FR3022907A1 - OSW-1 DERIVATIVES AND THEIR USE AS A MEDICINAL PRODUCT - Google Patents

Abstract

The present invention relates to a compound of formula (I) below: or a pharmaceutically acceptable salt and / or solvate thereof, its use in the treatment of cancer, pharmaceutical compositions containing it and methods of preparation thereof .

Description

The present invention relates to OSW-1 derivatives, their therapeutic use, especially in the treatment of cancer, and their method of synthesis. OSW-1 is a natural product belonging to the family of steroidal saponins and possessing anticancer properties. HO 0 SW-1 This is a potent cytotoxic in vitro (IC50 = 10-10-10-9M) on various cancer cell lines, while healthy cells are significantly less sensitive (Zhou et al., J. Nat. Cancer Inst., 2005, 97 (23), 1781-1785, Garcia-Prieto et al., J. Biol Chem, 2013, 288 (5), 3240-3250). Specifically, the cytotoxic action of OSW-1 on leukemic cells at a subnanomolar concentration is mediated by a time-dependent Ca2 + elevation leading to a loss of mitochondrial membrane potential, activation of caspase-3 and induction of apoptosis (Zhou et al., J. Nat Cancer Inst., 2005, 97 (23), 1781-1785, Garcia-Prieto et al., J. Biol Chem, 2013, 288 ( 5), 3240-3250). At the same time, OSW-1 treatment leads to the overexpression or inhibition of the expression of a large number of miRNAs known to be associated with cancer and involved in proliferation, survival and cell migration, polarity and the epithelio-mesenchymal transition (Jin et al., Mol Med Reports 2013, 7, 1831-1837). In 2011, Burgett et al. (Nature Chem Biol., 2011, 7, 639-647) have identified the target of OSW-1: it is the oxysterol binding protein (OBP) and its close paralog OSBP-related protein-4L (ORP4L ), a family of proteins involved in lipid metabolism, cell signaling, vesicular and non-vesicular traffic transport of sterols.

The compounds of this class carry a strongly hydrophobic steroid group and therefore have a very low solubility, especially in water where they are insoluble. The inventors of the present invention have surprisingly discovered that particular modifications of the structure of OSW-1, in particular with regard to the side chain, make it possible to obtain cytotoxic derivatives that are equally powerful and above all more soluble than OSW-1. 1 and its analogs previously described. In addition, these compounds are more formable because they carry amine functional groups that can be salified.

The present invention therefore more particularly relates to a compound of general formula (I): OH (I) or a salt and / or a pharmaceutically acceptable solvate thereof, wherein: - - - - represents a double or single bond , R1 represents one or more substituent (s) identical (s) or different (s) each representing independently of each other a hydrogen atom, a halogen atom (preferably fluorine) or a trifluoromethyl group, (Ci -C6) alkyl, (C1-C6) alkoxy, NR3R4, (CH2) mNR5R6, O (CH2) mNR7R8, or CO2R9, with R3 to R9 independently of one another a hydrogen atom or a (C1-C6) group ) optionally substituted alkyl, (preferably with a nitrogen and / or oxygen function), and m represents an integer between 1 and 6, 1:10 + - R2 represents -N-R11 N = N = N -O-R12 with : - either Rio represents a hydrogen atom or an optionally substituted (Ci-C6) alkyl group (preferably an unsubstituted ), and R11 represents a hydrogen atom or an optionally substituted (C1-C6) alkyl, optionally substituted aryl, optionally substituted (C1-C6) alkyl, Y1 (CH2) a1Y2R13, SO2R14, COR15, CO2R16 group, or CONR17R18, with Yi representing a single bond or a CO, CO2, CONR19 or SO2 group, Y2 representing an oxygen atom or an NR20 or SO2 group, where al represents an integer between let 6, R13 to R17 independently representing one another; another a hydrogen atom or an optionally substituted (C1-C6) alkyl, optionally substituted aryl or optionally substituted (C1-C6) alkyl (preferably a hydrogen or a C1-C6) alkyl group) and R18 to R20 independently of one another are hydrogen or optionally substituted (C1-C6) alkyl (preferably unsubstituted), or R11 and R11 together with the nitrogen atom carrying them an optionally substituted heterocycle, and R12 is optionally substituted (C1-C6) alkyl, optionally substituted aryl, optionally substituted (C1-C6) alkyl, Y3 (CH2) a2Y4R21, COR22, CO2R23, or CONR24R25, with Y3 being a single bond or a group CO, CO2 or CONR26, Y4 representing an oxygen atom, or an NR27 or SO2 group, a2 representing an integer between 1 and 6, R21 to R24 representing independently of each other a hydrogen atom or a group ( C1-C6) optionally substituted alkyl, optionally substituted aryl or optionally substituted (C1-C6) alkyl aryl (preferably hydrogen or (C1-C6) alkyl), and R25 and R26 independently represent one of the other a hydrogen atom or an optionally substituted (C1-C6) alkyl group (preferably unsubstituted).

When - - - - represents a single bond, the ring junction may be of cis or trans configuration. The compound of formula (I) may therefore adopt two different diastereoisomeric configurations and therefore be in the form of one or other of these diastereoisomers or in the form of a mixture thereof in all proportions. Similarly, the groups R 1 and R 2 may each have one or more asymmetric centers (such as an asymmetric carbon) and / or one or more C = C double bonds, which implies that these groups may adopt different stereoisomeric configurations. The compound of formula (I) may therefore be in the form of one of their diastereoisomers or in the form of a mixture of these in all proportions. By "pharmaceutically acceptable salts" of a compound is meant in the present invention salts which are pharmaceutically acceptable, as defined above, and which possess the desired pharmacological activity of the parent compound. These are in particular acid addition salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like; or formed with organic acids such as acetic acid, formic acid, benzenesulfonic acid, benzoic acid, camphorsulfonic acid, citric acid, ethanesulfonic acid, fumaric acid, glucoheptonic acid, gluconic acid, glutamic acid, glycolic acid, hydroxynaphthoic acid, 2-hydroxyethanesulfonic acid, lactic acid, maleic acid, malic acid, mandelic acid, methanesulfonic acid, muconic acid, 2-naphthalenesulfonic acid, propionic acid, salicylic acid, succinic acid, dibenzoyl-L-tartaric acid, tartaric acid, p-acid toluenesulphonic acid, trimethylacetic acid, glucaric acid, trifluoroacetic acid and the like. According to a particular embodiment, it will be a salt formed with formic acid or glucaric acid. The term "(Cx-Cy) alkyl" represents linear or branched, saturated hydrocarbon chains comprising from x to y carbon atoms. Thus, the term "(C 1 -C 6) alkyl" represents chains of 1 to 6 carbon atoms. It may be in particular a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl or hexyl group. The term "(C2-C6) alkenyl" represents a hydrocarbon chain, linear or branched, having at least one double bond and having 2 to 6 carbon atoms. By way of example, mention may be made of ethenyl or allyl groups. The term "(C1-C6) alkoxy" represents a (C1-C6) alkyl chain linked to the remainder of the molecule through an oxygen atom. By way of example, mention may be made of methoxy, ethoxy, propoxy, isopropoxy, butoxy or even tert-butoxy groups.

The term "trialkylsilyl" represents a group -SiAlkiAlk2A1k3 with Alki, Alk2 and Alk3 representing, independently of each other, a (C 1 -C 6) alkyl group as defined above. The term "aryl" represents an aromatic hydrocarbon group, preferably having from 6 to 10 carbon atoms, and comprising one or more contiguous rings, such as, for example, a phenyl or naphthyl group. Advantageously, it is phenyl. For the purposes of the present invention, the term "aryl (C 1 -C 6) alkyl" means an aryl group as defined above linked to the remainder of the molecule via a (C 1 -C 6) group. alkyl as defined above. It may be in particular a benzyl group. The term "heterocycle" represents either a stable monocycle of 4 to 7, preferably 5 to 6, members, or a stable bicycle whose rings are formed from 8 to 11 atoms, the unicycle and the bicycle may be either saturated or unsaturated (including aromatics), 1 to 4 of the atoms forming the ring (s) being a heteroatom independently selected from sulfur, nitrogen and oxygen atoms, the other atoms forming the ring (s) ( s) being carbon atoms. By way of example, mention may be made of furan, pyrrole, thiophene, azetidine, pyrrolidine, morpholine, homopiperazine, thiazole, isothiazole, oxadiazole, imidazole, oxazole, isoxazole, triazole, tetrazole, pyridine, piperidine, pyrazine, piperazine, tetrahydropyran and pyrimidine. quinazoline, quinoline, quinoxaline, benzofuran, benzothiophene, indoline, indolizine, benzothiazole, benzothienyl, benzopyran, benzoxazole, benzo [1,3] dioxole, benzoisoxazole, benzimidazole, chromane, chromene, dihydrobenzofuran, dihydrobenzothienyl, dihydroisoxazole, isoquinoline, dihydrobenzo [ 1,4] dioxin, imidazo [1,2-a] pyridine, furo [2,3-c] pyridine, 2,3-dihydro-1H-indene, [1,3] dioxolo [4,5-c] pyridine pyrrolo [1,2c] pyrimidine, pyrrolo [1,2-a] pyrimidine, tetrahydronaphthalene, benzo [b] [1,4] oxazine. Preferably, it is a 4- to 6-membered, preferably 5 or 6-membered saturated or unsaturated (including aromatic) monocycle, such as an azetidine, pyrrolidine, pyrrole, piperidine, morpholine or piperazine ring. homopiperazine, thiazole oxazole, triazole, or tetrazole, preferably morpholine or triazole (especially 1,2,3-triazole). By "optionally substituted" is meant, in the sense of the present invention, that the group in question is optionally substituted by one or more substituents which may be chosen in particular from a halogen atom, a nitrogen and / or oxygen function, a group SO2R28, CN, NO2, (C1-C6) alkyl optionally substituted with a nitrogen and / or oxygen function, (C1-C6) alkoxy, aryl (C1-C6) alkyl, heterocycle or aryl with R28 representing a group (Ci -C6) alkyl, aryl or aryl (C1-C6) alkyl, especially a (C1-C6) alkyl group optionally substituted by a nitrogen and / or oxygen function. By "nitrogen and / or oxygen function" is meant especially a group NR29R30, NR31COR32, NR33COOR34, NR35CONR36R37, OR38, OCOR39, OCOOR40, OCONR41R42, COR43, COOR44 or CONR45R46, preferably a group NR29R30 or OR38, with R29 to R46 representing , independently of one another, a hydrogen atom or a (C 1 -C 6) alkyl, aryl or aryl (C 1 -C 6) alkyl group, preferably a hydrogen atom or a (C 1 -C 6) alkyl group. For the purposes of the present invention, the term "stereoisomer" means a geometric isomer (or configuration isomer) or an optical isomer.

The geometric isomers result from the different position of the substituents on a double bond which can then have a Z or E configuration, also called cis or trans. The optical isomers result in particular from the different position in the space of the substituents on a carbon atom comprising 4 different substituents.

This carbon atom then constitutes a chiral center or asymmetric center. Optical isomers include diastereoisomers and enantiomers. Optical isomers which are images of each other in a mirror but not superimposable are referred to as "enantiomers". Optical isomers that are not mirror images of each other in a mirror are referred to as "diastereoisomers". An "asymmetric carbon" is a carbon atom substituted by four different groups (a group may be a hydrogen atom). Advantageously, the compounds according to the invention comprise one to five R 1 groups, preferably 1 to 2 more preferably only 1 R 1 group. In the latter case (only one R 1 group), the R 1 group will preferably be located in the para position on the phenyl ring relative to the carbonyl group. Advantageously, the group R 1 is a (C 1 -C 6) alkoxy group, in particular a methoxy group. Advantageously, represents a simple connection.

In a first embodiment, R2 is a group N3 Rlo. In a second embodiment, R2 is a group -N-R11, wherein: - either R10 represents a hydrogen atom or a (C1-C6) alkyl group optionally substituted (preferably unsubstituted), and R11 is hydrogen, optionally substituted (C1-C6) alkyl, optionally substituted aryl, optionally substituted (C1-C6) alkyl, Y1 (CH2) a1Y2R13, SO2R14, COR15, CO2R16, or CONR17R18, where Yi represents a single bond or a group CO, CO2, CONR19 or SO2, Y2 represents an oxygen atom or a group NR20 or SO2, where al represents an integer between let 6, R13 to R17 represent independently of each other a hydrogen atom or an optionally substituted (C1-C6) alkyl, optionally substituted aryl or optionally substituted (C1-C6) alkyl aryl (preferably a hydrogen atom or a group (C1-C6) alkyl), and R18 to R20 independently of one another is a hydrogen atom or an optionally substituted (C1-C6) alkyl group (preferably unsubstituted), or R10 and R11 form with the nitrogen atom which carries them an optionally substituted heterocycle .

