EP2225242A2 - Dérivés de n-heterocyclique-imidazoý1,2-a¨pyridine-2-carboxamides, leur préparation et leur application en thérapeutique - Google Patents

Dérivés de n-heterocyclique-imidazoý1,2-a¨pyridine-2-carboxamides, leur préparation et leur application en thérapeutique

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Publication number
EP2225242A2
EP2225242A2 EP08872909A EP08872909A EP2225242A2 EP 2225242 A2 EP2225242 A2 EP 2225242A2 EP 08872909 A EP08872909 A EP 08872909A EP 08872909 A EP08872909 A EP 08872909A EP 2225242 A2 EP2225242 A2 EP 2225242A2
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Prior art keywords
imidazo
carboxamide
pyridine
group
chloro
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EP08872909A
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German (de)
English (en)
French (fr)
Inventor
Jean-François Peyronel
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Sanofi SA
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Sanofi Aventis France
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • N-HETEROCYCLIC-MIDAZO DERIVATIVES [1 ; 2- ⁇ ] PYRIDINE-2-CARBOXAMIDES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION
  • 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 nuclear Nurr-1 receptors also called NR4A2, NOT, TESFUR 5 RNR-I, and HZF3.
  • X represents a heterocyclic group optionally substituted by one or more groups chosen independently of one another from the following atoms or groups: halogen, (C 1 -C 5 ) alkoxy, (C 1 -C 6 ) alkyl : cyano, oxydo, COOR 8 , the alkyl and alkoxy groups possibly being substituted with one or more halogen atoms;
  • R J represents a hydrogen atom, a halogen atom, a group (C r C 6 ) alkoxy, a group
  • R 2 represents one of the following groups:
  • a (C 1 -C 6 ) alkoxy group optionally substituted by one or more groups selected independently of each other from hydroxy, halogen, amino, NRaRb group,
  • a (C 1 -C 6 ) alkylsulfmyl group ; . a (C 1 -C 6 ) alkylsulfonyl group, a (((C 1 -C 6 ) alkyl) 3 ) silylethynyl group, a group -SO 2 -NR 9 Ri 0 ,.
  • phenyl optionally substituted by one or more groups independently selected from each other among the following atoms or groups: halogen, (C 1 - C s) alkoxy, cyano, NRaRb, -CO-R 5, -CO-NR 6 R 7 , -CO-OR 8 , a (C r C 6 ) alkyl group optionally substituted with one or more hydroxy or NRaRb;
  • R 3 represents a hydrogen atom, a (C 2 -C 6 ) alkyl group a (QC 6 ) alkoxy group or a halogen atom;
  • R 4 represents a hydrogen atom, a (QC 4 ) alkyl group, a (dC 4 ) alkoxy group or a fluorine atom;
  • R 5 represents a hydrogen atom, a phenyl group or a (C 1 -C 6 ) alkyl group
  • R e and R / identical or different, represent a hydrogen atom or a group (QC 5 ) alkyl or form, with the nitrogen atom which carries them, a 4- to 7-membered ring optionally including another heteroatom chosen from N, O or S
  • R 8 represents a group (QC 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
  • R 11 and R 1 which may be identical or different, represent a hydrogen atom or a (C 1 -C 5) alkyl group optionally substituted by one or more groups chosen independently of one another from a hydroxyl, a (QC 5 ) alkoxy group
  • a NRaRb group or form with the nitrogen atom which carries them a 4- to 7-membered ring
  • Ra and Rb are independently of each other hydrogen, (QC 5 ) alkyl or form with the nitrogen atom a 4- to 7-membered ring optionally comprising another heteroatom selected from O, S, N; except for compounds:
  • the compounds of formula (T) 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 (T) 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.
