EP1981861A2 - Nouvelle methode de synthese de l,4-morpholine-2,5-diones - Google Patents
Nouvelle methode de synthese de l,4-morpholine-2,5-dionesInfo
- Publication number
- EP1981861A2 EP1981861A2 EP07730853A EP07730853A EP1981861A2 EP 1981861 A2 EP1981861 A2 EP 1981861A2 EP 07730853 A EP07730853 A EP 07730853A EP 07730853 A EP07730853 A EP 07730853A EP 1981861 A2 EP1981861 A2 EP 1981861A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- radical
- hydrogen atom
- formula
- aryl
- preparation process
- 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- Withdrawn
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
- C07D265/32—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings with oxygen atoms directly attached to ring carbon atoms
Definitions
- the present invention relates to a novel method for synthesizing 1,4-morpholine-2,5-diones.
- non-toxic degradation products is an essential criterion in the preparation of targeted synthetic polymers as biodegradable and biocompatible matrices for entrapment and controlled release of active ingredients. Also these polymers are often formed from metabolic derivatives such as ⁇ -hydroxy acids or ⁇ -amino acids.
- the preparation of copolymers of ⁇ -hydroxylated acids and ⁇ -amino acids, polyesteramides called polydepsipeptides was begun a few decades ago. Early syntheses of polydepsipeptides were reported in the late 1960s and consisted of polycondensation of linear di- or tridepsipeptides (Stewart, FHC Aust, J.
- polydepsipeptides can thus be obtained by ring opening polymerization, as are the PLGAs from lactide and glycolide (Dechy-Cabaret, O. Martin-Vaca, B. and Bourissou, D., Chem Rev. 2004 , 104, 6147).
- an ⁇ -amino acid and a dihalogenated derivative are first condensed under Schotten-Bauman conditions (aqueous NaOH, dioxane) to give amino acid derivatives JV- (2- haloacyl) with yields of 50-60%.
- the morpholinediones are then obtained by intramolecular cyclization: either by sublimation of a mixture heated to dryness on a celite matrix (very variable yields 20-80%) (in't VeId, PJA, Dijkstra, PJ, van Lochem, JH; Feijen, J.
- the yields of isolated morpholine-2,5-dione are generally fairly average and the operating conditions of the cyclization step are rather harsh. Due to the high cis / trans inversion barrier of the amide bond, high reaction temperatures are required for this step, which explains the formation of degradation products. In addition, the key intramolecular cyclization step is inherently in competition with the formation of dimers and oligomers by intermolecular rather than intramolecular reaction. The Applicant has therefore considered a new route of synthesis of 1,4-morpholine-2,5-diones.
- the subject of the present invention is therefore a process for preparing 1,4-morpholine-2,5-diones of formula (I)
- R, R 1 , R 2 , R 3 and R 4 represent, independently, the hydrogen atom; halo; (C 2 -C 6 ) alkenyl; (C 3 -C 7 ) cycloalkyl; cyclohexenyl; a radical of formula - (CH 2 ) m -
- V represents a covalent bond, the oxygen or sulfur atom, or the radical -C (O) - O- or -NR N -;
- R N represents the hydrogen atom, a (C 1 -C 18) alkyl radical optionally substituted by one or more identical or different substituents chosen from halo and cyano, the aryl or aralkyl radical, the aryl and aralkyl radicals being optionally substituted by one or more identical or different substituents chosen from: - (CH 2 ) n -YZ, halo, nitro and cyano;
- W represents the hydrogen atom; a (CrC) alkyl radical optionally substituted with one or more identical or different substituents chosen from halo, benzoyl, benzyloxy and cyano; (C 2 -C 6 ) alkenyl; (C 2 -C 6 ) alkynyl; -SiR 5 R 6 R 7; aryl or aralkyl, the radicals benzoyl, benzyloxy, aryl and aralkyl being optionally substituted by one or more identical or different substituents chosen from: - (CH 2) n -Y-Z, halo, nitro and cyano;
- R 5 , R 6 and R 7 independently represent a (C 1 -C 4) alkyl or aryl radical
- Y represents -O-, -S- or a covalent bond
- Z represents the hydrogen atom or a (C 1 -C 6) alkyl optionally substituted by one or more identical or different halo radicals; or aralkyl;
- n and n independently represent an integer of 0 to 4.
