FR3026607A1 - COMPOUNDS FOR PRESERVING CELLS, TISSUES AND ORGANS, COMPOSITIONS AND USES - Google Patents

Abstract

The subject of the invention is the use of a compound of formula I or of one of its derivatives, salts, metabolites or prodrugs in the preparation of a composition making it possible to preserve or preserve in vivo, in vitro, or ex cells, tissues and / or organs, and preferably to prevent ischemia-reperfusion injury in case of tissue implantation and / or organ transplantation, as well as compositions comprising such a compound.

Description

Field of the Invention The invention relates to the use of a compound of formula I or a derivative thereof, salts, metabolites or prodrugs in the preparation of a composition for preserving or preserving in vivo, in vitro , or ex vivo cells, tissues and / or organs, and preferably to prevent ischemia-reperfusion injury (I / R) in the context of cell and / or tissue therapy, surgery or organ transplantation. It also relates to the compositions and kits comprising such a compound and their uses. Background In renal transplantation, only one third of patients on the waiting list are transplanted each year. This leads to the search for new sources of graft to try to remedy this shortage. The removal of organs from closed heart donors or so-called "marginal" donors with important co-morbidity factors that make them more fragile is a current trend. These considerations lead to a rethinking of the means of preservation and their relevance especially for this kind of donors. Currently, kidneys from brain-dead donors are required to be kept at 4 ° C (cold ischemia) until they are assigned to a compatible recipient and then transplanted. All organs in transplantation are exposed to ischemia / reperfusion syndrome (I / R) lesions. This syndrome currently includes a set of pathophysiological processes responsible for lesions in the graft. These lesions are related to hypothermia per se and hypoxia contemporaneous with conservation, but also to the warming associated with the reoxygenation of the organ during reperfusion (Rauen and de Groot, 2004). I / R, there is an increase in cell death induced by necrosis or apoptosis and involved in various injury processes.

I / R is one of the major factors responsible for the delayed recovery of function which leads to an additional cost of transplantation by prolonged hospitalization and the need for dialysis sessions, and especially an increased risk of rejection. acute and reduced graft survival in the long term. In the current context of lack of organs, I / R lesions are predominant with favoring factors such as donor age greater than 60 years, cold ischemia lasting longer than 24 hours (time lapse between definitive clamping of the aorta in the donor at the time of collection and reperfusion of the organ in the recipient), a warm ischemia associated and prolonged (time during which the organ is still in the body, in situ, no or poorly perfused), and the cause of encephalic death (stroke).

Other factors may be involved in non-primary function of the graft, including vascular complications (thrombosis or stenosis), infections, side effects of immunosuppressive agents, and non-adherence to treatment (Pratschke et al., 2008). To all these non-immunological factors may be added immunological factors that will determine the outcome of the graft. I / R is itself a non-immunologic factor that early influences the outcome of the graft for different organs (Shaw et al., 1985, Vacanti et al., 1987, Greig et al., 1989, Ploeg et al. 1993, Sheridan and Bonventre 2000, Weiss et al. To date, the most common mode of preservation for the grafts after their collection remains static preservation in a solution at 4 ° C, after the organ has been properly washed, usually by the same preservation solution. The main goal is to maintain the viability of different organs ex vivo for a period of time sufficient for their eventual transport from the collection center to the transplant centers, their allocation according to the degree of urgency, priority or better tissue compatibility and the use of all organs removed. The shelf life can be up to 48 hours (based on theoretical thermodynamic models and experimental data). The management of organs is very different depending on whether it is a vital organ such as the heart, liver and lung, or the kidney for which a delay in resumption of function of the graft is tolerable through the use of 'hemodialysis. It is accepted that the duration of preservation is one of the most important factors in the delayed recovery of graft function, with an ideal limit for the kidney at around 18 h (Opelz and Dohler, 2007). It appears that available conservation solutions can not comprehensively prevent I / R-related injury (Rauen and De Groot 2004, Salahudeen 2004 Jamieson and Friend 2008). Recent advances in the physiopathological mechanisms involved in I / R have highlighted the important components of this process (Salahudeen, 2004). The consequences of I / R damage affect all organs and the most tangible effect is the delayed recovery of function, which can be defined as the divergence between the functional capacity of the transplanted organ and the physiological needs of the recipient. I / R promotes the risk of acute rejection with evidence of an increase in proinflammatory cytokine production and activation of endothelial cells which, in conjunction with coagulation phenomena, imply hyperexpression of and MHC (major histocompatibility complex) class I and II antigens responsible for increased immunogenicity. Several studies have confirmed that patients with delayed function reversal immediately after transplant have a high percentage of acute rejection (Nicholson et al., 1996, Ojo et al., 1997). These facts remain relevant with the use of new immunosuppressive therapies (Mikhalski et al., 2008). However, several studies have shown that a decrease in I / R lesions (using a more appropriate conservation solution (Thuillier et al., 2011) or molecules (Thuillier et al., 2014)) could significantly limit this immune activation and protect the grafts).

For decades, principles of conservation have been based on principles and empirical evidence (Hicks et al., 2006). The two essential points being: - hypothermia around 4 ° C based on the principle of a 50% decrease in metabolism, by reducing the temperature in increments of 10 ° C; and - the composition of a preservation solution having to resemble the intracellular medium with an essentially hyperpotassic composition. There are a large number of conservation solutions. The solution of the University of Wisconsin or ViaSpanO, considered as the reference solution, is well known. Other solutions have also been developed since about fifteen years as IGL-1®, SCOTO, Celsior0 or Custodio10. Patent application WO 2010/065567 describes compositions comprising resveratrol making it possible to modulate the lifespan of cells, tissues, organs or organisms. The conservation solutions currently available, however, are far from fully meeting the physiopathological problems related to organ preservation and ischemia / reperfusion. If resveratrol has good protective properties during ischemia / reperfusion its extremely rapid metabolism in vivo and its strong photosensitivity limit its possible therapeutic applications. In addition, multi-organ solutions generally correspond to solutions developed for a particular organ whose use is then extended to other bodies (Karam et al., 2005), which only partially meets the specific objectives. to each of them. Despite an improvement in the performance of preservation solutions to limit I / R lesions, the percentages of primary non-function of the graft and deferred resumption of function remain significant.

SUMMARY OF THE INVENTION The subject of the invention is the use of a compound of formula (I) R1 (I) in which R1 and R3 represent, independently of one another, -OH, -OR4, or -O-C (= O) -R4, R2 is -H, -OH, -CN, -CF3, a halogen such as -F, -Cl, -I or -Br, NH2, -NHR5, -N ( R5) 2, -OR5, -O-C (= O) -R5 or a radical comprising a glycosyl group and having a molecular weight of less than 1000 g.mo1-1, R4 and R5 represent, independently of one of the other, a C1-C4 alkyl group, preferably a methyl. A represents CH2-CH2, CH = CH, a diradical derived from a heteroaryl alkyl or a heteroaryl alkenyl such as a radical of formula (Ta): R7 (Ta) in which R6 represents -OH, -OR4, or -O-C (= O) -R4 with R4 as defined above, R7 represents a radical comprising a glycosyl group and having a molecular weight of less than 1000 g.mo1-1, -H, -OH, -CN, -CF3 a halogen such as -F, -Cl, -I or -Br, NH2, -NHR5, -N (R5) 2, -OR5, or -O-C (= O) -R5 with R5 being as previously defined and A1 represents CH2-CH2 or CH = CH, or a pharmaceutically preferable salt thereof, in the preparation of a composition for preserving or preserving in vivo, in vitro, or ex vivo cells. , tissues, organs and / or part (s) of organ. Preferably, if A is CH = CH, R1, R2 and R3 are not simultaneously -OH, and if A is a radical of formula (Ta) with A1 is CH = CH, R1, R2, R3, R6 and R7 do not are not simultaneously -OH.

In certain embodiments, the invention relates to the use of a compound of formula (I) wherein R2, and / or R7 if present, are selected from radicals of formula (Ib) X4SPAC1n-GLYC ( 1b), in which - X is 0, S or NR8 with R8 is H or C1-C3 alkyl, preferably X is 0. - SPAC is a spacer group preferably comprising an ethylene glycol or polyethylene glycol unit, n is an integer of 1 or 0, and GLYC is a glycosyl radical preferably chosen from the group consisting of a glucosyl radical, a diglucosyl radical, a galactosyl radical and a digalactosyl radical. In a particular embodiment, the subject of the invention is the use of a compound of formula (I) in which: - A is CH 2 -CH 2 or CH = CH, - R 1 and R 3 represent, independently of one of the other, -OH, -OCH3, or -O-C (= O) CH3, preferably R1 = R3 and -R2 is preferably: R '\ \ NO-1-GLYC 1-0- <O_I-GLYC or where m is an integer from 1 to 10, preferably 2, 3, 4, 5 or 6, R 'is H or C 1 -C 3 alkyl, preferably -CH 3, and GLYC is selected from a glucosyl radical, a diglucosyl radical, a galactosyl radical, and a digalactosyl radical, preferably a glucosyl or galactosyl radical, in the preparation of a composition for preserving or preserving in vivo, in vitro or ex vivo cells, tissues, organs and / or part (s) organ. In another particular embodiment, the subject of the invention is the use of a compound of formula (I) chosen from compounds of formula (II): R7 (II), in which R1, R2, R3, R6 , R7 and A1 are as defined above, and salts thereof, preferably pharmaceutically acceptable salts thereof, in the preparation of a composition for preserving or preserving in vivo, in vitro, or ex vivo cells, tissues, organs and / or part (s) of organ.

A further object of the invention relates to the compounds of formula (I) or (II) as defined above, the pharmaceutically acceptable salts thereof, and the mixtures and combinations thereof, as well as their use in one or both of the applications mentioned in this text.

The invention thus relates to the use of a compound according to the invention in the preparation of a composition for preserving or preserving in vivo, in vitro, or ex vivo cells, tissues, organs and / or part (s) of organ, and preferably to prevent or treat ischemiereinfusion (I / R) lesions of cells, tissues, organs and / or part (s) of the organ in the context of cell and / or tissue therapy, d surgery or organ transplantation. The invention also relates to compositions comprising such a compound, or a mixture or a combination of such compounds. A preferred composition comprises a compound of formula (I) according to the invention in combination with an adjuvant chosen from glycerol, diglycerol, ethanol, polyethylene glycol (PEG) and propylene glycol (PG). Compositions of interest described herein include a static preservation composition or dynamic preservation (using an infusion machine) ex vivo of cells, tissues and / or organs (or part (s) of the organ ), an in vivo preservation composition of the cells, tissues and / or organs (or part (s) of organ) of the donor host or the recipient host, typically a reperfusion composition or a storage composition and / or or transporting a graft to the recipient host. The invention also covers kits, in particular: a kit for carrying out a method for preserving or preserving cells, tissues and / or organs (known as a kit for preserving or preserving cells, tissues and / or organs ") comprising at least one compound of interest according to the invention; a kit for carrying out a method for preserving or preserving cells, tissues and / or organs (called a "kit for preserving or preserving cells, tissues and / or organs") comprising at least one compound of interest according to the invention and a reperfusion solution, typically selected from ViaSpanO, IGL-le, SCOTO, Celsior0 or Custodio10, Kidney Preservation Solution (KPSO), Machine Preservation Solution (MPSO), SoltranO, Lifor0 and Steen®; a kit for the implementation of a method for preventing or treating the ischemia-reperfusion phenomenon that may affect or affect the recipient subject or host for which the cells, tissues, organs and / or part are intended (s) organ (called "prevention kit or treatment of I / R syndrome"). The at least one compound of interest according to the invention present in the kit is advantageously selected according to the target subject or recipient host as explained in the detailed description; a kit for carrying out a method of conditioning the subject or the donor host of the cells, tissues and / or organs (or part (s) of the organ) before the collection of said cells, tissues and or organs (called "prevention kit or treatment of I / R syndrome"). The at least one compound of interest according to the invention present in the kit is advantageously selected according to the donor subject or host concerned as explained in the detailed description; a kit for static or dynamic preservation, or preservation of cells, tissues and / or organs (or part (s) of organ) comprising. . at least one compound of interest according to the invention, and a universal pocket injector, and / or. a correspondence table indicating the dose to be used according to the indication. Also described are cellular systems (ie sets of cells organized together, said cells having been isolated from the body of a donor subject, for example a living being or a being in a brain-dead state whose organs are artificially kept functional), for example the composition of cells, tissues, organs or part of organs, brought into ex vivo contact with a compound of interest according to the invention, said cellular systems being intended to be used as a graft, as well as kits comprising at least one of these cellular systems having been exposed to at least one compound according to the invention, and optionally at least one compound according to the invention identical to or different from that already brought into contact with the cellular system. The subject of the invention is also the use of a compound as described above (including the corresponding pharmaceutically acceptable salts), or a kit as described above for preparing a composition according to the invention, for preserving or storing cells, tissues and / or organs or organ parts, to prevent and / or treat the phenomenon of ischemia-reperfusion, or to condition the subject or donor host cells, tissues and / or or organs.

The products (compounds, compositions, cellular systems such as a composition of cells, tissues, organs or parts of organs, and kits) comprising or having been exposed to a compound according to the invention are typically intended to be used in / on a mammal , preferably in / on a human being. FIGS. FIG. 1: Examples of compounds of interest made FIG. 2: Survival result when using molecules transformed into a hot ischemia condition.

