ZA200106180B - Thioamide derivatives. - Google Patents
Thioamide derivatives. Download PDFInfo
- Publication number
- ZA200106180B ZA200106180B ZA200106180A ZA200106180A ZA200106180B ZA 200106180 B ZA200106180 B ZA 200106180B ZA 200106180 A ZA200106180 A ZA 200106180A ZA 200106180 A ZA200106180 A ZA 200106180A ZA 200106180 B ZA200106180 B ZA 200106180B
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- ZA
- South Africa
- Prior art keywords
- lower alkyl
- compound
- group
- formula
- mol
- Prior art date
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- 150000003556 thioamides Chemical class 0.000 title description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 164
- -1 cyano, hydroxy Chemical group 0.000 claims description 151
- 150000001875 compounds Chemical class 0.000 claims description 103
- 229910052736 halogen Inorganic materials 0.000 claims description 78
- 150000002367 halogens Chemical group 0.000 claims description 74
- 229910052739 hydrogen Inorganic materials 0.000 claims description 67
- 239000001257 hydrogen Substances 0.000 claims description 65
- 125000003545 alkoxy group Chemical group 0.000 claims description 50
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 43
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 43
- 125000001589 carboacyl group Chemical group 0.000 claims description 42
- 125000003118 aryl group Chemical group 0.000 claims description 40
- 239000000460 chlorine Substances 0.000 claims description 35
- 125000004414 alkyl thio group Chemical group 0.000 claims description 34
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 33
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 33
- 125000001072 heteroaryl group Chemical group 0.000 claims description 25
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 22
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 18
- 125000003435 aroyl group Chemical group 0.000 claims description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
- 229910052801 chlorine Inorganic materials 0.000 claims description 13
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
- 150000002148 esters Chemical class 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 7
- 125000004104 aryloxy group Chemical group 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 3
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- 125000002837 carbocyclic group Chemical group 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 229910052727 yttrium Inorganic materials 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 141
- 239000000243 solution Substances 0.000 description 124
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 105
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 77
- 239000007787 solid Substances 0.000 description 75
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 74
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 71
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 66
- 238000004896 high resolution mass spectrometry Methods 0.000 description 63
- 238000000034 method Methods 0.000 description 62
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 59
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 59
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
- 229910001868 water Inorganic materials 0.000 description 56
- 239000000203 mixture Substances 0.000 description 52
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 52
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 50
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 49
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 48
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 47
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 44
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 43
- 229960005190 phenylalanine Drugs 0.000 description 43
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 38
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 32
- 210000004027 cell Anatomy 0.000 description 32
- 239000011541 reaction mixture Substances 0.000 description 31
- 239000010410 layer Substances 0.000 description 30
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 30
- 239000012267 brine Substances 0.000 description 29
- 238000001914 filtration Methods 0.000 description 29
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 28
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 25
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 24
- 239000000284 extract Substances 0.000 description 24