  • alkenyl group a linear or branched, mono- or poly-unsaturated aliphatic group, comprising, for example, one or two ethylenic unsaturations
  • an alkoxy group an -O-alkyl radical where the alkyl group is as previously defined
  • an alkynyl group a linear or branched, mono- or poly-unsaturated aliphatic group, for example comprising one or two ethylenic unsaturations
  • a heterocyclic group a mono or bicyclic group comprising from 5 to 10 atoms, of which from 1 to 4 heteroatoms chosen from N, O and S, this cycl
  • heterocycle groups By way of examples of heterocycle 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, fbrotriazole, pyrrolooxazole, imidazooxazole, pyrazolooxazole, furooxazole, oxazolooxazole, ox
  • the subject of the present invention is the compounds of formula (I), for which X, R 1 to R 4 are as defined above, and at least one of R 1, R 2 , R) and R 4 is other than a hydrogen atom, either as a base or as an acid addition salt, with the exception of N- (qumolin-7-yl) -6-trifluoromethylimidazo [1,2] pyridin-2-carboxamide, and with the exception of the compounds for which R 2 is a chlorine atom and X is chosen from a thiazol-2-yl, 5-methylpyridin-2-yl, 6-indolyl radical, 2,3-dihydro-benzo [1,4] dioxin-6-yl, 1,3-benzodioxol-5-yl, and benzothiazol-2-yl.
  • the present invention provides a first group of compounds of formula (T) 5 where:
  • X represents a heterocyclic group, this group being optionally partially saturated or oxidized and optionally substituted by one or more groups chosen independently of one another from the following atoms or groups: halogen, (C 1 -C 6 ) alkyl, said alkyl group possibly being substituted with one or more halogen atoms, a cyano, a COOR 8 group in which R 8 represents a (C 1 -C 6 ) alkyl group; R 1, R 2 , R 3 and R 4 being as defined in the general formula (I); in the form of a base or an acid addition salt; except for compounds:
  • the subject of the present invention is a second group of compounds of formula (I), for which:
  • X represents a thiazole, isothiazole, thiophene, pyrazole, thiadiazole, isozaxole, tetrazole, pyridine or pyrazine group, these groups being optionally partially saturated or oxidized and optionally substituted by one or more groups chosen independently of one another from the following atoms or groups : halogen, (C r C 6 ) alkyl, said alkyl group being optionally being substituted with one or more halogen atoms, a cyano, a COOR 8 group in which R 8 represents a (C 1 -C 4) alkyl group;
  • R 1, R 2 , R 3 and R 4 being as defined in the general formula (T); in the form of a base or an acid addition salt; except for compounds:
  • the subject of the present invention is a third group of compounds of formula (T), for which: R 1, R 3 and Rt represent a hydrogen atom; R 2 represents one of the following groups: a halogen atom,
  • the subject of the present invention is a fourth group of compounds of formula (T), for which:
  • X represents a thiazole, isothiazole, thiophene, pyrazole, thiadiazole, isozaxole, tetrazole, pyridine or pyrazine group, these groups being optionally partially saturated or oxidized and optionally substituted by one or more groups chosen independently of one another from the following atoms or groups halogen, (C 1 -C 6 ) alkyl, said alkyl group being optionally substituted by one or more halogen atoms, a cyano, a COORg group in which R 8 represents a (C 1 -C 6 ) alkyl group; R 1, R 3 and R 4 represent a hydrogen atom; R 2 represents one of the following groups: a halogen atom, . a phenyl group substituted with a (C 1 -C 6) alkyl group, itself substituted by a hydroxyl,
  • R 11 and R 12 are (C 1 -C 6 ) HIClCl, in the form of a base or an acid addition salt; except for compounds:
  • the subject of the present invention is a fifth group of compounds of formula (T) for which:
  • X represents a thiazole, isothiazole, thiophene, pyrazole, thiadiazole, isozaxole, tetrazole, pyridine or pyrazine group, the groups being optionally partially saturated or oxidized and optionally substituted with one or more cyano, methyl, halogen, CO 2 Me or CF 3 groups; ; R 1 , R 3 and R 4 represent a hydrogen atom;
  • R 2 represents a halogen or phenyl substituted with a hydroxymethyl group, or a methyl group, or an N-dimethyl group; excluding compounds for which R 2 is chloro and X is thiazol-2-yl or 5-methylpyridin-2-yl; in the form of a base or an acid addition salt.
