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Definitions

• the present invention relates to imidazo [1,2-a] pyridine-2-carboxamide derivatives, to their preparation and to their therapeutic application in the treatment or prevention of diseases involving Nurr-1 nuclear receptors, also called NR4A2, NOT, TINUR, RNR-I, and HZF3.
• X and Y form, with the nitrogen atom which carries them, a saturated or partially saturated mono- or bicyclic cyclic amine of 5 to 10 members optionally containing 1 to 4 additional heteroatoms chosen from O, S, N, optionally substituted by a halogen atom, a (C 1 -C 6 ) alkyl group, a (C 1 -C 6 ) alkoxy, cyano, NRaRb, COOR 8 group , the said (C 1 -C 6 ) alkyl and (C 1 -C 6 ) alkoxy groups being optionally substituted with one or more halogen atoms;
• R 1 represents a hydrogen atom, a halogen atom, a (C 1 -C 6 ) alkoxy group, a group
• (Ci-C 6) alkyl, NRcRd, alkyl and alkoxy being optionally substituted by one or more halogen atoms, hydroxy, amino or (Ci-Ce) alkoxy;
• R 2 represents one of the following groups:
• a (C 1 -C 6 ) alkyl group optionally substituted with one or more groups independently selected from hydroxy, halogen, NRaRb, (C 1 -C 6 ) alkoxy, phenyl,
• a (C 1 -C 6 ) alkoxy group optionally substituted with one or more groups chosen independently of one another from a hydroxy, a halogen atom, a group
• a (C 1 -C 6 ) alkylsulfonyl group a (((Ci-C) alkyl) 3) silylethynyl,. a group -SO 2 -NR 9 R 10 ,
• a phenyl group optionally substituted by one or more groups chosen independently of one another from the following atoms or groups: halogen, (Q-)
• a heterocyclic group optionally substituted with a halogen atom, a group
• R 3 represents a hydrogen atom, a (C 2 -C 6) alkyl, a (Ci-C ⁇ ) alkoxy or halogen;
• R t represents a hydrogen atom, a (C 1 -C 4 ) alkyl group, a group or a fluorine atom
• R 5 represents a hydrogen atom, a phenyl group or a (C 1 -C 8) alkyl group
• R 5 and R 7 which may be identical or different, represent a hydrogen atom or a (C 1 -C 6 ) alkyl group or form, with the nitrogen atom carrying them, a 4- to 7-membered ring optionally including another heteroatom selected from N, O or S
• Rg is (Ci-C 6) alkyl
• R 9 and R 10 which may be identical or different, represent a hydrogen atom or a (C 1 -C 6 ) alkyl group
• Ru and Rn which may be identical or different, represent a hydrogen atom or a (C 1 -C 6 ) alkyl group
• Ra and Rb are independently of one another are hydrogen, (C r C 6) alkyl group or form with the nitrogen atom which carries them a 4- to 7-membered ring
• Rc is hydrogen and Rd is (C1-C6) alkyl; with the exception of 2- (2,3-dihydro-1H-indol-1-ylcarbonyl) -5-methylimidazo [1,2-a] pyridine, and 2- (4-thiomorpholin-1-yl-carbonyl) 6-chloroimidazo [1,2-a] pyridine, in the form of a base or an acid addition salt.
• the compounds of formula (I) may comprise one or more asymmetric carbon atoms. They can therefore exist as enantiomers or diastereoisomers. These enantiomers, diastereoisomers, as well as their mixtures, including the racemic mixtures, form part of the invention.
• the compounds of formula (I) may exist in the form of bases or addition salts with acids. Such addition salts are part of the invention.
• salts can be prepared with pharmaceutically acceptable acids, but the salts of other acids that are useful, for example, for the purification or the isolation of the compounds of formula (I) are also part of the invention.
• the compounds of formula (I) may also exist in the form of hydrates or solvates, namely in the form of associations or combinations with one or more water molecules or with a solvent. Such hydrates and solvates are also part of the invention.
• a halogen atom a fluorine, a chlorine, a bromine or an iodine
• an alkyl group a linear, branched or cyclic saturated aliphatic group optionally substituted by a linear, branched or cyclic saturated alkyl group.
