.75 (6 H, s) 2.06 (1 H, s) 2.34 - 2.43 (1 H, m) 2.55 (2 H, s) 3.03 (2 H, s) 3.30 (4 H, s) 3.33 - 3.61 (9 H, m) 3.61 - 3.72 (1 H, m) 3.89 - 3.96 (1 H, m) 4.00 (3 H, s) 4.14 - 4.28 (2 H, m) 4.58 (1 H, d, J=1.96 Hz) 4.97 - 5.06 (1 H, m) 5.07 - 5.30 (3 H, m) 5.52 (1 H, s) 7.31 - 7.39 (1 H, m) 7.39 - 7.53 (4 H, m) 7.58 - 7.73 (5 H, m) 7.88 - 7.96 (2 H, m) MS (ESI) : [M+H]+992.6. Operating in an analogous way, but employing suitable substituted starting material the following compounds were obtained: O1-[1-methyl-1-(4-phenylphenyl)ethyl]O4-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-7-methoxy-4- [[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-6,11- dioxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] 1,4-diazepane-1,4-dicarboxylate 1H NMR (400 MHz, DMSO-d6) δ ppm 1.16 - 1.25 (m, 3 H) 1.51 - 1.75 (m, 8 H) 1.77 - 1.97 (m, 2 H) 2.02 - 2.10 (m, 1 H) 2.36 - 2.46 (m, 1 H) 2.54 - 2.63 (m, 2 H) 2.87 - 3.06 (m, 2 H) 3.26 - 3.32 (m, 4 H) 3.40 - 3.68 (m, 10 H) 3.82 - 3.89 (m, 1 H) 3.99 (s, 3 H) 4.16 - 4.23 (m, 2 H) 4.58 (br s, 1 H) 4.99 (br s, 1 H) 5.07 - 5.38 (m, 3 H) 5.50 - 5.55 (m, 1 H) 7.29 - 7.35 (m, 1 H) 7.35 - 7.48 (m, 4 H) 7.54 - 7.67 (m, 5 H) 7.89 - 7.94 (m, 2 H) 13.26 (br s, 1 H) 13.96 - 14.30 (m, 1 H) MS (ESI) : [M+H]+1006.6. [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1- azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-6,11-dioxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] 4-[methyl-[1-methyl-1- (4-phenylphenyl)ethoxy]carbonyl-amino]piperidine-1-carboxylate 1H NMR (400 MHz, 6 H) 2.05 - 2.15 (m, 1 H) 2.30 - 2.37 (m, 1 H) 2.60 - 2.71 (m, 2 H) 2.74 - 2.88 (m, 2 H) 2.89 - 3.09 (m, 2 H) 3.29 - 3.31 (m, 3 H) 3.37 - 3.41 (m, 1 H) 3.46 - 3.54 (m, 1 H) 3.61 - 3.71 (m, 1 H) 3.89 - 4.16 (m, 7 H) 4.18 - 4.24 (m, 2 H) 4.59 (d, J=2.20 Hz, 1 H) 4.96 - 5.03 (m, 1 H) 5.04 - 5.27 (m, 3 H) 5.47 - 5.58 (m, 1 H) 7.30 - 7.49 (m, 5 H) 7.55 - 7.73 (m, 5 H) 7.83 - 8.03 (m, 2 H) 13.24 - 13.31 (m, 1 H) 14.02 - 14.14 (m, 1 H). MS (ESI) : [M+H]+1020.4. [1-methyl-1-(4-phenylphenyl)ethyl]4-[methyl-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-7-methoxy-4- [[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-6,11- dioxo-3,4-dihydro-1H-tetracen-2-yl]ethoxy]carbonyl-amino]piperidine-1-carboxylate MS (ESI) : [M+H]+ [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-7-methoxy-4- [[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-6,11-dioxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] N-methyl-N-[2- [methyl-[1-methyl-1-(4-phenylphenyl)ethoxy]carbonyl-amino]ethyl]carbamate MS (ESI) : [M+H]+ [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1- azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-6,11-dioxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]N-[2,2-dimethyl-3- [methyl-[1-methyl-1-(4-phenylphenyl)ethoxy]carbonyl-amino]propyl]-N-methyl-carbamate 1H NMR (500 2.29 - 2.42 (2 H, m) 2.58 - 2.73 (2 H, m) 2.74 - 3.25 (12 H, m) 3.25 - 3.31 (3 H, m) 3.36 - 3.43 (1 H, m) 3.46 - 3.55 (1 H, m) 3.61 - 3.70 (1 H, m) 3.88 - 3.95 (1 H, m) 3.96 - 4.02 (3 H, m) 4.16 - 4.26 (2 H, m) 4.58 (1 H, s) 4.96 - 5.29 (4 H, m) 5.47 - 5.54 (1 H, m) 7.28 - 7.64 (9 H, m) 7.64 - 7.70 (1 H, m) 7.88 - 7.99 (2 H, m) 13.27 (1 H, s) 14.03 (1 H, s) HRMS (ESI) calcd for C56H65N3O16 [M+H]+1036.4438, found 1036.4445. [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1- azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-6,11-dioxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] 4-methylpiperazine-1- carboxylate (m, 3 H) 1.69 (dt, J=15.16, 5.89 Hz, 1 H) 1.87 - 1.93 (m, 1 H) 2.01 - 2.07 (m, 1 H) 2.22 - 2.25 (m, 3 H) 2.33 (br s, 4 H) 2.56 (br d, J=14.66 Hz, 1 H) 2.70 - 2.76 (m, 1 H) 2.77 - 2.82 (m, 1 H) 2.94 (d, J=18.50 Hz, 1 H) 3.14 (dd, J=18.69, 1.65 Hz, 1 H) 3.38 (s, 3 H) 3.39 - 3.62 (m, 6 H) 3.73 (ddd, J=11.40, 8.01, 2.93 Hz, 1 H) 4.01 (s, 3 H) 4.02 - 4.06 (m, 1 H) 4.06 - 4.10 (m, 1 H) 4.25 (d, J=2.93 Hz, 1 H) 4.53 (d, J=2.93 Hz, 1 H) 4.71 (s, 1 H) 5.06 (d, J=18.14 Hz, 1 H) 5.22 (dd, J=3.66, 2.02 Hz, 1 H) 5.26 (d, J=18.14 Hz, 1 H) 5.35 (t, J=5.59 Hz, 1 H) 7.54 (d, J=8.24 Hz, 1 H) 7.84 (t, J=8.15 Hz, 1 H) 7.97 (d, J=7.69 Hz, 1 H). HRMS (ESI) calcd for C38H45N3O14 [M+H]+ 768.2975, found 768.2970. Example 3 O4-[1-methyl-1-(4-phenylphenyl)ethyl]O1-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4- [[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo- 3,4-dihydro-1H-tetracen-2-yl]ethyl] piperazine-1,4-dicarboxylate O OOHO NH3 in MeOH (4 M, of O4-[1-methyl-1-(4- phenylphenyl)ethyl]O1-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6- methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-6,11-dioxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] piperazine-1,4-dicarboxylate (0.034 g, 0.034 mmol, 1.0 Eq.) in anhydrous dichloromethane (1.5 mL). Reaction was left at 4° C for 72 h. TLC showed complete conversion and formation of a new blue-violet spot. Solvent was evaporated to dryness by rotavapor and crude mixture was dissolved in minimum volume of DCM, added to a chromatographic column and eluted with DCM / Acetone: from 85 / 15 to 8 / 2 to give title compound (0.020 g, 59% Yield).1H NMR (400 MHz, DMSO-d6) δ ppm 1.21 - 1.27 (m, 3 H) 1.59 - 1.68 (m, 2 H) 1.75 (s, 6 H) 1.98 - 2.06 (m, 1 H) 2.23 - 2.31 (m, 1 H) 2.55 - 2.64 (m, 2 H) 2.84 - 3.01 (m, 2 H) 3.24 - 3.72 (m, 14 H) 3.89 - 3.98 (m, 1 H) 4.13 (s, 4 H) 4.24 (d, J=1.95 Hz, 1 H) 4.59 (d, J=2.34 Hz, 1 H) 5.03 - 5.09 (m, 1 H) 5.09 - 5.29 (m, 2 H) 5.37 - 5.44 (m, 2 H) 7.32 - 7.39 (m, 1 H) 7.39 - 7.50 (m, 4 H) 7.60 - 7.68 (m, 5 H) 7.84 - 7.90 (m, 1 H) 8.06 - 8.12 (m, 1 H) 9.64 - 9.69 (m, 1 H) 13.57 - 13.63 (m, 1 H). MS (ESI) : [M+H]+991.5. Operating in an analogous way, but employing suitable substituted starting material the following compounds were obtained: O1-[1-methyl-1-(4-phenylphenyl)ethyl]O4-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4- [[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo- 3,4-dihydro-1H-tetracen-2-yl]ethyl] 1,4-diazepane-1,4-dicarboxylate 1H NMR (400 MHz, (m, 2 H) 1.95 - 2.04 (m, 1 H) 2.24 - 2.30 (m, 1 H) 2.54 - 2.65 (m, 2 H) 2.82 - 3.01 (m, 2 H) 3.29 - 3.31 (m, 4 H) 3.38 - 3.72 (m, 10 H) 3.82 - 3.88 (m, 1 H) 4.12 (s, 5 H) 4.58 (br s, 1 H) 4.98 - 5.52 (m, 5 H) 7.27 - 7.35 (m, 1 H) 7.35 - 7.46 (m, 4 H) 7.55 - 7.66 (m, 5 H) 7.87 (t, J=7.91 Hz, 1 H) 8.08 (d, J=7.91 Hz, 1 H) 9.68 (br s, 1 H) 13.61 (br s, 1 H) 15.78 - 15.97 (m, 1 H) MS (ESI) : [M+H]+1005.6. [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11- trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]4-[methyl-[1- methyl-1-(4-phenylphenyl)ethoxy]carbonyl-amino]piperidine-1-carboxylate MS (ESI) : [M+H]+1019.8. [1-methyl-1-(4-phenylphenyl)ethyl]4-[methyl-[2-oxo-2- [(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo- 3,4-dihydro-1H-tetracen-2-yl]ethoxy]carbonyl-amino]piperidine-1-carboxylate MS (ESI) : [M+H]+ [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11- trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]N-methyl-N-[2- [methyl-[1-methyl-1-(4-phenylphenyl)ethoxy]carbonyl-amino]ethyl]carbamate H NMR (500 MHz, DMSO- (m, 6 H) 1.93 - 2.03 (m, 1 H) 2.21 - 2.34 (m, 1 H) 2.54 - 2.70 (m, 2 H) 2.71 - 3.03 (m, 8 H) 3.28 - 3.31 (m, 3 H) 3.41 (br s, 6 H) 3.61 - 3.69 (m, 1 H) 3.84 - 3.93 (m, 1 H) 4.09 - 4.17 (m, 4 H) 4.19 - 4.25 (m, 1 H) 4.53 - 4.62 (m, 1 H) 5.01 - 5.30 (m, 3 H) 5.31 - 5.49 (m, 2 H) 7.24 - 7.49 (m, 5 H) 7.51 - 7.72 (m, 5 H) 7.87 (t, J=8.13 Hz, 1 H) 8.01 - 8.13 (m, 1 H) 9.47 - 9.90 (m, 1 H) 13.50 - 13.75 (m, 1 H) 15.68 - 16.09 (m, 1 H). HRMS (ESI) calcd for C53H60N4O15 [M+H]+993.4128, found 993.4134. [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11- trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] N-[2,2-dimethyl-3- [methyl-[1-methyl-1-(4-phenylphenyl)ethoxy]carbonyl-amino]propyl]-N-methyl-carbamate 1H NMR (500 MHz, (2 H, m) 1.66 - 1.79 (6 H, m) 1.93 - 2.10 (1 H, m) 2.19 - 2.34 (1 H, m) 2.57 - 2.70 (2 H, m) 2.70 - 3.21 (12 H, m) 3.30 (3 H, s) 3.36 - 3.44 (1 H, m) 3.45 - 3.56 (1 H, m) 3.60 - 3.71 (1 H, m) 3.86 - 3.97 (1 H, m) 4.06 - 4.20 (4 H, m) 4.21 - 4.26 (1 H, m) 4.53 - 4.63 (1 H, m) 4.98 - 5.29 (3 H, m) 5.30 - 5.48 (2 H, m) 7.20 - 7.72 (10 H, m) 7.80 - 7.95 (1 H, m) 8.05 - 8.15 (1 H, m) 9.35 - 9.92 (1 H, m) 13.31 - 13.95 (1 H, m) 15.61 - 16.07 (1 H, m) HRMS (ESI) calcd for C56H66N4O15 [M+H]+1035.4598, found 1035.4597 [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11- trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]4-methyl piperazine-1-carboxylate (compd.2) HRMS (ESI) calcd for Example 4 [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11- trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]piperazine-1- carboxylate (compd.1) To a ethyl] O1-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4- [[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4- dihydro-1H-tetracen-2-yl]ethyl] piperazine-1,4-dicarboxylate (0.019 g, 0.019 mmol, 1.0 Eq.) in anhydrous dichloromethane (3.5 mL) in ice bath, a solution of 2,2-dichloroacetic acid (0.3 M, 1.3 mL, 0.383 mmol, 20 Eq.) (DCM) was added. Reaction was warmed to RT and stirred for 2h until starting material was no longer detectable by HPLC- MS. Reaction was diluted with DCM and then NaHCO3 sat. was added. The layers were separated and the aqueous one was extracted with DCM 3 times. Organic phases were reunited, and solvent was evaporated to dryness by rotavapor. The blue solid obtained was dissolved in a very small quantity of DCM and to this solution a mixture of EtO2 and Hexan (1:1) was added to give a blue precipitate. The blue solid was collected by filtration to give the title compound (0.012 g, 83% Yield). 1H NMR (600 MHz, DMSO-d6) δ ppm 1.24 (3 H, d, J=6.58 Hz) 1.56 - 1.69 (2 H, m) 2.01 (1 H, dd, J=14.40, 5.27 Hz) 2.26 (1 H, br d, J=13.40 Hz) 2.59 - 2.71 (6 H, m) 2.84 - 2.98 (2 H, m) 3.22 - 3.42 (9 H, m) 3.50 (1 H, dt, J=11.51, 3.62 Hz) 3.66 (1 H, ddd, J=11.47, 9.13, 2.66 Hz) 3.91 - 3.96 (1 H, m) 4.12 (3 H, s) 4.16 (1 H, qd, J=6.60, 1.45 Hz) 4.24 (1 H, d, J=2.09 Hz) 4.59 (1 H, d, J=2.00 Hz) 5.05 (1 H, dd, J=4.70, 3.07 Hz) 5.09 (1 H, d, J=17.98 Hz) 5.20 (1 H, d, J=17.98 Hz) 5.38 - 5.42 (2 H, m) 7.64 (1 H, dd, J=8.47, 0.89 Hz) 7.87 (1 H, t, J=8.08 Hz) 8.08 (1 H, dd, J=7.88, 1.02 Hz) 9.67 (1 H, br d, J=4.77 Hz) 13.60 (1 H, br d, J=4.72 Hz) 15.23 - 16.09 (1 H, m) HRMS (ESI) calcd for C37H44N4O13 [M+H]+753.2978, found 753.29714. Operating in an analogous way, but employing suitable substituted starting material the following compounds were obtained: [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11- trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]1,4-diazepane-1- carboxylate (compd.3) 1H J=6.58 Hz) 1.61 - 1.65 (2 H, m) 1.68 - 1.72 (1 H, m) 1.95 - 2.05 (1 H, m) 2.22 - 2.31 (1 H, m) 2.58 - 2.76 (5 H, m) 2.80 (1 H, br dd, J=5.25, 4.02 Hz) 2.85 - 2.90 (1 H, m) 2.92 - 2.97 (1 H, m) 3.30 - 3.32 (3 H, m) 3.31 - 3.34 (1 H, m) 3.34 - 3.44 (3 H, m) 3.45 - 3.53 (3 H, m) 3.62 - 3.70 (1 H, m) 3.93 (1 H, dd, J=6.38, 1.70 Hz) 4.12 (3 H, s) 4.14 - 4.18 (1 H, m) 4.24 (1 H, d, J=2.04 Hz) 4.59 (1 H, d, J=2.00 Hz) 5.06 (1 H, dd, J=4.41, 3.04 Hz) 5.10 (1 H, dd, J=18.01, 2.88 Hz) 5.21 (1 H, dd, J=18.01, 6.38 Hz) 5.38 (1 H, s) 5.40 (1 H, t, J=4.68 Hz) 7.64 (1 H, d, J=7.86 Hz) 7.87 (1 H, t, J=8.08 Hz) 8.08 (1 H, dd, J=7.83, 0.84 Hz) 9.67 (1 H, br d, J=4.45 Hz) 13.60 (1 H, br d, J=4.36 Hz) 15.53 - 16.14 (1 H, m). HRMS (ESI) calcd for C38H46N4O13 [M+H]+767.3134, found 767.31258. [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11- trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]4-(methylamino) piperidine-1-carboxylate (compd.4) - 1.71 (m, 2 H) 1.72 - 1.85 (m, 2 H) 1.94 - 2.07 (m, 1 H) 2.24 - 2.29 (m, 4 H) 2.49 (br s, 1 H) 2.58 - 2.73 (m, 2 H) 2.82 - 3.09 (m, 5 H) 3.31 (s, 3 H) 3.34 - 3.41 (m, 1 H) 3.47 - 3.55 (m, 1 H) 3.66 (ddd, J=11.44, 9.08, 2.54 Hz, 1 H) 3.79 - 3.92 (m, 2 H) 3.92 - 3.95 (m, 1 H) 4.12 (s, 3 H) 4.14 - 4.19 (m, 1 H) 4.24 (d, J=2.09 Hz, 1 H) 4.59 (d, J=2.04 Hz, 1 H) 5.03 - 5.12 (m, 2 H) 5.16 - 5.22 (m, 1 H) 5.37 - 5.44 (m, 2 H) 7.64 (dd, J=8.47, 0.84 Hz, 1 H) 7.87 (t, J=8.08 Hz, 1 H) 8.09 (dd, J=7.86, 1.00 Hz, 1 H) 9.67 (br d, J=4.50 Hz, 1 H) 13.61 (br d, J=4.72 Hz, 1 H). HRMS (ESI) calcd for C39H48N4O13 [M+H]+781.3291, found 781.3289.[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7- methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]N- methyl-N-(4-piperidyl)carbamate (compd.5) 1H NMR (600 MHz, DMSO-d6) Hz) 1.60 - 1.66 (1 H, m) 2.00 (1 H, br dd, J=14.35, 5.18 Hz) 2.27 (1 H, br d, J=13.49 Hz) 2.51 - 2.55 (3 H, m) 2.58 - 2.82 (5 H, m) 2.82 - 2.90 (1 H, m) 2.91 - 2.97 (1 H, m) 3.01 (2 H, br d, J=11.99 Hz) 3.31 (3 H, br s) 3.35 - 3.40 (1 H, m) 3.46 - 3.54 (1 H, m) 3.63 - 3.69 (1 H, m) 3.84 - 3.92 (1 H, m) 3.91 - 3.96 (1 H, m) 4.12 (3 H, s) 4.14 - 4.20 (1 H, m) 4.24 (1 H, d, J=2.04 Hz) 4.59 (1 H, d, J=1.95 Hz) 5.05 (1 H, br dd, J=4.61, 2.70 Hz) 5.10 (1 H, d, J=17.98 Hz) 5.16 - 5.27 (1 H, m) 5.39 (1 H, s) 5.40 (1 H, br s) 7.64 (1 H, d, J=7.67 Hz) 7.87 (1 H, t, J=8.08 Hz) 8.08 (1 H, dd, J=7.88, 0.98 Hz) 9.67 (1 H, br d, J=4.59 Hz) 13.60 (1 H, br d, J=4.68 Hz). HRMS (ESI) calcd for C39H48N4O13 [M+H]+781.3291, found 781.3297. 