The present Invention relates to multivalent fucose derivatives for use as a drug. More especially, the present Invention relates to multivalent fucose derivatives for use as a drug in the prevention or treatment of infections caused byAspergillusspp.

Invasive aspergillosis is a major cause of mortality in severely immunocompromised patients such as in allograft or leukemic patients. This pathogen is also involved in allergic forms that weaken the patient with cystic fibrosis, bronchopulmonar chronic obstructive disease (BPCO) and asthma, in aspergilloma and in chronic pulmonary aspergillosis. Nowadays the preventive and therapeutic strategies of these aspergillosis face problems of toxicity and resistance to antifungal agents.

The treatment of aspergillosis rests on azole derivatives (itraconazole, voriconazole, . . . ) which generate problems of innate or acquired resistance to treatment. However, amphotericin B, which has a broad spectrum, exhibits significant renal toxicity, whereas echinocandins, a new class of antifungals, have little activity onAspergillusspp. Apart from systemic treatments, the inhalation of antifungals constitutes today a therapeutic alternative but not conceivable in prophylaxis given the long-term toxicity.

One objective of the present invention is to provide a compound for use as a drug in the prophylaxis of infections caused byAspergillusspp.

Another aim of the present invention is to provide a compound for use as a drug in the treatment of infections caused byAspergillusspp.

Another aim of the present invention is to provide a compound bearing at least two fucose moieties.

The present invention relates to a compound bearing at least two fucose moieties for its use as a drug in the prevention or treatment of infections caused byAspergillusspp, said compound having a molecular weight comprised from 0.6 to 340 kDa, in particular from 0.6 to 2 kDa or from 1 to 7 kDa or from 2 to 10 kDa or from 5 to 340 kDa.

In particular, the molecular weight of the compound is from 0.6 to 2 kDa which includes a molecular weight of 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9 and 2 kDa. According to the present Invention, a compound with a molecular weight comprised from 0.6 to 2 kDa corresponds to a compound having a divalent scaffold. According to the present Invention, the expression “divalent scaffold” refers to a scaffold bearing 2 sites each covalently linked to a fucose moiety. Examples of divalent scaffold include alkyl chains and polyethylene glycol chains.

In particular, the molecular weight of the compound is from 1 to 7 kDa which includes a molecular weight of 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5 and 7 kDa.

According to the present Invention, a compound with a molecular weight comprised from 1 to 7 kDa corresponds to compound having a cyclic hexa- to octavalent scaffold. According to the present Invention, the expression “cyclic hexa- to octavalent scaffold” refers to a scaffold bearing 6, 7 or 8 sites each covalently linked to a fucose moiety, tethered through flexible linkers. Examples of cyclic hexa- to octavalent scaffold include calixarenes and cyclodextrins. In particular, the molecular weight of the compound is from 2 to 10 kDa which includes a molecular weight of 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5 and 10 kDa. According to the present Invention, a compound with a molecular weight comprised from 2 to 10 kDa corresponds to a compound having a polyhedral, cage-like, octavalent scaffold. According to the present Invention, the expression “polyhedral, cage-like, octavalent scaffold” refers to a scaffold bearing 8 sites each covalently linked to a fucose moiety. Examples of polyhedral, cage-like, octavalent scaffold include fullerenes and polyhedral oligomeric silsesquioxane (POSS).

In particular, the molecular weight of the compound is from 5 to 340 kDa which includes a molecular weight of 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 225, 250, 275, 300, 325 and 340 kDa.

According to the present Invention, a compound with a molecular weight comprised from 5 to 340 kDa corresponds to a compound having a linear ultravalent scaffold. According to the present Invention, the expression “linear ultravalent scaffold” refers to a scaffold bearing at least 23 sites each covalently linked to a fucose moiety. Examples of linear ultravalent scaffold include polymers such as pullulan and dextran.

According to the Invention, the expression “prevention” relates to prophylaxis and consists of measures taken for disease prevention, as opposed to disease treatment. Disease prevention relies on anticipatory actions.

According to the Invention, the expression “treatment” relates to all appropriate means for stopping a disease, or for curing a patient.

According to the Invention, the expression “infections caused byAspergillusspp” relates to infections that are caused by the fungus of theAspergillusgenus such as an aspergillosis.

The present Invention is based on the unexpected blocking of theAspergillusspp lectin AFL by the compound of the Invention. This lectin is found on the surface of theAspergillusspp spores and allows the fungus to adhere on the glycans of the host cells (Houser et al, Plos One, 2013, 8, e83077). The AFL lectin is also called FleA. This anti-adhesive property enables the compounds of the Invention to be used as a drug to prevent and/or treat diseases caused by theAspergillusspp.

In an advantageous embodiment, the present Invention relates to a compound for its use, said compound being of formula (I)
A-(D)i-B—C  (I)whereini is equal to 0 or 1;A is selected from

k being equal to 1, 2, or 3; k being in particular equal to 1;

r being comprised from 1 to 30, in particular from 1 to 4, from 5 to 9, from 10 to 15, from 16 to 20, from 21 to 25 or from 26 to 30;

s being comprised from 5 to 300; in particular from 60 to 80;

v being comprised from 0 to 10; in particular from 1 to 8; preferably v being equal to 3;B is of formula

C is of formula

y being equal to 0 or 1;X being selected from O, S or CH2;U being selected from


m being comprised from 0 to 8,


n being comprised from 0 to 8,


p being comprised from 1 to 10,








q being comprised from 1 to 10,


or

R1, R2, R3and R4being independently from each other selected from H, COCH3, NH2, NO2, NHAc, OH, OMe, COOH, COOMe, CONHMe, Cl, Br, I, F, SMe or Me;provided that y+n or y+m is different from 0;in particular, m being comprised from 1 to 5;in particular, n being comprised from 0 to 5;D being selected from


j being comprised from 0 to 8.

A is the scaffold, D is an optional spacer, B is a triazole spacer and C is a fucose moiety.

The dashed line “ . . . ” and the crossed lines “” indicate the sites of a selected group each covalently linked to its neighbor.

On a selected group, the presence of more than one dashed line “ . . . ” indicates the sites each covalently linked to identical substituents. This means that the scaffold A is always linked to more than one time the same (D)i-B—C group.

