NO323584B1 - Nye forbindelser, fremgangsmate for fremstilling og anvendelse av disse, farmasoytiske preparat inneholdende nevnte nye forbindelser samt nevnte nye forbindelser for medisinsk bruk. - Google Patents
Nye forbindelser, fremgangsmate for fremstilling og anvendelse av disse, farmasoytiske preparat inneholdende nevnte nye forbindelser samt nevnte nye forbindelser for medisinsk bruk. Download PDFInfo
- Publication number
- NO323584B1 NO323584B1 NO20023934A NO20023934A NO323584B1 NO 323584 B1 NO323584 B1 NO 323584B1 NO 20023934 A NO20023934 A NO 20023934A NO 20023934 A NO20023934 A NO 20023934A NO 323584 B1 NO323584 B1 NO 323584B1
- Authority
- NO
- Norway
- Prior art keywords
- acetamide
- phenyl
- hydroxypropoxy
- chlorophenoxy
- chloro
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 206
- 238000000034 method Methods 0.000 title claims description 30
- 238000002360 preparation method Methods 0.000 title claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 154
- 239000000203 mixture Substances 0.000 claims description 105
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 claims description 59
- -1 nitro, carboxyl Chemical group 0.000 claims description 56
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 50
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 47
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 45
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 30
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- 239000012453 solvate Substances 0.000 claims description 24
- 238000006243 chemical reaction Methods 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 18
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 17
- 229920006395 saturated elastomer Polymers 0.000 claims description 17
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 15
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 15
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 238000011282 treatment Methods 0.000 claims description 14
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 150000004702 methyl esters Chemical class 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 208000006673 asthma Diseases 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 239000001301 oxygen Substances 0.000 claims description 10
- GTDFBKVKKRBGIF-UHFFFAOYSA-N 3-(4-chlorophenoxy)pyrrolidine Chemical compound C1=CC(Cl)=CC=C1OC1CNCC1 GTDFBKVKKRBGIF-UHFFFAOYSA-N 0.000 claims description 9
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 8
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 8
- IMNDHOCGZLYMRO-UHFFFAOYSA-N n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC=CC=C1 IMNDHOCGZLYMRO-UHFFFAOYSA-N 0.000 claims description 8
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 8
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 8
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 7
- 239000004202 carbamide Substances 0.000 claims description 7