2,2-dichloroacetic acid;[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10- methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2- yl]ethyl] N-methyl-N-[2-(methylamino)ethyl]carbamate (compd.6 as dichloroacetic salt) HRMS (ESI) calcd for 2,2-dichloroacetic acid;[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10- methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2- yl]ethyl] N-[2,2-dimethyl-3-(methylamino)propyl]-N-methyl-carbamate (compd.7 dichloroacetic salt) found 797.3605. Example 5 [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11- trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]N-[2-[(2- hydroxyacetyl)-methyl-amino]ethyl]-N-methyl-carbamate (compd.9) To a solution of [[(2S,4R,6S,7S,9R,10S)-10- methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] N-methyl-N-[2-(methylamino)ethyl]carbamate (compd.6) (0.0075 g, 0.01 mmol,) in DCM (1mL), 2-hydroxyacetic acid (0.0015 g, 0.020 mmol, 2.0 equiv.) and DIPEA (0.0051 g, 0.040 mmol, 0.0069 mL, 4.0 equiv.) and then HATU, 98% (0.0057 g, 0.015 mmol, 1.5 equiv.) were added. Reaction mixture was stirred at rt for 3h until the starting material was no more detectable by HPLC-MS analysis. Reaction was washed with water (x2) and brine. Organic layer was then dried on Na2SO4 and evaporated by rotavapor. Crude was purified by chromatographic column on silica gel (DCM / MeOH from 99 / 1 to 97 / 3 ) to give title compound (0.005 g y=62% blue solid). HRMS (ESI) calcd for C39H48N4O15 [M+H]+813.3189, found 813.3199. Operating in an analogous way, but employing suitable substituted starting material the following compound was obtained: [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(1S,2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl- found 825.3198. Example 6 O5-(1-methyl-1-phenyl-ethyl) O1-(2,3,4,5,6-pentafluorophenyl) (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino) pentanedioate To a solution of compound (2S) -5-(1-methyl-1-phenyl-ethoxy)-5-oxo- pentanoic acid (500 mg, 1.03 mmol) (commercially available) in DCM (5 mL) was added EDCI (294.9 mg, 1.54 mmol) and 2,3,4,5,6-pentafluorophenol (188 mg, 1.03 mmol). The mixture was stirred at 25 °C for 1 hour. TLC (Petroleum ether: Ethyl acetate = 3:1) showed the reaction was complete. Reaction mixture extracted with DCM (10 mL x 2). The combined organic layers were washed with aq.NaCl (10 mL x 3), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give O5-(1-methyl-1-phenyl-ethyl) O1-(2,3,4,5,6-pentafluorophenyl) (2S)-2- (9H-fluoren-9-ylmethoxycarbonylamino)pentanedioate (650 mg, crude, yellow oil). (1-methyl-1-phenyl-ethyl)(4S)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-5-[[(1S)-1-[[(1S)-2-[4-(hydroxymethyl) anilino]-1-methyl-2-oxo-ethyl]carbamoyl]-2-methyl-propyl]amino]-5-oxo-pentanoate To a solution of (2S)-2- -3-methyl-butanamide (300 mg, 1.02 mmol) (commercially available) in DMF (5 mL) was added DIPEA (264 mg, 2.05 mmol, 357 µL) and O5-(1-methyl-1-phenyl-ethyl) O1-(2,3,4,5,6-pentafluorophenyl) (2S)-2-(9H-fluoren-9- ylmethoxycarbonylamino)pentanedioate (602 mg, 920 µmol). The mixture was stirred at 20 °C for 12 hours. LCMS showed the reaction was complete. The reaction mixture extracted with DCM (10 mL x 2). Combined organic layers were washed with aq.NaCl (10 mL x 3), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash silica gel chromatography (ISCO®; 4 g SepaFlash® Silica Flash Column, Eluent of 0~4% Methanol / Dichloromethane gradient @ 15 mL / min) to give (1-methyl-1-phenyl-ethyl) (4S)-4-(9H- fluoren-9-ylmethoxycarbonylamino)-5-[[(1S)-1-[[(1S)-2-[4-(hydroxymethyl)anilino]-1-methyl-2-oxo-ethyl]carbamoyl]-2- methyl-propyl]amino]-5-oxo-pentanoate (410 mg, 46.7% yield) as yellow solid. MS (ESI) : [M+H]+ 785.4 1H NMR (400 MHz, CH3OD) δ 7.76-7.82 (m, 2H), 7.63-7.70 (m, 2H) 7.54 (d, J = 8.3 Hz, 2H), 7.25-7.42 (m, 10H), 7.16- 7.22 (m, 1H), 4.52-4.56 (m, 2H), 4.34-4.49 (m, 3H), 4.13-4.27 (m, 3H), 2.38-2.46 (m, 2H), 2.02-2.14 (m, 2H), 1.83-1.93 (m, 1H), 1.74 (d, J = 2.6 Hz, 6H), 1.38-1.47 (m, 3H), 0.90-0.99 (m, 6H). (1-methyl-1-phenyl-ethyl) (4S)-4-amino-5-[[(1S)-1-[[(1S)-2-[4-(hydroxymethyl)anilino]-1-methyl-2-oxo-ethyl] carbamoyl]-2-methyl-propyl]amino]-5-oxo-pentanoate To a solution of (1- -5-[[(1S)-1-[[(1S)-2-[4- (hydroxymethyl)anilino]-1-methyl-2-oxo-ethyl]carbamoyl]-2-methyl-propyl]amino]-5-oxo-pentanoate (400 mg, 524 µmol) in ACN (6 mL) was added diethylamine (2 mL). The mixture was stirred at 20 °C for 2 hours. LCMS showed the reaction was complete. Reaction mixture was concentrated under vacuum to give the (1-methyl-1-phenyl-ethyl) (4S)-4-amino-5-[[(1S)-1-[[(1S)-2-[4-(hydroxymethyl)anilino]-1-methyl-2-oxo-ethyl]carbamoyl]-2-methyl-propyl]amino]- 5-oxo-pentanoate (280 mg) as a white solid. MS (ESI) : [M+H]+ 541.4 (1-methyl-1-phenyl-ethyl)(4S)-4-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-5-[[(1S)-1-[[(1S)-2-[4-(hydroxymethyl) anilino]-1-methyl-2-oxo-ethyl]carbamoyl]-2-methyl-propyl]amino]-5-oxo-pentanoate A mixture of -1-methyl-2-oxo- ethyl]carbamoyl]-2-methyl-propyl]amino]-5-oxo-pentanoate (280 mg, 518 µmol), (2,5-dioxopyrrolidin-1-yl) 6-(2,5- dioxopyrrol-1-yl)hexanoate (192 mg, 621 µmol), DIPEA (134 mg, 1.04 mmol, 180 µL) in DMF (4 mL) was degassed and purged with N2 for 3 times, then the mixture was stirred at 20 °C for 12 h under nitrogen atmosphere. LCMS showed the reaction was complete. Reaction mixture extracted with EtOAc (10 mL x 2). The combined organic layers were washed with aq.NaCl (10 mL x 3), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 4 g SepaFlash® Silica Flash Column, Eluent of 0~4% Methanol / Dichloromethane gradient @ 15 mL / min) to give (1-methyl-1-phenyl-ethyl) (4S)-4-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-5-[[(1S)-1-[[(1S)-2-[4-(hydroxymethyl)anilino]-1-methyl-2-oxo- ethyl]carbamoyl]-2-methyl-propyl]amino]-5-oxo-pentanoate (310 mg, 74.6% yield) as a yellow solid. MS (ESI) : [M+H]+ 734.7. (1-methyl-1-phenyl-ethyl) (4S)-4-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-5-[[(1S)-2-methyl-1-[[(1S)-1-methyl-2- [4-[(4-nitrophenoxy)carbonyloxymethyl]anilino]-2-oxo-ethyl]carbamoyl]propyl]amino]-5-oxo-pentanoate To a [[(1S)-1-[[(1S)-2-[4- (hydroxymethyl)anilino]-1-methyl-2-oxo-ethyl]carbamoyl]-2-methyl-propyl]amino]-5-oxo-pentanoate (290 mg, 395 µmol) in DMF (3 mL) was added DIPEA (102 mg, 790 µmol, 138 µL) and bis(4-nitrophenyl) carbonate (361 mg, 1.19 mmol) .The mixture was stirred at 25 °C for 16 hrs. LCMS showed the reaction was complete. Rreaction mixture was extracted with EtOAc (10 mL x 2). The combined organic layers were washed with aq.NaCl (10 mL x 3), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by prep-HPLC (column: F-Prepulite XPtC 1840*200mm*7um; mobile phase: [water (FA) - ACN]; gradient: 40%-80% B over 20.5 min) to give (1-methyl-1-phenyl-ethyl) (4S)-4-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-5-[[(1S)-2-methyl-1-[[(1S)-1-methyl-2-[4-[(4-nitrophenoxy)carbonyloxymethyl]anilino]-2-oxo- ethyl]carbamoyl]propyl]amino]-5-oxo-pentanoate (150 mg,52% yield) as a white solid. 