On a selected group, the presence of one dashed line “ . . . ” and one crossed lines “” indicate the sites each covalently linked to two different substituents.

For example, if the scaffold is A2


and the triazole spacer is B


then the formed A2-B group represents



The triazole spacer B


is linked to A-(D)iand C. The A-(D)igroup can either be linked to the nitrogen or to the carbon atom of the triazole, the C group being linked to the other atom. For example, if B is linked to A-(D)ithrough the nitrogen atom of the triazole, C is linked to the triazole through its carbon atom to form a A-(D)i-B—C group of formula



According to the present Invention, a polyethylene glycol group can be written as



The bold line “” appearing on the U groups represents the connection point to the X groups, U and X belonging to the fucose moiety C.

The zigzag bond “” means that the stereochemistry of the linked double bond is either Z or E.

In an advantageous embodiment, the present Invention relates to a compound for its use, said compound being of formula (I)
A-(D)i-B—C  (I)whereini is equal to 0 or 1;A is selected from

k being equal to 1, 2, or 3; k being in particular equal to 1;

r being comprised from 1 to 30, in particular from 1 to 4, from 5 to 9, from 10 to 15, from 16 to 20, from 21 to 25 or from 26 to 30;

s being comprised from 5 to 300; in particular from 60 to 80;

v being comprised from 0 to 10; in particular from 1 to 8: preferably v being equal to 3;B is of formula

C is of formula

y being equal to 1;X being selected from O, S or CH2;U being selected from


m being comprised from 0 to 8,


n being comprised from 0 to 8, or




q being comprised from 1 to 10,R1, R2, R3and R4being independently from each other selected from H, COCH3, NH2, NO2, NHAc, OH, OMe, COOH, COOMe, CONHMe, Cl, Br, I, F, SMe or Me;in particular, m being comprised from 1 to 5;in particular, n being comprised from 0 to 5;D being selected from


j being comprised from 0 to 8.

In an advantageous embodiment, the present Invention relates to a composition for its use as a drug in the prevention or the treatment of infections caused byAspergillusspp comprising a compound as defined above as active ingredient.

In an advantageous embodiment, the present Invention relates to a composition for its use comprising a compound as defined above as active ingredient, formulated for its human and/or animal use.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound of formula (I) as active ingredient, formulated for its human and/or animal use.

In an advantageous embodiment, the present Invention relates to a composition for its use comprising a compound as defined above as active ingredient, saidAspergillusspp beingAspergillussectionFumigati, AspergillussectionFlavi, AspergillussectionNigri, AspergillussectionNidulantes, Aspergillus oryzae, Aspergillus bombycis, Aspergillus nemius.

In particular, the present Invention relates to a composition for its use comprising a compound as defined above as active ingredient, saidAspergillusspp beingAspergillussectionFumigati, AspergillussectionFlavi, AspergillussectionNigri, AspergillussectionNidulantes, more particularly saidAspergillusspp beingAspergillussectionFumigati.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound of formula (I) as active ingredient, saidAspergillusspp beingAspergillussectionFumigati, AspergillussectionFlavi, AspergillussectionNigri, AspergillussectionNidulantes, Aspergillus oryzae, Aspergillus bombycis, Aspergillus nemius.

In particular, the present Invention relates to a composition for its use comprising a compound of formula (I) as active ingredient, saidAspergillusspp beingAspergillussectionFumigati, AspergillussectionFlavi, AspergillussectionNigri, AspergillussectionNidulantes, more particularly saidAspergillusspp beingAspergillussectionFumigati.

In an advantageous embodiment, the present Invention relates to a composition for its use comprising a compound as defined above as active ingredient, said infection being an aspergillosis, in particular an allergic broncho-pulmonary aspergillosis, an aspergilloma, a chronic pulmonary aspergillosis or an invasive pulmonary aspergillosis.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound of formula (I) as active ingredient, said infection being an aspergillosis, in particular an allergic broncho-pulmonary aspergillosis, an aspergilloma, a chronic pulmonary aspergillosis or an invasive pulmonary aspergillosis.

Aspergillosis is a group of diseases which can result fromAspergillusinfection and includes invasive aspergillosis, allergic broncho-pulmonary aspergillosis, chronic pulmonary aspergillosis and aspergilloma. Asthma is also complicated and exacerbated byAspergillusinfection (SAFS).Aspergillusaffects humans and birds and animals can also develop aspergillosis, commercially many plant diseases and food spoilage may be due toAspergillusinfection or contamination.

In an advantageous embodiment, the present Invention relates to a composition for its use comprising a compound as defined above as active ingredient, said compound being used by respiratory route, in particular by inhalation, by oral route or intravenously.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound of formula (I) as active ingredient, said compound of formula (I) being used by respiratory route, in particular by inhalation, by oral route or intravenously.

Inhalable preparations comprising a compound of the Invention include inhalable powders, propellant-containing metered dose aerosols or propellant-free inhalable solutions. Inhalable powders according to the invention containing the active substance may consist of the active substance on its own or of a mixture of the active substance with physiologically acceptable excipients. Within the scope of the present invention, the term “propellant-free inhalable solutions” also includes concentrates or sterile inhalable solutions ready for use.

Inhalable Powders:

if the active substance of the Invention is present in a mixture with physiologically acceptable excipients, the following physiologically acceptable excipients may be used to prepare the inhalable powders according to the invention: monosaccharides (e.g. glucose or arabinose), disaccharides (e.g. lactose, saccharose, maltose), oligo- and polysaccharides (e.g. dextran), polyalcohols (e.g. sorbitol, mannitol, xylitol), salts (e.g. sodium chloride, calcium carbonate) or mixtures of these excipients with one another. Preferably, mono- or disaccharides are used, while the use of lactose or glucose is preferred, particularly, but not exclusively, in the form of their hydrates.