- R, R 2 , R 3 and R 4 are as defined above and R a represents a leaving group of formula - (CH 2 ) m -VW as defined above with m which is equal to zero and V represents the radical -C (O) -O-,
- halo represents the fluoro, chloro, bromo or iodo radical, preferably chloro, fluoro or bromo.
- the term (CrC 6 ) alkyl represents an alkyl radical having 1 to 6 carbon atoms, linear or branched, such as the methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl, pentyl radicals. or amyl, isopentyl, neopentyl, 2,2-dimethylpropyl, hexyl, isohexyl or 1,2,2-trimethylpropyl.
- (C 1 -Cis) alkyl denotes an alkyl radical having from 1 to 18 carbon atoms, linear or branched, such radicals containing from 1 to 6 carbon atoms as defined above but also heptyl, octyl, 1 , 1,2,2-tetramethyl-propyl, 1,1,3,3-tetramethyl-butyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl.
- alkyl substituted with at least one halo radical it is necessary to understand any linear or branched alkyl chain containing at least one halo radical positioned along the chain such as for example -CHCl-CH 3 but also -CF 3 .
- the radical (CH 2 ), (i integer may represent m and n as defined above), represents a hydrocarbon chain, linear or branched, of i carbon atoms.
- the radical - (CTb) 3 - can represent -CH 2 -CH 2 -CHs- but also -CH (CH 3 ) -CH 2 -, -CH 2 -CH (CH 3 ) - or -C (CH 3 ) 2 -.
- (C 2 -C 6 ) alkenyl means a linear or branched (alkyl) hydrocarbon radical containing from 2 to 6 carbon atoms and having at least one unsaturation (double bond), for example vinyl, allyl, propenyl or butenyl; , pentenyl or hexenyl.
- (C 2 -C 6 ) alkynyl means a linear or branched (alkyl) hydrocarbon radical containing from 2 to 6 carbon atoms and having at least one double unsaturation (triple bond), for example an ethynyl, propargyl or butynyl radical; or pentynyl.
- (C 3 -C 7 ) cycloalkyl denotes a saturated carbon monocyclic system comprising from 3 to 7 carbon atoms, and preferably the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl rings.
- aryl represents an aromatic radical, consisting of a ring or condensed rings, such as, for example, the phenyl, naphthyl, fluorenyl or anthryl radical.
- aralkyl preferably denotes radicals in which the aryl radical is as defined above and the alkyl radical is a (Ci-C 6 ) alkyl as defined above such as for example benzyl or phenethyl.
- the invention more particularly relates to a process as defined above, for the preparation of compound of formula (I) wherein R 1 and R 2 represent, independently, halo; (C 2 -C 6 ) alkenyl; (C 3 -C 7 ) cycloalkyl; cyclohexenyl; or a radical of formula - (CH 2 ) m -VW.
- the invention more particularly also relates to a process as defined above, for the preparation of compound of formula (I) wherein R 1 represents the hydrogen atom,
- R, R 2 , R 3 and R 4 are as defined above, and R la represents a leaving group of formula - (CH 2 ) m -VW as defined above with m which is equal to zero and V, which represents the radical -C (O) -O-, is oxidized,
- R, R 1a , R 2 , R 3 and R 4 are as defined above, is treated with a cleavage agent to give the compound of formula (I) in which R 1 represents the hydrogen atom .
- the leaving group represented by R la is of formula - (CH 2 ) In -VW with m which is equal to zero, V represents the radical -C (O) -O-, and
- W represents a (C 1 -C 18 ) alkyl radical substituted by halo, benzoyl or benzyloxy; (C 2 -C 6 ) alkenyl; (C 2 -C 6 ) alkynyl; -SiR 5 R 6 R 7 ; aryl or aralkyl, the benzoyl, benzyloxy, aryl and aralkyl radicals being optionally substituted with one or more identical or different substituents chosen from: - (CH 2 ) n -YZ, halo, nitro and cyano;
- Y represents -O- or a covalent bond
- R 5 , R 6 and R 7 represent, independently, a (C 1 -C 6 ) alkyl or aryl radical.
