GOLD(I) COMPLEXES WITH FLUORINATED CARBENE-HETEROCYCLIC LIGANDS AND THEIR USE AS THERAPEUTIC AGENTS

Abstract

The present invention relates to a cationic or neutral gold(I) complex with fluorinated ligands of the NHC type as well as its uses as an anti-oxidant, anti-cancer, anti-bacterial and / or anti-parasitic agent and in particular an anti-leishmanial agent.

Description

Title of the invention: GOLD(I) COMPLEXES WITH FLUORINATED LIGANDS OF THE JV-HETERO CYCLIC CARBENE TYPE AND THEIR USE AS THERAPEUTIC AGENTS Technical field

[0001] The present invention relates to the general technical field of therapeutic molecules.

[0002] More particularly, the present invention provides new gold(I) complexes with fluorinated ligands of the V-hctcrocyclic carbene type (NHC for "N-heterocyclic carbenes" in English) as anti-oxidant, anti-cancer, anti-bacterial and anti-parasitic agents. These new complexes are particularly useful in the treatment of leishmaniasis. STATE OF THE PRIOR ART

[0003] Currently, the WHO has classified 20 neglected tropical diseases (NTDs) infecting one billion people in low-income populations in 149 countries. Among these NTDs, leishmaniasis threatens more than one billion people mainly in tropical regions such as Brazil, India, East Africa, but also in rich countries, especially around the Mediterranean Sea. In 2007, leishmaniasis was endemic in 88 countries and in 2012 in 98 countries. Note that the increasing number of cases is certainly underestimated because the notification of this disease is mandatory in only 33 / 98 countries concerned.

[0004] Leishmaniasis is an infectious disease caused by parasites of the genus Leishmania, which are transmitted to a host mammal such as, for example, humans, dogs, monkeys or rodents, through the bite of an infected sandfly (Phlebotomus sp. / Lutzomilla sp.).

[0005] Leishmaniasis includes several clinical forms, including visceral leishmaniasis (VL), which is fatal if untreated and causes approximately 20,000 to 30,000 deaths per year worldwide. It is due to the development of the intracellular amastigote form of the parasite, particularly in the liver and spleen, and more specifically in the mononuclear cells of its vertebrate host. The two main Leishmania species responsible for VL are L. infantum and L. donovani.

[0006] Concerning the treatment of leishmaniasis and in particular VL, there are currently few effective and safe drugs: amphotericin B, miltefosine, antimonial derivatives, pentamidine and paromomycin. Among them, miltefosine is the only drug available orally. These drugs have various disadvantages. Liposomal amphotericin B is prohibitively expensive. Some have serious side effects such as, for example, the nephrotoxicity of amphotericin B, the teratogenicity of miltefosine and cardiac arrhythmias and severe pancreatitis for antimonial derivatives. Finally, the latter and miltefosine show a growing lack of efficacy due to the emergence of resistant parasites. Fexinidazole, a 5-nitroimidazole, was recently in phase II clinical trials against VL but clearly showed a lack of efficacy and currently, there is no new chemical molecule entered into clinical trials.

[0007] The fight against leishmaniasis by traditional approaches, such as vector control and patient treatment, is hampered primarily by the difficulty of identifying new, inexpensive molecules capable of supporting industrial processes, secondly by the rapid development of drug resistance and thirdly by the lack of access to drugs for endangered populations. These issues are at the heart of WHO's concerns regarding the control of tropical diseases. It is necessary to strengthen basic knowledge by original approaches regarding the activity of a promising group of active molecules in the treatment of leishmaniasis.

[0008] In recent years, inventors have been working on the development of cationic and neutral gold(I) A^-heterocyclic carbene (NHC) complexes for biomedical applications, particularly for parasitic diseases.

[0009] In 2015, Paloque et al synthesized and tested cationic and neutral complexes of gold(I) with N-heterocyclic carbene ligand (NHC) functionalized by a quinoline [1]. The neutral complex of gold(I) with NHC ligand substituted by a methyl and a quinoline ("complex 6") is the most interesting of the complexes tested with a median inhibitory concentration (IC50) of 0.96 pM ± 0.55 pM and a selectivity index (SI) of 9.84 with SI = CC50 / IC50, CC50 = cytotoxicity concentrations of 50% on the murine macrophage cell line J774A.1 and this, against the amastigote stage of L. infantum.

[0010] In Zhang et al, 2018 [2], nine neutral gold(I) complexes with NHC ligand functionalized by at least one aryl group were tested in vitro on the pro-mastigote and axenic amastigote stages of L. infantum and compared to three anti-leishmanial drugs (amphotericin B, miltefosine and pentamidine). The complex in which the carbene is substituted by a benzyl and a mesityl presents, with respect to the amastigote stage, the lowest median inhibitory concentration (IC50) value (0.19 pM) and the highest selectivity index (SI) (40.29) with SI = CC50 / IC50 where CC50 = 50% cytotoxicity concentrations on the murine macrophage cell line J774A.1

[0011] Cationic gold(I) complexes comprising two NHC ligands substituted by triclosan have also been studied and tested on P. falciparum and L. infantum [3]. These complexes show little or no activity against the promastigote stage of L. infantum. On the other hand, two of these complexes referenced “complex 2a” and “complex 2e” are particularly effective against the axenic amastigote stage of L. infantum with respective IC50s of 0.21 pM and 0.39 pM.

[0012] NHC-based Au(I) and Ru(II) heterobimetallic complexes have also been described by Boselli et al, 2015 [4]. Both metals involved in these complexes are known for their biological activity, with the ruthenium(II)-containing unit also exhibiting luminescence properties. These complexes have much lower biological activities compared to the corresponding NHC-based Au(I) complexes.

[0013] It should also be emphasized that cationic and neutral gold(I) complexes with NHC ligand are not only known for their anti-leishmanial activity but also as anti-oxidant, anti-cancer, anti-bacterial and anti-parasitic agents [5].

[0014] Finally, gold(I) complexes with NHC ligand substituted by fluorinated radicals have already been described in the state of the art. For example, Perez et al, 2019 prepared neutral gold(I) complexes with NHC ligand substituted by a -C6F5 radical (complex 4c), these complexes being described as useful as catalytic precursors for reactions catalyzed by coining metals [6].

[0015] Due to their therapeutic interest and in particular in the context of a treatment against leishmaniasis, the inventors set themselves the goal of identifying new neutral or cationic complexes of gold(I) with NHC ligand which do not have the disadvantages of current anti-leishmanial drugs, are easy to synthesize and have an activity and selectivity at least identical and even superior to those of current drugs and / or those of the neutral or cationic complexes of gold(I) with NHC ligand already described. Statement of the invention

[0016] The present invention makes it possible to achieve the goal set by the inventors and to resolve all or part of the drawbacks of the reference drugs currently used in the treatment of leishmaniasis.

[0017] Indeed, the inventors' work has shown that the introduction of fluorinated ligands into gold(I) complexes with NHC-type ligands makes it possible to significantly increase the selectivity of the complexes thus obtained on the axenic amastigote form of L. infantum compared to the selectivity of the neutral or cationic gold(I) complexes with NHC ligand already described. It was not at all obvious that the introduction of fluorine atoms into these complexes would have such a consequence.

[0018] The results in terms of activity and selectivity of neutral or ca- complexes The NHC-type fluorinated ligand gold(I) complexes according to the invention are in the same range as those of the reference drugs currently used. Furthermore, the complexes, the subject of the present invention, are easily obtained by a synthesis in a few steps and easy purification with high yields.

[0019] Thus, the present invention relates to a gold(I) complex corresponding to one of the following formulas (I) or (II):

[0020] [Chem.l]

[0021] [Chem.2] (II)

[0022] in which • Ri, R2, R3, R4 and R5, identical or different, are independently selected from the group consisting of H, F, CnF2n+i, OCnF2n+i and SCnF2n+i with n equal to 1, 2, 3 or 4, provided that at least one of RB R2, R3, R4 and R5 is H and at least one other of Rb R2, R3, R4 and R5 is selected from the group consisting of F, CnF2n+i, OCnF2n+i and SCnF2n+1; • R' represents an optionally substituted alkyl group or an optionally substituted aryl group; • Y represents a halogen or a -SX group with X representing a residue of a ose with 5 or 6 atoms or one of its derivatives; and • Z represents a halide union, a nitrate anion (-NO3) or a non-coordinating anion.

[0023] When the gold(I) complex according to the invention corresponds to formula (I), this complex is a neutral gold(I) complex with a fluorinated ligand of the N-heterocyclic carbene type. It can also be designated by the expressions “neutral gold(I) complex with a fluorinated ligand of the NHC type”, “neutral gold(I) complex based on a fluorinated A-heterocyclic carbene” or even “neutral gold(I) complex based on a fluorinated NHC”. These expressions are equivalent and can be used interchangeably.

[0024] When the gold(I) complex according to the invention corresponds to formula (II), this complex is a cationic gold(I) complex comprising two fluorinated ligands of N-heterocyclic carbene type. It can also be designated by the expressions "cationic gold(I) complex comprising two fluorinated ligands of NHC type", "cationic gold(I) complex based on fluorinated bis(A-heterocyclic carbene)" or "cationic gold(I) complex based on fluorinated bis(NHC)". These expressions are equivalent and can be used interchangeably.

[0025] Note that, typically, in formula (II), the two Ri are identical, as are the two R2, the two R3, the two R4, the two R5 and the two R'.

[0026] In the gold(I) complexes of formula (I) or (II), Rb R2, R3, R4 and R5, which may be identical or different, are independently selected from the group consisting of H, F, CF3, C2F5, C3F7, C4F9, OCF3, OC2F5, OC3F7, OC4F9, SCF3, SC2F5, SC3F7 and SC4F9, provided that at least one of Rb R2, R3, R4 and R5 is H and at least one other of Rb R2, R3, R4 and R5 is selected from the group consisting of F, CF3, C2F5, C3F7, C4F9, OCF3, OC 2F5, OC3F7, OC4F9, SCF3, SC2F5, SC3F7 and SC4F9.

[0027] This condition, i.e. at least one of Rb, R2, R3, IC and R5 is a hydrogen, in fact excludes the case where the phenyl substituting one of the nitrogens of the carbene is a perfluorinated phenyl, notably described in [6].

[0028] In a particular embodiment of the gold(I) complexes of formula (I) or (II), Rb R2, R3, R, and R5, identical or different, are independently chosen from the group consisting of H, F, CF3, OCF3 and SCF3, provided that at least one of Rb R2, R3, R4 and R5 is H and that at least one other of Rb R2, R3, R4 and R5 is chosen from the group consisting of F, CF3, OCF3 and SCF3.

[0029] In a first embodiment of the gold(I) complexes of formula (I) or (II), one, two, three or four chosen from Rb R2, R3, R4 and R5 are one or more F, the other(s) being H.

[0030] In a first variant of this first embodiment, three chosen from Rb R2, R3, R4 and R5 are F, the others being H. Advantageously, R2, R3 and R5 are F.

[0031] In a second variant of this first embodiment, two chosen from R2, R3, R4 and R5 are F, the others being H. Advantageously, R1 and R4 are F.

[0032] In a third variant of this first embodiment, one of RB R2, R3, R4 and R5 is an F, the others being H. Advantageously, R5 is F.

[0033] In a second embodiment of the gold(I) complexes of formula (I) or (II), one, two, three or four chosen from RB R2, R3, R4 and R5 are one or more CF3, the other(s) being H.

[0034] In a first variant of this second embodiment, three chosen from RB R2, R3, R4 and R5 are CF3, the others being H. Advantageously, R2, R3 and R5 are CF3.

[0035] In a second variant of this second embodiment, two chosen from RB R2, R3, R4 and R5 are CF3, the others being H. Advantageously, Ri and R4 are CF3.

[0036] In a third variant of this second embodiment, one of Rb R2, R3, R4 and R5 is a CF3, the others being H. Advantageously, R5 is CF3.

[0037] In a third embodiment of the gold(I) complexes of formula (I) or (II), one, two, three or four chosen from Rb R2, R3, R4 and R5 are one or more OCF3s, the other(s) being H.

[0038] In a first variant of this third embodiment, three chosen from R 1, R2, R3, R4 and R5 are OCF3, the others being H. Advantageously, R2, R3 and R5 are OCF3.

[0039] In a second variant of this third embodiment, two chosen from R 1, R2, R3, R, and R5 are OCF3, the others being H. Advantageously, R1 and R4 are OCF3.

[0040] In a third variant of this third embodiment, one of RH R2, R3, R4 and R5 is an OCF3, the others being H. Advantageously, R5 is OCF3.

[0041] In a fourth embodiment of the gold(I) complexes of formula (I) or (II), one, two, three or four chosen from RH R2, R3, R4 and R5 are one or more SCF3, the other(s) being H.

[0042] In a first variant of this fourth embodiment, three chosen from Rb R2, R3, R, and R5 are SCF3, the others being H. Advantageously, R2, R3 and R5 are SCF3.