Propellant-Containing Inhalable Aerosols:

the propellant-containing inhalable aerosols which may be used according to the invention may contain a compound of the Invention dissolved in the propellant gas or in dispersed form. The propellant gases which may be used to prepare the inhalation aerosols according to the invention are known from the prior art. Suitable propellant gases are selected from among hydrocarbons such as n-propane, n-butane or isobutane and halohydrocarbons such as preferably fluorinated derivatives of methane, ethane, propane, butane, cyclopropane or cyclobutane. The propellant gases mentioned above may be used on their own or in mixtures thereof. Particularly preferred propellant gases are fluorinated alkane derivatives selected from TG134a (1,1,1,2-tetrafluoroethane), TG227 (1,1,1,2,3,3,3-heptafluoropropane) and mixtures thereof. The propellant-driven inhalation aerosols used within the scope of the use according to the invention may also contain other ingredients such as co-solvents, stabilisers, surfactants, antioxidants, lubricants and pH adjusters. All these ingredients are known in the art.

Propellant Free Inhalable Solutions:

the compounds of the Invention are, in particular, used to prepare propellant-free inhalable solutions and inhalable suspensions. Solvents used for this purpose include aqueous or alcoholic, preferably ethanolic solutions. The solvent may be water on its own or a mixture of water and ethanol. The solutions or suspensions are adjusted to a pH of 2 to 7, preferably 2 to 5, using suitable acids. The pH may be adjusted using acids selected from inorganic or organic acids. Examples of particularly suitable inorganic acids include hydrochloric acid, hydrobromic acid, nitric acid, sulphuric acid and/or phosphoric acid. Examples of particularly suitable organic acids include ascorbic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, fumaric acid, acetic acid, formic acid and/or propionic acid etc. Preferred inorganic acids are hydrochloric and sulphuric acids. It is also possible to use the acids which have already formed an acid addition salt with one of the active substances. Of the organic acids, ascorbic acid, fumaric acid and citric acid are preferred. If desired, mixtures of the above acids may also be used, particularly in the case of acids which have other properties in addition to their acidifying qualities, e.g. as flavorings, antioxidants or complexing agents, such as citric acid or ascorbic acid, for example.

Co-solvents and/or other excipients may be added to the propellant-free inhalable solutions used for the purpose according to the invention. Preferred co-solvents are those which contain hydroxyl groups or other polar groups, e.g. alcohols—particularly isopropyl alcohol, glycols—particularly propyleneglycol, polyethyleneglycol, polypropyleneglycol, glycolether, glycerol, polyoxyethylene alcohols and polyoxyethylene fatty acid esters.

The terms “excipients” and “additives” in this context denote any pharmacologically acceptable substance which is not an active substance but which can be formulated with the active substance or substances in the pharmacologically suitable solvent in order to improve the qualitative properties of the active substance formulation. Preferably, these substances have no pharmacological effect or, in connection with the desired therapy, no appreciable or at least no undesirable pharmacological effect. The excipients and additives include, for example, surfactants such as soya lecithin, oleic acid, sorbitan esters, such as polysorbates, polyvinylpyrrolidone, other stabilisers, complexing agents, antioxidants and/or preservatives which guarantee or prolong the shelf life of the finished pharmaceutical formulation, flavorings, vitamins and/or other additives known in the art. The additives also include pharmacologically acceptable salts such as sodium chloride as isotonic agents. The preferred excipients include antioxidants such as ascorbic acid, for example, provided that it has not already been used to adjust the pH, vitamin A, vitamin E, tocopherols and similar vitamins or provitamins occurring in the human body. Preservatives may be used to protect the formulation from contamination with pathogens. Suitable preservatives are those which are known in the art, particularly acetyl pyridinium chloride, benzalkonium chloride or benzoic acid or benzoates such as sodium benzoate in the concentration known from the prior art.

The compositions of the invention can also be in the form of sterile powders, granules, tablets, concentrated solutions or suspensions, or freeze-dried powders reconstituted with sterile water or saline.

Extemporaneous injection solutions and suspensions can be prepared from these sterile powders, granules, tablets, concentrated solutions or suspensions, or freeze-dried powders reconstituted with sterile water or saline before administration to the subject.

The suitable formulations for the desired administration route are known from the man skilled in the art and described, for example in: Remington, The science and Practice of Pharmacy, 22èmeédition, 2013, The Pharmaceutical Press.

In an advantageous embodiment, the present Invention relates to a composition for its use comprising a compound as defined above as active ingredient, said composition comprising from 1 mg to 1.4 g of active ingredient; in particular from 1 to 7 mg of active ingredient, or from 7 to 700 mg of active ingredient, or from 70 to 350 mg of active ingredient, or from 350 to 700 mg of active ingredient, or from 700 mg to 1.05 g of active ingredient, or from 1.05 to 1.4 g of active ingredient.

According to the present Invention, a dosage from 1 mg to 1.4 g of active ingredient, in particular from 1 to 7 mg of active ingredient, or from 7 to 700 mg of active ingredient, or from 70 to 350 mg of active ingredient, or from 350 to 700 mg of active ingredient, or from 700 mg to 1.05 g of active ingredient, or from 1.05 to 1.4 g of active ingredient, corresponds to a daily intake by nebulization to a human body.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound of formula (I) as active ingredient, said composition comprising from 1 mg to 1.4 g of active ingredient; in particular from 1 to 7 mg of active ingredient, or from 7 to 700 mg of active ingredient, or from 70 to 350 mg of active ingredient, or from 350 to 700 mg of active ingredient, or from 700 mg to 1.05 g of active ingredient, or from 1.05 to 1.4 g of active ingredient.

In an advantageous embodiment, the present Invention relates to a composition for its use comprising a compound as defined above as active ingredient, said composition comprising from 200 mg to 10 g of active ingredient; in particular from 400 mg to 7 g of active ingredient.

According to the present Invention, a dosage from 200 mg to 10 g of active ingredient, in particular from 400 mg to 7 g of active ingredient, corresponds to a daily intake by oral route to a human body.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound of formula (I) as active ingredient, said composition comprising from 200 mg to 10 g of active ingredient; in particular from 400 mg to 7 g of active ingredient.