• cyclic amines examples include benzoxazine, indoline, isoindoline, tetrahydroisoquinoline, morpholine, piperidine, pyrrolidine, pyrroline, tetrahydropyridine, tetrahydroquinoline, thiomorpholine, dihydroxybenzoxazine, tetrahydrothienopyridine; a heterocyclic group: mono or bicyclic group containing from 5 to 10 atoms, of which from 1 to 4 heteroatoms chosen from N, O and S, aromatic, unsaturated, saturated or partially saturated.
• heterocyclic groups mention may be made of: pyrrole, furan, thiophene, pyrazole, imidazole, triazole, tetrazole, oxazole, isoxazole, oxadiazole, thiazole, isothiazole, thiadiazole, pyridine, pyrimidine, pyrazine, pyridazine, triazine, furofuran , thienothiophene, pyrrolopyrrole, pyrroloimidazole, pyrrolopyrazole, pyrrolotriazole, imidazoimidazole, imidazopyrazole, furopyrrole, furoimidazole, furopyrazole, furotriazole, pyrrolooxazole, imidazooxazole, pyrazolooxazole, furooxazole, oxazolooxazole, oxazoloisoxazole
• a first group of compounds is constituted by the compounds for which R 2 is different from a hydrogen and chlorine atom and the other substituents are as defined above, in the form of a base or an acid addition salt.
• a second group of compounds is constituted by the compounds for which R 2 represents one of the following groups:
• a phenyl group optionally substituted with a -CO-R5 group, (C r C 6 ) alkyl itself optionally substituted by a hydroxyl;
• a heterocyclic group optionally substituted with a NRaRb, (C 1 -C 6) alkyl group optionally optionally substituted by a hydroxyl;
• R 5 represents a (C 1 -C 6 ) alkyl group
• Rn and Ri 2 which may be identical or different, represent a hydrogen atom or a group (C r C 6 ) alkyl;
• Ra and Rb are independently of each other hydrogen, (C 1 -C 6 ) alkyl; and the other substituents are as defined above, in the form of a base or an addition salt with an acid.
• R 2 represents one of the following groups:
• Rn and Ri 2 which may be identical or different, represent a hydrogen atom or a (C 1 -C 6 ) alkyl group
• Ra and Rb are independently of each other hydrogen, (C 1 -C 6 ) alkyl; and the other substituents are as defined above, in the form of a base or an addition salt with an acid.
• a fourth group of compounds is constituted by the compounds for which R 2 represents one of the following groups:
• a phenyl group optionally substituted with a group -CO-R 5 , (C 1 -C 6 ) alkyl itself optionally substituted with a hydroxyl;
• a pyridyl group optionally substituted by an amino group
• a pyrazolyl group optionally substituted by a furyl group optionally substituted with a hydroxymethyl group, an oxazolyl group, a triazolyl group, a pyrrolyl group or an imidazoyl group
• a pyridyl group optionally substituted by an amino group
• a pyrazolyl group optionally substituted by an amino group
• a pyrazolyl group optionally substituted with a hydroxymethyl group, an oxazolyl group, a triazolyl group, a pyrrolyl group or an imidazoyl group
• R 5 represents a group (Ci-C 6 ) alkyl
• Rn and Ri 2 identical or different, represent a hydrogen atom or a group (Q-
• a fifth group of compounds is constituted by the compounds for which X and Y form, with the nitrogen atom which carries them, a cyclic mono or bicyclic amine which is saturated or partially saturated, 5 to 10 members, optionally comprising an additional heteroatom selected from O or S, optionally substituted with a group selected from a halogen atom, and the other substituents are as defined above, in the basic state or from acid addition salt.
• a sixth group of compounds is constituted by the compounds for which -NXY represents a dihydrobenzoxazine, indoline, isoindoline, morpholine, piperidine, pyrrolidine, pyrroline, tetrahydropyridine, tetrahydroquinoline group, thiomorpholine, tetrahydrothienopyridine, optionally substituted by one or more halogen atoms; and the other substituents are as defined above, in the form of a base or an addition salt with an acid.
