ES2594156T3 - Cicloalquilaminas como inhibidores de la recaptación de monoaminas - Google Patents
Cicloalquilaminas como inhibidores de la recaptación de monoaminas Download PDFInfo
- Publication number
- ES2594156T3 ES2594156T3 ES07716419.2T ES07716419T ES2594156T3 ES 2594156 T3 ES2594156 T3 ES 2594156T3 ES 07716419 T ES07716419 T ES 07716419T ES 2594156 T3 ES2594156 T3 ES 2594156T3
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- Prior art keywords
- unsubstituted
- nmr
- substituted
- cyclohexyl
- mhz
- Prior art date
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- 239000003112 inhibitor Substances 0.000 title 1
- 230000000407 monoamine reuptake Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 66
- 239000000203 mixture Substances 0.000 claims abstract description 16
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 abstract 9
- 125000003118 aryl group Chemical group 0.000 abstract 8
- 125000004404 heteroalkyl group Chemical group 0.000 abstract 8
- 125000001072 heteroaryl group Chemical group 0.000 abstract 6
- 229910052739 hydrogen Inorganic materials 0.000 abstract 6
- 229910052736 halogen Inorganic materials 0.000 abstract 5
- 150000002367 halogens Chemical class 0.000 abstract 3
- 125000002252 acyl group Chemical group 0.000 abstract 2
- 125000000592 heterocycloalkyl group Chemical group 0.000 abstract 2
- 239000001257 hydrogen Substances 0.000 abstract 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 2
- 125000001424 substituent group Chemical group 0.000 abstract 2
- 125000003545 alkoxy group Chemical group 0.000 abstract 1
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 1
- 125000004429 atom Chemical group 0.000 abstract 1
- 125000004432 carbon atom Chemical group C* 0.000 abstract 1
- 125000005309 thioalkoxy group Chemical group 0.000 abstract 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 123
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 92
- 238000004128 high performance liquid chromatography Methods 0.000 description 45
- 238000000034 method Methods 0.000 description 45
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 42
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- 238000005160 1H NMR spectroscopy Methods 0.000 description 41
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 35
- 238000005481 NMR spectroscopy Methods 0.000 description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 26
- 230000015572 biosynthetic process Effects 0.000 description 22
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 20
- 235000019439 ethyl acetate Nutrition 0.000 description 19
- 150000003840 hydrochlorides Chemical class 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 14
- 239000012043 crude product Substances 0.000 description 13
- -1 3-substituted cyclohexyl Chemical group 0.000 description 12
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 12
- 238000010898 silica gel chromatography Methods 0.000 description 11
- 239000007787 solid Substances 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 7
- 230000003137 locomotive effect Effects 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 102000006441 Dopamine Plasma Membrane Transport Proteins Human genes 0.000 description 5
- 108010044266 Dopamine Plasma Membrane Transport Proteins Proteins 0.000 description 5
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000004808 supercritical fluid chromatography Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- JREVKQMXGBTVKI-UHFFFAOYSA-N 1-(3-fluorophenyl)cyclohexane-1-carbaldehyde Chemical compound FC1=CC=CC(C2(CCCCC2)C=O)=C1 JREVKQMXGBTVKI-UHFFFAOYSA-N 0.000 description 4