In an advantageous embodiment, the present Invention relates to a composition for its use comprising a compound as defined above as active ingredient, said composition comprising from 10 mg to 10 g of active ingredient; in particular from 50 mg to 7 g of active ingredient. According to the present Invention, a dosage from 10 mg to 10 g of active ingredient, in particular from 50 mg to 7 g of active ingredient, corresponds to a daily intravenous intake to a human body.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound of formula (I) as active ingredient, said composition comprising from 10 mg to 10 g of active ingredient; in particular from 50 mg to 7 g of active ingredient.

In an advantageous embodiment, the present Invention relates to a composition for its use comprising a compound as defined above as active ingredient, said composition comprising from 0.015 to 20 mg/kg of active ingredient; in particular from 0.015 to 0.1 mg/kg of active ingredient, or from 0.1 to 10 mg/kg of active ingredient, or from 1 to 5 mg/kg of active ingredient, or from 5 to 10 mg/kg of active ingredient, or from 10 to 15 mg/kg of active ingredient, or from 15 to 20 mg/kg of active ingredient.

According to the present Invention, a dosage from 0.015 to 20 mg/kg of active ingredient, in particular from 0.015 to 0.1 mg/kg of active ingredient, or from 0.1 to 10 mg/kg of active ingredient, or from 1 to 5 mg/kg of active ingredient, or from 5 to 10 mg/kg of active ingredient, or from 10 to 15 mg/kg of active ingredient, or from 15 to 20 mg/kg of active ingredient, corresponds to a daily intake by nebulization to a human body of 70 kg.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound of formula (I) as active ingredient, said composition comprising from 0.015 to 20 mg/kg of active ingredient; in particular from 0.015 to 0.1 mg/kg of active ingredient, or from 0.1 to 10 mg/kg of active ingredient, or from 1 to 5 mg/kg of active ingredient, or from 5 to 10 mg/kg of active ingredient, or from 10 to 15 mg/kg of active ingredient, or from 15 to 20 mg/kg of active ingredient.

In an advantageous embodiment, the present Invention relates to a composition for its use comprising a compound as defined above as active ingredient, said composition comprising from 3 mg/kg to 143 mg/kg of active ingredient; in particular from 6 mg/kg to 100 mg/kg of active ingredient.

According to the present Invention, a dosage from 3 mg/kg to 143 mg/kg of active ingredient, in particular from 6 mg/kg to 100 mg/kg of active ingredient, corresponds to a daily intake by oral route to a human body of 70 kg.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound of formula (I) as active ingredient, said composition comprising from 3 mg/kg to 143 mg/kg of active ingredient; in particular from 6 mg/kg to 100 mg/kg of active ingredient.

In an advantageous embodiment, the present Invention relates to a composition for its use comprising a compound as defined above as active ingredient, said composition comprising from 0.15 mg/kg to 143 mg/kg of active ingredient; in particular from 1 mg/kg to 100 mg/kg of active ingredient.

According to the present Invention, a dosage from 0.15 mg/kg to 143 mg/kg of active ingredient, in particular from 1 mg/kg to 100 mg/kg of active ingredient, corresponds to a daily intravenous intake to a human body of 70 kg.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound of formula (I) as active ingredient, said composition comprising from 0.15 mg/kg to 143 mg/kg of active ingredient; in particular from 1 mg/kg to 100 mg/kg of active ingredient.

In an advantageous embodiment, the present Invention relates to a composition for its use comprising a compound as defined above as active ingredient, said compound being in association with an antifungal agent such as an azole antifungal agent, a polyene antifungal agent or an echinocandin antifungal agent.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound of formula (I) as active ingredient, said compound being in association with an antifungal agent such as an azole antifungal agent, a polyene antifungal agent or an echinocandin antifungal agent.

The present Invention also relates to a method for the prevention or the treatment of infections caused byAspergillusspp comprising a step of administering a compound as defined above.

In an advantageous embodiment, the present Invention relates to a method for the prevention or the treatment of infections caused byAspergillusspp comprising a step of administering a compound of formula (I) as defined above.

The present Invention also relates to a compound bearing at least two fucose moieties and having a molecular weight comprised from 0.6 to 340 kDa, in particular from 0.6 to 2 kDa or from 1 to 7 kDa or from 2 to 10 kDa or from 5 to 340 kDa.

In particular, the molecular weight of the compound is from 0.6 to 2 kDa which includes a molecular weight of 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9 and 2.

In particular, the molecular weight of the compound is from 1 to 7 kDa which includes a molecular weight of 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5 and 7 kDa.

In particular, the molecular weight of the compound is from 2 to 10 kDa which includes a molecular weight of 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5 and 10 kDa.

In particular, the molecular weight of the compound is from 5 to 340 kDa which includes a molecular weight of 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 225, 250, 275, 300, 325 and 340 kDa.

In an advantageous embodiment, the present Invention relates to a compound, said compound being of formula (I)
A-(D)i-B—C  (I)whereini is equal to 0 or 1;A is selected from

k being equal to 1, 2, or 3: k being in particular equal to 1;

r being comprised from 1 to 30, in particular from 1 to 4, from 5 to 9, from 10 to 15, from 16 to 20, from 21 to 25 or from 26 to 30;

s being comprised from 5 to 300; in particular from 60 to 80;

v being comprised from 0 to 10; in particular from 1 to 8; preferably v being equal to 3;B is of formula

C is of formula

y being equal to 0 or 1;X being selected from O, S or CH2;U being selected from


m being comprised from 0 to 8,


n being comprised from 0 to 8,


p being comprised from 1 to 10,








q being comprised from 1 to 10,


or

R1, R2, R3and R4being independently from each other selected from H, COCH3, NH2, NO2, NHAc, OH, OMe, COOH, COOMe, CONHMe, Cl, Br, I, F, SMe or Me;provided that y+n or y+m is different from 0;in particular, m being comprised from 1 to 5;in particular, n being comprised from 0 to 5;D being selected from


j being comprised from 0 to 8.