In a first aspect, R10 and R11 do not form a ring with the nitrogen atom that carries them. In this case, advantageously, R 10 represents a hydrogen atom or a (C 1 -C 6) alkyl group. More particularly, R10 represents hydrogen or methyl.

R11 will especially represent a hydrogen atom or a (C1-C6) alkyl, aryl, (C1-C6) alkyl-aryl, Yi (CH2) a1Y2R13, 502R14, CORis, CO2R16, or CONR17Ris group. Preferably, R 11 will be hydrogen, (C 1 -C 6) alkyl, aryl (C 1 -C 6) alkyl, Y 1 (CH 2) 2 Y 2 R 13, 50 2 R 14, COR 15, or CONR 1 R 7. Y1 will preferably represent a single bond.

Y 2 will advantageously represent an oxygen atom or an SO 2 al group will in particular represent an integer between 1 and 4, especially 1 or 2, preferably 2. R 13 to R 17 advantageously represent, independently of each other, a hydrogen atom or a (C1-C6) alkyl, aryl or aryl (C1-C6) alkyl group, preferably a hydrogen atom or a (C1-C6) alkyl group, more preferably a (C1-C6) group alkyl. R18 to R20 will preferably represent, independently of each other, a hydrogen atom or a (C1-C6) alkyl group. R 11 may thus represent a (C 1 -C 6) alkyl group, in which case R 11 will preferably be a methyl, ethyl or isopropyl group. R11 may alternatively represent a group Yi (CH2) a1Y2R13 in which Y1 represents a single bond, Y2 is as defined above (and preferably an oxygen atom, or a group SO2), al represents 1 to 6, preferably 1 at 4, still more preferably 1 to 2, especially 2, and R13 is (C1-C6) alkyl. R11 may alternatively represent an optionally substituted (C1-C6) alkyl-aryl (in particular unsubstituted) group, preferably an optionally substituted (C1-C2) alkyl-aryl group (in particular unsubstituted). Aryl will be especially a phenyl group. R11 may finally represent a group SO2R14, COR15 or CONR17R18 with R14, R15 and R18 representing, independently of each other, a (C1-C6) alkyl group and R17 representing a hydrogen atom or a (C1-C6) group alkyl. In a second aspect, R10 and R11 form with the nitrogen atom which carries them an optionally substituted heterocycle, in particular the heterocycle will have 5 to 6 members. The heterocycle will in particular comprise 1 to 3 heteroatoms (including the nitrogen atom bearing the groups R10 and Ru) chosen from N and O. The heterocycle may in particular be chosen from the azetidine, pyrrolidine, pyrrole and piperidine rings. morpholine, piperazine, homopiperazine, thiazole, oxazole, triazole, or tetrazole, preferably morpholine or triazole (especially 1,2,3-triazole). This heterocycle will be optionally substituted with one or more substituents which may be chosen in particular from a halogen atom, a nitrogen and / or oxygen function, a SO 2 R 28, CN, NO 2, (C 1 -C 6) alkyl group optionally substituted by a nitrogen function. and / or oxygenated, (C1-C6) alkoxy, aryl- (C1-C6) alkyl, heterocycle or aryl with R28 representing a (C1-C6) alkyl, aryl or aryl- (C1-C6) alkyl group. Preferably, the heterocycle will be optionally substituted with a (C1-C6) alkyl group optionally substituted with a nitrogen and / or oxygenated function. The nitrogenous and / or oxygenated function will advantageously be a group NR29R30, NR31COR32, NR33COOR34, NR35CONR36R37, OR38, OCOR39, OCOOR40, OCONR41R42, COR43, COOR44 or CONR45R46, preferably a group NR29R30 or OR38. In particular, the heterocycle formed by R10 and R11 and the nitrogen atom which bears them NO / -N -N 0 \, - eoe-N1-1 \ 11x will be In a third embodiment R2 is a grouping: 0-R12 with R12 representing a (C1-C6) alkyl, aryl, aryl (C1-C6) alkyl, Y3 (CH2) a2Y4R21 group, COR22, C 02R23, or C ONR24R25 Advantageously R12 represents a group Y3 (CH2) a2Y4R21 with R 21 advantageously representing a (C 1 -C 6) alkyl group and a 2 advantageously representing 1 to 6, preferentially 1 to 4, more preferably 1 to 2, especially 2. In this case, Y 4 may in particular represent a group NR 27 or SO 2. , in particular S02. Y3 will advantageously represent a single bond or a CONR26 group, especially a CONR26 group, with R26 preferably representing a hydrogen atom or a (C1-C6) alkyl group, preferably a hydrogen atom. The compounds of the present invention may be selected from the compounds listed in the following Table: ## STR1 ## ## EQU1 ## ## STR5 ## ## STR5 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR5 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## 0) 0H 0 ° H) CDH 0 ° \) # 0 OH 0) -OH OH ee 0) \ 'HN HO O0 0 0 ee o 0- HN' O HO eige 0 \ p - 0-) j0 ## STR5 ## wherein O &sub1; O & numsp & numsp & numsp O OH . ## STR5 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## EQU1 ## where ## STR2 ## where ## STR2 ## Or a pharmaceutically acceptable salt and / or solvate thereof, such as a salt formed with formic acid. The subject of the present invention is also a compound according to the invention of formula (I) as defined above, for use as a compound of formula (I) as defined above. drug, especially for the treatment of cancer.

The present invention also relates to the use of a compound of formula (I) as defined above, for the manufacture of a medicament, in particular for the treatment of cancer. The present invention also relates to a method of treating cancer, comprising administering to a person in need of an effective dose of a compound of formula (I) as defined above. The cancer may be more particularly in this case colon cancer, breast cancer, kidney cancer, liver cancer, pancreatic cancer, prostate cancer, glioblastoma, lung cancer, neuroblastoma , an inflammatory myofibroblastic tumor, or lymphoma.

The present invention also relates to a pharmaceutical composition comprising at least one compound of formula (I) as defined above, and at least one pharmaceutically acceptable excipient. The pharmaceutical compositions according to the invention can be formulated especially for oral administration or by injection, said compositions being intended for mammals, including humans.

The active ingredient can be administered in unit dosage forms, in admixture with conventional pharmaceutical carriers, to animals or humans. The compounds of the invention as active ingredients can be used at doses of between 0.01 mg and 1000 mg per day, given as a single dose once a day or administered in several doses throughout the day, for example twice a day in equal doses. The dose administered per day is advantageously between 5 mg and 500 mg, more advantageously between 10 mg and 200 mg. It may be necessary to use doses out of these ranges which the skilled person can realize himself.

The pharmaceutical compositions according to the invention may also comprise at least one other active ingredient, such as an anticancer agent. The present invention also relates to a pharmaceutical composition comprising: (i) at least one compound of formula (I) as defined above, and (ii) at least one other active ingredient, such as an anticancer agent, in as a combination product, for simultaneous, separate or spread use over time. The present invention also relates to a pharmaceutical composition as defined above for its use as a medicament, in particular for the treatment of cancer. The present invention also relates to processes for preparing the compounds of formula (I) according to the invention. The present invention thus relates to a first process for preparing a compound of formula (I) according to the invention comprising the following steps: (1) condensation of a compound of formula (II) below: R2GP for which - - - - is as defined above, GPi represents a 0-protecting group and R2GP represents a group R2 as defined above optionally in protected form, with a compound of formula (III) below: OGP3 for which LGi represents a group leaving; GP2, GP3 and GP4 each represent, independently of each other, an O-protecting group; and R1GP represents a group R1 as defined above optionally in protected form, (2) deprotection of the protecting groups to give a compound of formula (I), (3) when - - - - represents a double bond, optionally reduction of the double bond to give a compound of formula (I) for which - - - - represents a single bond, and (4) optionally salification and / or solvation to give a compound of formula (I) according to the invention in the form of a pharmaceutically acceptable salt and / or solvate. For the purposes of the present invention, the term "protecting group" or "protecting group" is intended to denote a group that selectively blocks a reactive site in a multifunctional compound so that a chemical reaction can be selectively carried out at the level of another unprotected reactive site in the meaning conventionally associated with it in synthetic chemistry. For the purposes of the present invention, the term "O-protecting group" is intended to mean any substituent which protects the hydroxyl or carboxyl group, that is to say a reactive oxygen atom, against undesirable reactions such as cleavage groups. 0-protector described in Greene "Protective Groups In Organic Synthesis", (John Wiley & Sons, New York (1981)) and Harrison et al. "Compendium of Synthetic Organic Methods", Vols.1 to 8 (J. Wiley & Sons, 1971 to 1996) A hydroxyl group protected by an O-protecting group may be for example an ether, an ester, a carbonate, an acetal In particular, the 0-protecting groups comprise a (C 1 -C 6) alkyl group optionally substituted with one or more (especially 1 to 3) halogen atoms (such as chlorine atoms), such as methyl groups. ethyl, tertbutyl and 2,2,2-trichloroethyl; aryl (C 1 -C 6) alkyl, such as benzyl, the aryl ring being optionally substituted by one or more methoxy groups, such as benzyl groups (Bn) and p-methoxybenzyl (PMB), a trityl group of the formula -CAriAr 2 Ar 3, such as triphenylmethyl (also called trityl-Tr), (4-methoxyphenyl) diphenylmethyl (also called methoxytrityl-NMT) and bis- (4-methoxyphenyl) phenylmethyl (also called dimethoxytrityl - DMT) a methyl substitute group e of formula -CH2ORGP2 or -CH2SRGP2 (in particular -CH2ORGP2), such as methoxymethyl (MOM), benzyloxymethyl, 2-methoxyethoxymethyl (MEM), 2- (trimethylsilyl) ethoxymethyl and methylthiomethyl; a substituted ethyl group of formula -CH2CH2ORGp2 or -CH2CH2SRGp2 (in particular -CH2CH2ORGp2), such as the ethoxyethyl group (EE); a silyl group of formula - SiRGp3RGp4RGp5, such as trimethylsilyl (TMS), triethylsilyl (TES), t-butyldimethylsilyl (TBS or TBDMS) and t-butyldiphenylsilyl (TBDPS); a carbonyl group of formula -CO-RGP6, such as acetyl (Ac), pivaloyl (Piv or Pv) and benzoyl (Bz), or of formula -CO2-RGP7, such as allyloxycarbonyl (Alloc) and 9- fluorenylmethyloxycarbonyl (Fmoc); or a tetrahydropyranyl () (THP) or tetrahydrofuranyl (C) group; with Ari, Are and Ara representing, independently of each other, an aryl, such as phenyl, optionally substituted by one or more methoxy groups; RGP2 is (C1-C6) alkyl (such as methyl or ethyl) optionally substituted with aryl (such as phenyl), (C1-C6) alkoxy (such as methoxy) or trialkylsilyl (such as SiMe3); RGp3, RGP4 and RGP5 representing, independently of each other, a (C 1 -C 6) alkyl or aryl group (such as phenyl); and RGP6 and RGP7 independently of one another are (C1-C6) alkyl, (C2-C6) alkenyl, aryl, aryl (C1-C6) alkyl or 9-fluorenylmethyl. In particular, it will be a silyl group of formula -SiRGP3RGP4RGP5 (in particular TBDMS or TES) or an aryl-(C1-C6) alkyl group, the aryl ring being optionally substituted (preferably unsubstituted) by one or more methoxy groups (in particular Bn). For the purposes of the present invention, the term "N-protecting group" is intended to mean any substituent which protects a primary or secondary amine function against the undesirable reactions such as the N-protecting groups described in Greene "Protective Groups In Organic Synthesis", (John Wiley & Sons, New York (1981)) and Harrison et al. Compendium of Synthetic Organic Methods, Vols. 1 to 8 (J. Wiley & sons, 1971 to 1996). An amine function protected by an N-protecting group may be, for example, a carbamate, an amide, a sulfonamide, an N-alkyl derivative, an amino acetal derivative, an N-benzyl derivative, an imine derivative, an enamine derivative or a derivative. N-hetero. In particular, the N-protecting groups comprise a formyl group; an aryl group, such as phenyl, optionally substituted with one or more methoxy groups, such as p-methoxyphenyl (PMP); an aryl-C 1 -C 6 alkyl group, such as benzyl, the aryl ring being optionally substituted with one or more methoxy groups, such as benzyl (Bn), p-methoxybenzyl (PMB) and 3,4-dimethoxybenzyl ( DMPM); a group -CO-RGPI such as acetyl (Ac), pivaloyl (Piv or Pv), benzoyl (Bz) and p-methoxybenzylcarbonyl (Moz); a -OO 2 -RGPI group such as tbutyloxycarbonyl (Boc), trichloroethoxycarbonyl (TROC), allyloxycarbonyl (Alloc), benzyloxycarbonyl (Cbz or Z) and 9-fluorenylmethyloxycarbonyl (Fmoc); a -502-RGPI group such as phenylsulfonyl, tosyl (Ts or Tos) and 2-nitrobenzenesulfonyl (also called nosyl - Nos or Ns); and the like, with RGpi representing a (C 1 -C 6) alkyl group optionally substituted with one or more halogen aromas such as F or Cl; a (C2-C6) alkenyl group such as an allyl group; an aryl group, such as phenyl, optionally substituted with one or more groups selected from OMe (methoxy) and NO2 (nitro); an aryl (C 1 -C 6) alkyl group, such as benzyl, the aryl ring being optionally substituted with one or more methoxy groups; or a 9-fluorenylmethyl group.