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 125000004434 sulfur atom Chemical group 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 239000002671 adjuvant Substances 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 230000001225 therapeutic effect Effects 0.000 claims description 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 239000005864 Sulphur Chemical group 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 125000001188 haloalkyl group Chemical group 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- NBHJVKZDVXNVEZ-UHFFFAOYSA-N methyl 2-[3-[4-(4-fluorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]benzoate Chemical compound COC(=O)C1=CC=CC=C1OCC(O)CN1CCC(OC=2C=CC(F)=CC=2)CC1 NBHJVKZDVXNVEZ-UHFFFAOYSA-N 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical compound CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 4
- TYNSEKHUEZECTJ-UHFFFAOYSA-N 1-(2-aminophenoxy)-3-[4-(3,4-dichlorophenoxy)piperidin-1-yl]propan-2-ol;dihydrochloride Chemical compound Cl.Cl.NC1=CC=CC=C1OCC(O)CN1CCC(OC=2C=C(Cl)C(Cl)=CC=2)CC1 TYNSEKHUEZECTJ-UHFFFAOYSA-N 0.000 claims description 3
- AKWIFIHWWBVSPE-UHFFFAOYSA-N 1-[3-(4-chlorophenoxy)pyrrolidin-1-yl]-3-(2-methoxyphenoxy)propan-2-ol Chemical compound COC1=CC=CC=C1OCC(O)CN1CC(OC=2C=CC(Cl)=CC=2)CC1 AKWIFIHWWBVSPE-UHFFFAOYSA-N 0.000 claims description 3
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 claims description 3
- JWWRFTZGEXUHEH-UHFFFAOYSA-N 2-[3-[4-(4-chlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]-n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC=CC=C1OCC(O)CN1CCC(OC=2C=CC(Cl)=CC=2)CC1 JWWRFTZGEXUHEH-UHFFFAOYSA-N 0.000 claims description 3
- LSBDFXRDZJMBSC-UHFFFAOYSA-N Amide-Phenylacetic acid Natural products NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 claims description 3
- 102000009410 Chemokine receptor Human genes 0.000 claims description 3
- 108050000299 Chemokine receptor Proteins 0.000 claims description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 3
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 235000019256 formaldehyde Nutrition 0.000 claims description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims description 3
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 3
- 208000023504 respiratory system disease Diseases 0.000 claims description 3
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 2
- XHGDGEDAPFJBII-UHFFFAOYSA-N 1-[2-[3-[4-(3,4-dichlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]phenyl]ethanone Chemical compound CC(=O)C1=CC=CC=C1OCC(O)CN1CCC(OC=2C=C(Cl)C(Cl)=CC=2)CC1 XHGDGEDAPFJBII-UHFFFAOYSA-N 0.000 claims description 2
- CLRMKSASWXDYCE-UHFFFAOYSA-N 1-[2-[3-[4-(3,4-dichlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]phenyl]propan-1-one Chemical compound CCC(=O)C1=CC=CC=C1OCC(O)CN1CCC(OC=2C=C(Cl)C(Cl)=CC=2)CC1 CLRMKSASWXDYCE-UHFFFAOYSA-N 0.000 claims description 2
- PIUYRTBFRFXGSW-UHFFFAOYSA-N 1-[7-[3-[3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]indol-1-yl]ethanone Chemical compound C=12N(C(=O)C)C=CC2=CC=CC=1OCC(O)CN(C1)CCC1OC1=CC=C(Cl)C=C1 PIUYRTBFRFXGSW-UHFFFAOYSA-N 0.000 claims description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 claims description 2
- 230000003213 activating effect Effects 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000002837 carbocyclic group Chemical group 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 2
- 208000027866 inflammatory disease Diseases 0.000 claims description 2