- oxidation For the conversion of the ketone function of the compound (II) to ester function, several types of oxidation can be used; the oxidation can thus take place for example in the presence of an oxidizing agent such as a peracid or a peroxide (according to the Baeyer-Villiger oxidation reaction), in the presence of a metal catalyst (SI Murahashi et al Tetrahedron Lett., 1992, 33, 7557-7760 and C. BoIm et al., Tetrahedron Lett., 1993, 34, 3405-3408) or enzymatically (MD Mihovilovic et al., EW J. Org. 2002, 3711-3730).
- an oxidizing agent such as a peracid or a peroxide (according to the Baeyer-Villiger oxidation reaction)
- a metal catalyst SI Murahashi et al Tetrahedron Lett., 1992, 33, 7557-7760 and C. BoI
- a process according to the invention is carried out in the presence of an oxidizing agent according to the Baeyer-Villiger oxidation reaction.
- the oxidation reaction is carried out very preferably on the most congested side of the ketone, so that 1,4-morpholine-2,5-dione can be obtained very selectively.
- the oxidizing agent is used in the presence of a catalyst.
- the oxidizing agent (or oxidation agent) used for carrying out the process according to the invention may be a peracid or a peroxide.
- a peracid there may be mentioned trifluoroperacetic acid (TFPAA), peracetic acid (PAA), metachloroperbenzoic acid (m-CPBA), preferably in combination with Lewis acids (SnCl 4 , Sn (OTf ) 3 , Re (OTf) 3 ) or strong acids (sulfonic acids, Nafion-H, CF 3 COOH .
- peroxide As an example of peroxide, mention may be made of hydrogen peroxide (H 2 O 2 ); the hydrogen peroxide will be used alone or in the presence of a catalyst which may be a Lewis acid (such as BF 3 ) or a metal complex whether in the homogeneous phase (Mo, Re, Pt) or in the heterogeneous phase (zeolite d tin, tin hydrotalcite); mention may also be made of bis (trimethylsilyl) peroxide Me 3 SiOOSiMe 3 which will be used in the presence of a Lewis acid (Me 3 SiOTf, SnCl 4 or BF 3 -OEt 2 ).
- a catalyst which may be a Lewis acid (such as BF 3 ) or a metal complex whether in the homogeneous phase (Mo, Re, Pt) or in the heterogeneous phase (zeolite d tin, tin hydrotalcite); mention may also be made of bis (trimethylsilyl) peroxide Me 3
- the oxidizing agent is a peracid.
- the peracid is preferably used in the presence of a Lewis acid or a strong acid, and more particularly in the presence of a strong acid selected from sulphonic acids.
- the peracid is also preferentially used in the presence of a base and more particularly in the presence of an inorganic base.
- the peracid is metachloroperbenzoic acid (m-CPBA).
- Metachloroperbenzoic acid is preferably used in the presence of trifluoromethanesulfonic acid or a hydrogen carbonate or carbonate salt.
- the oxidizing agent is a peroxide.
- the subject of the present invention is a process as defined above, characterized in that said process is carried out at a temperature of between 20 and 80 ° C. in the presence of 1 to 3 molar equivalents of oxidant. relative to the substrate.
- the process is carried out in an organic solvent, in particular chlorinated, at a substrate concentration of between 0.01 M and 2 M.
- the oxidation agents mentioned above are in general commercial. Non-commercial agents may be synthesized according to methods known to those skilled in the art.
- trifluoroperacetic acid which is not commercially available can easily be obtained by the action of hydrogen peroxide H 2 O 2 on trifluoroacetic acid or trifluoroacetic anhydride CF 3 CO 2 H and (CF 3 CO) 2 O, respectively (R. Liotta et al, J Org Chem 1980, 45, 2887-2890, M. Anastasia et al., J.
- the reaction solvent is selected from organic solvents which do not interfere with the reaction.