In particular, it will be a group -OO2-RGpi such as Cbz. By "deprotection" is meant, in the sense of the present invention, the process by which a protecting group is removed once the selective reaction is complete. Some protecting groups may be preferred over others because of their convenience or relative ease of disposal.

By "leaving group" is meant, in the sense of the present invention, a chemical group that can be easily moved by a nucleophile during a nucleophilic substitution reaction, the nucleophile being more particularly an alcohol. Such a leaving group may be more particularly a halogen atom, a sulfonate or an imidate. The halogen atom can be a chlorine or bromine atom.

The sulphonate will be more particularly a group -SO 2 -R 'with R' representing a (C 1 -C 6) alkyl, aryl, aryl (C 1 -C 6) alkyl or (C 1 -C 6) alkyl-aryl group, said group being optionally substituted. with one or more halogen atoms such as fluorine. The sulphonate may in particular be a mesylate (CH3-S (O2) O-), a triflate (CF3-S (O) 20-) or a tosylate (p-Me-C6H4-S (O) 20-). The imidate will be more particularly a group -OC (= NH) -R "with R" representing a (C 1 -C 6) alkyl group optionally substituted with one or more halogen atoms such as chlorine or fluorine. The imidate may more particularly be a group -OC (= NH) CCl3 or -OC (= NH) CF3. Step (i): The condensation reaction can be carried out in a solvent such as dichloromethane. LGi will more particularly represent an imidate such as -OC (= NH) CCl3. In this case, the condensation reaction will advantageously be carried out in the presence of trimethylsilyl trimethanesulfonate. GPi, GP2, GP3 and GP4, which are identical or different, will advantageously represent a silyl group of formula -SiRGP3RGP4RGP5 with RGP3, RGP4 and RGP5 as defined above or an aryl-(C1-C6) alkyl group, the aryl ring being optionally substituted (preferably unsubstituted) with one or more methoxy groups. This could be a group TES, TBDMS or Bn. Preferably, GPi, GP2, GP3 and GP4 represent a silyl group of formula -SiRGP3RGP4RGP5 such as TES and TBMS and are advantageously identical. By group R1 or R2 "in a protected form" is meant more particularly that the NH, NH2, COOH functions (especially when R1 = CO2R9 with R9 = H) and OH (especially in the presence of a group Y4R21 = OH) present in these groups R1 and R2 may be in protected form by replacing a hydrogen atom of these functions with an N-protecting group for NH and NH2 or O-protecting for COOH and OH. The N-protecting group will be more particularly a -OO 2 -RGp1 group with RGpi as defined above, and in particular a Cbz group. The O-protecting group will more particularly be a silyl group of formula -SiRGP3RGP4RGP5 (in particular TBDMS or TES) or an aryl-(C1-C6) alkyl group, the aryl ring being optionally substituted (preferably unsubstituted) by one or more methoxy groups (in particular Bn). The compounds of formula (II) and (III) can be prepared by methods well known to those skilled in the art and illustrated in the experimental part below.

Step (ii): The deprotection step will be carried out under conditions well known to those skilled in the art.

For example, the 0-protecting groups TES and TBDMS may be deprotected in the presence of palladium chloride, bis acetonitrile. This reaction may be carried out in a solvent such as acetone. The 0-protecting group Bn and the N-protecting group Cbz may be deprotected in the presence of Raney nickel. This reaction may be carried out in a solvent such as ethanol, water and a mixture thereof.

Step (iii): The step of reducing the double bond can be carried out under conditions well known to those skilled in the art, for example in the presence of Raney nickel, especially in a solvent such as ethanol water and a mixture of these. Step (iv): The salification step may be carried out under conditions well known to those skilled in the art, in the presence of a pharmaceutically acceptable acid or base. When the compound is in a solvated form, this solvation generally takes place in the last stage of the process, the solvent of the solvated form being in this case the solvent of the reaction medium. Such a method is illustrated in more detail hereinafter according to different embodiments. According to a first embodiment, the present invention relates to a process for the preparation of a compound of formula (I) according to the invention for which R2 represents N3, characterized by the following successive stages: ## STR2 ## --- RiGP 0 \ ---. 0) O GP2O 0 0-GP4 Illa \ (al) substitution (a2) protection Ila + O-GP3 (a3) condensation GPI ° (a4) deprotection OO o) GP2O O \ Vla ## STR2 ## substituents of the general formula IVa for which A represents a leaving group such as OTs and is as defined in the general formula I, are replaced by sodium azide in a a solvent such as dimethylformamide; Substitution Va OH IVa HO (a2) the compound Va obtained, for which is as defined above is selectively protected in position 3 by an O-protecting group such as tertbutyldimethylsilyl using tertbutyldimethylsilyl chloride and a base such as DBU ( 1,8-Diazabicyclo [5.4.0] undec-7-ene) in a solvent such as THF (tetrahydrofuran); Protection Ila GPI ° (a3) a derivative of general formula Ma is condensed for which RiGp is as defined above, GP2, G133, and GP4 represent 0-protecting groups such as triethylsilyl, with the derivative of general formula IIa described previously in presence of trimethylsilyl trifluoromethanesulfonate in a solvent such as dichloromethane; O-GP3 Illa (a4) O-protected functions of the intermediate VIa thus obtained, are deprotected by treating with palladium chloride, bis acetonitrile in a solvent such as acetone to give a compound of formula la (compound of formula (I) with R2 = N3); O GRIO Vla IIa condensation CI3 0 GPI ° 23 OO GP2O 0 0 -G GP4 O GP2O O 0 -G GP4 O-GP3 deprotection R1 (a5) optionally, the compound of formula la obtained in the preceding step is salified in the presence of a pharmaceutically acceptable base to give a pharmaceutically acceptable salt of the compound of formula Ia. According to a second embodiment, the present invention relates to a process for the preparation of a compound of formula (I) according to the invention for which R 2 represents 1: 10 -N-R 11 with R 10 and R 11 as defined above. above and characterized by the following successive steps: OTs IIc or IId IIIa NR10R11 or NRiiGF or N3 C1 NI-1 o 9 (oo) o \ + (b3) condensation OH (b1) substitution (b2) protection GP1O NRioRii or NR11G1 = or N3 -0 GP3 GP1O X R1GP o GP1O \ o Vlb GP2O O0-GP4 \ --- R1GP 9 \ eo 0-GP4 OH 0-GP3 (b4) deprotection / reduction I lb Diagram 2 (131) is substituted derivatives of general formula IIb for which A represents a leaving group such as OTs, is as defined in general formula I and GPi represents an O-protecting group such as benzyl, with sodium azide R10 or HN amines. -R1 for which R10 and R11 are as defined above, in a solvent such as dimethylformamide to give a compound IIc porta a group N3 or NR10R11 (b2) in the case where the amine of compound IIc is secondary, it is then protected by a GP ', N-protecting group such as Cbz using benzyl chloroformate 10 in the presence of base such as K2CO3 in a solvent mixture such as water / THF to give a compound IId bearing a group NRiiGP '; NHR11 NRiiGP '(b3) according to (a3) by condensing derivatives of general formula Hia for which R1GP is as defined above, GP2, GP3, and GP4 represent 0-protecting groups such as triethylsilyl with derivatives of general formula IIc or IId previously described; IIc Ilb OTs substitution GP1O protection OH IId GP1O IIc NRioRii OH 27 or NIRliGP 'or N3 CI3 NH 0 0 condensation O GP20 O-GP3 O-GP4 GPI 0 Ilc or IId NRioRii or NR11 GP' or N3 Illa GRIO Vlb O-GP4 9 (0) GP2O 0 O-GP3 (b4) the deprotection of the 0-protected and N-protected functions of the intermediate VIb and, when R2 represents the azide, its reduction to amine, are obtained by treating the intermediate VIb by a suspension of Raney nickel in a solvent mixture such as EtOH and water to give a compound of formula Ib (compound of formula (I) with R2 = NR10R11); (b4) deprotection / reduction (b5) according to (a5).

According to a third embodiment, the present invention relates to a process for the preparation of a compound of formula (I) according to the invention for which R 2 represents: F 10 -N-R 11 with R 10 and R 11 as defined above , or - ° -R12 with R12 as defined above, characterized by the following successive steps: NR10R11 or NR11 GP 'or N3 28 e (0 0 PiGP 0 0 \) 0 GP20 0 0-GP4 \ GP 0 Vlb O -GP3 OTs IIb GP1O (cl) substitution (c2) OH (c3) protection O-GP3 NRioRii condensation or NRiiGP 'or OR12 OH NR10R11 or Ri iGI: v or OR12 GP1O Ile GP1O _ \ R1GP OO \ VIc 29 + (c4) O-deprotection O-GP3 NR10R11 or NR115P or OR12 ## STR1 ## according to (131) by substituting derivatives of general formula IIb as defined for (131) and whose alcohol function is protected by an O-protecting group such as R10 benzyl or tertbutyldimethylsilyl, or by HN-R amines 11 for which R10 and R11 are as defined above, in a solvent such as dimethylformamide, or with an alcohol HO-R12, or by other methods well known to those skilled in the art, especially in the presence of carbonate of potassium, potassium iodide and amine R24R25NH with R24 and R25 as defined above to give access to a R2 = -000NR24R25 (c2) group according to (b2); (c3) according to (b3); (c4) according to (a4); (c5) the deprotection of the N-protected functions and the possible reduction of the double bond of the intermediate VII are obtained by treatment with a suspension of Raney nickel in a mixture of solvents such as EtOH and water for give a compound of formula Ic (compound of formula (I) with R2 = NR10Ri or OR12) (c5) N-deprotection / reduction OH (c6) according to (a5).

The present invention also relates to a second process for the preparation of a compound of formula (I) according to the invention for which R2 represents a 1,2,3-triazol-1-yl group optionally substituted by a (C 1 -C 6) group. alkyl optionally substituted with a nitrogen and / or oxygenated function, comprising the following steps: (1) reaction of a compound of formula (I) for which R2 = N3 with a compound of formula = R with R representing H or a group (Ci -C6) alkyl optionally substituted with a nitrogen function and / or oxygenated to give a compound of formula (Id) following (corresponding to a compound of formula (I) for which R2 represents a 1,2,3-triazol-1-group optionally substituted by a (C 1 -C 6) alkyl group optionally substituted by a nitrogen and / or oxygenated function): NR 10 R 11 or NR 11 GP 'or OR 12 R 1 GP HO VII OH OH O OH OH OH OH OH OH OH (Id) for which R and R1 are as defined above, (2) when - - - - represents a double bond, optionally reduction of the double bond to give a compound of formula (Id) for which - - - - represents a single bond, and (3) optionally salification and / or solvation to give a compound of formula (Id) according to the invention in the form of a salt and / or a pharmaceutically acceptable solvate.

Step (1): The compound (Id) corresponds to a compound of formula (I) according to the invention for which R2 represents a 1,2,3-triazol-1-yl group optionally substituted with a (C 1 -C 6) group alkyl optionally substituted with a nitrogen and / or oxygen function. The reaction of step (1) can be carried out in a solvent such as methanol, THF, water and a mixture thereof. This reaction can be carried out in the presence of sodium (R) -54 (S) -1,2-dihydroxyethyl-4-hydroxy-2-oxo-2,5-dihydrofuran-3-olate and copper sulfate pentahydrate. The group R represents a (C 1 -C 6) alkyl group optionally substituted with a nitrogen and / or oxygen function. The nitrogen and / or oxygenated function will advantageously be a group NR29R30, NR31COR32, NR33COOR34, NR35CONR36R37, OR38, OCOR39, OCOOR40, OCONR41R42, COR43, COOR44 or CONR45R46, preferably a group NR29R30 or OR38, with R29 to R45 as defined above. Step (2): see step (iii) Step (3): see step (iv) The present invention also relates to a third process for preparing a compound of formula (I) according to the invention for which R2 represents a group NR10R11, R10 and R11 not forming a ring with the nitrogen atom which carries them, comprising the following steps: (a) reduction of a compound of formula (VIa) below: N O-GP3 (VIa) for which - - - -, RiGP, GPi, GP2, GP3 and GP4 are as defined above, to give a compound of formula (VId) below: O-GP3 (VId) 15 for which - - - -, RiGP, GPi, GP2 , GP3 and GP4 are as defined above, (b) optionally substitution of the compound of formula (VId) obtained in step (a) above to give a compound of formula (VIe) below: NPloPii O-GP3 (VIe) for which, R10, R11, R1GP, GP1, GP2, GP3 and GP4 are as defined above, at least one of R10 and R11 not representing a hydrogen atom, (c) deprotection of the protecting groups to give a compound of formula (I) with R2 = NR10R11, (d) when represents a double bond, optionally reduction of the double bond to give a compound of formula (I) for which - - - - represents a single bond and R2 = NRioRi 1, and (e) optionally salification and / or solvation to give a compound of formula (I) according to the invention in the form of a salt and / or a pharmaceutically acceptable solvate.