[0043] In a second variant of this fourth embodiment, two chosen from Ri, R2, R3, R4 and R5 are SCF3, the others being H. Advantageously, Ri and R4 are SCF3.

[0044] In a third variant of this fourth embodiment, one of Rb R2, R3, R4 and R5 is an SCF3, the others being H. Advantageously, R5 is SCF3.

[0045] By “alkyl group” is meant an alkyl group, linear, branched or cyclic, comprising from 1 to 15 carbon atoms, in particular from 1 to 12 carbon atoms and, in particular, from 1 to 8 carbon atoms, said alkyl group possibly comprising at least one heteroatom and / or at least one carbon-carbon double or triple bond.

[0046] By "heteroatom" is meant, in the context of the present invention, an atom chosen from the group consisting of nitrogen, oxygen, phosphorus, sulfur, silicon, fluorine, chlorine and bromine.

[0047] By "substituted alkyl group" is meant, in the context of the present invention, an alkyl group as previously defined substituted by one or more groups, identical or different, chosen from the group consisting of a halogen; an amine; a diamine; a carboxyl; a carboxylate; an aldehyde; an ester; an ether; a thioether; a ketone; a hydroxyl; an optionally substituted alkyl; an amide; a sulphonyl; a sulphoxide; a sulphonic acid; a sulphonate; a nitrile; a nitro; an acyl; an epoxy; a phosphonate; an isocyanate; a thiol; a glycidoxy and an acryloxy.

[0048] By “halogen” is meant, in the context of the present invention, an atom chosen from the group consisting of iodine, fluorine, chlorine and bromine.

[0049] As particular examples of optionally substituted alkyl groups that can be used for R', mention may be made of methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl, heptyl, octyl and nonyl. Advantageously, R' is isopropyl.

[0050] By "aryl group" is meant, in the context of the present invention, any hydrocarbon group comprising an aromatic cycle or several aromatic cycles, identical or different, linked (i.e. fused) or connected by a single bond or by a hydrocarbon chain, an aromatic cycle having from 3 to 20 carbon atoms, in particular from 3 to 14 carbon atoms and, in particular, from 3 to 8 carbon atoms and possibly comprising a heteroatom.

[0051] By "substituted aryl group" is meant, in the context of the present invention, an aryl group as previously defined substituted by one or more groups, identical or different, chosen from the group consisting of a halogen; an amine; a diamine; a carboxyl; a carboxylate; an aldehyde; an ester; an ether; a thioether; a ketone; a hydroxyl; an optionally substituted alkyl; an amide; a sulphonyl; a sulphoxide; a sulphonic acid; a sulphonate; a nitrile; a nitro; an acyl; an epoxy; a phosphonate; an isocyanate; a thiol; a glycidoxy and an acryloxy.

[0052] As particular examples of optionally substituted aryl groups which can be used for R', mention may be made of phenyl, biphenyl, mesityl, benzyl, naphthyl, quinolyl, pyridine, bipyridine, pyrrole, methyl-pyrrole, ethyl-pyrrole, thiophenol and methyl phenyl sulfide. Advantageously, R' is mesityl, benzyl, quinolyl, methyl pyrrole, methyl phenyl sulfide or bipyridine.

[0053] In the gold(I) complexes of formula (I) according to the invention, Y may be a halogen as previously defined. Advantageously, Y is a chlorine or a bromine. In particular, Y is a chlorine.

[0054] Alternatively, in the gold(I) complexes of formula (I) according to the invention, Y may be a -SX group with X representing a residue of a 5 or 6 carbon atom ose or one of its derivatives.

[0055] By "residue of a 5 or 6 carbon atom ose" is meant a residue obtained from the corresponding 5 or 6 carbon atom ose by elimination of a hydroxyl radical. Thus, the covalent bond in formula (I) between S and X involves S and a carbon atom of the residue of a 5 or 6 carbon atom ose.

[0056] By "5-carbon ose" also designated by the term "pentose", we mean in particular deoxyribose, ribose, arabinose, xylose, lyxose, ribulose and xylulose.

[0057] By "6-carbon ose" also designated by the term "(deoxy)hexoses", we mean in particular allose, altrose, galactose, glucose, dextrose, gulose, idose, mannose, talose, fructose, psicose, sorbose, tagatose, fucose and rhamnose.

[0058] These oses can be of L or D configuration.

[0059] By "derivative of a residue of a ose with 5 carbon atoms" and "derivative of a residue of a ose with 6 carbon atoms" is meant a residue of a ose with 5 carbon atoms or with 6 carbon atoms as previously defined in which at least one hydrogen atom and / or at least one hydroxyl radical of a residue of a ose as previously defined is substituted by an atom or a chemical group such as a halogen atom, an alkyl group, a hydroxyalkyl group, a thioalkyl group, a sulfhydryl group, an acetyl group, a silyl group, an acyl group, a sulfonyl group, an amine group, a sulfoalkyl ether group, a sulfate group, a phosphate group, a carboxyl group, a carboxylester group, a quaternary ammonium group, a group glucosyl, a maltosyl group, a chlorotriazinyl group or a quaternary ammonium group.

[0060] As a particular example of a -SX group used in the gold(I) complexes of formula (I), mention may be made of 2,3,4,6-Tetra-O-acetyl-l-thio-[3-D-glucopyranosato.

[0061] In the gold(I) complexes of formula (II), Z may represent a halide anion such as a chloride anion, a fluoride anion, a bromide anion or an iodide anion. Advantageously, Z represents a chloride anion or a bromide anion. In particular, Z represents a chloride union.

[0062] In gold(I) complexes of formula (II), Z may be a non-coordinating union.

[0063] As used herein, the term "uncoordinated union" is used interchangeably with the term "weakly coordinated union" and means a union that either no longer coordinates to a connection or is only weakly coordinated to a connection and thus remains sufficiently flexible to be deflected by a neutral Lewis nozzle. Any uncoordinated union known to those skilled in the art is usable within the scope of the present invention.Conveniently, this non-coordinating union can be chosen from the group consisting of tetrufluoroborute (BF4 ), hexufluorophosphute (PF6 ), benzenesulfonute (CH5SO3 ), bis(trifluoromethunesulfonyl)imide ((N[SO2(CF3)]2) ), methunesulfonute (mesylute, CH3SO3 ), perchlorute (C1O4 ), tetruchlorouluminute (AICI4 ), tetrukis[3,5-bis(trifluoromethyl)phenyl]borute (B[3,5-(CF3)2C6H3]4 ), tetrukis(hexu-fluoroisopropyl)uluminute (A1[OC(CF3)3]4 ), tetrukis(pentufluorophenyl)borute (B[C6F5 ]4 ), p-toluenesulfonute (tosylute, CH3C6H4SO2 ) and trifluoromethunesulfonute (triflute, CF3SO3 ).

[0064] Alternatively, the gold(I) complex of formula (I) may be any of the complexes listed in Tube 1 below.

[0065] The present invention relates to a gold(I) complex according to the present invention for use as a medicament. Such a medicament is usable not only in human medicine but also in veterinary medicine. Therefore, subjects likely to receive such a medicament in particular in the treatment of one or more pathologies as defined below include animals, in particular mammals and, in particular, human beings. More specific examples of such subjects include human beings, non-human primates, dogs, cats, horses, sheep, goats, pigs, sheep, lupins, guinea pigs or rodents.

[0066] Thus, the present invention relates to a pharmaceutical composition comprising, as active principle, a gold(I) complex according to the invention and a pharmaceutically acceptable vehicle.

[0067] By "pharmaceutically acceptable vehicle" is meant according to the present invention any substance which is added to a gold(I) complex according to the present invention to promote its transport, avoid substantial degradation of said composition and / or increase its half-life. Advantageously, such a pharmaceutically acceptable vehicle is sterile and pyrogenic. It is chosen according to the type of application of the pharmaceutical composition of the invention and in particular according to its mode of administration.

[0068] The pharmaceutical composition according to the invention is therefore constituted by at least one gold(I) complex according to the present invention in free form or in the form of a salt. addition with a pharmaceutically acceptable acid, in the pure state or in the form of a composition in which it is associated with any other pharmaceutically compatible product. The pharmaceutical compositions according to the invention can be used systemically; parenterally, for example intravenously, intraarterially, intraperitoneally, intrathecally, intraventricularly, intrasternally, intracranially, intramuscularly or subcutaneously; topically; orally; rectally; intranasally or by inhalation.

[0069] As solid compositions for oral administration, tablets, pills, powders, etc. may be used in which at least one gold(I) complex according to the invention is mixed with one or more inert diluents conventionally used, and optionally with other substances such as, for example, a lubricant, a colorant, a coating, etc.

[0070] As liquid compositions for oral or ocular administration, it is possible to use pharmaceutically acceptable suspensions, solutions, emulsions, syrups containing conventionally used inert diluents, and possibly other substances such as wetting agents, sweeteners, thickeners, etc.

[0071] Sterile compositions for parenteral administration may be aqueous or non-aqueous solutions, suspensions or emulsions. As the solvent or vehicle, water, propylene glycol, vegetable oils or other suitable organic solvents may be used. These compositions may also contain adjuvants, such as wetting agents, isotonizing agents, emulsifiers, etc.

[0072] The compositions for topical administration may be, for example, creams, lotions, mouthwashes, nasal or eye drops or aerosols.

[0073] Those skilled in the art will recognize that the amount of a gold(I) complex according to the invention to be administered will be an amount that is sufficient to induce an improvement in the adverse symptoms to be treated. Such an amount may vary depending, among other things, on factors such as the age, weight, general physical condition of the subject, etc. and may be determined on a case-by-case basis. The amount may also vary depending on the other components of a treatment protocol. Those skilled in the art will recognize that these parameters are normally developed during clinical trials. Furthermore, the administration of a complex according to the present invention may be in single or divided doses.

[0074] As already mentioned in [5], cationic and neutral gold(I) complexes with NHC ligand are not only known for their anti-leishmanial activity but also as anti-oxidant, anti-cancer, anti-bacterial and anti-parasitic agents. The complexes according to the invention are therefore useful in all these therapeutic applications.

[0075] In a first embodiment, the gold(I) complex according to the invention is useful as an antioxidant agent. Thus, the present invention relates to a gold(I) complex according to the present invention or a pharmaceutical composition according to the present invention for use in the treatment and / or prevention of a disorder or pathology in which free radicals are involved. Examples of such disorders or pathologies include aging, coronary heart disease, diabetes, arthritis, epilepsy, stroke, Parkinson's disease, Alzheimer's disease, autoimmune disease and neurodegenerative disease.

[0076] In a second embodiment, the gold(I) complex according to the invention is useful as an anti-cancer agent. It should be noted that this anti-cancer activity may be linked, directly or indirectly, to the aforementioned antioxidant activity. The present invention therefore relates to a gold(I) complex according to the present invention or a pharmaceutical composition according to the present invention for use in the treatment and / or prevention of cancer. By way of illustration and not limitation of cancers, mention may be made of melanoma, colorectal cancer, colon cancer, Kaposi's sarcoma, glioblastoma, ovarian cancer, breast cancer, liver cancer, pancreatic cancer, lung cancer, bladder cancer, prostate cancer or neuroendocrine tumors.

[0077] In a third embodiment, the gold(I) complex according to the invention is useful as an antibacterial agent. Thus, the present invention relates to a gold(I) complex according to the present invention or a pharmaceutical composition according to the present invention for use in the treatment and / or prevention of a disorder or pathology induced by bacteria. By way of illustration and not limitation of such bacteria, mention may be made of Gram- bacteria such as Helicobacter pylori, A cine-tobacter baumannii, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa and Gram+ bacteria such as Enterococcus faecium, Enterococcus faecalis, Staphylococcus epidermidis and Staphylococcus aureus.

[0078] In a fourth embodiment, the gold(I) complex according to the invention is useful as an anti-parasitic agent. Thus, the present invention relates to a gold(I) complex according to the present invention or a pharmaceutical composition according to the present invention for use in the treatment and / or prevention of a disorder or pathology induced by parasites. By way of illustration and not limitation of such parasites, mention may be made of parasites of the genus Trypanosoma such as T. brucei, T. gambiense, T. cruzi, T. equiperdum and T. congolenze, and parasites of the genus Leishmania.

[0079] Indeed, in a particular embodiment of this fourth form of implementation, the gold(I) complex according to the invention is useful as an anti-leishmanial agent. Thus, the present invention relates to a gold(I) complex according to the present invention or a pharmaceutical composition according to the present invention for use in the treatment and / or prevention of leishmaniasis. As illustrative and non-limiting examples of parasites capable of inducing such leishmaniasis, mention may be made of L. donovani, L. infantum, L. chagasi, L. mexicana, L. amazonensis, L. venezuelensis, L. Tropica; L. major; L. aethiopica, L. (Viannia.) braziliensis, L. (V.) guyanensis, L. (V.) panamensis and L. (V.) peruvian.

[0080] In other words, the present invention relates to a method for treating and / or preventing a disorder or pathology as previously defined. This method consists of administering to said subject an effective amount of a gold(I) complex according to the present invention or of a pharmaceutical composition according to the present invention.