- 238000004809 thin layer chromatography Methods 0.000 description 24
- 239000007858 starting material Substances 0.000 description 22
- 238000004458 analytical method Methods 0.000 description 21
- 239000002274 desiccant Substances 0.000 description 21
- 239000000725 suspension Substances 0.000 description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 20
- 108010008212 Integrin alpha4beta1 Proteins 0.000 description 18
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 18
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 18
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- 239000003921 oil Substances 0.000 description 16
- 238000011282 treatment Methods 0.000 description 16
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 16
- 230000027455 binding Effects 0.000 description 15
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 15
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 15
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 14
- ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 13
- 239000000872 buffer Substances 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 125000001424 substituent group Chemical group 0.000 description 12
- 208000006673 asthma Diseases 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 239000012230 colorless oil Substances 0.000 description 11
- 201000006417 multiple sclerosis Diseases 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 10
- VSDUZFOSJDMAFZ-VIFPVBQESA-N methyl L-phenylalaninate Chemical compound COC(=O)[C@@H](N)CC1=CC=CC=C1 VSDUZFOSJDMAFZ-VIFPVBQESA-N 0.000 description 10
- 238000010790 dilution Methods 0.000 description 9
- 239000012895 dilution Substances 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 238000004007 reversed phase HPLC Methods 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- 238000010898 silica gel chromatography Methods 0.000 description 9
- 239000011701 zinc Substances 0.000 description 9
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 8
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 235000019270 ammonium chloride Nutrition 0.000 description 8
- 239000012131 assay buffer Substances 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 239000000428 dust Substances 0.000 description 8
- 210000003979 eosinophil Anatomy 0.000 description 8
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 8
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 7
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 229910002091 carbon monoxide Inorganic materials 0.000 description 7
- 239000011369 resultant mixture Substances 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 238000003818 flash chromatography Methods 0.000 description 6
- 125000005843 halogen group Chemical group 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 5
- 102000016359 Fibronectins Human genes 0.000 description 5
- 108010067306 Fibronectins Proteins 0.000 description 5
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 5
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-Phenylalanine Natural products OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 5
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 5
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 5
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
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- 239000003814 drug Substances 0.000 description 5
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- 125000006239 protecting group Chemical group 0.000 description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 description 5
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- JBLIDPPHFGWTKU-UHFFFAOYSA-N 2,6-dichlorobenzoyl chloride Chemical compound ClC(=O)C1=C(Cl)C=CC=C1Cl JBLIDPPHFGWTKU-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
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- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
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- JBDSSBMEKXHSJF-UHFFFAOYSA-N cyclopentanecarboxylic acid Chemical compound OC(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-N 0.000 description 4
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- 210000003038 endothelium Anatomy 0.000 description 4
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- BTHMRXRBXYHLRA-FVGYRXGTSA-N methyl (2s)-2-amino-3-(4-nitrophenyl)propanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CC1=CC=C([N+]([O-])=O)C=C1 BTHMRXRBXYHLRA-FVGYRXGTSA-N 0.000 description 4