Step (a): This reduction reaction of the azide function can be carried out under conditions well known to those skilled in the art, for example in the presence of triphenylphosphine as reducing agent. The reaction can be carried out in THF as a solvent. Step (b): This substitution reaction can be carried out under conditions well known to those skilled in the art.

The reaction may be carried out in the presence of a compound of formula RioLG2 or RiiLG2 with R10 and R11 as defined above and other than a hydrogen atom and LG2 representing a leaving group. It may be a halogen atom such as a chlorine atom. When the group R 11 has a carbonyl unit linked to the group LG2, LG2 may also be an imidazole or a group -OC (O) Alk with Alk representing a (C1-C6) alkyl group. The reaction may be carried out in the presence of a base such as pyridine or triethylamine. The dichloromethane may be used as a solvent for this reaction. If R10 and R11 each represent a group other than a hydrogen atom, two successive substitution reactions can be carried out, the first substitution reaction preferably aimed at introducing the substituent R11. Step (c): see step (ii) Step (d): see step (iii) Step (e): see step (iv) The intermediate and final compounds may be, if desired, purified according to one or more methods of purification selected from extraction, filtration, silica gel chromatography, preparative HPLC on normal or reverse phase, crystallization. The raw materials used in the methods described above are commercial or easily accessible to those skilled in the art according to methods described in the literature. EXAMPLES The following abbreviations were used: DMAP: N, N-Dimethylaminopyridine DMI: Dimethylformamide ES: Electrospray HPLC: High Performance Liquid Chromatography NMR: Nuclear Magnetic Resonance THF: Tetrahydrofuran SYNTHESIS OF COMPOUNDS ACCORDING TO THE INVENTION The compounds of the present invention can be synthesized using the synthesis routes described below or using synthetic methods known to those skilled in the art. Mass and NMR spectra confirm the structures of the compounds. The following examples illustrate the invention without limiting its scope.

ANALYTICAL MEHTODES by HPLC: Method A: phase A: water / 0.04% NH3, phase B: Acetonitrile total flow: 0.80 mL / min Column: X-Bridge RP18, 3.0 * 50 mm, 2.2 iam, 40 ° C Binary gradient: Time (min) 0 6.2 7.20 7.50 Route B (%) 50 100 100 10 Method B: phase A: water / 0.05% formic acid, phase B: Acetonitrile / 0.05% formic acid total flow rate: 2 mL / min XbridgeShield-RPC18, 4.6x50 mm, 3.5 i.tm Binary gradient: Time (min) 0 4 4.25 4.4 5 B-way (%) 3 100 100 3 3 Method C: phase A : water / 0.1% formic acid, phase B: Acetonitrile / 0.1% formic acid 30 total flow rate: 2 mL / min XbridgeShield-RPC18, 4.6x50 mm, 3.5 i.tm Binary gradient: 25 Time (min) 0 4.25 4,4 5 B (%) 3 100 100 3 3 INTERMEDIAIRES: Intermediate 1: Intermediate 1 is obtained according to the method described by Denance, M et al., Steroids, 2006, 71 (7), 599-602. Intermediates 2: Intermediate 2a: HO 0.5 g (0.87 mmol) of intermediate 1 is placed in the presence of NaN 3 (0.11 g, 1.74 mmol) in 7 ml of DMI in the microwave at 125 ° C. for 5 min. The medium is taken up in water and extracted with AcOEt. After dry concentration of the organic phases, the residue obtained is purified on flash silica (heptane / AcOEt gradient: 100/0 to 50/50 over 30 min). Intermediate 2a is isolated as a white solid with a yield of 78%. (ES, m / z): [M-H + HCO2Hf = 488 C13 NMR, (100 MHz, CDCl3, ppm): 13.1; 17.7; 18.2; 19.4; 20.7; 23.7; 29.8; 31.5; 31.6; 31.8; 33.6; 34.5; 36.0; 36.5; 36.8; 37.2; 39.8; 42.2; 42.3; 50.1; 54.5; 57.9; 61.4; 71.8; 72.4; 121.5; 140.9.

Intermediates 2b-i: Intermediates 2b-2i are prepared according to the method described for intermediate 2a using different alkylating agents. R-0 Intermediate Intermediates obtained RA Yield ES, m / z (2R, 6R) -6 - ((3S, 10R, 13S, -16S, 17R) -3- (benzyloxy) -16-hydroxy-10 , 13-dimethy1-2,3,4,7,8,9, - 10,11,12,13,14,15,16,17- tetradecahydro-1Hcyclopenta [a] phenanthren17-yl) -2-methylheptyl 4- methylbenzenesulfonate (Qin, HJ et al., Tet.Let., 2006, 47 (19), 3217-3219) 2b Bn NHMe 50% 522, [M + H] + 2c Bn NMe2 84% 536, [M + H] + 2d Bn NHEt 80% 580, [M-H + HCO2H] - 2nd Bn NHiPr 73% 550, [M + H] + 2f Bn NH (CH2) 20Me 84% 566, [M + Hr 2g Bn / - \ 75% 578, [M + H] + N 0 2h Bn 0 25% 614, [M + Hr HN ...., S (:) 11 '' 2i Bn N3 100% 556, [M + Na] + Intermediates 3: Intermediate 3a: 0.29 g (0.55 mmol) of steroid 2b is placed in the presence of benzyl chloroformate (0.14 g, 0.83 mmol) and sodium bicarbonate (93 mg, 1.12 mmol ) in 8 mL of THF / H20: 3/1 and then the mixture is stirred for 4 hours at room temperature. After extraction and dry concentration of the organic phases, the residue obtained is purified on flash silica (CH 2 Cl 2 / AcOEt gradient: 100/0 to 90/10 over 20 min). Steroid 3a is obtained as a white solid (0.33 g) with a yield of 90%. (ES, m / z): [M + Na] + = 678 C13 NMR (100 MHz, CDCl3, ppm): 13.0; 17.2; 18.1; 19.3; 20.7; 23.4; 28.4; 29.8; 31.2; 31.4; 31.8; 32.1; 34.1; 35.0; 36.5; 36.6; 36.9; 37.1; 39.1; 39.8; 42.2; 50.1; 54.5; 55.2; 61.3; 66.9; 69.9; 72.2; 78.5; 121.3; 127.4 (2 carbons); 127.5 (2 carbons); 127.7; 127.8; 128.3 (2 carbons); 128.4 (2 carbons); 137.1; 139.1; 141.1. Intermediates 3b-e: Intermediates 3b-e are prepared according to the method described for Intermediate 3a: A Intermediates 3b-e: Intermediates AB Yield ES, m / z 3b NHEt NEtCbz 88% 692, [M + Na] + 3c NHiPr NiprCbz 98% 683, [M] + 3d NH (CH2) 20Me N [(CH2) 2OMe] Cbz 77% 722, [M + Na] + 3rd NH (CH2) 2SO2Me N [(CH2) 2SO2Me] Cbz 100% 770, [M + Na] + Intermediates 4: Intermediate 4a: Intermediate 4a is prepared according to the method described by Chen B. et al., Tetrahedron, 2003, 59 (17), p. 3183-3188 from (3S, 10R, 13S, 16S, 17R) -17 - ((2R, 6R) -7-hydroxy-6-methylheptan-2-yl) -10,13-dimethyl-2,3,4, 7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta [a] phenanthrene-3,16-diol (prepared according to the method described by Zheng, D. et al., Biorg Med Chem Let, 2011, 21 (11), 3257-3260). 0-TBDMS TBDMS-O Intermediate 4b: Intermediate 4b is prepared from Intermediate 2a according to the method described for Intermediate 4a with a yield of 99%.

TBDMS, (ES, m / z): [M-OH] + = 540 C13 NMR, (100 MHz, CDCl3, ppm): -4.5 (2 carbons); 13.1; 17.7; 18.2; 18.8; 19.4; 20.7; 23.7; 25.9 (3 carbons); 29.8; 31.5; 31.8; 32.1; 33.6; 34.5; 36.0; 36.6; 36.8; 37.3; 39.9; 42.2; 42.8; 50.2; 54.5; 57.9; 61.4; 72.5; 72.6; 120.9; 142.2. Intermediate 5: OTs TBDMS-0 Intermediate 4a (0.15 g, 0.77 mmol) is placed in 7 mL of THF in the presence of Et3N (0.34 mL, 2.43 mmol) and tetrabutylammonium fluoride 1M in THF (0.89 mL, 0.89 mmol). The mixture is stirred at room temperature for 4 h and then concentrated to dryness. The residue obtained is purified on flash silica (heptane / AcOEt gradient: 100/0 to 60/40 over 25 min). The intermediate is isolated as a white solid (0.23 g) with a yield of 56%. This solid (0.44 mmol) is then placed in 5 ml of dichloromethane, in the presence of 5.4 mg (0.044 mmol) of DMAP, 0.184 ml (1.32 mmol) of triethylamine and 0.10 g (0.53 mmol). ) tosyl chloride. This mixture is stirred at room temperature overnight and then taken up in water and extracted with dichloromethane. After drying and dry concentration of the organic phases, the residue obtained is purified on flash silica (heptane / AcOEt gradient: 100/0 to 80/20 over 25 min).

Intermediate 5 is isolated as a white solid (0.27 g) with a yield of 89%. (ES, m / z): [M-TBS + HCOOHT = 617 Intermediates 6: Intermediate 6a: HN TBDMS 0 Intermediate 5 (0.13 g, 0.19 mmol) is placed in 2 mL of DMI in the presence of benzylamine (0.063 ml, 0.57 mmol) and potassium iodide (0.096 g, 0.57 mmol). The mixture is stirred at 120 ° C. for 2 h and then taken up in water and extracted with ethyl acetate. After drying and dry concentration of the organic phases, the residue obtained is purified on flash silica (CH 2 Cl 2 / AcOEt gradient: 100/0 to 85/15 over 30 min). Intermediate 6a is isolated as a white solid (0.077 g) with a yield of 64%. (ES, m / z): [M + H] + = 622 Intermediate 6b: TBDMS Intermediate 6b is prepared from Intermediate 5 according to the method described for Intermediate 6a. Compound 6b is obtained as a solid with a yield of 66%. (ES, m / z): [M + H] + = 636 O Intermediate 7: 1 - "2 S 1 O 0.36 g (0.54 mmol) from (2R, 6R) -6- ( (3S, 10R, 13S, 16S, 17R) -3- (benzyloxy) -16-hydroxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15, 16,17-tetradecahydro-1H-cyclopenta [a] phenenanthren-17-yl) -2-methylheptyl 4-methylbenzenesulfonate (prepared according to the method described by Qin, HJ et al., Tet.Let., 2006, 47 (19) , 3217-3219) is placed in the presence of 2- (methylsulfonyl) ethanamine hydrochloride (0.26 g, 1.63 mmol), potassium carbonate (0.22 g, 1.63 mmol) and iodide of potassium (0.27 g, 1.63 mmol) in 10 mL of DMI and then the mixture is heated at 120 ° C for 2h.

After concentration to dryness, the residue is taken up with saturated potassium bicarbonate solution and extracted with AcOEt. After drying and dry concentration of the organic phases, the residue obtained is purified on flash silica (gradient: CH 2 Cl 2 / MeOH: 100/0 to 90/10 in 30 min). Compound 7 is obtained in the form of a white gum (0.18 g) with a yield of 54%. (ES, m / z): [M-H + HCOOHT = 702 C13 NMR, (100MHz, CDCl3, ppm): 13.1; 16.9; 18.2; 19.4; 20.7; 23.5; 28.4; 29.7; 31.5; 31.8; 32.4; 33.5; 34.9; 35.7; 36.6; 36.9; 37.2; 39.1; 39.9; 41.8; 42, 2; 50.2; 54.4; 54.5; 61.6; 69.9; 70.4; 72.4; 78.5; 121.3; 127.4; 127.6 (2 carbons); 128.4 (2 carbons); 138.8; 141.1; 156.4.

Dioside: Dioside 1 is prepared according to the method described by Deng, S. et al., J. Org. Chem., 1999, 64, 202-208.