- BRHWKZMRINCYQP-UHFFFAOYSA-N methyl 2-[[2-[3-[3-(4-fluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]benzoyl]amino]acetate Chemical compound COC(=O)CNC(=O)C1=CC=CC=C1OCC(O)CN1CC(OC=2C=CC(F)=CC=2)CC1 BRHWKZMRINCYQP-UHFFFAOYSA-N 0.000 claims description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 2
- DOGCLONVLOHUCQ-VDWUQFQWSA-N n-[2-[(2s)-3-[(3s)-3-[(4-chlorophenyl)methyl]pyrrolidin-1-yl]-2-hydroxypropoxy]phenyl]acetamide;hydrochloride Chemical compound Cl.CC(=O)NC1=CC=CC=C1OC[C@@H](O)CN1C[C@@H](CC=2C=CC(Cl)=CC=2)CC1 DOGCLONVLOHUCQ-VDWUQFQWSA-N 0.000 claims description 2
- ZCGQELYDYMAKCP-UHFFFAOYSA-N n-[2-[3-[3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-4-fluorophenyl]acetamide Chemical compound CC(=O)NC1=CC=C(F)C=C1OCC(O)CN1CC(OC=2C=CC(Cl)=CC=2)CC1 ZCGQELYDYMAKCP-UHFFFAOYSA-N 0.000 claims description 2
- GWTPBGQICZEEFZ-UHFFFAOYSA-N n-[2-[3-[3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-5-fluorophenyl]acetamide Chemical compound CC(=O)NC1=CC(F)=CC=C1OCC(O)CN1CC(OC=2C=CC(Cl)=CC=2)CC1 GWTPBGQICZEEFZ-UHFFFAOYSA-N 0.000 claims description 2
- URYJDFQDXMKSBD-UHFFFAOYSA-N n-[2-[3-[4-(4-chlorobenzoyl)piperazin-1-yl]-2-hydroxypropoxy]-5-cyanophenyl]acetamide Chemical compound CC(=O)NC1=CC(C#N)=CC=C1OCC(O)CN1CCN(C(=O)C=2C=CC(Cl)=CC=2)CC1 URYJDFQDXMKSBD-UHFFFAOYSA-N 0.000 claims description 2
- VWHUXRFAAKDQJN-UHFFFAOYSA-N n-[3-acetyl-2-[3-[3-(4-fluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-5-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC(C)=CC(C(C)=O)=C1OCC(O)CN1CC(OC=2C=CC(F)=CC=2)CC1 VWHUXRFAAKDQJN-UHFFFAOYSA-N 0.000 claims description 2
- DLQCCFVENFUHSQ-UHFFFAOYSA-N n-[4-[1-[3-(2-acetylphenoxy)-2-hydroxypropyl]piperidin-4-yl]oxyphenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1OC1CCN(CC(O)COC=2C(=CC=CC=2)C(C)=O)CC1 DLQCCFVENFUHSQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000004212 difluorophenyl group Chemical group 0.000 claims 2
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 1
- QHFFUNPIGPVCDI-UHFFFAOYSA-N 1-[2-[3-[3-(3,4-difluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]phenyl]ethanone Chemical compound CC(=O)C1=CC=CC=C1OCC(O)CN1CC(OC=2C=C(F)C(F)=CC=2)CC1 QHFFUNPIGPVCDI-UHFFFAOYSA-N 0.000 claims 1
- BHQCLOGTSTZCTH-UHFFFAOYSA-N 1-[3-(4-fluorophenoxy)pyrrolidin-1-yl]-3-(1h-indol-7-yloxy)propan-2-ol Chemical compound C=1C=CC=2C=CNC=2C=1OCC(O)CN(C1)CCC1OC1=CC=C(F)C=C1 BHQCLOGTSTZCTH-UHFFFAOYSA-N 0.000 claims 1
- YBZLGBDIUOVESN-UHFFFAOYSA-N 1-[4-(4-fluorophenoxy)piperidin-1-yl]-3-(2-methoxyphenoxy)propan-2-ol Chemical compound COC1=CC=CC=C1OCC(O)CN1CCC(OC=2C=CC(F)=CC=2)CC1 YBZLGBDIUOVESN-UHFFFAOYSA-N 0.000 claims 1
- LHHACTKLABTCQF-UHFFFAOYSA-N [amino(hydroxy)methylidene]-methylazanium;chloride Chemical compound Cl.CNC(O)=N LHHACTKLABTCQF-UHFFFAOYSA-N 0.000 claims 1
- XTKDAFGWCDAMPY-UHFFFAOYSA-N azaperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCN(C=2N=CC=CC=2)CC1 XTKDAFGWCDAMPY-UHFFFAOYSA-N 0.000 claims 1
- 230000009286 beneficial effect Effects 0.000 claims 1
- 239000012876 carrier material Substances 0.000 claims 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 125000001207 fluorophenyl group Chemical group 0.000 claims 1
- MXJURQMLRCSLNO-UHFFFAOYSA-N methyl 2-[[2-[3-[3-(3,4-difluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]benzoyl]amino]acetate Chemical compound COC(=O)CNC(=O)C1=CC=CC=C1OCC(O)CN1CC(OC=2C=C(F)C(F)=CC=2)CC1 MXJURQMLRCSLNO-UHFFFAOYSA-N 0.000 claims 1