In a particular embodiment, the present invention relates to a compound bearing at least two fucose moieties and having a molecular weight comprised from 0.6 to 340 kDa, in particular from 0.6 to 2 kDa or from 1 to 7 kDa or from 2 to 10 kDa or from 5 to 340 kDa.said compound being of formula (I)
A-(D)i-B—C  (I)whereini is equal to 0 or 1;A is selected from

k being equal to 1, 2, or 3; k being in particular equal to 1;

r being comprised from 1 to 30, in particular from 1 to 4, from 5 to 9, from 10 to 15, from 16 to 20, from 21 to 25 or from 26 to 30;

s being comprised from 5 to 300; in particular from 60 to 80;

v being comprised from 0 to 10; in particular from 1 to 8; preferably v being equal to 3;B is of formula

C is of formula

y being equal to 0 or 1;X being selected from O, S or CH2;U being selected from


m being comprised from 0 to 8,


n being comprised from 0 to 8,


p being comprised from 1 to 10,








q being comprised from 1 to 10,


or

R1, R2, R3and R4being independently from each other selected from H, COCH3, NH2, NO2, NHAc, OH, OMe, COOH, COOMe, CONHMe, Cl, Br, I, F, SMe or Me;provided that y+n or y+m is different from 0;in particular, m being comprised from 1 to 5;in particular, n being comprised from 0 to 5;D being selected from


j being comprised from 0 to 8.

In an advantageous embodiment, the present Invention relates to a compound of formula (I)
A-(D)i-B—C  (I)whereini is equal to 0 or 1;A is selected from

k being equal to 1, 2, or 3; k being in particular equal to 1;

r being comprised from 1 to 30, in particular from 1 to 4, from 5 to 9, from 10 to 15, from 16 to 20, from 21 to 25 or from 26 to 30;

s being comprised from 5 to 300; in particular from 60 to 80;

v being comprised from 0 to 10; in particular from 1 to 8; preferably v being equal to 3;B is of formula

C is of formula

y being equal to 1;X being selected from O, S or CH2;U being selected from


m being comprised from 0 to 8,


n being comprised from 0 to 8, or




q being comprised from 1 to 10,R1, R2, R3and R4being independently from each other selected from H, COCH3, NH2, NO2, NHAc, OH, OMe, COOH, COOMe, CONHMe, Cl, Br, I, F, SMe or Me;in particular, m being comprised from 1 to 5;in particular, n being comprised from 0 to 5;D being selected from


j being comprised from 0 to 8.

In another advantageous embodiment, the present Invention relates to a compound of formula (I-A1), A being of formula A1, in particular selected from


k being equal to 1;Di, B and C being as defined in formula (I).

In another advantageous embodiment, the present Invention relates to a compound of formula (I-A2), A being of formula A2, in particular selected from

r being equal to 1;

r being equal to 2

r being equal to 3;

r being equal to 4;

r being equal to 7;

r being equal to 11

r being equal to 19;

r being equal to 27Di, B and C being as defined in formula (I).

In another advantageous embodiment, the present Invention relates to a compound of formula (I-A3), A being of formula A3, in particular selected from

s being equal to ˜66;Di, B and C being as defined in formula (I).

The dextran scaffold (A3) is a polymer scaffold. This polymer being polydisperse, the amount of glucose monomer units in the scaffold cannot be exactly defined. In particular, the dextran scaffolds according to the Invention have a polydispersity index, PDI, inferior of 1.50. Therefore, the A group of formula (A3-1) has an approximate number of 68 glucose units (s equal to ˜66); “an approximate number of 68 glucose units” referring to a PDI of 1.43.

In another advantageous embodiment, the present Invention relates to a compound of formula (I-A4), A being of formula A4, in particular selected from

Di, B and C being as defined in formula (I).

In another advantageous embodiment, the present Invention relates to a compound of formula (I-B), B being selected from B1 or B2

A, Diand C being as defined in formula (I).

In another advantageous embodiment, the present Invention relates to a compound of formula (I-C), C being selected from C1, C2 or C3

A, B and Dibeing as defined in formula (I).

In formula C1, X is an oxygen atom, m and n are equal to 0.

In formula C2, X is an oxygen atom, m is equal to 0 and n is comprised from 0 to 8.

In formula C3, X is an oxygen atom, m is equal to 1 and n is equal to 0.

In another advantageous embodiment, the present Invention relates to a compound of formula (I-C2), C being selected from

A, B and Dibeing as defined in formula (I).

In (C2-1), the X group is an O, m is equal to 0 and n is equal to 2. In (C2-2), the X group is an O, m is equal to 0 and n is equal to 4.

In another advantageous embodiment, the present Invention relates to a compound of formula (I-BC), said compound comprising the groups[B2-C1],[B2-C2],[B2-C2-1],[B2-C2-2], or[B1-C3];A being as defined in formula (I).

In another advantageous embodiment, the present Invention relates to a compound of formula (I), said compound being selected from[A1-B2-C1],[A1-B2-C2],[A1-B2-C2-1],[A1-B2-C2-2][A1-1-B2-C1],[A1-1-B2-C2],[A1-1-B2-C2-1], or[A1-1-B2-C2-2]

According to the Invention, the compound of formula [A1-1-B2-C2-1] represents



The Inventors have found that α-cyclodextrine derivatives (a cyclodextrine having six glucose units) of the Invention, bearing six fucose moieties, have a particularly strong affinity for anAspergilluslectin associated with a particularly strong anti-adhesive property to this lectin. According to an aspect of the Invention, the α-cyclodextrine derivatives of the Invention have a particularly strong affinity for, associated with a particularly strong anti-adhesive property to, the AFL lectin.

The affinity to theAspergilluslectin AFL is, for example, measured by the Isothermal titration calorimetry (ITC) method described in Example 35. Isothermal titration calorimetry is a method often used to measure the thermodynamic constants of the interaction between a biomolecule and a synthetic compound. It is the only technique to measure both the enthalpic and entropic parameters of binding, without modification of the partners involved. This method is based on the estimation of the release of heat upon formation of the compound-receptor linkage in a microcalorimeter having two cells. One contains ultra-pure water maintained at a precise temperature and serves as a reference cell; the other contains a protein solution at a fixed concentration (FIG. 1-I). To this solution, the apparatus adds a precise volume of a compound solution at regular intervals of time, with stirring. This injection then generates a variation of heat with respect to the reference cell which is compensated by a heating resistor. The power needed to maintain the temperature is then recorded for all compound injections. The integration of the raw data in the form of a graph (FIGS. 1-II and1-III) gives access to the dissociation constant Kd, to the stoichiometric data and enthalpy data (ΔH) of bonding. From this data it is then possible to determine the free enthalpy (ΔG) and the entropy variation of the system (ΔS). The dissociation constant obtained from the equilibrium slope indicates the compound-protein thermodynamic affinity, while the energy difference between the lower plate and the upper plate gives the enthalpy value. This demonstrates the contribution of hydrogen bonds and Van der Waals energies to the bond formed. The values of free enthalpy and entropy can be deduced from the first data acquired thanks to the equations of thermodynamics. Entropy gives us the part of the conformational aspects like the loss of degrees of freedom.