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- ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical compound BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 description 3
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- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 3
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- YGIKMOCQLWESCS-UHFFFAOYSA-N ethyl 1-(4-methylsulfanylbutyl)cyclobutane-1-carboxylate Chemical compound CSCCCCC1(C(=O)OCC)CCC1 YGIKMOCQLWESCS-UHFFFAOYSA-N 0.000 description 3
- SMVBADCAMQOTOV-UHFFFAOYSA-N ethyl cyclobutanecarboxylate Chemical compound CCOC(=O)C1CCC1 SMVBADCAMQOTOV-UHFFFAOYSA-N 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
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Classifications
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- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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]
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C327/00—Thiocarboxylic acids
- C07C327/38—Amides of thiocarboxylic acids
- C07C327/46—Amides of thiocarboxylic acids having carbon atoms of thiocarboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C327/00—Thiocarboxylic acids
- C07C327/38—Amides of thiocarboxylic acids
- C07C327/48—Amides of thiocarboxylic acids having carbon atoms of thiocarboxamide groups bound to carbon atoms of six-membered aromatic rings
-
- 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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/56—Amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
- C07D233/30—Oxygen or sulfur atoms
- C07D233/32—One oxygen atom
- C07D233/38—One oxygen atom with acyl radicals or hetero atoms directly attached to ring nitrogen atoms
-
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
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- Chemical & Material Sciences (AREA)
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- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Photoreceptors In Electrophotography (AREA)
- Pyridine Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
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US12047599P | 1999-02-18 | 1999-02-18 |
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ZA200106180B true ZA200106180B (en) | 2002-10-28 |
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ZA200106180A ZA200106180B (en) | 1999-02-18 | 2001-07-26 | Thioamide derivatives. |
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EP (1) | EP1154993B1 (id) |
JP (1) | JP2002537286A (id) |
KR (1) | KR100649819B1 (id) |
CN (1) | CN1213025C (id) |
AT (1) | ATE278664T1 (id) |
AU (1) | AU773388B2 (id) |
BR (1) | BR0008280A (id) |
CA (1) | CA2362831C (id) |
CZ (1) | CZ20012980A3 (id) |
DE (1) | DE60014588T2 (id) |
DK (1) | DK1154993T3 (id) |
ES (1) | ES2228458T3 (id) |
HK (1) | HK1044330A1 (id) |
HR (1) | HRP20010595B1 (id) |
HU (1) | HUP0200155A3 (id) |
ID (1) | ID30129A (id) |
IL (2) | IL144636A0 (id) |
MA (1) | MA26769A1 (id) |
NO (1) | NO20014018L (id) |
NZ (1) | NZ513254A (id) |
PL (1) | PL349461A1 (id) |
PT (1) | PT1154993E (id) |
RU (1) | RU2245874C2 (id) |
SI (1) | SI1154993T1 (id) |
TR (1) | TR200102399T2 (id) |
WO (1) | WO2000048994A1 (id) |
YU (1) | YU58701A (id) |
ZA (1) | ZA200106180B (id) |
Families Citing this family (35)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6939855B2 (en) * | 1997-07-31 | 2005-09-06 | Elan Pharmaceuticals, Inc. | Anti-inflammatory compositions and method |
US6680195B1 (en) * | 1997-11-26 | 2004-01-20 | Inhibitex, Inc. | Extracellular matrix-binding proteins from staphylococcus aureus |
US6521626B1 (en) * | 1998-03-24 | 2003-02-18 | Celltech R&D Limited | Thiocarboxamide derivatives |
US6380387B1 (en) | 1999-12-06 | 2002-04-30 | Hoffmann-La Roche Inc. | 4-Pyrimidinyl-n-acyl-l phenylalanines |
US6388084B1 (en) | 1999-12-06 | 2002-05-14 | Hoffmann-La Roche Inc. | 4-pyridinyl-n-acyl-l-phenylalanines |
WO2001055231A1 (fr) * | 2000-01-26 | 2001-08-02 | Mitsui Chemicals, Inc. | Polymeres olefiniques et leurs procedes de production |
WO2001070670A1 (fr) * | 2000-03-23 | 2001-09-27 | Ajinomoto Co., Inc. | Nouveau derive de phenylalanine |
US6960597B2 (en) * | 2000-06-30 | 2005-11-01 | Orth-Mcneil Pharmaceutical, Inc. | Aza-bridged-bicyclic amino acid derivatives as α4 integrin antagonists |
DK1317426T3 (da) * | 2000-09-14 | 2006-01-09 | Gruenenthal Gmbh | Betal-thio-aminosyrer |
US20090297611A1 (en) * | 2003-07-31 | 2009-12-03 | Robinson Cynthia B | Combination of dehydroepiandrosterone or dehydroepiandrosterone-sulfate with a tyrosine kinase inhibitor, delta opioid receptor antagonist, neurokinin receptor antagonist, or vcam inhibitor for treatment of asthma or chronic obstructive pulmonary disease |