- SJHKDUFERPKWDB-UHFFFAOYSA-N methyl 2-[[2-[3-[3-(4-fluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]benzoyl]amino]-2-methylpropanoate Chemical compound COC(=O)C(C)(C)NC(=O)C1=CC=CC=C1OCC(O)CN1CC(OC=2C=CC(F)=CC=2)CC1 SJHKDUFERPKWDB-UHFFFAOYSA-N 0.000 claims 1
- CWDJLXQIDVZQDR-UHFFFAOYSA-N methyl 3-[2-[3-[4-(4-chlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC=C1OCC(O)CN1CCC(OC=2C=CC(Cl)=CC=2)CC1 CWDJLXQIDVZQDR-UHFFFAOYSA-N 0.000 claims 1
- YZVNDBXUNUQOLW-UHFFFAOYSA-N methyl 3-[2-[3-[4-(4-fluorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC=C1OCC(O)CN1CCC(OC=2C=CC(F)=CC=2)CC1 YZVNDBXUNUQOLW-UHFFFAOYSA-N 0.000 claims 1
- SOMAAHQRBOTAQC-UHFFFAOYSA-N n-[2-[3-(8-chloro-1,3,4,5-tetrahydropyrido[4,3-b]indol-2-yl)-2-hydroxypropoxy]-5-phenylphenyl]acetamide Chemical compound C=1C=C(OCC(O)CN2CC=3C4=CC(Cl)=CC=C4NC=3CC2)C(NC(=O)C)=CC=1C1=CC=CC=C1 SOMAAHQRBOTAQC-UHFFFAOYSA-N 0.000 claims 1
- QNSCIKGEWXTILN-UHFFFAOYSA-N n-[2-[3-(8-chloro-1,3,4,5-tetrahydropyrido[4,3-b]indol-2-yl)-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OCC(O)CN1CC(C2=CC(Cl)=CC=C2N2)=C2CC1 QNSCIKGEWXTILN-UHFFFAOYSA-N 0.000 claims 1
- MXKQEHHKHKNZBG-UHFFFAOYSA-N n-[2-[3-[3-(3,4-dichlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-4-fluorophenyl]acetamide Chemical compound CC(=O)NC1=CC=C(F)C=C1OCC(O)CN1CC(OC=2C=C(Cl)C(Cl)=CC=2)CC1 MXKQEHHKHKNZBG-UHFFFAOYSA-N 0.000 claims 1
- WRNUCGIPGKQDBE-UHFFFAOYSA-N n-[2-[3-[3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-4-methylphenyl]pyrrolidine-1-carboxamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1CC(OC=2C=CC(Cl)=CC=2)CN1CC(O)COC1=CC(C)=CC=C1NC(=O)N1CCCC1 WRNUCGIPGKQDBE-UHFFFAOYSA-N 0.000 claims 1
- FREBHOAWPILZSJ-UHFFFAOYSA-N n-[2-[3-[3-(4-fluorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]-5-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC(C)=CC=C1OCC(O)CN1CC(OC=2C=CC(F)=CC=2)CC1 FREBHOAWPILZSJ-UHFFFAOYSA-N 0.000 claims 1
- GVLNVGJZBPOHOU-UHFFFAOYSA-N n-[2-[3-[3-[(4-fluorophenoxy)methyl]piperidin-1-yl]-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OCC(O)CN1CC(COC=2C=CC(F)=CC=2)CCC1 GVLNVGJZBPOHOU-UHFFFAOYSA-N 0.000 claims 1
- SXANOEDUEPQSBI-UHFFFAOYSA-N n-[2-[3-[4-(4-chlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]-5-fluorophenyl]acetamide Chemical compound CC(=O)NC1=CC(F)=CC=C1OCC(O)CN1CCC(OC=2C=CC(Cl)=CC=2)CC1 SXANOEDUEPQSBI-UHFFFAOYSA-N 0.000 claims 1
- ICWBUYRSEOTAHD-RPBOFIJWSA-N n-[2-[[(1r,2r)-2-[4-(3,4-dichlorophenoxy)piperidin-1-yl]-1-hydroxycyclopentyl]methoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OC[C@]1(O)[C@H](N2CCC(CC2)OC=2C=C(Cl)C(Cl)=CC=2)CCC1 ICWBUYRSEOTAHD-RPBOFIJWSA-N 0.000 claims 1
- XHRTZTLTIGTBSV-UHFFFAOYSA-N n-[3-acetyl-2-[3-[4-(4-chlorophenoxy)piperidin-1-yl]-2-hydroxypropoxy]-5-methylphenyl]acetamide Chemical compound CC(=O)NC1=CC(C)=CC(C(C)=O)=C1OCC(O)CN1CCC(OC=2C=CC(Cl)=CC=2)CC1 XHRTZTLTIGTBSV-UHFFFAOYSA-N 0.000 claims 1
- YVITYRDMYGRNNV-UHFFFAOYSA-N n-[4-[1-[3-(2-acetamidophenoxy)-2-hydroxypropyl]piperidin-4-yl]oxyphenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1OC1CCN(CC(O)COC=2C(=CC=CC=2)NC(C)=O)CC1 YVITYRDMYGRNNV-UHFFFAOYSA-N 0.000 claims 1