- UOFSKBVHBCPJEQ-UHFFFAOYSA-N 1-(3-fluorophenyl)cyclohexane-1-carbonitrile Chemical compound FC1=CC=CC(C2(CCCCC2)C#N)=C1 UOFSKBVHBCPJEQ-UHFFFAOYSA-N 0.000 description 4
- JCPLIJBMSKJFQE-UHFFFAOYSA-N 1-[1-(3-fluorophenyl)cyclohexyl]-n-methylmethanamine Chemical compound C=1C=CC(F)=CC=1C1(CNC)CCCCC1 JCPLIJBMSKJFQE-UHFFFAOYSA-N 0.000 description 4
- 241000581650 Ivesia Species 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 239000007832 Na2SO4 Substances 0.000 description 4
- 102000008092 Norepinephrine Plasma Membrane Transport Proteins Human genes 0.000 description 4
- 108010049586 Norepinephrine Plasma Membrane Transport Proteins Proteins 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- AWFDYLNQFMKXDE-UHFFFAOYSA-N [1-(3,4-difluorophenyl)cyclohexyl]methanamine;hydrochloride Chemical compound Cl.C=1C=C(F)C(F)=CC=1C1(CN)CCCCC1 AWFDYLNQFMKXDE-UHFFFAOYSA-N 0.000 description 4
- 230000001430 anti-depressive effect Effects 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 229910052681 coesite Inorganic materials 0.000 description 4
- 229910052906 cristobalite Inorganic materials 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- DIOWQSMFSBKMCS-UHFFFAOYSA-N n,n-dimethyl-1-(1-naphthalen-2-ylcyclohexyl)ethanamine Chemical compound C=1C=C2C=CC=CC2=CC=1C1(C(N(C)C)C)CCCCC1 DIOWQSMFSBKMCS-UHFFFAOYSA-N 0.000 description 4
- OMEZNRIAKKKRHT-UHFFFAOYSA-N n-methyl-1-[1-[4-(trifluoromethyl)phenyl]cyclohexyl]methanamine Chemical compound C=1C=C(C(F)(F)F)C=CC=1C1(CNC)CCCCC1 OMEZNRIAKKKRHT-UHFFFAOYSA-N 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 150000003141 primary amines Chemical class 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 235000012239 silicon dioxide Nutrition 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 229910052682 stishovite Inorganic materials 0.000 description 4
- 230000009182 swimming Effects 0.000 description 4
- 229910052905 tridymite Inorganic materials 0.000 description 4
- KSOVGRCOLZZTPF-QMKUDKLTSA-N (1s,2s,3r,4r)-3-[[5-fluoro-2-[3-methyl-4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound N([C@H]1[C@H]([C@@]2([H])C[C@@]1(C=C2)[H])C(N)=O)C(C(=CN=1)F)=NC=1NC(C=C1C)=CC=C1N1CCN(C)CC1 KSOVGRCOLZZTPF-QMKUDKLTSA-N 0.000 description 3
- PCJBHHMLVZKWRN-UHFFFAOYSA-N 1-[1-(2,4-dichlorophenyl)cyclohexyl]-n,n-dimethylmethanamine Chemical compound C=1C=C(Cl)C=C(Cl)C=1C1(CN(C)C)CCCCC1 PCJBHHMLVZKWRN-UHFFFAOYSA-N 0.000 description 3
- SRNVXFJZALSVQF-UHFFFAOYSA-N 1-[1-(2,4-dichlorophenyl)cyclohexyl]-n-methylmethanamine Chemical compound C=1C=C(Cl)C=C(Cl)C=1C1(CNC)CCCCC1 SRNVXFJZALSVQF-UHFFFAOYSA-N 0.000 description 3
- ZJNJPYFFMXVAGY-UHFFFAOYSA-N 1-[1-(3,4-dichlorophenyl)cyclohexyl]-n-methylethanamine Chemical compound C=1C=C(Cl)C(Cl)=CC=1C1(C(C)NC)CCCCC1 ZJNJPYFFMXVAGY-UHFFFAOYSA-N 0.000 description 3
- RBTTVTNVCSFPKD-UHFFFAOYSA-N 1-[1-(3,4-difluorophenyl)cyclohexyl]-n,n-dimethylmethanamine;hydrochloride Chemical compound Cl.C=1C=C(F)C(F)=CC=1C1(CN(C)C)CCCCC1 RBTTVTNVCSFPKD-UHFFFAOYSA-N 0.000 description 3
- WBMNVGKXODDUFS-UHFFFAOYSA-N 1-[1-(3,4-difluorophenyl)cyclohexyl]-n-methylmethanamine;hydrochloride Chemical compound Cl.C=1C=C(F)C(F)=CC=1C1(CNC)CCCCC1 WBMNVGKXODDUFS-UHFFFAOYSA-N 0.000 description 3
- FLAQOJMPRHHQFA-UHFFFAOYSA-N 1-[1-(3-chloro-4-fluorophenyl)cyclohexyl]-n-methylmethanamine Chemical compound C=1C=C(F)C(Cl)=CC=1C1(CNC)CCCCC1 FLAQOJMPRHHQFA-UHFFFAOYSA-N 0.000 description 3
- YEMZPAKBIRTBDG-UHFFFAOYSA-N 1-[1-(3-fluorophenyl)cyclohexyl]-n,n-dimethylmethanamine Chemical compound C=1C=CC(F)=CC=1C1(CN(C)C)CCCCC1 YEMZPAKBIRTBDG-UHFFFAOYSA-N 0.000 description 3