[0081] Other characteristics and advantages of the present invention will become apparent to those skilled in the art upon reading the examples below given for illustrative and non-limiting purposes, with reference to the appended [Fig.l]. Brief description of the drawings

[0082] [Fig.l] is a schematic of the synthesis of proligands 6-20 and gold(I) complexes according to the invention 21-40.

[0083] DETAILED DESCRIPTION OF PARTICULAR EMBODIMENTS I. Synthesis of the complexes according to the invention.

[0084] 1.1. Synthesized complexes.

[0085] Table 1 below lists the different complexes synthesized according to the invention. These neutral complexes correspond to the formula (I) as previously defined with the Y group representing either a chlorine atom (“1” in column Y of Table 1) or a 2,3,4,6-Tetra-O-acetyl-l-thio-[3-D-glucopyranosato group (“2” in column Y of Table 1). The -C9H6N group corresponds to a quinolyl group.

[0086] [Tables 1] Table 1 Complexe -Ri -¾ -Rs -r4 -Rs -RJ Y 21 -H -H -H -« -OCF3 -CHrC5Hs 1 22 -cf3 -H -H -cf3 -H -CrirCriL 1 23 -ocf3 -H -H -H -H -CFh-QHs : 1 24 -H -H -H -H -F -CH2-Cg«s : 1 25 -H -H -H -H -cf5 -CH2-C6Hj 1 26 -H -H -H -H -ocf3 CHUri]; 1 27 -CFS -H -H -CF3 -H CHICHE 1 28 -Oc-Fs -H -H -H -H -CHlCHsh 1 29 -H -H -H -H -F -CHiCHjh 1 30 -H -H -H -H -CFS -CH(CHsh 1 31 -H -H -H -H -ocf3 1 32 -cf3 -H -H -cf3 -ri -ÇgH&N 1 33 -QŒj -H -H -H -H -CriLN 1 34 -H -H -H -H -F -CgHjN 1 35 -H -H -H -H -CFj -CgH6N 1 36 -H -H -H -H -OCF3 -CH(CH3)2 2 37 -cf5 -H -H -CFî -H -CHlCHsF 2 38 -OC F 5 -H -H -H -H -CHrCsris 2 39 -cf3 -H -H -cf3 -ri -CHrCsris 2 40 -H -H -H -H -F -ch2-c6h5 2 41 -H -H -H -H -SCF3 -CH2-£sH5 1 42 -H -H -H -H -SCFs -CHPU. 1

[0087] 1.2. Principe de la synthèse.

[0088] Substituted imidazoles 1, 2 and 3 were prepared by copper-catalyzed N-arylation of Timidazole with 4-(trifluoromethoxy)iodobenzene for 1, 1,3-bis(trifluoromethyl)-5-bromobenzene for 2 or 3-(trifluoromethoxy)iodobenzene for 3 in the presence of K2CO3 and CuSO4.

[0089] Proligands 6-8, 11-13 and 16-18 were readily obtained after a quaternization step of 1-benzylimidazole for 6-8, 2-bromopropane for 11-13 and 2-chloroquinoline for 16-18 with l-(4-fluorophenyl)-lH-imidazole ([Fig.l]). Proligands 9, 10, 14, 15, 19 and 20 were readily obtained in one step after a quaternization step of 1-benzylimidazole for 9 and 10, 2-bromopropane for 14 and 15 and 2-chloroquinoline for 19 and 20 with l-(4-fluorophenyl)-l / / -imidazole ([Fig.l]).

[0090] Gold(I) complexes 21-30 were synthesized via the transmetallation route involving the soft base Ag2O, followed by the subsequent addition of Au(SMe2)Cl ([Fig.l]). Gold(I) complexes 31-35 were prepared by direct metalation involving K2CO3 and Au(SMe2)Cl ([Fig.l]). Gold(I) complexes 36-40 were obtained by chloride exchange of complexes 21-23, 27 and 29 with thio-[3-D-glucose tetraacetate] in the presence of NaOH (Scheme 1). Gold(I) complexes 41 and 42 were synthesized via the silver transmetallation route.

[0091] 1.3. Detailed protocol of syntheses.

[0092] A. General protocol for the synthesis of fluoroarylimidazoles 1-5

[0093] In a pressure flask, two equivalents of imidazole, one equivalent of fluoraryl bromide, one equivalent of K2CO3 and a catalytic amount of CuSO4 were mixed at 205°C for 72 h. After cooling to room temperature, the crude product was extracted with MeOH and filtered through a pad of celite to give the desired solid.

[0094] 1-(4-(Trifluoromethoxy)phenyl)-1H-imidazole (1). From imidazole (2.36 g, 34.73 mmol), 4-(trifluoromethoxy)iodobenzene (5 g, 17.36 mmol) and K2CO3 (2.4 g, 17.36 mmol). Yellow solid (2.69 g, 68%). 'H NMR (400 MHz, CDC13): <5 7.66 (t, J = 1.1 Hz, 1H), 7.27-7.19 (m, 2H), 7.17-7.11 (m, 2H), 7.08 (t, J = 1.4 Hz, 1H), 7.01 (t, J = 1.1 Hz, 1H). 13C NMR (101 MHz, CDC13): <5 147.70 (IC), 135.71 (IC), 135.34 (IC), 130.51 (IC), 122.46 (2C), 122.24 (2C), 120.54 (IC), 117.97 (IC). 19F NMR (376 MHz, CDC13): <5 -58.42 (3F). HMRS (ES+): Wedge, for Ci0H8F3N2O 229.0591, found 229.0589.

[0095] l-(3,5-Bis(trifluorométhyl)phényl)-lH-imidazole (2). A partir d’imidazole (2,32 g, 34,12 mmol), l,3-bis(trifluorométhyl)-5-bromobenzène (5 g, 17,06 mmol) et K2CO3 (2,36 g, 17,06 mmol). Solide blanc (3,87 g, 81%). ‘H NMR (400 MHz, CDC13): <5 7.95 (t, J = 1.1 Hz, 1H), 7.89-7.81 (m, 3H), 7.37 (t, J = 1.4 Hz, 1H), 7.23 (t, J = 1.1 Hz, 1H). 13C NMR (101 MHz, CDC13): <5 138.58 (IC), 135.42 (IC), 133.57 (2C), 131.58 (2C), 122.57 (2C), 121.32 (IC), 120.81 (IC), 117.83 (IC). 19F NMR (376 MHz, CDC13 ): <5 -63.27 (6F). HMRS (ES+): Cale, pour CnH7F6N2 281,0512, trouvé 281,0513.

[0096] l-(3dTrifluoromethoxy)phenyl)-lH-imidazole (3). From imidazole (1.42 g, 20.82 mmol), 3-(trifluoromethoxy)iodobenzene (3 g, 10.41 mol) and K2CO3 (1.44 g, 10.41 mol). Yellow solid (1.71 g, 72%). >H NMR (400 MHz, CDC13): <5 7.70 (t, J = 1.1 Hz, 1H), 7.30 (t, J = 8.2 Hz, 1H), 7.16-7.08 (m, 3H), 7.03-6.99 (m, 2H). 13C NMR (101 MHz, CDC13): <5 149.77 (IC), 138.38 (IC), 135.23 (IC), 130.97 (IC), 130.62 (IC), 120.18 (IC), 119.15 (IC), 119.07(lC), 117.72 (IC), 113.81 (IC). 19FNMR (376 MHz, CDC13): <5 -58.23 (3F). HMRS (ES+): Cale, for C10H8F3N2O 229.0591, found 229.0589.

[0097] B. General protocol for the synthesis of benzylimidazolium salts 6-10

[0098] Under a nitrogen atmosphere, a mixture of one equivalent of a fluoroarylimidazole (300 mg) and 1.1 equivalents of benzyl chloride in dry CH3CN (10 mL) was stirred at 80°C for 3 days. The solution was then evaporated, the resulting solid was washed with diethyl ether and dried under vacuum to give the desired solid.

[0099] 3-Benz.yl-l-(4-(trifluoromethoxy)phenyl)-lH-imidaz.ol-3-ium chloride (6). From 1 (300 mg, 1.31 mmol) and benzyl chloride (0.17 mL, 1.44 mmol). White solid (409 mg, 88% yield). 1H NMR (400 MHz, DMSO-t / 6): <5 10.54 (pseudot, J = 1.6 Hz, 1H), 8.44 (t, J = 1.9 Hz, 1H), 8.15 (t, J = 1.8 Hz, 1H), 8.08-7.99 (m, 2H), 7.75-7.65 (m, 2H), 7.64-7.55 (m, 2H), 7.48-7.35 (m, 3H), 5.59 (s, 2H). 13C NMR (101 MHz, DMSO-d6): <5 149.03 (IC), 136.66 (IC), 135.01 (IC), 134.19 (IC), 129.37 (2C), 129.26 (IC), 129.11 (2C), 124.71 (2C), 123.69 (IC), 123.19 (2C), 122.21 (IC), 120.04 (IC), 52.70 (IC). 19F NMR (376 MHz, DMSO-d6): <5 -57.00 (3F). HMRS (ES+): Cale, for C17H14F3N2O, 319.1063, found 319.1058.

[0100] Chlorure de 3-Benzyl-l-(3,5-bis(trifluoromethyl)phenyl)-lH-imidazol-3-ium (7). A partir de 2 (300 mg, 1,07 mmol) et de chlorure de benzyle (0,13 mL, 1,17 mmol). Solide blanc (280 mg, 64% de rendement). 1H NMR (400 MHz, CDC13): <5 11.90 (pseudot, J = 1.6 Hz, 1H), 8.68 (t, J = 2.0 Hz, 1H), 8.57 (s, 2H), 7.88 (t, J = 1.8 Hz, 1H), 7.78 (s, 1H), 7.57-7.47 (m, 2H), 7.24-7.12 (m, 3H), 5.65 (s, 2H). 13C NMR (101 MHz, CDC13): <5 136.74 (IC), 135.88 (IC), 133.69 (2C), 132.84 (IC), 129.40 (IC), 129.19 (2C), 129.05 (2C), 123.68 (IC), 123.27 (IC), 122.55 (2C), 122.18 (2C), 121.81 (IC), 53.51 (IC). 19F NMR: (376 MHz, CDC13): <5 -62.87 (6F). HMRS (ES+): Cale, pour Ci8H13F6N2371,0992, trouvé 371,0983.

[0101] Chlorure de 3-Benzyl-l-(3-(trifluoromethoxy)phenyl)-lH-imidazol-3-ium chloride (8 ). A partir de 3 (300 mg, 1,31 mmol) et de chlorure de benzyle (0,17 mL, 1,44 mmol). Solide blanc (380 mg, 82% de rendement). 1H NMR (400 MHz, DMSO-t / 6): <5 10.73 (pseudot, J = 1.6 Hz, 1H), 8.52 (t, J = 1.9 Hz, 1H), 8.20 (t, J = 1.8 Hz, 1H), 8.05 (d, J = 2.4 Hz, 1H), 7.99 (ddd, J = 8.3, 2.2, 0.8 Hz, 1H), 7.80 (t, J = 8.3 Hz, 1H), 7.66-7.56 (m, 3H), 7.47-7.34 (m, 3H), 5.61 (s, 2H). 13C NMR (101 MHz, DMSO-d6): <5 149.26 (IC), 136.84 (IC), 136.52 (IC), 135.01 (IC), 132.48 (IC), 129.33 (2C), 129.24 (IC), 129.17 (2C), 123.71 (IC), 122.35 (IC), 121.96 (IC), 121.42 (IC), 120.40 (IC), 115.72 (IC), 52.67 (IC). 19F NMR (376 MHz, DMSO-d6): <5 -56.90 (3F). HMRS (ES+): Cale, pour Ci7Hi4F3N2O 319,1063, trouvé 319,1058.

[0102] Chlorure de 3-Benzyl-l-(4-fluorophenyl)-lH-imidazol-3-ium chloride (9). A partir de l-(4-fluorophényl)-l / / -imidazole (4) (303 mg, 1,87 mmol) et de chlorure de benzyle (0,24 mL, 2,05 mmol). Solide blanc (280 mg, 52% de rendement). 1H NMR (400 MHz, DMSO-d6): <5 10.56 (pseudot, J = 1.9 Hz, 1H), 8.40 (t, J = 1.9 Hz, 1H), 8.16 (t, J = 1.8 Hz, 1H), 8.00-7.90 (m, 2H), 7.64-7.57 (m, 2H), 7.58-7.47 (m, 2H), 7.45-7.37 (m, 3H), 5.59 (s, 2H). 13C NMR (101 MHz, DMSO-d6): <5 169.21 (IC), 162.27 (IC), 136.79 (IC), 135.82 (IC), 129.28 (2C), 128.68 (IC), 128.21 (2C), 127.86 (2C), 123.76 (IC), 123.00 (IC), 116.17 (2C), 52.60 (IC). 19F NMR (376 MHz, DMSO-d6): <5 -111.65 (1F). HMRS (ES+): Cale, pour Ci6H14FN2 253,1147, trouvé 253,1141.

