KR20120007566A - 기질 금속단백분해효소 억제제 - Google Patents
기질 금속단백분해효소 억제제Info
- Publication number
- KR20120007566A KR20120007566A KR1020127000264A KR20127000264A KR20120007566A KR 20120007566 A KR20120007566 A KR 20120007566A KR 1020127000264 A KR1020127000264 A KR 1020127000264A KR 20127000264 A KR20127000264 A KR 20127000264A KR 20120007566 A KR20120007566 A KR 20120007566A
- Authority
- KR
- South Korea
- Prior art keywords
- alkyl
- substituted
- compound
- aryl
- ethyl
- 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.)
- Ceased
Links
- 239000003771 matrix metalloproteinase inhibitor Substances 0.000 title 1
- 229940121386 matrix metalloproteinase inhibitor Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 134
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 95
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 25
- 238000000034 method Methods 0.000 claims abstract description 25
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 23
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 23
- 125000002877 alkyl aryl group Chemical group 0.000 claims abstract description 20
- 125000003118 aryl group Chemical group 0.000 claims abstract description 19
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 6
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims abstract description 5
- 229910002091 carbon monoxide Inorganic materials 0.000 claims abstract description 5
- 125000000524 functional group Chemical group 0.000 claims abstract description 4
- 125000001475 halogen functional group Chemical group 0.000 claims abstract 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 31
- -1 cyano, hydroxy, nitro, amino Chemical group 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 208000027866 inflammatory disease Diseases 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 239000012453 solvate Substances 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 208000023275 Autoimmune disease Diseases 0.000 claims description 5
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 150000001408 amides Chemical class 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000002950 monocyclic group Chemical group 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 239000001301 oxygen Chemical group 0.000 claims description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
- 239000011593 sulfur Chemical group 0.000 claims description 3
- 229940124597 therapeutic agent Drugs 0.000 claims description 3
- FBIZVDRWRLXUPV-UHFFFAOYSA-N 2-[2-(1,3-dioxoisoindol-2-yl)ethyl]-3-hydroxy-5-(4-phenylphenyl)pentanoic acid Chemical compound O=C1C2=CC=CC=C2C(=O)N1CCC(C(O)=O)C(O)CCC(C=C1)=CC=C1C1=CC=CC=C1 FBIZVDRWRLXUPV-UHFFFAOYSA-N 0.000 claims description 2
- HBKOYSSZMRCIIP-UHFFFAOYSA-N 2-[2-(1,3-dioxoisoindol-2-yl)ethyl]-3-hydroxy-5-[4-(4-methylsulfanylphenyl)phenyl]pentanoic acid Chemical compound C1=CC(SC)=CC=C1C(C=C1)=CC=C1CCC(O)C(C(O)=O)CCN1C(=O)C2=CC=CC=C2C1=O HBKOYSSZMRCIIP-UHFFFAOYSA-N 0.000 claims description 2
- VNIQUALILQYNQH-UHFFFAOYSA-N 3-hydroxy-2-[2-(3-methyl-2,4-dioxopyrimidin-1-yl)ethyl]-5-(4-pyrimidin-5-ylphenyl)pentanoic acid Chemical compound O=C1N(C)C(=O)C=CN1CCC(C(O)=O)C(O)CCC1=CC=C(C=2C=NC=NC=2)C=C1 VNIQUALILQYNQH-UHFFFAOYSA-N 0.000 claims description 2
- WRTBLWFQLQBUBR-UHFFFAOYSA-N 3-hydroxy-2-[2-(3-methyl-2,4-dioxopyrimidin-1-yl)ethyl]-5-[4-[4-(trifluoromethoxy)phenyl]phenyl]pentanoic acid Chemical compound O=C1N(C)C(=O)C=CN1CCC(C(O)=O)C(O)CCC1=CC=C(C=2C=CC(OC(F)(F)F)=CC=2)C=C1 WRTBLWFQLQBUBR-UHFFFAOYSA-N 0.000 claims description 2