The anti-adhesive property is, for example, measured according to the method described in Example 36. The anti-adhesive strategy is based on the inhibition of the conidia adhesion at the surface of the broncho-pulmonary epithelium. These spores present a particularly high adhesion potential on alveolar pneumocytes forming the epithelium. The first step aims at obtaining an alveolar pneumocytes layer in a 96 wells plate. Therefore approximately 40 000 cells are introduced in each well and are incubated for 7 days at 37° C. During this incubation time, the cells will deposit at the bottom of the wells in a homogeneous manner to reach a confluence and leave no empty space between the cells which come into contact with each other. In parallel,Aspergillus fumigatusis grown at 37° C. for 3 to 5 days. The spores are then carefully harvested in a PBS buffer solution while avoiding taking those which have evolved into filaments (hyphae). This solution is diluted to a concentration of 1 to 2×106spores/mL and then preincubated with the various fucoside derivatives of the Invention in variable concentration. This step allows the fucoside derivatives of the Invention to interact beforehand with the lectin AFL onAspergillus fumigatus. Each of these solutions is then added to a well containing the layer of pneumocytes and then incubated at 37° C. for 45 minutes. The compounds having a large anti-adhesive potential will reduce the spore binding ability. Thus, after incubation, the spores present in the supernatant are eliminated by three rinsing steps. The spores adhered to the cellular layer are then counted under a microscope on an average surface of 400 pneumocytes. This method is schematized onFIG. 3.

In another advantageous embodiment, the present Invention relates to a compound of formula (I), said compound being selected from[A2-B2-C1],[A2-4-B2-C1],[A2-5-B2-C1],[A2-6-B2-C1],[A2-7-B2-C1],[A2-8-B2-C1],[A4-B2-C1],[A4-B2-C2],[A4-B2-C2-1][A4-B2-C2-2],[A4-1-B2-C1],[A4-1-B2-C2],[A4-1-B2-C2-1],[A4-1-B2-C2-2],[A3-B1-C3], or[A3-1-B1-C3],or said compound being selected from



The present Invention also relates to a compound bearing at least two fucose moieties for its use as a drug, said compound having a molecular weight comprised from 0.6 to 340 kDa, in particular from 0.6 to 2 kDa or from 1 to 7 kDa or from 2 to 10 kDa or from 5 to 340 kDa.

In particular, the molecular weight of the compound is from 0.6 to 2 kDa which includes a molecular weight of 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9 and 2.

In particular, the molecular weight of the compound is from 1 to 7 kDa which includes a molecular weight of 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5 and 7 kDa.

In particular, the molecular weight of the compound is from 2 to 10 kDa which includes a molecular weight of 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5 and 10 kDa.

In particular, the molecular weight of the compound is from 5 to 340 kDa which includes a molecular weight of 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 125, 150, 175, 200, 225, 250, 275, 300, 325 and 340 kDa.

In an advantageous embodiment, the present Invention relates to a compound for its use, said compound being of formula (I)
A-(D)i-B—C  (I)whereini is equal to 0 or 1;A is selected from

k being equal to 1, 2, or 3; k being in particular equal to 1;

r being comprised from 1 to 30, in particular from 1 to 4, from 5 to 9, from 10 to 15, from 16 to 20, from 21 to 25 or from 26 to 30;

s being comprised from 5 to 300; in particular from 60 to 80;

v being comprised from 0 to 10; in particular from 1 to 8; preferably v being equal to 3;B is of formula

C is of formula

y being equal to 0 or 1;X being selected from O, S or CH2;U being selected from


m being comprised from 0 to 8,


n being comprised from 0 to 8,


p being comprised from 1 to 10,








q being comprised from 1 to 10,


or

R1, R2, R3and R4being independently from each other selected from H, COCH3, NH2, NO2, NHAc, OH, OMe, COOH, COOMe, CONHMe, Cl, Br, I, F, SMe or Me;provided that y+n or y+m is different from 0;in particular, m being comprised from 1 to 5;in particular, n being comprised from 0 to 5;D being selected from


j being comprised from 0 to 8.

In an advantageous embodiment, the present Invention relates to a compound for its use, said compound being of formula (I)
A-(D)i-B—C  (I)whereini is equal to 0 or 1;A is selected from

k being equal to 1, 2, or 3; k being in particular equal to 1;

r being comprised from 1 to 30, in particular from 1 to 4, from 5 to 9, from 10 to 15, from 16 to 20, from 21 to 25 or from 26 to 30;

s being comprised from 5 to 300; in particular from 60 to 80;

v being comprised from 0 to 10; in particular from 1 to 8; preferably v being equal to 3;B is of formula

C is of formula

y being equal to 1;X being selected from O, S or CH2;U being selected from


m being comprised from 0 to 8,


n being comprised from 0 to 8, or




q being comprised from 1 to 10,R1, R2, R3and R4being independently from each other selected from H, COCH3, NH2, NO2, NHAc, OH, OMe, COOH, COOMe, CONHMe, Cl, Br, I, F, SMe or Me;in particular, m being comprised from 1 to 5;in particular, n being comprised from 0 to 5;D being selected from


j being comprised from 0 to 8.