[0103] Chlorure de 3-Benzyl-l-(4-(trifluoromethyl)phenyl)-lH-imidazol-3-ium chloride (10 ). A partir de l-(4-(trifluorométhyl)phényl)-l / / -imidazole (5) (500 mg, 2,35 mmol) et de chlorure de benzyle (3,03 mL, 2,59 mmol). Solide blanc (709 mg, 89% de rendement). >H NMR (400 MHz, CDC13): <5 11.53 (pseudot, J = 1.6 Hz, 1H), 8.29 (t, J = 2.0 Hz, 1H), 7.96 (d, J = 8.4 Hz, 2H), 7.67 (t, J = 1.8 Hz, 1H), 7.50-7.41 (m, 4H), 7.11-7.04 (m, 3H), 5.57 (s, 2H). 13C NMR (101 MHz, CDC13): <5 136.87 (IC), 135.97 (IC), 132.91 (IC), 131.52(1C), 129.35 (IC), 129.14 (2Q, 128.97 (2Q, 127.40 (2Q, 123.24 (IC), 122.95 (IC), 121.82 (2Q, 121.17 (IC), 53.23 (IC). 19F NMR (376 MHz, CDC13): <5 -63.04 (3F). HMRS (ES+): Cale, pour C17H14F3N2303,1112, trouvé 303,1109.

[0104] C. General protocol for the synthesis of isopropylimidazolium salts 11-15

[0105] Under a nitrogen atmosphere, one equivalent of a fluoroarylimidazole was dissolved in 2-bromopropane (3 mL). The mixture was stirred at 85°C for 2 days. The solution was then evaporated, the resulting solid was washed with diethyl ether and dried under vacuum to give the desired solid.

[0106] Bromure de 3-Isopropyl-l-(4-(trifluorométhoxy)phényl)-lH-imidazol-3-ium (11). A partir de 1 (318 mg, 1,39 mmol). Solide blanc (217 mg, 45% de rendement). ’H NMR (400 MHz, CDC13): <5 10.89 (pseudot, J = 1.7 Hz, 1H), 8.11 (t, J = 1.9 Hz, 1H), 8.08-7.93 (m, 2H), 7.83 (t, J = 1.9 Hz, 1H), 7.33-7.23 (m, 2H), 5.04 (hept, J = 6.7 Hz, 1H), 1.60 (d, J= 6.7 Hz, 6H). 13C NMR (101 MHz, CDC13): <5 149.70 (IC), 134.53 (IC), 132.70 (IC), 123.78 (2C), 122.48 (2C), 121.53 (IC), 121.32 (IC), 120.10 (IC), 54.01 (IC), 23.02 (2C). 19F NMR (376 MHz, CDC13): <5 -57.96 (3F). HMRS (ES+): Cale, pour Ci3Hi4F3N2O 271.1064, trouvé 271,1058.

[0107] l-(3,5-Bis(trifluoromethyl)phenyl)-3-isopropyl-lH-imidazol-3-ium bromide (12). From 2 (300 mg, 1.07 mmol). White solid (82 mg, 19% yield). 'H NMR (400 MHz, CDCl3): <5 11.36 (pseudot, J = 1.7 Hz, 1H), 8.68-8.58 (m, 2H), 8.43 (t, J = 2.0 Hz, 1H), 8.05 (t, J = 1.9 Hz, 1H), 7.97-7.89 (m, 1H), 5.12 (hept, J = 6.7 Hz, 1H), 1.71 (d, J= 6.7 Hz, 6H). 13C NMR (101 MHz, CDC13): <5 135.89 (IC), 135.56 (IC), 133.79 (2C), 123.61 (IC), 123.15 (2C), 122.21 (IC), 122.04 (2C), 121.90 (IC), 54.57 (IC), 22.98 (2C). 19F NMR (376 MHz, CDC13): <5 -62.70 (6F). HMRS (ES+): Shim, for C14H13F6N2 323.0981, found 323.0983.

[0108] Bromure de 3-Isopropyl-l-(3-(trifluorométhoxy)phényl)-lH-imidazol-3-ium (13). A partir de 3 (300 mg, 1,31 mmol). Solide blanc (460 mg, 100% de rendement). *H NMR (400 MHz, CDC13): <5 10.86 (pseudot, J = 1.7 Hz, 1H), 8.02 (t, J = 2.0 Hz, 1H), 7.90 (t, J = 1.9 Hz, 1H), 7.85 (ddd, J = 8.3, 2.3, 0.8 Hz, 1H), 7.65 (d, J = 2.3 Hz, 1H), 7.42 (d, J = 8.3 Hz, 1H), 7.14 (ddd, J = 8.3, 2.2, 1.1 Hz, 1H), 5.01 (hept, J = 6.7 Hz, 1H), 1.52 (d, J= 6.7 Hz, 6H). 13C NMR (101 MHz, CDC13): <5 149.69 (IC), 135.48 (IC), 134.62 (IC), 131.84 (IC), 121.85 (IC), 121.74 (IC), 121.33 (IC), 120.70 (IC), 120.57 (IC), 114.86 (IC), 54.02 (IC), 22.92 (2C). 19F NMR (376 MHz, CDC13): <5 -58.00 (3F). HMRS (ES+): Cale, pour C13H14F3N2O 271,1063, trouvé 271,1058.

[0109] Bromure de l-(4-Fhiorophényl)-3-isopropyl-lH-imidazol-3-ium (14). A partir de 4 (300 mg, 1,85 mmol). Solide blanc (438 mg, 83% de rendement). 'H NMR (400 MHz, CDC13): <5 10.72 (pseudot, J = 1.7 Hz, 1H), 7.96 (t, J = 2.0 Hz, 1H), 7.87-7.81 (m, 2H), 7.79 (t, J = 1.9 Hz, 1H), 7.11-6.99 (m, 2H), 4.99 (hept, J = 6.7 Hz, 1H), 1.54 (d, J = 6.8 Hz, 6H). 13C NMR (101 MHz, CDC13): <5 162.76 (IC), 134.35 (IC), 130.56 (IC), 124.22 (2C), 121.57 (IC), 121.23 (IC), 117.21 (2C), 53.84 (IC), 23.05 (2C). 19F NMR (376 MHz, CDC13): <5 -110.07 (1F). HMRS (ES+): Cale, pour C12H14FN2 205,1145, trouvé 205,1141.

[0110] Bromure de 3-Isopropyl-1-(4-(trifluoromethyl)phenyl)-lH-imidazol-3-ium (15). A from 5 (500 mg, 2.36 mmol). White solid (490 mg, 62% yield). 'H NMR (400 MHz, DMSO-d6): <5 10.95 (pseudot, J = 1.7 Hz, 1H), 8.22 (t, J = 2.0 Hz, 1H), 8.17-8.08 (m, 2H), 7.83 (t, J = 1.9 Hz, 1H), 7.70-7.56 (m, 2H), 5.00 (hept, J = 6.7 Hz, 1H), 1.57 (d, J = 6.7 Hz, 6H), 1.56. 13C NMR (101 MHz, CDC13): <5 138.36 (IC), 134.65 (IC), 131.66 (IC), 127.46 (2C), 123.09 (IC), 122.42 (2C), 121.73 (IC), 121.48 (IC), 54.14 (IC), 22.99 (2C). 19F NMR (376 MHz, CDC13): <5 -62.98 (3F). HMRS (ES+): Cale, for Ci3Hi4F3N2 255.1116, found 255.1109.

[0111] D. General protocol for the synthesis of quinolylimidazolium salts 16-20

[0112] In a pressure flask, one equivalent of fluoroarylimidazole and 1.05 equivalent of 2-chloroquinoline were mixed at 170°C for 18 h. After cooling to room temperature, the crude product was dissolved in CH2Cl2 and precipitated with diethyl ether, the resulting solid was filtered and dried under vacuum to give the desired solid.

[0113] Chlorure de 3-(Quinolin-2-yl)-1-(4-(trifluoromethoxy)phenyl)-lH-imidazol-3-ium ( 16). A partir de 1 (216 mg, 0,95 mmol) et 2-chloroquinoléine (162 mg, 0,99 mmol). Solide beige (251 mg, 67% de rendement). >H NMR (300 MHz, DMSO-d6): <5 >H NMR 11.19 (pseudot, J = 1.7 Hz, 1H), 8.95 (t, J = 1.9 Hz, 1H), 8.88 (d, J = 8.8 Hz, 1H), 8.72 (t, J = 2.0 Hz, 1H), 8.55 (d, J = 8.8 Hz, 1H), 8.34-8.22 (m, 2H), 8.20-8.10 (m, 2H), 7.95 (ddd, J = 8.4, 6.8, 1.5 Hz, 1H), 7.85-7.59 (m, 3H). 13C NMR (75 MHz, DMSO-d6 ): <5 149.39 (IC), 145.92 (IC), 145.63 (IC), 141.74 (IC), 136.00 (IC), 134.01 (IC), 132.22 (IC), 128.82 (IC), 128.76 (IC), 128.54 (IC), 128.35 (IC), 125.16 (2C), 123.16 (2C), 122.89 (IC), 120.43 (IC), 120.40 (IC), 113.57 (IC). 19F NMR (282 MHz, DMSO-d6) <5 -56.93 (3F). HMRS (ES+): Cale, pour C19H13F3N3O 356,1007, trouvé 356,1011.

[0114] Chlorure de l-(3,5-Bis(trifluoromethyl)phenyl)-3-(quinolin-2-yl)-lH-imidazol-3-ium (17). À partir de 2 (600 mg, 2,13 mmol) et 2-chloroquinoléine (367 mg, 2,24 mmol). Solide beige (396 mg, 42% de rendement). ’H NMR (400 MHz, DMSO-6?6): <5 11.35 (pseudot, J = 1.9 Hz, 1H), 9.01 (t, J = 1.9 Hz, 1H), 8.93-8.91 (m, 4H), 8.5-8.48 (m, 1H), 8.46 (s, 1H), 8.21 (dd,J=8.2, 1.4 Hz, 1H), 8.14 (d,J= 8.5 Hz, 1H), 7.98 (ddd, J = 8.4, 6.9, 1.4 Hz, 1H), 7.80 (ddd, J = 8.1, 6.8, 1.2 Hz, 1H). 13C NMR (101 MHz, DMSO-d6): <5 145.97 (IC), 145.53 (IC), 141.92 (IC), 136.83 (IC), 136.65 (IC), 132.35 (IC), 132.26 (2C), 128.88 (IC), 128.76 (IC), 128.68 (IC), 128.44 (IC), 124.50 (2C), 124.21 (IC), 123.08 (IC), 123.01 (2C), 120.44 (IC), 113.48 (IC). 19FNMR (376 MHz, DMSO-d6) <5 -61.12 (6F). HMRS (ES+): Cale, pour C20H12F6N3 408.0932, trouvé 408.0935.

[0115] Chlorure de 3-(Quinolin-2-yl)-l-(3-(trifluoromethoxy)phenyl)-lH-imidazol-3-ium ( 18). A partir de 3 (216 mg, 0,95 mmol) et 2-chloroquinoléine (163 mg, 0,10 mmol). Solide blanc (206 mg, 53% de rendement). 'H NMR (300 MHz, DMSO-t / 6): <5 11.17 (pseudot, J = 1.9 Hz, 1H), 8.96 (t, J = 1.9 Hz, 1H), 8.90 (d, J = 8.8 Hz, 1H), 8.75 (t, J = 1.8 Hz, 1H), 8.52 (d, J = 8.8 Hz, 1H), 8.27-8.12 (m, 4H), 8.00-7.67 (m, 4H). 13C NMR (101 MHz, DMSO-d6): <5 149.28 (IC), 145.94 (IC), 145.61 (IC), 141.78 (IC), 136.34 (IC), 136.09 (IC), 132.53 (IC), 132.27 (IC), 128.83 (IC), 128.77 (IC), 128.59 (IC), 128.38 (IC), 122.91 (IC), 122.69 (IC), 121.90 (IC), 120.46 (IC), 120.45 (IC), 1116.21 (IC), 113.56 (IC). 19FNMR (376 MHz, DMSO-d6): <5 -56.81 (3F). HMRS (ES+): Cale, pour Ci9Hi3F3N3O 356,1016, trouvé 356,1011.

[0116] Chlorure de l-(4-Fluorophenyl)-3-(quinolin-2-yl)-lH-imidazol-3-ium (19). A partir de 4 (200 mg, 1,23 mmol) et 2-chloroquinoléine (208 mg, 1,27 mmol). Solide beige (165 mg, 42% de rendement). 'H NMR (300 MHz, DMSO-6?6): <5 10.87 (pseudot, J = 1.6 Hz, 1H), 8.92-8.88 (m, 2H), 8.62 (t, J = 1.9 Hz, 1H), 8.38 (d, J = 8.8 Hz, 1H), 8.21-8.06 (m, 4H), 7.97 (ddd, J= 8.5, 6.9, 1.5 Hz, 1H), 7.79 (ddd, J= 8.1, 7.0, 1.2 Hz, 1H). 13C NMR (101 MHz, DMSO-d6): <5 163.00 (IC), 145.97 (IC), 145.66 (IC), 141.80 (IC), 135.67 (IC), 132.30 (IC), 131.59 (IC), 128.83 (IC), 128.77 (IC), 128.60 (IC), 128.34 (IC), 125.43 (2C), 123.08 (IC), 120.38 (IC), 117.51 (2C), 113.40 (IC). 19 F NMR (376 MHz, DMSO-d6): <5 -110.85 (1F). HMRS (ES+): Cale, pour C18H13FN3 290,1093, trouvé 290,1094.