Dioxide 1: (2S, 3R, 4R, 5R) -2 - (((3R, 4R, 5S) -3-acetoxy-2-hydroxy-5 - ((triethyl silyl) oxy) Tetrahy-dim-2H-pyran-4-yl) oxy) -4,5-bis ((triethylsilyl) oxy) tetrahydro-2H-pyran-3-yl-4-methoxybenzoate From (2S, 3R, 4S, 5R) -2- (benzyloxy) oxane-3,4,5-triol, the dioside 1 is obtained in colorless oil form with a yield of 2.6%. OC) Ho. ") ~ Si," O 0 '. ) ## STR1 ## EtOH FFS 'Si 0 0 0 \ 0 0) LCI BnOH H DMAP, TESCI R1 HO °. O OH Pyridine O BF3 Et20, DCM R1 OH OH CCI3CN, DBU, DCM (ES, m / z): [M + H20 ] + = 818.9 HPLC (method A): Tr = 6.21 min H NMR (400 MHz, CDCl 3, ppm): 8.037-7.985 (m, 4H), 6.946-6.918 (m, 4H), 5.036 (s) , 1H), 5.024-4.707 (m, 3H), 4.012-3.726 (m, 11H), 3.279-3.165 (m, 1H), 1.908 (s, 3H), 1.001-0.843 (m, 27H), 0.693-0.506. (m, 18H) COMPOUNDS ACCORDING TO THE INVENTION: Example 1: (2S, 3R, 4S, 5R) -2 - (((2S, 3R, 4S, 5S) -3-acetoxy-2- (((3S, 10R, -13S, -16S) -17- ((2R, 6R) -7-azido-6-methylheptan-2-yl) -3-hydroxy-10,13-dimethyl-2, 3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta [a] phenenanthren-16-yl) oxy) -5-hydroxytetrahydro-2H-pyran -4-yl) oxy) -4,5-dihydroxytetrahydro-2H-pyran-3-yl-4-methoxybenzoate Example 1 is synthesized according to Method 1: Step 1: 0.34 g (0.358 mmol) of activated dioside 1 in the form of 2- (2,2,2-trichloro-1 iminoethoxy) (method described by Deng, S. et al., J. Org. Chem., 1999, 64, 202-208) and 0.1 g (0.18 mmol) of intermediate 4b are placed in 10 mL of dichloromethane in the presence of 4: 3 sieve (0.7 g, 0.18 g). mmol) and stirred at room temperature for 15 min. After cooling to -65 ° C, a 0.14 M solution of trimethylsilyl trifluoromethanesulfonate (1.79 mL) in CH 2 Cl 2 was added dropwise and the mixture was stirred for 30 min. After addition of 0.5 mL of Et3N and filtration on Celite®, the medium is concentrated to dryness. The residue obtained is purified on flash silica (heptane / CH 2 Cl 2 gradient: 100/0 to 50/50 in 25 min) and isolated with a yield of 54%. N = N + N O- HO Step 2: 0.13 g (0.097 mmol) of the preceding intermediate is placed in 4.8 mL of acetone and 0.2 mL of water in the presence of palladium chloride, bis (acetonitrile) ( 7.5 mg, 0.029 mmol). The medium is stirred for 3h at room temperature, filtered through Celite® and then concentrated to dryness. The residue obtained is purified on flash silica (CH 2 Cl 2 / MeOH gradient: 100/0 to 90/10 in 25 min). Compound 1 is isolated as an orange solid (0.021 g) with a yield of 24%. Orange solid (ES, m / z): [M-H + HCO2HT = 928.37 HPLC (method C): Tr = 4.02 nm C13 NMR, (100MHz, CD30D, ppm): 13.1; 18.1; 18.6; 19.8; 21.0; 21.9; 23.4; 30.6; 32.3; 32.9 (2 carbons); 34.7; 36.0; 37.3; 37.5; 37.7; 38.5; 41.0; 43.0; 43.3; 51.7; 56.1; 56.3; 58.7; 62.1; 66.3; 66.7; 69.8; 71.0; 72.1; 72.4; 75.3; 75.8; 81.2; 82.6; 103.9; 104.3; 114.8 (2 carbons); 122.3; 123.6; 133.2 (2 carbons); 142.3; 165.4; 167.1; 170.9.

Example 2: (2S, 3R, 4S, 5R) -2 - (((2S, 3R, 4S, 5S) -3-acetoxy-2 - (((3S, 10R, 13S, 16 S, 17R) - 17 - ((2R, 6R) -7-amino-6-methylheptan-2-yl) -3-yloxy-10,13-dimethyl-2,3,7,7,8,9, 10, 11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta [a] -phenenanthren-16-yl) oxy) -5-hydroxytetrahydro-2H-pyran-4-yl) oxy) 4, 5-dihydroxytetrahydro-2H-pyran-3-yl-4-methoxybenzoate Example 2 is synthesized according to method 2: Step 1: glycosylation of the steroid 2i by dioside 1 under the conditions described in step Step 1: 0.096 g (0.10 mmol) of intermediate is placed in 5 mL of EtOH in the presence of 200 μl of a suspension of Raney nickel (50% in the water). The mixture is stirred for 4 days at 50 ° C. in a sealed tube. After concentration to dryness, the residue obtained is purified on flash silica (CH 2 Cl 2 / MeOH gradient: 100/0 to 90/10 in 30 minutes). Compound 2 is isolated as a white solid (0.053 g) with a yield of 35%. White solid (ES, m / z): [M + H] + = 858.52 HPLC (method C): Tr = 2.24 min C13 NMR (125 MHz, CD30D, ppm): 13.2; 17.4; 18.5; 19.8; 21.0; 21.9; 23.6; 30.3; 32.3; 32.9; 33.3 (2 carbons); 35.4; 36.6; 36.8; 37.7; 38.5; 41.0; 43.0; 43.4; 46.6; 51.7; 56.0; 56.1; 62.1; 66.1; 66.5; 69.5; 70.9; 72.3; 72.4; 75.1; 75.6; 81.0; 82.6; 103.4; 103.6; 114.8 (2 carbons); 122.3; 123.6; 133.2 (2 carbons); 142.3; 165.3; 167.0; 171.0.

Example 3: (2 S, 3R, 4S, 5R) -2 - (((2S, 3R, 4S, 5S) -3-acetoxy-5-hydroxy-2 - (((3S, 10R, 13S, 16S, 17R) -3-hydroxy-10,13-dimethyl-17 - ((2R, 6R) -6-methyl-7- (methylamino) heptan-2-yl) -2,3 4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta [a] phenanthren-16-yl) oxy) tetrahydro-2H-pyran-4-yl oxy) -4,5-dihydroxytetrahydro-2H-pyran-3-yl-4-methoxybenzoate HN-O-O-OHOH Example 3 is synthesized according to method 2 from the steroid 3a and dioside 1 (yield: 50%). White solid (ES, m / z): [M + H] + = 872.37 HPLC (method C): Tr = 2.24 min H NMR C13, (100MHz, CD30D, ppm): 13.2; 18.2; 18.6; 19.8; 21.0; 21.9; 23.6; 30.5; 32.3; 32.9 (2 carbons); 33.6; 36.0; 36.6; 37.3 (2 carbons); 37.7; 38.5; 41.0; 43.0; 43.3; 51.7; 56.1; 56.3; 58.9; 62.1; 66.3; 66.6; 69.7; 71.0; 72.2; 72.4; 75.2; 75.7; 81.2; 82.6; 103.8; 104.1; 114.8 (2 carbons); 122.3; 123.6; 133.2 (2 carbons); 142.3; 165.4; 167.0; 171.0. Example 4: (2S, 3R, 4S, 5R) -2 - (((2S, 3R, 4S, 5S) -3-acetoxy-2 - (((3S, 10R, -13S, -16S, -17R) formate ) - ((2R, 6R) -7- (dimethylamino) -6-methylheptan-2-yl) -3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,10, 11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta [a] -phenenanthren-16-yl) oxy) -5-hydroxytetrahydro-2H-pyran-4-yl) oxy) -4.5 Example 4 is synthesized according to method 3: Step 1: glycosylation of steroid 3a by dioside 1 under the conditions described in step 1 of the method 1. Step 2: deprotection of the silyl groups with palladium chloride, bis-acetonitrile under the conditions described in step 2 of method 1. Step 3: deprotection of benzyl with Raney nickel under the conditions described in step 2 of method 2.

Compound 4 is isolated after purification by HPLC as a white solid (0.059 g) with a yield of 35%. White solid (ES, m / z): [M + H] + = 886.45 HPLC (method C): Tr = 2.32 min C13 NMR (125 MHz, CD30D, ppm): 13.4; 17.8; 18.5; 20.0; 21.1; 22.0; 23.7; 30.2; 31.2; 32.4; 33.0 (2 carbons); 35.5; 36.5; 36.9; 37.8; 38.6; 41.2; 43.2; 43.5; 44.7 (2 carbons); 51.9; 56.2 (2 carbons); 62.3; 66.3; 66.5; 66.7; 69.8; 71.1; 72.6; 72.7; 75.3; 75.9; 81.5; 82.7; 103.4; 103.9; 114.9 (2 carbons); 122.4; 123.8; 133.9 (2 carbons); 142.5; 165.5; 167.1; 171.2.

Example 5: (2S, 3R, 4S, 5R) -2 - (((2S, 3R, 4S, 5S) -3-acetoxy-2 - (((3S, 5S, 10S, -135, -16S) formate, 17R) -17 - ((2R, 6R) -7- (dimethylamino) -6-methylheptan-2-yl) -3-hydroxy-10, -13-dimethylhexadecahydro-1H-cyclopenta [a] phenanthren-16-yl) oxy) -5-hydroxytetrahydro-2H-pyran-4-yl) oxy) -4,5-dihydroxytetrahydro-2H-pyran-3-yl 4-methoxybenzoate O-OAc O HO H 0> OH O OH This compound (of which the double bond was reduced by Raney nickel) is obtained in a mixture with the compound of Example 4 and isolated by HPLC with a yield of 7%. White solid (ES, m / z): M + = 888.43 HPLC (method C): Tr = 2.38 min C13 NMR, (125 MHz, CD30D, ppm): 12.9 30.0; 30.1; 31.2; 32.3; 33.4; 36.3; 36.74.77 (2 carbons); 46.4; 55.8; 56.0; 56.2, 72.7; 75.3; 75.9; 81.5; 82.8; 103.4; 103.9; 114.9 (2 carbons); 123.8; 133.3 (2 carbons); 165.5; 167.1; 171.2. Example 6: (2S, 3R, 4S, 5R) -2 - (((2S, 3R, 4S, 5S) -3-acetoxy-5-hydroxy-2 - (((3S, -10R, -13S, 16S, 17R) -3-hydroxy-17 - ((2R, 6R) -7- (isopropylamino) -6-methylheptan-2-yl) -10,13-dimethyl-2,3,4,7,8,9, 10,11,12,13,14,15,16,17-Tetradecahydro-1H-cyclo-H) .0H, 13.6, 17.7, 18.4, 21.1, 22.2, 23, 6, 25.4, 36.8 (2 carbons), 38.3, 39.0, 41.4, 43.9, 62.5, 66.2, 66.5, 66.7, 69, 8, 71.1, 72.0, penta [a] phenen-16-yl) oxy) tetrahydro-2H-pyran-4-yl) oxy) -4,5-dihydroxytetrahydro-2H-pyran-3-yl-methoxybenzoate Example 6 is synthesized according to method 3 from steroid 3c and dioside 1 (yield = 7%). White solid (ES, m / z): [M + H] + = 900.42 HPLC (method C): Tr = 2.37 min C13 NMR, (125 MHz, CD30D, ppm): 13.4; 17.8; 18.6; 19.3; 19.4; 20.0; 21.1; 22.1; 23.8; 30.4; 32.4; 33.0 (3 carbons); 35.7; 36.6; 37.0; 37.8; 38.6; 41.2; 43.2; 51.9; 52.2; 52.5; 52.8; 56.2 (2 carbons); 62.3; 66.3; 66.6; 69.6; 71.0; 72.5; 72.6; 75.2; 75.7; 81.3; 82.8; 103.5; 103.7; 114.9 (2 carbons); 122.4; 123.8; 133.3 (2 carbons); 142.5; 165.5; 167.1; 171.2.