1H NMR: (400 MHz, CH3OD) δ 8.32 (d, J = 9.3 Hz, 2H), 7.63-7.70 (m, 2H) 7.26-7.52 (m, 8H), 7.16-7.26 (m, 1H), 6.76- 6.84 (m, 2H), 5.23-5.32 (m, 2H), 4.45-4.53 (m, 1H), 4.35-4.42 (m, 1H), 4.18-4.23 (m, 1H), 3.48-3.53 (m, 2H), 2.41-2.51 (m, 2H), 2.25 (t, J = 7.3 Hz, 2H), 2.03-2.18 (m, 2H), 1.86-1.96 (m, 1H), 1.72-1.79 (m, 6H), 1.56-1.70 (m, 4H), 1.46 (d, J = 7.0 Hz, 3H), 1.28-1.37 (m, 2H), 0.99 (dd, J = 7.2, 9.1 Hz, 6H). Operating in an analogous way, but employing suitable substituted starting material the following compound was obtained: allyl (4S)-4-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-5-[[(1S)-2-methyl-1-[[(1S)-1-methyl-2-[4-[(4-nitrophenoxy) carbonyloxymethyl]anilino]-2-oxo-ethyl]carbamoyl]propyl]amino]-5-oxo-pentanoate MS (ESI) : Example 7 O1-[[4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]propanoyl]amino] phenyl]methyl]O4-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10- methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2- yl]ethyl] piperazine-1,4-dicarboxylate (compd.1a) To 6- methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] piperazine- 1-carboxylate ( 0.003 g, 0.0040 mmol, 1.0 Eq. Compd 1 ) and triethylamine (0.0016 g, 0.0022 mL, 0.0159 mmol, 4.0 Eq.) in N,N-dimethylformamide (1 mL), [4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]propanoyl]amino]phenyl]methyl (4- nitrophenyl) carbonate (0.0034 g, 0.0052 mmol, 1.3 Eq.)(commercially available) was added. Reaction was stirred at RT for 2 h until starting material was no longer detectable by HPLC-MS analysis. Solvent was evaporated to dryness by rotavapor. The crude mixture was dissolved in minimum volume of DCM, added to column and eluted with DCM / MeOH (95 / 5) to give the title compound (0.003 g, 59% Yield). 1H NMR (600 MHz, DMSO-d6) δ ppm 0.78 - 0.91 (m, 6 H) 1.13 - 1.21 (m, 2 H) 1.23 (br d, J=6.45 Hz, 4 H) 1.30 (d, J=7.08 Hz, 3 H) 1.44 - 1.54 (m, 4 H) 1.58 - 1.68 (m, 1 H) 1.92 - 2.05 (m, 2 H) 2.07 - 2.21 (m, 2 H) 2.26 (br d, J=13.53 Hz, 1 H) 2.59 - 2.69 (m, 2 H) 2.82 - 2.98 (m, 2 H) 3.31 (s, 3 H) 3.33 - 3.55 (m, 12 H) 3.62 - 3.69 (m, 1 H) 3.91 - 3.96 (m, 1 H) 4.12 (s, 3 H) 4.16 (dd, J=8.54, 6.90 Hz, 2 H) 4.22 - 4.25 (m, 1 H) 4.38 (quin, J=7.07 Hz, 1 H) 4.59 (d, J=1.95 Hz, 1 H) 5.02 (s, 2 H) 5.05 (br d, J=3.32 Hz, 1 H) 5.09 - 5.15 (m, 1 H) 5.20 - 5.26 (m, 1 H) 5.35 - 5.47 (m, 2 H) 6.96 - 7.03 (m, 2 H) 7.31 (d, J=8.58 Hz, 2 H) 7.58 (d, J=8.54 Hz, 2 H) 7.64 (br d, J=8.31 Hz, 1 H) 7.80 (d, J=8.63 Hz, 1 H) 7.87 (t, J=8.06 Hz, 1 H) 8.09 (dd, J=7.83, 0.79 Hz, 1 H) 8.16 (d, J=6.95 Hz, 1 H) 9.67 (br s, 1 H) 9.95 (s, 1 H) 13.60 (br s, 1 H) 15.87 (br s, 1 H); HRMS (ESI) calcd for C63H76N8O20 [M+H]+1265.5249, found 1265.5227. Operating in an analogous way, but employing suitable substituted starting material the following compounds were obtained: O1-[[4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]-5-ureido-pentanoyl] amino]phenyl]methyl]O4-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10- methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2- yl]ethyl] piperazine-1,4-dicarboxylate (compd.2a) 1.57 - 1.71 (m, 3 H) 1.92 - 2.04 (m, 2 H) 2.07 - 2.21 (m, 2 H) 2.26 (br d, J=12.85 Hz, 1 H) 2.59 - 2.70 (m, 2 H) 2.82 - 3.06 (m, 4 H) 3.29 - 3.31 (m, 3 H) 3.33 (s, 11 H) 3.48 - 3.52 (m, 1 H) 3.62 - 3.69 (m, 1 H) 3.91 - 3.95 (m, 1 H) 4.12 (s, 3 H) 4.14 - 4.17 (m, 1 H) 4.16 - 4.19 (m, 1 H) 4.23 (d, J=2.09 Hz, 1 H) 4.37 (br d, J=5.77 Hz, 1 H) 4.59 (d, J=1.95 Hz, 1 H) 5.02 (s, 2 H) 5.04 - 5.07 (m, 1 H) 5.12 (d, J=17.98 Hz, 1 H) 5.20 - 5.26 (m, 1 H) 5.36 - 5.44 (m, 4 H) 5.96 (br t, J=5.77 Hz, 1 H) 6.94 - 7.05 (m, 2 H) 7.30 (d, J=8.58 Hz, 2 H) 7.59 (d, J=8.54 Hz, 2 H) 7.62 - 7.66 (m, 1 H) 7.79 (d, J=8.67 Hz, 1 H) 7.87 (t, J=8.08 Hz, 1 H) 8.03 - 8.11 (m, 2 H) 9.68 (br d, J=4.59 Hz, 1 H) 9.99 (s, 1 H) 13.60 (br d, J=4.18 Hz, 1 H) 15.87 (s, 1 H) HRMS (ESI) calcd for C66H82N10O21 [M+H]+1351.5729, found 1351.5717. O1-[[4-[[2-[[(2S)-2-[[2-[[2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]acetyl]amino]acetyl]amino]-3-phenyl- propanoyl]amino]acetyl]amino]phenyl]methyl] O4-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4- [[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo- 3,4-dihydro-1H-tetracen-2-yl]ethyl] piperazine-1,4-dicarboxylate (compd.3a) (m, 2 H) 1.44 - 1.48 (m, 2 H) 1.56 - 1.69 (m, 1 H) 2.00 (br dd, J=14.37, 5.11 Hz, 1 H) 2.10 (t, J=7.49 Hz, 2 H) 2.21 - 2.30 (m, 1 H) 2.58 - 2.71 (m, 2 H) 2.78 - 2.99 (m, 2 H) 2.80 - 2.86 (m, 1 H) 3.07 (dd, J=13.85, 4.50 Hz, 1 H) 3.31 (s, 3 H) 3.33 - 3.95 (m, 14 H) 3.37 (br s, 1 H) 3.69 (s, 2 H) 3.86 (d, J=5.72 Hz, 2 H) 3.93 (br d, J=6.22 Hz, 1 H) 4.12 (s, 3 H) 4.14 - 4.19 (m, 1 H) 4.23 (d, J=2.04 Hz, 1 H) 4.50 (ddd, J=9.56, 8.04, 4.56 Hz, 1 H) 4.59 (d, J=2.00 Hz, 1 H) 5.03 (s, 2 H) 5.04 - 5.07 (m, 1 H) 5.09 - 5.25 (m, 2 H) 5.36 - 5.44 (m, 2 H) 6.97 - 7.00 (m, 2 H) 7.14 - 7.22 (m, 1 H) 7.25 (d, J=4.36 Hz, 2 H) 7.24 - 7.27 (m, 2 H) 7.32 (d, J=8.58 Hz, 2 H) 7.61 (d, J=8.54 Hz, 2 H) 7.64 (d, J=8.36 Hz, 1 H) 7.87 (t, J=8.08 Hz, 1 H) 8.03 (t, J=5.68 Hz, 1 H) 8.06 (t, J=5.74 Hz, 1 H) 8.08 (d, J=7.49 Hz, 1 H) 8.17 (d, J=7.90 Hz, 1 H) 8.39 (t, J=5.81 Hz, 1 H) 9.67 (br d, J=4.31 Hz, 1 H) 9.85 (s, 1 H) 13.60 (br d, J=4.00 Hz, 1 H) 15.87 (br s, 1 H). HRMS (ESI) calcd for C70H80N10O22 [M+H]+1413.5522, found 1413.5525. O4-[[4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]propanoyl]amino] phenyl]methyl]O1-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10- methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2- yl]ethyl] 1,4-diazepane-1,4-dicarboxylate (compd.4a)

