NOVOS INIBIDORES DA ACETILCOLINESTERASE E USOS DOS MESMOS PARA PREVENÇÃO E TRATAMENTO DE TRANSTORNOS COMPULSIVOS E TRANSTORNOS NEURODEGENERATIVOS

Abstract

The present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt and / or solvate thereof. The present invention also relates to the use of the compound of formula (I) as a drug, in particular for preventing or treating compulsive disorders and related behaviors, including addiction, obsessive-compulsive disorders and eating disorders, and neurodegenerative disorders such as Parkinson's disease or Alzheimer's disease.

Description

[0001] The present invention relates to novel acetylcholinesterase inhibitors, particularly useful in the prevention and / or treatment of acetylcholine-related disorders, such as compulsive disorders, including eating disorders, addiction, obsessive-compulsive disorders and neurodegenerative disorders. Background of the invention

[0002] Acetylcholine (ACh) is an important neuromodulator of the striatal network and the main transmitter at the neuromuscular junction. After its exocytotic release, the action of ACh is rapidly interrupted by its hydrolysis, which is catalyzed by an enzyme called acetylcholinesterase (AChE). AChE inhibitors (AChEIs) inhibit this reaction and prevent the breakdown of ACh into choline and acetate. In this way, AChEIs increase extracellular levels and the duration of ACh action in both the central nervous system and the neuromuscular junction.

[0003] The applicant recently discovered that striatal ACh also plays an important role in obsessive-compulsive disorders, particularly eating disorders (Favier, et al., The Journal of Clinical Investigation, 2020, 130, 12, (pp. 6616-6630). Eating disorders such as anorexia nervosa and bulimia nervosa, in both fully syndromic and subclinical forms, affect up to 10% of the population. Anorexia nervosa has the highest mortality rates of all mental health disorders (« 5% per decade). Eating disorders result from aberrant processing of habitual behavior. Understanding the neuronal basis of anorexia nervosa is currently very limited and, consequently, there are no specific biological or pharmacological treatments for this dramatic condition. Petition 870260059145, dated 06 / 17 / 2026, page 16 / 117 2 / 51

[0004] Cholinergic interneurons are essential regulators of the striatum and habit formation. To investigate the role of ACh in habit behaviors, the Applicant specifically silenced ACh signaling in the striatum in a murine model with a deletion of the vesicular acetylcholine transporter (VAChTcKO mice). The Applicant then demonstrated that VAChTcKO mice had decreased ACh transmission and became more prone to excessive habits. To understand whether these excessive habits could lead to dysfunctional eating, the Applicant then used a pathological eating model in VAChTcKO mice: the activity-based anorexia model (ABA, a model of anorexia nervosa (Klenotich and Dulawa, 2012)). In the ABA model, mutant mice lacking ACh in the striatum were more prone to self-starvation than control mice.

[0005] Based on these unexpected findings, the inventors hypothesized that acetylcholinesterase inhibitors could be useful in the prevention and / or treatment of obsessive-compulsive disorders.

[0006] Although several acetylcholinesterase inhibitors are currently available on the market, especially those targeted at Alzheimer's disease, they often cause serious side effects (dizziness, nausea and vomiting, heart problems, etc.).

[0007] Therefore, there is a constant need for new acetylcholinesterase inhibitors with improved affinity for AChE and limited peripheral effect. Summary of the present invention

[0008] In this context, the inventors surprisingly designed and developed new acetylcholinesterase inhibitors (AChEIs) that are exclusively active in the brain (and not in the body). This mode of action, therefore, limits the neuromuscular action of AChEIs and peripheral side effects. Petition 870260059145, dated 06 / 17 / 2026, page 17 / 117 3 / 51 unwanted. These new compounds have proven useful in the prevention and / or treatment of compulsive disorders, especially eating disorders such as anorexia.

[0009] According to a first aspect, the present invention relates to a compound of formula (I): or a pharmaceutically acceptable salt and / or solvate thereof, wherein it represents a single or double bond, X is an oxygen atom or an N-OH group. R1 and R2 are each independently H, an optionally substituted nitrogen heterocyclyl group, an optionally substituted C1-C1e aliphatic chain or an optionally substituted aryl group, wherein up to 4 methylene units of said aliphatic chain are optionally substituted by O, C(O), NH or N-alkyl C1-C1e, provided that at least one of R1 and R2 is an optionally substituted nitrogen-containing heterocyclyl group. Li and Lu are each independently a divalent radical derived from a C1-C12 aliphatic chain, wherein one or more, preferably one to four, methylene units are optionally substituted by arylene, -O-, -S-, -C(=O)-, -SO2 or -N(Ci-Ce alkyl)-, wherein said aliphatic chain is optionally substituted, pen are each independently 0 or 1, with the condition that p is 1 when R1 is an optionally substituted nitrogen-containing heterocyclyl group and en is 1 when R2 is an optionally substituted nitrogen-containing heterocyclyl group, and Petition 870260059145, dated 06 / 17 / 2026, p. 18 / 117 4 / 51 R' is H, halogen, an optionally substituted C1-C6 aliphatic chain, an optionally substituted aryl, an optionally substituted heteroaryl or an optionally substituted C1-C6 alkyl-aryl, wherein up to 4 methylene units of said aliphatic chain are optionally substituted by O, C(O), NH or C1-C6 N-alkyl.

[0010] According to a second aspect, the present invention relates to a pharmaceutical composition comprising at least one compound of formula (I) as defined above, a pharmaceutically acceptable salt and / or solvate thereof and at least one pharmaceutically acceptable excipient.

[0011] According to a third aspect, the present invention also relates to the compound of formula (I), a pharmaceutically acceptable salt and / or solvate thereof or the pharmaceutical composition according to the invention for use as a medicament.

[0012] The present invention also relates to the use of a compound of formula (I) according to the invention, a pharmaceutically acceptable salt and / or solvate thereof or the pharmaceutical composition according to the invention as a medicament or for the manufacture of a medicament.

[0013] The present invention also relates to a method for preventing and / or treating compulsive disorders, including addiction, eating disorders and obsessive-compulsive disorders, and Alzheimer's disease, comprising administering to a person in need an effective dose of a compound of formula (I), a pharmaceutically acceptable salt and / or solvate thereof, or the pharmaceutical composition according to the invention. Detailed description Definitions

[0014] The term stereoisomers used in this invention refers to configurational stereoisomers and more particularly to optical isomers. Optical isomers that are not images Petition 870260059145, dated 06 / 17 / 2026, p. 19 / 117 5 / 51 mirror images of each other are therefore designated as diastereomers, and optical isomers, which are non-superimposable mirror images, are designated as enantiomers. An equimolar mixture of two enantiomers of a chiral compound is designated as a racemic mixture or racemate.

[0015] For the purposes of the invention, the term "pharmaceutically acceptable" is intended to mean what is useful for the preparation of a pharmaceutical composition and what is generally safe and non-toxic for pharmaceutical use.

[0016] The term "pharmaceutically acceptable salt and / or solvate" is intended to mean, within the scope of the present invention, a salt and / or solvate of a compound that is pharmaceutically acceptable, as defined above, and that possesses the pharmacological activity of the corresponding compound.

[0017] Pharmaceutically acceptable salts include: (1) acid addition salts formed with inorganic acids, such as hydrochloric, hydrobromic, sulfuric, nitric and phosphoric acids and the like; or formed with organic acids, such as acetic, benzenesulfonic, fumaric, glucoheptonic, gluconic, glutamic, glycolic, hydroxynaphthoic, 2-hydroxyethanesulfonic, lactic, maleic, malic, mandelic, methanesulfonic, muconic, 2-naphthalenesulfonic, propionic, succinic, dibenzoyl-L25 tartaric, tartaric, p-toluenesulfonic, trimethylacetic and trifluoroacetic acids and the like, and (2) base addition salts formed when an acidic proton present in the compound is replaced by a metal ion, such as an alkali metal ion, an alkaline earth metal ion or an aluminum ion; or coordinated with an organic or inorganic base. Acceptable organic bases include diethanolamine, ethanolamine, N-methylglucamine, triethanolamine, tromethamine and Petition 870260059145, dated 06 / 17 / 2026, page 20 / 117 6 / 51 similar. Acceptable inorganic bases include aluminum hydroxide, calcium hydroxide, potassium hydroxide, sodium carbonate, and sodium hydroxide.

[0018] Acceptable solvates for the therapeutic use of the compounds of the present invention include conventional solvates, such as those formed during the last step of the preparation of the compounds of the invention due to the presence of solvents. As an example, we can cite solvates due to the presence of water (these solvates are also called hydrates) or ethanol.

[0019] The term halogen, as used in the present invention, refers to an atom of fluorine, bromine, chlorine or iodine.

[0020] The term Cx-Cy aliphatic chain designates a linear or branched hydrocarbon chain, fully saturated or containing one or more unsaturations, but not aromatic, comprising x and y carbon atoms, notably from 1 to 12 carbon atoms, preferably from 1 to 6 carbon atoms. According to the present invention, the term aliphatic chain includes alkyl, alkenyl or alkynyl groups, substituted or unsubstituted, linear or branched.

[0021] The term C1-Cs alkyl, as used in the present invention, refers to a saturated monovalent hydrocarbon chain, linear or branched, containing from 1 to 6 carbon atoms, including, but not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, n-hexyl and the like.

[0022] The term C2-C6 alkenyl, as used in the present invention, refers to a linear or branched monovalent unsaturated hydrocarbon chain containing from 2 to 6 carbon atoms and comprising at least one double bond, including, but not limited to, ethenyl, propenyl, butenyl, pentenyl, hexenyl and the like.

[0023] The term C2-C6 alkynyl, as used in the present invention, refers to an unsaturated hydrocarbon chain. Petition 870260059145, dated 06 / 17 / 2026, p. 21 / 117 7 / 51 Monovalent, linear or branched, containing from 2 to 6 carbon atoms and comprising at least one triple bond including, but not limited to, ethinyl, propynyl, butynyl, pentinyl, hexynyl and the like.