Figure 3: Survival result when using different solvents in hot ischemia condition. Figure 4: Survival result when using molecules transformed into cold ischemia condition. Figure 5: Survival result when using different solvents in cold ischemia condition. Detailed Description of the Invention The inventors have developed compounds of interest to preserve the integrity of mammalian cells, typically human cells, to prevent ischemia-reperfusion injury and, where appropriate, to repair cells. having suffered such injuries. The inventors have also synthesized and selected the compounds according to the invention for their beneficial actions. The latter are indeed responsible for an increase in the energy production (ATP production) by the mitochondria present in the cells to be preserved and / or preserved, a limitation of the mitochondrial DNA lesions consecutive to the phenomenon 20 ischemia-reperfusion, prolongation of the ex vivo cell, tissue and organ storage life, significant acceleration of function recovery of in vivo grafted tissues or organs, and increased survival graft in vivo. Reperfusion markers include, but are not limited to, the time to recovery of organ function, the function of the organ (eg, plasma creatinine level or sodium reabsorption to kidney or transaminase levels). plasma levels for the liver), tissue integrity assessed by histological methods. The compounds identified by the inventors can be used to preserve or preserve in vivo, in vitro, or ex vivo cells, tissues and / or organs. Thus, the present invention relates to the use of a compound of formula (I) wherein R1 and R3 represent, independently of one another, -OH, -OR4, or -O-C (= O) -R4, R2 represents -H, -OH, -CN, -CF3, halogen, NH2, -NHR5, -N (R5) 2, -OR5, -O-C (= O) -R5 or a radical comprising a glycosyl group, said radical having a molecular weight of less than 1000 g.mol -1, R 4 and R 5 represent, independently of one another, a C 1 -C 4 alkyl group, A represents CH 2 -CH 2, CH = CH, a diradical derived from a heteroaryl alkyl or a heteroaryl alkenyl such as a radical of formula (Ta): R7 (Ta) in which - R6 represents -OH, -OR4, or -O-C ( = 0) -R4 with R4 as defined above, - R7 represents a radical comprising a glycosyl group and having a molecular weight of less than 1000 g.mo1-1, -H, -OH, -CN, -CF3, a halogen, NH2, -NHR5, -N (R5) 2, -OR5, or -O-C (= O) -R5 with R5 being as defined above, and -A1 represents CH2-CH2 or C H = CH, or a salt thereof, preferably pharmaceutically acceptable, in the preparation of a composition for preserving or preserving in vivo, in vitro, or ex vivo cells, tissues and / or organs ( or part (s) of organ). In certain embodiments, the compound of formula (A) is such that: if A is CH = CH, R1, R2 and R3 are not simultaneously -OH, and / or if A is a radical of formula (Ta) with A1 is CH = CH, R1, R2, R3, R6 and R7 are not simultaneously -OH.

In certain embodiments, the compound of formula (A) is such that: A is CH = CH, R1 = R2 = OMe and R3 = OH or a salt thereof.

In the meaning of the invention, a halogen atom includes Br, Cl, I or F, preferably Br and Cl. A C1-C4 alkyl group includes methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert -butyl, and sec-butyl. C1-C3 alkyl group includes methyl, ethyl, propyl and isopropyl groups.

For the purposes of the invention, the term "radical comprising a group (or glycosyl group") is understood to mean a radical comprising at least one glycosyl unit A glycosyl radical includes radicals derived from mono-, di- or tri-saccharides and their analogues for example, diglucosyl, glucosyl, galactosyl or digalactosyl radicals The "glycosyl" radical may be directly attached to the remainder of the structure of the compound of formula (I) or via a spacer group.

Thus, the "radical comprising a glycosyl group" may further comprise one or more additional chemical moieties such as a "spacer group". The "radical comprising a glycosyl group" typically has a molecular weight of less than 1000 g / mol, preferably less than 800 g / mol, for example between 100 g / mol and 700 g / mol. . The term "spacer group" or "spacer chain" ("linker" in English) means a chemical entity that makes it possible to bind two or more molecular entities together. In the context of the present invention, the spacer group is preferably a bifunctional entity for linking the glycosyl group to the rest of the structure of the compound of formula (I). The spacer group can be of any type. The spacer group can be chosen from a polymeric or oligomeric chain, a peptide, a polypeptide such as a polyglycine or a polylysine, an oligo- or a polysaccharide, a hydrocarbon-based chain optionally interrupted by one or more heteroatoms, preferably -0- or -S-, and / or with one or more chemical groups of -NHC (O) -, -OC (O) -, -NH-, -NH-C (O) -NH- and / or optionally comprising a or more rings or heterocycles of 5 to 6 atoms, a combination or repeats thereof. Preferably, the spacer group comprises a polyether type unit such as polyethylene glycol (PEG) or polypropylene glycol. In the context of the present invention, the spacer group may be chosen so as to improve the solubility of the compound of formula (I) in water. It goes without saying that the spacer group is generally chosen so as not to significantly alter the protective properties of the compounds of formula (I) for the preservation or preservation of cells, organs or tissues. The spacer group may be further selected so as not to alter the binding properties of the glycosyl moiety to its biological receptor.

The presence of a glycosyl group in the structure of the compound of formula (I) may make it possible to improve the solubility of the compound in water. The glycosyl group can furthermore make it possible to target a specific organ or tissue and / or to promote the intracellular penetration of the compound of formula (I).

Thus, in a particular embodiment, the subject of the invention is the use of a compound of formula (I) in which R2, and / or R7, if present, are chosen from radicals of formula (Ib): X-ISPAC111-GLYC (Ib), wherein - X is 0, S or NR8 with R8 is H or C1-C3 alkyl, preferably 0, - SPAC is a spacer group, - n is an integer of 1 or 0, preferably n is 1, and - GLYC is a glycosyl radical, or a pharmaceutically acceptable salt thereof.

R7 is present if A is a radical of formula (Ia). R7 is absent if A is CH2-CH2 or CH = CH. SPAC is a spacer group as defined above. In some embodiments, SPAC comprises an ethylene glycol unit or a polyethylene glycol. By "polyethylene glycol" is meant the sequence of 2 to 20, preferably 2 to 10, ethylene glycol monomers. By way of example, R2, and / or R7 if present, may be chosen from: 0-I-GLYC 0-1-GLYC OR where m is an integer of 1 to 10, preferably 2, 3, 4, 5 or 6, and R 'is H or C 1 -C 3 alkyl preferably -CH 3 In any of the embodiments above, GLYC is preferably selected from the group consisting of a glucosyl radical, a diglucosyl radical, a galactosyl radical, and a digalactosyl radical. A galactosyl radical denotes a radical derived from C1-substituted 13-D-galactopyranose. A glucosyl radical denotes a radical derived from C1-substituted 13-D-glucopyranose. The GLYC unit may be chosen according to the type of cell, tissue or organ that it is desired to preserve or preserve, and / or depending on the donor or the recipient potential of said cell, tissue or organ.

By way of example, R2, and / or R7 if present, may be chosen from: ## STR2 ## and OH ## STR1 ## represents H or a C 1 -C 3 alkyl. In a particular aspect, the subject of the invention is the use of a compound of formula (I) R 1 (I) in which A represents CH 2 -CH 2 or CH = CH, and R1, R2 and R3 are as defined above, provided that if A is CH = CH, R1, R2 and R3 are not simultaneously -OH, or a salt thereof such as a pharmaceutically acceptable salt. in the preparation of a composition for preserving or preserving in vivo, in vitro, or ex vivo cells, tissues and / or organs (or part (s) of organ). In some embodiments, A is -CH = CH-. The double bond may be indifferently in cis or trans conformation, preferably in trans conformation. In this embodiment, the compound of formula (I) can be used in the form of a mixture of cis and trans isomers. Preferably, the compound of formula (I) may be used in the form of a mixture enriched in trans isomer, that is to say comprising at least 60 mol%, preferably at least 70 mol% or even minus 90 mol% trans isomer.

In a further embodiment, the compound of formula (I) is characterized in that: - A is CH2-CH2 or CH = CH, preferably CH2-CH2, - R1 and R3 represent, independently of one of the other, -OH, -OCH3, or -O-C (= O) CH3, preferably R1 = R3, and - R2 is selected from -OH, -OCH3, -O-C (= O) CH3 or a radical comprising a glycosyl group and having a molecular weight of less than 1000 g.mo1-1 as defined above. In particular R2 may be selected from the radicals of formula (Ib): -X-ISPAC111-GLYC (Ib), wherein - X is 0, S or NR8 with R8 is H or C1-C3 alkyl, preferably X is 0, - SPAC is a spacer group, preferably comprising an ethylene glycol or polyethylene glycol unit, - n is an integer of 1 or 0, preferably n is 1 and - GLYC is a glycosyl radical, preferably a glucosyl radical, a radical In a more specific embodiment, R2 may be selected from: ## STR1 ## wherein m is an integer ranging from 1 to 10, preferably 2, 3, 4, 5 or 6, and R 'is H or C 1 -C 3 alkyl, preferably-CH 3, and GLYC is selected from a glucosyl radical, a diglucosyl radical, a galactosyl radical, and a digalactosyl radical, preferably a glucosyl or galactosyl radical. By way of example, the compound of formula (I) may thus be chosen from compounds of formula (I) having one of the following combinations of characteristics: (i) A = CH 2 -CH 2, 121 = R 3 = OH and R 2 is NNN OH (ii) - A = CH = CH, R 1 = R 3 = O Me and R 2 is OH OH OH, N. ## STR5 ## wherein R 1 = R = R = OH, and R 1 = R = OH, and the salts thereof.

Preferably, the compounds corresponding to the combinations (ii) - (iii) are in trans conformation. The compounds of this particular embodiment are preferably intended to be placed in contact with cells, tissues, organs (or portions thereof) from or intended typically for transplantation, resuscitation (eg artificial liver including cartridges functional cells) and cosmetic surgery. Target subjects are for example selected from subjects suffering from diabetes, organ terminal failure, cardiovascular pathology, etc. Target organs are, for example, chosen from the pancreas (in whole or in part, for example, Langerhans' islets), the lungs, the liver, the heart, the kidneys, the cornea, the muscles, the bones, the intestines, and the like. Composite members (eg, face or member) Compounds of interest for the practice of the present invention are compounds of formula (I) wherein A is a radical of formula (Ta). Indeed, as shown in the examples, the compounds derived from viniferine (compounds II, III, IV, V and VIII) may exhibit improved activity compared to their analogs derived from resveratrol (compounds I and VII). Thus, according to a further aspect, the invention relates to the use of a compound of formula formula (II): R7 (II), wherein R1, R2, R3, R6, R7 and A1 are as defined above in the context of formula (I), or a salt thereof, for example a pharmaceutically acceptable salt, in the preparation of a composition for preserving or preserving in vivo, in vitro, or ex vivo cells, tissues and / or organs (or part (s) of organ). As defined above, in a preferred embodiment, if A1 is CH = CH, then R1, R2, R3, R6 and R7 are not simultaneously -OH.

Preferred compounds have a formula (II) wherein: R1, R2, R3 and R6 are independently -OH, -OCH3, or -O-C (= O) CH3, preferably R1, R2, R3 and R6 are the same - R7 represents -H, -OH, -CN, -CF3, a halogen such as -F, -Cl, -I or -Br, NH2, -NHR5, -N (R5) 2, -OR5, -0- C (= O) -R5 with R5 is a C1-C4 alkyl, preferably a methyl, or a radical comprising a glycosyl group and having a molecular weight of less than 1000 g.mo1-1 as defined above. Particularly preferred compounds have a formula (II) in which: R 1, R 2, R 3 and R 6 independently represent -OH, -OCH 3, or -O-C (= O) CH 3, preferably R 1, R 2, R 3 and R 6 are identical, - R7 represents -H, -OH, -CN, -CF3, a halogen such as -F, -Cl, -I or -Br, NH2, -NHR5, -N (R5) 2, -0R5, -0 -C (= O) -R5 with R5 a C1-C4 alkyl, preferably a methyl, -OCH3, -O-C (= O) -CH3, or a radical of formula (Ib) -X-ISPAC111-GLYC (Ib), wherein - X is 0, S or NR8 with R8 is H or C1-C3 alkyl preferably 0, - SPAC is a spacer group, preferably comprising an ethylene glycol or polyethylene glycol unit, - n is a integer equal to 1 or 0, preferably n is 1 and - GLYC is a glycosyl radical, preferably a glucosyl radical, a diglucosyl radical, a galactosyl radical, or a digalactosyl radical. Preferably, R7 is chosen from: R '0 O GLYC OR where m is an integer from 1 to 10, preferably 2, 3, 4, 5 or 6, R 'is H or a C1-C3 alkyl, preferably -CH3, and GLYC is selected from a glucosyl radical, a diglucosyl radical, a galactosyl radical, and a digalactosyl radical, preferably a glucosyl or galactosyl radical.

