EP2043643A2 - Utilisation de dérivés d'imidazo[1, 2-a]pyridine-2-carboxamides en thérapeutique - Google Patents
Utilisation de dérivés d'imidazo[1, 2-a]pyridine-2-carboxamides en thérapeutiqueInfo
- Publication number
- EP2043643A2 EP2043643A2 EP07803835A EP07803835A EP2043643A2 EP 2043643 A2 EP2043643 A2 EP 2043643A2 EP 07803835 A EP07803835 A EP 07803835A EP 07803835 A EP07803835 A EP 07803835A EP 2043643 A2 EP2043643 A2 EP 2043643A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- sub
- formula
- compound
- treatment
- prevention
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 239000003814 drug Substances 0.000 title claims abstract description 13
- BEHYAANJUKYBTH-UHFFFAOYSA-N imidazo[1,2-a]pyridine-2-carboxamide Chemical class C1=CC=CC2=NC(C(=O)N)=CN21 BEHYAANJUKYBTH-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 39
- 238000011282 treatment Methods 0.000 claims abstract description 17
- 239000002253 acid Substances 0.000 claims abstract description 15
- 150000003839 salts Chemical class 0.000 claims abstract description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 14
- 238000002360 preparation method Methods 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 10
- 230000006806 disease prevention Effects 0.000 claims abstract description 5
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims abstract description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000000460 chlorine Substances 0.000 claims abstract description 4
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 4
- 239000001257 hydrogen Substances 0.000 claims abstract description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229910003827 NRaRb Inorganic materials 0.000 claims abstract description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 3
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- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 abstract description 5
- 229910052736 halogen Inorganic materials 0.000 abstract description 3
- 150000002367 halogens Chemical class 0.000 abstract description 3
- 125000004429 atom Chemical group 0.000 abstract 1
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 description 17
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- BIQRPLMAKJWHIH-UHFFFAOYSA-N 1h-imidazo[4,5-b]pyridine-2-carboxylic acid Chemical compound C1=CN=C2NC(C(=O)O)=NC2=C1 BIQRPLMAKJWHIH-UHFFFAOYSA-N 0.000 description 2
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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- PFKFTWBEEFSNDU-UHFFFAOYSA-N 1,1'-Carbonyldiimidazole Substances C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
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- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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- A61P25/24—Antidepressants
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- 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
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- 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
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- 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]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
- the present invention relates to the therapeutic application of imidazo [1,2-a] pyridine-2-carboxamide derivatives in the treatment or prevention of diseases involving nuclear Nurr-1 receptors also called NR4A2, NOT, TINUR , RNR-I, and HZF3.
- R 1, R 2 , R 3 and R 4 represent a hydrogen atom and X is a phenyl group optionally substituted by one or more groups chosen independently of one another from the following halogen atoms or groups;
- Ra and Rb are independently of each other, hydrogen, (Ci-C 6 ) alkyl or form with the nitrogen atom a 4- to 7-membered ring, in the base or salt state of acid addition for the preparation of a medicament for the treatment and prevention of diseases in which the NOT receptor is involved.
- a first group of compounds consists of compounds for which:
- R 3 is methyl and X is unsubstituted phenyl; or R 1 is methyl and X is unsubstituted phenyl in the form of a base or an acid addition salt.
- 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 may be prepared with pharmaceutically acceptable acids, but the salts other acids useful, for example, for the purification or isolation of compounds of formula
- 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.
- the compounds of general formula (T) can be prepared according to the process described in Scheme 1.
- Lane A consists in preparing the 2-amino-pyridines of formula (IT) 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., 1997, 50, 719-725 and J.G. Lombardino, J. Org. Chem. (1965), 30 (7), 2403 for example.
- TU 2-oxo-N-arylpropionamide
- 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 is OH, or halogen or Q-C 6 ) alkoxy with an arylamine X - ⁇ H2 (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.
- 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.
- a coupling agent such as CDI, EDCI, HATU or HBTU
- the amine (VI) can be reacted 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 (1977). ), 18, 4171) or zirconium terbutylate.
- 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 (I) may be subjected, if desired and if necessary, to obtain products of formula (I) or may be converted into other products of formula (I) in one or more of the reaction reactions. following, in any order: a) a hydroxyl functional conversion reaction to alkoxy function, b) a catalytic coupling reaction of a halogen derivative and an organometallic derivative such as stannic or boronic to introduce a methyl substituent, ) a reaction of protection of the reactive functions, d) a reaction of elimination of the protective groups that can carry the protected reactive functions, e) a salification reaction with a mineral or organic acid or a base to obtain the corresponding salt, f ) a resolving reaction of the racemic enantiomeric forms, said products of formula (I) thus obtained being, if appropriate, in all the isomeric forms possible; racemic, enantiomeric and diastereoisomeric
- the compounds according to the invention have been the subject of pharmacological tests for determining their modulatory effect on NOT.