[0024] The term “C1-C12 alkanediyl”, as used in the present invention, refers to a linear or branched divalent saturated hydrocarbon chain containing from 1 to 12 carbon atoms, including, but not limited to, methanedyl (methylene), ethanediyl, propanediyl, butanediyl, pentanediyl, hexanediyl and the like.

[0025] The term “C1-C12 alkenediyl”, as used in the present invention, refers to a linear or branched divalent unsaturated hydrocarbon chain containing from 1 to 12 carbon atoms and comprising at least one double bond, including, but not limited to, ethenediyl, propenediyl, butenediyl, pentenediyl, hexenediyl and the like.

[0026] The term aryl group, as used in the present invention, refers to an aromatic hydrocarbon group preferably comprising 6 to 12 carbon atoms and comprising one or more fused rings, such as, for example, but not limited to, a phenyl or naphthyl group. Advantageously, it is a phenyl group.

[0027] The term “heterocyclic group”, as used in the present invention, refers to an aromatic or non-aromatic, saturated or unsaturated, monocyclic or polycyclic group (comprising fused, bridging or spiral rings) preferably comprising from 5 to 10, notably 5, 6, 9 or 10 atoms in the ring(s), wherein one or more, notably from one to four, advantageously one or two, carbon atom(s) of the ring(s), each being substituted with heteroatoms selected from a sulfur atom, an oxygen atom and a nitrogen atom. When the heterocyclyl group is a “nitrogen-containing heterocyclyl group”, it means that Petition 870260059145, dated 06 / 17 / 2026, page 22 / 117 8 / 51 at least one of the heteroatoms in the ring(s) is a nitrogen atom. It is not excluded that a “nitrogen-containing heterocyclyl group”, according to the invention, comprises oxygen atom(s) and / or sulfur atom(s) in the ring(s), in addition to at least one nitrogen atom. The nitrogen-containing heterocyclyl group according to the invention may be in its cationic form when it is linked to the rest of the molecule through a nitrogen atom, thus having a valence of 4.

[0028] When said heterocyclyl group is an aromatic compound, it may be referred to as a “heteroaryl” in the present disclosure. Examples of “nitrogen-containing heteroaryls” include, without limitation, pyrrolyl, pyridyl, thiazinyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, pyridazinyl, purinyl, pyrimidinyl, pyrazinyl, triazinyl, quinolinyl, isoquinolinyl, isoindolial, or indolyl. Preferably, in the context of the present invention, a nitrogen-containing heteroaryl is not a pyridyl.

[0029] When said heterocyclyl group is a non-aromatic compound, it may be referred to as a “heterocycloalkyl” in the present disclosure. Examples of “nitrogen-containing heterocycloalkyl” include, without limitation, piperidinyl, piperizinyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, thiazolidinyl, isothiazolidinyl, indolinyl and isoindolinyl.

[0030] The term “C1-C6-aryl alkyl”, as used in the present invention, refers to an alkyl group as defined above, substituted with an aryl group as defined above. Advantageously, a “C1-C6-aryl alkyl” is a benzyl group.

[0031] In the context of the present invention, an optionally substituted group means that the group in question is optionally replaced with one or more, preferably one or two, substituents that may be selected in particular. Petition 870260059145, dated 06 / 17 / 2026, p. 23 / 117 9 / 51 halogen, C1-C1 alkyl, C1-C1 haloalkyl, C2-C6 alkene, C2-C6 alkyne, aryl, N3, oxo, NRaRb, CORc, CO2Rd, CONReRf, ORg, N+RhRiRj, CN and NO2, where Raa Rjsion, independently of each other, H, C1-C1 alkyl or aryl, preferably H or C1-C1 alkyl. Advantageously, an optionally substituted group is substituted with one or two substituents selected from the group consisting of C1-C1 alkyl and ORg where Rg is H or C1-C1 alkyl.

[0032] The term Ci-Ce haloalkyl refers to a Ci-Ce alkyl chain as defined above, in which one or more hydrogen atoms are replaced by a halogen atom selected from fluorine, chlorine, bromine or iodine, preferably a fluorine atom. For example, it is a CF3 group.

[0033] In the context of the present invention, “unsaturated” means that the hydrocarbon chain may contain one or more unsaturations, that is, a C=C double bond or a C=C triple bond, advantageously one.

[0034] The term “leaving group” refers to an atom or group of atoms that are readily able to detach from a molecule with a lone pair, breaking the bond between it and the molecule.

[0035] The term “pharmaceutical composition” in the context of the present invention is understood to mean a composition with preventive and curative properties. [003β] The term “prodrug” refers to a typically pharmacologically inactive or less active derivative of an active drug that undergoes biotransformation in cellular or in vivo to release the active drug through chemical or enzymatic reactions. In the context of the invention, “pharmacologically inactive or less active derivative” means that the prodrug does not exhibit relevant activity with respect to inhibiting the active site of acetylcholinesterase in an in vivo environment. Petition 870260059145, dated 06 / 17 / 2026, page 24 / 117 10 / 51 vitro. However, the oxidized form is active in in cellular and in vivo assays because these conditions allow the transformations necessary to deliver the active drug. Prodrugs can offer many advantages over original drugs, such as greater penetration into the brain and, consequently, greater brain activity, greater stability, and better bioavailability.

[0037] In the context of the invention, prodrug compounds, as defined in the present disclosure, possess enhanced brain activity. After penetration into the brain, the prodrug compounds are oxidized to provide the corresponding active drugs, namely, potent acetylcholinesterase inhibitors. Compounds of formula (I)

[0038] The compound of formula (I) for use according to the present invention may be in the form of a stereoisomer or a mixture of stereoisomers, such as a mixture of enantiomers, diastereomers or tautomers, notably a racemic mixture.

[0039] In the context of the present invention, the nitrogen atoms of the compound of formula (I) may have a valence of 3 or a valence of 4. When they have a valence of 4, for example, when they are protonated, the nitrogen atoms are in the cationic form.

[0040] In particular, with regard to R1 and / or R2, the nitrogen-containing heterocyclyl group may be linked to the rest of the molecule via a carbon atom or a nitrogen atom. When linked to the rest of the molecule via a nitrogen atom, said nitrogen atom may have a valence of 3 or a valence of 4. When said nitrogen atom has a valence of 4, it is in its cationic form, i.e., an ammonium atom. This occurs mainly when the heterocyclyl group is a heteroaryl group. Petition 870260059145, dated 06 / 17 / 2026, page 25 / 117 11 / 51

[0041] In particular, the nitrogen of the piperidine moiety containing the benzyl group in the compound of formula (I) may have a valence of 3 or a valence of 4. When said nitrogen atom has a valence of 4, it is in its cationic form, that is, an ammonium.

[0042] In the context of the present invention, the nitrogen-containing heterocyclyl group, referring to R1 and / or R2, normally does not contain any other heteroatom besides nitrogen atom(s).

[0043] In the context of the present invention, the nitrogen-containing heterocyclyl group, referring to R1 and / or R2, is selected from the group consisting of pyrrolyl, pyridyl, thiazinyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, pyridazinyl, purinyl, pyrimidinyl, pyrazinyl, triazinyl, quinolinyl, isoquinolinyl, isoindolyl, indolyl, piperidinyl, piperizinyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, thiazolidinyl, isothiazolidinyl, dihydroquinolinyl, dihydroisoquinolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, indolinyl and isoindolinyl, optionally substituted.

[0044] According to some embodiments, R1 and R2 are each independently either an optionally substituted nitrogen-containing heterocyclyl group or an optionally substituted C1C6 aliphatic chain, wherein up to 4 methylene units of said aliphatic chain are optionally substituted by O, C(O), NH or C1-C6 N-alkyl, provided that at least one of R1 and R2 is an optionally substituted nitrogen-containing heterocyclyl group.

[0045] According to some embodiments, R1 and R2 are each independently an optionally substituted nitrogen-containing heterocyclyl group, as defined below, identical or different. Petition 870260059145, dated 06 / 17 / 2026, p. 26 / 117 12 / 51

[0046] According to preferred embodiments, R1 and R2 are different, one of R1 and R2 is an optionally substituted nitrogen-containing heterocyclyl group, as defined below, and the other is H, an optionally substituted C1-C6 aliphatic chain or an optionally substituted aryl, preferably H, an optionally substituted C1-C6 aliphatic chain, such as C1-C6 alkyl or an optionally substituted aryl, such as phenyl, more preferably H, a C1-C6 alkyl or an aryl, such as phenyl, even more preferably a C1-C6 alkyl including a methyl, an ethyl, a propyl, a tert-butyl, an n-butyl, notably a methyl.

[0047] According to a preferred embodiment, R1 and / or R2, preferably one of R1 and R2, is a heterocyclyl group containing nitrogen optionally substituted with 1 to 4 nitrogen atoms replacing the carbon atom in the ring, preferably 1 or 2, more preferably 1.

[0048] According to a preferred embodiment, R1 and / or R2, preferably one of R1 and R2, is an optionally substituted nitrogen-containing heterocyclyl group selected from the group consisting of pyrrolyl, pyridyl, thiazinyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, pyridazinyl, purinyl, pyrimidinyl, pyrazinyl, triazinyl, quinolinyl, isoquinolinyl, isoindolyl, indolyl, piperidinyl, piperizinyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, thiazolidinyl, isothiazolidinyl, dihydroquinolinyl, dihydroisoquinolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, indolinyl and isoindolinyl.

[0049] In a particular embodiment, R1 and / or R2, preferably one of R1 and R2, is a heteroaryl containing optionally substituted nitrogen, notably selected from the group consisting of pyrrolyl, thiazinyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, Petition 870260059145, dated 06 / 17 / 2026, page 27 / 117 13 / 51 pyridazinyl, purinyl, pyrimidinyl, pyrazinyl, triazinyl, quinolinyl, isoquinolinyl, isoindolyl or indolyl.

