Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
  • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
  • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
  • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
  • C07D213/81—Amides; Imides
  • C07D213/82—Amides; Imides in position 3
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P35/00—Antineoplastic agents
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
  • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Definitions

• the present invention relates to novel anticancer compounds, the compositions containing them and their therapeutic application, especially as anticancer agents.
• the invention also relates to the process for the preparation of these compounds as well as to some of the intermediate products.
• WO 99/31064 discloses anticancer compounds of formula (A):
• G represents in particular the group - (CRgRio) m -R8 in which m is 0 or 1, Rg and R 10 may represent a hydrogen atom or an alkyl group and R 8 represents an aralkyl group, a monocyclic aromatic or heteroaromatic group may contain 1 to 3 heteroatoms (N, O or S) or a bicyclic or tricyclic aromatic group.
• R 8 may be optionally substituted with: halogen, - CN, alkyl, fluoroalkyl, cycloalkyl, aralkyl, aryl, -OH, hydroxyalkyl, alkoxy (-Oalkyl), aryloxy (-Oaryl), mercapto (-SH), alkylthio (-Salkyl) ), arylthio (-Saryl), carboxy (-COOH), carboxyalkyl (alkyl-COOH), carboxyalkényle (-alkenyl-COOH), alkoxycarbonyl (- COOalkyl), nitro (-NO2), amino (-NH 2), aminoalkyl (-alkyl-NH 2 ), monoalkylamino (-NHalkyl), di-alkylamino (-N (alkyl) 2 ).
• US 2006/0040956 discloses anti-cancer compounds of formula (B): in which A can represent the ring and R 2 represents a group chosen from H, halogen, -OR 3 , oxo, -SR 3 , -CO 2 R 3 , -COR 3 , -CONR 3 R 3 , -NR 3 R 3 , -SO 2 NR 3 R 3 , - NR 3 COOR 3 , -NR 3 COR 3 , cycloalkyl, optionally substituted phenyl, alkyl, cyano, nitro, ...
• WO 00/50399 discloses biologically active compounds, usable as anticancer agents, of formula (C):
• Z is CH or N and R 1-4 are carbohydrate groups.
• R 4 may be the group 6 wherein A is a single bond or a carbohydrate group and R 7 is a carbohydrate group.
• the 8 compounds described are characterized by one of the following reasons:
• halogen atom a fluorine, chlorine, bromine or iodine atom
• Alkyl group a saturated aliphatic hydrocarbon group comprising from 1 to 10 carbon atoms (advantageously from 1 to 6 carbon atoms) of formula C n H 2n + 1 -, obtained by removing a hydrogen atom from an alkane.
• the alkyl group can be linear or branched. By way of examples, mention may be made of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, 2,2-dimethylpropyl and hexyl groups;
• Alkylene group a divalent group of formula -CH 2n- , obtained by removing two hydrogen atoms from an alkane on two different carbon atoms of said alkane;
• Alkoxy group an -O-alkyl group, wherein the alkyl group is as defined above;
• Cycloalkyl group a cyclic alkyl group comprising between 3 and 8 carbon atoms, all the carbon atoms being involved in the cyclic structure.
• pyrrolidinyl piperidinyl, piperazinyl or N- (C 1 -C 4 ) alkyl-piperazinyl, azepanyl, thiomorpholinyl, 1-oxo-thiomorpholinyl, 1, 1-dioxothiomorpholinyl groups.
• the present invention relates to a compound of formula (I):
• W represents:
• k is an integer that is 0 or 1;
• n is an integer that is 0, 1 or 2;
• R 1 represents a hydrogen atom, a (C 1 -C 6) alkyl, (C 3 -C 6) cycloalkyl or phenyl group optionally substituted by the trifluoromethyl group;
• R'i represents a hydrogen atom or a group (CrC ⁇ Jalkyl
• R 2 represents: a (C 3 -C 6 ) cycloalkyl group