- XVWKFDLTGXGYKL-UHFFFAOYSA-N n-[5-chloro-2-[3-[3-(4-chlorophenoxy)pyrrolidin-1-yl]-2-hydroxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC(Cl)=CC=C1OCC(O)CN1CC(OC=2C=CC(Cl)=CC=2)CC1 XVWKFDLTGXGYKL-UHFFFAOYSA-N 0.000 claims 1
- 238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 265
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 174
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 132
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 119
- 238000005481 NMR spectroscopy Methods 0.000 description 110
- 239000000243 solution Substances 0.000 description 108
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 87
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 71
- 235000019439 ethyl acetate Nutrition 0.000 description 65
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 63
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Classifications
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/12—Oxygen or sulfur atoms
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- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/14—Nitrogen atoms not forming part of a nitro radical
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- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
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- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
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- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
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- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- 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
- C07D401/12—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 chain containing hetero atoms as chain links
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- 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
- C07D403/12—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 chain containing hetero atoms as chain links
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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SE0003979A SE0003979D0 (sv) | 2000-10-31 | 2000-10-31 | Novel Compounds |
PCT/SE2001/000403 WO2001062728A1 (fr) | 2000-02-25 | 2001-02-23 | Nouveaux composes |
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AT (2) | ATE280153T1 (fr) |
AU (3) | AU783475B2 (fr) |
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CO5300399A1 (es) | 2000-02-25 | 2003-07-31 | Astrazeneca Ab | Heterocicliocs que contienen nitrogeno, proceso para su preparacion y composiciones farmaceuticas que los contienen |
AR028948A1 (es) * | 2000-06-20 | 2003-05-28 | Astrazeneca Ab | Compuestos novedosos |
US7005439B2 (en) * | 2000-06-20 | 2006-02-28 | Astrazeneca Ab | Compounds |
AR035230A1 (es) * | 2001-03-19 | 2004-05-05 | Astrazeneca Ab | Compuestos de bencimidazol, proceso para su preparacion, composicion farmaceutica, proceso para la preparacion de dicha composicion farmaceutica, y usos de estos compuestos para la elaboracion de medicamentos |
SE0101038D0 (sv) * | 2001-03-23 | 2001-03-23 | Astrazeneca Ab | Novel compounds |
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SE0104251D0 (sv) * | 2001-12-14 | 2001-12-14 | Astrazeneca Ab | Novel compounds |