[0050] In another particular embodiment, R1 and / or R2, preferably one of R1 and R2, is an optionally substituted nitrogen-containing heterocycloalkyl, notably selected from the group consisting of piperidinyl, piperizinyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, thiazolidinyl, isothiazolidinyl, dihydroquinolinyl, dihydroisoquinolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, indolinyl and isoindolinyl.

[0051] Preferably, R1 and / or R2, when it is a nitrogen-containing heterocyclyl group, is unsubstituted or substituted with one or more substituents, preferably one or two, more preferably one, selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkene, C2-C6 alkyne, aryl, N3, oxo, NH2, NH-C1-C6 alkyl, N(C1-C6 alkyl)2, C(O)H, CO2-C1-C6 alkyl, CO2H, CN and NO2, preferably halogen, such as Cl, OH, NH2, C1-C6 alkyl, such as a methyl, and O-C1-C6 alkyl, such as a methoxy.

[0052] Preferably, R1 and / or R2, of R1 and R2, is a corresponding group of formulas: preferably one at a time of the following R8(A) (B) in what R3a and R8 are each independently selected from the group consisting of H, halogen, OH, NH2, NH-C1-C6 alkyl, a C1-C6 aliphatic chain, aryl, heteroaryl and C1-C6 alkyl-aryl, wherein up to 4 methylene units of said aliphatic chain are optionally substituted by O, C(O), NH or N-C1-C6 alkyl, said aliphatic chain being, Petition 870260059145, dated 06 / 17 / 2026, p. 28 / 117 14 / 51 optionally substituted aryl, heteroaryl or alkylaryl groups, or one or more of the pairs R3-R4, R4-R5, R5-R6 and R6-R7, together with the carbon atoms to which they are attached, form an optionally substituted aromatic or non-aromatic ring of 5 or 6 members, R9 and R10 are each independently one or more substituents selected from the group consisting of H, a Ci-Ce aliphatic chain, aryl, heteroaryl and Ci-Ce alkyl-aryl, wherein up to 4 methylene units of said aliphatic chain are optionally substituted by O, C(O), NH or NCi-Ce alkyl, said aliphatic chain, aryl, heteroaryl or alkyl-aryl being optionally substituted. represents a single or double bond, and represents the bond between R1 and the rest of the molecule.

[0053] It is understood that, in formula (C), R9 is one or more substituent(s) attached to the carbon atom(s) of the ring containing nitrogen and R10 is one or more substituent(s) attached to the carbon atom(s) of the phenyl moiety attached to the rest of the molecule.

[0054] More preferably, R3a R8 are each selected independently from the group consisting of H, halogen, OH, NH2, NH-Ci-Ce alkyl, a Ci-Ce alkyl and aryl, such as phenyl, or one or more of the pairs R3-R4, R4-R5, R5-R6 and R6-R7 form, together with the carbon atoms to which they are attached, an aromatic or non-aromatic ring of 5 or 6 members, unsubstituted or substituted with one or more, preferably one, substituent selected from halogen, OH, NH2, NH-Ci-Ce alkyl, Ci-Ce alkyl and O-Ci-Ce alkyl.

[0055] According to the preferred embodiments, R8 is H or C1-C1 alkyl, such as methyl, ethyl or isopropyl, notably methyl. Petition 870260059145, dated 06 / 17 / 2026, p. 29 / 117 15 / 51

[0056] According to preferred embodiments, one of the pairs R3-R4, R4-R5, R5-R6 and R6-R7 forms, together with the carbon atoms to which they are attached, a 6-membered aromatic ring, such as a phenyl, unsubstituted or substituted by one or more, preferably one, substituent selected from halogen, OH, NH2, NH-C1-C6 alkyl, C1-C6 alkyl and C1-C6 O-alkyl, such as methoxy, the other radicals between R3 and R7 being H.

[0057] According to preferred embodiments, R9 and R10 are each independently one or more substituents, preferably one, selected from the group consisting of H, a C1-C6 alkyl, halogen, OH, NH2 and NH-C1-C6 alkyl. More preferably, R9 is a substituent selected from the group consisting of OH and halogen, such as Cl, and R10 is H.

[0058] When R1 or R2 has the formula (B), as defined above, the nitrogen to which the rest of the molecule is attached can be neutral or cationic, depending on the bonds^ that said nitrogen forms in the ring, said bonds being single or double, on the condition that the valence of the nitrogen is never greater than 4.

[0059] In a specific embodiment, R1 and / or R2, preferably one of R1 and R2, is an optionally substituted 8- to 10-membered nitrogen-containing bicyclic heterocyclyl group, notably selected from the group consisting of quinolinyl, isoquinolinyl, dihydroquinolinyl, dihydroisoquinolinyl, unsubstituted or substituted with one or more, preferably one, substituent selected from halogen, OH, NH2, NH-C1-C6 alkyl, C1-C6 alkyl or C1-C6 O-alkyl, such as methoxy.

[0060] Formula (I) as defined herein covers active compounds, that is, drugs and prodrugs thereof.

[0061] According to a particular embodiment, when the compound of formula (I) is a prodrug, R1 and / or R2, Petition 870260059145, dated 06 / 17 / 2026, p. 30 / 117 16 / 51 preferably one of R1 and R2 is an optionally substituted nitrogen-containing heterocycloalkyl group, meaning that the ring is not aromatic. In such an embodiment, if the other R1 or R2 is also an optionally substituted nitrogen-containing heterocyclyl group, it is preferably an identical or different nitrogen-containing heterocycloalkyl group. According to such an embodiment, the heterocycloalkyl group can undergo an oxidation reaction when the prodrug enters the brain to deliver the active drug.

[0062] Therefore, according to a specific embodiment, when the compound of formula (I) is a drug, R1 or R2, when being a nitrogen-containing heterocyclyl group, is an optionally substituted nitrogen-containing heteroaryl, meaning that the ring is aromatic. In such embodiment, if the other R1 or R2 is also an optionally substituted nitrogen-containing heterocyclyl group, it is preferably an identical or different nitrogen-containing heterocycloaryl.

[0063] Thus, in a prodrug according to the invention, the optionally substituted nitrogen-containing heterocycloalkyl group, referring to R1 and / or R2, is preferably selected from the group consisting of pyrrolyl, thiazinyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, pyridazinyl, purinyl, pyrimidinyl, pyrazinyl, triazinyl, quinolinyl, isoquinolinyl, isoindolyl and indolyl, preferably quinolinyl and isoquinolinyl.

[0064] In a drug according to the invention, the optionally substituted nitrogen-containing heteroaryl group, referring to R1 and / or R2, is preferably selected from the group consisting of piperidinyl, piperizinyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, thiazolidinyl, isothiazolidinyl, dihydroquinolinyl, dihydroisoquinolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, indolinyl and Petition 870260059145, dated 06 / 17 / 2026, page 31 / 117 17 / 51 isoindolinyl, preferably dihydroquinolinyl, dihydroisoquinolinyl, tetrahydroquinolinyl and tetrahydroisoquinolinyl.

[0065] In the context of the present invention, the medicinal compound is the oxidized form of the corresponding prodrug compound. For example, if the prodrug contains a heterocycloalkyl group, it is oxidized and therefore aromatized in the corresponding drug, resulting in the corresponding heteroaryl group.

[0066] X is preferably an oxygen atom.

[0067] Li and L2 are each independently ligands corresponding to a divalent radical derived from a C1-C12 aliphatic chain, wherein one or more, preferably one to four, more preferably one or two, methylene units are optionally substituted by arylene, —O—, -S-, -C(=O)-, -SO2- or -N(C1-Cg alkyl)-, wherein said aliphatic chain is optionally substituted by one or more, preferably one, substituent selected from OH, halogen, C1-C6 alkyl or aryl, preferably OH or C1-C6 alkyl.

[0068] According to a preferred embodiment, L1 and L2 are each independently a divalent radical derived from an unsubstituted C1-C12 aliphatic chain, preferably a C1-C12 alkanediyl, a C2-C12 alkenediyl or a ligand of formula -CH=, notably a C1-C6 alkanediyl or a ligand of formula -CH=. More preferably, L1 and L2 are each independently a methylene group or a ligand of formula -CH=. It is understood that when the ligand is of formula -CH=, it is directly linked to R1 via the double bond and to the oxygen atom via the single bond.

[0069] In the compound of formula (I), nep are each independently 0 or 1, with the condition that p is 1 when R1 is a heterocyclyl group containing optionally substituted nitrogen and en is 1 when R2 is a heterocyclyl group Petition 870260059145, dated 06 / 17 / 2026, p. 32 / 117 18 / 51 containing optionally substituted nitrogen. p can therefore be 0 or 1 when R1 is not a heterocyclyl group containing optionally substituted nitrogen, and en can therefore be 0 or 1 when R2 is not a heterocyclyl group containing optionally substituted nitrogen. Preferably, p is 0 when R1 is not a heterocyclyl group containing optionally substituted nitrogen, and en is 0 when R2 is not a heterocyclyl group containing optionally substituted nitrogen. In other words, when R1 or R2 is not a heterocyclyl group containing optionally substituted nitrogen, said R1 or R2 is preferably directly linked to the oxygen atom by the indanone group, and not through an L1 or L2 ligand.

[0070] According to the preferred embodiment, R' is H, halogen, C1-C6 alkyl, aryl, heteroaryl or C1-C6 alkylaryl, said alkyl, aryl, heteroaryl or alkyl-aryl unsubstituted or substituted with one or more, preferably one, substituent selected from OH, halogen, C1-C6 alkyl or aryl, notably OH or C1-C6 alkyl. Preferably, R' is H, a halogen, or a C1-C6 alkyl group, such as methyl or ethyl. More preferably, R' is H.