US20050026879A1 (en) * | 2003-07-31 | 2005-02-03 | Robinson Cynthia B. | Combination of dehydroepiandrosterone or dehydroepiandrosterone-sulfate with a tyrosine kinase inhibitor, delta opioid receptor antagonist, neurokinin receptor antagonist, or VCAM inhibitor for treatment of asthma or chronic obstructive pulmonary disease |
US20050069227A1 (en) * | 2003-09-29 | 2005-03-31 | Mark Steele | Flexible package having integrated slit member |
US20050176755A1 (en) * | 2003-10-31 | 2005-08-11 | Dyatkin Alexey B. | Aza-bridged-bicyclic amino acid derivatives as alpha4 integrin antagonists |
JP2007522225A (ja) * | 2004-02-10 | 2007-08-09 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | A4インテグリン拮抗薬としてのピリダジノン |
BRPI0506676A (pt) * | 2004-02-10 | 2007-05-15 | Janssen Phamaceutica N V | piridazinona uréias como antagonistas de integrinas alfa4 |
JP2007528397A (ja) * | 2004-03-10 | 2007-10-11 | メルク エンド カムパニー インコーポレーテッド | Vla−4アンタゴニスト |
JP4649476B2 (ja) * | 2004-08-16 | 2011-03-09 | メルク・シャープ・エンド・ドーム・コーポレイション | Vla−4拮抗薬 |
US7641325B2 (en) * | 2004-10-04 | 2010-01-05 | Kodak Graphic Communications Group Canada | Non-conductive fluid droplet characterizing apparatus and method |
WO2006081986A1 (en) * | 2005-02-07 | 2006-08-10 | F.Hoffmann-La Roche Ag | Bambuterol and integrin inhibitor combination |
WO2006094640A2 (en) * | 2005-03-04 | 2006-09-14 | F.Hoffmann-La Roche Ag | Roflumilast and integrin inhibitor combination and method of treatment |
CZ2005337A3 (cs) * | 2005-05-26 | 2007-01-10 | Universita Karlova v Praze, Farmaceutická fakulta v Hradci Králové | Antimykotické a antimykobakteriální thiosalicylanilidy a způsob jejich přípravy |
AU2006337137B2 (en) | 2005-12-29 | 2012-06-14 | Tersera Therapeutics Llc | Multicyclic amino acid derivatives and methods of their use |
EP2510941A3 (en) | 2007-02-20 | 2013-01-23 | Merrimack Pharmaceuticals, Inc. | Methods of treating multiple sclerosis by administration of alpha-fetoprotein in combination with an integrin antagonist |
DK2224954T3 (en) * | 2007-11-07 | 2014-03-03 | Celldex Therapeutics Inc | Antibodies that bind human dendritic and epithelial cell 205 (DEC-205) |
EP2860260A1 (en) | 2008-04-11 | 2015-04-15 | Merrimack Pharmaceuticals, Inc. | Human serum albumin linkers and conjugates thereof |
CN102282168A (zh) | 2008-11-18 | 2011-12-14 | 梅里麦克制药股份有限公司 | 人血清白蛋白接头以及其结合物 |
US8343706B2 (en) * | 2010-01-25 | 2013-01-01 | International Business Machines Corporation | Fluorine-free fused ring heteroaromatic photoacid generators and resist compositions containing the same |
BR112014009144A8 (pt) | 2011-10-17 | 2017-06-20 | Univ Muenster Westfaelische Wilhelms | avaliação do risco de pml e métodos com base na mesma |
US20150202287A1 (en) | 2012-08-30 | 2015-07-23 | Merrimack Pharmaceuticals, Inc. | Combination therapies comprising anti-erbb3 agents |
CA3115830C (en) | 2018-10-30 | 2023-09-12 | Gilead Sciences, Inc. | Compounds for inhibition of .alpha.4.beta.7 integrin |
JP7214882B2 (ja) | 2018-10-30 | 2023-01-30 | ギリアード サイエンシーズ, インコーポレイテッド | アルファ4ベータ7インテグリン阻害剤としてのイミダゾピリジン誘導体 |
AU2019373240B2 (en) | 2018-10-30 | 2023-04-20 | Gilead Sciences, Inc. | Quinoline derivatives as alpha4beta7 integrin inhibitors |
US11224600B2 (en) | 2018-10-30 | 2022-01-18 | Gilead Sciences, Inc. | Compounds for inhibition of alpha 4 beta 7 integrin |
US11578069B2 (en) | 2019-08-14 | 2023-02-14 | Gilead Sciences, Inc. | Compounds for inhibition of α4 β7 integrin |
CN113683499B (zh) * | 2021-09-10 | 2024-01-30 | 上海皓鸿生物医药科技有限公司 | 一种制备杜韦利西布中间体的方法 |
Family Cites Families (24)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BE584914A (id) | 1958-11-24 | |||
US3527793A (en) | 1967-08-18 | 1970-09-08 | Bristol Myers Co | Phenylglycine derivatives |
IT1190378B (it) | 1985-06-21 | 1988-02-16 | Isf Spa | Derivati pirrolidonici |
US5039805A (en) | 1988-12-08 | 1991-08-13 | Hoffmann-La Roche Inc. | Novel benzoic and phenylacetic acid derivatives |
US5463116A (en) | 1991-07-30 | 1995-10-31 | Ajinomoto Co., Inc. | Crystals of N- (trans-4-isopropylcyclohexlycarbonyl)-D-phenylalanine and methods for preparing them |
CA2191979A1 (en) | 1994-06-20 | 1995-12-28 | Muneo Takatani | Condensed imidazole compounds, their production and use |
US6306840B1 (en) | 1995-01-23 | 2001-10-23 | Biogen, Inc. | Cell adhesion inhibitors |
US5804595A (en) | 1995-12-05 | 1998-09-08 | Regents Of The University Of Minnesota | Kappa opioid receptor agonists |