In some embodiments, A1 is -CH = CH-, which double bond may be in cis or trans conformation, preferably trans. According to one aspect of the invention, when A1 is -CH = CH-, the compound of formula (II) can be used in the form of a mixture of cis and trans isomers. Preferably, it is a mixture enriched in trans isomers that is to say comprising at least 60 mol%, preferably at least 70 mol% or even at least 90 mol% of trans isomers. Examples of particularly preferred compounds of formula (II) according to the invention have one of the following combinations of radicals: i. R 1 -R 2 -R 3 -R 6 -OH, and Al-CH 2 -CH 2; R 1 -R 2 --R 3 --R 6 - - -OMe, and Al = CH = CH, R 1 -R 2 --R 3 --R 6 - -OMe, and AI CH 2 -CH 2; iv. R1 = R2 = R3 = R6 = -0Me, R7 = H, and A1 = CH = CH, y. R1 = R2 = R3 = R6 = -OH, R7 = HetAi = CH = CH vi. R1 = R2 = R3 = R6 = -0Me, R7 = F and A1 = CH = CH vii. R1 = R2 = R3 = R6 = -OH, R7 = F and A1 = CH = CH, viii. R1 = R2 = R3 = R6 = -0Me, R7 = CF3 and A1 = CH = CH ix. R1 = R2 = R3 = R6 = -OH, R7 = CF3 and A1 = CH = CH, x. R1 = R2 = R3 = R6 = -0Me, R7 = -CN and A1 = CH = CH, xi. R1 = R2 = R3 = R6 = -0Me, R7 = -CN and A1 = CH = CH; xii. R1 = R2 = R3 = R6 = -OH, R7 = -CN and A1 = CH = CH; xiii. R1 = R2 = R3 = R6 = OH, A1 = CH = CH and OH HO OH R7 is N.O. R1 = R2 = R3 = R6 = OMe, A1 = CH = CH and HO ## STR1 ## is R1 = R3 = R6 = OH, R1 = CH2-CH2 and R7 HO is ## STR2 ## R 1 = R 2 = R 3 = R 6 = OH, Al = CH 2 -CH 2, and R 7 is O with R 'is H or C 1 -C 3 alkyl, preferably H or CH 3, Wherein R1 = R2 = R3 = R6 = OH, A1 = CH = CH, and OH OH O - R7 is 0 with R 'is H or C 1 -C 3 alkyl, preferably H or CH 3, as well as salts thereof, such as pharmaceutically acceptable salts The compounds of formula (II) have a plurality of asymmetric carbons. According to the present invention, a compound of formula (II) may be used in the form of a mixture of diastereoisomers, in the form of a racemic mixture, in the form of a mixture enriched in one enantiomer or in enantiomerically pure form. In certain preferred embodiments, the compound of formula (II) has the stereochemistry as e in the figure (Ha) below: R7 (IIa) Within the meaning of the invention, the term "salt" any salt of a compound of formula (I) wherein the counterion or ions are adapted to be contacted with cells, organs or tissues, in vitro or in vivo. Examples of such salts are lithium, sodium, calcium, or potassium salts. When the compound is intended for in vivo use, pharmaceutically acceptable salts are preferably used, such as as sodium salts. In some embodiments, the compound of the invention has one or more phenol functions. The compound can thus be in the form of phenolates. The counter-cation of the phenolate functional group (s) is preferably selected from Na, I (±, Lit, and Ca 'and combinations thereof.) In some embodiments, all the phenol functions of the compound are The compound according to the invention may thus be in the form of a sodium, potassium, lithium or calcium polyphenolate, for example the compound may be a lithium salt of viniferine, or a viniferine sodium salt or a viniferine calcium salt Additional objects of the invention relate to a compound of formula (I), for example a compound of formula (II), as defined above, a metabolite, a derivative, a prodrug thereof, pharmaceutically acceptable salts thereof, and compositions comprising such a compound, a mixture or a combination of compounds according to the invention, as well as their uses in one and / or the other applications mentioned Within the meaning of the invention, a "prodrug of a compound of formula (I)" designates a compound whose metabolization in vivo, ex vivo or in vitro - that is to say by a cell or by cellular machinery - leads to the formation of compound I wherein A represents CH2-CH2 or CH = CH, and R1, R2 and R3 are as defined above, provided that if A is CH2 = CH2, R1, R2 and R3 are not simultaneously -OH, or a salt thereof such as a pharmaceutically acceptable salt. The term "cellular machinery" means any protein, in particular any enzyme, organelle or supramolecular complex (such as microsomes) obtained from a cell.

By way of example, the compound (I) in which R1, R2 = OMe, and R3 = R '\ 1-0- <0 can be metabolized in vitro by plasma esterases and constitutes a prodrug of the compound of formula ( I). Preferably, the prodrugs of the compound of formula (I) are chosen from compounds of formula (I) is characterized in that: - A is CH2-CH2 or CH = CH, preferably CH = CH, - R1 and R3 represent , independently of one another, -OH, -OCH3, or -O-C (= O) CH3, preferably R1 = R3, and R '1-0- <- R2 = 0 or a salt thereof -this. 0-1-GLYC The compounds of formula (I) can be easily obtained by chemical synthesis by a person skilled in the art. In this respect, the experimental part presents synthesis schemes. Certain compounds according to the invention may be typically obtained by hemi-synthesis, for example from viniferine isolated by extraction from vine oaths.

As shown in the examples, certain molecules such as glycerol make it possible to potentiate the tissue preservation properties of the compounds according to the invention, whereas these molecules do not in themselves have activity. Thus, in a preferred embodiment of the invention, the compound or compounds of formula (I), preferably of formula (II), are used in combination with an adjuvant chosen from glycerol, diglycerol, ethanol, polyethylene glycol (PEG) and propylene glycol (PG). Preferably, for the implementation of the invention according to its various aspects (see below), one of the particularly preferred compounds of formula (II) described above or one of their acceptable salts is used. on a pharmaceutical level, alone or in combination with one of the adjuvants described in this text. The invention thus relates to the use of a compound according to the invention in the preparation of a composition making it possible to preserve or preserve in vivo, in vitro or ex vivo cells, tissues and / or organs, and preferably to prevent or treat ischemia-reperfusion (I / R) lesions of cells, tissues, organs and / or organ parts, eg lesions resulting from cold ischemia and / or hot ischemia, in the context of cellular and / or tissue therapy, surgery, for example aortic surgery or cardiac surgery, typically coronary bypass surgery, or organ transplantation.

The invention can be typically carried out on one of the following organs (or part of organ or composite organ): kidneys, lungs, liver, pancreas, heart, cornea, muscles, bones and intestines. Similarly, the cells targeted by the invention are advantageously chosen from renal, cardiac, pulmonary, hepatic, corneal, intestinal, vascular, bone, muscular, skin and progenitor cells cells, in particular endothelial progenitor cells or mesenchymal cells typically derived from bone marrow or adipose tissue. Another particular object of the invention relates to the use of a compound according to the invention for preventing and / or treating heart failure or heart failure, preferably in combination with an active substance used by the medical profession for this indication. , for example a betablocker, an angiotensin converting enzyme inhibitor, an aldosterone antagonist, an angiotensin II receptor antagonist, etc., in a subject at risk of developing, or diagnosed as, suffering, insufficiency or heart failure, said subject being preferably a mammal, typically a human being. For the purposes of the invention, the term "treatment" means slowing or blocking the development of a disease or associated symptoms, or the curing of said disease. The prevention of a disease means, in turn, the fact of reducing the risk of the appearance of a disease within a given group of individuals. The invention also relates to compositions comprising such a compound, a mixture or a combination of such compounds. A preferred composition according to the invention thus comprises at least one compound of formula (I) according to the invention in combination with an adjuvant preferably chosen from glycerol, diglycerol, ethanol, polyethylene glycol (PEG) and propylene. glycol (PG).

Compositions of interest described in the present text comprise a composition for storing or preserving, static or in ex vivo machine, cells, tissues, organs and / or part of an organ, a composition for preserving or preserving the cells in vivo, tissues and / or organs of the donor host or recipient host, typically a preservation (or reperfusion) composition or a storage and / or transport composition of a graft in the recipient host. A typical composition according to the invention is a commercial solution solution solution in which at least one compound of formula (I) according to the invention has been added to the desired concentration.

Although the storage (static or dynamic), reperfusion, and storage or transport solutions have a wide range of different compositions, there is no anticipation of major incompatibility between the typical constituents and the compound. A preservation or conservation solution (static or dynamic) typically comprises ions (I (±, Na, etc.), buffers (HEPES, Histidine, etc.), impermants (glucose, raffinose, etc.), colloids (eg, hydroxyethyl starch, dextrans, etc.) (e.g., Niu Y. et al., Nat Rev. Nephrol, 2012, May 1, 8 (6): 339-47, PMID: 22549229) .A reperfusion solution comprises typically elements similar to the preservation solution, in different concentrations (see for example Yaghoubi A. et al., J Cardiovasc Thorac Res 2011; 3 (4): 123-7. PMID: 24250969).

A storage and transport solution (for example, tissues or cells) typically comprises the same elements, to which nutrients such as amino acids (glutamate, aspartate, glutamine, etc.), hormones (insulin, etc.) are generally added. (See, for example, Kay MD et al., J Surg Res., Nov. 2011; 171 (1): 275-82. PMID: 20421110). A preferred organ preservation or preservation solution, for example the University of Wisconsin solution, comprises, apart from the compound (s) of interest of formula I according to the invention: 30 mM Na, 125 mM K ±, 5 mM Mg 2, 5mM s042-, 25mM H2P042-, 30mM Raffinose, 100mM Lactobionate, 5mM adenosine, 4mM glutathione, 1mM allopurinol, 50g.1-1 hydroxyethyl starch. The concentration of the compound of formula (I) is generally in a range from 5 to 25 mg / l, preferably from 5 to 20 mg / l, for example 5 to 15 mg / l, and even more Preferably 10 to 20 mg.1-1 or 10 to 15 mg.1-1. A range of 5 to 25mg.1-1 includes a range of 5 to 15, 5 to 14, 5 to 13, 5 to 12, 5 to 11, 5 to 10, 5 to 9, to 8, 5 to 7 and 5 to 6 mg.1-1, or a range of 10 to 20, 10 to 15, 10 to 14, 10 to 13, 10 to 12, 10 to at 11 mg. A preferred concentration of the compound of formula (I) is 12.5 mg. Also described are cellular systems (ie sets of cells organized together, said cells having been isolated from the body of a donor subject, for example a living being or a brain dead being whose organs are artificially kept functional), for example the composition of cells, tissues, organs or part of organs, brought into contact in vitro or ex vivo with a compound of interest according to the invention, said cellular systems being intended to be used as a graft, as well as kits comprising at least one of these cellular systems. The invention also covers kits, in particular: a kit for carrying out a method for preserving or preserving cells, tissues and / or organs (known as a kit for preserving or preserving cells, tissues and / or organs ") comprising at least one compound according to the invention, and preferably a cellular system as defined above intended to be brought into contact with said compound according to the invention; a kit for carrying out a method for preserving or preserving cells, tissues and / or organs (called a "kit for preserving or preserving cells, tissues and / or organs") comprising a compound according to the invention and a reperfusion solution, typically selected from ViaSpanO, 1GL-1e, SCOTO, Celsior0 or Custodio10, Kidney Preservation Solution (KPSO), Machine Preservation Solution (MPSO), SoltranO, Lifor0 and Steen®, and preferably a cellular system such as defined above intended to be brought into contact with said compound according to the invention; a kit comprising at least one cellular system comprising or having been exposed to at least one compound according to the invention, and possibly at least one compound according to the invention that is identical to or different from that already put in contact with the cellular system; a kit for the implementation of a method for preventing or treating the phenomenon of ischemia-reperfusion likely to affect or affecting the subject or the recipient host for which the cells, tissues and / or organs are intended ( called "prevention kit or treatment of I / R syndrome"). The compound of interest according to the invention present in the kit is advantageously selected according to the target subject or recipient host; a kit for carrying out a method for conditioning the subject or the donor host of the cells, tissues and / or organs before the collection of said cells, tissues and / or organs (called "prevention kit or treatment of I / R syndrome "). The compound of interest according to the invention present in the kit is advantageously selected according to the subject or the donor host concerned. a kit comprising a compound according to the invention, preferably a compound of formula (I) in which: A is CH 2 -CH 2 or CH = CH, R 1 and R 3 represent, independently of one another, OH, -OCH3, or -O-C (= O) CH3, preferably R1 = R3 and - R2 is preferably R '\ \ NO-1-GLYC 1-0- <0-I-GLYC or where m is an integer ranging from 1 to 10, preferably 2, 3, 4, 5 or 6, R 'is H or a C 1 -C 3 alkyl, preferably-CH 3, and GLYC is selected from a glucosyl radical, a diglucosyl radical, a galactosyl radical, and a digalactosyl radical, preferably a glucosyl or galactosyl radical, said kit preferably including a universal pocket injector and / or a correspondence table indicating the dose to be used according to the indication (static preservation, dynamic preservation, storage of cells for transport and insulation, etc.). The kits according to the invention may further comprise one or more consumables such as a culture medium, a buffer solution or an explanatory note. The invention also relates to the use of a compound of formula (I) as described above (including corresponding pharmaceutically acceptable salts), or a kit as described above to prepare a composition according to the invention. invention, for preserving or preserving cells, tissues and / or organs, for preventing and / or treating the phenomenon of ischemia-reperfusion, for conditioning the donor subject or host of cells, tissues and / or organs, or to prevent and / or treat heart failure or heart failure. Products comprising or having been exposed to a compound according to the invention (compounds, compositions, cellular systems such as a composition of cells, tissues, organs or parts of organs, and kits) are typically intended for use in a mammal, preferably in a human being. When the compound of interest according to the invention is to be directly put in contact with the donor or recipient host, this "contacting" corresponds to a step of administering said compound to said host. The compound of interest can be administered systemically or locally. Suitable routes of administration include, but are not limited to, the oral, intravenous, intraarterial, intranasal, intradermal, subcutaneous, intramuscular, intraperitoneal, intraocular and intracranial routes. Preferred routes of administration are the oral, intravenous, subcutaneous, intraperitoneal, intranasal, and intracranial routes. The dose to be administered and the administration schedule depend on the subject concerned, in particular, its weight, the chosen route of administration, and its sensitivity to the compound of interest and the desired effect. Those skilled in the art will know, by routine tests, for example by analyzing the disorders developed by the subject, typically by the non-human mammal, or through post-mortem histological studies, to determine the dose and the pattern. adequate administration. Typically, the daily dose to be administered may range from 200 ng / kg to 100 mg / kg, preferably from 0.01 mg / kg to 30 mg / kg. The administration schedule may comprise the administration of a single dose or several doses over several hours, or even days or weeks.