[0071] In a specific embodiment, R1 is an optionally substituted nitrogen-containing heterocyclyl group, as defined in the present disclosure, R' is H or a C1C6 alkyl, such as methyl or ethyl, p is 1, n is 0 and R2 is a C1-C6 alkyl including a methyl, an ethyl, a propyl, a tert-butyl, an n-butyl. Preferably, R1 is an optionally substituted nitrogen-containing heterocyclyl group, as defined in the present development, p is 1, L1 is a divalent radical derived from a C1-C12 aliphatic chain, preferably a methylene or a ligand of formula -CH=, R2 is methyl, n is 0 and R' is H.

[0072] According to specific embodiments, in the compound of formula (I), R1 is selected from the group consisting of quinolinyl, isoquinolinyl, dihydroquinolinyl, diPetition 870260059145, dated 17 / 06 / 2026, p. 33 / 117 19 / 51 hydroisoquinolinyl, unsubstituted or substituted with one or more, preferably one, substituent selected from halogen, OH, NH2, NH-C1-C6 alkyl, C1-C6 alkyl or O-alkyl C1-C6, as methoxy, R2 is methyl, n is 0, p is 1, Li is a divalent radical derived from an aliphatic C1-C12 chain, preferably a methylene or a ligand of formula -CH=; and R' is H.

[0073] In another embodiment, R2 is an optionally substituted nitrogen-containing heterocyclyl group, as defined in the present disclosure, R' is H or a C1-C6 alkyl, such as methyl or ethyl, p is 0, n is 1 and R1 is a C1-C6 alkyl including a methyl, an ethyl, a propyl, a tert-butyl, an n-butyl. Preferably, R2 is an optionally substituted nitrogen-containing heterocyclyl group, as defined in the present disclosure, p is 0, L2 is a divalent radical derived from a C1-C12 aliphatic chain, preferably a methylene or a ligand of formula -CH=, R1 is methyl, n is 1 and R' is H.

[0074] In other embodiments, in the compound of formula (I), R2 is selected from the group consisting of quinolinyl, isoquinolinyl, dihydroquinolinyl, dihydroisoquinolinyl, unsubstituted or substituted with one or more, preferably one, substituent selected from halogen, OH, NH2, NH-C1-C6 alkyl, C1-C6 alkyl or C1-C6 O-alkyl, as methoxy, R1 is methyl, n is 1, p is 0, L2 is a divalent radical derived from an aliphatic C1-C12 chain, preferably a methylene or a ligand of formula -CH=; and R' is H.

[0075] According to a preferred embodiment, the compound of formula (I) is selected from the group consisting of: Petition 870260059145, dated 06 / 17 / 2026, p. 34 / 117 20 / 51 1, m = 1 4, m = 1 2, m = 2 5, m = 2 3, m = 3 6, m = 3 7, m = 1 10, m = 1 8, m = 2 11, m = 2 9, m = 3 12, m = 3 13, m=1 14, m=2 16,m=1 17,m=2 18,m=3 21, m=3 22, m=1 23, m=2 24, m=3 25,m=1 26,m=2 27,m=3 28,m=1 29,m=2 30,m=3 Petition 870260059145, dated 06 / 17 / 2026, p. 35 / 117 21 / 51 37, m=l 38, m=2 39, m=3 43, m = 1 44, m=2 Petition 870260059145, dated 06 / 17 / 2026, p. 36 / 117 22 / 51 5758 5960 6162 6364 Petition 870260059145, dated 06 / 17 / 2026, p. 37 / 117 23 / 51 Petition 870260059145, dated 06 / 17 / 2026, p. 38 / 117 24 / 51

[0076] In some embodiments, the compound of formula (I) is selected from the group consisting of compounds 1' to 76' in which X is N-OH and the remaining substituents are, respectively, as defined in compounds 1 to 76 above. For example, in compound 1', X is N-OH, and the other substituents are as in compound 1, that is, R' is H, R2 is CH3, Li is -CH2-, p is 1, n is 0 and R1 is dihydroquinolinyl.

[0077] In a particular embodiment, the compound of formula (I) according to the invention is a prodrug as defined above, notably selected from the group consisting of: 3, m = 3 6, m = 3 Petition 870260059145, dated 06 / 17 / 2026, p. 39 / 117 25 / 51 m = 3 m = 3 13, m=1 14, m=2 16,m=1 17,m=2 18,m=3 21, m=3 22, m=1 23, m=2 24, m=3 25, m=155 26,m=2 27,m=3

[0078] In a particular embodiment, the compound of formula (I) according to the invention is a drug as defined above, notably selected from the group consisting of: Petition 870260059145, dated 06 / 17 / 2026, p. 40 / 117 26 / 51 28, m=1 29, m=2 30, m=3 31, m=1 34, m=1 32, m=2 35, m=2 33, m=3 36, m=3 37, m=1 38, m=2 39, m=3 40, m=1 41, m=2 43, m = 1 44, m = 2 50, m=2 51, m=3 54, m=3 Petition 870260059145, dated 06 / 17 / 2026, p. 41 / 117 27 / 51 Petition 870260059145, dated 06 / 17 / 2026, p. 42 / 117 28 / 51 64 66 70 Petition 870260059145, dated 06 / 17 / 2026, p. 43 / 117 29 / 51 compound of formula (I) according to the invention is selected from the group consisting of: Petition 870260059145, dated 06 / 17 / 2026, p. 44 / 117 30 / 51 Xj r \ Y- 1 o 57 ρϊι \ ( T ΪΪΡ ^-Ah, 1 ο 59 Cl in> CT^ \\ 1 o 63 0 A AM AN<^ Ύ AZ / ΑΑΑ / θ'^^^ (j 75 e sais de cloridrato / XX3 XXXj d.....Λ·-! CD + + ω 5 ο ft ZA Λ*--\ \ \ / T \ / A / / \ç y / AM azH oHz= / rxww - <· oo —oo —oo \= / <1 Y__ / ] σ> Y__ / / σ> Y__ / / cn J \ o> 1 \ >t· 1 \ ro / \ oo y^oo^A / o^ay ϊ AAD ΌΑ uA A?^Aj + + + Petition 870260059145, dated 06 / 17 / 2026, p. 45 / 117 31 / 51

[0080] In a more preferred embodiment, the compound of formula (I) according to the invention is: or hydrochloride salt thereof. Method for preparing a compound of formula (I)

[0081] The compound of formula (I), as described above, or a pharmaceutically acceptable salt and / or solvate thereof, can be obtained by conventional methods well known in the art. In particular, the compound of formula (I) as described above, or a pharmaceutically acceptable salt and / or solvate thereof, can be obtained by a method comprising the following steps: (a) reaction of a compound of formula (II): Rcur (Lx)v-LV (II) where — is a single or double bond, Rx is an optionally substituted nitrogen-containing heterocyclyl group, as defined above. Lx is a divalent radical derived from an aliphatic C1-C12 chain as defined above, v is 0 or 1 and LV is a leaving group, with a compound of formula (III) or (III'): Petition 870260059145, dated 06 / 17 / 2026, page 46 / 117 32 / 51 X is an oxygen atom or an N-OH group. Ri is R2-(L2)n as defined above, with the condition that R2 is not an optionally substituted nitrogen-containing heterocyclyl group, in particular Ri is a methyl group, Rii is R1-(L1)p as defined above, with the condition that R1 is not an optionally substituted nitrogen-containing heterocyclyl group, in particular Rii is a methyl group, and R' is as defined above, (b) optionally reacting the compound of formula (III) or (III') with a compound of formula (IV) Ry ^(LyU-LV (IV), where — is a single or double bond, Ry is a heterocilyl containing optionally substituted nitrogen, as defined above. Ly is a divalent radical derived from an aliphatic C1-C12 chain as defined above, w is 0 or 1 and LV is an exit group.

[0082] The compounds of formula (II), (III), (III') and (IV) can be obtained according to methods well known to those skilled in the art. It is understood that the preferred embodiments mentioned for the compound of formula (I) in the present disclosure are applicable to compounds (II), (III), (III') and (IV).

[0083] It is understood that when the compound of formula (II) reacts with the compound of formula (III), Rx is typically as defined above for R1, Lx is typically as defined above for L1 and v is typically as defined above for pe when applicable, in the compound of formula (IV), Ry is typically as defined above for R2, Ly is typically as defined above for L2 and en is typically as defined above for n. Petition 870260059145, dated 06 / 17 / 2026, page 47 / 117 33 / 51

[0084] It is also understood that when the compound of formula (II) reacts with the compound of formula (III'), Rx is typically as defined above for R2, Lx is typically as defined above for L2 and v is typically as defined above for ne, when applicable, in the compound of formula (IV), Ry is typically as defined above for R1, Ly is typically as defined above for L1 and en is typically as defined above for p.

[0085] LV is notably selected from the group consisting of halogen, preferably Cl, and sulfonate ester group, such as mesylate or tosylate group.

[0086] In preferred embodiments, in the compound of formula (III), Ri is a methyl group and R' is H. The synthesis of the preferred compounds of formula (III) is described notably in Wang, Wei; Guangdong Huagong, 2015, Vol.42(17), p.73-74 and EP296560 A2.

[0087] Optionally, additional protection / deprotection and / or functionalization steps well known to those skilled in the art may occur before or after the reaction between compounds of formula (II) and (III) or (III') to provide the compound of formula (I) with suitable substituents, as described above.

[0088] In particular, after step (a) and before step (b), the compound of formula (III) or (III') can be deprotected at the position containing, respectively, the Riou Rii substituent, that is, the Riou Rii group can be removed to provide an OH group at the corresponding position, so that said -OH can react with compound (IV) to provide a compound of formula (I) in which R1 and R2 are both a nitrogen-containing heterocyclyl group.

[0089] According to a preferred embodiment, only one of R1 and R2 is a nitrogen-containing heterocyclyl group. According to this embodiment, step (b) is not performed and the compound R1n- group (III) corresponds to the R2-(L2)n- group in the final compound. Petition 870260059145, dated 06 / 17 / 2026, p. 48 / 117 34 / 51 of formula (I) or the Rii group in compound (III') corresponds to the R1-(L1)p- group in the final compound of formula (I).