TW200303304A (en) | 2002-02-18 | 2003-09-01 | Astrazeneca Ab | Chemical compounds |
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SE0400208D0 (sv) | 2004-02-02 | 2004-02-02 | Astrazeneca Ab | Chemical compounds |
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TW200738634A (en) * | 2005-08-02 | 2007-10-16 | Astrazeneca Ab | New salt |
TW200734305A (en) * | 2005-08-02 | 2007-09-16 | Astrazeneca Ab | New salt III |
CN101516863A (zh) * | 2006-07-18 | 2009-08-26 | 阿斯利康(瑞典)有限公司 | 制备取代的2-乙酰基氨基-烷氧基苯的方法 |
GB0702456D0 (en) | 2007-02-08 | 2007-03-21 | Astrazeneca Ab | New combination |
WO2008136754A1 (fr) * | 2007-05-07 | 2008-11-13 | Astrazeneca Ab | Nouveaux dérivés de benzyl-2-oxo-pipérazinyl/7-oxo/5-oxa-[1,4]-diazépanyl/2-oxo- tétrahydropyrimidinyle |
WO2008150231A1 (fr) * | 2007-06-08 | 2008-12-11 | Astrazeneca Ab | Nouveaux composés hétérocycliques utilisés dans le traitement de troubles respiratoires, des voies aériennes, ou de troubles inflammatoires |
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WO2011003007A1 (fr) | 2009-07-01 | 2011-01-06 | Albany Molecular Research, Inc. | Antagonistes de mch-1 dazabicycloalcane-indole et dazabicycloalcane-pyrrolo-pyridine, procédés de préparation, et utilisation de ceux-ci |
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GB0913345D0 (en) | 2009-07-31 | 2009-09-16 | Astrazeneca Ab | New combination 802 |
WO2011061527A1 (fr) | 2009-11-17 | 2011-05-26 | Astrazeneca Ab | Combinaisons qui comprennent un modulateur du récepteur glucocorticoïde, destinées au traitement de maladies respiratoires |
WO2011073662A1 (fr) | 2009-12-17 | 2011-06-23 | Astrazeneca Ab | Association d'une benzoxazinone et d'un autre agent pour le traitement de maladies respiratoires |
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GB201021979D0 (en) | 2010-12-23 | 2011-02-02 | Astrazeneca Ab | New compound |
GB201021992D0 (en) | 2010-12-23 | 2011-02-02 | Astrazeneca Ab | Compound |
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CN104710419B (zh) * | 2015-03-18 | 2017-05-24 | 中国药科大学 | 四氢吡啶[4,3‑b]骈吲哚类化合物、其制备方法及医药用途 |
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-
2001
- 2001-02-22 CO CO01014299A patent/CO5300399A1/es not_active Application Discontinuation
- 2001-02-23 CN CNB018084842A patent/CN1187326C/zh not_active Expired - Fee Related
- 2001-02-23 EP EP01908558A patent/EP1263725B1/fr not_active Expired - Lifetime
- 2001-02-23 NZ NZ520719A patent/NZ520719A/en unknown
- 2001-02-23 EP EP01908557A patent/EP1263724B1/fr not_active Expired - Lifetime
- 2001-02-23 DE DE60110900T patent/DE60110900T2/de not_active Expired - Fee Related
- 2001-02-23 BR BR0108677-4A patent/BR0108677A/pt not_active IP Right Cessation
- 2001-02-23 RU RU2002122100/04A patent/RU2265011C2/ru not_active IP Right Cessation
- 2001-02-23 CA CA002400435A patent/CA2400435A1/fr not_active Abandoned
- 2001-02-23 MX MXPA02008241A patent/MXPA02008241A/es active IP Right Grant
- 2001-02-23 JP JP2001561737A patent/JP2003523999A/ja not_active Withdrawn
- 2001-02-23 AR ARP010100842A patent/AR029806A1/es not_active Application Discontinuation
- 2001-02-23 KR KR1020027011129A patent/KR20020075450A/ko not_active Application Discontinuation
- 2001-02-23 EE EEP200200470A patent/EE05001B1/xx not_active IP Right Cessation