Example 7: (2S, 3R, 4S, 5R) -2 - (((2S, 3R, 4S, 5S) -3-acetoxy-5-hydroxy-2 - (((3S, -10R 13S, 16S, 17R) -3-hydroxy-174 (2R, 6R) -74 (2-methoxyethyl) amino) -6-methylheptan-2-yl) -10,13-dimethy1-2, 3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta [a] phenenanthren-16-yl) oxy) tetrahyrid-2H-pyran-4 Example 7 is synthesized according to method 3 from steroid 3d and dioside 1 (yield = 6%). ). White solid (ES, m / z): [M + H] + = 916.44 HPLC (method C): Tr = 2.34 min C13 NMR (125 MHz, CD30D, ppm): 13.4; 17.7; 18.6; 20.0; 21.1; 22.1; 23.7; 30.4; 32.4 (2 carbons); 33.0 (2 carbons); 35.8; 36.7; 36.9; 37.8; 38.6; 41.2; 43.2; 43.5; 48.6; 51.9; 55.2; 56.2 (2 carbons); 59.5; 62.3; 66.4; 66.6; 68.4; 69.6; 71.1; 72.5; 72.6; 75.3; 75.7; 81.3; 82.8; 103.6; 103.7; 114.9 (2 carbons); 122.4; 123.8; 133.3 (2 carbons); 142.5; 165.5; 167.1; 171.1. Example 8: (2S, 3R, 4S, 5R) -2 - (((2S, 3R, 4S, 5S) -3-acetoxy-5-hydroxy-2 - (((3S, -5S, 10S, 13S) formate 16S, 17R) -3-hydroxy-17 - ((2R, 6R) -7 - ((2-methoxyethyl) amino) -6-methylheptan-2-yl) -10,13-dimethylhexadecahydro-1H-cyclo embedded image [a] phenanthren-16-yl) oxy) tetrahydro-2H-pyran-4-yl) oxy) -4,5-dihydroxytetrahydro-2H-pyran-3-yl 4-methoxybenzoate O HN O- pAc HO OH 01 This compound (the double bond of which was reduced by Raney nickel) is obtained in a mixture with the compound of example I let by HPLC in a yield of 2%). White solid (ES, m / z): [M + H] + = 918.50 HPLC (method C): Tr = 2.38 min C13 NMR, (125 MHz, CD30D, ppm): 12.9; 13.6; 17.7, 30.4; 32.3; 32.4; 33.4; 35.7; 36.7 (4 carbons); 38.35.5; 56.0 (2 carbons); 56.2; 59.5; 62.5; 66.3; 66.6-75.3; 75.8; 81.3; 82.8; 103.5; 103.7; 114.9 (2 carbons); 123.8; 133.3 (2 carbons); 165.5; 167.1; 171.0. Example 9: (2S, 3R, 4S, 5R) -2 - (((2S, 3R, 4S, 5S) -3-acetoxy-2 - (((3S, 10R, -13S, -16S, -17R ) - ((2R, 6R) -7- (ethyl (2-methoxyethyl) amino) -6-methylheptan-2-yl) -3-hydroxy-10,13-dimethyl-2,3,4,7, 8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta [a] phenanthren-16-yl) oxy) -5-hydroxytetrahydro-2H-pyran-4-yl) oxy -4,5-dihydroxytetrahydro-2H-pyran-3-yl 4-methoxybenzoate; 18.5; 21.1; 22.3; 23.7; 30.0; ; 39.0; 41.4; 43.8; 46.4; 48.6; ; 68.4; 69.6; 71.1; 72.0; 72.5; HO Example 9 is synthesized according to method 3 from steroid 3d and dioside 1 (yield = 17%). White solid (ES, m / z): [M + H] + = 944.61 HPLC (Method C): Tr = 2.40 min C13 NMR, (100MHz, CD30D, ppm): 11.9; 13.2; 18.8; 19.0; 19.9; 21.1; 21.9; 23.5; 30.5; 32.3; 32.7; 32.9 (2 carbons); 37.4 (2 carbons); 37.4; 37.6; 37.7; 38.5; 41.0; 43.0; 43.3; 50.1; 51.7; 54.6; 56.1; 56.3; 59.1; 62.0; 62.9; 66.4; 66.7; 69, 8; 71.0; 72.0; 72.1; 72.4; 75.2; 75.8; 81.3; 82.7; 103.9; 104.4; 114.8 (2 carbons); 122.4; 123.6; 133.2 (2 carbons); 142.3; 165.3; 167.0; 170.9. Example 10: (2S, 3R, 4S, 5R) -2 - (((2S, 3R, 4S, 5S) -3-acetoxy-2 - (((3S, 10R, 13S, -16S, 17R) - 174 ( 2R, 6R) -7- (ethylamino) -6-methylheptan-2-yl) -3-hydroxy-10,13-dimethyl-2,4,4,8,8,10,10,11,12,13, 14,15,16,17-tetradecahydro-1H-cyclopenta [a] phenenanthren-16-yl) oxy) -5-hydroxytetrahydro-2H-pyran-4-yl) oxy) -4,5-dihydroxytetrahydro-2H-pyran 3-yl 4-methoxybenzoate Example 10 is synthesized according to method 3 from steroid 3b and dioside 1 (yield = 6%). White solid (ES, m / z): [M + H] + = 886.38 HPLC (method C): Tr = 2.34 min C13 NMR, (125 MHz, CD30D, ppm): 11.7; 13.4; 17.7; 18.6; 20.0; 21.1; 22.1; 23.7; 30.4; 32.4; 32.8; 33.0 (2 carbons); 35.6; 36.6; 36.9; 37.8; 38.6; 41.2; 43.2 (2 carbons); 44.9; 51.9; 54.9; 56.2 (2 carbons); 62.3; 66.3; 66.6; 69.6; 71.0; 72.5; 72.6; 75.3; 75.7; 81.3; 82.8; 103.5; 103.7; 114.9 (2 carbons); 122.4; 123.8; 133.3 (2 carbons); 142.5; 165.5; 167.1; 171.2. Example 11: (2S, 3R, 4S, 5R) -2 - (((2S, 3R, 4S, 5S) -3-acetoxy-2 - (((3S, 5S, 10S, -13S, -16) formate S, 17R) -17 - ((2R, 6R) -7- (ethylamino) -6-methylheptan-2-yl) -3-hydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta [a] phenanthren-16- yl) oxy) -5-hydroxytetrahydro-2H-pyran-4-yl) oxy) -4,5-dihydroxytetrahydro-2H-pyran-3-yl-4-methoxybenzoate HN-1 54 O-OAc OH OH 0> OH HN-- This compound (whose double bond has been reduced by Raney nickel) is obtained in a mixture with the compound of Example 10 and isolated by HPLC with a yield of 2%. %).

White solid (ES, m / z): [M + H] + = 888.48 HPLC (method C): Tr = 2.38 nm C13 NMR (125 MHz, CD30D, ppm): 11.7; 12.9; 13.6; 17.7; 18.5; 21.2; 22.2; 23.7; 30.1; 30.4; 32.3; 32.8; 33.4; 35.7; 36.6; 36.7; 36.8; 36.9; 38.3; 39.0; 41, 4; 43.8; 44.9; 46.4; 54.9; 56.0 (2 carbons); 56.2; 62.4; 66.4; 66.6; 69.6; 71.1; 72.0; 72.5; 75.3; 75.7; 81.3; 82.8; 103.5; 103.7; 114.9 (2 carbons); 123.8; 133.3 (2 carbons); 165.5; 167.1; 171.2. Example 12: (2S, 3R, 4S, 5R) -2 - (((2S, 3R, 4S, 5S) -3-acetoxy-5-hydroxy-2 - (((35, -10R, 13S, 16S) formate 17R) -3-hydroxy-10,13-dimethyl-1774 (2R, 6R) -6-methyl-7-morpholinoheptan-2-yl) -2,3,4,7,8,9,10,11, 12,13,14,15,16,17-Tetradecahydro-1H-cyclopenta [a] phenenanthren-16-yl) oxy) tetrahydro-2H-pyran-4-yl) oxy) -4,5-dihydroxytetrahydro-2Hpyran-3 Example 12 is synthesized according to method 3 from steroid 2g and dioside 1 (yield = 3%). White solid (ES, m / z): [M + Hr = 928.46 HPLC (method C): Tr = 2.34 min C13 NMR, (125 MHz, CD30D, ppm): 13.4; 18.6 (2 carbons); 20.0; 21.1; 22.1; 23.8; 30.4; 30.8; 32.4; 33.0; 36.5; 37.0; 37.1; 37.8; 38.6; 41.2; 43.2 (2 carbons); 51.9; 55.0 (2 carbons); 56.2; 56.3; 62.4; 66.6; 66.8; 67.1 (3 carbons); 69.6; 71.2; 72.4; 72.6; 75.4; 76.0; 81.6; 82.8; 103.9; 104.0; 114.9 (2 carbons); 122.5; 123.8; 133.3 (2 carbons); 142.5; 165.5; 167.1; 171.1. Example 13: (2S, 3R, 4S, 5R) -2 - (((2S, 3R, 4S, 5S) -3-acetoxy-5-hydroxy-2 - (((3S, 5S, -10S, 13S) formate 16S, 17R) -3-hydroxy-10,13-dimethyl-17 - ((2R, 6R) -6-methyl-7-morpholinoheptan-2-yl) hexadecahydro-1H-cyclopenta [a] phenanthren-16-yl oxy) tetrahydro-2H-pyran-4-yl) oxy) -4,5-dihydroxytetrahydro-2H-pyran-3-yl-4-methoxybenzoate HO pAc O HO H 0 0 H) LOH; 18.5; 21.1; 22.3; 23.8; 30.1; ; 37.0; 38.3; 39.0; 41.4; 43.8; ; 66.7; 66.8; 67.0 (2 carbons); This compound (whose double bond was reduced by Raney nickel) is obtained in admixture with the compound of Example 12 and isolated by HPLC in a yield of 1%).

White solid (ES, m / z): [M + H] + = 930.48 HPLC (method C): Tr = 2.38 min C13 NMR (125 MHz, CD30D, ppm): 12.9; 13.6; 18.4, 30.3; 30.7; 32.3; 33.4; 36.3; 36.7 (2 carbons); 36.8 to 46.4; 54.9 (2 carbons); 56.0 (2 carbons); 56.2; 62.5 to 67.1; 69.9; 71.2; 72.0; 72.5; 75.4; 76.0; 81.6; 82.8; 103.8; 104.0; 114.9 (2 carbons); 123.8; 133.2 (2 carbons); 165.5; 167.1; 171.1. Example 14: (2S, 3R, 4S, 5R) -2 - (((2R, 3R, 4S, 5S) -3-acetoxy-5-hydroxy-2 - (((3S, 10R, 13S, 16S) formate, 17R) -3-hydroxy-10,13-dimethyl-1774 (2R, 6R) -6-methyl-7 - ((2- (methylsulfonyl) ethyl) amino) heptan-2-yl) -2,3,4, 7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta [a] phenanthren-16-yl) oxy) tetrahydro-2H-pyran-4-yl) oxy) -4,5-Dihydroxytetrahydro-2H-pyran-3-yl-methoxybenzoate O HN O-OH OH OH OH O-1 Example 14 is synthesized according to Method 3 from steroid 3e and dioside 1 (yield = 58%). White solid (ES, m / z): [M + H] + = 964.45 HPLC (Method C): Tr = 2.32 min C13 NMR (125 MHz, CD30D, ppm): 13.4 32.4; 33.0 (2 carbons); 33.3; 35.4; 36.4, 43.6; 51.9; 52.3; 56.0; 56.2; 56.3; 62.4-75.4; 75.9; 81.6; 82.8; 103.4; 103.9; 115.0 (2 carbons); 122.4; 123.7; 133.3 (2 carbons); 142.5; 165.6; 167.2; 171.5. Example 15: (2S, 3R, 4S, 5R) -2 - (((2R, 3R, 4S, 5S) -3-acetoxy-5-hydroxy-2 - (((3S, 5S, 10S, 13S) formate, 16S, 17R) -3-hydroxy-10,13-dimethyl-17 - ((2R, 6R) -6-methyl-7- ((2- (methylsulfonyl) ethyl) amino) heptan-2-yl) hexadecahydro-1H cyclopenta [α] phenanthren-16-yl) oxy) tetrahydro-2H-pyran-4-yl) oxy) -4,5-dihydroxytetrahydro-2H-pyran-3-yl-4-methoxybenzoate P; 18.0; 18.5; 20.0; 21.1; 22.1; 23.7; 30.2; ; 36.9; 37.8; 38.6; 41.2; 41.7; 42.3; 43.2; ; 66.6; 66.7; 69.8; 71.1; 72.6 (2 carbons); This compound (whose double bond has been reduced by Raney nickel) is obtained in a mixture with the compound of Example 14 and isolated by HPLC in a yield of 3%.