• a seventh group of compounds is constituted by the compounds for which:
• -NXY represents a dihydrobenzoxazine, indoline isoindoline, morpholine, piperidine, pyrrolidine, pyrroline, tetrahydropyridine, tetrahydroquinolea, thiomorpholine, tetrahydrothienopyridine group, optionally substituted with a halogen atom;
• R 2 represents one of the following groups: a (C 1 -C 6 ) alkoxy group, a group NR 11 R 12 ,
• a phenyl group optionally substituted with a group chosen from a halogen, a (C 1 -C e) alkoxy group, a (C r C 6 ) alkyl group optionally substituted by a hydroxyl or a C (O) R 5 group ,
• R 5 represents a (C 1 -C 6 ) alkyl group
• R 11 and R 12 which may be identical or different, represent a hydrogen atom or a (C 1 -C 6 ) alkyl group
• Ra and Rb are independently of each other hydrogen, (C 1 -C 6 ) alkyl; R 1 , R 3 and R 4 represent a hydrogen atom, in the form of a base or an addition salt with an acid.
• R 1 , R 3 and R 4 represent a hydrogen atom, in the form of a base or an addition salt with an acid.
• -NXY represents a dihydrobenzoxazine, indoline group optionally substituted with a fluorine atom, isoindoline, morpholine, piperidine, pyrrolidine, pyrroline, tetrahydropyridine, tetrahydroquinoline, thiomorpholine, tetrahydrothienopyridine;
• R 2 represents a methoxy group, a phenyl group substituted by a hydroxymethyl, hydroxyethyl, hydroxy-methyl-ethyl, acetyl, N-dimethyl group, a pyridyl group optionally substituted with an amino group, a pyrazolyl group, a furyl group optionally substituted with a hydroxymethyl group, an oxazolyl group, a triazolyl group, a pyrrolyl group or an imidazoyl group;
• R 1, R 3 and R 4 represent a hydrogen atom, in the form of a base or an addition salt with an acid.
• a ninth group of compounds is constituted by the compounds for which NXY represents a dihydrobenzoxazine, indoline, isoindoline, tetrahydroisoquinoline, morpholine, piperidine, pyrrolidine, pyrroline, tetrahydropyridine, tetrahydroquinoline group, thiomorpholine, tetrahydrothienopyridine, these groups being optionally substituted by a fluorine atom; R 1, R 3 and R 4 represent a hydrogen atom;
• R 2 represents a methoxy group or a phenyl group substituted by a hydroxymethyl or N-dimethyl group, in the form of a base or an addition salt with an acid.
• the compounds of general formula (I) can be prepared according to the process described in scheme 1.
• the first synthetic route (transformation A 2 ) consists in preparing, according to methods known to those skilled in the art, a 2-amino-pyridine of formula (II), in which R 1 , R 2 , R 3 and R 1 are defined as above, then to form the imidazo [1,2- ⁇ ] pyridine ring by condensation of a halogenated derivative of 2-oxo-propionamide (lu) in which HaI represents a chlorine, bromine or iodine atom and X and Y are defined as previously by analogy with the methods described by JJ. Bourguignon et al. in Aust. J. Chem., 50, 719 (1997) and by JG Lombardino in J. Org. Chem., 30, 2403 (1965) for example.
• formula (II) in which R 1 , R 2 , R 3 and R 1 are defined as above
• the halogenated derivatives of 2-oxo-propionamide (DI) can be obtained for example according to the method described by R. Kluger et al. in J. Am. Chem. Soc., 106, 4017 (1984).
• the 2-amino-pyridines of formula (JI) in which R 1 , R 2 , R 3 and R 4 are defined as above can be prepared for example by transformation A 1 , ie:
• the second synthesis route (B 2 transformation) consists in coupling an imidazopyridine-2-carboxylic acid or one of its derivatives of formula (VI) in which R 1 , R 2 , R 3 and R 4 are defined as previously, W represents a hydroxy group, a halogen atom or a group (CrC 6 ) alkoxy with a cyclic amine X-NH-Y of formula (VII), in which X and Y are defined as above, according to methods known from skilled person.
• the acid may be converted beforehand into one of its reactive derivatives such as acid halide, anhydride, mixed anhydride or activated ester and then reacted with the amine (VII) in the presence of a base such as diisopropylethylamine, triethylamine or pyridine, in an inert solvent such as THF, DMF or dichloromethane.