[0117] Chlorure de 3-Quinolyl-l-(4-(trifluoromethyl)phenyl)-lH-imidazol-3-ium (20). A partir de 5 (200 mg, 0,94 mmol) et 2-chloroquinoléine (162,0 mg, 0,99 mmol). Solide beige (292 mg, 83% de rendement). 'H NMR (400 MHz, DMSO-t / 6): <5 11.31 (pseudot, J = 1.6 Hz, 1H), 8.97 (t, J = 1.9 Hz, 1H), 8.88 (d, J = 8.8 Hz, 1H), 8.81 (t, J = 1.9 Hz, 1H), 8.58 (d, J = 8.8 Hz, 1H), 8.38 (d, J = 8.3 Hz, 2H), 8.20-8.11 (m, 4H), 7.96 (ddd, J = 8.2, 6.9, 1.5 Hz, 1H), 7.78 (ddd, J = 8.1, 6.9, 1.2 Hz, 1H). 13C NMR (101 MHz, DMSO-6?6): <5 145.91 (IC), 145.60 (IC), 141.74 (IC), 138.12 (IC), 136.21 (IC), 132.23 (IC), 130.57 (IC), 128.82 (IC), 128.77 (IC), 128.57 (IC), 128.37 (IC), 127.76 (2C), 124.10 (IC), 123.63 (2C), 122.59 (IC), 120.57 (IC), 113.62 (IC). 19F NMR (376 MHz, DMSO-d6): <5 -61.13 (3F). HMRS (ES+): Cale, pour Ci9H13F3N3 340,1063, trouvé 340,1062.

[0118] E. Protocole général pour la synthèse des complexes d’or(I) 21-30

[0119] Under a nitrogen atmosphere and protection from light, one equivalent of an imidazolium salt and 0.48 equivalent of Ag2O were dissolved in dry CH2Cl2 and stirred at room temperature for 18 h. 1.07 equivalent of Au(SMe2)Cl was then added and the resulting mixture was stirred for 2 h. After filtration through a pad of celite, the solvent was removed under pressure and the solid was dried in vacuo to give the desired complex as a white solid.

[0120] Complexe 21. À partir de 6 (100 mg, 0,28 mmol), Ag2O (30 mg, 0,13 mmol) and Au(SMe2) (88 mg, 0,30 mmol). Solide blanc (148 mg, 96% de rendement). *H NMR (300 MHz, DMSO-d6): <5 7.94-7.89 (m, 3H), 7.83 (d, J = 2.0 Hz, 1H), 7.65-7.57 (m, 2H), 7.51-7.32 (m, 5H), 5.49 (s, 2H). 13C NMR (101 MHz, DMSO-d6): <5 169.23 (IC), 148.62 (IC), 138.28 (IC), 136.73 (IC), 129.28 (2C), 128.70 (IC), 128.22 (2C), 127.66 (2C), 123.67 (IC), 123.21 (IC), 122.54 (2C), 120.43 (IC), 54.67 (IC). 19F NMR (376 MHz, DMSO-d6) <5 -56.85 (3F). HMRS (DCI-CH3+): Cale, pour Ci7H13AuF3N2O 515,0635, trouvé 515,0646.

[0121] Complexe 22. À partir de 7 (118 mg, 0,29 mmol), Ag2O (33 mg, 0,14 mmol) et Au(SMe2)Cl (91 mg, 0,31 mmol). Solide blanc (170 mg, 97% de rendement). *H NMR (300 MHz, DMSO-d6): <5 8.61 (s, 2H), 8.38-8.29 (m, 1H), 8.07 (d, J= 2.1 Hz, 1H), 7.86 (d, J = 2.1 Hz, 1H), 7.53-7.32 (m, 5H), 5.50 (s, 2H). 13C NMR (101 MHz, DMSO-6?6): <5 170.07 (IC), 140.82 (IC), 136.57 (IC), 131.60 (2C), 129.25 (2C), 128.71 (IC), 128.24 (2C), 127.07 (2C), 123.75 (IC), 123.41 (IC), 123.22 (IC), 123.20 (2C), 54.74 (IC). 19F NMR (376 MHz, DMSO-d6): <5 -61.26 (6F). HMRS (DCI-CH4+): Cale, pour Ci8Hi2AuF6N2567,0568, trouvé 567,0570.

[0122] Complexe 23. À partir de 8 (103 mg, 0,29 mmol), Ag2O (33 mg, 0,14 mmol) et (91 mg, 0,31 mmol). Solide blanc (150 mg, 94% de rendement). *H NMR (400 MHz, DMSO-d6): <5 7.94-7.81 (m, 4H), 7.73 (dd, J= 8.2 Hz, 1H), 7.58 (ddd, J= 8.3, 2.3, 1.1 Hz, 1H), 7.50-7.33 (m, 5H), 5.49 (s, 2H). 13C NMR (101 MHz, DMSO-d6): <5 169.39 (IC), 148.78 (IC), 140.63 (IC), 136.68 (IC), 131.79 (IC), 129.28 (2C), 128.71 (IC), 128.25 (2C), 124.71 (IC), 123.57 (IC), 123.26 (IC), 121.89 (IC), 120.46 (IC), 118.74 (IC), 54.73 (IC). 19F NMR (376 MHz, DMSO-d6): <5 -56.77 (3F). HMRS (DCI-CH4+): Cale, pour Ci7Hi3AuF3N2O 515,0657, trouvé 515,0646.

[0123] Complexe 24. À partir de 9 (100 mg, 0,35 mmol), Ag2O (39 mg, 0,17 mmol) et Au(SMe2)Cl (112 mg, 0,38 mmol). Solide blanc (146 mg, 86% de rendement). *H NMR (400 MHz, DMSO-d6): <5 7.84 (d, J= 2.0 Hz, 1H), 7.82-7.77 (m, 3H), 7.47-7.34 (m, 7H), 5.47 (s, 2H). 13C NMR (101 MHz, DMSO-d6): <5 169.21 (IC), 162.28 (IC), 136.79 (IC), 135.83 (IC), 129.28 (2C), 128.68 (IC), 128.21 (2C), 127.87 (2C), 123.76 (IC), 123.00 (IC), 116.77 (2C), 54.59 (IC). 19FNMR (376 MHz, DMSO) <5-112.59 (1F). HMRS (ES+): Cale, pour Ci8H16AuFN3 (M+ + CH3CN) 490,1000, trouvé 490,0994.

[0124] Complexe 25. À partir de 10 (100 mg, 0,30 mmol), Ag2O (33 mg, 0,14 mmol) et Au(SMe2)Cl (95 mg, 0,32 mmol). Solide blanc (135 mg, 84% de rendement). 'H NMR (300 MHz, DMSO-d6): <5 8.05-7.97 (m, 4H), 7.95 (d, J = 2.0 Hz, 1H), 7.87 (d, J= 2.1 Hz, 1H), 7.54-7.27 (m, 5H), 5.50 (s, 2H). 13C NMR (75 MHz, DMSO-d6): <5 169.32 (IC), 142.52 (IC), 136.68 (IC), 129.79 (IC), 129.30 (2C), 128.73 (IC), 128.25 (2C), 127.18 (2C), 126.44 (2C), 124.27 (IC), 123.48 (2C), 54.79 (IC). 19F NMR (282 MHz, DMSO-d6): <5 -61.03 (3F).HMRS (ES+): Cale, pour C19H16AuF3N3 (M+ + CH3CN) 540,0962, trouvé 540,0963.

[0125] Complexe 26. À partir de 11 (100 mg, 0,29 mmol), Ag2O (33 mg, 0,14 mmol) et Au(SMe2)Cl (91 mg, 0,31 mmol). Solide blanc (134 mg, 92% de rendement). 'H NMR (400 MHz, DMSO-d6): <5 7.93-7.85 (m, 4H), 7.64-7.58 (m, 2H), 4.99 (hept, J= 6.8 Hz 1H), 1.52 (dd, J= 6.8, 1.5 Hz, 6H). 13C NMR (75 MHz, DMSO-d6): <5 167.60 (IC), 148.54 (IC), 138.49 (IC), 127.59 (2C), 123.59 (IC), 122.53 (2C), 120.44 (IC), 119.59 (IC), 54.41 (IC), 23.16 (2C). 19F NMR (282 MHz, DMSO-d6): <5 -56.84 (3F). HMRS (ES+): Cale. For Ci3H13Auf3N2O 467.07, found 467.06. HMRS (DCI-CH4+): Cale, pour Ci3H13AuF3N2O 467,0647 trouvé 467,0646.

[0126] Complexe 27. À partir de 12 (60 mg, 0,15 mmol), Ag2O (16 mg, 0,07 mmol) et Au(SMe2)Cl (47 mg, 0,16 mmol). Solide blanc (83 mg, 100% de rendement). 'H NMR (300 MHz, DMSO-d6): <5 8.58 (s, 2H), 8.33 (s, 1H), 8.06 (d, J= 2.1 Hz, 1H), 7.96 (d, J = 2.1 Hz, 1H), 5.01 (hept, J = 6.7 Hz, 1H), 1.52 (d, J= 6.7 Hz, 6H). 13C NMR (75 MHz, DMSO-d6): <5 168.42 (IC), 141.01 (IC), 131.61 (2C), 126.92 (2C), 123.62 (IC), 123.19(2C), 123.10 (IC), 119.86 (IC), 54.59 (IC), 23.09 (2C). 19FNMR (376 MHz, DMSO-d6): <5 -61.30 (6F). HMRS (DCI-CH4+): Cale, pour C14H12AuF6N2 519,0544 trouvé, 519,0570.

[0127] Complexe 28. À partir de 13 (101 mg, 0.29 mmol) Ag2O (33 mg, 0.14 mmol) and Au(SMe2)Cl (91 mg, 0.31 mmol). White solid (143 mg, 98% de rendement). 'H NMR (400 MHz, DMSO-d6): <5 7.92-7.90 (m, 2H), 7.88-7.78 (m, 2H), 7.72 (dd, J= 8.1 Hz, 1H), 7.57 (ddd, J= 8.3, 2.2, 1.1 Hz, 1H), 4.99 (hept, J = 6.7 Hz, 1H), 1.52 (d, J= 6.7 Hz, 6H). 13C NMR (101 MHz, DMSO-d6): <5 167.75 (IC), 148.78 (IC), 140.83 (IC), 131.79 (IC), 124.62 (IC), 123.48 (IC), 121.79 (IC), 120.46 (IC), 119.66 (IC), 118.63 (IC), 54.49 (IC), 23.13 (2C). 19F NMR (376 MHz, DMSO-d6): <5 -56.77 (3F). HMRS (DCI-CH4+): Cale, pour C13H13AuF3N2O 467,0646, trouvé 467,0646.

[0128] Complexe 29. À partir de 14 (103 mg, 0,36 mmol) Ag2O (39 mg, 0,17 mmol) et Au(SMe2)Cl (115 mg, 0,39 mmol). Solide blanc (157 mg, 100% de rendement). 'H NMR (400 MHz, DMSO-d6): <5 7.88 (d, J= 2.1 Hz, 1H), 7.82 (d, J= 2.1 Hz, 1H), 7.81-7.73 (m, 2H), 7.49-7.38 (m, 2H), 4.98 (hept, J = 6.7 Hz, 1H), 1.52 (d, J= 6.7 Hz, 6H). 13C NMR (101 MHz, DMSO-d6): <5 167.59 (IC), 162.21 (IC), 136.04 (IC), 127.79 (2C), 123.66 (IC), 119.37 (IC), 116.76 (2C), 54.28 (IC), 23.18 (2C). 19FNMR (376 MHz, DMSO-d6) <5 -112.77 (1F). HMRS (DCI-CH4+): Cale, pour C12H13AuFN2 401,0726, trouvé 401,0728.

[0129] Complex 30. From 15 (100 mg, 0.30 mmol) Ag2O (33 mg, 0.14 mmol) and Au(SMe2)Cl (94 mg, 0.32 mmol). White solid (141 mg, 97% yield). 'H NMR (300 MHz, DMSO-d6): <5 8.07-7.86 (m, 6H), 5.00 (hept, J= 6.7 Hz, 1H), 1.53 (d, J = 6.7 Hz, 6H). 13C NMR (101 MHz, DMSO-d6): <5 167.66 (IC), 142.72 (IC), 129.56 (IC), 127.16 (2C), 126.36 (2C), 124.27 (IC), 123.40 (IC), 119.87 (IC), 54.56 (IC), 23.14 (2C). 19F NMR (282 MHz, DMSO-d6): <5 -61.02 (3F). HMRS (ES+): Cale, for C 15H16AuF3N3 (M+ + CH3CN) 492.0964, found 492.0962.