The compound of interest can be formulated using a pharmaceutically acceptable carrier - such as saline or isotonic solution - or using one or more excipients such as a diluent, a binder, a stabilizer, an emulsifier, an adjuvant etc. Alternatively, the compound of interest may be incorporated into the subject's diet or hydration beverage.

The following examples are intended to illustrate more fully the invention without limiting its scope.

EXAMPLES Materials and Methods Part A: Chemistry 1- Synthesis of the compound (s) of interest 5-R / E) -2- (4-methoxyphenypethanyl) -3-methoxyphenol HO MeOH OH K2CO3 PEG 200, MeI Hoe.y.- To a solution of 15.0 g (38.4 mmol, 1 equiv) of Polydatin in 500 mL of polyethylene glycol 200, 16.0 g (115.2 mmol, 3 equiv.) was added. of K2CO3 and 7.5 mL of methyl iodide (115.2 mmol, 3 equiv) are added at 20 ° C. The solution is left at 20 ° C. with stirring for 15 hours TLC control (eluent EtOAc / MeOH 9/1) ) shows that all the starting material is consumed Then a volume of 300 mL of water is added to the solution at 20 ° C. The aqueous phase is extracted with EtOAc (4x100 mL) The organic phases are combined and washed with 2x100 mL of water and 3x100 mL of saturated NaC1, dried over MgSO4, filtered and then evaporated under reduced pressure The product is obtained in the form of a yellow solid (m = 11.61 g, 72%), and is used directly inThe next step: A mass of 11.61 g (27.8 mmol, 1 equiv) of the methyl product is dissolved in 500 mL of MeOH. After complete dissolution, 13.5 ml of H 2 SO 4 are added at 20 ° C., and the solution is then stirred magnetically for 48 hours at 40 ° C. A control by TLC (eluent EtOAc / MeOH 9/1) shows that all the starting material is consumed.

Then 400 ml of NaHCO3 are added at 0 ° C. The aqueous phase is extracted with EtOAc (3x300 mL). The organic phases are combined and washed with 2x300 ml of water and 300 ml of NaCl, dried over MgSO 4, filtered and then evaporated under reduced pressure. After purification on a column (eluent: EtOAc then EtOAc / MeOH: 98/2) the compound I is obtained in the form of a solid (m = 5.36 g, Yd = 75%). NMR 1F1 (400 MHz, CDCl3) 3.81 (s, 3H, OMe), 3.83 (s, 3H, OMe), 6.32 (t, J = 2.2 Hz, 1H, H4), 6.58 (t, J = 1.6 Hz, 1H). , H2), 6.62 (t, J = 1.7 Hz, 1H, H6), 6.88-6.91 (m, 3H, Hc = c, Hr + HO, 7.01 (d, J = 16.2 Hz, 1H, Hc = c), 7.43 (d, J = 8.6 Hz, 2H, H3 +/- H5) NMR 13 C (75MHz, CDCl3) 55.41 (CH3), 55.42 (CH3), 100.30 (C4), 103.80 (C2), 105.43 (C6), 113.89 (Cr + CO, 125.93 (Cd = c), 128.03 (C3, CF5), 128.52 (Cc = c), 129.39 (Cq), 139.35 (Cq), 156.66 (Cq), 158.84 (Cq), 160.44 ( MS m / z = 257 [M + H], 270 [M + Ft + Na].

Viniferine 12b HO OH 2 liters of alcohol dye obtained from 15 kg of extruded sieves diluted in 2 liters of pentane are added to 3.2 liters of a saturated solution of sodium chloride.

The protocol is repeated 3 times. The organic phases are then combined and washed with 2 liters of water saturated with sodium chloride and dried over anhydrous magnesium sulfate. After concentration in vacuo, the dry extract thus obtained is purified on an automatic chromatography column of Combiflash Torrent PHC13 type on a prepacker silica column (750 g) using a gradient obtained from a ternary acetone-isopropanol-pentane mixture. The c-viniferine is thus obtained pure and in crystalline form. Mp = 230 ° C, 1H NMR (DMSO-d6) 7.12 (d, J = 9Hz, 2H, H2a + H6a), 6.66 (d, J = 9Hz, 2H, H3a + H5a), 7.11 (d, J = 8.5 Hz, 2H, H2b H6b), 6.74 (d, J = 8.5 Hz, 2H, H2b + H6b), 5.32 (d, J = 5Hz, 1H, H7a), 4.39 (d, J = 5Hz, 1H, Elsa), 6.81 (d, J = 16.5 Hz, 1H, Elsb), 6.56 (d, J = 16.5 Hz, 1H, H7b), 6.59 (d1, J = 2 Hz, 1H, Hi4b), 6.23 (d, J = 1.5 Hz, 1H, H12a), 6.05 (sl, 1H, H10a + H14a H12b). 13C NMR (DMSO-d6) 160.7, 158.7, 158.6, 157.8, 157.5, 145.5, 134.8, 131.5, 128.9, 127.7, 127.6, 127.0, 121.8, 118.2, 115.6, 115.2, 105.4, 103.1, 101.1, 95.9, 92.4, 55.1 . FAB MS m / z 455 [M + 1] 455 5-R2S, 3S) -6- (acetyloxy) -2-14-acetyloxyphenyl] -4-R / E) -2- (4- (acetyloxy) phenypethenyl] - 2,3-dihydro-3-benzofuranyl] -1,3-diacetate-1,3-benzenediol II HO AcCI AcO Compound II THF, Et3N OAc OH A mass of 6.0 g (0.485 mmol, 1 equiv) of viniferine dissolved in 60 1 ml of anhydrous THF is added to 60 ml of Et 3 N and then at 0 ° C. to a volume of 5.61 ml (0.079 mmol, 6 equiv) of an acetyl chloride solution The reaction medium which has become brown It is left stirring at 20 ° C. for 1 night before being hydrolysed with 60 ml of water The aqueous phase is extracted with 3 × 25 ml of EtOAc The organic phases are combined and washed with 2 × 25 ml of water and 1 ml of saturated NaCl, dried over MgSO 4, filtered and then evaporated under reduced pressure After purification on a column (eluent: EP / EtOAc: 7/3, 65/35, 6/4) the compound II is obtained in the form of a solid (m = 6.14 g, Yd = 70%).) Mp: 78 ° C (ethyl acetate); 1H NMR (400MHz, CDCl3) 7.32 (d, J = 8.5Hz, 2H, H2a + H6a), 7.16 (d, J = 8.6Hz, 1H, H2bH6b), 7.08 (d, J = 8.6Hz, 2H, m.p. H3a + H5a), 6.96 (d, J = 8.6 Hz, 2H, H3b H5b), 6.93 (d, J = 1.9 Hz, 1H, Hi2b), 6.84-6.89 (m, 3H, Hgb H10a H14a H12a), 6.63 ( d, J = 2.0 Hz, 1H, Hi4b), 6.52 (d, J = 16.3 Hz, 1H, H7b), 5.60 (d, J = 6.9 Hz, 1H, H7a), 4.60 (d, J = 6.9 Hz, 1H). , 18-18), 2.33 (s, 3H, CH3), 2.29 (s, 3H, CH3), 2.26 (s, 3H, CH3), 2.25 (s, 6H, OCH3). 13C NMR (75 MHz, CDCl3) 169.55 (Cq), 169.50 (Cq), 168.82 (Cq), 161.05 (Cq), 152.22 (Cq), 151.79 (Cq), 150.80 (Cq), 150.50 (Cq), 1144.51 ( Cq), 138.15 (Cq), 135.45 (Cq), 134.54 (Cq), 130.5 (C8b), 127.87 (C6a + C2a), 1126.83 (C6b + C2b), 124.17 (C7b), 123.97 (Cq), 122.11 (C3a); + C5a), 121.90 (C3b + C5b), 118.70 (Cma + C10a), 114.94 (C12a), 110.82 (C12b) 102.99 (C14b), 92.84 (C7a), 56.83 (C8a), 21.33 (Me), 21.26 (Me). ), 21.22 (0Me) MS m / z = 664 [M + 1, 682 [M + -H + Na], 725 [M + -H + + Na + + K +]) 3- (3,5-dimethoxyphenyl) -2,3-Dihydro-6-methoxy-2- (4-methoxyphenyl) -41 (1E) -2- (4-methoxyphenyl) ethenyl- (2S, 3S) -benzofuran III. To a mass of 0.15 g (0.33 mmol, 1 equiv) of viniferine dissolved in 5 ml of anhydrous DMI under an inert atmosphere is added 78 mg of NaH (0.33 mmol, 6 equiv) at -5 ° C. portion. When the addition is complete, the reaction medium is stirred for 30 minutes at the same temperature. Then 120 11.1 CH3I (0.33 mmol, 6 equiv) are added while maintaining the medium at -5 ° C. When the addition is complete, the temperature of the reaction medium is brought to ambient temperature. After 18h, the medium is hydrolysed with 20 ml of Hz °. The aqueous phase thus obtained is extracted with 3 × 25 mL of EtOAc. The organic phases are combined and washed with 2 × 25 ml of water and 25 ml of saturated NaCl, dried over MgSO 4, filtered and then evaporated under reduced pressure. After purification on a column (eluent: EP / EtOAc: 8/2), the compound III is obtained in the form of a transparent oil (yield = 58%). Transparent oil, 1H NMR (400MHz, CDCl3) 7.28 (d, J = 8.8Hz, 2H, H2a + H6a), 7.12 (d, J = 8.7Hz, 1H, H3a + H5a), 6.87 (d, J = 8.8 Hz, 2H, H6b H2b), 6.86 (d, J = 16.5 Hz, 1H, H8b), 6.77 (d, J = 8 Hz, 2H, H3b H5b), 6.71 (d, J = 2.1 Hz, 1H, Hi2b ), 6.66 (d, J = 16.5 Hz, 1H, H7b), 6.51 (d, J = 2.2 Hz, 1H, Hi4b), 6.35 (s, 3H, H10a + H12a + H14a), 5.51 (d, J = 6) Hz, 1H, H7a), 4.50 (d, J = 6Hz, 1H, H8a), 3.85 (s, 3H, OCH3), 3.79 (s, 3H, OCH3), 3.77 (s, 3H, OCH3), 3.73. (s, 3H, OCH3). 13 C NMR (75 MHz, CDCl3) 161.43 (Cq), 161.24 (Cq), 161.18 (Cq), 159.53 (Cq), 159.35 (Cq), 145.73 (Cq), 135.43 (Cq), 133.69 (Cq), 129.41 ( Cq), 127.71 (C2a + C6a), 126.97 (C3a + C5a), 113.25 (C7b), 119.60 (Cq), 114.06 (C2b + C6b), 114.01 (C3b + C5b), 105.94 (C14a + Cl0a), 102.46 ( C12b), 98.93 (C12a) 95.08 (C14b), 93.04 (C7a), 56.96 (C8a), 55.59 (OMe), 55.38 (OMex2), 55.32 (OMe), 55.30 (OMe). HMRS (ET) calcd for C33H3006 525.227284, found 525.227165. Compound III HO DMF, MeI OH Me0 NaH OMe OMe Dihydroviniferin HO H2 HO Pd / C OH OH The viniferine (0.1 g, 0.22 mmol, 1 equiv.) Is solubilized in a mixture of ethyl acetate-acetic acid (5/1, 15 ml), then degassed under Argon. The palladium on charcoal (5%, 40 mg) is added and the mixture is degassed again using Argon. Hydrogen (15 psi) is then bubbled in the medium for 4 hours. The mixture is filtered on celite, evaporated under reduced pressure. The compound is purified on a silica column and obtained (67 mg) with 67% yield. Transparent oil; RIVIN 1E1 (400 MHz, Acetone d6) 8.57 (sl, 1H, OH), 8.42 (sl, 1H, OH), 8.37 (sl, 2H, OH), 8.19 (sl, 1H, OH), 7.26 (d, J) = 8.5 Hz, 2H, H2a H6a), 6.79 (d, J = 6.45 Hz, 1H, H2b H6b), 6.78 (d, J = 6.3 Hz, 2H, H3b H5b), 6.63 (d, J = 8.6 Hz, 2H) , H3a + H5b), 6.26 (d, J = 2.1 Hz, 1H, Hi2b), 6.24 (t, J = 2.2 Hz, 1H, H12a), 6.16 (d, J = 2.1 Hz, 1H, Hi4b), 6.35 ( d, J = 2.2 Hz, 2H, H10a + H14a), 5.31 (d, J = 5.8 Hz, 1H, H7a), 4.16 (d, J = 5.8 Hz, 1H, Elsa), 2.52-2.68 (m, 4H, CH2-CH2).