[0005] 1H (3 H, d, J=7.13 Hz) 1.40 - 1.54 (4 H, m) 1.60 - 1.65 (1 H, m) 1.66 - 1.71 (1 H, m) 1.73 - 1.81 (1 H, m) 1.88 - 2.04 (2 H, m) 2.05 - 2.21 (2 H, m) 2.26 (1 H, br d, J=13.99 Hz) 2.57 - 2.71 (2 H, m) 2.83 - 2.90 (1 H, m) 2.92 - 2.98 (1 H, m) 3.31 (3 H, s) 3.33 - 3.57 (12 H, m) 3.62 - 3.69 (1 H, m) 3.93 (1 H, br d, J=6.27 Hz) 4.12 (3 H, s) 4.14 - 4.20 (2 H, m) 4.23 (1 H, d, J=1.95 Hz) 4.38 (1 H, quin, J=7.07 Hz) 4.59 (1 H, d, J=1.82 Hz) 4.95 - 5.02 (2 H, m) 5.06 (1 H, br s) 5.09 - 5.16 (1 H, m) 5.16 - 5.25 (1 H, m) 5.37 - 5.43 (2 H, m) 6.99 (2 H, s) 7.24 - 7.32 (2 H, m) 7.51 - 7.59 (2 H, m) 7.64 (1 H, d, J=8.45 Hz) 7.80 (1 H, d, J=8.63 Hz) 7.86 (1 H, t, J=8.08 Hz) 8.08 (1 H, d, J=7.81 Hz) 8.14 (1 H, br d, J=6.90 Hz) 9.67 (1 H, br d, J=4.09 Hz) 9.87 - 9.98 (1 H, m) 13.60 (1 H, br d, J=3.86 Hz) 15.86 (1 H, s); HRMS (ESI) calcd for C64H78N8O20 [M+H]+1279.5405, found 1279.5392. O4-[[4-[[2-[[(2S)-2-[[2-[[2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]acetyl]amino]acetyl]amino]-3-phenyl- propanoyl]amino]acetyl]amino]phenyl]methyl] O1-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4- [[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo- 3,4-dihydro-1H-tetracen-2-yl]ethyl] 1,4-diazepane-1,4-dicarboxylate (compd.5a) (m, 2 H) 1.65 - 1.69 (m, 1 H) 1.75 - 1.80 (m, 1 H) 1.98 - 2.05 (m, 1 H) 2.08 - 2.12 (m, 2 H) 2.23 - 2.29 (m, 1 H) 2.58 - 2.63 (m, 1 H) 2.64 - 2.69 (m, 1 H) 2.79 - 2.85 (m, 1 H) 2.85 - 2.93 (m, 2 H) 3.04 - 3.09 (m, 1 H) 3.30 (s, 3 H) 3.31 - 3.91 (m, 19 H) 3.92 (br d, J=6.45 Hz, 1 H) 4.06 - 4.18 (m, 4 H) 4.23 (d, J=1.77 Hz, 1 H) 4.46 - 4.50 (m, 1 H) 4.58 (d, J=1.50 Hz, 1 H) 4.95 - 5.07 (m, 3 H) 5.08 - 5.24 (m, 2 H) 5.36 - 5.44 (m, 2 H) 6.96 (s, 2 H) 7.13 - 7.20 (m, 1 H) 7.23 - 7.26 (m, 4 H) 7.27 (br d, J=8.36 Hz, 2 H) 7.51 - 7.60 (m, 2 H) 7.63 (d, J=8.45 Hz, 1 H) 7.86 (t, J=8.08 Hz, 1 H) 8.00 - 8.10 (m, 3 H) 8.16 (br d, J=7.86 Hz, 1 H) 8.37 (br s, 1 H) 9.67 (br s, 1 H) 9.82 (br s, 1 H) 13.59 (br s, 1 H) 15.85 (br s, 1 H). HRMS (ESI) calcd for C71H82N10O22 [M+H]+1427.5678, found 1427.5707. [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11- trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]4-[[4-[[(2S)-2-[[(2S)- 2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]propanoyl]amino]phenyl]methoxy carbonyl-methyl-amino]piperidine-1-carboxylate (compd.6a) 1H J=7.13 Hz, 3 H) 1.39 - 1.73 (m, 11 H) 1.93 - 1.98 (m, 1 H) 1.99 - 2.04 (m, 1 H) 2.09 - 2.19 (m, 2 H) 2.26 (br d, J=13.35 Hz, 1 H) 2.59 - 2.74 (m, 4 H) 2.76 - 2.96 (m, 4 H) 3.31 (s, 3 H) 3.47 - 3.55 (m, 2 H) 3.63 - 3.68 (m, 1 H) 3.92 - 3.95 (m, 1 H) 3.98 - 4.07 (m, 3 H) 4.12 (s, 3 H) 4.13 - 4.17 (m, 2 H) 4.23 (d, J=2.09 Hz, 1 H) 4.37 (t, J=7.04 Hz, 1 H) 4.59 (d, J=2.00 Hz, 1 H) 5.01 (br s, 2 H) 5.04 - 5.07 (m, 1 H) 5.10 (br d, J=17.85 Hz, 1 H) 5.16 - 5.24 (m, 1 H) 5.38 - 5.41 (m, 1 H) 5.41 (s, 1 H) 6.99 (s, 2 H) 7.29 (d, J=8.54 Hz, 2 H) 7.57 (d, J=8.58 Hz, 2 H) 7.64 (dd, J=8.51, 0.89 Hz, 1 H) 7.80 (d, J=8.63 Hz, 1 H) 7.87 (t, J=8.08 Hz, 1 H) 8.08 (dd, J=7.86, 0.95 Hz, 1 H) 8.14 (d, J=6.95 Hz, 1 H) 9.67 (br d, J=4.45 Hz, 1 H) 9.93 (s, 1 H) 13.59 (br d, J=4.72 Hz, 1 H) 15.86 (s, 1 H). HRMS (ESI) calcd for C65H80N8O20 [M+Na]+1315.5381, found 1315.5423. [4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]propanoyl]amino] phenyl]methyl4-[methyl-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10- methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2- yl]ethoxy]carbonyl-amino]piperidine-1-carboxylate (compd.7a)