[0090] According to a preferred embodiment, the compound of formula (III) or (III') is obtained from donepezil by selective deprotection of one of the two methoxy groups contained in the indanone moiety, for example, using strong basic conditions. In this embodiment, Riou Rii, respectively, is a methyl group.

[0091] In the method of preparing a compound of formula (I), an intermediate compound obtained at the end of a reaction step or the final compound obtained at the end of the reaction can be separated from the reaction medium by methods well known to those skilled in the art, such as by extraction, evaporation of the solvent or by precipitation or crystallization (followed by filtration).

[0092] The compound in question can also be purified, if necessary, by methods well known in the art, such as recrystallization, distillation, column chromatography (e.g., silica gel) or high-performance liquid chromatography (HPLC). Pharmaceutical composition

[0093] The present invention also relates to a pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and at least one compound of formula (I) as described above or a pharmaceutically acceptable salt and / or solvate thereof.

[0094] According to some embodiments, the pharmaceutical composition of the present invention comprises from 0.1 mg to 5 mg, preferably from 0.1 mg to 2.5 mg of a compound of formula (I) or a pharmaceutically acceptable salt and / or solvate thereof.

[0095] The pharmaceutical compositions of the invention may be intended for oral or parenteral administration (including, but not limited to, subcutaneous, intramuscular, intravenous), intraperitoneal, ocular, intravitreal, topical, sublingual, Petition 870260059145, dated 06 / 17 / 2026, page 49 / 117 35 / 51 preferably intraperitoneal, oral or intravenous administration. The active ingredient can be administered in unit doses for administration, mixed with conventional pharmaceutical vehicles, to animals, preferably mammals, including humans.

[0096] For oral administration, the pharmaceutical composition may be in solid or liquid form (solution or suspension).

[0097] A solid composition may be in the form of tablets, gelatin capsules, powders, granules, and the like. In tablets, the active ingredient may be mixed with pharmaceutical carriers such as gelatin, starch, lactose, magnesium stearate, talc, gum arabic, and the like before being compressed. Tablets may be further coated, primarily with sucrose or other suitable materials, or may be treated to have prolonged or delayed activity. In powders or granules, the active ingredient may be mixed or granulated with dispersing agents, humectants or suspending agents, and with flavor enhancers or sweeteners. In gelatin capsules, the active ingredient may be introduced into soft or hard gelatin capsules in the form of powder or granules, as mentioned above, or in the form of a liquid composition, as mentioned below.

[0098] A liquid composition may contain the active ingredient together with a sweetener, a flavor enhancer or a suitable colorant in a solvent such as water. The liquid composition may also be obtained by suspending or dissolving a powder or granules, as mentioned above, in a liquid such as water, juice, milk, etc. It may be, for example, a syrup or an elixir.

[0099] For parenteral administration, the composition may be in the form of an aqueous suspension or solution that may contain suspending agents and / or wetting agents. The composition is Petition 870260059145, dated 06 / 17 / 2026, page 50 / 117 36 / 51 advantageously sterile. It may be in the form of an isotonic solution (compared to blood). Therapeutic uses

[0100] The compound of formula (I), its salt and / or pharmaceutically acceptable solvate, or the pharmaceutical composition according to the invention act as acetylcholinesterase inhibitors, that is, they are able to inhibit the hydrolysis of acetylcholine into choline and acetate, thus allowing an increase in the duration of action of acetylcholine in the central nervous system.

[0101] The present invention relates to a compound of formula (I) according to the invention or to a pharmaceutically acceptable salt and / or solvate thereof or a pharmaceutical composition according to the invention for use as a medicament, in particular in the prevention and / or treatment of an acetylcholinesterase-associated disorder.

[0102] In other words, the present invention relates to the use of a compound of formula (I) according to the invention or a pharmaceutically acceptable salt and / or solvate thereof, or a pharmaceutical composition according to the invention for the manufacture of a medicament, notably intended for the prevention and / or treatment of a disorder associated with acetylcholinesterase.

[0103] In other words, the present invention relates to the use of a compound of formula (I) according to the invention or a pharmaceutically acceptable salt and / or solvate thereof or a pharmaceutical composition according to the invention for the prevention and / or treatment of a disorder associated with acetylcholinesterase.

[0104] In other words, the present invention relates to a method for the prevention and / or treatment of a disorder associated with acetylcholinesterase, comprising administering to a person in need of an effective dose a compound of formula (I) according to the invention or a pharmaceutically graded salt and / or solvate. Petition 870260059145, dated 06 / 17 / 2026, p. 51 / 117 37 / 51 acceptable of the same or a pharmaceutical composition according to the invention.

[0105] According to some embodiments, the compound of formula (I) or a pharmaceutically acceptable salt and / or solvate thereof for use in the prevention and / or treatment of an acetylcholinesterase-associated disorder is administered to an individual in need thereof at a daily dose ranging from 0.005 mg / kg to 0.5 mg / kg, preferably from 0.01 mg / kg to 0.1 mg / kg, more preferably from 0.01 mg / kg to 0.05 mg / kg, even more preferably from 0.01 mg / kg to 0.03 mg / kg.

[0106] An acetylcholine-associated disorder is preferably selected from the group consisting of compulsive disorders and related behaviors, including addiction, obsessive-compulsive disorders and eating disorders, and neurodegenerative disorders such as Parkinson's disease or Alzheimer's disease. The term "eating disorders" includes, in the context of the present invention, anorexia, notably anorexia nervosa, bulimia, notably bulimia nervosa, and the compulsive dimension of obesity. By "compulsive dimension of obesity," it is understood, within the scope of the present invention, that obese overweight patients frequently demonstrate compulsive eating behaviors (see Houben et al., Journal of Health Psychology, 2019 Volume 24, pp. 1145-1152).

[0107] In particular, the compound of formula (I) according to the invention or a pharmaceutically acceptable salt and / or solvate thereof is useful for preventing or treating compulsive disorders and related behaviors, including addiction, obsessive-compulsive disorders and eating disorders, notably eating disorders such as anorexia nervosa and bulimia nervosa. Description of the figures

[0108] Figure 1: Experiment No. 1: Effect of daily doses of 0.03 mg / kg of donquina (i.e., compound 56) and donepezil on Petition 870260059145, dated 06 / 17 / 2026, page 52 / 117 38 / 51 VGLUT3T8I / T81 mice versus saline control in an activity-based anorexia (ABA) model. A wild-type (WT) group treated with saline solution was used as a control. (A) Measurement of food intake (% of baseline) during the 7 or 8 days of the food restriction phase in WT mice (n = 8, circles), VGLUT3T8I / T8I mice treated daily with 0.03 mg / kg of donquina (n = 7, triangles), and VGLUT3T8I / T8I mice treated daily with saline solution (n = 8, squares). (B) Body weight was monitored daily, and mice with less than 75% of body weight from baseline were considered anorexic.During the food restriction phase of the ABA trial: percentage of mice with body weight equal to or greater than 75% of their baseline body weight in WT mice (n=8, solid line), in VGLUT3T8I / T8I mice treated daily with 0.03 mg / kg of donquina (n=7, dashed line), and in VGLUT3T8I / T8I mice treated with saline solution (n=8, dashes). Experiment #2: Effect of daily doses of 0.01 mg / kg of donquina (i.e., compound 56) versus donepezil (0.03 mg / kg) and saline control in VGLUT3T8I / T8I mice in an activity-based anorexia (ABA) model. (C) Measurement of food intake (% of baseline) during the 7 or 8 days of the food restriction phase in VGLUT3T8I / T8I mice treated daily with 0.01 mg / kg of donquina (n=7, triangles), VGLUT3T8I / T8I mice treated daily with 0.03 mg / kg of donepezil (n=8, squares) and VGLUT3T8I / T8I mice treated with saline solution (n=8, circles).(D) During the food restriction phase of the ABA test: percentage of mice with weight equal to or greater than 75% of baseline body weight in VGLUT3T8I / T8I mice treated with saline solution (n=8, solid line), in VGLUT3T8I / T8I mice treated daily with 0.01 mg / kg of donquina (n=7, dashed line) and in VGLUT3T8I / T8I mice treated daily with 0.03 mg / kg of donepezil (n=8, dashes). Petition 870260059145, dated 06 / 17 / 2026, p. 53 / 117 39 / 51 Examples 1) Synthesis 1.1) Material

[0109] Air- and moisture-sensitive manipulations were performed under nitrogen or in vacuo using standard Schlenk techniques. Anhydrous solvents (Et2O, EtOH, DCM, MeOH CH3CN, THE, toluene, and hexane) were purchased from Sigma-Aldrich (Merck KGaA, Darmstadt, Germany). All other chemicals were purchased from Alfa Aesar (Karlsruhe, Germany), Sigma Aldrich, and TCI Europe (Boerenveldseweg, Belgium) and used without further purification unless otherwise indicated. Analytical thin-layer chromatography (TLC) was performed using Merck SIL G / UV254 plates. Compounds were visualized by UV light exposure or by immersing the plates in solutions of phosphomolybdic acid, ninhydrin, or potassium permanganate, followed by heating. Flash column chromatography was performed using silica gel 60 (Sigma-Aldrich, St. Louis, USA). NMR spectra were recorded on Brucker Avance III nanobay spectrometers at 300 MHz or 400 MHz.The 1H and 13C NMR chemical shifts (δ) are expressed in parts per million (ppm) relative to the TMS scale. Coupling constants J are expressed in Hz. The following abbreviations are used for the multiplicities of the proton spectra: s: singlet, d: doublet, t: triplet, q: quartet, qt: quintuple, sp: septuplet, m: multiplet, br.: wide, dd: double doublet, dt: double triplet. Coupling constants (J) are reported in Hertz (Hz). Mass spectrometry was performed at the mass spectrometry service of the University of Paris Descartes, in perfusion mode or using a Shimadzu Nexera X2 HPLC system (Kyoto, Japan) and a High Resolution Orbitrap Exactive mass spectrometer (Thermo Fisher, San Jose, USA). Purification by HPLC was performed using a Gilson analytical instrument (Villiers-le-Bel, France). Petition 870260059145, dated 06 / 17 / 2026, page 54 / 117 40 / 51 1.2) Synthesis and characterization General procedure A • Step 1: synthesis of the iodo-1-alkylquinoline derivative