• a base such as diisopropylethylamine, triethylamine or pyridine
• an inert solvent such as THF, DMF or dichloromethane.
• the coupling may also be carried out in the presence of a coupling agent such as CDI, EDCI 3 HATU or HBTU under the same conditions without isolating a reactive intermediate.
• the amine (VII) can be reacted with an ester of the acid of formula (VI) in the presence of a catalyst such as trimethylaluminum according to the method of Weinreb, S. et al (Tet Lett. 1977), 18, 4171) or zirconium terbutylate.
• a catalyst such as trimethylaluminum according to the method of Weinreb, S. et al (Tet Lett. 1977), 18, 4171) or zirconium terbutylate.
• the imidazopyridine-2-carboxylic acid derivatives of formula (VI) in which R 1 , R 2 , R 3 and R 4 are defined as above and W is hydroxy or halogen are prepared by condensation of a 2-aminopyridine of formula (II) wherein R 1 , R 2 , R 3 and R 4 are defined as above on a 3-halogeno-2-oxo-propionic acid ester of formula (VIU) in which HaI represents a halogen and W is (Q-C6) alkoxy, under the conditions similar to those used for the condensation of a derivative of formula (H) on a derivative of formula (ItI), followed if necessary by the conversion of the ester to acid and then to acid chloride or other reactive derivative (transformation B 1 ).
• the third synthesis route (C 2 conversion) consists in coupling a derivative of general formula (EK) in which R 1 , R 3 , R 4 , X and Y are defined as above and Z represents a halogen atom such as bromine or iodine, a sulfonyloxy group or a reactive group such as boryl, stannyl or silyl on a derivative of formula R 2 -Z '(V) in which R 2 is defined as above and
• Z ' represents a reactive group such as a boryl, stannyl or silyl group or a hydrogen atom when Z represents a halogen atom or a sulphonyloxy group, or - Z' represents a halogen atom such as bromine or iodine when Z represents a reactive group such as a boryl, stannyl or silyl group or a hydrogen atom.
• Imidazopyridine-2-carboxylic acids or their derivatives of formula (X) in which R 1 , R 3 and R 4 are defined as above, W is (C 1 -C 6 ) alkoxy, hydroxy or halogen and Z represents a boryl group, stannyl or silyl or a halogen atom can be prepared (Di transformation) by condensation of a 2-aminopyridine of formula (IV), wherein R 1 , R 3 and R 4 are defined as above and Z represents a boryl group , stannyl or silyl or a halogen atom, with a 3-halo-2-oxo-propionic acid ester of formula (Vm), wherein Hal represents a halogen and W is a (Ci-C 6 ) alkoxy group, under the conditions similar to those mentioned above for the condensation of 2-aminopyridines of formula (II) with a derivative of formula (VII), to obtain imidazopyridine-2-carboxylic acids or their derivative
• Imidazopyridine-2-carboxylic acids or their derivatives of formula (VI), in which R 1 , R 2 , R 3 and R 4 are defined as above, W is (dC 6 ) alkoxy, hydroxy or halogen may also be prepared ( transformation Ei) by coupling of a derivative of general formula (X), in which R 1 , R 3 and R 4 are defined as above, W is (C 1 -C 6 ) alkoxy and Z represents a halogen atom such that bromine or iodine, a sulfonyloxy group or a reactive group such as boryl, stannyl or silyl on a derivative of formula R 2 -Z '(V) in which R 2 is defined as above and
• Z 1 represents a reactive group such as a boryl, stannyl or silyl group or a hydrogen atom when Z represents a halogen atom or a sulphonyloxy group, or - Z 1 represents a halogen atom such as bromine or iodine when Z represents a reactive group such as a boryl, stannyl or silyl group or a hydrogen atom, optionally followed by the conversion of the ester to acid and then to acid chloride or other reactive derivative.
• This synthetic route consists of the conversion of a compound of general formula (XI), (XII) or (X ⁇ i), in which R 1, R 3 , R 4 , X, Y and W are defined as above and V represents a precursor group allowing the construction of the heterocycle of formula R 2 according to the methods known to those skilled in the art.