• R3 represents at least one substituent of the pyridine ring chosen from a hydrogen or fluorine atom, a (CrC 4 ) alkyl group, a cyano or -NR c R d in which R c and Rd represent a hydrogen atom or a (CrC 4 ) alkyl group.
• Z and Z ' represent N or CH. More particularly, Z and Z 'may respectively represent N and CH; CH and CH or N and N:
• the group - (C 1 -C 4 ) alkylene-CH CH- may be E or Z.
• n is an integer which can be 0, 1 or 2.
• R 1 represents a hydrogen atom, a (C 1 -C 6 ) alkyl, (C 3 -C 6 ) cycloalkyl group, for example cyclopropyl, or the phenyl group optionally substituted by the trifluoromethyl group.
• R 1 represents a hydrogen atom or the group (CrC 2) alkyl, more particularly R 1 represents a hydrogen atom, R 1 and / or R 1 may be chosen from those described in Table I.
• R 2 represents:
• the heterocycloalkyl group formed by R 3 and R b may be, for example, the pyrrolidinyl group
• the heterocycloalkyl group formed by R 3 and R b may be optionally substituted by one or more substituents, which are identical to or different from each other when there are several of them, chosen from: -OH; (CrC 4 ) alkoxy: for example methoxy; (CrC 4 ) alkyl: for example methyl.
• the substituted heterocycloalkyl may be the 3-hydroxypiperidinyl group
• the pyridine ring may comprise from 1 to 4 substituents R 3 chosen from a hydrogen or fluorine atom, a (CrC 4 ) alkyl group, a cyano or -NR c R d in which R c and R d represent a hydrogen atom or a (CrC 4 ) alkyl group R 3 may be chosen from those described in Table I
• R 3 is in the 5 and / or 6 position on the py ⁇ dine ring. 3 is 1 and / or R 3 is in position 5 or 6 on the pyndine nucleus as shown below position 6 position 5
• R 3 is even more preferably in the 6-position.
• R 3 represents a hydrogen atom, -NH 2 or CN
• R 1 is (C 1 -C 4 ) alkyl
• the (CrC 4 ) alkylene group of W denotes more particularly the group - (CH 2 ) I-4 -
• R 1 is phenyl optionally substituted with trifluoromethyl
• the compounds of the invention may exist in the form of bases or addition salts with acids. Such addition salts are also part of the invention. These salts are advantageously 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 also form part of the invention.
• the compounds according to the invention may also exist in the form of hydrates or solvates, namely in the form of combinations or combinations with one or more molecules of water or with a solvent. Such hydrates and solvates are also part of the invention.
• the compounds may have one or more asymmetric carbon atoms. They can therefore exist as enantiomers or diastereoisomers. These enantiomers, diastereoisomers, as well as their mixtures are part of the invention.
• the N-oxides of compounds containing an amine or a nitrogen atom are also part of the invention.
• the subject of the invention is the process for preparing the compounds of the invention as well as some of the reaction intermediates.
• step (i) a Sonogashira type coupling between Pi and P 2 is performed to obtain P 3 .
• HaI represents a halogen atom (chlorine, bromine, iodine)
• ALK represents the group (Cr
• C 4 ) alkylene and PG represents a group protecting the amine function, for example BOC.
• the coupling is carried out in the presence of a palladium complex (in the oxidation state (0) or
• the palladium complex may be for example
• Pd (PPh 3 ) 4 PdCl 2 (PPh 3 ) 2 , Pd (OAc) 2 , PdCl 2 (dppf) or bis (di-tert-butyl (4-dimethylaminophenyl) phosphine) dichloropalladium (II).
• a copper (I) salt such as cuprous chloride, is generally required as a cocatalyst of the palladium complex.