[0130] F. General protocol for the synthesis of gold(I) complexes 31-35

[0131] Under a nitrogen atmosphere, one equivalent of an imidazolium salt, 1.08 equivalents of Au(SMe2)Cl and two equivalents of K2CO3 were dissolved in 10 mL of acetone and heated under reflux for 18 h. The solvent was then evaporated, the crude product was dissolved in DCM (10 mL) and filtered through a silica pad. The solvent was concentrated in vacuo and the addition of pentane resulted in the precipitation of a solid, which was dried in vacuo to give the desired complex as a white solid.

[0132] Complexe 31. À partir de 16 (63 mg, 0,14 mmol), Au(SMe2)Cl (50 mg, 0,17 mmol) et K2CO3 (44 mg, 0,32 mmol). Solide blanc (39 mg, 41% de rendement). *H NMR (300 MHz, CD3CN): <5 8.63-8.47 (m, 2H), 8.15-8.03 (m, 3H), 7.98-7.85 (m, 3H), 7.73 (ddd, J= 8.2, 6.9, 1.2 Hz, 1H), 7.67 (d, J= 2.1 Hz, 1H), 7.57-7.53 (m, 2H). 13C NMR (101 MHz, CD3CN): <5 169.80 (IC), 149.36 (IC), 149.14 (IC), 146.38 (IC), 139.59 (IC), 138.26 (IC), 131.11 (IC), 128.64 (IC), 128.08 (IC), 127.92 (IC), 127.66 (IC), 127.51 (2C), 123.08 (IC), 121.92 (2C), 121.49 (IC), 117.56 (IC), 116.17 (IC). 19F NMR (376 MHz, CD3CN): <5 -58.66 (3F). HMRS (DCLCH4+): Cale, pour C19H12AuF3 N3O 552,0577, trouvé 552,0598.

[0133] Complexe 32. À partir de 17 (53 mg, 0,12 mmol), Au(SMe2)Cl (38 mg, 0,13 mmol) et K2CO3 (33 mg, 0,24 mmol). Solide blanc (62 mg, 81% de rendement). ’H NMR (300 MHz, DMSO-J6): <5 8.79 (dd, J= 8.5, 1.5 Hz, 1H), 8.76-8.68 (s, 2H), 8.48-8.38 (m, 3H), 8.33 (d, J= 2.2 Hz, 1H), 8.19-8.09 (m, 2H), 7.94 (ddd, J= 8.5, 6.9, 1.5 Hz, 1H), 7.77 (ddd, J = 8.2, 6.9, 1.2 Hz, 1H). 13C NMR (101 MHz, DMSO-J6): <5 170.16 (IC), 149.63 (IC), 146.34 (IC), 141.03 (IC), 140.58 (IC), 131.82 (IC), 131.66 (2C), 128.91 (IC), 128.69 (IC), 128.34 (IC), 128.20 (IC), 127.41 (2C), 124.20 (IC), 123.67 (IC), 123.22 (2C), 122.69 (IC), 116.97 (IC). 19F NMR (376 MHz, DMSO-d6): <5 -61.24 (6F). HMRS (DCI-CH4+): Cale, pour CzoHnAuFgNj 604,0529, trouvé 604,0523.

[0134] Complexe 33. À partir de 18 (90 mg, 0,23 mmol), Au(SMe2)Cl (74 mg, 0,25 mmol) et K2CO3 (64 mg, 0,46 mmol). Solide blanc (65 mg, 48% de rendement). *H NMR (300 MHz, DMSO-J6): <5 8.76 (dd, J= 8.9, 1.2 Hz, 1H), 8.45-8.37 (m, 2H), 8.20-8.08 (m, 3H), 8.02-7.89 (m, 3H), 7.82-7.73 (m, 2H), 7.63 (ddd, J= 8.4, 2.3, 1.1 Hz, 1H). 13C NMR (101 MHz, DMSO-d6): <5 169.42 (IC), 149.73 (IC), 148.80 (IC), 146.33 (IC), 140.82 (IC), 140.44 (IC), 131.88 (IC), 131.74 (IC), 128.91 (IC), 128.64 (IC), 128.26 (IC), 128.15 (IC), 124.99 (IC), 124.08 (IC), 122.59 (IC), 122.26 (IC), 120.50 (IC), 119.05 (IC), 117.07 (IC). 19F NMR (282 MHz, DMSO-d6) <5 -56.76 (3F). HMRS (DCI-CH4+): Cale, pour C19H12AuF3N3O 552,0585, trouvé 552,0598.

[0135] Complexe 34. À partir de 19 (114 mg, 0,35 mmol), Au(SMe2)Cl (112 mg, 0,38 mmol) et K2CO3 (97 mg, 0,70 mmol). Solide blanc (73 mg, 40% de rendement). 1 H NMR (300 MHz, DMSO-d6): <5 8.76 (d, J= 8.7 Hz, 1H), 8.42-8.36 (m, 2H), 8.18-8.09 (m, 3H), 7.95-7.90 (m, 3H), 7.79-7.73 (m, 1H), 7.53-7.47 (m, 2H). 13C NMR (101 MHz, DMSO-d6): <5 169.21 (IC), 162.51 (IC), 149.77 (IC), 146.34 (IC), 140.41 (IC), 136.05 (IC), 131.73 (IC), 128.90 (2C), 128.65 (IC), 128.23 (IC), 128.13 (2C), 124.30 (IC), 122.35 (IC), 117.03 (2C), 116.75 (IC). 19F NMR (282 MHz, DMSO-6?6): <5 -112.05 (1F). HMRS (DCI-CH4+): Cale, pour Cj8H12AuFN3 486,0682, trouvé 486,0681.

[0136] Complexe 35. À partir de 20 (71 mg, 0,19 mmol), Au(SMe2)Cl (62 mg, 0,21 mmol) et K2CO3 (53 mg, 0,38 mmol). Solide blanc (51 mg, 47% de rendement). 'H NMR (400 MHz, DMSO-d6): <5 8.78 (d, J= 8.7 Hz, 1H), 8.48-8.37 (m, 2H), 8.23 (d, J= 2.2 Hz, 1H), 8.20-8.03 (m, 6H), 7.94 (ddd, J= 8.4, 6.9, 1.5 Hz, 1H), 7.77 (ddd, J = 8.1, 6.9, 1.2 Hz, 1H). 13C NMR (101 MHz, DMSO-d6): <5 169.32 (IC), 149.73 (IC), 146.32 (IC), 142.74 (IC), 140.48 (IC), 131.77 (IC), 130.03 (IC), 128.91 (IC), 128.66 (IC), 128.30 (IC), 128.18 (IC), 127.26 (2C), 127.22 (2C), 124.27 (IC), 124.00 (IC), 122.81 (IC), 117.10 (IC). 19F NMR (376 MHz, DMSO-d6): <5 -61.03 (3F). HMRS (DCI-CH4+ ): Cale, pour Ci9Hi2AuF3N3 536,0626, trouvé 536,0649.

[0137] G. Protocole général pour la synthèse des complexes d’or(I) 36-40

[0138] Under a nitrogen atmosphere and protected from light, a Schlenk tube was charged with one equivalent of thio-[3-D-glucose tetraacetate in 2 ml of degassed acetone. One equivalent of 1 M NaOH was added and the mixture was stirred at room temperature for 30 min. After this, the reaction mixture was transferred to a solution of a gold(I) complex (0.9 equivalent) in degassed acetone (2 ml) at 0°C. At the end of the addition, the ice bath was removed and the mixture was stirred for 18 h at room temperature. After evaporation of the solvent, the crude product was dissolved in CH2Cl2 and the solution was filtered through a silica pad. The solvent was concentrated in vacuo and the addition of pentane led to the precipitation of a solid, which was dried in vacuo to give the desired complex as a white solid.

[0139] Complexe 36. A partir de tétraacétate de thio-[3-D-glucose (36 mg, 0,1 mmol) et complexe 21 (50 mg, 0,09 mmol). Solide blanc (55 mg, 70%). *H NMR (300 MHz, CDC13): <5 7.91-7.73 (m, 2H), 7.52-7.32 (m, 7H), 7.20 (d, J= 2.0 Hz, 1H), 7.07 (d, J = 2.0 Hz, 1H), 5.72-5.45 (m, 2H), 5.12 (ddd, J= 9.3, 7.1, 2.1 Hz, 1H), 5.01-4.87 (m, 3H), 4.15 (dd, J= 12.2, 4.9 Hz, 1H), 4.03 (dd, J= 12.2, 2.5 Hz, 1H), 3.66 (ddd, J = 10.0, 4.9, 2.5 Hz, 1H), 2.05 (s, 3H), 2.01 (s, 3H), 1.99 (s, 3H), 1.96 (s, 3H). 13C NMR (101 MHz, CDC13): <5 182.69 (IC), 170.70 (IC), 170.26 (IC), 169.85 (IC), 169.44 (IC), 149.13 (IC), 137.50 (IC), 134.96 (IC), 129.17 (2C), 128.86 (IC), 128.18 (2C), 126.14 (2C), 122.09 (2C), 121.60 (IC), 121.11 (IC), 120.31 (IC), 83.01 (IC), 77.59 (IC), 75.63 (IC), 74.19 (IC), 68.98 (IC), 62.89 (IC), 55.28 (IC), 21.12 (IC), 20.73 (IC), 20.62 (IC), 20.60 (IC). 19F NMR (376 MHz, CDC13): <5 -57.85 (3F). HMRS (DCI-CH4+): Cale, pour C31H33AuF3N2O10S: 879,1437 trouvé 879,1474.

[0140] Complexe 37. À partir de tétraacétate de thio-[3-D-glucose (62 mg, 0,17 mmol) et complexe 22 (91 mg, 0,15 mmol). Solide blanc (93 mg, 59%). 'H NMR (400 MHz, CDC13): <5 8.22 (d, J= 1.5 Hz, 2H), 8.02 (s, 1H), 7.56-7.37 (m, 5H), 7.30 (d, J= 2.0 Hz, 1H), 7.18 (d, J= 1.9 Hz, 1H), 5.75-5.51 (m, 2H), 5.11 (ddd, J= 9.3, 7.4, 1.7 Hz, 1H), 5.02-4.93 (m, 3H), 4.15 (dd, J= 12.2, 5.0 Hz, 1H), 4.03 (dd, J= 12.2, 2.4 Hz, 1H), 3.68 (ddd, J= 10.0, 5.0, 2.4 Hz, 1H), 2.03 (s, 3H), 2.01 (s, 3H), 1.97 (s, 3H), 1.96 (s, 3H). 13C NMR (101 MHz, CDC13): <5 183.69 (IC), 170.76 (IC), 170.25 (IC), 169.78 (IC), 169.55 (IC), 140.33 (IC), 134.62 (IC), 133.25 (2C), 129.33 (2C), 129.10 (IC), 128.18 (2C), 125.21 (IC), 125.18 (IC), 122.83 (IC), 121.92 (IC), 121.28 (IC), 120.64 (2C), 83.03 (IC), 77.46 (IC), 75.71 (IC), 74.26 (IC), 69.01 (IC), 62.91 (IC), 55.50 (IC), 21.03 (IC), 20.70 (IC), 20.65 (2C). 19F NMR (376 MHz, CDC13): <5 -62.78 (6F). HMRS (DCI-CH4+): Cale, pour C32H32AuF6N2O9S: 931.1367 trouvé 931,1398.

[0141] Complexe 38. A partir de tétraacétate de thio-[3-D-glucose (36 mg, 0,1 mmol) et complexe 23 (50 mg, 0,09 mmol). Solide blanc (72 mg, 91%). 'H NMR (400 MHz, CDC13): <5 7.94 (ddd, J= 8.1, 2.1, 0.9 Hz, 1H), 7.67 (dd, J= 8.2 Hz, 1H), 7.49-7.35 (m, 7H), 7.22 (d, J = 2.0 Hz, 1H), 7.08 (d, J = 2.0 Hz, 1H), 5.53-5.49 (m, 2H), 5.10 (ddd, J = 9.5, 8.5, 2.1 Hz, 1H), 5.02-4.84 (m, 3H), 4.13 (dd, J= 12.2, 4.9 Hz, 1H), 4.03 (dd, J= 12.2, 2.4 Hz, 1H), 3.66 (ddd, J= 10.1, 4.9, 2.4 Hz, 1H), 2.04 (s, 3H), 2.02 (s, 3H), 1.99 (s, 3H), 1.97 (s, 3H). 13C NMR (101 MHz, CDC13): <5 182.91 (IC), 170.75 (IC), 170.22 (IC), 169.84 (IC), 169.59 (IC), 149.52 (IC), 140.26 (IC), 134.88 (IC), 131.15 (IC), 129.19 (2C), 128.89 (IC), 128.18 (2C), 123.57 (IC), 121.48 (IC), 121.45 (IC), 121.14 (IC), 120.33 (IC), 117.36 (IC), 83.03 (IC), 77.51 (IC), 75.60 (IC), 74.28 (IC), 68.93 (IC), 62.88 (IC), 55.34 (IC), 21.11 (IC), 20.74 (IC), 20.67 (IC), 20.65 (IC). 19F NMR (376 MHz, CDC13): <5 -57.78 (3F).HMRS (DCI-CH4+): Cale, for C3iH33AuF3N2OioS: 879.1456 found 879.1474. .