  • the subject of the present invention is a sixth group of compounds of formula (I) for which:
  • X represents a thiazole, imidazole, pyridine, pyrazine, benzothiazole, benzodioxole, pyrazole, isozaxole, thiophene, tetrazole, thiadiazole or isothiazole group, these groups being optionally partially saturated or oxidized and optionally substituted with one or more cyano, methyl or halogen groups, CO 2 Me or CF 3 ; R 1 , R 3 and R 4 represent a hydrogen atom;
  • R 2 represents a halogen atom or a phenyl group substituted by a hydroxymethyl group, or a methyl group, or an N-dimethyl group, in the form of a base or an addition salt with an acid, with the exception compounds:
  • the compounds of general formula (I) can be prepared according to the process described in scheme 1.
  • Route A consists in preparing the 2-amino-pyridines of formula (H) according to the methods known to those skilled in the art and in forming the imidazo [1,2- ⁇ ] pyridine ring by condensation on a 2-oxo derivative.
  • -N-aryl-propionamide (HT) wherein HaI represents a chlorine, bromine or iodine atom and X is defined as above, by analogy with the methods described by JJ. Bourguignon et al. in Aust. J. Chem., 50, 719 (1997) and by J. G. Lombardino in J. Org. Chem., 30, 2403 (1965) for example.
  • the halogenated derivatives of 2-oxo-N-aryl-propionamide (HT) can be obtained according to the method described by R. Kluger et al. in J. Am. Chem. Soc., 106, 4017 (1984).
  • the second synthesis route B, C consists in coupling an imidazopyridine-2-carboxylic acid or one of its derivatives, of formula (IV) in which Y represents a hydroxyl group, a halogen atom or a group (C r C 6 ) alkoxy with a heteroarylamine X-NH 2 (VI), wherein X is defined as above, according to methods known to those skilled in the art.
  • 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 (VI) 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 can also be carried out in the presence of a coupling agent such as CDI, EDCI, HATU or HBTU under the same conditions without isolating a reactive intermediate.
  • the amine can be reacted (VT) with an ester of the acid of formula (IV) in the presence of a catalyst such as trimethylaluminum according to the method of Weinreb, S. et al (Tet Lett, 18, 4171 (1977)) or terbutylate of zirconium.
  • a catalyst such as trimethylaluminum according to the method of Weinreb, S. et al (Tet Lett, 18, 4171 (1977)) or terbutylate of zirconium.
  • the imidazopyridine-2-carboxylic acids and their derivatives of formula (IV) can be obtained by condensing the appropriate 2-aminopyridines on an ester of 3-halo-2-oxo-propionic acid according to the method described by JG Lombardino in J. Org. Chem., 30 (7), 2403 (1965), then deprotecting the ester to acid and converting the acid if appropriate to one of its derivatives.
  • the products of formula (T), and their precursors of formula (H) or (IV), may be subjected, if desired and if necessary, to obtain products of formula (T) or may 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
  • Example 5 6-Iodo-N- (pyridin-2-yl) imidazo [1,2-b] pyridine-2-carboxainide (Table No. 5)
  • a suspension of 1 g of 6-iodo-imidazo [1, Ethyl 2- ⁇ ] pyridine-2-carboxylate, 330 mg of 2-pyridylamine, 92 mg of 1-hydroxy-7-azabenzotriazole (HOAt) and 787 mg of zirconium tertbutylate in 12 mL of toluene are stirred for 16 hours at room temperature. room temperature and then refluxed for 6 hours. After cooling, the medium is diluted in ethyl acetate and filtered.
  • the solid is taken up in dichloromethane and a saturated aqueous solution of sodium hydrogencarbonate.
  • the filtrate is concentrated to dryness, taken up in water and dichloromethane, the organic phase is separated, dried and concentrated to dryness.
  • the solids obtained from both sides are combined and triturated with dichloromethane to give 1.42 g of 6-iodo-N- (pyridin-2-yl) imidazo [1,2-a] pyridine-2-carboxamide under the shape of a pale yellow solid.