• a copper salt such as, for example, the Pd 2 (dba) 3 , P (t-Bu) 3 , and 3 N system in THF (Eur J. Org Chem 2000, 3679).
• the coupling is carried out in the presence in a basic medium, which may be, for example, K 2 CO 3 , NaHCO 3 , and 3 N, K 3 PO 4 , Ba (OH) 2 , NaOH, KF, CsF, Cs 2 CO 3.
• the coupling can be conducted in a mixture of a polar solvent, for example DMF.
• the temperature is between 50 and 120 ° C.
• the duration of the reaction may in some cases exceed long (see conditions of ex.1.3.).
• step (ii) P 3 is deprotected, for example by treatment in acidic medium when PG represents BOC.
• the solvent may be THF.
• Step (i) Sonogashira is coupled in step (i) between P 5 and P 2 to obtain P 6 , then in step (ii), and P 6 is reacted with the amine R 2 NH 2 to obtain P 3 .
• Steps (iii) and (iv) are similar to steps (ii) and (iii) of Scheme 1.
• partial hydrogenation means not completely hydrogenating all the -C ⁇ C- bonds of the starting material; for this purpose, it is possible to use, for example, a deactivated or partially deactivated hydrogenation catalyst, such as for example the Lindlar catalyst (typically it is Pd / CaCO 3 deactivated with quinoline or lead acetate). ).
• a deactivated or partially deactivated hydrogenation catalyst such as for example the Lindlar catalyst (typically it is Pd / CaCO 3 deactivated with quinoline or lead acetate).
• the partial hydrogenation thus leads to a mixture of the starting material and the products comprising the double and the triple bond which can then be separated by chromatography.
• step (i) P 8 and the Pg acrylate are reacted to obtain P 10 (Bohlmann-Ratz reaction, in this regard, see Bagley Synthesis 2007, 2459).
• step (ii) the ester function of P 10 is saponified and acidified to obtain the acid equivalent of Pi 0 , which then reacts in step (iii) with the amine R 2 NH 2 for d obtain P 11 (amidification).
• An acid activator such as BOP or (O-benzotriazol-1-yl) -N, N, N ', N'-tetramethyluronium tetrafluoroborate (TBTU) may be used.
• Steps (iv) and (v) are similar to steps (ii) and (iii) of Scheme 1.
• step (i) P 12 is reacted with the acrylate Pg to obtain P 13 (Bohlmann-Ratz reaction).
• step (ii) the ester function of P 13 is saponified and acidified to obtain the acid equivalent of P 13 , which then reacts in step (iii) with the amine R 2 NH 2 to give obtain P 14 (amidification).
• An acid activator such as BOP or (O-benzotriazol-1-yl) -N, N, N ', N'-tetramethyluronium tetrafluoroborate (TBTU) may be used.
• Steps (iv) and (v) are similar to steps (ii) and (iii) of Scheme 1.
• a protic solvent such as an alcohol or water or in an aprotic solvent such as THF (see also ex.1.1. ).
• aniline a strong base such as for example LiHMDS (((CH 3 ) 3 Si) 2 NLi) is added and the reaction is carried out under heat (see also ex.3.3).
• LiHMDS (((CH 3 ) 3 Si) 2
• P 16 can also be obtained from the commercial compound 5-pyrimidinecarboxylic acid, 2,4-dichloroethyl ester:
• Pi is obtained from amide Pie acid using the amine R 2 NH 2 or a salt of this amine, for example the hydrochloride.
• Amidification can advantageously be carried out in the presence of an acid activator (also called “coupling agent”) such as for example benzotriazol-1-yloxytris (dimethylamino) -phosphonium hexafluorophosphate (or BOP, CAS No. 56602-33- 6, see also Castro, B., Dormoy, JR Tetrahedron Letter 1975, 16, 1219).
• the reaction is preferably carried out in the presence of a base (such as triethylamine) at room temperature, in a solvent such as tetrahydrofuran (THF) or dimethylformamide (DMF). See ex.1.2.