[0110] Optionally substituted quinoline (5 g, 31.40 mmol) was refluxed with appropriate iodoalkyl (15.6 mL, 157 mmol) for 48 h. The reaction mixture was cooled to room temperature and Et2O was added. The mixture was triturated and the residue was washed with Et2O to yield the corresponding 1-alkylquinolinium iodide as a solid. The compound was used without further purification. The optionally substituted 1-alkylquinolinium iodide was then added for 5 minutes to a solution of MeMgBr (3 M in DCM, 19.43 mL, 58.3 mmol) at 0 °C. The reaction mixture was stirred at this temperature for 1 h, then for 2 h at room temperature. Water was added slowly, followed by a concentrated HCl solution until two layers formed, then ammonium chloride was added and the solution was alkalized with ammonia. The organic layer was washed with water, dried over MgSO4 and concentrated under vacuum to produce the appropriate dihydroquinoline, which was used directly in the next step without purification. The dihydroquinoline was refluxed in EtOH (40 mL) with iodine (9.6 g) for 15 min and cooled to room temperature. The resulting residue was filtered and washed with EtOH and Et2O to obtain the corresponding 1-alkylmethylquinoline-1-io iodide. Optionally substituted 1-alkyl-methylquinoline-1-iodide 100 mg (0.29 mmol, 1 eq) was dissolved in 15 mL of yellowish-yellow dichloromethane (DCM).After dissolution, approximately 90 pL (0.64 mmol, 2.2 eq) of triethylamine (TEA) was added. The reddish-brown solution darkened to a dark brown color. After five minutes, iodine (0.29 mmol, 1 eq) was added. After 3 hours, iodine was added again (0.29 mmol, 1 eq). The reaction was... Petition 870260059145, dated 06 / 17 / 2026, page 55 / 117 41 / 51 stirred for 60 hours at room temperature. The mixture was purified as follows: The solvent was removed under vacuum (black-brown oily liquid). 5 mL of cyclohexane were added, which turned pink. The cyclohexane was removed after 1 hour and the remainder was removed under vacuum. The reaction mixture was diluted with DCM (30 mL) and washed with saturated NaCl solution (2 x 20 mL). The solvent was removed in vacuo. TLC and ninhydrin tests showed triethylammonium in water. The NMR spectrum still showed an excess of TEA. The reaction mixture was diluted with DCM (3 mL) and filtered through 1 cm of silica gel DCM / MeOH (1:0 ^ 95:5). Generally, purification is not necessary; the crude product is used for addition to abacavir or formed in situ. Specific example: Synthesis of the H2-QUIN intermediate Scheme 1. Synthetic scheme for the synthesis of H2-QUIN 6-methoxy-1-isopropylquinoline-1-iodide

[0111] 6-methoxyquinoline (5 g, 31.40 mmol) was refluxed with iodopropane (15.6 mL, 157 mmol) for 48 h. The reaction mixture was cooled to room temperature and Et2O was added. The mixture was triturated and the residue was washed with Et2O to yield the titrant compound (9.4 g, 91%) as a yellow solid; 1H-NMR (400 MHz, DMSO-d6) δ 9.44 (dd, 1 H, J = 1.5, 6.0 Hz, ArH), 9.11 (d, 1H, J = 8.4 Hz, ArH), 8.67 (d, 1H, J =9.9 Hz, ArH), 8.14 (dd, 1 H, J = 6.0, 8.3 Hz, ArH), 7.94 (d, 1 H, J = 3.0 Hz, ArH), 7.90 (dd, 1 H, J = 7.3, 9.0 Hz, ArH), 5.86(h, H, J = 6.5 Hz, CHCH3), 4 (s, 3 H, OCH3), 1.70 (d, 6 H, J =6.5 Hz, CHCH3). 1-Isopropyl-6-methoxy-2-methylquinolin-1-iodide P1

[0112] 1-Isopropyl-6-methoxyquinoline-1-iodide (10 g, 29.15 mmol) was added over 5 min to a solution of MeMgBr (3 M in DCM, 19.43 mL, 58.3 mmol) at 0 °C. The mixture of Petition 870260059145, dated 06 / 17 / 2026, page 56 / 117 42 / 51 reaction was stirred at this temperature for 1 h, then for h at room temperature. Water was added slowly, followed by a concentrated HCl solution until two layers formed, then ammonium chloride was added and the solution was alkalized with ammonia. The organic layer was washed with water, dried over MgSO4 and concentrated in vacuo to produce dihydroquinoline (6.02 g), which was used directly in the next step without purification. The dihydroquinoline was refluxed in EtOH (40 mL) with iodine (9.6 g) for 15 min and cooled to room temperature. The resulting residue was filtered and washed with EtOH and Et2O to obtain 1-isopropyl-6-methoxy-2-methylquinolin-1-iodide (9.2 g) with a yield of 88%; 1H-NMR (400 MHz, DMSO-d6) δ 8.93 (d, 1 H, J = 8.6 Hz, ArH), 8.65 (d, 1 H, J = 9.9 Hz, ArH), 8.04 (d, 1 H, J = 8.5 Hz, ArH), 7.85 (d, 1 H, J = 8.5 Hz, ArH), 7.85 (d, 1 H, J = 7.7 Hz, ArH (d, 1H, J = 8.5 Hz, ArH), 5.65 (sp, 1 H, J = 6.5 Hz, CHCH3), 3.99 (s, 3 H, CH3), 1.85 (d, 6 H, J = 6.5 Hz, CHCH3 ). Synthesis of 2-(iodomethyl)-1-isopropyl-6methoxyquinoline-1-io (H2-QUIN) iodate.

[0113] 100 mg (0.29 mmol, 1 eq) of 1-isopropyl-6-methoxy-2-methylquinoline 1-iodide was dissolved in 15 mL of yellowish-yellow dichloromethane (DCM). After dissolution, approximately 90 µL (0.64 mmol, 2.2 eq) of triethylamine (TEA) was added. The reddish-brown solution darkened to a dark brown color. After five minutes, 74 mg (0.29 mmol, 1 eq) of iodine was added. After 3 hours, another 74 mg (0.29 mmol, 1 eq) of iodine was added. The reaction was stirred for 60 hours at room temperature. The mixture was purified as follows: the solvent was removed in vacuo (blackish-brown oily liquid). 5 mL of cyclohexane was added, which turned pink. Cyclohexane was removed after 1 hour, and the remainder was removed under vacuum. The reaction mixture was diluted with DCM (30 mL) and washed with saturated NaCl solution. Petition 870260059145, dated 06 / 17 / 2026, page 57 / 117 43 / 51 (2 x 20 mL). The solvent was removed in vacuum. TLC and ninhydrin tests showed triethylammonium in the water. The NMR spectrum still showed an excess of TEA. The reaction mixture was diluted with DCM (3 mL) and filtered through 1 cm of DCM / MeOH silica gel (1:0 ^ 95:5). Normally, there is no need for purification; the crude product is used for addition to abacavir or formed in situ. • Step 2: coupling with donepezil

[0114] Donepezil (1 g, 2.6 mmol) was demethylated at position 5 by reaction with NaCN (1.25 g, 26 mmol) in DMSO (10 mL). The reaction was stirred at 100°C for two days, cooled, diluted with water, and extracted with dichloromethane. The aqueous solution was acidified with concentrated HCl and extracted with dichloromethane. The organic layer was dried over MgSO4 and evaporated to give the corresponding intermediate (500 mg).

[0115] In a flask under argon equipped with a magnetic stirring bar, the intermediate (61 mg, 0.164 mmol), silver acetate (AgOAc) (2.13 mg, 12.8 qmol), and 1,2-bis(diphenylphosphino)ethane (dppe) (5.1 mg, 12.8 qmol) are placed. Then, 0.64 mL of DMF is added. The mixture is stirred at room temperature for 10 minutes and then at 10 °C. Next, the iodo-1-alkylquinolinium derivative from step 1 (0.1 g, 0.213 mmol) and LiHMDS (2.8 mg, 17 qmol) are added. The reaction medium is left under these conditions for 8 hours until the reagents are consumed. Finally, following thin-layer chromatography, we performed a separation of fractions by column chromatography (Cyclohexane / EtOAc 7:3). The compounds were obtained with yields of 3 to 10%. Specific example: Synthesis of compound 56 donepezil A7 56 Intermediate A7: Petition 870260059145, dated 06 / 17 / 2026, page 58 / 117 44 / 51

[0116] 1H-NMR(400 MHz, CDCl3) δ 7.30-7.20 (m,3H, aromatic), 7.19-7.15 (m, 2H, aromatic), 7.10 (s,1H, aromatic), 6.85 (s, 1H, aromatic), 3.85 (s, 3H, OCH3), 3.43 (s, 2H, NCH2Ph), 3.15 (dd, 1H), 2.90-2.80 (m, 2H), 2.66 (m,2H), 1.93-1.83 (m, 3H), 1.69-1.55 (m, 2H), 1.40 (m, 1H), 1.35-1.15 (m, 3H). Compound 56: (income = 10%)