RIVIN C (75 MHz, Acetone d6) 36.08 (C7b), 36.47 (C8b), 57.10 (C8a), 94.07 (C7a), 95.59 (C10a), 102.09 (C12a), 107.12 (Ciob + C12b), 109.30 (C14a) ), 115.79 (C3a + C5a), 116.13 (C3b + C5b), 120.20 (Cq), 128.07 (C2a + C6a), 130.19 (C2b + C6b), 133.41 (Cq), 133.84 (Cq), 140.98 (Cq), 147.39 (Cq), 156.29 (Cq), 158.16 (Cq), 159.51 (Cq), 159.79 (Cq), 162.06 (Cq).

HMRS (ET) calcd for C28E124NaO6 479.1479, found 479.146525 3- (3,5-dimethoxyphenyl) -2,3-dihydro-6-methoxy-2- (4-methoxyphenyl) -412- (4-methoxyphenyl) ethyl- (2S); The compound 11 (0.072 g, 0.14 mmol, 1 equiv) is solubilized in an ethyl acetate-acetic acid mixture (5/1, 5H). 9 ml), then degassed under Argon. The palladium on carbon (5%, 25 mg) is added and the mixture is degassed again using Argon. Hydrogen (15 psi) is then bubbled in the medium for 4 hours. The mixture is filtered on celite, evaporated under reduced pressure. Compound V is purified on a silica column and obtained (72 mg) with 99% yield. Yellow oil; 1 H NMR (400 MHz, CDCl 3) 7.16 (d, J = 8.6 Hz, 2H, H 3? H 5?), 6.86 (d, J = 8.8 Hz, 1H, H 2? + H 6?), 6.79 (d, J = 9 Hz, 2H, H6b H2b), 6.70 (d, J = 8.7 Hz, 2H, H3b H5b), 6.39 (m, 1H, H12a), 6.37 (m, 1H, Hi2b), 6.29 (m, 3H, Hi4b ± H14a ± H10a), 6.35 (s, 3H, H10a + H12a + H14a), 5.43 (d, J = 4Hz, 1H, H7a), 4.11 (d, J = 4Hz, 1H, Elsa), 3.80 (s, 6H, OCH3), 3.73 (s, 9H, OCH3), 2.42-2.58 (m, 4H, CH2-CH2). 13 C NMR (75 MHz, CDCl3) 35.33 (C7b), 35.90 (Csb), 55.36 (OMe), 55.47 (OMe), 55.53 (OMe), 55.63 (OMe), 57.05 (C8a), 93.19 (C7a), 93.80 (C10a). ), 98.95 (C12a), 106.22 (C14a + C12b), 107.71 (Ciob), 113.73 (C3b + C5b), 114.17 (C6a + C2a), 120.29 (Cq), 127.09 (C6a + C5a), 129.52 (C6b + C2b) ), 133.85 (Cq), 133.95 (Cq), 140.21 (Cq), 146.15 (Cq), 157.94 (Cq), 159.63 (Cq), 161.24 (Cq), 161.33 (Cq). WALLS (ET) calcd for C33H3506 [1 \ 44H +] 527.2428, found 527.2442.25 Compound VI Synthesis Scheme 1) Demethylation BC13, DCM 2) Cycloaddition [3 + 2]; 12 OH 3) Deacetylation HHN = N% OH Me0 OMe Me0 HO Compound VI 1. Addition of a PEG chain on pD-glucose penta acetate 242- (2-chloroethoxy) eboxylethyl, 2,3,4,64 etraacetate hD-Glucopyranoside To a solution of 2.00 g (5.128 mmol, 1 equiv) of PD-glucose penta acetate in 24 mL of anhydrous CH 2 Cl 2, 1.12 mL (7.71 mmol, 1.5 equiv) of 2- [2- (2-chloroethoxy)). ethoxy] ethanol and 3.2 mL (26 mmol, 5 equiv) of BF3 .Et2O are added at 20 ° C. The solution is stirred magnetically for 20 hours at 20 ° C. A TLC control (eluent EP / EtOAc 40/60) shows that all the starting material is consumed. Then the solution is hydrolysed with 15 mL of NaHCO3 added at 0 ° C. The aqueous phase is extracted with CH2Cl2 (3x15 mL). The organic phases are combined and washed with 2x15 mL of water and 20 mL of saturated NaC1, dried over MgSO4, filtered and then evaporated under reduced pressure. After purification on a column (eluent: EP / EtOAc: 1/9, 2/8, 3/7) the compound II is obtained in the form of a yellow oil (m = 2.33 g, yield = 91%). Rf = 0.53 (EP / EtOAc: 40/60), not visible to UV and revealed using phosphomolybdic acid.

Unranked formula = C201-131012C1 Colorless oil; 1 H NMR (400 MHz, CDCl 3) 5.21 (t, J = 9.4 Hz, 1H, H 3), 5.07 (t, J = 6.3 Hz, 1H, H 4), 4.98 (t, J = 8 Hz, 1H, H 2), 4.64 (d, J = 8.0 Hz, 1H, H1), 4.27 (dd, J = 12.3 Hz, J = 4.7 Hz, 1H, H6), 4.13 (dd, J = 12.2 Hz, J = 2.3 Hz, 1H, H6). ), 3.95 (td, J = 11.0 Hz, J = 3.8 Hz, 1H, H5), 3.80-3.63 (m, 12H, CH2-PEG), 2.10-2.06-2.04-2.02 (4s, 12H, CH3C00). 13 C NMR (75 MHz, CDCl3) 170.6-170.1-169.5-169.4 (4xC0), 100.7 (Cl), 73.0 (C3), 71.7 (C2), 71.2 (C4, CH2), 70.6 (CH2), 70.4 (C5) , 69.0 (CH2), 68.4 (C6, CH2), 61.9-42.8 (2CH2), 20.6 (4xCH3) MS (ES +) m / z = 521.49 [M + Na +] 2-12- (2-azidoethoxy) ethoxy ] ethyl, 2,3,4,6-tetraacetate 13-D-Glucopyrallositle 12 To a solution of 0.5 g (1.003 mmol, 1 equiv) of the compound H in 5 mL of anhydrous DMF at 20 ° C., under an atmosphere of argon is added a mass of 0.33 g (5.015 mmol, 5 equiv) of sodium azide. The solution is heated at 80 ° C. under an argon atmosphere and left stirring for 5 hours. TLC (EtOAc / EP 6/4 eluent) shows that all of the starting material has reacted. The solution is filtered on celite by rinsing with CH 2 Cl 2 and then evaporated. The residue is purified by flash chromatography on silica gel (eluent EtOAc / MeOH: 95/5, 9/1). Azide 12 is obtained in the form of a yellow oil (m = 0.45 g, yield = 88%).

Rf = 0.78 (EtOAc / MeOH: 9/1); not visible with UV and revealed with phosphomolybdic acid. Unranked formula = C201-131012N3 Yellow oil; NMR1F1 (400 MHz, CDCl3) 5.21 (t, J = 9.4 Hz, 1H, H3), 5.07 (t, J = 6.3Hz, 1H, H4), 4.98 (t, J = 8Hz, 1H, H2), 4.64 (d, J = 8.0 Hz, 1H, H1), 4.27 (dd, J = 12.3 Hz, J = 4.7 Hz, 1H, H6), 4.13 (dd, J = 12.2 Hz, J = 2.3 Hz, 1H, H6) , 3.95 (td, J = 11.0 Hz, J = 3.8 Hz, 1H, H5), 3.80-3.63 (m, 10H, CH2-PEG), 3.39 (t, J = 6.8 Hz, 2H, CH2N3), 2.08-2.042 .01-1.99 (4s, 12H, CH3C00). 13 C NMR (75 MHz, CDCl3) 170.6-170.1-169.5-169.4 (4xC0), 100.9 (Cl), 73.0 (C3), 71.9 (C2), 71.5 (C4), 70.8-70.6-70.2-69.2 (C5, 4xCH2) 68.7 (C6), 62.2-55.8 (2xCH2), 20.8 (4xCH3) MS (ES +) m / z = 528.41 [M + Na +] 1- (2-propyn-1-yloxy) -3-methoxy- 5-1 (1E) -2-14-methoxyphenylthienyl-benzene 13 MeO OMe To a solution of 0.1 g (0.325 mmol, 1 equiv) of compound I in 4 mL of anhydrous DMF at 20 ° C, 20 mg ( 0.4875 mmol, 1.5 equiv) of NaH and 44 μL (0.4875 mmol, 1.5 equiv) of propargyl bromide are added at 0 ° C. The solution is stirred magnetically for 1 night at 20 ° C. TLC control (eluent EtOAc / EP 20/80) shows that compound 2 is consumed. Then the solution is neutralized with 10 mL of water added at 0 ° C. The aqueous phase is extracted with EtOAc (3x15 mL). The organic phases are combined and washed with 2x15 mL of water and 15 mL of saturated NaC1, dried over MgSO4, filtered and then evaporated under reduced pressure. After purification on a column (eluent: EP / EtOAc: 95/5, 9/1), the compound 13 is obtained in the form of a solid (m = 0.1013 g, yield = 90%). Rf = 0.57 (EP / EtOAc: 8/2); visible with UV and revealed using phosphomolybdic acid.

Mp: 80.5 ° C; Whitish solid; NMR (400 MHz, CDCl3)? 7.45 (t, J = 8.6Hz, 2H, FI11 + H13), 7.04 (d, J = 16.3Hz, 1H, Hs), 6.88-6.92 (m, 3H, H10 + H14); H7), 6.71 (dd, J = 1.4 Hz, J = 1.9 Hz, 1H, H4), 6.69 (t, J = 1.4 Hz, J = 1.9 Hz, 1H, H6), 6.45 (t, J = 2.24 Hz, 1H, H 2), 4.71 (d, J = 2.4 Hz, 1H, CH 2), 3.83 (s, 6H, OMe), 2.55 (t, J = 2.4 Hz, 1H, CH). 13 C NMR (75 MHz, CDCl 3) δ 160.82 (Cq), 159.39 (Cq), 158.82 (Cq), 139.71 (Cq), 129.76 (C7), 128.88 (Cq), 127.75 (C15 + C13), 126.29 (Cs), 114.06 (C10 + C14), 105.14 (C4), 105.05 (C6), 100.42 (C2) 78.43 (CH), 75.52 (Cq), 55.83 (CH2), 55.31 (OMe), 55.24 (OMe). HMRS (ET) calcd for C19F11903 [1H44H +] 295.1332, found 295.1329. 1- (2-Propyn-1-yloxy) -5-1 (1E) -2-14-phenylethenyl-benzene To a solution of 0.5 g (1.70 mmol, 1 equiv) of compound 13 in 25 g. mL of anhydrous DCM at 0 ° C, 1.830 g (5.10 mmol, 3 equiv) of Bu4NI and 8.5 mL (8.50 mmol, 5 equiv., O1M in DCM) of BC13 are added. The solution is stirred magnetically for 15 minutes at 0 ° C. TLC control (eluent EtOAc / EP 20/80) shows that compound 13 is consumed. Then the solution is neutralized with 10 mL of water added at 0 ° C. The aqueous phase is extracted with EtOAc (3x15 mL). The organic phases are combined and washed with 2x15 mL of saturated Na 2 S 2 O 3 and 15 mL of saturated NaCl, dried over MgSO 4, filtered and evaporated under reduced pressure. After purification on a column (eluent: EP / EtOAc), compound 14 is obtained in the form of a solid (m = 0.130 g, yield = 29%). 1 H NMR (400 MHz, Acetone d6) δ 8.55 (s, 1H, OH), 8.47 (s, 1H, OH), 7.43 (d, J = 8.6 Hz, 2H, H ,, + E113), 7.10 (d, J = 16.2 Hz, 1H, H8), 6.94 (d, J = 16.2 Hz, 1H, H7), 6.83 (t, J = 8.6 Hz, 1H, H10 + H14), 6.70 (m, 1H, H4), 6.67. (m, 1H, H6), 6.39 (t, J = 2.2Hz, H2), 4.76 (d, J = 2.4Hz, 1H, CH2), 3.09 (t, J = 2.4Hz, 1H, CH). 13 C NMR (75 MHz, d6-Acetone) 56.32 (CH2), 76.89 (CH), 79.95 (Cq), 102.21 (C2), 104.91 (C4), 107.49 (C6), 116.46 (C10 + C14), 126.55 (C7) 128.82 (CH + Cl3), 129.73 (CO, 130.06 (Cq), 141.02 (Cq), 158.33 (Cq), 159.57 (Cq), 160.19 (Cq) Compound 15 OAc Ac00Ac N = N OAc 0 HO OH 0.1 Compound 14 (0.376 mmol, 1 equiv) and 0.189 g of compound 12 (0.376 mmol, 1 equiv) are solubilized in EtOH-H2O-BuOH (16-5-5 ml) 20 mg of copper sulfate (0.15 mmol, 0.4 equiv) and 80 mg of sodium ascorbate (0.752 mmol, 2 equiv) are added and the stirring is maintained overnight at room temperature TLC control (eluent EtOAc / EP 1/1 ) shows that the compound 15 is consumed Then 10 ml of water are added The aqueous phase is extracted with EtOAc (3x15 ml) The organic phases are combined and washed with 2x15 ml of water and 15 ml saturated NaCl, dried over MgSO 4, filtered and then evaporated under reduced pressure, after column purification ( eluent: EP / EtOAc) Compound 15 is obtained as an oil (m = 0.192 g; Yield = 66%).