- KXJLRFIYARWGFH-UHFFFAOYSA-N 5-[4-(4-acetylphenyl)phenyl]-2-[2-(1,3-dioxoisoindol-2-yl)ethyl]-3-hydroxypentanoic acid Chemical compound C1=CC(C(=O)C)=CC=C1C(C=C1)=CC=C1CCC(O)C(C(O)=O)CCN1C(=O)C2=CC=CC=C2C1=O KXJLRFIYARWGFH-UHFFFAOYSA-N 0.000 claims description 2
- MSYHSDYSURKJEX-UHFFFAOYSA-N 5-[4-(4-acetylphenyl)phenyl]-3-hydroxy-2-[2-(3-methyl-2,4-dioxopyrimidin-1-yl)ethyl]pentanoic acid Chemical compound C1=CC(C(=O)C)=CC=C1C(C=C1)=CC=C1CCC(O)C(C(O)=O)CCN1C(=O)N(C)C(=O)C=C1 MSYHSDYSURKJEX-UHFFFAOYSA-N 0.000 claims description 2
- UIZCUKPUFVLHGU-UHFFFAOYSA-N 5-[4-(4-cyanophenyl)phenyl]-2-[2-(1,3-dioxoisoindol-2-yl)ethyl]-3-hydroxypentanoic acid Chemical compound O=C1C2=CC=CC=C2C(=O)N1CCC(C(O)=O)C(O)CCC(C=C1)=CC=C1C1=CC=C(C#N)C=C1 UIZCUKPUFVLHGU-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims 3
- NPLXOLKSKYCTIJ-UHFFFAOYSA-N 2-[2-(1,3-dioxoisoindol-2-yl)ethyl]-3-hydroxy-5-[4-[4-(trifluoromethoxy)phenyl]phenyl]pentanoic acid Chemical compound O=C1C2=CC=CC=C2C(=O)N1CCC(C(O)=O)C(O)CCC(C=C1)=CC=C1C1=CC=C(OC(F)(F)F)C=C1 NPLXOLKSKYCTIJ-UHFFFAOYSA-N 0.000 claims 1
- TYNXKLBAMDKDHF-UHFFFAOYSA-N 3-hydroxy-2-[2-(3-methyl-2,4-dioxopyrimidin-1-yl)ethyl]-5-(4-phenylphenyl)pentanoic acid Chemical compound O=C1N(C)C(=O)C=CN1CCC(C(O)=O)C(O)CCC1=CC=C(C=2C=CC=CC=2)C=C1 TYNXKLBAMDKDHF-UHFFFAOYSA-N 0.000 claims 1
- BHLJQPGIHDTZBX-UHFFFAOYSA-N 3-hydroxy-2-[2-(3-methyl-2,6-dioxopyrimidin-1-yl)ethyl]-5-(4-phenylphenyl)pentanoic acid Chemical compound O=C1N(C)C=CC(=O)N1CCC(C(O)=O)C(O)CCC1=CC=C(C=2C=CC=CC=2)C=C1 BHLJQPGIHDTZBX-UHFFFAOYSA-N 0.000 claims 1
- NAAQNJLBTAIZDO-UHFFFAOYSA-N 5-[4-(1-benzofuran-2-yl)phenyl]-2-[2-(1,3-dioxoisoindol-2-yl)ethyl]-3-hydroxypentanoic acid Chemical compound O=C1C2=CC=CC=C2C(=O)N1CCC(C(O)=O)C(O)CCC1=CC=C(C=2OC3=CC=CC=C3C=2)C=C1 NAAQNJLBTAIZDO-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- 108010000684 Matrix Metalloproteinases Proteins 0.000 abstract description 10
- 102000002274 Matrix Metalloproteinases Human genes 0.000 abstract description 10
- 238000002360 preparation method Methods 0.000 abstract description 9
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 abstract description 7
- 239000003112 inhibitor Substances 0.000 abstract description 7
- 125000006168 tricyclic group Chemical group 0.000 abstract description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 49
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
- 238000006243 chemical reaction Methods 0.000 description 40
- 239000000243 solution Substances 0.000 description 40
- 239000000203 mixture Substances 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 239000002904 solvent Substances 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 239000000543 intermediate Substances 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 238000003756 stirring Methods 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 13
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 12
- 239000000725 suspension Substances 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- 239000003054 catalyst Substances 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- 239000003039 volatile agent Substances 0.000 description 9