• V can represent:
• a 2-haloacyl group such as bromoacetyl, or 1-halo-2-oxoalkyl, such as 1-bromo-2-oxoethyl, which can be converted, for example, into thiazolyl, imidazolyl or oxazolyl group by treatment; by thiourea, thioamide, guanidine, urea or amide derivatives,
• alkynyl group such as ethynyl
• 1,2,3-triazol-4-yl group an alkynyl group, such as ethynyl, which can be converted into a 1,2,3-triazol-4-yl group
• an acyl group such as formyl which can be converted, for example, to 1,3-dioxolanyl-2 or oxazolyl group;
• a cyano group which can be converted, for example, to dihydroimidazolyl (2) or 1,3,4-triazol-2-yl group.
• the compounds of general formula (XI) can be obtained from compounds of formula (XII), under the conditions described for the preparation of compounds (I) from derivatives of imidazopyridine-2-carboxylic acid of formula (VI) by B 2 transformations.
• imidazopyridine-2-carboxylic acid derivatives of general formula (XII) can be obtained from amino-pyridines of formula (XIH) under the conditions described for the conversion of amino-pyridines of formula (II) into compounds of formula general (I) by transformation A 2 .
• the products of formula (I), and their precursors of formula (II) or (IV), may be subjected, if desired and if necessary, to obtain fo ⁇ nule products (I) or to be converted into other products of formula (I) to one or more of the following transformation reactions, in any order: a) esterification reaction or amidification of acid function, b) ester function hydrolysis reaction in acid function, c ) an amine functional amidification reaction, d) a hydroxyl functional transformation reaction with an alkoxy function, e) an alcohol function oxidation reaction with an aldehyde or ketone function, f) a transformation reaction of the aldehyde or ketone functions.
• an organometallic such as an organomagnesium compound
• a conversion reaction of the aldehyde or ketone functions to the oxime derivative g) a conversion reaction of the aldehyde or ketone functions to the oxime derivative, h) a nitrile radical conversion reaction to an aldehyde function, i) a reaction of conversion of nitrile radical to ketone function, j) an alkenyl or alkenyl group oxidation reaction, k) an aldehyde or ketone functional group olefintion reaction,
• Example 1 (Compound No. 1): ⁇ 3- [2- (Piperidin-1-ylcarbonyl) imidazo [1,2-a] pyridin-6-yl] phenyl ⁇ methanol
• Example 2 (Compound No. 2): ⁇ 3- [2- (2,3-Dihydro-4H-1,4-benzoxazin-4-ylcarbonyl) imidazo [1,2-a] pyridin-6-yl] phenyl ⁇ methanol
• Example 4 (Compound No. 4): 2- (1,2,5,6-Tetrahydropyridin-1-yl) carbonyl-N-dimethyl-imidazo [1,2-a] pyridin-6-amine
• This product is prepared by saponifying ethyl 6-methoxy-5-methylimidazo [1,2-a] pyridine-2-carboxylate under conditions similar to those described for the preparation of 6-dimethylamino-imidazo [1] acid. , 2- ⁇ ] pyridine-2-carboxylic acid.
• Ethyl (6-pyridin-2-yl) imidazo [1,2-a] pyridine-2-carboxylate A mixture of 3.18 g of cesium carbonate, 25 ml of dioxane, 9.3 ml of water, 500 mg of 2-iodopyridine, 89 mg of [1,3-bis (diphenylphosphino) ferrocene] dichloropalladium and 848 mg of hydrobromide (1: 1) of 6- (4,4,5,5-tetramethyl-1, Ethyl 3,2-dioxaborolan-2-yl) imidazo [1,2-a] pyridine-2-carboxylate is heated for 2 hours at 110 ° C., then partially concentrated and diluted with dichloromethane and filtered.
• 6- (1-Triphenylmethyl-1H-imidazol-4-yl) imidazo [1,2-a] pyridine-2-carboxylic acid 500 mg of 6- (1-triphenylmethyl-1H-imidazol-4-yl) imidazo ethyl [1,2-a] pyridine-2-carboxylate are saponified under conditions similar to those described for the preparation of intermediate 4 (step 4.3) to give 346 mg of 6- (1-triphenylmethyl) 1H-imidazol-4-yl) imidazo [1,2-a] pyridine-2-carboxylic acid.