[0006] 1H 1.29 (3 H, d, J=7.08 Hz) 1.40 - 1.77 (8H, m) 1.86 - 2.22 (4 H, m) 2.26 (1 H, br d, J=13.40 Hz) 2.58 - 2.64 (2 H, m) 2.64 - 2.97 (9 H, m) 3.30 (3 H, s) 3.35 - 3.38 (1 H, m) 3.48 - 3.52 (1 H, m) 3.62 - 3.70 (1 H, m) 3.91 - 3.94 (1 H, m) 4.00 (1 H, br d, J=11.13 Hz) 4.06 (2 H, br s) 4.12 (3 H, s) 4.13 - 4.17 (1 H, m) 4.13 - 4.17 (1 H, m) 4.23 (1 H, d, J=2.09 Hz) 4.37 (1 H, quin, J=7.03 Hz) 4.58 (1 H, d, J=1.95 Hz) 4.99 (2 H, br s) 5.03 - 5.06 (1 H, m) 5.07 - 5.12 (1 H, m) 5.17 - 5.23 (1 H, m) 5.39 (1 H, t, J=4.65 Hz) 5.41 (1 H, s) 6.98 (2 H, s) 7.29 (2 H, d, J=8.58 Hz) 7.57 (2 H, d, J=8.58 Hz) 7.63 (1 H, dd, J=8.56, 0.84 Hz) 7.80 (1 H, d, J=8.63 Hz) 7.87 (1 H, t, J=8.08 Hz) 8.08 (1 H, dd, J=7.81, 0.95 Hz) 8.14 (1 H, d, J=6.90 Hz) 9.68 (1 H, br d, J=4.36 Hz) 9.94 (1 H, s) 13.59 (1 H, br d, J=4.63 Hz) 15.86 (1 H, s); HRMS (ESI) calcd for C65H80N8O20 [M+H]+1293.5562, found 1293.5594. [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11- trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] N-[2-[[4-[[(2S)-2- [[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]-5-ureido-pentanoyl]amino] phenyl]methoxycarbonyl-methyl-amino]ethyl]-N-methyl-carbamate (compd.8a) 1H (2 H, m) 2.23 - 2.32 (2 H, m) 2.55 - 3.10 (12 H, m) 3.28 - 3.32 (3 H, m) 3.33 - 3.44 (7 H, m) 3.45 - 3.71 (2 H, m) 3.85 - 3.97 (1 H, m) 4.12 (3 H, s) 4.15 - 4.21 (2 H, m) 4.21 - 4.27 (1 H, m) 4.31 - 4.44 (1 H, m) 4.59 (1 H, s) 4.87 - 5.27 (5 H, m) 5.34 - 5.48 (4 H, m) 5.90 - 6.03 (1 H, m) 6.99 (2 H, s) 7.21 - 7.33 (2 H, m) 7.53 - 7.60 (2 H, m) 7.61 - 7.69 (1 H, m) 7.76 - 7.83 (1 H, m) 7.83 - 7.92 (1 H, m) 8.02 - 8.13 (2 H, m) 9.61 - 9.76 (1 H, m) 9.91 - 10.07 (1 H, m) 13.45 (1 H, br s) 15.77 - 15.95 (1 H, m); HRMS (ESI) calcd for C66H84N10O21 [M+H]+1353.5886, found 1353.5924. [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11- trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] N-[2-[[4-[[(2S)-2- [[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]propanoyl]amino]phenyl] methoxycarbonyl-methyl-amino]ethyl]-N-methyl-carbamate (compd.9a) 1H - 1.33 (3 H, m) 1.39 - 1.54 (4 H, m) 1.57 - 1.70 (2 H, m) 1.90 - 2.04 (2 H, m) 2.04 - 2.19 (2 H, m) 2.21 - 2.31 (1 H, m) 2.54 - 3.04 (10 H, m) 3.25 - 3.53 (11 H, m) 3.59 - 3.73 (1 H, m) 3.85 - 3.96 (1 H, m) 4.07 - 4.19 (5 H, m) 4.19 - 4.26 (1 H, m) 4.28 - 4.43 (1 H, m) 4.54 - 4.64 (1 H, m) 4.90 - 5.23 (5 H, m) 5.30 - 5.45 (2 H, m) 6.92 - 7.04 (2 H, m) 7.19 - 7.33 (2 H, m) 7.53 - 7.60 (2 H, m) 7.59 - 7.70 (1 H, m) 7.74 - 7.95 (2 H, m) 8.02 - 8.12 (1 H, m) 8.12 - 8.29 (1 H, m) 9.47 - 9.79 (1 H, m) 9.84 - 10.01 (1 H, m) 13.38 - 13.76 (1 H, m) 15.72 - 16.03 (1 H, m). HRMS (ESI) calcd for C63H78N8O20 [M+H]+ 1267.5405, found 1267.5383. [4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]propanoyl]amino] phenyl]methylN-[2,2-dimethyl-3-[methyl-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4- [[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo- 3,4-dihydro-1H-tetracen-2-yl]ethoxy]carbonyl-amino]propyl]-N-methyl-carbamate (compd.10a) H, m) 1.39 - 1.52 (4 H, m) 1.57 - 1.66 (2 H, m) 1.99 (2 H, br s) 2.06 - 2.21 (2 H, m) 2.22 - 2.31 (1 H, m) 2.55 - 2.72 (4 H, m) 2.80 - 3.24 (12 H, m) 3.26 - 3.56 (7 H, m) 3.60 - 3.72 (1 H, m) 3.90 - 3.95 (1 H, m) 4.11 (3 H, br s) 4.13 - 4.20 (2 H, m) 4.20 - 4.27 (1 H, m) 4.29 - 4.44 (1 H, m) 4.59 (1 H, s) 4.90 - 5.24 (5 H, m) 5.32 - 5.46 (3 H, m) 6.99 (2 H, s) 7.29 (1 H, br d, J=6.56 Hz) 7.55 - 7.61 (1 H, m) 7.61 - 7.71 (1 H, m) 7.77 - 7.93 (1 H, m) 8.06 - 8.13 (1 H, m) 8.12 - 8.26 (1 H, m) 9.55 - 9.79 (1 H, m) 9.85 - 10.04 (1 H, m) 13.35 - 13.79 (1 H, m) 15.61 - 16.03 (1 H, m); HRMS (ESI) calcd for C66H84N8O20 [M+H]+ 1309.5875, found 1309.5903. O1-[[4-[[(2S)-2-[[(2S)-2-[[(2S)-5-allyloxy-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-5-oxo-pentanoyl]amino]-3- methyl-butanoyl]amino]propanoyl]amino]phenyl]methyl] O4-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7- methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl] oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] piperazine-1,4-dicarboxylate MS (1-methyl-1-phenyl-ethyl) (4S)-4-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-5-[[(1S)-2-methyl-1-[[(1S)-1-methyl-2- [4-[[methyl-[2-[methyl-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10- methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2- yl]ethoxy]carbonyl-amino]ethyl]carbamoyl]oxymethyl]anilino]-2-oxo-ethyl]carbamoyl]propyl]amino]-5-oxo- pentanoate MS O4-[[4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-5-(1-methyl-1-phenyl-ethoxy)-5-oxo- pentanoyl]amino]-3-methyl-butanoyl]amino]propanoyl]amino]phenyl]methyl]O1-[2-oxo-2-[(2S,4S)-2,5,12- trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo [7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]1,4-diazepane-1,4-dicarboxylate O O O MS (ESI) 2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11- trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] 4-[2-[[[2-[[(2S)-2- [[2-[[2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]acetyl]amino]acetyl]amino]-3-phenyl-propanoyl]amino] acetyl]amino]methoxy]acetyl]-1,4-diazepane-1-carboxylate (compd.15a) [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11- trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] N-[2-[[2-[[[2-[[(2S)- 2-[[2-[[2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]acetyl]amino]acetyl]amino]-3-phenyl-propanoyl]amino] acetyl]amino]methoxy]acetyl]-methyl-amino]ethyl]-N-methyl-carbamate (compd.14a) HRMS (ESI) calcd for C65H80N10O22 [M+H]+1353.5521, found 1353.5574. [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] N-[2-[[2-[[[(2S)-2-[[(2S)-2-[6-(2,5- dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]propanoyl]amino]methoxy]acetyl]-methyl-amino]ethyl]-N- methyl-carbamate (compd.16a) [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(1S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] N-[2-[[2-[[[(2S)-2-[[(2S)-2-[6-(2,5- dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]propanoyl]amino]methoxy]acetyl]-ethyl-amino]ethyl]-N- ethyl-carbamate (compd.17a) Example 8 [2-oxo-2-[(2S,4R)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4S,6S,7R,9R,10S)-10-methoxy-6-methyl-5,8,11- trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] 4-[2-[[[2-[[(2R)-2- [[2-[[2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]acetyl]amino]acetyl]amino]-3-phenyl-propanoyl]amino]acetyl] amino]methoxy]acetyl]-1,4-diazepane-1-carboxylate (compd.15a) To a -10- methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] 1,4-diazepane-1-carboxylate (0.0041 g, 0.0053 mmol, 1.0 equiv.) in N,N-dimethylformamide (1 mL), DIPEA (0.0010 g, 0.0080 mmol, 0.0014 mL, 1.5 equiv. compd. 3), 2-[[[2-[[(2S)-2-[[2-[[2-[6-(2,5-dioxopyrrol-1- yl)hexanoylamino]acetyl]amino]acetyl]amino]-3-phenyl-propanoyl]amino]acetyl]amino]methoxy]acetic acid (0.0043 g, 0.0070 mmol, 1.3 equiv.) and HATU (0.0026 g, 0.0070 mmol, 1.3 equiv.) were added . reaction was stirred at RT for 2h. Reaction was diluted with DCM and washed with aqueous NaHCO3. The aqueous phases combined were further extracted with DCM (8 times), then the reunited organic phases were washed with brine, dried with anhydrous sodium sulfate, filtered and evaporated under vacuum. The crude obtained was purified by flash DCM / MeOH 97 / 3- 92 / 8 to provide [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl- 5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] 4-[2-[[[2-[[(2R)-2- [[2-[[2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]acetyl]amino]acetyl]amino]-3-phenyl- propanoyl]amino]acetyl]amino]methoxy]acetyl]-1,4-diazepane-1-carboxylate (0.0052 g, 71% Yield, blue solid) HRMS (ESI) calcd for C66H80N10O22 [M+H]+1365.5521, found 1365.5563. Operating in an analogous way, but employing suitable substituted starting material the following compound was obtained: [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11- trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] N-[2-[[2-[[[2-[[(2S)- 2-[[2-[[2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]acetyl]amino]acetyl]amino]-3-phenyl-propanoyl]amino] acetyl]amino]methoxy]acetyl]-methyl-amino]ethyl]-N-methyl-carbamate (compd.14a) Example 9 (4S)-4-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-5-[[(1S)-2-methyl-1-[[(1S)-1-methyl-2-oxo-2-[4-[[4-[2-oxo-2- [(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1- azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethoxy]carbonylpiperazine-1- carbonyl]oxymethyl]anilino]ethyl]carbamoyl]propyl]amino]-5-oxo-pentanoic acid (compd.11a) To -5-oxo- pentanoyl]amino]-3-methyl-butanoyl]amino]propanoyl]amino]phenyl]methyl] O4-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6- imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4- yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] piperazine-1,4-dicarboxylate (6.8 mg 0.0047 mmol) in THF (3 mL), tetrakis(triphenylphosphine)palladium (0.0082 g, 0.0071 mmol, 1.5 equiv.) and tributyltin hydride, 98% (0.0021 g, 0.0071 mmol, 0.0019 mL, 1.5 equiv.) were added. The reaction was stirred RT 4 h. Solvent was evaporated to dryness by rotavapor. The residue was dissolved with DMSO and injected directly in a Interchim Puriflash XS470 on C18 column eluting with buffer AcONH4 / acetonitrile (from 70 / 30 to 0 / 100). Fractions were checked by HPLC-MS and those containing the mixture of products (starting and final) were extracted, evaporated and combined. Residue was the loaded on a flash chromatography (silica) and eluted with DCM / MeOH 95 / 5- 92 / 8 to obtain (4S)-4-[6-(2,5-dioxopyrrol- 1-yl)hexanoylamino]-5-[[(1S)-2-methyl-1-[[(1S)-1-methyl-2-oxo-2-[4-[[4-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7- methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11- oxo-3,4-dihydro-1H-tetracen-2-yl]ethoxy]carbonylpiperazine-1- carbonyl]oxymethyl]anilino]ethyl]carbamoyl]propyl]amino]-5-oxo-pentanoic acid (1.1 mg, 16% yield) MS (ESI) : [M+2H]2+698.0. Example 10(4S)-4-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-5- [[(1S)-2-methyl-1-[[(1S)-1-methyl-2-[4-[[methyl-[2-[methyl-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6- methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethoxy] carbonyl-amino]ethyl]carbamoyl]oxymethyl]anilino]-2-oxo-ethyl]carbamoyl]propyl]amino]-5-oxo-pentanoic acid (compd.12a) [[(1S)-1- methyl-2-[4-[[methyl-[2-[methyl-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10- methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2- yl]ethoxy]carbonyl-amino]ethyl]carbamoyl]oxymethyl]anilino]-2-oxo-ethyl]carbamoyl]propyl]amino]-5-oxo-pentanoate (0.008 g, 0.0053 mmol, 1.0equiv.) in dichloromethane (1 mL) in ice bath, a solution of 2,2-dichloroacetic acid (0.35 mL, 0.105 mmol, 20.0 Eq.) (DCM) was added. Reaction was warmed to RT. After 4h a solution of 2,2-dichloroacetic acid (0.35 mL, 0.105 mmol, 20.0 Eq.) (DCM) was added and the stirred for 3 h more. The reaction was evaporated to half the volume and ethyl ether was added to give a blue precipitate. The blue solid was filtered, washed with ethyl ether and dried under vacuum. The solid was dissolved in minimum volume of DCM / MeOH, loaded to column and eluted with DCM / MeOH 95 / 5 and then with DCM / MeOH / CH3COOH 18 / 1 / 0.1 to give (4S)-4-[6-(2,5-dioxopyrrol-1-yl) hexanoylamino]-5-[[(1S)-2-methyl-1-[[(1S)-1-methyl-2-[4-[[methyl-[2-[methyl-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6- imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl] oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethoxy]carbonyl-amino]ethyl]carbamoyl]oxymethyl]anilino]-2-oxo-ethyl] carbamoyl]propyl]amino]-5-oxo-pentanoic acid (B, 0.0044 g, 0.0032 mmol, 60% Yield). HRMS (ESI) calcd for C68H85N9O23 [M+H]+1398.5831, found 1396.5873 Operating in an analogous way, but employing suitable substituted starting material the following compounds were obtained: (4S)-4-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-5-[[(1S)-2-methyl-1-[[(1S)-1-methyl-2-oxo-2-[4-[[4-[2-oxo-2- [(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1- azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethoxy]carbonyl-1,4-diazepane- 1-carbonyl]oxymethyl]anilino]ethyl]carbamoyl]propyl]amino]-5-oxo-pentanoic acid (compd.13a) HRMS (ESI) Example 11 [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11- trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]N-[2-[6-(2,5- dioxopyrrol-1-yl)hexanoyl-methyl-amino]ethyl]-N-methyl-carbamate To a 6-imino-7-methoxy-4- [[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4- dihydro-1H-tetracen-2-yl]ethyl] N-methyl-N-[2-(methylamino)ethyl]carbamate ( 0.008 g, 0.0067 mmol, 1.0 Eq.) and triethylamine (0.0047 mL, 0.034 mmol, 5.0 Eq.) in N,N-dimethylformamide (1 mL), 6-maleimidohexanoic acid N- hydroxysuccinimide ester (0.0036 g, 0.012 mmol, 1.75 Eq.) was added. Reaction was stirred at RT until SM was no longer detectable by HPLC-MS analysis. Reaction was diluted with DCM and washed with NaHCO3 twice. Reunited aqueous phases were extracted with DCM 3 times. Reunited organics layers were anydrified with Na2SO4and then solvent was evaporated to dryness by rotavapor. The crude mixture was dissolved in minimum volume of DCM, added to column and eluted with DCM / EtOH (from 100 / 2 to 100 / 4) to give the title compound (0.004 g, 63% Yield). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.12 - 1.32 (5 H, m) 1.36 - 1.54 (4 H, m) 1.56 - 1.69 (2 H, m) 1.93 - 2.31 (4 H, m) 2.54 - 2.73 (2 H, m) 2.74 - 3.02 (8 H, m) 3.22 - 3.55 (11 H, m) 3.60 - 3.72 (1 H, m) 3.88 - 3.98 (1 H, m) 4.07 - 4.19 (4 H, m) 4.20 - 4.28 (1 H, m) 4.53 - 4.64 (1 H, m) 4.98 - 5.27 (3 H, m) 5.34 - 5.51 (2 H, m) 6.90 - 7.08 (2 H, m) 7.60 - 7.73 (1 H, m) 7.79 - 7.97 (1 H, m) 8.04 - 8.15 (1 H, m) 9.45 - 9.91 (1 H, m) 13.38 - 13.82 (1 H, m) 15.59 - 16.14 (1 H, m); HRMS (ESI) calcd for C47H57N5O16 [M+H]+948.3873, found 948.3872.