DE19548709A1 (de) | 1995-12-23 | 1997-07-03 | Merck Patent Gmbh | Tyrosinderivate |
JP2000506538A (ja) | 1996-03-29 | 2000-05-30 | ジー.ディー.サール アンド カンパニー | メタ―置換フェニレン誘導体 |
AU2536097A (en) * | 1996-03-29 | 1997-10-22 | G.D. Searle & Co. | Para-substituted phenylpropanoic acid derivatives as integrin antagonists |
DE19654483A1 (de) | 1996-06-28 | 1998-01-02 | Merck Patent Gmbh | Phenylalanin-Derivate |
CA2291778A1 (en) * | 1997-05-29 | 1998-12-03 | Merck & Co., Inc. | Heterocyclic amide compounds as cell adhesion inhibitors |
AU8163398A (en) * | 1997-06-23 | 1999-01-04 | Pharmacia & Upjohn Company | Inhibitors of alpha4beta1mediated cell adhesion |
CN1265672A (zh) * | 1997-07-31 | 2000-09-06 | 伊兰药品公司 | 能抑制由vla-4介导的白细胞粘连的磺酰化二肽化合物 |
JP2003517424A (ja) * | 1997-07-31 | 2003-05-27 | エラン・ファーマシューティカルズ・インコーポレーテッド | Vla−4が介在する白血球接着を阻害する4−アミノ−フェニルアラニン型化合物 |
EP0994895A1 (en) * | 1997-07-31 | 2000-04-26 | Elan Pharmaceuticals, Inc. | Dipeptide compounds which inhibit leukocyte adhesion mediated by vla-4 |
EP1005446B1 (en) * | 1997-08-22 | 2004-02-25 | F. Hoffmann-La Roche Ag | N-aroylphenylalanine derivatives |
CA2301377C (en) * | 1997-08-22 | 2009-10-06 | F. Hoffmann-La Roche Ag | N-aroylphenylalanine derivatives |
US6229011B1 (en) * | 1997-08-22 | 2001-05-08 | Hoffman-La Roche Inc. | N-aroylphenylalanine derivative VCAM-1 inhibitors |
ATE289991T1 (de) * | 1997-12-23 | 2005-03-15 | Aventis Pharma Ltd | Substituierte beta-alaninen |
ATE273273T1 (de) | 1998-02-26 | 2004-08-15 | Celltech Therapeutics Ltd | Phenylalaninderivate als inhibitoren von alpha4 integrinen |
US6521626B1 (en) | 1998-03-24 | 2003-02-18 | Celltech R&D Limited | Thiocarboxamide derivatives |
GB9811159D0 (en) | 1998-05-22 | 1998-07-22 | Celltech Therapeutics Ltd | Chemical compounds |
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2000
- 2000-02-10 NZ NZ513254A patent/NZ513254A/en unknown
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- 2000-02-10 CA CA002362831A patent/CA2362831C/en not_active Expired - Fee Related
- 2000-02-10 JP JP2000599735A patent/JP2002537286A/ja active Pending
- 2000-02-10 DK DK00903680T patent/DK1154993T3/da active
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- 2000-02-10 WO PCT/EP2000/001058 patent/WO2000048994A1/en active IP Right Grant
- 2000-02-10 AT AT00903680T patent/ATE278664T1/de not_active IP Right Cessation
- 2000-02-10 ID IDW00200101770A patent/ID30129A/id unknown
- 2000-02-10 BR BR0008280-5A patent/BR0008280A/pt not_active Application Discontinuation
- 2000-02-10 SI SI200030513T patent/SI1154993T1/xx unknown
- 2000-02-10 AU AU25475/00A patent/AU773388B2/en not_active Ceased
- 2000-02-10 CZ CZ20012980A patent/CZ20012980A3/cs unknown
- 2000-02-10 ES ES00903680T patent/ES2228458T3/es not_active Expired - Lifetime
- 2000-02-10 TR TR2001/02399T patent/TR200102399T2/xx unknown
- 2000-02-10 EP EP00903680A patent/EP1154993B1/en not_active Expired - Lifetime
- 2000-02-10 RU RU2001124596/04A patent/RU2245874C2/ru not_active IP Right Cessation
- 2000-02-10 DE DE60014588T patent/DE60014588T2/de not_active Expired - Lifetime
- 2000-02-10 YU YU58701A patent/YU58701A/sh unknown
- 2000-02-10 IL IL14463600A patent/IL144636A0/xx active IP Right Grant
- 2000-02-10 PL PL00349461A patent/PL349461A1/xx not_active Application Discontinuation
- 2000-02-10 CN CNB008043973A patent/CN1213025C/zh not_active Expired - Fee Related
- 2000-02-10 KR KR1020017010495A patent/KR100649819B1/ko not_active IP Right Cessation
- 2000-02-17 US US09/505,903 patent/US6288267B1/en not_active Expired - Fee Related
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2001
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- 2001-05-23 US US09/864,032 patent/US6426348B1/en not_active Expired - Fee Related
- 2001-05-23 US US09/863,579 patent/US6458844B2/en not_active Expired - Fee Related
- 2001-05-23 US US09/864,104 patent/US6423728B1/en not_active Expired - Fee Related
- 2001-05-23 US US09/863,567 patent/US6479666B2/en not_active Expired - Fee Related
- 2001-07-26 ZA ZA200106180A patent/ZA200106180B/en unknown
- 2001-07-30 IL IL144636A patent/IL144636A/en not_active IP Right Cessation
- 2001-08-08 MA MA26290A patent/MA26769A1/fr unknown
- 2001-08-10 HR HR20010595A patent/HRP20010595B1/xx not_active IP Right Cessation
- 2001-08-17 NO NO20014018A patent/NO20014018L/no not_active Application Discontinuation
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2002
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