• P 2 is obtained from P 17 according to Scheme 12 by converting the alcohol function to the amine function via the intermediary Pie carrying the mesyl leaving group, and then protecting P 19 with PG.
• Sodium azide can also be used in place of NH 3 to give an azide function, which is then converted to an amino function (see Tetrahedron Scheme II, 1987, 43 (21), 5145-58 and Scheme 1 of Tetrahedron 2008, 64, 3578-3588). See prep.1.
• Pi 7 can be either commercially available (for example, 3-Butyn-1 -ol CAS No. 927-74-2 or 2-Propyn-1 -ol CAS No. 107-19-7) is prepared according to known methods. of the man of the art.
• P 4 can be either commercial or prepared according to methods known to those skilled in the art.
• the hydrogenation conditions may be those described in Examples 19 and 20 of WO 00/46179 or in Synlett 2001, 10, 1623-1625.
• the compounds 3-picolylamine (CAS No. 3731-52-0), 3- (2-aminoethyl) pyridine (CAS No. 20173-24-4), 2-amino-5-aminomethylpyridine (CAS No. 156973-09- 0), 2-methyl-5-aminomethylpyridine (CAS No. 56622-54-9), 3-methyl-5-aminomethylpyridine (CAS No. 771574-45-9), 2- (BOC-amino) -5-aminomethyl -pyridine (CAS No. 187237-37-2), 2,5-diaminopyridine (CAS No. 4318-76-7) are commercial products.
• 2-Amino-5-aminomethylpyridine can also be prepared according to EP 0607804.
• 5-Aminomethyl-2- (dimethylamino) pyridine (CAS No. 354824-17-2) is commercially available or can be prepared according to the Journal of Agricultural and Food Chemistry. 2008, 56 (1), 204-212.
• 2-Amino-3-methyl-5-aminomethylpyridine (CAS No. 187163-76-4) can be obtained by catalytic hydrogenation of the 6-amino-5-methyl-nicotinonitrile compound (CAS No. 183428-91-3), the amino function being doubly protected by the BOC.
• the catalytic hydrogenation of 6-methylamino-3-pyridinecarbonitrile (CAS No. 261715-36-0) provides access to 2-methylamino-5-aminomethylpyridine.
• Case 1 is reacted with triphosgene 6 Pi for Pi 7.
• Pi 7 is then reacted with a halide R 1 HaI in the presence of a strong base, e.g. NaH, in a polar solvent, e.g. DMF.
• the halide is more particularly an iodide (eg ethyl iodide).
• the reaction with triphosgene can be carried out in refluxing dioxane for a long time (see ex.2.1.).
• Another approach is described in Scheme 15 and consists in reacting the acyl azide P 20 with the amine P 4 according to a Curtius rearrangement. The conditions of the reactions are illustrated by those of ex.3.2.
• Ps is obtained by reaction between the Weinberg P 22 amide and an ethynyl magnesium HC ⁇ CMgHal halide, for example bromide.
• P 22 can be obtained from P 21 and O, N-dimethylhydroxylamine according to the conditions detailed in Synth. Comm. 2003, 33 (23), 4013-4018 or in Synth. Comm. 2001, 37 (13), 201 1-2019 or in the presence of an acid activator such as BOP as detailed in ex.5.1.
• 4-Amino cyclohexanecarboxylic acid (cis or trans) is a commercial product.
• PG represents more particularly the BOC.
• the Pg acrylate is either commercially available or can be obtained as described on page 945 of Helv.Chim.Acta 1973, 56 (3), 944-958.
• the preparation of Pg from imino ethers (the synthesis of which is itself described in JACS 1945, 67, 1017) is also described on page 8 of DE 2406198 or on page 11 of DE 2239815.
• compound P12 is also described on page 8 of DE 2406198 or on page 11 of DE 2239815.
• P 24 corresponds to the compound P 23 which is protected on the function
• P 23 can be a commercial product, for example 3,3-dimethyl-2-pyrrolidinone (CAS No. 4831-43-0), 3,3-dimethyl-piperidinone
• Amines R 2 NH 2 are commercial products or already described in published documents:
• N- (2-aminoethyl) thiamorpholin-1-oxide CAS No. 1017791-77-3, sold by Sinova Inc. 3 Bethesda Metro Center, Suite 700, Bethesda, MD, 20814, USA.
• a method for obtaining the compounds for which R 2 represents a group (CrC 6 ) alkyl substituted with the group -NR a R b in which R 3 and R b together with the nitrogen atom to which they are connected form (C 4 -C 6 ) heterocycloalkyl optionally comprising in the ring the group -S (O) q with q 0, 1 or 2 or the group -NH- or -N (dC 4 ) alkyl is described in Scheme 18 and is inspired by scheme 3 of Bioorg. Med. Chem. 2007, 15, 365-373 or diagram 2 of Bioorg. Med. Chem. Lett. 2008, 18, 1378-1381:
• a protecting group to protect one or more chemical function (s), including a primary or secondary amine function.
• PG protecting group
• R 3 and R b both represent a hydrogen atom
• the amidification of Schemes 8, 9 or 10 is carried out using for R 2 NH 2 the compound 2 HN- (CrC ⁇ ) alkyl-NH-PG, where PG is advantageously BOC (tert-butoxycarbonyl) .Also, when the heterocycloalkyl group formed by R 3 and R b represents the group
• the chemical function (s) is / are then obtained (s) by a deprotection step (final or intermediate) whose conditions depend on the nature of the protected function (s) and protective group used.
• a deprotection step final or intermediate
• the deprotection step is carried out in acidic medium using, for example, HCl or trifluoroacetic acid.
• the corresponding salt (hydrochloride or trifluoroacetate) is thus obtained, if appropriate.
• the salts are obtained during the deprotection step described above or by contacting the acid and the compound in its base form.
• N-oxides of the compounds containing an amine or a nitrogen atom are prepared according to the methods known to those skilled in the art by reaction of the amine with organic peracids such as peracetic acids, trifluoroperacetic acids, performic, perbenzoic or its derivatives such as 3-chloroperbenzoic acid, at temperatures between 0 0 C and 90 0 C, preferably at temperatures below 50 0 C.
• organic peracids such as peracetic acids, trifluoroperacetic acids, performic, perbenzoic or its derivatives such as 3-chloroperbenzoic acid
• the invention relates to a pharmaceutical composition
• a pharmaceutical composition comprising a compound as defined above in combination with a pharmaceutically acceptable excipient.
• the excipient is selected from the usual excipients known to those skilled in the art according to the pharmaceutical form and the desired mode of administration.
• the mode of administration can be, for example, orally or intravenously.
• the subject of the invention is a medicinal product which comprises a compound as defined above as well as the use of a compound as defined above, for the manufacture of a medicament. It can be useful for treating a pathological condition, especially cancer.
• the drug (as well as a compound the invention) can be administered in combination with one (or more) anticancer drugs. This treatment can be administered simultaneously, separately or sequentially. The treatment will be adapted by the practitioner according to the patient and the tumor to be treated.
• the invention also relates to a method for treating the pathologies indicated above which comprises the administration to a patient of an effective dose of a compound according to the invention or a pharmaceutically acceptable salt thereof. hydrates or solvates.
• the compounds were analyzed by HPLC-UV-MS coupling (liquid chromatography, ultraviolet (UV) detection and mass detection).
• the apparatus used consists of an Agilent chromatographic chain equipped with an Agilent diode array detector and a ZQ Waters single quadrupole mass spectrometer or a Quattro-MicroWaters triple quadrupole mass spectrometer.