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 150000002366 halogen compounds Chemical class 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 229940088598 enzyme Drugs 0.000 description 6
- 125000005843 halogen group Chemical group 0.000 description 6
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 239000000010 aprotic solvent Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 230000003647 oxidation Effects 0.000 description 5
- 238000007254 oxidation reaction Methods 0.000 description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- TYHGKLBJBHACOI-UHFFFAOYSA-N (4-methoxyphenyl)methyl 2,2,2-trichloroethanimidate Chemical compound COC1=CC=C(COC(=N)C(Cl)(Cl)Cl)C=C1 TYHGKLBJBHACOI-UHFFFAOYSA-N 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 235000019270 ammonium chloride Nutrition 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 229910052987 metal hydride Inorganic materials 0.000 description 4
- 150000004681 metal hydrides Chemical class 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 239000002480 mineral oil Substances 0.000 description 4
- 235000010446 mineral oil Nutrition 0.000 description 4
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- 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 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 3
- 206010006895 Cachexia Diseases 0.000 description 3
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 229910052796 boron Inorganic materials 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 239000000375 suspending agent Substances 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 229940035893 uracil Drugs 0.000 description 3
- HZQLUIZFUXNFHK-UHFFFAOYSA-N 1-(bromomethyl)-4-phenylbenzene Chemical group C1=CC(CBr)=CC=C1C1=CC=CC=C1 HZQLUIZFUXNFHK-UHFFFAOYSA-N 0.000 description 2
- ZQXCQTAELHSNAT-UHFFFAOYSA-N 1-chloro-3-nitro-5-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC(Cl)=CC(C(F)(F)F)=C1 ZQXCQTAELHSNAT-UHFFFAOYSA-N 0.000 description 2
- JBKINHFZTVLNEM-UHFFFAOYSA-N 2-bromoethoxy-tert-butyl-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OCCBr JBKINHFZTVLNEM-UHFFFAOYSA-N 0.000 description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- 201000004624 Dermatitis Diseases 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 201000005569 Gout Diseases 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- 240000007472 Leucaena leucocephala Species 0.000 description 2
- 102100027998 Macrophage metalloelastase Human genes 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
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- A—HUMAN NECESSITIES
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
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- A—HUMAN NECESSITIES
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/4035—Isoindoles, e.g. phthalimide
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- A—HUMAN NECESSITIES
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
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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
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
- C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/10—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Transplantation (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Macromonomer-Based Addition Polymer (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Anti-Oxidant Or Stabilizer Compositions (AREA)
- Soft Magnetic Materials (AREA)