In a particular embodiment, the present invention relates to a compound bearing at least two fucose moieties for its use as a drug, said compound having a molecular weight comprised from 0.6 to 340 kDa, in particular from 0.6 to 2 kDa or from 1 to 7 kDa or from 2 to 10 kDa or from 5 to 340 kDa;said compound being of formula (I)
A-(D)i-B—C  (I)whereini is equal to 0 or 1;A is selected from

k being equal to 1, 2, or 3; k being in particular equal to 1

r being comprised from 1 to 30, in particular from 1 to 4, from 5 to 9, from 10 to 15, from 16 to 20, from 21 to 25 or from 26 to 30;

s being comprised from 5 to 300; in particular from 60 to 80;

v being comprised from 0 to 10; in particular from 1 to 8; preferably v being equal to 3;B is of formula

C is of formula

y being equal to 0 or 1;X being selected from O, S or CH2;U being selected from


m being comprised from 0 to 8,


n being comprised from 0 to 8,


p being comprised from 1 to 10,








q being comprised from 1 to 10,


or

R1, R2, R3and R4being independently from each other selected from H, COCH3, NH2, NO2, NHAc, OH, OMe, COOH, COOMe, CONHMe, Cl, Br, I, F, SMe or Me;provided that y+n or y+m is different from 0;in particular, m being comprised from 1 to 5;in particular, n being comprised from 0 to 5;D being selected from


j
j being comprised from 0 to 8.

In an advantageous embodiment, the present Invention relates to a composition for its use as a drug comprising a compound as defined above as active ingredient.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound as defined above as active ingredient, formulated for its human and/or animal use.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound of formula (I) as active ingredient, formulated for its human and/or animal use.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound as defined above as active ingredient, said compound being used by respiratory route, in particular by inhalation.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound of formula (I) as active ingredient, said compound of formula (I) being used by respiratory route, in particular by inhalation.

Inhalable preparations comprising a compound of the Invention include inhalable powders, propellant-containing metered dose aerosols or propellant-free inhalable solutions. Inhalable powders according to the invention containing the active substance may consist of the active substance on its own or of a mixture of the active substance with physiologically acceptable excipients. Within the scope of the present invention, the term “propellant-free inhalable solutions” also includes concentrates or sterile inhalable solutions ready for use.

Inhalable powders: if the active substance of the Invention is present in a mixture with physiologically acceptable excipients, the following physiologically acceptable excipients may be used to prepare the inhalable powders according to the invention: monosaccharides (e.g. glucose or arabinose), disaccharides (e.g. lactose, saccharose, maltose), oligo- and polysaccharides (e.g. dextran), polyalcohols (e.g. sorbitol, mannitol, xylitol), salts (e.g. sodium chloride, calcium carbonate) or mixtures of these excipients with one another. Preferably, mono- or disaccharides are used, while the use of lactose or glucose is preferred, particularly, but not exclusively, in the form of their hydrates.

Propellant-containing inhalable aerosols: the propellant-containing inhalable aerosols which may be used according to the invention may contain a compound of the Invention dissolved in the propellant gas or in dispersed form. The propellant gases which may be used to prepare the inhalation aerosols according to the invention are known from the prior art. Suitable propellant gases are selected from among hydrocarbons such as n-propane, n-butane or isobutane and halohydrocarbons such as preferably fluorinated derivatives of methane, ethane, propane, butane, cyclopropane or cyclobutane. The propellant gases mentioned above may be used on their own or in mixtures thereof. Particularly preferred propellant gases are fluorinated alkane derivatives selected from TG134a (1,1,1,2-tetrafluoroethane), TG227 (1,1,1,2,3,3,3-heptafluoropropane) and mixtures thereof. The propellant-driven inhalation aerosols used within the scope of the use according to the invention may also contain other ingredients such as co-solvents, stabilisers, surfactants, antioxidants, lubricants and pH adjusters. All these ingredients are known in the art.

Propellant-free inhalable solutions: the compounds of the Invention are, in particular, used to prepare propellant-free inhalable solutions and inhalable suspensions. Solvents used for this purpose include aqueous or alcoholic, preferably ethanolic solutions. The solvent may be water on its own or a mixture of water and ethanol. The solutions or suspensions are adjusted to a pH of 2 to 7, preferably 2 to 5, using suitable acids. The pH may be adjusted using acids selected from inorganic or organic acids. Examples of particularly suitable inorganic acids include hydrochloric acid, hydrobromic acid, nitric acid, sulphuric acid and/or phosphoric acid. Examples of particularly suitable organic acids include ascorbic acid, citric acid, malic acid, tartaric acid, maleic acid, succinic acid, fumaric acid, acetic acid, formic acid and/or propionic acid etc. Preferred inorganic acids are hydrochloric and sulphuric acids. It is also possible to use the acids which have already formed an acid addition salt with one of the active substances. Of the organic acids, ascorbic acid, fumaric acid and citric acid are preferred. If desired, mixtures of the above acids may also be used, particularly in the case of acids which have other properties in addition to their acidifying qualities, e.g. as flavourings, antioxidants or complexing agents, such as citric acid or ascorbic acid, for example.

Co-solvents and/or other excipients may be added to the propellant-free inhalable solutions used for the purpose according to the invention. Preferred co-solvents are those which contain hydroxyl groups or other polar groups, e.g. alcohols—particularly isopropyl alcohol, glycols—particularly propyleneglycol, polyethyleneglycol, polypropyleneglycol, glycolether, glycerol, polyoxyethylene alcohols and polyoxyethylene fatty acid esters.

The terms “excipients” and “additives” in this context denote any pharmacologically acceptable substance which is not an active substance but which can be formulated with the active substance or substances in the pharmacologically suitable solvent in order to improve the qualitative properties of the active substance formulation. Preferably, these substances have no pharmacological effect or, in connection with the desired therapy, no appreciable or at least no undesirable pharmacological effect. The excipients and additives include, for example, surfactants such as soya lecithin, oleic acid, sorbitan esters, such as polysorbates, polyvinylpyrrolidone, other stabilisers, complexing agents, antioxidants and/or preservatives which guarantee or prolong the shelf life of the finished pharmaceutical formulation, flavourings, vitamins and/or other additives known in the art. The additives also include pharmacologically acceptable salts such as sodium chloride as isotonic agents. The preferred excipients include antioxidants such as ascorbic acid, for example, provided that it has not already been used to adjust the pH, vitamin A, vitamin E, tocopherols and similar vitamins or provitamins occurring in the human body. Preservatives may be used to protect the formulation from contamination with pathogens. Suitable preservatives are those which are known in the art, particularly acetyl pyridinium chloride, benzalkonium chloride or benzoic acid or benzoates such as sodium benzoate in the concentration known from the prior art.