  • Example 7 6- [3- (Hydroxymethyl) phenyl] -N- (pyridin-2-yl) imidazo [1,2-a] pyridine-2-carboxamide and its hydrochloride (1: 1) (Table No. 7) )
  • the compounds according to the invention have been the subject of pharmacological tests for determining their modulatory effect on NOT.
  • the activity of the compounds according to the invention was evaluated on a cell line (N2A) endogenously expressing the Nurr1 mouse receptor and stably transfected with the NOT binding response element (NBRE) coupled to the luciferase reporter gene.
  • N2A a cell line endogenously expressing the Nurr1 mouse receptor and stably transfected with the NOT binding response element (NBRE) coupled to the luciferase reporter gene.
  • EC50 are between 0.01 and 1000 nM. The tests were carried out according to the procedure described below.
  • 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 grown to confluence in 75 cm 2 culture flasks containing DMEM supplemented with 10% fetal calf serum, 4.5 g / L glucose and 0.4 mg / ml Geneticin. .
  • the cells are recovered with 0.25% trypsin for 30 seconds and then resuspended in DMEM without phenol red containing 4.5 g / l of glucose, 10% of delipidated serum Hyclone and deposited in white plates 96 wells with transparent bottom.
  • the cells are deposited at a rate of 60,000 per well in 75 ⁇ L for 24 hours before adding the products.
  • 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 luminescence counter for microplates after being sealed with an adhesive film.
  • the products are prepared in the form of 10 -2 M stock solution and 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.
  • Compounds Nos. 4, 7, 8 and 39 showed an EC 50 of 2.2 nM, 0.04 nM, 0.5 nM and 10.5 nM, respectively.
  • the compounds according to the invention can therefore be used for the preparation of medicaments for their therapeutic application in the treatment or prevention of diseases involving NOT receptors.
  • the invention relates to medicaments which comprise a compound of formula (T), or an addition salt thereof to a pharmaceutically acceptable acid.
  • the subject of the invention is medicaments which comprise a compound chosen from a compound of formula (I) as defined above, as well as 6-chloro-N- (2,3-dihydro-1).
  • Neurodegenerative diseases such as Parmonson'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; diseases psychiatric disorders 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 immuno-mediated diseases; osteoporosis; cancers.
  • Parkinson's disease eg, supranuclear progressive paralysis,
  • the present invention relates to a compound chosen from the compounds of formula (I) as defined above, as well as 6-chloro-N- (2,3-dihydro-1,4-benzodioxin-6-yl) imidazo [1, 2- ⁇ ] pyridine-2-carboxamide, 6-chloro-N- (5-methyl-pyridin-2-yl) imidazo [1,2-a] pyridine-2-carboxamide, N- ( 1,3-benzodioxol-5-yl) -6-chloro-imidazo [1,2-a] pyridine-2-carboxamide, 6-chloro-N- (thiazol-2-yl) -imidazo [1, 2- ⁇ ] pyridine-2-carboxamide, N- (benzothiazol-2-yl) -6-chloro-irnidazo [1,2-a] pyridine-2-carboxamide, 6-chloro-N- (1H- indol-6-yl) -imidazo [1,2- ⁇
  • the present invention relates to the use of a compound selected from the group of compounds as defined above, for the preparation of a medicament for the treatment and prevention of one ( e) the diseases, disorders or disorders mentioned above.
  • a compound selected from the group of compounds as defined above for the preparation of a medicament for the treatment and prevention of one ( e) the diseases, disorders or disorders mentioned above.
  • These compounds could also be used as a treatment associated with stem cell transplants and / or transplants.
  • the present invention relates to pharmaceutical compositions comprising, as active principle, a compound as defined above.
  • These pharmaceutical compositions contain an effective dose of at least one compound chosen from the group of compounds as defined above, as well as at least one pharmaceutically acceptable excipient.
  • 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 as defined above, may 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: Compound according to the invention 50.0 mg
  • 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 according to the invention, or one of its pharmaceutically acceptable salts.