Claims

CLAIMS 1. An imino-anthracycline derivative of formula (I): OO HO A O wherein:A is a group selected from: Rc Rc ,Het a 3- to 8- Cb is 3- to 8- membered carbocycle; Q is nitrogen or CH; Ra, Rb and Rc are independently hydrogen, a straight or branched (C1-C6) alkyl, or -(CH2CH2O)jCH3,wherein: j is an integer from 1 to 8; R1 and R2 are independently hydrogen, a straight or branched (C1-C6) alkyl, halogen or R1 and R2 taken together form a 3- to 6-membered carbocycle; n, n1 and n2 are independently an integer from 0 to 6; or a pharmaceutically acceptable salt thereof.

2. An imino-anthracycline derivative of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof wherein: A is a group selected from (IIa)-(IIg) wherein: Het is a 5- to 7- membered heterocycle;Cb is 5- to 7- membered carbocycle; Q is nitrogen or CH; Ra, Rb and Rc are independently hydrogen, a straight or branched (C1-C6) alkyl or -(CH2CH2O)jCH3wherein: j is an integer from 1 to 4; R1 and R2 are independently hydrogen, a straight or branched (C1-C6) alkyl, halogen or R1 and R2 taken together form a 3- to 6-membered carbocycle and n, n1and n2are independently an integer from 0 to 4.

3. An imino-anthracycline derivative of formula (I) according to claim 2 or a pharmaceutically acceptable salt thereof wherein: A is a group selected from: Ra ,,Ra, Rc are a or or - jCH3 wherein: j is an integer from 1 to 4.

4. An imino-anthracycline-linker reagent of formula (Ia):O O HO A1 O L wherein:A1 is a group selected from: Rc Rc * * ,Het a 3- to 8- Cb is 3- to 8- membered carbocycle; Q is nitrogen or CH; Rb and Rc are independently hydrogen, a straight or branched (C1-C6) alkyl or -(CH2CH2O)jCH3wherein: j is an integer from 1 to 8; R1 and R2 are independently hydrogen, a straight or branched (C1-C6) alkyl, halogen or R1 and R2 taken together form a 3- to 6-membered carbocycle; n, n1and n2are independently an integer from 0 to 6; * is attachment point of the A1 group to the linker L and L is a linker of formula (IV): WPE G RM (IV)wherein: W is independently null or a self immolative system selected from the group consisting of:* * ,R3 and R4 are, each independently, hydrogen, halogen, straight or branched (C1-C4) alkyl, straight or branched (C1-C4) hydroxyalkyl, -O(CH2-CH2O)zCH3, or -(CH2-CH2O)zCH3; wherein: z is an integer from 1 to 24; Su is group selected from (VIa)-(VIc): HO C H O H O O O O * is G orRM; PE is independently null, dipeptidic, tripeptidic or tetrapeptidic moiety, consisting of any combination of natural L-aminoacids or unnatural D-aminoacids; G is independently null or selected from the group consisting of (VIIa)-(VIIg): * y yy is an integer from 0 to 24; k is an integer from 0 to 8; * is the attachment point to the RM group; RM is a reactive moiety selected from the group consisting of (VIIIa)-(VIIIj): ,R5 R6 are, or or branched (C1-C4) hydroxyalkyl, straight or branched (C1-C4) haloalkyl or, R5 and R6 taken together form a 3- to 6-membered carbocycle; R7 is hydrogen, (C1-C4) alkyl or an electron-withdrawing group selected from the group consisting of NO2 and CN; r is an integer from 0 to 7; m is an integer from 1 to 8; X is a halogen.

5. An imino-anthracycline-linker reagent of formula (Ia), according to claim 4 wherein: A1 is a group selected from:*** * ,Rc are or or - jCH3 wherein: j is an integer from 1 to 4; and L is a linker of formula (IV) wherein: W is independently null or a self immolative system selected from the group consisting of: * Su HOH N, *Su is group selected from (VIa)-(VIc); PE is a dipeptide, tripeptide or tetrapeptide moiety, consisting of any combination of natural L-aminoacids and unnatural D aminoacids selecting from: glycine, alanine, leucine, valine, citrulline, phenylalanine, glutamicacid and aspartic acid wherein the C-terminal aminoacid residue is linked to W, or to A1 when W is null, and the N-terminal aminoacid residue is linked to G or to RM when G is null. G is null or selected from the group consisting of (VIIa)-(VIIg): wherein: y is an integer from 0 to 12; k is an integer from 0 to 8; RM is selected from a group (VIIIa)-(VIIIj): wherein: R5, R6 and R7 are hydrogen; r is an integer from 0 to 4; m is an integer from 1 to 8; X is chlorine or bromine.

6. An imino-anthracycline-linker reagent of formula (Ia), according to claim 5 wherein: A1 is selected from the group consisting of (IIIa’), (IIIa”), (IIIb’), (IIIc’), (IIIe’’), (IIIe’’’), (IIIf’) and (IIIg’) wherein: Rb and Rc are independently straight (C1-C6) alkyl or -(CH2CH2O)jCH3 wherein: j is an integer from 1 to 4; and L is a linker of formula (IV) wherein: W is independently null or a self immolative system selected from the group consisting of: * Su HOH N, *Su is group selected from (VIa)-(VIc); PE is a dipeptide selected from valine-alanine and valine-citrulline, or a tripeptide selected from phenylalanine- leucine-glycine, glutamic acid-valine-alanine and glutamic acid-valine-citrulline or the tetrapeptide glycine- glycine-phenylalanine-glycine, wherein the C-terminal aminoacid residue is linked to W and the N-terminal aminoacid residue is linked to G or RM when G is null; G is null or selected from the group consisting of (VIIa)-(VIIg):wherein: y is an integer from 0 to 8; k is an integer from 0 to 5; RM is a reactive moiety selected from the group (VIIIa)-(VIIIj): wherein: R5, R6 and R7 are hydrogen, r is an integer from 0 to 4; m is an integer from 1 to 4; X is bromine.

7. An imino-anthracycline-linker reagent of formula (Ia), according to claim 6 wherein: L is a linker (IVa)-(IVh):,r is an integer from 0 to 4.