- organic solvents such as aliphatic or aromatic chlorides (such as dichloromethane, chloroform, dichloroethane, chlorobenzene or a dichlorobenzene).
- radicals R 1 and R 2 of the general formula (I) as defined in the present application are equivalent and therefore interchangeable.
- the compound (I) can also be obtained from the morpholidione of formula (Ia)
- R la is a leaving group of formula -C (O) -OW, after cleavage of this leaving group R la .
- Various reagents and conditions well known to those skilled in the art and detailed in various works allow cleavage of the R group as defined above and after decarboxylation leading to compound (I) wherein the group R 1 represents a hydrogen atom.
- labile groups Ri a there may be mentioned benzyloxycarbonyl, (benzyloxy) methoxycarbonyl,
- the present invention more particularly relates to a process as defined above, characterized in that R represents the hydrogen atom or a radical of formula - (CHa) 1n -VW with V which represents a covalent bond or the radical -C (O) -O- and W an optionally substituted aralkyl radical; R 1 , R 2 , R 3 and R 4 represent, independently, the hydrogen atom or a radical of formula ⁇ (CH 2 ) m -VW with V which represents a covalent bond and W a radical (QC ⁇ alkyl.
- the present invention more particularly relates to a process as defined above, characterized in that R represents the hydrogen atom or an optionally substituted aralkyl radical.
- the present invention more particularly relates to a process as defined above, characterized in that the aryl term of the aryl and aralkyl radicals is the phenyl radical and m is equal to zero or one.
- the present invention more particularly relates to a process as defined above, characterized in that R represents the hydrogen atom or the benzyl radical, R 1 and R 2 , represent, independently, the atom of hydrogen or the methyl or ethyl radical, and R 3 and R 4 represent, independently, the hydrogen atom or a methyl radical.
- the present invention also relates to a process for the preparation of 1,4-morpholine-2,5-dione of formula (I)
- R, R 1 , R 2 , R 3 and R 4 represent, independently, the hydrogen atom; halo; (C 2 -C 6 ) alkenyl; (C 3 -C 7 ) cycloalkyl; cyclohexenyl; a radical of formula - (CH 2 ) m -
- V represents a covalent bond, the oxygen or sulfur atom, or the radical -C (O) - O- or -NR N -;
- R N and W represent, independently, the hydrogen atom, a (CrO) alkyl radical optionally substituted by one or more identical or different substituents chosen from halo and cyano, the aryl or aralkyl radical, the aryl and aralkyl radicals being optionally substituted with one or more identical or different substituents selected from: - (CH 2 ) n -YZ, halo, nitro and cyano;
- Y represents -O-, -S- or a covalent bond
- Z represents the hydrogen atom or a radical optionally substituted with one or more identical or different halo radicals; or aralkyl;
- n and n independently represent an integer of 0 to 4.
- R, R 1 , R 2 , R 3 and R 4 are as defined above.
- the subject of the present invention is also compounds of formula (I) and especially compounds (I) as obtained according to the process defined above.
- the subject of the present invention is also compounds of formula (Ib)
- R b represents an arylalkyl radical
- Ru, R 3b and R 4b independently represent the hydrogen atom; halo; (C 2 -C e) alkenyl; (C 3 -C 7 ) cycloalkyl; cyclohexenyl; or a radical of formula - (CH 2 VV-W;
- R 2b represents halo; (C 2 -C 6 ) alkenyl; (C 3 -C 7 ) cycloalkyl; cyclohexenyl; a radical of formula - (CH 2 VV-W;
- V represents a covalent bond, the oxygen or sulfur atom, the -C (O) -O- or -NRN- radical;
- R N represents the hydrogen atom; a (C 1 -C 18 ) alkyl radical optionally substituted with one or more identical or different substituents chosen from halo and cyano; the aryl or aralkyl radical, the aryl and aralkyl radicals being optionally substituted by one or more identical or different substituents chosen from: - (CH 2 ) n -YZ, halo, nitro and cyano;
- W represents the hydrogen atom, a (C 1 -C 1 s) alkyl radical optionally substituted with one or more identical or different substituents chosen from halo, benzoyl, benzyloxy and cyano; (C 2 -C 6 ) alkenyl; (C 2 -C 6 ) alkynyl; -SiR 5 R 6 R 7 ; the aryl or aralkyl radical, the benzoyl, benzyloxy, aryl and aralkyl radicals being optionally substituted by one or more identical or different substituents chosen from: - (CH 2 ) n -YZ, halo, nitro and cyano;
- R 5 , R 6 and R 7 represent, independently, a (C 1 -C 6 ) alkyl or aryl radical;
- Y represents -O-, -S- or a covalent bond
- Z represents the hydrogen atom or a (C 1 -C e) alkyl radical optionally substituted by one or more identical or different halo radicals; or aralkyl;
- n and n independently represent an integer of 0 to 4.