• ethyl 6-iodo-imidazo [1,2-a] pyridine-2-carboxylate 100 mg of ethyl 6-iodo-imidazo [1,2-a] pyridine-2-carboxylate, 135 mg of 1- (triisopropylsilyl) -pyrrole-3-boronic acid and 18 mg of tetrakis (triphenylphosphine) palladium ( 0) are degassed under vacuum and then suspended, under argon, in a degassed mixture of 1.5 mL of 1,2-dimethoxyethane, 1.5 mL of ethanol and 316 ⁇ L of aqueous 2N sodium carbonate solution.
• reaction mixture is heated at reflux for 4 hours, then cooled, diluted and stirred with a mixture of 5 mL of half-saturated aqueous sodium bicarbonate solution and 5 mL of dichloromethane.
• the organic phase is dried over sodium sulphate, filtered and concentrated to dryness under reduced pressure.
• the residue is chromatographed on silica eluting with a mixture of ethyl acetate and hexane (50/50).
• This product is prepared under conditions similar to those described for the preparation of intermediate 7 (step 7.1) by replacing 1- (triisopropylsilyl) -pyrrole-3-boronic acid with furan-2-boronic acid.
• aqueous phase is extracted with 200 ml of ethyl acetate and the combined organic phases are washed with brine and dried over sodium sulphate, filtered and concentrated to dryness under reduced pressure.
• the residue is chromatographed on silica eluting with a gradient of ethyl acetate and hexane (80/20 to 100/0). The fractions containing the expected product are combined and concentrated to dryness under reduced pressure to give 530 mg of ethyl 6- (oxazol-2-yl) imidazo [1,2-a] pyridine-2-carboxylate in the form of a yellow powder.
• Ethyl 13.3 6- (1H-1,2,4-triazol-3-yl) imidazo [1,2-a] pyridine-2-carboxylate
• a suspension of 580 mg of 6- [hydrazino (imino) methyl] ethyl imidazo [1,2-a] pyridine-2-carboxylate in 6 ml of formic acid is heated for 20 hours at 85 ° C.
• the reaction mixture is concentrated to less than 20% of its initial volume and diluted with 20 ml of water. Solid sodium carbonate is added at 0-5 ° C. until the pH is 8-9.
• a mixture of 4 g of ethyl 6-iodo-imidazo [1,2-a] pyridine-2-carboxylate, 2.63 ml of ethynyl-trimethylsilane, 888 mg of dichloro-bis (triphenylphosphine) palladium is degassed under empty. 240 mg of degassed N, N-dimethylformamide, 3.52 ml of triethylamine are added. The reaction mixture is degassed under argon and then stirred at 50 ° C. for 50 hours and then cooled, diluted with 20 ml of water.
• 6- (1H-1,2,3-Triazol-4-yl) imidazo [1,2-a] pyridine-2-carboxylic acid 125 mg of 6- (1H-1,2,3-triazol-3) ethyl (1-ethyl) imidazo [1,2- ⁇ ] pyridine-2-carboxylate are saponified under conditions analogous to those described for the preparation of intermediate 4 (step 4.3) to give 72 mg of 6- ( 1H-1,2,3-triazol-3-yl) imidazo [1,2-a] pyridine-2-carboxylic acid as a white solid.
• CF 3 COOH represents a compound in the form of trifluoroacetate, the ratio in parentheses is the ratio (acid: base), Table 1
• the compounds according to the invention have been the subject of pharmacological tests for determining their modulatory effect on NOT.
• N2A N2A
• NBRE NOT binding response element
• the Neuro-2A cell line comes from a standard commercial source (ATCC).
• the Neuro-2A clone was obtained from a spontaneous tumor from an albino mouse A strain by RJ Klebe et al. This Neuro-2A line is then stably transfected with 8NBRE-luciferase. N2A-8NBRE cells are cultured to confluence in culture flasks
• the products are applied in 25 ⁇ l and incubated for a further 24 hours.
• an equivalent volume (100 ⁇ L) of Steadylite is added to each well, then waited for 30 minutes to obtain a complete lysis of the cells and the maximum production of the signal.