[0117] 1H-NMR(400 MHz, CDCL·) δ δ 9.34 (d, 1H, NH), 8.80(d, 1H, aromatic), 8.47 (d, 1H, aromatic), 8.41 (d, 1H, aromatic), 8.56 (s, 1H, aromatic), 8.26 (s, 1H, aromatic), 7.94 (d,1H, aromatic), 7.50-7.45 (m, 2H, aromatic), 7.40-7.35 (m,2H, aromatic), 7.15 (s, 1H, aromatic), 6.92 (s, 1H, aromatic), 4.05 (s, 3H, OCH3); 3.96 (s, 3H, OCH3), 3.13 (s, 2H, NCH2Ph), 3.05 (s,1H); 3.01 (m, 1H), 2.90-2.80 (m, 2H), 2.67 (m, 2H), 2.051.80 (m, 3H), 1.69-1.55 (m, 2H), 1.40 (m, 1H), 1.35-1.20(m, 3H). Characterization of the compounds of the invention Compound 62: (income = 3.5%)

[0118] 1H-NMR(400 MHz, CDCL·) δ 9.77 (d, 1H, NH), 8.91(d, 1H, aromatic), 8.23-8.09 (m, 1H, aromatic), 7.86 (d,2H, aromatic), 7.70 (m, 2H, aromatic), 7.40-7.35 (m,2H, aromatic), 7.17 (s, 1H, aromatic), 6.89 (s, 2H, aromatic), 5.92 (s, 2H, CH2); 4.68 (s, 3H, OCH3), 3.13 (s, 2H, NCH2Ph), 3.05 (s, 1H); 3.01 (m, 1H), 2.90-2.80 (m, 2H), 2.67 (m, 2H), 2.051.80 (m, 3H), 1.69-1.55 (m, 2H), 1.45 (m, 3H). Composite 64: (income = 4.20%) Petition 870260059145, dated 06 / 17 / 2026, p. 59 / 117 45 / 51

[0119] 1H-NMR (400 MHz, CDCI3) δ 8.95 (d, 1H), 8.41-8.16 (m, 3H, aromatic), 8.08 (m, 1H) 7.85 (m, 1H), 7.75 (m, 1H), 7.62 (m, 1H); - 7.30 (m, 5H), 7.13 (d, 1H), 6.94 (s, 1H); 5.00(s, 2H); 3.86 (s, 3H); 3.75 (s, 3H); 3.16 (s, 2H); 3.22 (3H); 2,842.51 (m, 4H); 2.05-1.85 (m, 2H); 1.59-1.25 (m.5H). Composto 63: (rendimento = 3,26%)

[0120] 1H-RMN(400 MHz, CDCL·) δ 8.30 (d, 2H), 8.00 (m,2H), 7.82 (s, 1H), 7.48 (m, 2H),7.35- 7.15 (m, 6H), 6.93 (s,1H); 6.31 (s, 2H); 3.94 (m, 6H); 3.53 (s, 2H); 3.35 (1H); 2.92-2.85 (m, 2H); 2.15-1.90 (m, 4H); 1.57 (m, 2H), 1.37-1.20 (m, 5H). Composto 75 (rendimento = 9,15%) 7.21 (m, 1H), 6.91 (m, 1H); 4,26 (m, 1H); 3.98(s, (3H); 3.87 (s, 2H); 3.70-3.27 (3H); 2.60-2.34 (m, 4H); 2.36-2.21 (m, 2H); 1.61-1.28 (m, 5H); 0.98-0.82 (d, 6H). Petition 870260059145, on 06 / 17 / 2026, page. 60 / 117 46 / 51 Composto 76 (rendimento = 6,48%)

[0122] 1H-RMN(400 MHz, CDCla) δ 8.92 (s, 2H), 8.13 (m, 3H), 7.85 (m, 1H), 7.71 (m, 1H), 7.52-7.30 (m, 5H), 7.13 (d,1H), 6.82 (s, 1H); 5.23 (s, 3H); 3.92 (s, 3H); 3.48 (m, 3H);3.12 (1H); 2.86 (m, 1H); 2.63-2.30 (m, 4H); 2.25 (m,2H), 1.37-1.20 (m,11H). General Procedure B

[0123] Donepezil (1 g, 2.6 mmol) was demethylated at position 5 by reaction with NaCN (1.25 g, 26 mmol) in DMSO (10 mL). The reaction was stirred at 100 °C for two days, cooled, diluted with water, and extracted with dichloromethane. The aqueous solution was acidified with concentrated HCl and extracted with dichloromethane. The organic layer was dried over MgSO4 and evaporated to give the corresponding intermediate (500 mg).

[0124] In an argon-conditioned flask equipped with a magnetic stirring bar, the intermediate (61 mg, 0.164 mmol) was stirred for 3 h at room temperature with K2CO3 (25 mg, 0.25 mmol, 1.5 equiv), iodomethyl bromide (4 equiv), and DMF (2 mL). The mixture was then extracted with dichloromethane, and after evaporation, the crude compound was used without further purification with the quinoline derivative. The quinoline derivative (3.14 mmol, 2 eq) was refluxed with crude iodo-donepezyl derivative (15.7 mmol, 5 eq) in anhydrous THF for 48 h. The reaction mixture was cooled to room temperature, and Et2O was added. The mixture was ground, and the residue was washed with Et2O to yield the titrant compound as a brown solid with a yield of 2.45 to 10.3%. Petition 870260059145, dated 06 / 17 / 2026, pp. 61 / 117 47 / 51 Compound 59: (yield = 5.43%) 5H) 1H) 4H) δ 7.65

[0125] 1H-RMN(400 MHz, CDCL) 7.21-7.09 4.19 (s 2.60-2.45 (m 3H), 7.49 (m (m 2H) 6.92 (s 1H) 5.38 (s 2H), 5.31 (s 3H) 3.49 (s, 2H) 3.22 (m 1H) 2.90-2.40 (m (m 4H) 2.05-1.80 (m 2H) 1.57-1.35 (m 2H) 1.30-1.10 (m, 3H). Composto 58: (rendimento = 2,45%)

[0126] 1H-RMN(400 MHz, CDCI3) δ 8.94 (d, 1H), 8.78 (d 1H aromatico), 8,18 (m, 2H, aromatico), 7,75 (d, 1H, aromatico) 7.65-7.35 (m, 6H, aromático) 7,19 (s, 1H, aromatico), 7,13 (s 1H, aromático), 5.65 (s 2H CH2); 3.91 (s, 3H); 3.71 (s, 2H) 3.55 (m, 1H); 2.95 (s 2H); 2.60-2.22 (m, 6H), 1.80-1.54 (m 5H). Composto 57: (rendimento 10.3% Petition 870260059145, dated 06 / 17 / 2026, p. 62 / 117 48 / 51

[0127] 1H-NMR (400 MHz, CDCI3) δ 8.95 (d, 1H), 8.19 (d, 2H, aromatic), 8.08 (m, 2H) 7.85 (m, 2H), 7.62 (m, 2H), 7.52-7.30 (m, 5H), 7.13 (d, 1H), 6.98 (s, 1H); 5.44 (s, 2H); 4.10 (s, 2H); 3.92 (s, 3H); 3.48 (m, 1H); 3.24 (2H); 2.6-2.34 (m, 4H); 2,011.82 (m, 2H); 1.61-1.28 (m, 5H). 2) Efficacy of donquina (i.e., compound 56) in ACh-deprived mutant mice in the ABA model.

[0128] Self-starvation behaviors are modeled in the activity-based anorexia test (ABA) (Klenotich, SJ, Dulawa, 2012 Methods Mol Biol 829, 377-93). In this test, animals are housed in the presence of a running wheel. Access to food is progressively restricted over a period of 8 days. For these animal experiments, a hypocholinergic mouse model was used. The atypical vesicular transporter type 3 (VGLUT3) is expressed by all striatal cholinergic interneurons (El Mestikawy et al. 2011, Nat Rev Neurosci 12(4), 204-16).

[0129] In 2015, the El Mestikawy team discovered a p.T8I variant of VGLUT3 expressed in patients suffering from substance use disorder and eating disorders (Sakae et al. Mol Psychiatry, 2015, 20(11), 1448-59). Mice expressing this variant (VGLUT3T8I / T8I mice) have reduced cholinergic tone in the striatum and are more vulnerable to self-starvation in the ABA model. In other words, VGLUT3T8I / T8I mice exhibit the same main symptomatology as anorexic patients and are considered a model of choice for anorexia. Activity-based anorexia model (ABA)

[0130] The ABA model was performed as described by Klenotich and Dulawa (Klenotich, SJ, Dulawa, 2012 Methods Mol Biol 829, 377-93) and as previously reported (Favier, M., et al.. J Clin Invest 130, 6616-6630 (2020)). For habituation, all mice were housed individually in cages with running wheels for 7 days, with unrestricted access to food, water and Petition 870260059145, dated 06 / 17 / 2026, p. 63 / 117 49 / 51 running wheel. After the adaptation period, all mice were kept in the same cages with running wheels for another 8 days. Access to food was progressively restricted, from 8 h (day 1) to 2 h (day 8) per day. Body weight and food intake were measured daily before and after food access, respectively. Mice that lose more than 25% of their initial body weight (baseline) are considered “anorexic.” The days until the mice reached 75% or less of their baseline body weight provided a measure of survival. For the pharmacological treatment experiment, mice received daily intraperitoneal injections of donquina (i.e., compound 56, at 0.03 or 0.01 mg / kg, diluted in 0.9% NaCl), donepezil (reference compound, at 0.03 mg.kg-1, diluted in 0.9% NaCl), or control saline solution (NaCl) at 0.9% by weight.The mice were treated daily 30 minutes before the start of food access, during both the baseline and food restriction phases.

[0131] Figure 1(A) illustrates that administration of donquina (i.e., compound 56) at a dose of 0.03 mg / kg per day for 7 days to VGLUT3T8I / T8I mice leads to a similar level of food intake as that of wild-type mice treated with saline. In contrast, VGLUT3T8I / T8I mice treated with saline tend to eat less and exhibit self-starvation / anorexia behavior.