- V represents the radical -C (O) -O- and m is equal to zero
- R 11 represents the hydrogen atom and R 2b the radical of formula - (CH 2 ) m -VW with m which is equal to 1 and V which represents the radical -C (O) -O-, then W does not represent the hydrogen atom.
- the present invention more particularly relates to compounds of formula (I b) as defined above, and characterized in that R b represents a hydrogen atom or a radical of formula - (CEK) with nI -vw V which represents a covalent bond or the radical -C (O) -O-; and R 2b represents a radical of formula - (CH 2 ) m -VW with V which represents a covalent bond or the radical -C (O) -O-.
- R 11 represents a hydrogen atom or a (C 1 -C 6 ) alkyl radical and R 2b represents a (C 1 -C 6 ) alkyl radical.
- the compounds of formula (I b ) as defined above are such that the aryl term of the aryl and aralkyl radicals is the phenyl radical.
- the present invention more particularly relates to compounds of formula (I b ) as defined above, and characterized in that R b represents the optionally substituted benzyl radical.
- the present invention more particularly relates to compounds of formula (I b ) as defined above, and characterized in that R 3b and R 4b represent, independently, the hydrogen atom or a radical (C 1 C 6 ) alkyl.
- R 3b represents the hydrogen atom
- R 4b represents the hydrogen atom or a (C 1 -C 6 ) alkyl radical.
- the present invention more particularly relates to the compounds of formula (I) as defined above, and characterized in that R 11 , represents the atom hydrogen, methyl, carboxy or benzyloxycarbonyl, R 2b a methyl radical, R 3b and IUb the hydrogen atom, and R b the benzyl radical.
- the subject of the present invention is also the use of the compounds of formula (I) or (I b ) and in particular the compounds (I) or (I b ) as obtained according to the process defined above, for the preparation of polydepsipeptides.
- (II) can be obtained by a 3-step route from (1).
- the formation of the compound (2) from the compound (1) can be carried out according to HC Brown et al., J. Am. Chem. Soc. 1988, 110, 1539-1546.
- the synthesis step of the compound (3) can be carried out according to M. Conrad et al., Ber. 1898, 31, 2726-2731.
- the final cyclization step is carried out spontaneously after treatment of (3) with benzylamine (2.2 equiv.) In tetrahydrofuran according to FaIk, H. et al. Monatsch. Chem., GE 113, 1982, 11, 1329-1348.
- (II) can also be obtained from 3-methyl tetramic acid (7).
- the formation of the compound (7) from the compound (4) can be carried out according to Koech, P. et al., Org. Lett. 2004, 6, 691-694 with a yield of 98% over the three stages.
- the final stage of formation of the compound (II) can be carried out according to Page, P. C. B. et al., Org. Lett. 2003, 5, 353-355 with a yield of 78% isolated product.
- Step 2 oxidation of the keto-amide (II) to 4-benzyl-6,6-dimethyl-1,4-morpholine-2,5-dione
- Step 1 synthesis of the precursor (II): 1-benzyl-3-carboxybenzyl-3-methylpyrrolidine-2,4-dione
- Step 2 oxidation of the ketoamide (II) to 4-benzyl-6-carboxybenzyl-6-methyl-1,4-morpholine-2,5-dione (2a)
- (2a) is then converted to 4-benzyl-6-methyl-1,4-mo ⁇ holine-2,5-dione in a single pot.