- UFFRBOMGNQGCAY-UHFFFAOYSA-N 1-[1-(4-chlorophenyl)cyclohexyl]-n,n-dimethylmethanamine Chemical compound C=1C=C(Cl)C=CC=1C1(CN(C)C)CCCCC1 UFFRBOMGNQGCAY-UHFFFAOYSA-N 0.000 description 3
- UGQDLLYCIMKVNZ-UHFFFAOYSA-N 1-[1-(6-fluoronaphthalen-2-yl)cyclohexyl]-n-methylmethanamine Chemical compound C=1C=C2C=C(F)C=CC2=CC=1C1(CNC)CCCCC1 UGQDLLYCIMKVNZ-UHFFFAOYSA-N 0.000 description 3
- QLLCAGAXRJJPDA-UHFFFAOYSA-N 1-[4-(trifluoromethyl)phenyl]cyclohexane-1-carbaldehyde Chemical compound C1=CC(C(F)(F)F)=CC=C1C1(C=O)CCCCC1 QLLCAGAXRJJPDA-UHFFFAOYSA-N 0.000 description 3
- RZOBDKWPVHNHIC-UHFFFAOYSA-N 1-[4-(trifluoromethyl)phenyl]cyclohexane-1-carbonitrile Chemical compound C1=CC(C(F)(F)F)=CC=C1C1(C#N)CCCCC1 RZOBDKWPVHNHIC-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- TWWFGVBNOZIDQX-UHFFFAOYSA-N [1-(1,3-benzodioxol-5-yl)cyclohexyl]methanamine Chemical compound C=1C=C2OCOC2=CC=1C1(CN)CCCCC1 TWWFGVBNOZIDQX-UHFFFAOYSA-N 0.000 description 3
- YZSUPDYMUSVHAR-UHFFFAOYSA-N [1-(4-fluoronaphthalen-1-yl)cyclohexyl]methanamine Chemical compound C=1C=C(F)C2=CC=CC=C2C=1C1(CN)CCCCC1 YZSUPDYMUSVHAR-UHFFFAOYSA-N 0.000 description 3
- PGGTUNCWXAFOIJ-UHFFFAOYSA-N [1-[4-(trifluoromethyl)phenyl]cyclohexyl]methanamine Chemical compound C=1C=C(C(F)(F)F)C=CC=1C1(CN)CCCCC1 PGGTUNCWXAFOIJ-UHFFFAOYSA-N 0.000 description 3
- 239000000935 antidepressant agent Substances 0.000 description 3
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- VECQSYDTGJGEFK-UHFFFAOYSA-N n,n-dimethyl-1-(1-phenylcyclohexyl)methanamine;hydrochloride Chemical compound Cl.C=1C=CC=CC=1C1(CN(C)C)CCCCC1 VECQSYDTGJGEFK-UHFFFAOYSA-N 0.000 description 3
- SYDXJSKTVHXBGQ-UHFFFAOYSA-N n,n-dimethyl-1-[1-[3-(trifluoromethyl)phenyl]cyclohexyl]methanamine Chemical compound C=1C=CC(C(F)(F)F)=CC=1C1(CN(C)C)CCCCC1 SYDXJSKTVHXBGQ-UHFFFAOYSA-N 0.000 description 3
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- IBODDUNKEPPBKW-UHFFFAOYSA-N 1,5-dibromopentane Chemical compound BrCCCCCBr IBODDUNKEPPBKW-UHFFFAOYSA-N 0.000 description 2
- UKMRWNNKRBSVIH-UHFFFAOYSA-N 1-(1-naphthalen-1-ylcyclohexyl)ethanamine Chemical compound C=1C=CC2=CC=CC=C2C=1C1(C(N)C)CCCCC1 UKMRWNNKRBSVIH-UHFFFAOYSA-N 0.000 description 2
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- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
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- PAFZNILMFXTMIY-UHFFFAOYSA-N Cyclohexylamine Natural products NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 1
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- 101710114597 Sodium-dependent serotonin transporter Proteins 0.000 description 1
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- XLJMAIOERFSOGZ-UHFFFAOYSA-N anhydrous cyanic acid Natural products OC#N XLJMAIOERFSOGZ-UHFFFAOYSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
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- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
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- 230000005764 inhibitory process Effects 0.000 description 1
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- YCCXQARVHOPWFJ-UHFFFAOYSA-M magnesium;ethane;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C YCCXQARVHOPWFJ-UHFFFAOYSA-M 0.000 description 1
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- ZXAIYPYVRUXIRT-UHFFFAOYSA-N n-[[1-(3,4-dichlorophenyl)cyclohexyl]methyl]-n-ethylethanamine Chemical compound C=1C=C(Cl)C(Cl)=CC=1C1(CN(CC)CC)CCCCC1 ZXAIYPYVRUXIRT-UHFFFAOYSA-N 0.000 description 1