[0142] Complex 39. From thio-[3-D-glucose tetraacetate (29 mg, 0.08 mmol) and complex 27 (39 mg, 0.07 mmol). White solid (40 mg, 65%). 'H NMR (400 MHz, CDC13): <5 8.20 (d, J= 1.5 Hz, 2H), 7.99 (s, 1H), 7.31 (d, J= 2.0 Hz, 1H), 7.27 (d, J = 2.1 Hz, 1H), 54 (hept. 5.13-5.02 (m, 2H), 4.99-4.92 (m, 2H), 4.21 (dd, J = 12.2, 5.0 Hz, 1H), 4.06 (dd, J = 12.2, 2.5 Hz, 1H), 3.69 (ddd, J = 9.5, 5.0, 2.4 Hz, 1H), 2.03 (s, 3H), 2.01 (s, 3H), 2.00 (s, 3H), 1.97 (s, 3H), 1.63 (d, J = 6.8 Hz, 6H). 13C NMR (101 MHz, CDC13): <5 182.46 (IC), 170.76 (IC), 170.23 (IC), 169.62 (2C), 140.58 (IC), 133.14 (2C), 125.17 (2C), 123.29 (IC), 122.67 (IC), 121.94 (IC), 121.02 (IC), 118.24 (IC), 82.99 (IC), 77.52 (IC), 75.57 (IC), 74.23 (IC), 68.98 (IC), 62.97 (IC), 54.19 (IC), 23.34 (IC), 23.26 (IC), 20.99 (IC), 20.78 (IC), 20.64 (2C). 19F NMR (376 MHz, CDC13): <5 -62.78 (6F). HMRS (DCI-CH4+): Cale, pour C28H32AuF6N2 O9S: 883,1369 trouvé 883,1398.

[0143] Complexe 40. À partir de tétraacétate de thio-[3-D-glucose (47 mg, 0,13 mmol et complexe 29 (52 mg, 0,12 mmol). Solide blanc (75 mg, 82%). 'H NMR (400 MHz, CDC13): <5 7.79-7.66 (m, 2H), 7.32-7.25 (m, 2H), 7.18 (d, J = 2.0 Hz, 1H), 7.15 (d, J = 2.1 Hz, 1H), 5.23 (hept, J = 6.8 Hz, 1H), 5.11 (, J = 9.2, 7.4, 1.7 Hz, 1H), 5.01-4.84 (m, 3H), 4.20 (dd, J = 12.2, 4.8 Hz, 1H), 4.05 (dd, J = 12.2, 2.4 Hz, 1H), 3.68 (ddd, J = 10.0, 4.8, 2.4 Hz, 1H), 2.06 (s, 3H), 2.03 (s, 6H), 2.02 (s, 3H), 1.57 (d, J = 6.8 Hz, 6H). 13C NMR (101 MHz, CDC13): <5 181.62 (IC), 170.74 (IC), 170.30 (IC), 169.80 (IC), 169.57 (IC), 163.72 (IC), 161.24 (IC), 126.64 (IC), 126.55 (IC), 121.50 (IC), 116.92 (IC), 116.77 (IC), 116.54 (IC), 83.01 (IC), 77.71 (IC), 75.46 (IC), 74.19 (IC), 68.91 (IC), 62.92 (IC), 53.62 (IC), 23.39 (IC), 23.30 (IC,), 21.15 (IC), 20.81 (IC), 20.67 (IC), 20.64 (IC). 19F NMR (376 MHz, CDC13): <5 -111.62 (1F). HMRS (DCI-CH4+): Cale, pour C26H33AuFN2O9S: 765,1528 trouvé 765,1556.

[0144] H. Protocol for the synthesis of precursors of gold(I) complexes 41 and 42 and of these complexes

[0145] l-{4-[(trifluoromethyl)sulfanyl]phenyl}-lH-imidaz.ole (V) of formula (A):

[0146] [Chem.3] (HAS)

[0147] In a pressure flask, imidazole (264.15 mg, 3.88 mmol), l-bromo-4-(trifluoromethylsulfanyl)benzene (500 mg, 1.94 mmol), K2CO3 (268.11 mg, 1.94 mmol) and a catalytic amount of CuSO4 were mixed at 180°C for 48 h. After cooling to room temperature, the crude product was extracted with MeOH and filtered, and the solvent was evaporated under reduced pressure. The product was purified by column chromatography on silica gel with a mixture of CH2Cl2 and MeOH (90 / 10) as eluent to give a yellow solid (382.8 mg, 80% yield). >H NMR (400 MHz, CD3CN) <5 8.08-7.99 (m, 1H, H2), 7.86-7.75 (m, 2H, H8), 7.67-7.57 (m, 2H, H7), 7.55-7.45 (m, 1H, H5), 7.21-7.12 (m, 1H, H4).13C NMR (101 MHz, CD3CN) <5 139.64 (IC, C2), 137.97 (2C, C8), 135.65 (IC, C9), 130.52 (IC, C6), 129.75 (IC, CF3, q, J = 307.1 Hz), 121.83 (IC, C4), 121.63 (2C, C7), 117.30 (IC, C5).19F NMR (376 MHz, CDC13) <5 -42.70 (3F, CF3). HMRS (ES+): Cale, pour C10H8F3N2S245,0360 trouvé 245,0361 [M+H+],

[0148] Chlorure de 3-Benzyl-l-{4-[(trifluorométhyl)sulfanyl]phényl}-lH-imidazol-3-ium (6’ ) de formule (B)

[0149] [Chem.4]

[0150] Under a nitrogen atmosphere, 1' (130 mg, 0.53 mmol) and benzyl chloride (0.07 mL, 0.61 mmol) were dissolved in dry CH3CN (10 mL) and the mixture was stirred at 80°C for 5 days. The solution was then evaporated, the resulting solid was washed with ether and dried in vacuo to give a white solid (130.3 mg, 66% yield). 'H NMR (400 MHz, CDC13) <5 11.61 (t, J = 1.6 Hz, 1H, H2), 8.24 (t, J = 1.9 Hz, 1H, H5), 8.04-7.92 (m, 2H, H7), 7.73 (t, J = 1.8 Hz, 1H, H4), 7.72-7.64 (m, 2H, H8), 7.61-7.46 (m, 2H, H12), 7.27-7.15 (m, 3H, H13, H14), 5.68 (s, 2H, H10). 13C NMR (101 MHz, CDC13) <5 137.92 (2C, C8), 136.28 (IC, C2), 136.12 (IC, C9), 132.97 (IC, C6), 129.49 (IC, Cil), 129.30 (2C, C7), 129.11 (2C, C13), 129.00 (IC, CF3, q, J = 308.7 Hz), 126.57 (IC, C4), 123.27 (IC, C5), 122.35 (2C, C12), 121.08 (IC, C14), 53.42 (IC, CIO). 19F NMR (376 MHz, CDC13) <5 -42.17 (3F, CF3). HMRS (ES+): Wedge, for C17H14N2F3S 335.0830 found 335.0838 [M-Cl ].

[0151] 3-Isopropyl-l-(4-((trifluoromethyl)thio)phenyl)-lH-imidazol-3-ium bromide (11') of formula (C)

[0152] [Chem.5] Br

[0153] In a pressure flask, 1' (125 mg, 0.59 mmol) was dissolved in 2-bromopropane (3 mL) and the mixture was stirred at 80°C for one week. The solvent was evaporated under reduced pressure, and the solid washed with diethyl ether and dried to give a yellow solid (58.2 mg, 27% yield). 1H NMR (300 MHz, CD3CN) <5 10.32 (dt, J= 1.8, 0.9 Hz, 1H, H2), 8.13-8.01 (m, 3H, H4, H7), 7.98-7.91 (m, 2H, H8), 7.88 (t, J= 1.9 Hz, 1H, H5), 4.89 (qq, J= 6.7 Hz, 1H, H10), 1.65 (d, J= 6.7 Hz, 6H, H11). 13C NMR (75 MHz, CD3CN) <5 137.83 (2C, C8), 137.24 (IC, C2), 134.92 (IC, C6), 129.62 (q, J = 307.2 Hz, IC, CF3), 125.55 (IC, C9), 123.41 (2C, C7), 121.63 (IC, C4), 121.19 (IC, C5), 53.94 (IC, CIO), 21.99 (2C, Cil). 19F NMR (282 MHz, CD 3CN) ô -43.38 (3F, CF,). HMRS (ES+): Cale, for C13H14F3N2S 287.0830 found 287.0830 [M-Br ]. Complex 41 of formula (D)

[0154] [Chem.6]

[0155] Under nitrogen atmosphere, 6' (80 mg, 0.22 mmol) and Ag2O (27.04 mg, 0.12 mmol) were dissolved in dry CH2Cl2, the mixture was stirred at room temperature for 18 h. Au(SMe2)Cl (69.8 mg, 0.24 mmol) was added and mixed for 2 h. The solution was filtered through a pad of celite and the solvent was removed under reduced pressure to give a white solid (119.8 mg, 98% yield). 1H NMR (400 MHz, CD3CN) <5 7.88 (s, 4H, H7, H8), 7.54-7.27 (m, 7H, H4, H5, H12, H13, H14), 5.48 (s, 2H, H10). 13C NMR (101 MHz, CD3CN) <5 170.32 (IC, C2), 141.61 (IC, C6), 137.27 (2C, C13), 135.99 (Cil), 129.66 (q, J = 307.1 Hz, IC, CF3), 128.93 (2C, C8), 128.49 (IC, C9), 127.94 (2C, C12), 126.37 (2C, C7), 124.70 (IC C14), 122.51 (IC, C5), 122.31 (IC, C4), 54.95 (IC, CIO). 19F NMR (376 MHz, CD3CN) ô -43.37 (3F, CF,). HMRS (ES+): Wedge, for C19H16AuF3N3S 572.0683 found 572.0682 [M-Cl +CH3CN]. Complex 42 of formula (E)

[0156] [Chem.7]

[0157] Under nitrogen atmosphere, 9' (47.7 mg, 0.13 mmol) and Ag2O (14.79 mg, 0.064 mmol) were dissolved in dry CH2Cl2, the mixture was stirred at room temperature for 18 h. Au(SMe2)Cl (41.53 mg, 0.14 mmol) was added and mixed for 2 h. The solution was filtered through a pad of celite and the solvent was removed under reduced pressure to give a white solid (61.9 mg, 92% yield). 'H NMR (400 MHz, CDC13) <5 7.94-7.66 (m, 4H, H7, H8), 7.27 (d, J= 2.1 Hz, 1H, H5), 7.23 (d, J= 2.1 Hz, 1H, H4), 5.26 (qq, J= 6.8 Hz, 1H, H10), 1.57 (d, J= 6.8 Hz, 6H, Hll). 13C NMR (101 MHz, CDC13) <5 169.54 (IC, C2), 141.18 (IC, C9), 137.36 (2C, C8), 129.22 (q, J = 308.4 Hz, IC, CF3), 125.67 (2C, C7), 125.59 (IC, C6), 121.67 (IC, C5), 117.77 (IC, C4), 54.46 (IC, CIO), 23.29 (2C, Cil). 19F NMR (376 MHz, CDC13) ô -42.11 (3F, CF3f HMRS (ES+): Cale, for Cj5H16AuF3N3S 524.0683 found 524.0679 [M-Cl +CH3CN].

[0158] II. Anti-leishmanial activity and cytotoxicity of the complexes of the invention.

[0159] II. 1. Anti-leishmanial activity on axenic amastigotes of L. infantum.

[0160] L. infantum promastigotes (MHOM / MA / 67 / ITMAP-263, CNR Leishmania, Montpellier, France, expressing luciferase activity) were cultured in RPMI 1640 medium supplemented with 10% fetal calf serum (FCS), 2 mM L-glutamine and antibiotics (100 U / mL penicillin and 100 pg / mL streptomycin) and harvested in log phase of growth by centrifugation at 900 g for 10 min. The supernatant was carefully removed and replaced with the same volume of complete RPMI 1640 medium at pH 5.4 and incubated for 24 h at 24°C. The promastigotes were then incubated (5% CO2 humid incubator) for 24 h at 37°C leading to their transformation into axenic amastigotes.

[0161] L. infantum amastigotes were incubated at a density of 2 x 106 parasites / ml in sterile 96-well plates with various concentrations of complexes dissolved in DMSO (final DMSO concentration less than 0.5% v / v), in duplicate. Appropriate controls [DMSO, amphotericin B, miltefosine, pentamidine and fexi-nidazole (Sigma Aldrich)] were added to each set of experiments.