- 2001-02-23 WO PCT/SE2001/000405 patent/WO2001062757A1/fr not_active Application Discontinuation
- 2001-02-23 PL PL01358281A patent/PL358281A1/xx not_active Application Discontinuation
- 2001-02-23 US US10/204,789 patent/US6927222B2/en not_active Expired - Fee Related
- 2001-02-23 PT PT01908558T patent/PT1263725E/pt unknown
- 2001-02-23 ES ES01908558T patent/ES2227140T3/es not_active Expired - Lifetime
- 2001-02-23 EP EP01908559A patent/EP1263760A1/fr not_active Withdrawn
- 2001-02-23 AU AU36300/01A patent/AU783475B2/en not_active Ceased
- 2001-02-23 WO PCT/SE2001/000404 patent/WO2001062729A1/fr active IP Right Grant
- 2001-02-23 US US10/204,754 patent/US6951874B2/en not_active Expired - Fee Related
- 2001-02-23 AU AU36299/01A patent/AU783496B2/en not_active Ceased
- 2001-02-23 KR KR1020027011128A patent/KR20020076338A/ko not_active Application Discontinuation
- 2001-02-23 CN CNB018084125A patent/CN1229343C/zh not_active Expired - Fee Related
- 2001-02-23 CN CN01808426A patent/CN1426412A/zh active Pending
- 2001-02-23 KR KR1020027011127A patent/KR100752033B1/ko not_active IP Right Cessation
- 2001-02-23 PT PT01908557T patent/PT1263724E/pt unknown
- 2001-02-23 SI SI200130239T patent/SI1263725T1/xx unknown
- 2001-02-23 CZ CZ20022870A patent/CZ20022870A3/cs unknown
- 2001-02-23 US US10/204,790 patent/US6943188B2/en not_active Expired - Fee Related
- 2001-02-23 DK DK01908557T patent/DK1263724T3/da active
- 2001-02-23 JP JP2001562539A patent/JP2003524011A/ja active Pending
- 2001-02-23 JP JP2001561736A patent/JP2003523998A/ja not_active Withdrawn
- 2001-02-23 IL IL15120201A patent/IL151202A0/xx unknown
- 2001-02-23 AT AT01908558T patent/ATE280153T1/de not_active IP Right Cessation
- 2001-02-23 DE DE60106581T patent/DE60106581T2/de not_active Expired - Fee Related
- 2001-02-23 CA CA002400293A patent/CA2400293A1/fr not_active Abandoned
- 2001-02-23 ES ES01908557T patent/ES2241796T3/es not_active Expired - Lifetime
- 2001-02-23 IL IL15120801A patent/IL151208A0/xx unknown
- 2001-02-23 SK SK1213-2002A patent/SK12132002A3/sk unknown
- 2001-02-23 BR BR0108679-0A patent/BR0108679A/pt not_active IP Right Cessation
- 2001-02-23 CA CA002400434A patent/CA2400434A1/fr not_active Abandoned
- 2001-02-23 NZ NZ520718A patent/NZ520718A/en unknown
- 2001-02-23 WO PCT/SE2001/000403 patent/WO2001062728A1/fr active IP Right Grant
- 2001-02-23 AU AU36301/01A patent/AU3630101A/en not_active Abandoned
- 2001-02-23 HU HU0300922A patent/HUP0300922A2/hu unknown
- 2001-02-23 BR BR0108678-2A patent/BR0108678A/pt not_active IP Right Cessation
- 2001-02-23 MX MXPA02008244A patent/MXPA02008244A/es active IP Right Grant
- 2001-02-23 SI SI200130366T patent/SI1263724T1/xx unknown
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- 2001-02-23 MX MXPA02008243A patent/MXPA02008243A/es unknown
- 2001-02-23 DK DK01908558T patent/DK1263725T3/da active
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2002
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- 2002-08-19 NO NO20023933A patent/NO20023933L/no not_active Application Discontinuation
- 2002-08-22 IS IS6520A patent/IS6520A/is unknown
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2003
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