Yellow oil; 1 H NMR (400 MHz, CDCl 3) 8.55 (s, 1H, OH), 8.54 (s, 1H, OH), 8.06 (s, 1H, H max), 7.42 (d, J = 6.7 Hz, 2H, Hu + E 111) , 7.12 (d, J = 16.4 Hz, 1H, Hs), 6.94 (d, J = 16.4 Hz, 1H, H7), 6.84 (d, J = 6.7 Hz, 2H, H10 + H14), 6.78 (t, J). = 1.68 Hz, 1H, H4), 6.65 (t, J = 1.6 Hz, 1H, H6), 6.43 (t, J = 2.2 Hz, 1H, H2), 5.19 (t, J = 9.3 Hz, 1H, H3 sugar) , 5.14 (s, 2H, H15), 4.96 (t, J = 9.8 Hz, 1H, H4 sugar), 4.85 (t, J = 9.7 Hz, 1H, hsucre), 4.70 (d, J = 8.04 Hz, 1H, Hsucre) ), 4.57 (t, J = 5.1 Hz, 1H, Hm), 4.20 (dd, J = 12.3 Hz, J = 4.9 Hz, 1H, H6sugar), 4.03 (dd, J = 12, 2 Hz, J = 2.4 Hz , Hsugar), 3.82-3.89 (m, 6H, H22 ± H5sugar + 2xCH2PEG), 3.43-3.68 (m, 4H, 2xCH2PEG) 1.96 (s, 3H, CH3C00), 1.92 (s, 3H, CH3C00), 1.91 (s). , 3H, CH3C00), 1.89 (s, 3H, CH3C00).

R1VIN 13C (75 MHz, CDCl3) 20.35 (CH3C00), 20.41 (CH3C00), 20.42 (CH3C00), 50.51 (Cm), 62.19 (C15), 62.46 (C6 sugar), 63.48 (C5 sugar), 69.12 (C4 sugar), 69.66 ( CpEG), 69.82 (CpEG), 70.53 (CpEG), 70.80 (CpEG), 70.93 (CpEG), 71.90 (CpEG), 72.10 (C2sugar), 73.26 (Csugar), 101.16 (Cisucre), 101.94 (C2), 104.49 ( C4), 106.90 (C6), 116.19 (C16 + C14), 125.02 (Cm), 126.36 (C7), 128.56 (C13 + C11), 129.37 (Cs), 140.74 (Cq), 143.99 (Cq), 158.04 (Cq). ), 159.36 (Cq), 160.71 (Cq). HMRS (ET) calcd for C37H46N3O15 [M ++ H +] 772.2923, found 772.2924. ## STR6 ## 156 mg (0.202 mmol, 1 equiv) of compound 15 are dissolved in 3 mL of anhydrous methanol. The solution is cooled to 0 ° C. and 44 mg (0.808 mol, 4 equiv) of MeONa are added. The solution is stirred for 2 h and then neutralized with an acidic resin (Amberlist 15) for 20 min. The solution is filtered on sintered and concentrated. Chromatography of the crude reaction product (eluent: DCM / MeOH 9/1) makes it possible to isolate 44 mg (yield 36%) of compound VII in the form of a colorless oil. 1 H NMR (400 MHz, CD 30D) 8.19 (s, 1H, H max), 7.34 (d, J = 8.65 Hz, 2H, E11 + E113), 6.98 (d, J = 16.3 Hz, 1H, Hs), 6.82 (d. , J = 16.4 Hz, 1H, H7), 6.73 (d, J = 8.61 Hz, 2H, Hi + H +4), 6.63 (si, 1H, H4), 6.55 (si, 1H, H6), 6.31 (t, J). = 2.1 Hz, 1H, H2), 5.17 (s, 2H, Hi5), 4.62 (t, J = 4.94 Hz, 1H, Hm), 4.22 (d, J = 7.8 Hz, 1H, Hisgar), 3.78-3.88 ( m, 4H, H22 + H5sugar + H6sugar), 3.51-3.63 (m, 10H, 4xCH2PEG + H6sugar + H4sugar) 3.1-3.22 (m, 2H, H3sugar + H2sugar) - R1VIN 13C (75MHz, CD30D) 52.31 (Cm ), 61.77 (C15), 62.70 (C6 sugar), 69.66 (C4 sugar + C5 sugar), 70.03 (C22), 71.34 (CpEG), 71.38 (Csugar), 71.55 (CpEG), 75.06 (C3 sugar), 77.92 (CpEG), 77.95 (CpEG), 102.51 (C2), 104.40 (Csug), 105.93 (C6 + C4), 116.52 (C10 + C14), 126.58 (C7), 127.05 (Cm), 128.96 (C13 + C11), 130.06 (C8), 130.24 (Cq), 141.42 (Cq), 144.09 (Cq), 158.53 (Cq), 159.78 (Cq), 160.71 (Cq).

HMRS (ET) calcd for C29H37N3Na0ii [M ++ Na] 626.2320, found 626.2318. Synthetic Scheme of Compound VII 12 + 13 Cycloaddition [3 + 2] 1 OAc Ac00Ac N = N OAc 0 16 MeOH MeOH MeOH anhydrous 0 ° C Amberlyst OHOH OMe N = N OH o MeO Compound VII Compound 16 OAc Ac00Ac N 0.280 g of compound 13 (0.952 mmol, 1 equiv) and 0.480 g of compound 12 (0.952 mmol, 1 equiv.) Are solubilized in a mixture of THF-H20-BuOH (24-12-12 ml). ). 51 mg of copper sulphate (0.380 mmol, 0.4 equiv) and 160 mg of sodium ascorbate (1.90 mmol, 2 equiv) are added and stirring is maintained overnight at room temperature. TLC control (eluent EtOAc / EP 1/1) shows that compound 13 is consumed. Then 10 mL of water is added. The aqueous phase is extracted with EtOAc (3x15 mL). The organic phases are combined and washed with 2x15 mL of water and 15 mL of saturated NaCl, dried over MgSO 4, filtered and evaporated under reduced pressure. After purification on a column (eluent: EP / EtOAc), compound 16 is obtained in the form of a yellow oil (m = 0.528 g, yield = 70%). 1 H NMR (400 MHz, CDCl 3) 7.85 (s, 1H, H max), 7.44 (d, J = 8.72 Hz, 2H, H L + H 13), 7.04 (d, J = 16.3 Hz, 1H, H 8), 6.87-6.91 (m, 3H, H 7 H 10 ± H 14), 6.75 (s 1, 1H, H 4), 6.67 (s 1, 1H, H 6), 6.47 (t, J = 2.16 Hz, 1H, H 2), 5.24 (s, 2H, H 15). ), 5.16 (t, J = 9.5 Hz, 1H, H3sugar), 5.05 (t, J = 9.84 Hz, 1H, H4 sugar), 4.96 (t, J = 9.6 Hz, 1H, hsucre), 4.57 (t, J = 4.94 Hz, 1H, Hm), 4.49 (d, J = 7.97 Hz, 1H, Hisgar), 4.22 (dd, J = 12.32 Hz, J = 4.64 Hz, 1H, H6 sugar), 4.15 (dd, J = 12, 2 Hz, J = 2.4 Hz, Hsugar), 3.82-3.89 (111.6H, H22 + H5Sugar + 2xCH2PEG), 3.433.68 (m, 4H, 2xCH2PEG) 2.05 (s, 3H, CH3C00), 2.04 (s, 3H, CH3C00), 1.99 (s, 3H, CH3C00), 1.98 (s, 3H, CH3C00).

Compound VII 328 mg (0.410 mmol, 1 equiv.) Of compound 16 are dissolved in 10 mL of anhydrous methanol. The solution is cooled to 0 ° C. and 88 mg (1.64 mmol, 4 equiv) of MeONa are added. The solution is stirred for 2 h and then neutralized with an acidic resin (Amberlist 15) for 20 min. The solution is filtered on sintered and concentrated. Chromatography of the crude reaction product (eluent: DCM / MeOH 9/1) makes it possible to isolate 44 mg (% yield) of compound VII in the form of a colorless oil. 1 H NMR (400 MHz, CD 30D) 8.28 (s, 1H, H max), 7.47 (d, J = 8.72 Hz, 2H, H 1 + 1 - 113), 7.10 (d, J = 16.3 Hz, 1H, H 8) , 6.95 (d, J = 16.4 Hz, 1H, H7), 6.90 (d, J = 8.72 Hz, 2H, H10 + H14), 6.78 (sl, 1H, H4), 6.71 (sl, 1H, H6), 6.47. (S1, 1H, H2), 5.24 (s, 2H, H15), 4.64 (t, J = 4.88 Hz, 1H, Hm), 4.25 (d, J = 7.78 Hz, 1H, Hsugar), 3.89-4.00 (111). , 3H, H22 + H5sugar), 3.83 (dd, J = 2.04 Hz, J = 10.08 Hz), 3.78 (s, 6H, OMe), 3.37-3.68 (m, 10H, 4xCH2PEG + H6sugar + H4sugar) 3.15-3.26 (m, 2H, H3sugar + H2sugar). 13 C NMR (75 MHz, CD30D) 13 C NMR (75 MHz, CD 30 D) 52.26 (C21), 55.73 (OMO, 55.78 (OMe), 61.88 (C15), 62.69 (Csucre), 69.64 (C4 sugar + Cssucre), 70.03 (C22) ), 71.31 (CpEG), 71.36 (Csugar), 71.55 (CpEG), 75.03 (Csugar), 77.92 (CpEG), 77.94 (CpEG), 101.58 (C2), 104.38 (Clsugar), 106.13 (C6 + C4), 115.14 (C10 + C14), 127.05 (C7), 127.21 (Cm), 127.25 (Cq), 128.92 (C13 + C11), 130.07 (Cs), 131.28 (Cq), 141.37 (Cq), 160.73 (Cq), 160.98 ( Cq), 162.48 (Cq) HMRS (ET) calcd for C311142N3011 [M ++ H-], 632.2814 found 632.2821 Compound VIII 1) Protection Me0 OHC NaH, DMF OH 18 19 Viniferin 2) Selective oxidation meo CHO OMe 17 OMe Iji 1) NaBH4, Et20 o 2) SOC12 CI IlPMe3, toluene o CHO Propargyl bromide MeOAc = AcObeta0Ac 17 + 110 Aqueous Wittig N ----- N OAc 112 OMe Me0 Me0 Cycloaddition [3 + 2] OMe Compound VIII OMe Me0 1 OH =: H041.6, .. 0-OH \, 1: ---- N \ N OH MeO OMe5 Compound 17 3.5 g of compound III (6.65 mmol, 1 equiv.) Are solubilized in a THFH20 mixture of water (226-120 mL). To this solution is added at room temperature, a solution of RuC13 at 0.035 M (13.7 mL), then a mixture of Oxone and NaHCO3 (12.2 g / 5.3 g) in small portions over 10 min. The addition is complete, the reaction medium is stirred at room temperature overnight, before being hydrolysed with a saturated solution of Na 2 S 2 O 3. The aqueous phase is extracted with EtOAc (3x15 mL). The organic phases are combined and washed with 2x15 mL of water and 15 mL of saturated NaCl, dried over MgSO 4, filtered and evaporated under reduced pressure. After purification on a column (eluent: EP / EtOAc), the compound 17 is obtained in the form of a colorless oil (m = 1.37 g, yield = 49%). Colorless oil; 1 H NMR (400 MHz, CDCl 3) 9.75 (s, 1H, CHO), 7.22 (d, J = 8.6 Hz, 2H, H 3? H 5?), 6.94 (d, J = 2.32 Hz, 1H, H?), 6.87 (d, J = 8.77 Hz, 2H, H2a + H6a), 6.77 (d, J = 2.28 Hz, 1H, H6), 6.33 (t, J = 2.24 Hz, 1H, H4b), 6.27 (d, J = 2.24 Hz, 2H). , H2b H6b), 5.57 (d, J = 5.57 Hz, 1H, H2), 4.79 (d, J = 5.6, 1H, H3), 3.86 (s, 3H, OMe), 3.79 (s, 3H, OMe), 3.72 (s, 6H, OMe). Compound 18 To a solution of 4-hydroxybenzaldehyde (10 g, 81.9 mmol, 1 equiv) in 50 ml of anhydrous DIVII was added at 0 ° C, 3.473 g of NaH (86.8 mol, 1.06 equiv). The reaction medium under the action of the base thickens. It is then diluted with 30 ml of anhydrous DMF. A solution of propargyl bromide at 80% in tolèune (13.6 ml, 122 mmol, 1.5 equiv) is added dropwise to the reaction medium, still maintained at 0 ° C. After the addition is complete, the medium is stirred and the temperature is raised to RT. After 6h, the medium is hydrolysed with 40 ml of water. The aqueous phase is extracted with EtOAc (3x15 mL). The organic phases are combined and washed with 25 ml of water and 2 × 25 ml of saturated NaCl, dried over MgSO 4, filtered and then evaporated under reduced pressure. After purification on a column (eluent: EP / EtOAc), the compound 18 is obtained in the form of a light brown solid (m = 13.1 g, yield = quantitative).