The compositions of the invention can also be in the form of sterile powders, granules, tablets, concentrated solutions or suspensions, or freeze-dried powders reconstituted with sterile water or saline.

Extemporaneous injection solutions and suspensions can be prepared from these sterile powders, granules, tablets, concentrated solutions or suspensions, or freeze-dried powders reconstituted with sterile water or saline before administration to the subject.

The suitable formulations for the desired administration route are known from the man skilled in the art and described, for example in: Remington, The science and Practice of Pharmacy, 22èmeédition, 2013, The Pharmaceutical Press.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound as defined above as active ingredient, said composition comprising from 1 mg to 1.4 g of active ingredient; in particular from 1 to 7 mg of active ingredient, or from 7 to 700 mg of active ingredient, or from 70 to 350 mg of active ingredient, or from 350 to 700 mg of active ingredient, or from 700 mg to 1.05 g of active ingredient, or from 1.05 to 1.4 g of active ingredient.

According to the present Invention, a dosage from 1 mg to 1.4 g of active ingredient, in particular from 1 to 7 mg of active ingredient, or from 7 to 700 mg of active ingredient, or from 70 to 350 mg of active ingredient, or from 350 to 700 mg of active ingredient, or from 700 mg to 1.05 g of active ingredient, or from 1.05 to 1.4 g of active ingredient, corresponds to a daily intake by nebulization to a human body.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound of formula (I) as active ingredient, said composition comprising from 1 mg to 1.4 g of active ingredient; in particular from 1 to 7 mg of active ingredient, or from 7 to 700 mg of active ingredient, or from 70 to 350 mg of active ingredient, or from 350 to 700 mg of active ingredient, or from 700 mg to 1.05 g of active ingredient, or from 1.05 to 1.4 g of active ingredient.

In an advantageous embodiment, the present Invention relates to a composition for its use comprising a compound as defined above as active ingredient, said composition comprising from 200 mg to 10 g of active ingredient; in particular from 400 mg to 7 g of active ingredient.

According to the present Invention, a dosage from 200 mg to 10 g of active ingredient, in particular from 400 mg to 7 g of active ingredient, corresponds to a daily intake by oral route to a human body.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound of formula (I) as active ingredient, said composition comprising from 200 mg to 10 g of active ingredient; in particular from 400 mg to 7 g of active ingredient.

In an advantageous embodiment, the present Invention relates to a composition for its use comprising a compound as defined above as active ingredient, said composition comprising from 10 mg to 10 g of active ingredient; in particular from 50 mg to 7 g of active ingredient. According to the present Invention, a dosage from 10 mg to 10 g of active ingredient, in particular from 50 mg to 7 g of active ingredient, corresponds to a daily intravenous intake to a human body.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound of formula (I) as active ingredient, said composition comprising from 10 mg to 10 g of active ingredient; in particular from 50 mg to 7 g of active ingredient.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound as defined above as active ingredient, said composition comprising from 0.015 to 20 mg/kg of active ingredient; in particular from 0.015 to 0.1 mg/kg of active ingredient, or from 0.1 to 10 mg/kg of active ingredient, or from 1 to 5 mg/kg of active ingredient, or from 5 to 10 mg/kg of active ingredient, or from 10 to 15 mg/kg of active ingredient, or from 15 to 20 mg/kg of active ingredient.

According to the present Invention, a dosage from 0.015 to 20 mg/kg of active ingredient, in particular from 0.015 to 0.1 mg/kg of active ingredient, or from 0.1 to 10 mg/kg of active ingredient, or from 1 to 5 mg/kg of active ingredient, or from 5 to 10 mg/kg of active ingredient, or from 10 to 15 mg/kg of active ingredient, or from 15 to 20 mg/kg of active ingredient, corresponds to a daily intake by nebulization to a human body of 70 kg.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound of formula (I) as active ingredient, said composition comprising from 0.015 to 20 mg/kg of active ingredient; in particular from 0.015 to 0.1 mg/kg of active ingredient, or from 0.1 to 10 mg/kg of active ingredient, or from 1 to 5 mg/kg of active ingredient, or from 5 to 10 mg/kg of active ingredient, or from 10 to 15 mg/kg of active ingredient, or from 15 to 20 mg/kg of active ingredient.

In an advantageous embodiment, the present Invention relates to a composition for its use comprising a compound as defined above as active ingredient, said composition comprising from 3 mg/kg to 143 mg/kg of active ingredient; in particular from 6 mg/kg to 100 mg/kg of active ingredient.

According to the present Invention, a dosage from 3 mg/kg to 143 mg/kg of active ingredient, in particular from 6 mg/kg to 100 mg/kg of active ingredient, corresponds to a daily intake by oral route to a human body of 70 kg.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound of formula (I) as active ingredient, said composition comprising from 3 mg/kg to 143 mg/kg of active ingredient; in particular from 6 mg/kg to 100 mg/kg of active ingredient.

In an advantageous embodiment, the present Invention relates to a composition for its use comprising a compound as defined above as active ingredient, said composition comprising from 0.15 mg/kg to 143 mg/kg of active ingredient; in particular from 1 mg/kg to 100 mg/kg of active ingredient.

According to the present Invention, a dosage from 0.15 mg/kg to 143 mg/kg of active ingredient, in particular from 1 mg/kg to 100 mg/kg of active ingredient, corresponds to a daily intravenous intake to a human body of 70 kg.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound of formula (I) as active ingredient, said composition comprising from 0.15 mg/kg to 143 mg/kg of active ingredient; in particular from 1 mg/kg to 100 mg/kg of active ingredient.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound as defined above as active ingredient, said compound being in association with an antifungal agent such as an azole antifungal agent, a polyene antifungal agent or an echinocandin antifungal agent.

In another advantageous embodiment, the present Invention relates to a composition for its use comprising a compound of formula (I) as active ingredient, said compound being in association with an antifungal agent such as an azole antifungal agent, a polyene antifungal agent or an echinocandin antifungal agent.