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EP08872909A 2008-01-02 2008-12-31 Dérivés de n-heterocyclique-imidazoý1,2-a¨pyridine-2-carboxamides, leur préparation et leur application en thérapeutique Withdrawn EP2225242A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0800003A FR2925901B1 (fr) 2008-01-02 2008-01-02 DERIVES DE N-HETEROCYCLIQUE-IMIDAZO°1,2-a!PYRIDINE-2- CARBOXAMIDES, LEUR PREPARATION ET LEUR APPLICATION EN THERAPEUTIQUE
PCT/FR2008/001834 WO2009106749A2 (fr) 2008-01-02 2008-12-31 Dérivés de n-heterocyclique-imidazo[1,2-a]pyridine-2-carboxamides, leur préparation et leur application en thérapeutique

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EP2225242A2 true EP2225242A2 (fr) 2010-09-08

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AU (1) AU2008351927A1 (pt)
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FR2903108B1 (fr) * 2006-07-03 2008-08-29 Sanofi Aventis Sa Utilisation de derives d'imidazo[1,2-a] pyridine-2-carboxamides en therapeutique.
UY33801A (es) 2010-12-13 2013-06-28 Array Biopharma Inc COMPUESTOS SUSTITUIDOS DE N-(1H-INDAZOL-4IL)IMIDAZO[1,2-a]PIRIDIN-3-CARBOXAMIDA COMO INHIBIDORES DE LA TIROSINA QUINASA RECEPTORA DE TIPO III
WO2012147890A1 (ja) * 2011-04-27 2012-11-01 持田製薬株式会社 新規アゾール誘導体
WO2014103801A1 (ja) * 2012-12-28 2014-07-03 株式会社新日本科学 イミダゾピリジン誘導体を有効成分として含むｏｃｔ３活性阻害剤又はｏｃｔ３検出剤
WO2020201773A1 (en) * 2019-04-05 2020-10-08 Storm Therapeutics Ltd Mettl3 inhibitory compounds
WO2022074379A1 (en) * 2020-10-06 2022-04-14 Storm Therapeutics Limited Mettl3 inhibitory compounds
EP4596548A1 (en) * 2024-02-05 2025-08-06 Ludwig-Maximilians-Universität Nurr1 modulators

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US5260303A (en) * 1991-03-07 1993-11-09 G. D. Searle & Co. Imidazopyridines as serotonergic 5-HT3 antagonists
US7544803B2 (en) * 2004-01-23 2009-06-09 Amgen Inc. Vanilloid receptor ligands and their use in treatments
FR2903107B1 (fr) * 2006-07-03 2008-08-22 Sanofi Aventis Sa Derives d'imidazopyridine-2-carboxamides, leur preparation et leur application en therapeutique
JP5358962B2 (ja) * 2007-02-06 2013-12-04 住友化学株式会社 組成物及び該組成物を用いてなる発光素子
AU2008345225A1 (en) * 2007-12-21 2009-07-09 University Of Rochester Method for altering the lifespan of eukaryotic organisms

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BRPI0821992A2 (pt) 2015-06-23
EA201070813A1 (ru) 2010-12-30
UY31587A1 (es) 2009-08-03
CL2008003933A1 (es) 2010-02-12
WO2009106749A2 (fr) 2009-09-03
CN101910172A (zh) 2010-12-08
IL206671A0 (en) 2010-12-30
CO6331306A2 (es) 2011-10-20
ZA201004643B (en) 2011-09-28
MA32059B1 (fr) 2011-02-01
FR2925901B1 (fr) 2011-03-04
MX2010007349A (es) 2010-08-18
JP2011509250A (ja) 2011-03-24
TW200934777A (en) 2009-08-16
AR070072A1 (es) 2010-03-10
CA2710860A1 (fr) 2009-09-03
FR2925901A1 (fr) 2009-07-03
KR20100099244A (ko) 2010-09-10
UY3816Q (es) 2008-09-30
WO2009106749A3 (fr) 2010-05-06
US20100317673A1 (en) 2010-12-16
AU2008351927A1 (en) 2009-09-03

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