Mp 85 ° C; 1 H NMR (400 MHz, CDCl 3) 9.89 (s, 1H, CHO), 7.85 (d, J = 8.84 Hz, 2H, H 2 ± H 6), 7.08 (d, J = 8.72 Hz, 2H, H 3 ± H 5), 4.77. (d, J = 2.36 Hz, 2H, CH 2), 2.56 (t, J = 2.4 Hz, 1H, CH).

Compound 19 To a solution of compound 18 (13.1 g, 81.9 mmol, 1 equiv) in 131 mL of DCM was added at RT silica (16.7 g) and NaBH4 (3.19 g). The reaction medium is stirred for 20 minutes, then 20 ml of anhydrous MeOH are added thereto. After stirring for 1 h at RT, the mixture is filtered and the silica is rinsed with acetone. The reaction medium is concentrated in vacuo and the crude compound is used in the next step. To a solution of the above compound (1 g, 6.17 mmol, 1 equiv) in 15.5 mL of anhydrous THF is added at 0 ° C pyridine (64E) and thionyl chloride (2.8 mL, 38.5 mol, 6.25 equiv. .). The reaction medium is stirred for 30 min at 0 ° C. and then 24 h at RT before being hydrolysed (20 mL H 2 O). The aqueous phase is extracted with EtOAc (3x15 mL). The organic phases are combined and washed with 25 ml of water and 2 × 25 ml of saturated NaCl, dried over MgSO 4, filtered and then evaporated under reduced pressure. After purification on a column (eluent: EP / EtOAc), compound 19 is obtained in the form of a brown oil (m = 0.592 g, yield = 53%).

NMR1H NMR (400 MHz, CDCl3) 7.34 (d, J = 8.81 Hz, 2H, H2 +/- H6), 6.96 (d, J = 8.77 Hz, 2H, H3 +/- H5), 4.71 (d, J = 2.4 Hz, 2H) , CH 2), 4.57 (s, 2H, CH 2 Cl), 2.53 (t, J = 2.4 Hz, 1H, CH). Compound I10 To a solution of compound 19 (0.345 g, 0.655 mmol, 1 equiv) in 10 ml of anhydrous toluene previously degassed with Argon is added a solution of trimethylphosphine at 1M in toluene (6.1 mL, 6.09 mmol, 1.1 equiv.) at RT. After stirring for 4 h at RT, a TLC control (EtOAc / PE eluent) shows that compound 19 is consumed. The crude reaction product is then concentrated and the residue obtained is washed with ethyl acetate and dried under vacuum. The compound I10 is thus obtained in the form of a light brown solid (1.32 g, 93%). Mp> 280 ° C, 1 H NMR (400 MHz, CDCl 3) 7.25 (dd, J = 8.84 Hz, J = 2.73 Hz, 2H, H arom), 7.07 (d, J = 8.28 Hz, 2H, H arom), , J = 2.4 Hz, 2H, CH 2), 3.64 (d, J = 18.6 Hz, 2H, CH 2 Cl), 2.98 (t, J = 2.4 Hz, 1H, CH) 1.82 (s, 3H, Me), 1.78 (s). , 6H, Me).

Compound III To a solution of the compound I10 (0.084 g, 0.330 mmol, 2 equiv) in water (1 mL) is added to TA lutine (0.084 g, 0.330 mmol, 2 equiv). The medium is stirred for 30 minutes, then a solution of compound 17 (0.070 g, 0.165 mmol, 1 equiv) in anhydrous THF (0.8 mL) is added. The reaction medium is heated at 90 ° C. for 2 hours. TLC control (eluent EtOAc / EP 2/8) shows that compound 17 is consumed. Then 10 mL of water is added. The aqueous phase is extracted with EtOAc (3x15 mL). The organic phases are combined and washed with 2x15 mL of water and 15 mL of saturated NaCl, dried over MgSO 4, filtered and evaporated under reduced pressure. After purification on a column (eluent: EP / EtOAc), compound III is obtained in the form of a yellow oil (Z / E ratio = 2/1) (m = 0.051 g, yield = 78%). NMR1EI (400 MHz, CDCl3) 7.26 (m, 2H, El3a + H5a), 7.14 (d, J = 8.72 Hz, 2H, H2b + H6b), 6.84-6.89 (m, 5H, H2a + H6a + H3b + H5b ± H7b), 6.73 (d, J = 2.16 Hz, 1H, Hiob), 6.61 (d, J = 16.32 Hz, 1H, H8b), 6.47 (d, J = 2.12 Hz, 1H, Hi2b), 6.36 (s, 3H). , Hioa + Hua + H14a), 5.53 (d, J = 6Hz, El7a), 4.66 (d, J = 2.4Hz, CH2), 4.51 (d, J = 6Hz, Elsa), 3.86 (s, 3H, OMe), 3.80 (s, 3H, OMe), 3.74 (s, 6H, OMe), 2.51 (t, J = 2.4 Hz, CH).

Compound 112 Me0 OAc AcOAcAc NN 0 N 0 OAc 6c 5c o 1 c 0.050 g of compound III (0.095 mmol, 1 equiv) and 0.47 g of compound 12 (0.952 mmol, 1 equiv) are solubilized in an EtOH- H2O-BuOH (4-2.5-2.5 mL). 51 mg of copper sulphate (0.037 mmol, 0.4 equiv) and 19 mg of sodium ascorbate (0.19 mmol, 2 equiv) are added and stirring is maintained overnight at room temperature. TLC control (eluent EtOAc / EP 3/7) shows that compound III is consumed. Then 10 mL of water is added. The aqueous phase is extracted with EtOAc (3x15 mL). The organic phases are combined and washed with 2x15 mL of water and 15 mL of saturated NaCl, dried over MgSO 4, filtered and evaporated under reduced pressure. After purification on a column (eluent: EP / EtOAc), the compound 112 is obtained in the form of a translucent oil (m = 0.061 g, yield = 62%). 1 H NMR (400 MHz, CDCl 3) δ 7.80 (s, 1H, H 5 C), 7.24 (d, J = 8.6 Hz, 2H, H 2a + H 6a), 7.12 (d, J = 8.73 Hz, 2H, H 2bH 6b), 6.83. 6.88 (m, 5H, H3a + Elsa + H3b H5b ± H7b), 6.73 (d, J = 2.16Hz, 1H, Hiob), 6.59 (d, J = 16.29Hz, 1H, H8b), 6.46 (d, J = 2.12 Hz, 1H, Hi2b), 6.36 (s, 3H, H10a + H12a + H14a), 5.51 (d, J = 5.92 Hz, El7a), 5.18 (m, 3H, H3 Sugar + 5.06 (t, J = 9.8 Hz, 1H, H4sugar), 4.97 (m, 1H, H2sugar), 4.49-4.55 (III, 3H, H6c Hsugar), 4.22 (dd, J = 12.3 Hz, J = 4.66 Hz, 1H, H6sugar), 4.15 (dd, J); = 12, 2 Hz, J = 2.4 Hz, 1H, H6sugar), 3.90 (III, 1H, H5sugar), 3.85 (S, 3H, OMe), 3.79 (s, 3H, OMe), 3.73 (s, 6H, OMe) ), 3.55-3.70 (m, 10H, 4xCH2PEG + H7c) 2.05 (s, 3H, CH3C00), 2.04 (s, 3H, CH3C00), 1.99 (s, 3H, CH3C00), 1.98 (s, 3H, CH3C00). Compound VIII MeOH 60 mg (0.0569 mmol, 1 equiv) of the compound III are dissolved in an anhydrous MeOHHF (2-1 mL) The solution is cooled to 0 ° C. and 12.2 is added. mg (0.230 mmol, 4 equiv) Me0Na The solution is stirred e for 2 h and then neutralized with an acidic resin (Amberlist 15) for 20 min. The solution is filtered on sintered and concentrated. Chromatography of the crude reaction product (eluent: DCM / MeOH 9/1) makes it possible to isolate 40 mg (yield 80%) of compound IX in the form of a colorless oil. NMR1E1 (400 MHz, CDCl3) 8.05 (s, 1H, H5), 7.24 (d, J = 8.72Hz, 2H, H2a + H6a), 7.11 (d, J = 8.65Hz, 2H, H2bH6b), 6.84- 6.90 (m, 5H, H3a + Elsa + H3b H5b ± H7b), 6.74 (d, J = 2.08Hz, 1H, Hiob), 6.61 (d, J = 16.32Hz, 1H, H8b), 6.42 (d, J = 2.09 Hz, 1H, Hi2b), 6.37 (t, J = 2.2 Hz, 2H, H10a + H14a), 6.34 (d, J = 2.2Hz, H12a), 5.45 (d, J = 6.48Hz, El7a), 5.12 ( S, 1H, 4.56 (t, J = 4.96 Hz, 2H, H6c), 4.51 (d, J = 6.49, 1H, H8a), 6.24 (dd, J = 7.76 Hz, J = 2.28 Hz, 1H, Hisgar), 3.93 (m, 1H, H4sugar), 3.84 (t, J = 4.84 Hz, H7c), 3.82 (s, 3H, OMe), 3.53-3.58 (m, 15H, 2x0Me + H3sugar + H5sugar + Hsugar + 6xCH2PEG), 3.19 -3.22 (m, 3H, CH2PEG + H2sugar) 13C NMR (75 MHz, CD30D) δ 50.46 (C6), 55.72 (OMe), 55.81 (OMex2), 56.03 (OMe), 58.25 (C7a), 62.35 (C7) ,), 62.71 (Csugar), 69.63 (C4sugar), 70.30 (Csugar), 71.30 (C7), 71.30 (CpEG), 71.35 (CpEG), 71.38 (CpEG), 71.54 (CpEG), 75.03 (C2sugar), 94.54 (Ca), 96.00 (C12b), 99.89 (C10a + C14a), 103.41 (Ciob), 104.40 (Clsugar), 107.07 (C12a), 115. (C3a + C5a), 116.06 (C3b + C5b), 121.13 (Cq), 124.62 (C8b), 126.22 (C5), 128.78 (C2b + C6b), 130.36 (C7b), 131.90 (Cq), 134.77 (Cq); ), 136.63 (Cq), 144.70 (Cq), 144.70 (Cq), 147.08 (Cq), 159.40 (Cq), 161.11 (Cq), 162.75 (Cq), 162.80 (Cq).

HMRS (ET) calcd for C37E146N3NaO5 [M4H-], 908.3576 found 908.3607. Compound IX To a solution of viniferine (100 mg, 0.220 mol, 1 equiv) in anhydrous DCM (5 mL) is added at 0 ° C 49 mg of CaH (1.1 mmol, 5 equiv). After stirring for 1/2 hour at 0 ° C., 6 ml of anhydrous MeOH are added dropwise to the reaction medium. The addition is complete, the medium is left stirring at RT for 12 hours. TLC control shows that viniferine is totally consumed. The reaction medium is then concentrated under vacuum and taken up with 5 mL of ultrapure water and filtered through Celite. After 24h of freeze-drying, compound IX is obtained pure in a yield of 100% in the form of a yellow solid. Mp> 280 ° C, 1H NMR (400MHz, MeOH) δ 7.14 (d, J = 8.5Hz, 2H, H2a + H6a), 7.04 (d, J = 8.6Hz, 1H, H6b H2b), 6.82 (d, J = 16.4 Hz, 1H, H8b), 6.76 (d, J = 8.6 Hz, 2H, H3a + Compound IX H5a), 6.63-6.65 (m, 3H, H3bH5bH12b), 6.57 (d, J = 16.5 Hz, 1H, H7b), 6.25 (d, J = 2Hz, 1H, H14b), 6.16 (m, 3H, Hioa + Hi2a + Hi4a), 5.36 (d, J = 6.52Hz, 1H, H7a), 4.34 (d, J); = 6.61 Hz, 1H, H8a). FAB MS m / z 476 [M + Na + + 42cH].

Compound X Li0 OLi To a solution of viniferine (100 mg, 0.220 mol, 1 equiv) in anhydrous DCM (5 mL) is added at 0 ° C. 700 μl of a solution of CH3Li at 1.6 M in THF. (1.1 mmol, 5 equiv). After stirring for 1/2 hour at 0 ° C., 6 ml of anhydrous MeOH are added dropwise to the reaction medium. The addition is complete, the medium is left stirring at RT for 20 min. TLC control shows that viniferine is totally consumed. The reaction medium is then concentrated in vacuo, and washed with 5 mL of Et 2 O and sintered.