- Lubricants (AREA)
- Adhesives Or Adhesive Processes (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
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| GB0321538.1 | 2003-09-13 | ||
| GBGB0321538.1A GB0321538D0 (en) | 2003-09-13 | 2003-09-13 | Therapeutically useful compounds |
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| KR1020067005114A Division KR20060120648A (ko) | 2003-09-13 | 2004-09-10 | 기질 금속단백분해효소 억제제 |
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| KR1020137014317A Division KR20130079628A (ko) | 2003-09-13 | 2004-09-10 | 기질 금속단백분해효소 억제제 |
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|---|---|
| KR20120007566A true KR20120007566A (ko) | 2012-01-20 |
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| KR1020067005114A Ceased KR20060120648A (ko) | 2003-09-13 | 2004-09-10 | 기질 금속단백분해효소 억제제 |
| KR1020137014317A Ceased KR20130079628A (ko) | 2003-09-13 | 2004-09-10 | 기질 금속단백분해효소 억제제 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020067005114A Ceased KR20060120648A (ko) | 2003-09-13 | 2004-09-10 | 기질 금속단백분해효소 억제제 |
| KR1020137014317A Ceased KR20130079628A (ko) | 2003-09-13 | 2004-09-10 | 기질 금속단백분해효소 억제제 |
Country Status (28)
| Country | Link |
|---|---|
| US (3) | US7601729B2 (enExample) |
| EP (3) | EP2042488B1 (enExample) |
| JP (3) | JP2007505081A (enExample) |
| KR (3) | KR20120007566A (enExample) |
| CN (1) | CN1849306B (enExample) |
| AT (2) | ATE502922T1 (enExample) |
| AU (1) | AU2004272280C1 (enExample) |
| BR (1) | BRPI0413791A (enExample) |
| CA (1) | CA2538315C (enExample) |
| CY (1) | CY1109400T1 (enExample) |
| DE (2) | DE602004031991D1 (enExample) |
| DK (1) | DK1663970T3 (enExample) |
| ES (2) | ES2314436T3 (enExample) |
| GB (1) | GB0321538D0 (enExample) |
| HR (1) | HRP20080668T3 (enExample) |
| IL (1) | IL173305A (enExample) |
| IS (2) | IS2622B (enExample) |
| MA (1) | MA28039A1 (enExample) |
| MX (1) | MXPA06002458A (enExample) |
| NO (1) | NO20060540L (enExample) |
| NZ (2) | NZ573479A (enExample) |
| PL (1) | PL1663970T3 (enExample) |
| PT (1) | PT1663970E (enExample) |
| RU (2) | RU2370488C2 (enExample) |
| SG (1) | SG145685A1 (enExample) |
| SI (1) | SI1663970T1 (enExample) |
| WO (1) | WO2005026120A1 (enExample) |
| ZA (1) | ZA200602070B (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0321538D0 (en) * | 2003-09-13 | 2003-10-15 | Glaxo Group Ltd | Therapeutically useful compounds |
| PL1856063T3 (pl) * | 2005-02-22 | 2012-07-31 | Sun Pharmaceutical Ind Ltd | Pochodne kwasu 5-fenylopentantowego jako inhibitory metaloproteinazy macierzy do leczenia astmy i innych chorób |
| AU2013200728B2 (en) * | 2006-08-22 | 2014-12-18 | Sun Pharmaceutical Industries Limited | Matrix metalloproteinase inhibitors |
| KR101467590B1 (ko) * | 2006-08-22 | 2014-12-01 | 랜박시 래보러터리스 리미티드 | 매트릭스 메탈로프로테나제 저해제 |
| CN102015606B (zh) | 2007-06-08 | 2015-02-04 | 满康德股份有限公司 | IRE-1α抑制剂 |
| FR2949463B1 (fr) * | 2009-08-26 | 2011-09-16 | Commissariat Energie Atomique | Inhibiteurs de mmp |
| JP2013537533A (ja) | 2010-07-30 | 2013-10-03 | ランバクシー ラボラトリーズ リミテッド | マトリックスメタロプロテイナーゼ阻害剤 |
| EA201390404A1 (ru) | 2010-09-24 | 2013-09-30 | Ранбакси Лабораториз Лимитед | Ингибиторы матричной металлопротеиназы |
| WO2014083229A1 (es) | 2012-11-28 | 2014-06-05 | Administración General De La Comunidad Autónoma De Euskadi | Uso de inhibidores de metaloproteasas en el tratamiento de enfermedades hepáticas poliquísticas |