• the liquid chromatography / mass spectrometry (LC / MS) spectra were recorded in electrospray (ESI) positive mode, in order to observe the ions resulting from the protonation of analyzed compounds (MH + ) or the formation of adducts with other cations such as Na + , K + , etc.
• the ionization parameters are as follows: cone voltage: 20 V; capillary voltage: 3 kV; source temperature: 120 ° C. desolvation temperature: 450 ° C .; gas desolvation: N 2 at 450 L / h.
• HPLC conditions are selected from one of the following methods
• Example 1 6- ⁇ 4- [3- (6-Amino-pyridin-3-ylmethyl) -ureido] -butyl-2-ethylamino-N-methyl-nicotinamide (Compound No. 5, Scheme 1) 1.1. 6-chloro-2-ethylamino-nicotinic acid
• Example 2 6-r4 - ( ⁇ R (6-Aminopyridin-3-yl) methyl-carbamoyl ⁇ amino) butyll- ⁇ K2- (1,1-dioxidothiomorpholin-4-yl) ethyl-2-ethylamino-nicotinamide (Compound No. 19, illustrates diagram 2) 2.1. 7-chloro-1-ethyl-2H-pyridor-2,3-c / iri, 3-oxazin-2,4 (1H) -d-one
• Example 4 6- (4- (3 - ((6-Aminopyridin-3-yl) methyl) ureido) -2-methylbutan-2-yl) -N-methyl-2- (phenylamino) nicotinamide (Compound No. 34 illustrates diagram 9)
• a solution of 1.07 g of the compound obtained in the preceding step is added dropwise. in 25 ml of THF, a solution of 500 mg of DMAP, 0.54 ml of triethylamine and 1 g of DSC in 20 ml of THF. After stirring for 5 minutes at RT, 1.27 g of bis-but-butyl 5- (aminomethyl) pyridin-2-ylcarbamate are added. After 12 h at RT, the medium is concentrated and then taken up in DCM. The organic phase is washed with saturated NaHCO 3 solution and then with brine then dried over MgSO 4 and then evaporated. 3.89 g of a crude product are obtained which is purified by chromatography on silica gel to give 2 g of the desired compound.
• Example 5 6 - ((1s, 4s) -4- (3 - ((6-aminopyridin-3-yl) methyl) ureido) cyclohexyl) -2-
• This compound is prepared according to the procedure described in Example 1 .6. from the compound of Preparation 2 and the compound of Example 1.5.
• n-Bu n-butyl
• t-Bu tert-butyl
• i-Pr isopropyl
• Cy cyclopropyl
• Table II Chemical name of certain compounds of Table I (obtained from the Autonom ® software):
• HCT116 ATCC-CCL247
• PC3 ATCC-CRL1435.
• Proliferation and cell viability were determined in a test using 3- (4,5-dimethylthiazol-2-yl) -5- (3-carboxymethoxyphenyl) -2- (4-sulfophenyl) -2H-tetrazolium (MTS) according to Fujishita T. et al.

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• General Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Pharmacology & Pharmacy (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Pyridine Compounds (AREA)
• Plural Heterocyclic Compounds (AREA)

Applications Claiming Priority (2)

Publications (1)

Family

ID=40823131

Family Applications (1)

Country Status (8)

Families Citing this family (1)

Family Cites Families (3)

• 2009
  • 2009-03-24 FR FR0901366A patent/FR2943670B1/fr not_active Expired - Fee Related
• 2010
  • 2010-03-22 US US13/258,847 patent/US20120094986A1/en not_active Abandoned
  • 2010-03-22 JP JP2012501350A patent/JP2012521397A/ja not_active Withdrawn
  • 2010-03-22 EP EP10715960A patent/EP2411367A1/de not_active Withdrawn
  • 2010-03-22 WO PCT/FR2010/050512 patent/WO2010109123A1/fr not_active Ceased
  • 2010-03-23 TW TW099108577A patent/TW201102368A/zh unknown
  • 2010-03-23 AR ARP100100921A patent/AR075921A1/es unknown
  • 2010-03-24 UY UY0001032516A patent/UY32516A/es not_active Application Discontinuation

Non-Patent Citations (1)

Also Published As

Similar Documents

Legal Events