White solid (ES, m / z): [M + H] + = 966.45 HPLC (method C): Tr = 2.37 nm C13 NMR (125 MHz, CD30D, ppm): 12.9; 13.6; 18.1; 18.5; 21.1; 22.3; 23.7; 30.1; 30.3; 32.3; 33.3; 33.4; 35.8; 36.6; 36.7; 36.8; 37.0; 38.3; 39.0; 41.4; 41, 7; 43.4; 43.8; 46.4; 52.8; 55.9; 56.0; 56.2; 56.3; 62.5; 66.6; 66.7; 69.8; 71.1; 72, 0, 72.6; 75.4; 75.9; 81.4; 82.8; 103.6; 103.9; 114.9 (2 carbons); 123.7; 133.4 (2 carbons); 165.5; 167.2; 171.4. Example 16: (2S, 3R, 4S, 5R) -2 - (((2S, 3R, 4S, 55) -3-acetoxy-2 - (((3S, 10R, 13S, 16S, 17R) - 174 (2R) 6R) -7- (benzylamino) -6-methylheptan-2-yl) -3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14 , 15,16,17-tetradecahydro-1H-cyclopenta [a] phenenanthren-16-yl) oxy) -5-hydroxytetrahydro-2H-pyran-4-yl) oxy) -4,5-dihydroxytetrahydro-2H-pyran-3 Example 16 is synthesized according to method 1 from steroid 6a and dioside 1 (yield = 38%). White solid (ES, m / z): [M + H] + = 948.48 HPLC (method C): Tr = 2.72 min C13 NMR, (100MHz, CD30D, ppm): 13.2; 18.4; 18.7; 19.8; 21.0; 21.9; 23.4; 30.5; 32.3; 32.9 (2 carbons); 33.5; 36.7; 37.2; 37.3 54.2; 55.9; 56.1; 56.3; 61.9; 66.3; 66.6; 69.7, 82.6; 103.8; 104.1; 114.8 (2 carbons); 122.3; 123.6 (2 carbons); 128.8; 129.7 (2 carbons); 130.0 (2 carbons); 133.2 (2 carbons); 142.3; 165.3; 167.0; 171.0. Example 17: (2S, 3R, 4S, 5R) -2 - (((2S, 3R, 4S, 5S) -3-acetoxy-2 - (((3S, 10R, 13S, -16S, 17R) formate ) - ((2R, 6R) -7- (benzyl (methyl) amino) -6-methylheptan-2-yl) -3-hydroxy-10,13-dimethyl-2,3,4,7,8 , 9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta [a] phenenanthren-16-yl) oxy) -5-hydroxytetrahydro-2H-pyran-4-yl) oxy) -4,5-dihydroxy tetrahydro-2H-pyran-3-yl 4-methoxybenzoate; 37.7; 38.5; 41.0; 43.0; 43.3; 51.7; ; 71.0; 72.1; 72.4; 75.2; 75.7; 81.2; Example 17 is synthesized according to method 1 from steroid 6b and dioside 1 (yield = 36%). White solid (ES, m / z): [M + H] + = 962.42 HPLC (method C): Tr = 2.52 min C13 NMR (125 MHz, CD30D, ppm): 13.4 31.2; 32.4; 33.0 (2 carbons); 36.0; 36.7 51.9; 56.2 (2 carbons); 62.3 (2 carbons); 64.2; 66.5; 66.7; 69.8; 71.1; 72.6 (2 carbons); 75.3; 75.8; 81.4; 82.8; 103.6; 103.9; 114.9 (2 carbons); 122.4; 123.8; 130.3 (2 carbons); 130.6; 132.1 (2 carbons); 133.3 (2 carbons); 138.6; 142.5; 165.5; 167.1; 171.2. Example 18: (2S, 3R, 4S, 5R) -2 - (((2R, 3R, 4S, 5S) -3-acetoxy-5-hydroxy-2 - (((3S, 10R, 13 S, 16S, 17R) -3-hydroxy-10,13-dimethyl-17 - ((2R, 6R) -6-methyl-7- (4- ((methylamino) methyl) -1H-1,2,3 triazol-1-yl) heptan-2-yl) -2,3,4,7,8,9,10,11,12,13,14,15,16,17- tetradecahydro-1H-cyclopenta [a] phenanthren 16-yl) oxy) tetrahydro-2H-pyran-4-yl) oxy) -4,5-dihydroxytetrahydro-2H-pyran-3-ylmethoxybenzoate (0HLOH, 18.1, 18.6; 0, 21.2, 22.1, 23.5, 30.4, 37.0, 37.8, 38.7, 41.2, 42.2, 43.2, 43.5; Example 18 is synthesized according to Method 4: 0.12 g (0.13 mmol) of Compound 1 is placed in a solution of 3.5 ml / ml. mL of methanol, 1 mL of THF and 0.5 mL of water 0.05 g, (0.24 mmol) of (R) -5 - ((S) -1,2-dihydroxyethyl) -4-hydroxy Sodium 2-oxo-2,5-dihydrofuran-3-olate followed by 0.06 g (0.24 mmol) of copper sulfate pentahydrate and 0.05 ml (0.59 mmol) of N-methylprop-2-yn The mixture is added to the ultrasonic bath for 7 minutes. After concentration to dryness, the residue obtained is purified on flash silica (gradient CH 2 Cl 2 / MeOH / NH 4 OH: 100/0/0 to 80/20 in 20 minutes). Compound 18 is isolated as an orange solid (0.077 g) in 59% yield. Orange solid (ES, m / z): [M + H] + = 953.45 HPLC (Method C): Tr = 2.46 nm C13 NMR, (100 MHz, CD30D, ppm): 13.2; 17.8; 18.6; 19.9; 21.1; 21.9; 23.3; 30.5; 32.3; 32.9 (2 carbons); 35.1; 35.6; 35.7; 37.1; 37.3; 37.7; 38.5; 41.0; 43.0; 43.3; 46.2; 51.7; 56.1; 56.2; 57.1; 62.2; 66.4; 66.7; 69.8; 71.0; 72.2; 72.4; 75.2; 75.8; 81.2; 82.5; 103.9; 104.0; 114.8 (2 carbons); 122.3; 123.6; 125.2; 133.2 (2 carbons); 142.3; 145.1; 165.3; 167.1; 170.9. Example 19: (2S, 3R, 4S, 5R) -2 - (((2S, 3R, 4S, 5S) -2 - (((3S, 10R, 13S, 16S, 17R) ((2R, 6R) -7-acetamido-6-methylheptan-2-yl) -3-yloxy-10,13-dimethyl-2,3,4,7,8,9,10,11, 12,13,14,15,16,17-tetradecahydro-1H-cyclopenta [a] phenen-16-yl) oxy) -3-acoxy-5-hydroxy-tetrahydro-2H-pyran-4-yl) oxy) 4,5-Dihydroxytetrahydro-2H-pyran-3-yl 4-methoxybenzoate Example 19 is synthesized according to method 5: Step 1: glycosylation of steroid 4b by dioside 1 under the conditions described in step 1 of the method 1.

Step 2: The azide of the intermediate obtained in the preceding step (0.095 g, 0.071 mmol) is placed in a solution of 5 mL of THF and 1.5 mL of water. Triphenylphosphine is added (0.056 g, 0.21 mmol) and then the mixture is stirred for 40h at room temperature. After filtration through Celite®, the medium is concentrated to dryness and the residue obtained is purified on flash silica (CH 2 Cl 2 / MeOH gradient: 100/0 to 90/10 in 20 minutes).

Step 3: 0.074 g (0.056 mmol) of intermediate obtained in the preceding step is placed in the presence of 9.10 μl of pyridine (0.113 mmol) in 2 ml of dichloromethane at 0 ° C. under argon. 0.011 ml (0.119 mmol) of acetic anhydride is added and the mixture is stirred overnight at room temperature. The reaction medium is washed with water, and then the organic phases are concentrated to dryness after drying. The residue obtained is used as it is for the next step. Step 4: Desilylation of the intermediate obtained in the preceding step under the conditions described in step 2 of method 1. The compound 19 is isolated in the form of a brown solid (0.027 g) with a yield of 41%. (ES, m / z): [M + H] + = 900.43 HPLC (Method C): Tr = 3.25 NM C13 NMR, (100MHz, CD30D, ppm): 13.1; 18.1; 18.6; 19.8; 21.0; 21.9; 22.6; 23.5; 30.5; 32.2; 32.8 (2 carbons); 34.4; 36.4; 37.5; 37.6 (2 carbons); 38.4; 41.0; 43.0; 43.2; 46.7; 51.7; 56.0; 56.2; 62.0; 66.3; 66.7; 69.8; 71.0; 72.1; 72.4; 75.2; 75.8; 81.2; 82.6; 103.8; 104.3; 114.7 (2 carbons); 122.6; 123.5; 133.1 (2 carbons); 142.2; 165.2; 167.0; 170.9; 173.0. Example 20: (2S, 3R, 4S, 5R) -2 - (((2S, 3R, 4S, 5S) -3-acetoxy-5-hydroxy-2 - (((3S, 10R, 13 S, 16S, 17R) -3-hydroxy-10,13-dimethyl-1774 (2R, 6R) -6-methyl-7- (methylsulfonamido) heptan-2-yl) -2,3,4,7,8, 9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta [a] phenenanthren-16-yl) oxy) tetrahydro-2H-pyran-4-yl) oxy) -4,5 EXAMPLE 20 is synthesized according to method 5 from steroid 4b and dioside 1, using in step 3 methylsulfonyl chloride instead of acetic anhydride. (yield = 20%). White solid (ES, m / z): [M-H f = 934.31 HPLC (method C): Tr = 3.42 min C13 NMR, (100 MHz, CD30D, ppm): 13.2; 18.1; 18.7; 19.8; 21.0; 21.9; 23.3; 30.6; 32.3; 32.9 (2 carbons); 34.8; 35.9; 37.3; 37.7 (2 carbons); 38.5; 39.7; 41.0; 43.0; 43.3; 50.1; 51.7; 56.1; 56.3; 62.1; 66.4; 66.7; 69.9; 71.1; 72.2; 72.5; 75.3; 75.9; 81.2; 82.5; 103.5; 104.4; 114.8 (2 carbons); 122.4; 123.6; 133.2 (2 carbons); 142.3; 165.3; 167.1; 171.1. Example 21: (2S, 3R, 4S, 5R) -2 - (((2S, 3R, 4S, 5S) -3-acetoxy-5-hydroxy-2 - (((3S, 10R, 13S, 16S, 17R) -3-hydroxy-10,13-dimethyl-1774 (2R, 6R) -6-methyl-7- (3-methylureido) heptan-2-yl) -2,3,4,7 , 8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta [a] phenenanthren-16-yl) oxy) tetrahydro-2H-pyran-4-yl) oxy) - EXAMPLE 21 is synthesized according to method 5 from steroid 4b and dioside 1 using in step 3 N-methyl-1H-2H-dihydroxy-tetrahydro-2H-pyran-3-yl-4-methoxybenzoate. imidazole-1-carboxamide instead of acetic anhydride (yield = 10%). White solid (ES, m / z): [M + H] + = 915.42 HPLC (Method C): Tr = 3.23 min C13 NMR (100 MHz, CD30D, ppm): 13.4; 18.3; 18.8; 20.0; 21.2; 22.1; 23.6; 27.3; 30.7; 32.4; 33.1 (2 carbons); 35.3; 36.6; 37.6; 37.7; 37.9; 38.7; 41.2; 43.2; 43.5; 47.5; 51.9; 56.3; 56.5; 62.3; 66.6; 66.9; 70.1; 71.2; 72.4; 72.6; 75.5; 76.0; 81.4; 82.8; 104.1; 104.5; 114.9 (2 carbons); 122.5; 123.8; 133.4 (2 carbons); 142.5; 162.0; 165.6; 167.3; 171.2.

Example 22: (2S, 3R, 4S, 5R) -2 - (((2R, 3R, 4S, 5S) -3-acetoxy-5-hydroxy-2 - (((3S, 10R, 13 S, 16S, 17R) -3-hydroxy-10,13-dimethyl-17 (2R, 6R) -6-methyl-7 - (((2- (methylsulfonyl) ethyl) carbamoyloxy) heptan-2-yl); -2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro1H-cyclopenta [a] phenanthren-16-yl) oxy) tetrahydro-2H-pyran-4 Example 22 is synthesized according to method 3 from steroid 7 and dioside 1 (yield = 39%). White solid (ES, m / z): [M + H] + = 1008.47 HPLC (method C): Tr = 3.40 min C13 NMR (125 MHz, CD30D, ppm): 13.1; 17.3; 18.7; 19.8; 21.0; 21.9; 23.4; 30.5; 32.3; 32.9 (2 carbons); 34.1; 35.2; 36.0; 37.4; 37.5; 37.7; 38.5; 41.0; 41.4; 43.0; 43.3; 51.7; 54.8; 56.1; 56.3; 62.2; 66.4; 66.7; 69.8; 70.9; 71.1; 72.2; 72.4; 75.3; 75.8; 81.2; 82.5; 103.8; 104.3; 114.8 (2 carbons); 122.3; 123.6; 133.2 (2 carbons); 142.3; 159.0; 165.3; 167.1; 171.0. Example 23: (2S, 3R, 4S, 5R) -2 - (((2R, 3R, 4S, 5S) -3-acetoxy-5-hydroxy-2 - (((3S, 5S, 10S, 13S, 16S, 17R) -3-hydroxy-10,13-dimethyl-17 (2R, 6R) -6-methyl-7 - (((2- (methylsulfonyl) ethyl) carbamoyloxy) heptan-2-yl) hexadecahydro-1H- cyclopenta [a] phenen-16-yl) oxy) tetrahydro-2H-pyran-4-yl) oxy) -4,5-dihydroxytetrahydro-2H-pyran-3-yl-4-methoxybenzoate. compound (whose double bond was reduced by Raney nickel) is obtained in a mixture with the compound of Example 22 and isolated by HPLC in a yield of 3%).