| RU2743424C2 (ru) | 2016-02-12 | 2021-02-18 | Астеллас Фарма Инк. | Производные тетрагидроизохинолина |
| JP7143334B2 (ja) * | 2017-06-13 | 2022-09-28 | エシコン エルエルシー | 治癒を制御させる手術用ステープラ |
Family Cites Families (21)
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| DE4102024A1 (de) * | 1991-01-24 | 1992-07-30 | Thomae Gmbh Dr K | Biphenylderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| AU2199195A (en) * | 1994-04-28 | 1995-11-29 | Uniroyal Chemical Company, Inc. | Fungicidal azole derivatives |
| EP0865431A2 (en) * | 1995-12-06 | 1998-09-23 | Astra Pharmaceuticals Limited | Compounds |
| IL120669A (en) | 1996-04-19 | 2001-04-30 | Akzo Nobel Nv | Benzoheterocyclic benzylamine derivatives and pharmaceutical compositions containing them |
| HRP970246B1 (en) * | 1996-05-15 | 2002-04-30 | Bayer Ag | Substituted oxobutric acids as matrix metalloprotease inhibitors |
| US6242616B1 (en) | 1996-12-03 | 2001-06-05 | The Trustees Of The University Of Pennsylvania | Synthetic techniques and intermediates for polyhydroxy, dienyl lactone derivatives |
| US20050065353A1 (en) | 1996-12-03 | 2005-03-24 | Smith Amos B. | Synthetic techniques and intermediates for polyhydroxy dienyl lactones and mimics thereof |
| US6096904A (en) | 1996-12-03 | 2000-08-01 | The Trustees Of The University Of Pennsylvania | Synthetic techniques and intermediates for polyhydroxy, dienyl lactone derivatives |
| US6870058B2 (en) | 1996-12-03 | 2005-03-22 | The Trustees Of The University Of Pennsylvania | Compounds which mimic the chemical and biological properties of discodermolide |
| US5789605A (en) | 1996-12-03 | 1998-08-04 | Trustees Of The University Of Pennsylvania | Synthetic techniques and intermediates for polyhydroxy, dienyl lactones and mimics thereof |
| US5804581A (en) * | 1997-05-15 | 1998-09-08 | Bayer Corporation | Inhibition of matrix metalloproteases by substituted phenalkyl compounds |
| US6608052B2 (en) * | 2000-02-16 | 2003-08-19 | Boehringer Ingelheim Pharmaceuticals, Inc. | Compounds useful as anti-inflammatory agents |
| WO2002083642A1 (en) * | 2001-04-13 | 2002-10-24 | Boehringer Ingelheim Pharmaceuticals, Inc. | Compounds useful as anti-inflammatory agents |
| AU2003261319A1 (en) * | 2002-08-01 | 2004-02-23 | Bristol-Myers Squibb Company | Hydantoin derivatives as inhibitors of matrix metalloproteinases and/or tnf-alpha converting enzyme |
| JP2006506446A (ja) * | 2002-11-19 | 2006-02-23 | ガルデルマ・リサーチ・アンド・デヴェロップメント・エス・エヌ・セ | ＰＰＡＲ−γ型レセプターを活性化する新規二芳香族化合物、および化粧品組成物または薬剤組成物におけるその使用 |
| GB0312654D0 (en) * | 2003-06-03 | 2003-07-09 | Glaxo Group Ltd | Therapeutically useful compounds |
| GB0314488D0 (en) * | 2003-06-20 | 2003-07-23 | Glaxo Group Ltd | Therapeutically useful compounds |
| GB0319069D0 (en) * | 2003-08-14 | 2003-09-17 | Glaxo Group Ltd | Therapeutically useful compounds |
| GB0321538D0 (en) * | 2003-09-13 | 2003-10-15 | Glaxo Group Ltd | Therapeutically useful compounds |
| PL1856063T3 (pl) | 2005-02-22 | 2012-07-31 | Sun Pharmaceutical Ind Ltd | Pochodne kwasu 5-fenylopentantowego jako inhibitory metaloproteinazy macierzy do leczenia astmy i innych chorób |
| KR101467590B1 (ko) | 2006-08-22 | 2014-12-01 | 랜박시 래보러터리스 리미티드 | 매트릭스 메탈로프로테나제 저해제 |
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2003
- 2003-09-13 GB GBGB0321538.1A patent/GB0321538D0/en not_active Ceased