[0132] Figure 1(B) shows that all (100%) VGLUT3T8I / T8I mice treated with saline solution had less than 75% of their baseline body weight after 8 days in the ABA test. On the other hand, administration of daily doses of 0.03 mg / kg of donquina prevents VGLUT3T8I / T8I mice from losing weight, as 60% of them still weigh at least 75% of their baseline body weight after 8 days, which is similar to the wild-type control group treated with saline solution. Similarly, Figure 1C shows that doses Petition 870260059145, dated 06 / 17 / 2026, pp. 64 / 117 Daily doses of 0.01 mg / kg of donquina (50 / 51) also saved mice from self-starvation, as approximately 90% of the mice weighed at least 75% of their baseline body weight after 8 days. Overall, these data exemplify that donquina is a suitable and effective treatment for anorexic behaviors.

[0133] In comparison, the same experiment was performed with a known acetylcholinesterase inhibitor, donepezil (see figures 1(C) and 1(D)). Figure 1(C) shows that donquina, at a lower dose (0.01 mg / kg), is more efficient than donepezil at 0.03 mg / kg in reducing food restriction in VGLUT3T8I / T8I mice. Figure 1(D) shows that a daily dose of 0.03 mg / kg of donepezil is less efficient in reducing the number of VGLUT3T8I / T8I mice that lose weight to 75% of their baseline body weight or less than a daily dose of 0.01 mg / kg of donquina. 3) Inhibition of acetylcholinesterase (AChE) 3.1) Procedure

[0134] A solution of each compound tested is prepared by dissolving the compound in a 1 mM DMSO stock solution and diluting with water to the following concentrations: 100 nM, 10 nM and 1 nM.

[0135] The procedure for testing the Sigma Aldrich MAK119 kit (colorimetric test) was followed as described: The working reagent (MAK119C) from the kit is prepared fresh and used within 30 minutes. Solution A is prepared by dissolving the working reagent (192 mg) in 19.2 ml of assay buffer (MAK119A) from the kit. A solution B made with 200 mL of water and 200 mL of Calibrator (MAK119B from the kit) is distributed into separate wells of the 96-well plate. 10 mL of the tested compound solution are added to the wells, and then 190 mL of solution A are added to all sample wells. The negative control wells are prepared by adding solutions A and B, without adding the solution of Petition 870260059145, dated 06 / 17 / 2026, pp. 65 / 117 51 / 51 compound tested, and positive control wells are prepared by adding solutions A, B and 1μM donepezil. The plate was incubated at room temperature for 2 min and the initial absorbance at 412 nm (A412)ini was measured. After 10 min of incubation at room temperature, the final measurement (A412) was taken.

[0136] The following calculation was then obtained: (A4i2)blank Inhibition was calculated by comparing the absorbance of samples containing the tested compounds at 412 nm (A412) and the absorbance of the negative and positive controls after 12 min of incubation. 3.2) Results Table 1 Tested Compound % Inhibition (100nM) % Inhibition (10nM) % Inhibition (1nM) 56 100 75 50 62 100 100 59 100 100 57 100 100 76 100 100 63 75 75 75 64 100 100 25 75 100 100 Donepezil 100 75 25

[0137] These results show that the compounds of the invention are at least as efficient, and for some of them more efficient, than donepezil in inhibiting acetylcholinesterase.

Claims

1. Compound, characterized in that it has the formula (I): or a pharmaceutically acceptable salt and / or solvate thereof, wherein represents a single or double bond, and X is an oxygen atom or an N-OH group, R1 and R2 are each independently H, an optionally substituted nitrogen-containing heterocyclyl group, an optionally substituted C1-C6 aliphatic chain or an optionally substituted aryl group, wherein up to 4 methylene units of said aliphatic chain are optionally substituted by O, C(O), NH or C1-C6 N-alkyl, provided that at least one of R1 and R2 is an optionally substituted nitrogen-containing heterocyclyl group, L1 and L2 are each independently a divalent radical derived from a C1-C12 aliphatic chain, wherein one or more, preferably one to four, methylene units are optionally substituted by arylene, —O—, -S-, -C(=O)-, -SO2 or -N(C1-C6 alkyl)-,wherein the said aliphatic chain is optionally substituted, p' is each independently 0 or 1, provided that p is 1 when R1 is an optionally substituted nitrogen-containing heterocyclyl group and p is 1 when R2 is an optionally substituted nitrogen-containing heterocyclyl group, and R' is H, halogen, an optionally substituted C1-C6 aliphatic chain, an optionally substituted aryl, an optionally substituted heteroaryl or an optionally substituted C1-C6-aryl alkyl, wherein up to 4 methylene units of said aliphatic chain are optionally substituted by O, C(O), NH or N-C1-C6 alkyl.

2. Compound according to claim 1, characterized in that the optionally substituted nitrogen-containing heterocyclyl group is selected from the group consisting of pyrrolyl, pyridyl, thiazinyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, pyridazinyl, purinyl, pyrimidinyl, pyrazinyl, triazinyl, quinolinyl, isoquinolinyl, isoindolyl, indolyl, piperidinyl, piperizinyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, thiazolidinyl, isothiazolidinyl, dihydroquinolinyl, dihydroisoquinolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, indolinyl and isoindolinyl.

3. Compound according to claim 1 or 2, characterized in that R1 and / or R2, preferably one of R1 and R2, is a group corresponding to one of the following formulas: R10 R9 R8 (B) (C) wherein R3 to R8 are each independently selected from the group consisting of H, halogen, OH, NH2, NH-C1-C6 alkyl, a C1-C6 aliphatic chain, aryl, heteroaryl and C1-C6 alkyl aryl, wherein up to 4 methylene units of said aliphatic chain are optionally substituted by O, C(O), NH or C1-C6 N-alkyl, said aliphatic, aryl, heteroaryl or alkyl-aryl chain being optionally substituted, or Petition 870250066871, dated 07 / 31 / 2025, p.84 / 102 3 / 10 one or more of the pairs R3-R4, R4-R5, R5-R6 and R6-R7 form, together with the carbon atoms to which they are attached, an optionally substituted aromatic or non-aromatic ring of 5 or 6 members, R9 and R10 are each independently one or more substituents selected from the group consisting of H, an aliphatic C1-C6 chain, aryl, heteroaryl and C1-C6 alkyl-aryl, wherein up to 4 methylene units of said aliphatic chain are optionally substituted by O, C(O), NH or N-alkyl C1-C6, said aliphatic, aryl, heteroaryl or alkyl-aryl chain being optionally substituted. represents a single or double bond, er represents the bond between R1 and the rest of the molecule.

4. Compound according to claim 3, characterized in that R8 is H or C1-C6 alkyl, such as methyl.

5. Compound according to claim 3 or 4, characterized in that one of the pairs R3-R4, R4-R5, R5-R6 and R6-R7 form, together with the carbon atoms to which they are attached, a 6-membered aromatic ring, unsubstituted or substituted with one or more substituents selected from halogen, OH, NH2, NH-C1-C6 alkyl, C1-C6 alkyl and C1-C6 O-alkyl, the other radicals between R3 and R7 being H.

6. Compound according to claim 3 or 4, characterized in that R9 is a substituent selected from the group consisting of OH and halogen and R10 is H.

7. Compound according to any one of claims 1 to 6, characterized in that R1 and / or R2, preferably one of R1 and R2, is selected from the group consisting of quinolinyl, isoquinolinyl, dihydroquinolinyl, dihydroisoquinolinyl, unsubstituted or substituted with one or more substituents selected from OH, C1-C6 alkyl or C1-C6 O-alkyl.

8. Compound according to any one of claims 1 to 7, characterized in that one of R1 and R2 is an optionally substituted nitrogen-containing heterocyclyl group, as defined in any one of claims 1 to 7, and the other is H, an optionally substituted C1-C6 aliphatic chain or an optionally substituted aryl, preferably H, a C1-C6 alkyl or a phenyl, more preferably a C1-C6 alkyl including a methyl, an ethyl, a propyl, a tert-butyl, an n-butyl, notably a methyl.

9. Compound according to any one of claims 1 to 8, characterized in that L1 and L2 are each independently a methylene group or a ligand of formula -CH=.

10. Compound according to any one of claims 1 to 9, characterized in that R' is H.

11. A compound according to any one of claims 1 to 10, characterized in that X is an oxygen atom.

12. Compound according to any one of claims 1 to 11, characterized in that it is selected from the group consisting of: 1, m = 1 4, m = 1 2, m = 2 3, m = 3 5, m = 2 6, m = 3 Petition 870250066871, dated 07 / 31 / 2025, p. 86 / 102 5 / 10 10, m = 1 11, m = 2 12, m = 3 13, m=1 14, m=2 15, m=3 κι b)m O / \ YVy^ '-O-'''^^'^7 19, m=1 20, m=2 21, m=3 16, m=1 17, m=2 18, m=3 25, m=1 26, m=2 27, m=3 Petition 870250066871, of 07 / 31 / 2025, p. 87 / 102 6 / 10 31, m=1 34,m=1 32, m=2 35,m=2 33, m=3 36,m=3 -^1¾^ 37, m=1 38, m=2 39, m=3 '°WN 43, m = 1 44, m=2 45, m= 3 49, m=1 50, m=2 51, m=3 40, m=1 41, m=2 54, m=3 Petition 870250066871, of 07 / 31 / 2025, p. 88 / 102 7 / 10 Petition 870250066871, of 07 / 31 / 2025, p. 89 / 102 8 / 10 Petition 870250066871, dated 07 / 31 / 2025, p. 90 / 102 9 / 10 comprising a compound, as defined in any of claims 1 to 12, and a pharmaceutically acceptable excipient.

14. Compound according to any one of claims 1 to 12, or composition according to claim 13, characterized in that it is for use as a medicament.

15. Compound according to any one of claims 1 to 12, or composition according to claim 13, characterized by being for use in the prevention and / or treatment of compulsive disorders and related behaviors, including addiction, obsessive-compulsive disorders and eating disorders, and neurodegenerative disorders, such as Parkinson's disease or Alzheimer's disease, notably eating disorders, including anorexia, bulimia and obesity.

16. Invention of a product, composition, kit or use, characterized by comprising one or more elements disclosed in this patent application.

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