White solid (ES, m / z): [M + H] + = 1010.44 HPLC (method C): Tr = 3.49 nm C13 NMR (125 MHz, CD30D, ppm): 12.9; 13.5; 17.4; 18.8; 21.2; 22.3; 23.5; 30.1; 30.7; 32.3; 33.4; 34.2; 35.3; 36.2; 36.7; 36.8; 37.5; 37.6; 38.3; 39.0; 41.4; 41.6; 43.8; 46.4; 55.0; 56.0; 56.2 (2 carbons); 62.5; 66.6; 66.8; 70.0; 71.0; 71.2; 72.3; 72.4; 75.4; 76.0; 81.4; 82.7; 104.0; 104.4; 115.0 (2 carbons); 123.7; 133.3 (2 carbons); 157.5; 165.5; 167.2; 171.2. PHARMACOLOGICAL EVALUATION Cell culture. The cells A549 (non-small cell lung carcinoma - ATCC CCL-185) and HCT 116 (colorectal carcinoma - ATCC CCL-247) were cultured in Minimum Essential Medium Eagle (MEM) medium with 5% fetal calf serum ( FCS). Namalwa cells (Burkitt's Lymphoma - ATCC CRL-1432) were cultured in Dulbecco's Modified Eagle Medium (DMEM) with 10% FCS and RPMI-1640 medium with 10% FCS respectively. All media contained a mixture of fungizone (1.25 lag / mL) and penicillin-streptomycin (100 U / 100 lag / mL). The cells were maintained under standard culture conditions and maintained at 37 ° C, 5% CO2 and 95% moisture.

Antiproliferative activity on a panel of 3 tumor lines. The antiproliferative activities of the compounds of the invention were measured using an "ATPlite proliferation assay" kit (Perkin Elmer, Villebon sur Yvette, France) on 2 cell lines. The cells were seeded in 96-well plates (103 cells / well for A549, 1.5.103 cells / well for HCT116 and 3.104 cells / well for Namalwa) at a concentration allowing the cells to be in the exponential phase of growth. throughout the 72h of treatment. Adherent cells (A549 and HCT116) are seeded the day before treatment to allow their adhesion. The cells are treated with increasing doses of compound (11 μl of a 10X solution at 1% DMSO - 6 wells / condition). To eliminate any problems of plastic adhesion, the pipette tips were changed between two successive dilutions. Cells were incubated at 37 ° C, 5% CO2 for 72h. Cell viability was then measured by assaying ATP released by living cells. For each dose of compound, the percentage of living cells relative to the solvent control was calculated. The IC50 values (50% effector concentration) were determined using the GraphPad software algorithm (GraphPad Software Inc., CA, USA) corresponding to a sigmoidal dose-response analysis (nonlinear regression model, with slope Hill variable). Compound A-549 (IC50, M) HCT116 (IC50, M) Namalwa (IC50, M) OSW-1 7.78E-10 * 1.78E-10 3.07E-10 1 3.21E-10 6.23E-10 9.59E-10 12 2.22E-10 5.30E-10 6.29E-10 23 6.45E-10 8.94E-10 8.13E-10 * Mimaki Y. et al., Bioorg. Med. Chem. Lett., 1997, 7 (5), 633-636.

Claims (15)

REVENDICATIONS1. A compound of the following general formula (I): OH (I) or a pharmaceutically acceptable salt and / or solvate thereof, wherein: - - - represents a double or single bond, - R1 represents one or more substituents (s) identical (s) or different (s) each representing independently of each other a hydrogen atom, a halogen atom, preferably fluorine, or a trifluoromethyl, (Ci-C6) alkyl, (Ci -C6) alkoxy, NR3R4, (CH2) ', NR5R6, O (CH2) mNR7R8, or CO2R9, with R3 to R9 representing independently of each other a hydrogen atom or an optionally substituted (C1-C6) alkyl group, and m represents an integer from 1 to 6, wherein R 2 represents -N-R 11 -N = N + = N-, -O-R 12 with: either R 10 represents a hydrogen atom or a group C6) optionally substituted alkyl, and R11 represents a hydrogen atom or an optionally substituted (C1-C6) alkyl group, optionally substituted aryl, ary1- (C1-C6) alkyl optionally substituted, Y1 (CH2), IY2R13, SO2R14, COR15, CO2R16, or CONRI7R18, with Y1 representing a single bond or a group CO, CO2, CONR19 or SO2, Y2 representing an oxygen atom or an NR20 or SO2 group, al represents an integer between let 6, R13 to R17 representing independently of each other a hydrogen atom or an optionally substituted (C1-C6) alkyl group, optionally substituted aryl or optionally substituted (C1-C6) alkyl-aryl and R18 to R20 independently of one another being hydrogen or optionally substituted (C1-C6) alkyl; or R10 and R11 together with the nitrogen atom carrying them an optionally substituted heterocycle, and Wherein R 12 is optionally substituted (C1-C6) alkyl, optionally substituted aryl, optionally substituted (C1-C6) alkyl, Y3 (CH2) a2Y4R21, COR22, CO2R23, or CONR24R-25, with Y3 being a single bond; or a group C O, CO2 or CONR26, Y4 representing an oxygen atom, or a group NR27 or SO2, a2 representing an integer between 1 and 6, R21 to R24 representing independently of each other a hydrogen atom or a group ( C 1 -C 6) optionally substituted alkyl, optionally substituted aryl or optionally substituted aryl (C 1 -C 6) alkyl, and - R 25 and R 26 independently of one another represent a hydrogen atom or a (C 1 -C 6) alkyl group optionally substituted. 2. Compound according to claim 1, characterized in that R1 represents one or more identical or different substituent (s), preferably a substituent in the para position, each representing independently of one another a group ( C1-C6) alkoxy, such as methoxy. 3. Compound according to one of claims 1 and 2, characterized in that R2 + - N = - N = N represents a group - 30 4. Compound according to one of claims 1 and 2, characterized in that R2 Rio represents a group -N-R11 for which R10 represents a hydrogen atom or a group (C1-C6) alkyl and R11 represents a hydrogen atom. hydrogen or a (C 1 -C 6) alkyl or aryl (C 1 -C 6) alkyl group. 5. Compound according to one of claims 1 and 2, characterized in that R2 110 represents a group N-R11 for which R10 represents a hydrogen atom or a group (C1-C6) alkyl and R11 represents Y1 (CE12) in which Y 1 is a single bond, Y 2 is as defined in claim 1, wherein al represents an integer between 1 and 6, preferably between 1 and 4, more preferably between 1 and 2, and R 13 represents a group (Ci C6) alkyl. 6. Compound according to one of claims 1 and 2, characterized in that R2 R10 represents a group N-R11 for which R10 represents a hydrogen atom or a group (C1-C6) alkyl and R11 represents a group SO2R14, COR15 or CONRI7R18 with R14, R15, R18 representing, independently of each other, a (C1-C6) alkyl group and R17 representing a hydrogen atom or a (C1-C6) alkyl group. 7. Compound according to one of claims 1 and 2, characterized in that R2 510 represents a group for R10 and R11 form with the nitrogen atom a heterocycle selected from morpholine and triazole rings, optionally substituted with a group ( C1-C6) alkyl optionally substituted with NR29R30 or OR38 with R29, R30 and R38 representing, independently of one another, a hydrogen atom or a (C1-C6) alkyl group. 8. Compound according to one of claims 1 and 2, characterized in that R2 represents an O-R12 group for which R12 represents a group Y3 (CH2) a2Y4R21 in which R21 represents a (C1-C6) alkyl group, a2 represents an integer between 1 and 6, preferably between 1 and 4, more preferably between 1 and 2, Y4 represents a NR27 or SO2 group, preferably SO2, and Y3 represents a single bond or a CONR26 group, preferably a CONR26 group, with R 26 representing a hydrogen atom or a (C 1 -C 6) alkyl group. 9. Compound according to claim 1, characterized in that it is selected from the following compounds: HO el o. ## EQU1 ## ## STR2 ## ## STR1 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR1 ## ## STR2 ## ## STR2 ## ## STR1 ## ## EQU2 ## ## STR2 ## ## STR2 ## ## STR1 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ) ## STR1 ## If 0 pAc - HO e O., HN_I- b HO * if 0 \ 0 0 the 02 0-) \ S ° \ 2 - ° H 0 r011 -0 ° OH) e 0 OH d> .0H O O O 11 ## STR2 ## ## STR2 ## ## STR2 ## ## STR2 ## ## STR1 ## ## STR1 ## ## STR2 ## ## STR1 ## ## STR5 ## O - 0 - 0 - O - 0 - 0 - 0 - O - O - O - O - O - O - O - O - O - O - O - O - 0 - ## STR2 ## ## STR2 ## wherein a pharmaceutically acceptable salt and / or solvate thereof is present in the formula (I); such as a salt formed with formic acid. 10. A compound according to any one of claims 1 to 9 for use as a medicament. 11. A compound according to any one of claims 1 to 9 for use as a medicament for the treatment of cancer. 12. Pharmaceutical composition comprising at least one compound of formula (I) according to any one of claims 1 to 9, and at least one pharmaceutically acceptable excipient. 13. Process for preparing a compound of formula (I) according to any one of claims 1 to 9 comprising the following steps: (i) condensation of a compound of formula (II) below: R2GP GPI () for which - - - - is as defined in claim 1, GP 1 represents an O-protecting group and R2GP represents a group R2 as defined in claim 1, optionally in protected form, with a compound of formula (III) below: LG1 I ----- RiGP 0 OP \> o G P20 O \ OG P4 OGP3 for which LG1 represents a leaving group; GP2, GP3 and GP4 each represent, independently of each other, an O-protecting group; and R 1 Gp is R 1 as defined in Claim 1, optionally in protected form, (ii) deprotecting the protecting groups to give a compound of formula (I), (iii) when - - - - is a double bond optionally reducing the double bond to give a compound of formula (I) for which - - - - represents a single bond, and (iv) optionally salification and / or solvation to give a compound of formula (I) in the form of a pharmaceutically acceptable salt and / or solvate. 14. Process for the preparation of a compound of formula (I) according to any one of claims 1 to 9, for which R2 represents a 1,2,3-triazol-1-yl group optionally substituted with a group (C 1). C6) alkyl optionally substituted with a nitrogen and / or oxygenated function, comprising the following steps: (1) reacting a compound of formula (I) wherein R2 = N3 with a compound of formula = R with R representing H or a (C 1 -C 6) alkyl group optionally substituted with a nitrogen and / or oxygen function to give a compound of the following formula (Id): 5OH (Id) for which R is as defined above and - - - - and R 1 are as defined in claim 1, (2) when = represents a double bond, optionally reduction of the double bond to give a compound of formula (Id) for which - represents a single bond, and (3) optionally salification and / or solvation to give a compound of formula (Id) as a salt and / or a pharmaceutically acceptable solvate. 15. Process for the preparation of a compound of formula (I) according to any one of claims 1 to 9, wherein R2 represents a NR10R1 group, R10 and R11 not forming a ring with the nitrogen atom which the gate, comprising the following steps: (a) reduction of a compound of formula (VIa) below: N3O-GP3 (VIa) for which GPI, GP2, GP3 and GP4 each represent, independently of one another, a group 0-protector, RIGA represents a group R1 as defined in claim 1, optionally in protected form and = is as defined in claim 1, to give a compound of formula (VId) below: GP1.0 O-GP3 ( V1d) for which RiGp, GP1, GP2, GP3 and GP4 are as defined above and - is as defined in claim 1, (b) optionally substitution of the compound of formula (VId) obtained in step (a) ) to give a compound of the following formula (VIe): ## STR2 ## RIGA, GP1, GP2, GP3 and GP4 are as defined above and ==, R10 and R11 are as defined in claim 1, at least one of R10 and R11 not representing a hydrogen atom (c) deprotecting the protecting groups to give a compound of formula (I) with R2 = NRIORI I, (d) when - - - - represents a double bond, optionally reducing the double bond to give a compound of formula (I) for which - - - - represents a single bond and R2 = NRioRi 1, and (e) optionally salification and / or solvation to give a compound of formula (I) in the form of a salt and / or a pharmaceutically acceptable solvate.