- a solution of (2a) in 30 mL of toluene is stirred under atmospheric pressure of hydrogen in the presence of 10% Pd / C at room temperature for twelve hours.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR0600662A FR2896502B1 (fr) | 2006-01-25 | 2006-01-25 | Nouvelle methode de synthese de 1,4-morpholine-2,5-diones |
PCT/FR2007/000135 WO2007085729A2 (fr) | 2006-01-25 | 2007-01-24 | Nouvelle methode de synthese de l,4-morpholine-2,5-diones |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1981861A2 true EP1981861A2 (fr) | 2008-10-22 |
Family
ID=36636457
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP07730853A Withdrawn EP1981861A2 (fr) | 2006-01-25 | 2007-01-24 | Nouvelle methode de synthese de l,4-morpholine-2,5-diones |
Country Status (8)
Country | Link |
---|---|
US (1) | US20100036120A1 (fr) |
EP (1) | EP1981861A2 (fr) |
JP (1) | JP2009528982A (fr) |
CN (1) | CN101374822A (fr) |
CA (1) | CA2640031A1 (fr) |
FR (1) | FR2896502B1 (fr) |
RU (1) | RU2008134461A (fr) |
WO (1) | WO2007085729A2 (fr) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103012238A (zh) * | 2013-01-11 | 2013-04-03 | 华东理工大学 | 一种n-取代-1h-吡咯的制备方法 |
EP3603650A1 (fr) | 2018-08-01 | 2020-02-05 | Edix O Sarl | Compositions injectables et a duree d'action prolongee pour leur utilisation dans le traitement de maladies de l'ongle et/ou pour accelerer la croissance de l'ongle |
WO2020025683A1 (fr) | 2018-08-01 | 2020-02-06 | Edix-O Sarl | Compositions injectables a duree d'action prolongee pour leur utilisation dans le traitement de maladie de l'ongle et/ou pour accelerer la croissance de l'ongle |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3392169A (en) * | 1965-09-02 | 1968-07-09 | Monsanto Co | 3, 6-dioxo-2-morpholine acetic acids and process for making them |
US5877278A (en) * | 1992-09-24 | 1999-03-02 | Chiron Corporation | Synthesis of N-substituted oligomers |
DE4440193A1 (de) * | 1994-11-10 | 1996-05-15 | Bayer Ag | Verwendung von Dioxomorpholinen zur Bekämpfung von Endoparasiten, neue Dioxomorpholine und Verfahren zur ihrer Herstellung |
-
2006
- 2006-01-25 FR FR0600662A patent/FR2896502B1/fr not_active Expired - Fee Related
-
2007
- 2007-01-24 RU RU2008134461/04A patent/RU2008134461A/ru not_active Application Discontinuation
- 2007-01-24 CN CN200780003517.4A patent/CN101374822A/zh active Pending
- 2007-01-24 EP EP07730853A patent/EP1981861A2/fr not_active Withdrawn
- 2007-01-24 JP JP2008551822A patent/JP2009528982A/ja not_active Abandoned
- 2007-01-24 US US12/162,334 patent/US20100036120A1/en not_active Abandoned
- 2007-01-24 WO PCT/FR2007/000135 patent/WO2007085729A2/fr active Application Filing
- 2007-01-24 CA CA002640031A patent/CA2640031A1/fr not_active Abandoned
Non-Patent Citations (1)
Title |
---|
See references of WO2007085729A2 * |
Also Published As
Publication number | Publication date |
---|---|
WO2007085729A2 (fr) | 2007-08-02 |
CN101374822A (zh) | 2009-02-25 |
FR2896502A1 (fr) | 2007-07-27 |
WO2007085729A3 (fr) | 2008-04-24 |
RU2008134461A (ru) | 2010-02-27 |
FR2896502B1 (fr) | 2010-09-24 |
CA2640031A1 (fr) | 2007-08-02 |
US20100036120A1 (en) | 2010-02-11 |
JP2009528982A (ja) | 2009-08-13 |
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