- MWCFXXYOMLDMRG-UHFFFAOYSA-N n-[[1-(3,4-dichlorophenyl)cyclohexyl]methyl]cyclopropanamine;hydrochloride Chemical compound Cl.C1=C(Cl)C(Cl)=CC=C1C1(CNC2CC2)CCCCC1 MWCFXXYOMLDMRG-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000002560 nitrile group Chemical group 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
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- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
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- 238000003756 stirring Methods 0.000 description 1
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Classifications
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- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/10—Systems containing only non-condensed rings with a five-membered ring the ring being unsaturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
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-
2007
- 2007-01-05 KR KR1020087019131A patent/KR101294014B1/ko not_active Expired - Fee Related
- 2007-01-05 ES ES07716419.2T patent/ES2594156T3/es active Active
- 2007-01-05 CA CA2636324A patent/CA2636324C/en active Active
- 2007-01-05 EP EP07716419.2A patent/EP1976513B1/en active Active
- 2007-01-05 AU AU2007205114A patent/AU2007205114B2/en not_active Ceased
- 2007-01-05 NZ NZ569630A patent/NZ569630A/en not_active IP Right Cessation
- 2007-01-05 CN CN200780008105.XA patent/CN101394847B/zh not_active Expired - Fee Related
- 2007-01-05 JP JP2008549588A patent/JP5432526B2/ja not_active Expired - Fee Related
- 2007-01-05 WO PCT/US2007/000376 patent/WO2007081857A2/en not_active Ceased
- 2007-01-05 RU RU2008132320A patent/RU2430913C2/ru active
- 2007-01-05 US US11/649,927 patent/US20070203111A1/en not_active Abandoned
- 2007-01-05 BR BRPI0706365-2A patent/BRPI0706365A2/pt not_active Application Discontinuation
- 2007-02-05 ZA ZA200806145A patent/ZA200806145B/xx unknown
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- 2008-07-03 IL IL192613A patent/IL192613A/en active IP Right Grant
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2010
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2011
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2013
- 2013-05-10 JP JP2013100267A patent/JP2013209390A/ja not_active Withdrawn
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2014
- 2014-09-30 US US14/502,532 patent/US9868718B2/en active Active
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- 2017-12-08 US US15/836,261 patent/US10562878B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| RU2430913C2 (ru) | 2011-10-10 |
| US20150126511A1 (en) | 2015-05-07 |
| AU2007205114A1 (en) | 2007-07-19 |
| CA2636324A1 (en) | 2007-07-19 |
| RU2008132320A (ru) | 2010-02-20 |
| EP1976513B1 (en) | 2016-08-24 |
| JP5432526B2 (ja) | 2014-03-05 |
| JP2009531277A (ja) | 2009-09-03 |
| ZA200806145B (en) | 2010-02-24 |
| NZ569630A (en) | 2011-09-30 |
| US9868718B2 (en) | 2018-01-16 |
| RU2011119990A (ru) | 2012-11-27 |
| KR20080083201A (ko) | 2008-09-16 |
| KR101294014B1 (ko) | 2013-08-09 |
| US20180230120A1 (en) | 2018-08-16 |
| WO2007081857A2 (en) | 2007-07-19 |
| CN101394847B (zh) | 2017-05-24 |
| EP1976513A4 (en) | 2012-04-18 |
| AU2007205114B2 (en) | 2012-11-08 |
| IL192613A (en) | 2015-11-30 |
| US10562878B2 (en) | 2020-02-18 |
| CN101394847A (zh) | 2009-03-25 |
| EP1976513A2 (en) | 2008-10-08 |
| BRPI0706365A2 (pt) | 2011-03-22 |
| WO2007081857A3 (en) | 2007-11-08 |
| US8877975B2 (en) | 2014-11-04 |
| US20070203111A1 (en) | 2007-08-30 |
| US20100190861A1 (en) | 2010-07-29 |
| JP2013209390A (ja) | 2013-10-10 |
| IL192613A0 (en) | 2009-09-22 |
| CA2636324C (en) | 2012-03-20 |
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