- EC50's 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).
- ATCC American Type Culture Collection
- N2A-8NBRE cells were cultured 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. After one week of culture, 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. well transparent background.
- the cells are deposited at a rate of 60,000 per well in 75 ⁇ L for 24 hours before the addition of 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 wait 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 in the form of stock solution at 10 -2 M, then diluted in 100% DMSO.Each concentration of product is diluted beforehand in culture medium before incubation with the cells thus containing 0.625% final of DMSO.
- Compounds Nos. 1 and 2 showed an EC 50 of 5.5 nM and 17 nM, respectively.
- the direct binding between compounds of the invention and the human NOT receptor was evaluated using SPR (surface plasmon resonance) technology.
- SPR surface plasmon resonance
- the protein is immobilized covalently to the matrix and the molecule to be studied is injected into the chamber containing the sensor chip.
- the signal is directly proportional to the amount of product attached to the protein.
- the binding assays were performed in a BIACORE S51 instrument (Biacore Inc., Piscataway NJ).
- the entire GST-NOT protein (NOT-FL) was provided by Invitrogen (PV3265).
- the ligand binding domain of NOT was expressed and purified as described in Nature 423, 555-560.
- CM5 sensor chip Biacore Inc.
- HBS-N buffer 10 mM HEPES, 0.15 M NaCl, 3 mM EDTA, pH 7.4
- the stock solutions of the compounds to be studied at 1.5 mM in DMSO are serially diluted in elution buffer (50 mM HEPES pH8, 150 mM NaCl, 10 mM MgCl 2 , 2% DMSO, 1 mM DTT) at room temperature. concentrations ranging from 3.75 at 0.1 ⁇ M. Each concentration of product is injected at 4 ° C. for 1 minute at 30 ⁇ l / min. The dissociation was recorded for 5 minutes without any other procedure of regeneration of the surface. The signals obtained are corrected by testing each product concentration on an unmodified (white) dextran surface. The signal due to the migration buffer is deduced from the total signal ("double referencing") as well as the effect of the DMSO. The signal analysis is performed using the Biacore S51 analysis software (version 1.2.1). The compounds are then classified according to their maximum binding level and kinetic binding parameters to the immobilized protein.
- compound No. 1 has a medium affinity.
- 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.
- These drugs find their therapeutic use, especially in the treatment and prevention of neurodegenerative diseases such as Parkinson's disease, Alzheimer's, tauopathies (eg, supranuclear progressive paralysis, fronto-temporal dementia, corticobasal degeneration, Pick's disease), multiple sclerosis; 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 such as vascular diseases, atherosclerosis, inflammation of the joints, osteoarthritis, rheumatoid arthritis osteoarthritis, allergic inflammatory diseases such as asthma and finally the treatment of osteoporosis, cancers.
- 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 according to the invention.
- These pharmaceutical compositions contain an effective dose of at least one compound according to the invention, or a pharmaceutically acceptable salt of said compound, 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 of formula (I) above, or its salt, can to 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 according to the invention, or one of pharmaceutically acceptable salts thereof.
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- Hospice & Palliative Care (AREA)
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR0606013A FR2903108B1 (fr) | 2006-07-03 | 2006-07-03 | Utilisation de derives d'imidazo[1,2-a] pyridine-2-carboxamides en therapeutique. |
PCT/FR2007/001127 WO2008003858A2 (fr) | 2006-07-03 | 2007-07-03 | Utilisation de dérivés d'imidazo[1, 2-a]pyridine-2-carboxamides en thérapeutique |
Publications (1)
Publication Number | Publication Date |
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EP2043643A2 true EP2043643A2 (fr) | 2009-04-08 |
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Application Number | Title | Priority Date | Filing Date |