[0162] The luciferase activity of axenic amastigotes was then estimated, 80 pL of each well was transferred to white 96-well plates, Steady Glow® (Promega) was added according to the manufacturer's instructions, and the plates were incubated (37 °C) for 2 min. Luminescence was measured using a Microbeta Luminescence Counter (PerkinElmer).

[0163] The 50% inhibitory concentration (IC50) was defined as the drug concentration required to inhibit the metabolic activity of L. infantum amastigotes by 50% compared to the control. The IC50 values ​​were calculated by nonlinear regression analysis processed on dose-response curves, using the Ta-bleCurve 2D V5 software. The IC50 values ​​represent the average of three independent experiments.

[0164] II.2. Evaluation of cytotoxicity.

[0165] The evaluation of the cytotoxicity of the complexes according to the invention by MTT test on the Thpl cell line (human monocyte cell line) was carried out according to Mosmann with slight modifications. Briefly, cells (0.77.105 cells / ml) in 200 pL of the complete medium [RPMI 1640 supplemented with 10% fetal calf serum (FCS), 2 mM L-glutamine and antibiotics (100 U / ml) penicillin and 100 pg / ml streptomycin)]-!- PMA (50 ng / ml) were seeded in each well of 96-well plates and incubated at 37°C under a humidified atmosphere of 5% CO 2 with 95% air. After a 96-h incubation, the plates were washed 3 times with medium and 100 µl of medium was added. Various concentrations and appropriate controls were then added (100 µl) and the plates were incubated for 72 h at 37°C.

[0166] Each well was then examined under a microscope for possible precipitate formation before aspiration of the medium. MTT solution (0.5 mg / ml in RPMI, 100 µl) was then added to each well. The cells were incubated for 2 h at 37°C. The MTT solution was then removed and DMSO (100 µl) was added to dissolve the resulting formazan crystals. The plates were shaken vigorously (300 rpm) for 5 min.

[0167] Absorbance was measured at 570 nm with a microplate spectrophotometer. DMSO was used as a blank and doxorubicin (Sigma Aldrich) as a positive control. CC50s were calculated by nonlinear regression analysis processed on dose-response curves, using TableCurve 2D V5 software.

[0168] II.3. Results.

[0169] The anti-leishmanial potency of proligands 6-20 and gold(I) complexes 21-40 was evaluated in vitro on the axenic amastigote stage of Leishmania infantum, (corresponding to the stage responsible for the disease in humans) by determining their 50% inhibitory concentrations (IC50) and compared to three reference drugs different anti-leishmania (amphotericin B, pentamidine and miltefosine) and the drug candidate fexinidazole.

[0170] In order to evaluate their selectivity, the cytotoxicity of these complexes was evaluated in vitro on the human acute monocytic leukemia cell line Thpl and the corresponding CC50 values ​​were compared with those of the reference drug doxorubicin giving access to selectivity indices (SI = CC50 / IC50). The results are summarized in Table 2.

[0171] The carbene precursors were inactive with IC50 values ​​above 50 pM, except for the imidazolium salt 17 which was moderately active but rather toxic.

[0172] In contrast, all gold(I) complexes 21-40 were active against the clinically relevant axenic amastigote form of L. infantum, with IC50 values ​​in the nanomolar range with IC50 values ​​of 0.77 to 0.09 pM, except 22 which displayed an IC50 value of 1.53 pM.

[0173] Regarding the anti-leishmanial activity for gold(I) complexes bearing a benzyl group, it appears that this series is active with IC50 values ​​in the nanomolar range as well (IC50 = 0.25-0.77 pM) except complex 22 which displays an IC50 value of 1.53 pM.

[0174] The IC50 values ​​for the complexes bearing an isopropyl group were 2 to 3 times better than the IC50 values ​​for the same complexes but bearing a benzyl group with IC50 values ​​in the nanomolar range (IC50 = 0.13-0.5 pM). Thus, the introduction of an isopropyl group instead of a benzyl group appears to favor anti-leishmanial activity.

[0175] Interestingly, the compounds with the introduction of a quinolyl group showed better IC50 values ​​than the isopropyl and benzyl analogues with an anti-leishmanial activity of 0.09 pM to 0.12 pM, except for complex 32 which shows an IC50 value of 0.19 pM but is still better than the corresponding complex bearing an isopropyl group (complex 27 with an IC50 of 0.41 pM). These derivatives showed an activity equivalent to that of the reference amphotericin B with an IC50 of 0.075 pM.

[0176] All gold(I) complexes (except 22) showed the same or better activity compared to the anti-leishmanial drugs miltefosine (IC50 = 0.71 pM), pentamidine (IC50 = 10.54 pM) and the drug candidate fexinidazole (IC50 = 3.4 pM).

[0177] In order to evaluate the cytotoxicity of gold(I) complexes, they were tested in vitro on the Thpl cell line.

[0178] Biological results showed that gold(I) complexes exhibited low cytotoxicity on the human Thpl cell line with CC50 values ​​ranging from 12.21 to 88.79 pM compared to the values ​​of the reference drugs amphotericin B (CC50 = 10.49 pM) and miltefosine (CC50 = 35.02 pM). Pentamidine and fexi-nidazole were less cytotoxic with CC50 values ​​above 50 pM and 355 pM respectively.

[0179] Gold(I) complexes bearing a benzyl or isopropyl group were the least cytotoxic (CC50 = 14.93-88.79 pM) but complexes with a quinolyl group were even less cytotoxic (CC50 = 12.21-53.02 pM).

[0180] All synthesized compounds showed very good selectivity indices (SI = 47.09-474.17) with the best value for 34. These SI values ​​were better than for pentamidine (SI>4.74) and in the same range for the other reference drugs (SI = 139.87 for amphotericin B, SI = 53.06 for miltefosine and > 104.41 for the drug candidate fexinidazole).

[0181] The 36-40 complexes showed very good anti-leishmanial activity with an IC50 ranging from 0.14 to 0.30 pM. These complexes had low cytotoxicity with CC50 ranging from 3.99 to 12.46 pM, in the same values ​​as amphotericin B. All these preliminary results for the 36-40 complexes lead to good selectivity indices ranging from 13 to 54, equivalent to that of miltefosine.

[0182] [Tables2] Ta o is at 2 Compounds or Complexes AxenKjues & L tn / ontom Clss ( pM F Thpl CG, tuMF selectivity index CCss / lG, Si 6 >5Û - ​​7 >53 - 8 >53 - - 9 >50 - ; - 30 >53 - - 11 >59 - - 12 >50 - - Î5 >59 - 14 >50 - 15 >50 - - 16 >50 - - 17 14.50 44.4S 3 07 18 >59 - — 19 >50 20 >59 - - 21 0.28 13.89 67.85 22 1.53 71.88 47.99 25 0.77 48.9S 62.55 24 9.25 13.29 71.89 25 0.53 20.SS 68.21 26 0.13 24.92 118.53 27 0.41 49.65 129.72 28 0.50 88.75 178.52 29 0.25 45.51 173.50 30 0.14 18.97 133.82 31 9.19 13.38 136.42 32 0.19 12.20 65.03 33 9.09 22.21 129.70 34 0.11 53.02 474.27 35 0.12 25.47 130.05 36 0.23 12.46 55.92 37 0.14 4.40 30.63 38 0.30 £.94 23.15 39 n 77 5.13 28.79 4S 0.30 3.99 23.43 Amohoiéricme S5 0.075 10.49 139.87 Miitéfosinet 0.71 35.02 49.32. ?8htam^ne,> 10.54 >59 >4.74 FexmMazsse3 3.4 >355 >204.42 Doxorubicin3 0.70 '^offenne of three dependent expâ encss. 3 Affsntwftérsane B, and feniïsidKaîe ​​have been incorporated as reference drugs. anti-inmarsieris drug candidates. : Doxorubicin was used as a positive cytotoxic control.

[0183] Gold(I) complexes 41 and 42 were tested in the same way but in separate experiments. The results for these complexes are summarized in Table 3. These complexes show activities and selectivities very close to mil-tefosine, better than pentamidine and slightly less than amphotericin B.

[0184] [Tables3] Table 3 Amastrgotes complexes oxenrceived from L infantum Clse (hMF Thpl «MtW CCh / ICso selectivity index SI 41 0.34 + 0.03 15.84 ± 2.86 46.58 42 0.15+.0.04 16.24 ±3.27 108.27 Amphotericin A 0.06 ± 0.01 13.13 ± 0.92 218.83 Miltefosine® 0.46 + 0.04 35.02 ± 2.98 76.13 Pentamidine 1.36 + C 31 65.87+7.49 48.43 Doxorubicin11 - 0.7 + 0.06 - 5 Mayenne of three independent experiments. Amphotericin B and miltefosme were used as reference drugs for anti-ishmarial drug candidates. - Doxorubicin was used as a positive cytotoxicity control. REFERENCES

[0185] [1] Paloque et al, 2015, “Synthesis, characterization, and antileishmanial activities of gold(I) complexes involving quinoline functionalized AMieterocyclic carbenes”, European Journal of Medicinal Chemistry, vol. 94, pages 22-29.

[0186] [2] Zhang et al, 2018, “Synthesis, characterization, and antileishmanial activities of neutral iV-heterocyclic carbenes gold(I) complexes”, European Journal of Medicinal Chemistry, vol. 143, pages 1635-1643.

[0187] [3] Ouji et al, 2020, “Design, synthesis and efficacy of hybrid triclosan-gold based molécules on artemisinin-resistant Plasmodium falciparum and Leishmania infantum parasites », ChemistrySelect, vol. 5, pages 619-625.

[0188] [4] Boselli et al, 2015, « Synthesis, structures, and biological studies of heterobi- metallic Au(I)-Ru(II) complexes involving A-heterocyclic carbene- based multidentate ligands », Organometallics, vol. 34, pages 1046-1055.

[0189] [5] Mora et al, 2019, « Recent advances in gold-NHC complexes with biological properties », Chem. Soc. Rev., vol. 48, pages 447-462.

[0190] [6] Delgado-Rebollo et al, 2019, « Coinage métal complexes bearing fluorinated N - heterocyclic carbene ligands », Journal of Organometallic Chemistry, vol. 898, 120856.

Claims

Claims

1. Gold(I) complex corresponding to one of the following formulae (I) or (II): [Chem. 8] [Chem.9] in which • Rb R2, R3, R4 and R5, identical or different, are independently selected from the group consisting of H, F, CnF2n+i, OCnF2n+i and SCnF2n+i with n equal to 1, 2, 3 or 4, provided that at least one of Rb R2, R3, R4 and R5 is H and at least one other of Rb R2, R3, R4 and R5 is selected from the group consisting of F, CnF2n+b OCnF2n+i and SCnF2n+i; • R' represents an optionally substituted alkyl group or an optionally substituted aryl group; • Y represents a halogen or a -SX group with X representing a residue of a 5 or 6 atom sugar or one of its derivatives; and • Z represents a halide anion, a nitrate anion (-NO3) or a non-coordinating anion, provided that, when the gold(I) complex has formula (I) and that Ri = R2 = R4 = H, R3 = R5 = F and Y = Cl, R' is not a 2,4-difluorophenyl.

2. Gold(I) complex according to claim 1, characterized in that RB R2, R3, R4 and R5, identical or different, are independently chosen from the group consisting of H, F, CF3, OCF3 and SCF3, provided that at least one of Rb R2, R3, R4 and R5 is H and that at least one other of RB R2, R3, R4 and R5 is chosen from the group consisting of F, CF3, OCF3 and scf3.

3. Gold(I) complex according to claim 1 or 2, characterized in that said R' is isopropyl.

4. Gold(I) complex according to claim 1 or 2, characterized in that said R' is a mesityl, a benzyl, a quinolyl, a methyl-pyrrole, a methyl phenyl sulfide or a bipyridine.

5. Gold(I) complex according to any one of claims 1 to 4, characterized in that said Y is chlorine.

6. Gold(I) complex according to any one of claims 1 to 4, characterized in that said -SX group is 2,3,4,6-Tetra-O-acetyl-l-thio-[3-D-glucopyranosato.

7. A pharmaceutical composition comprising, as active ingredient, a gold(I) complex according to any one of claims 1 to 6 or chloro-[1,3-bis(2,4-difluorophenyl)imidazolin-2-ylidene] gold(I) and a pharmaceutically acceptable carrier.

8. Gold(I) complex according to any one of claims 1 to 6 or chloro-[1,3-bis(2,4-difluorophenyl)imidazolin-2-ylidene] gold(I), for use as an antioxidant, as an antibacterial agent and / or as an antiparasitic agent.

9. A gold(I) complex for use according to claim 8, said gold(I) complex being useful as an anti-leishmanial agent.

10. 0 Gold(I) complex according to any one of claims 1 to 6 or chloro-[1,3-bis(2,4-difluorophenyl)imidazolin-2-ylidene] gold(I) or a pharmaceutical composition according to claim 7, for use in the treatment and / or prevention of leishmaniasis.

11. A gold(I) complex according to any one of claims 1 to 6, for use as an anti-cancer agent.