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2004
- 2004-09-10 US US10/571,443 patent/US7601729B2/en not_active Expired - Fee Related
- 2004-09-10 EP EP08163972A patent/EP2042488B1/en not_active Expired - Lifetime
- 2004-09-10 BR BRPI0413791-4A patent/BRPI0413791A/pt not_active IP Right Cessation
- 2004-09-10 SI SI200431008T patent/SI1663970T1/sl unknown
- 2004-09-10 HR HR20080668T patent/HRP20080668T3/xx unknown
- 2004-09-10 SG SG200805432-2A patent/SG145685A1/en unknown
- 2004-09-10 WO PCT/EP2004/010319 patent/WO2005026120A1/en not_active Ceased
- 2004-09-10 MX MXPA06002458A patent/MXPA06002458A/es active IP Right Grant
- 2004-09-10 RU RU2006106850/04A patent/RU2370488C2/ru not_active IP Right Cessation
- 2004-09-10 KR KR1020127000264A patent/KR20120007566A/ko not_active Ceased
- 2004-09-10 PT PT04765231T patent/PT1663970E/pt unknown
- 2004-09-10 ES ES04765231T patent/ES2314436T3/es not_active Expired - Lifetime
- 2004-09-10 AT AT08163972T patent/ATE502922T1/de not_active IP Right Cessation
- 2004-09-10 JP JP2006525794A patent/JP2007505081A/ja active Pending
- 2004-09-10 KR KR1020067005114A patent/KR20060120648A/ko not_active Ceased
- 2004-09-10 CN CN200480026229.7A patent/CN1849306B/zh not_active Expired - Fee Related
- 2004-09-10 ES ES08163972T patent/ES2362954T3/es not_active Expired - Lifetime
- 2004-09-10 CA CA2538315A patent/CA2538315C/en not_active Expired - Fee Related
- 2004-09-10 DK DK04765231T patent/DK1663970T3/da active
- 2004-09-10 NZ NZ573479A patent/NZ573479A/en not_active IP Right Cessation
- 2004-09-10 DE DE602004031991T patent/DE602004031991D1/de not_active Expired - Lifetime
- 2004-09-10 DE DE602004017622T patent/DE602004017622D1/de not_active Expired - Lifetime
- 2004-09-10 AT AT04765231T patent/ATE413384T1/de active
- 2004-09-10 NZ NZ545211A patent/NZ545211A/en not_active IP Right Cessation
- 2004-09-10 EP EP10176905A patent/EP2295408A1/en not_active Withdrawn
- 2004-09-10 PL PL04765231T patent/PL1663970T3/pl unknown
- 2004-09-10 KR KR1020137014317A patent/KR20130079628A/ko not_active Ceased
- 2004-09-10 EP EP04765231A patent/EP1663970B1/en not_active Expired - Lifetime
- 2004-09-10 AU AU2004272280A patent/AU2004272280C1/en not_active Ceased
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2006
- 2006-01-23 IL IL173305A patent/IL173305A/en not_active IP Right Cessation
- 2006-01-26 IS IS8268A patent/IS2622B/is unknown
- 2006-02-02 NO NO20060540A patent/NO20060540L/no not_active Application Discontinuation
- 2006-03-10 ZA ZA200602070A patent/ZA200602070B/en unknown
- 2006-03-14 MA MA28873A patent/MA28039A1/fr unknown
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2008
- 2008-11-07 US US12/266,767 patent/US8263602B2/en not_active Expired - Fee Related
- 2008-11-26 RU RU2008146479/04A patent/RU2008146479A/ru not_active Application Discontinuation
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2009
- 2009-01-27 CY CY20091100090T patent/CY1109400T1/el unknown
- 2009-08-19 IS IS8843A patent/IS8843A/is unknown
- 2009-09-01 US US12/551,892 patent/US8343986B2/en not_active Expired - Fee Related
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2011
- 2011-06-14 JP JP2011132261A patent/JP2011231118A/ja not_active Withdrawn
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2012
- 2012-01-25 JP JP2012012663A patent/JP2012107031A/ja active Pending
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