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EP07803835A Withdrawn EP2043643A2 (fr) | 2006-07-03 | 2007-07-03 | Utilisation de dérivés d'imidazo[1, 2-a]pyridine-2-carboxamides en thérapeutique |
Country Status (13)
Country | Link |
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US (1) | US20090149494A1 (ko) |
EP (1) | EP2043643A2 (ko) |
JP (1) | JP2009541473A (ko) |
KR (1) | KR20090034861A (ko) |
CN (1) | CN101484168A (ko) |
AU (1) | AU2007271010A1 (ko) |
BR (1) | BRPI0714317A2 (ko) |
CA (1) | CA2656363A1 (ko) |
FR (1) | FR2903108B1 (ko) |
IL (1) | IL195949A0 (ko) |
MX (1) | MX2008016550A (ko) |
RU (1) | RU2009103302A (ko) |
WO (1) | WO2008003858A2 (ko) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
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FR2903107B1 (fr) * | 2006-07-03 | 2008-08-22 | Sanofi Aventis Sa | Derives d'imidazopyridine-2-carboxamides, leur preparation et leur application en therapeutique |
FR2925906B1 (fr) * | 2008-01-02 | 2010-08-20 | Sanofi Aventis | COMPOSES DE N-PHENYL-IMIDAZO°1,2-a!PYRIDINE-2-CARBOXAMIDES, LEUR PREPARATION ET LEUR APPLICATION EN THERAPEUTIQUE |
FR2925903B1 (fr) * | 2008-01-02 | 2011-01-21 | Sanofi Aventis | DERIVES 6-HETEROCYCLIQUE-IMIDAZO°1,2-a!PYRIDINE-2- CARBOXAMIDES, LEUR PREPARATION ET LEUR APPLICATION EN THERAPEUTIQUE |
FR2925900B1 (fr) * | 2008-01-02 | 2011-03-04 | Sanofi Aventis | DERIVES DE N-PHENYL-IMIDAZO°1,2-a!PYRIDINE-2-CARBOXAMIDES, LEUR PREPARATION ET LEUR APPLICATION EN THERAPEUTIQUE |
JP6284490B2 (ja) * | 2012-12-28 | 2018-02-28 | 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 |
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US6379666B1 (en) * | 1999-02-24 | 2002-04-30 | Edward L. Tobinick | TNF inhibitors for the treatment of neurological, retinal and muscular disorders |
DE10117184A1 (de) * | 2001-04-05 | 2002-10-17 | Gruenenthal Gmbh | Substituierte Imidazol[1,2-a]-pyridin-3-yl-amid- und -aminverbindungen |
GB0303503D0 (en) * | 2003-02-14 | 2003-03-19 | Novartis Ag | Organic compounds |
FR2903107B1 (fr) * | 2006-07-03 | 2008-08-22 | Sanofi Aventis Sa | Derives d'imidazopyridine-2-carboxamides, leur preparation et leur application en therapeutique |
FR2925901B1 (fr) * | 2008-01-02 | 2011-03-04 | Sanofi Aventis | DERIVES DE N-HETEROCYCLIQUE-IMIDAZO°1,2-a!PYRIDINE-2- CARBOXAMIDES, LEUR PREPARATION ET LEUR APPLICATION EN THERAPEUTIQUE |
FR2925900B1 (fr) * | 2008-01-02 | 2011-03-04 | Sanofi Aventis | DERIVES DE N-PHENYL-IMIDAZO°1,2-a!PYRIDINE-2-CARBOXAMIDES, LEUR PREPARATION ET LEUR APPLICATION EN THERAPEUTIQUE |
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2006
- 2006-07-03 FR FR0606013A patent/FR2903108B1/fr not_active Expired - Fee Related
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2007
- 2007-07-03 RU RU2009103302/15A patent/RU2009103302A/ru not_active Application Discontinuation
- 2007-07-03 KR KR1020097000051A patent/KR20090034861A/ko not_active Application Discontinuation
- 2007-07-03 AU AU2007271010A patent/AU2007271010A1/en not_active Abandoned
- 2007-07-03 CA CA002656363A patent/CA2656363A1/fr not_active Abandoned
- 2007-07-03 BR BRPI0714317-6A2A patent/BRPI0714317A2/pt not_active IP Right Cessation
- 2007-07-03 WO PCT/FR2007/001127 patent/WO2008003858A2/fr active Application Filing
- 2007-07-03 JP JP2009517334A patent/JP2009541473A/ja not_active Withdrawn
- 2007-07-03 EP EP07803835A patent/EP2043643A2/fr not_active Withdrawn
- 2007-07-03 CN CNA2007800252246A patent/CN101484168A/zh active Pending
- 2007-07-03 MX MX2008016550A patent/MX2008016550A/es active IP Right Grant
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2008
- 2008-12-15 IL IL195949A patent/IL195949A0/en unknown
- 2008-12-17 US US12/337,018 patent/US20090149494A1/en not_active Abandoned
Non-Patent Citations (1)
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See references of WO2008003858A2 * |
Also Published As
Publication number | Publication date |
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WO2008003858A3 (fr) | 2008-04-17 |
JP2009541473A (ja) | 2009-11-26 |
WO2008003858A2 (fr) | 2008-01-10 |
FR2903108B1 (fr) | 2008-08-29 |
US20090149494A1 (en) | 2009-06-11 |
CA2656363A1 (fr) | 2008-01-10 |
AU2007271010A1 (en) | 2008-01-10 |
MX2008016550A (es) | 2009-02-12 |
BRPI0714317A2 (pt) | 2014-06-24 |
FR2903108A1 (fr) | 2008-01-04 |
CN101484168A (zh) | 2009-07-15 |
KR20090034861A (ko) | 2009-04-08 |
RU2009103302A (ru) | 2010-08-10 |
IL195949A0 (en) | 2009-09-01 |
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