After 24h of lyophilization, the compound X is obtained pure in a yield of 100% in the form of a reddish solid. Mp> 280 ° C, 1H NMR (400 MHz, CDCl 3) 6.97 (d, J = 6.6Hz, 2H, H 2a + H 6a), 6.92 (d, J = 6.6Hz, 1H, H 6bH 2 O), 6.76 (d, J); = 16.2 Hz, 1H, H8b), 6.58 (d, J = 6.5 Hz, 2H, H3a + H5ba), 6.47-6.54 (m, 4H, Hi2b H7b H3b H5b), 6.09 (d, J = 2Hz, 1H, Hioa), 6.06 (d, J = 2Hz, 1H, H14a), 6.03 (d, J = 2Hz, 1H, H12a + Hiob), 5.23 (d, J = 6.2 Hz, 1H, H7a), 4.26 (d , J = 6.2 Hz, 1H, H8a). FAB mb / z 454 [M + 52cH]. Compound XI Na0 ONa To a solution of viniferine (100 mg, 0.220 mol, 1 equiv) in anhydrous DCM (5 mL) is added at 0 ° C 25.5 mg NaH (1.1 mmol, 5 equiv). After stirring for 1/2 hour at 0 ° C., 6 ml of anhydrous MeOH are added dropwise to the reaction medium. The addition is complete, the medium is left stirring at RT for 12 hours. TLC control shows that viniferine is totally consumed. The reaction medium is then concentrated under vacuum and taken up with 5 mL of ultrapure water and filtered through Celite. After 24h of lyophilization, the compound XI is obtained pure in a yield of 100% in the form of a yellow solid. Mp> 280 ° C, 1H NMR (400 MHz, CDCl 3) δ 7.02 (d, J = 8.5 Hz, 2H, H 2a + H 6a), 6.94 (d, J = 8.6Hz, 1H, H 6bH 2b), 6.69 (d, J = 16.2 Hz, 1H, H8b), 6.61 (d, J = 8.5 Hz, 2H, H3a + H5ba), 6.50-6.56 (m, 4H, Hi2b H7b H3b H5b), 6.11 (d, J = 2 Hz, 1H). , 6.08 (d, J = 2Hz, 1H, H14a), 6.06 (d, J = 2Hz, 1H, Hi2a + Hiob), 5.26 (d, J = 6.3Hz, 1H, H7a), d, J = 6.3 Hz, 1H, H8a). FAB MS m / z 498 [M + 2x Na ++ 3xEl]. Part B: Biological Evaluations The benefits of the compounds against ischemia reperfusion injury were tested in two in vitro models reproducing the situations of hot ischemia and cold ischemia. These two models are based on the primary culture of endothelial cells of human aorta, the endothelial cell being the interface between the blood and the organ, therefore the first concerned by the stress of ischemia reperfusion. The involvement of the endothelial cell in the immune response makes it more of a cell type essential in the study of the consequences of ischemia reperfusion. The quality of protection is measured using an 'XTT' kit, the principle of which is the mitochondrial dehydrogenase reduction of tetrazolium salt XTT into a soluble dye. Thus the quantification of the production of this dye (by spectrometry) allows a relative measurement of the amount of mitochondria in the sample. This test makes it possible to control the cells' ability to produce energy and thus their viability. The measurements are normalized to the level of dye present in the control cells (not subject to stress). -Harmal ischemia: in this model, synchronized cells (by 16h in depleted culture medium) are washed in PBS and then incubated in PBS under anoxic conditions (95% N2, 5% CO2), in a humid chamber, at 37 ° C , for 6 hours. At the end of this interval, the cells are washed in PBS and incubated in depleted medium for 20 hours to measure their survival. The molecule tested is used during the anoxic phase, diluted in PBS at the dose of 12.5 mg.1-1.

It is noted that native Viniferin in combination with ethanol is protective against the lesions incurred following the anoxic phase (see Figure 2). The compounds I, VI, VII, IX, X and XI are also capable of protecting the endothelial cells from the lesions incurred following the anoxic phase under the condition of hot ischemia. The results appearing in FIG. 4 show the effectiveness of viniferine in combination with an adjuvant chosen from glycerol, ethanol, polyethylene glycol (PEG) and propylene glycol (PG). Glycerol, polyethylene glycol (PEG) and propylene glycol (PG) are particularly suitable for preservation solutions intended for clinical use. These results demonstrate the possible use of one or other of the compounds I, VI, VII, IX, X and XI with one of said adjuvants. Under these conditions, the synchronized cells are washed in PBS and then incubated in conservation solution University of Wisconsin (UW, one of the two most used in the world) under anoxic conditions (95% N2, 5% CO2), in a humid chamber at 4 ° C for 24 hours. At the end of this interval, the cells are washed in PBS and incubated in depleted medium for 20 hours to measure their survival. The molecule tested is used during the anoxic phase, diluted in the UW at the dose of 12.5 mg.1-1. It is also noted here (see FIG. 4) that native Viniferin, in combination with ethanol, is protective, even very protective, against the lesions incurred following the anoxic / hypothermic phase.

Compounds I, II, IV, VI, VII, VIII, IX, X and XI are also capable of protecting the endothelial cells from the lesions incurred following the anoxic phase under the cold ischemia condition. Compound X is particularly effective. In this model also, we show that the combination of a compound of formula (I) of interest with an adjuvant chosen from glycerol, ethanol, polyethylene glycol (PEG) and propylene glycol (PG), and of Preferably, glycerol, polyethylene glycol (PEG) and propylene glycol (PG) are advantageous (see FIG. 5).

Claims (10)

REVENDICATIONSI. Use of a compound of formula (I) R1 (I) wherein, R1 and R3 represent, independently of one another, -OH, -O124, or -O-C (= O) -R4, R2 represents -H, -OH, -CN, -CF3, NH2, a halogen such as -F, -Cl, -I or -Br, NH2, -NHR5, -N (R5) 2, -OR5, -O-C (= O) -R5 or a radical comprising a glycosyl group and having a molecular weight of less than 1000g.mori, 114 and R5 represent, independently of one another, a C1-C4 alkyl group, A represents CH2- CH 2, CH = CH, a diradical derived from a heteroaryl alkyl or a heteroaryl alkenyl such as a radical of formula (la): R 7 (1a) in which - R 6 represents -OH, -OR 4, or -O- C (= O) -R4 with R4 as defined above, - R7 represents a radical comprising a glycosyl group and having a molecular weight of less than 1000 g.mol1-1, -H, -OH, -CN, -CF3, a halogen as -F, -Cl, -I or -Br, NH2, -NHR5, -N (R5) 2, -OR5, or -O-C (= O) -R5 with R5 being as previously defined, and AI represents CH2 -CH2 or CH = CH, provided that if A is CH = CH, R1, R2 and R3 are not simultaneously -OH and provided that if A is a radical of formula (la) with A1 is CH = CH, R1 R2, R3, R6 and 127ne are not simultaneously -OH; or a salt thereof, for example pharmaceutically acceptable, for the preparation of a composition for preserving or preserving in vivo, in vitro, or ex vivo cells, tissues, organs and / or part (s) member. 2. Use according to claim 1 of a compound of formula (I) wherein A = CH-CH, RI = R2-OMe and R3 = OH or a salt thereof. 3. Use according to claim 1 of a compound of formula (1) in which R2, and / or R7, if present, are chosen from radicals of formula (Ib): X1SPACJ-GLYC (1b), in which - X is 0, S or NR8 with R8 is H or C1-C3 alkyl, preferably X is 0. - SPAC is a spacer group preferably comprising an ethylene glycol or polyethylene glycol unit, n is an integer 1 or 0, and GLYC is a glycosyl radical preferably selected from the group consisting of a glucosyl radical, a diglucosyl radical, a galactosyl radical and a digalactosyl radical. 4. Use according to claim 1 of a compound of formula (I) in which: A is CH2-CH2 or CH = CH, - R1 and R3 represent, independently of one another, -OH, -OCH3 or -O-C (-O) CH3, preferably R1 = R1 and - R2 is preferably 0 GLYC GLYC where m is an integer from 1 to 10, preferably 2, 3, 4, 5 or 6, R 'is H or C 1 -C 3 alkyl, preferably CH 3, and GLYC is selected from a glucosyl radical, a diglucosyl radical, a galactosyl radical, and a digalactosyl radical, preferably a glucosyl or galactosyl radical. 5. Use according to claim 1 of a compound of formula (I) in which the compound of formula (I) is chosen from compounds of formula (II): R7 (u) in which R1, R2, R3, R6, 12.1 and A1 are as defined in claim 1, and the pharmaceutically acceptable salts thereof. 6. Use according to claim 5 of a compound of formula (I), wherein R1, R2, R3 and R6 independently represent -OH, -OCH3, or -O-C (= O) CH3, preferably R1, R2, R3 and R6 are the same, R7 is -H, -OH, -CN, -CF3, halogen such as -F, -Cl, -I or -Br, NH2, -NHRs, -N (R5) 2, - OR5, -O-C (---- O) -R5 with R5 a C1-C4 alkyl, preferably a methyl, or R7 represents a radical of formula -X- [SPAC] -GLYC (lb) in which X is 0, S or NR8 with R8 is H or C1-C3 alkyl, preferably X is 0, SPAC is a spacer group preferably comprising an ethylene glycol or polyethylene glycol unit, n is an integer of 1 or 0 and GLYC is a glycosyl radical, preferably selected from the group consisting of a glucosyl radical, a diglucosyl radical, a galactosyl radical and a digalactosyl radical. 7. Use according to claim 6 of a compound of formula (I) wherein R7 is selected from R '0f GLYC rn GLYC where m is an integer ranging from 1 to 10, preferably 2, 3, 4, 5 or 6 , R 'is H or a C 1 -C 3 alkyl, preferably CH 3, and GLYC is selected from a glucosyl radical, a diglucosyl radical, a galactosyl radical, and a digalactosyl radical, preferably a glucosyl or galactosyl radical. 8. Use according to claim 5 of a compound of formula (I), said compound being chosen from compounds of formula (II) having one of the following combinations of radicals: I. R1-R2-R3-R6-R7 - OH, and AI = CH2-CH2; ii. R1 = R2 = R3 = R6 = R7 = -0Me, and A1 = CH = CH; H1, R1 R2 = R3 = R6 = R7 = -0Me, and AI = CH2-CH2; iv. R1 = R2 = R3 = R6 = -0Me, R7 = H, and A1 = CH-CH; v. R1 = R2 = R3 = R6 = -OH, R7 = F1 and A1 = CH = CH vi. R1 = R2 = R3 = R6 = -0Me, R7 = F and At = CH = CH vii. R1 = R2 = R3 = R5 = -OH, = F and Al = CH = CH; viii. R1 = R2 = R3 = R6 = -OM; R7 = CF3 and AI = CH-CHix. R1 = R2 = R3 = R6 = -OH, R7 = CF3 and AI = CH-CH; x. R1 = R2 = R3 = R6 = -0Me, R7 = -CN and A1 = CH = CH; xi. R1 = R2 = R3 = R6 = -0Me, R1 = -CN and AI = CH-CH; xii. R1 = R2 = R3 = R6 = -OH, R7 = -CN and AI = CH = CH, xiii. R1 = R2 = R3 = R4 - = OH, A1 = CH = CH and R7 is I. R1 = R2 = R3 = R6 = OMe, Ai = CH = CH and OH R7 is xiv. R1 = R2 = R3 = R6 = OH, A1 = C112-CH2 and R7 is OH HO. OH OH xv. R1 = R1 = R3 = R6 = OH, A1 = CH2-CH2, and R7 is with R1 is 1-1 or C1-C3 alkyl, preferably H or C1-13, xvi. R1 = R2 = R3 R = OH, A1 = CH = CH, and R7 is 0 with R 'is H or C1-C3 alkyl, preferably H or CH3, and salts thereof, such as pharmaceutically acceptable salts thereof. 9. Use of a compound of formula (I) as defined in any one of claims 1 to 8 in combination with an adjuvant selected from glycerol, diglycerol, ethanol, polyethylene glycol (PEG) and the propylene glycol (PG). 10. Use of a compound of formula (1) as defined in any one of claims 1 to 9 for the preparation of a composition for preventing or treating ischemia-reperfusion (EN) lesions of cells, tissues , organs and / or part (s) of organ. I 1. An ex vivo static or dynamic preservation composition of cells, tissues, organs and / or part (s) of organ, said composition comprising a compound of formula (I) as defined in any one of claims 1 to 9. In vivo preservation composition of the cells, tissues and / or organs of the donor host, said composition comprising a compound of formula (1) as defined in any one of claims 1 to 9. reperfusion composition or storage or transport composition of a graft in the recipient host, said composition comprising a compound of formula (I) as defined in any one of claims 1 to 9. Composition according to one of the Claims 11 to 13, characterized in that the concentration of the compound of formula (I) is between 5 mgr and 25 mg. 15. Use according to one of claims 1 to 9 wherein the preserved or preserved cells are selected from renal, cardiac, pulmonary, hepatic, corneal, intestinal, vascular, bone, muscle cells, skin cells and progenitor cells. especially endothelial or mesenchymal progenitor cells derived from bone marrow or adipose tissue. 16. Composition according to one of claims 11 to 14 wherein the preserved or preserved cells are selected from renal, cardiac, pulmonary, hepatic, corneal, intestinal, vascular, bone, muscle cells, skin cells and progenitor cells. especially endothelial or mesenchymal progenitor cells derived from bone marrow or adipose tissue. 17, kit for the preservation of cells, tissues and organs comprising: at least one compound as defined in claim 1, preferably as defined in claim 5, and a preservation or reperfusion solution, for example chosen from ViaSpan 1GL-11D, SCOT®, Celsior® or Custodiol®, Kidney Preservation Solution (KPS131)), Preservation Machine Solution (mPse), Soltrane *, Lifar® and Steen®. 18. Kit for static or dynamic preservation, or preservation of cells, tissues, organs and / or part (s) comprising: - at least one compound as defined in claim 1, preferably as defined in claim 4, and - a universal pocket injector, and / or - a correspondence table indicating the dose to be used according to the indication. 19. Use of a kit according to one of claims 17 or 18 for preparing a composition according to one of claims 11 to 14.