8. An imino-anthracycline derivative of formula (I) according to claim 1 and imino-anthracycline-linker reagent of formula (Ia), according to claims 4 selected from the group consisting of: 2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]piperazine-1-carboxylate (compd.1);[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4- [[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]4-methylpiperazine-1- carboxylate (compd 2); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]1,4-diazepane-1-carboxylate (compd.3); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]4-(methylamino)piperidine-1- carboxylate (compd.4); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]N-methyl-N-(4-piperidyl) carbamate (compd.5); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]N-methyl-N-[2-(methylamino) ethyl]carbamate (compd.6); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]N-[2,2-dimethyl-3-(methylamino) propyl]-N-methyl-carbamate (compd.7); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]4-(2-hydroxyacetyl)-1,4- diazepane-1-carboxylate(compd.8); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] N-[2-[(2-hydroxyacetyl)-methyl- amino]ethyl]-N-methyl-carbamate (compd.9); O1-[[4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]propanoyl]amino]phenyl] methyl]O4-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl- 5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]piperazine-1,4- dicarboxylate (compd.1a); O1-[[4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]-5-ureido-pentanoyl]amino] phenyl]methyl]O4-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6- methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]piperazine- 1,4-dicarboxylate (compd.2a); O1-[[4-[[2-[[(2S)-2-[[2-[[2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]acetyl]amino]acetyl]amino]-3-phenyl-propanoyl] amino]acetyl]amino]phenyl]methyl]O4-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4- [[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4- dihydro-1H-tetracen-2-yl]ethyl]piperazine-1,4-dicarboxylate (compd.3a); O4-[[4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-l)hexanoylamino]-3-methyl-butanoyl]amino] propanoyl] amino]phenyl] methyl]O1-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]- 11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]1,4-diazepane-1,4-dicarboxylate (compd.4a); O4-[[4-[[2-[[(2S)-2-[[2-[[2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]acetyl]amino]acetyl]amino]-3-phenyl-propanoyl] amino]acetyl]amino]phenyl]methyl]O1-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4- [[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4- dihydro-1H-tetracen-2-yl]ethyl] 1,4-diazepane-1,4-dicarboxylate (compd.5a); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl]4-[[4-[[(2S)-2-[[(2S)-2-[6-(2,5- dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]propanoyl]amino]phenyl]methoxycarbonyl-methyl- amino]piperidine-1-carboxylate (compd.6a); [4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]propanoyl]amino]phenyl]methyl 4-[methyl-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl- 5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethoxy]carbonyl- amino]piperidine-1-carboxylate (compd.7a); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] N-[2-[[4-[[(2S)-2-[[(2S)-2-[6-(2,5- dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]-5-ureido-pentanoyl]amino]phenyl]methoxycarbonyl- methyl-amino]ethyl]-N-methyl-carbamate (compd.8a); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] N-[2-[[4-[[(2S)-2-[[(2S)-2-[6-(2,5- dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]propanoyl]amino]phenyl]methoxycarbonyl-methyl-amino] ethyl]-N-methyl-carbamate (compd.9a); [4-[[(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]propanoyl]amino]phenyl]methyl N-[2,2-dimethyl-3-[methyl-[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10- methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl] ethoxy]carbonyl-amino]propyl]-N-methyl-carbamate (compd.10a); (4S)-4-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-5-[[(1S)-2-methyl-1-[[(1S)-1-methyl-2-oxo-2-[4-[[4-[2-oxo-2-[(2S,4S)- 2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo [7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethoxy]carbonylpiperazine-1-carbonyl]oxymethyl] anilino]ethyl]carbamoyl]propyl]amino]-5-oxo-pentanoic acid (compd.11a); (4S)-4-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-5-[[(1S)-2-methyl-1-[[(1S)-1-methyl-2-[4-[[methyl-[2-[methyl-[2-oxo-2- [(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1- azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethoxy]carbonyl- amino]ethyl]carbamoyl]oxymethyl]anilino]-2-oxo-ethyl]carbamoyl]propyl]amino]-5-oxo-pentanoic acid (compd.12a); (4S)-4-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-5-[[(1S)-2-methyl-1-[[(1S)-1-methyl-2-oxo-2-[4-[[4-[2-oxo-2-[(2S,4S)- 2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo [7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethoxy]carbonyl-1,4-diazepane-1-carbonyl] oxymethyl]anilino]ethyl]carbamoyl]propyl]amino]-5-oxo-pentanoic acid (compd.13a);[2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4- [[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa-1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] N-[2-[[2-[[[2-[[(2S)-2-[[2- [[2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]acetyl]amino]acetyl]amino]-3-phenyl-propanoyl]amino]acetyl]amino] methoxy]acetyl]-methyl-amino]ethyl]-N-methyl-carbamate (compd.14a); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] 4-[2-[[[2-[[(2S)-2-[[2-[[2-[6-(2,5- dioxopyrrol-1-yl)hexanoylamino]acetyl]amino]acetyl]amino]-3-phenyl-propanoyl]amino]acetyl]amino]methoxy]acetyl]- 1,4-diazepane-1-carboxylate (compd.15a); [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(2S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] N-[2-[[2-[[[(2S)-2-[[(2S)-2-[6-(2,5- dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]propanoyl]amino]methoxy]acetyl]-methyl-amino]ethyl]-N- methyl-carbamate (compd.16a) and [2-oxo-2-[(2S,4S)-2,5,12-trihydroxy-6-imino-7-methoxy-4-[[(1S,4R,6S,7S,9R,10S)-10-methoxy-6-methyl-5,8,11-trioxa- 1-azatricyclo[7.4.0.02,7]tridecan-4-yl]oxy]-11-oxo-3,4-dihydro-1H-tetracen-2-yl]ethyl] N-[2-[[2-[[[(2S)-2-[[(2S)-2-[6-(2,5- dioxopyrrol-1-yl)hexanoylamino]-3-methyl-butanoyl]amino]propanoyl]amino]methoxy]acetyl]-ethyl-amino]ethyl]-N- ethyl-carbamate (compd.17a).

9. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I), as defined in claim 1, and at least one pharmaceutically acceptable excipient, carrier or diluent.

10. A pharmaceutical composition according to claim 9 further comprising one or more chemotherapeutic agents.

11. A therapeutic combination comprising (a) a compound of formula (I), as defined in claim 1 and (b) one or more chemotherapeutic agents.

12. A compound of formula (I), as defined in claim 1, for use as a medicament.

13. A compound of formula (I), as defined in claim 1, for use in a method for treating cancer.

14. A compound for use according to claim 13 characterized in that the cancer is is selected from the group consisting of: carcinomas, such as bladder, breast, kidney, liver, colon, lung, including small cell lung cancer, esophagus, gall- bladder, ovary, pancreas, stomach, cervix, prostate, and skin, including squamous cell carcinoma; hematopoietic tumors of lymphoid lineage including leukemia, acute lymphocitic leukemia, acute lymphoblastic leukemia, B-cell lymphoma, angioimmunoblastic T-cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, hairy cell lymphoma and Burkitt's lymphoma; hematopoietic tumors of myeloid lineage, including acute and chronic myelogenous leukemias, myelodysplastic syndrome and promyelocytic leukemia; tumors of mesenchymal origin, including fibrosarcoma and rhabdomyosarcoma; tumors of the central and peripheral nervous system, including glioma, glioblastoma, glioblastoma multiforme, astrocytoma, oligodendroglioma, paraglioma, neuroblastoma, and schwannomas; and other tumors, including melanoma, uveal melanoma, seminoma, teratocarcinoma, osteosarcoma, adrenocortical cancer, xeroderma pigmentosum, keratoxanthoma, thyroid cancers, such as papillary thyroid carcinoma and medullary thyroid carcinoma, Kaposi's sarcoma, chondrosarcoma, and cholangiocarcinoma.

15. Use of a compound of formula (I), as defined in claim 1, in the manufacture of a medicament for treating cancer.

16. A method for treating cancer, which comprises administering to a mammal in need thereof an effective amount of a compound of formula (I) as defined in claim 1.

17. The method of claim 16 wherein the mammal in need thereof is a human.

18. A compound of formula (Ia), as defined in claim 4, for use in the preparation of conjugates.

19. Use of a compound of formula (Ia), as defined in claim 4, in the preparation of conjugates.

20. Process for the preparation of imino-anthracycline of formula (I), or pharmaceutical acceptable salt thereof, as defined in claim 1, said process comprises the following steps: Step 1) reaction of a compound of formula (IX): OO HO OH with a suitable compound of formula, (Bpoc),tert- or 4- or (C1-C6) alkyl, -(CH2CH2O)jCH3, or a protecting group orthogonal to Bpoc, Boc or MMT, preferably N-allyloxycarbonyl (Alloc); Het, Cb, Q , R1, R2 , n, n1and n2are as defined in claim 1; Step 2) reaction of the so obtained compound of formula (XI):A' withof formula (XII): A' wherein A’ is as defined in step 1.Step 3) removal of the protecting group / s from compound of formula (XII), to give a compound of formula (I) wherein A is selected from theone of Ra, Rb or Rc is hydrogen and Het, Cb, Q, R1, R2, n, n1and n2are as defined in claim 1; or alternative, Step 4) reaction of a compound of formula (IX) with the intermediate of formula (XIII): (XIII) wherein A is selected from the group consisting of (IIa)–(IIg):Rc Rc ,R1, R2 , n, n1and n2are as defined in claim 1; Step 5) reaction of the so obtained compound of formula (XIV): wherein A is defined in step 4, with of formula (I):wherein A is defined above under19. Process for the preparation of imino-anthracycline-linker reagent of formula (Ia), or pharmaceutical acceptable salt thereof, as defined in claim 4, said process comprises the following steps: Step 6) reaction of a compound of formula (Ia)’:O OH OO A1Rc Rc ,(XIV): L (XIV)wherein LG is a group selected from chlorine, p-Nitrophenol, imidazole, HO-, -O-succiminidyl or -O-acetyl and L is a linker of formula (IV): WPE G RM (IV)wherein W, PE, G and RM are as defined in claim 4, to give a compound (Ia). OO HO A1 O L wherein A1 and L are as defied

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