• the plates are then measured in a microplate luminescence counter after being sealed with an adhesive film.
• the products are prepared as a stock solution at 10 -2 M, then diluted in 100% DMSO Each product concentration is previously diluted in culture medium before incubation with the cells thus containing 0.625% final DMSO.
• the subject of the invention is a medicinal product which comprises a compound chosen from the compounds of formula (I) as defined above, 2- (2,3-dihydro-1H-indol-1 -ylcarbonyl) -5-methylimidazo [1,2-a] pyridine and the 2- (4-thiomorpholin-1-ylcarbonyl) -6-chloroimidazo [1,2-a] pyridine, and the addition salts of these compounds with a pharmaceutically acceptable acid, and more particularly which comprises a formula (I) or an addition salt thereof with a pharmaceutically acceptable acid.
• neurodegenerative diseases such as Parkinson's disease, Alzheimer's, tauopathies (eg, supranuclear progressive paralysis, fronto-temporal dementia, corticobasal degeneration, Pick's disease); brain trauma such as ischemia and head trauma and epilepsy; psychiatric illnesses such as schizophrenia, depression, substance dependence, attention deficit disorder and hyperactivity disorder; inflammatory diseases of the central nervous system such as multiple sclerosis, encephalitis, myelitis and encephalomyelitis and other inflammatory diseases such as vascular diseases, atherosclerosis, inflammation of the joints, osteoarthritis, rheumatoid arthritis; osteoarthritis, Crohn's disease, ulcerative colitis; allergic inflammatory diseases such as asthma, autoimmune diseases such as type 1 diabetes, lupus, scleroderma, Guillain-Barré Syndrome, Addison's disease and other immune-mediated diseases; osteoporosis; cancers.
• neurodegenerative diseases such as Parkinson's disease, Alzheimer's, tauopathies (e
• the present invention relates to a compound chosen from a compound of formula (I) as defined above, 2- (2,3-dihydro-1H-indol-1-ylcarbonyl) -5-methylimidazo [1,2- ⁇ ] ] pyridine and 2- (4-thiomorpholin-1-ylcarbonyl) -6-chloroimidazo [1,2-a] pyridine, and the addition salts of these compounds with a pharmaceutically acceptable acid, for the treatment and the prevention of one of the aforementioned diseases.
• these drugs find their use in the treatment and prevention of one of the aforementioned diseases, with the exception of cancers.
• the present invention relates to the use of a compound chosen from the compounds mentioned above, for the preparation of a medicament for the treatment and prevention of one of the diseases mentioned above. above.
• the present invention relates to pharmaceutical compositions comprising, as active principle, a compound chosen from the group of compounds defined above.
• These pharmaceutical compositions contain an effective dose of at least one compound chosen from the group of compounds defined above, or a pharmaceutically acceptable salt, of said compound, as well as at least one excipient. pharmaceutically acceptable.
• Said excipients are chosen according to the pharmaceutical form and the desired mode of administration, from the usual excipients which are known to those skilled in the art.
• compositions of the present invention for oral, sublingual, subcutaneous, intramuscular, intravenous, topical, local, intratracheal, intranasal, transdermal or rectal administration, the active ingredient selected from the group of compounds defined below.
• the above, or its salt can be administered in unit dosage form, in admixture with conventional pharmaceutical excipients, to animals and humans for the prophylaxis or treatment of the above disorders or diseases.
• Suitable unit dosage forms include oral forms such as tablets, soft or hard capsules, powders, granules and oral solutions or suspensions, sublingual, oral, intratracheal, intraocular, intranasal forms of administration. by inhalation, topical, transdermal, subcutaneous, intramuscular or intravenous administration forms, rectal administration forms and implants.
• the compounds according to the invention can be used in creams, gels, ointments or lotions.
• a unitary form of administration of a compound according to the invention in tablet form may comprise the following components:
• the dosage appropriate to each patient is determined by the physician according to the mode of administration, the weight and the response of said patient.
• the present invention also relates to a method of treatment of the pathologies indicated above which comprises the administration, to a patient, of an effective dose of a compound chosen from the group of compounds defined herein. above, or a pharmaceutically acceptable salt thereof.

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