ES2204711T3 - Acrilamidas de quinuclidina. - Google Patents
Acrilamidas de quinuclidina.Info
- Publication number
- ES2204711T3 ES2204711T3 ES00971959T ES00971959T ES2204711T3 ES 2204711 T3 ES2204711 T3 ES 2204711T3 ES 00971959 T ES00971959 T ES 00971959T ES 00971959 T ES00971959 T ES 00971959T ES 2204711 T3 ES2204711 T3 ES 2204711T3
- Authority
- ES
- Spain
- Prior art keywords
- aza
- bicyclo
- propenamide
- oct
- methyl
- 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.)
- Expired - Lifetime
Links
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 90
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 26
- 150000003839 salts Chemical class 0.000 claims abstract description 26
- 238000011282 treatment Methods 0.000 claims abstract description 24
- 238000011321 prophylaxis Methods 0.000 claims abstract description 20
- 230000006735 deficit Effects 0.000 claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 15
- 208000028017 Psychotic disease Diseases 0.000 claims abstract description 6
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 3
- -1 -CO 2 R 5 Chemical group 0.000 claims description 43
- 208000035475 disorder Diseases 0.000 claims description 19
- 125000003118 aryl group Chemical group 0.000 claims description 16
- 125000001072 heteroaryl group Chemical group 0.000 claims description 16
- 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 claims description 15
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 claims description 15
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 229960002715 nicotine Drugs 0.000 claims description 14
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 125000004434 sulfur atom Chemical group 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims description 6
- 208000019901 Anxiety disease Diseases 0.000 claims description 6
- 230000036506 anxiety Effects 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 230000036407 pain Effects 0.000 claims description 6
- 201000000980 schizophrenia Diseases 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 206010026749 Mania Diseases 0.000 claims description 5
- 208000016620 Tourette disease Diseases 0.000 claims description 5
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 5
- 230000003935 attention Effects 0.000 claims description 5
- 230000001713 cholinergic effect Effects 0.000 claims description 5
- 208000013403 hyperactivity Diseases 0.000 claims description 5
- 208000000044 Amnesia Diseases 0.000 claims description 4
- 208000020925 Bipolar disease Diseases 0.000 claims description 4
- 241000282414 Homo sapiens Species 0.000 claims description 4
- 208000023105 Huntington disease Diseases 0.000 claims description 4
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 4
- 208000028683 bipolar I disease Diseases 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 210000000225 synapse Anatomy 0.000 claims description 4
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 3
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 3
- OCAWQQJWTRIKGZ-AEBAWRHJSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(1h-imidazol-2-ylsulfanyl)prop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)\C=C\SC1=NC=CN1 OCAWQQJWTRIKGZ-AEBAWRHJSA-N 0.000 claims description 3
- 208000026139 Memory disease Diseases 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 230000019771 cognition Effects 0.000 claims description 3
- 230000006984 memory degeneration Effects 0.000 claims description 3
- 208000023060 memory loss Diseases 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- OVBCUYMXSLVZNW-JXMROGBWSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(1,3-benzothiazol-2-ylsulfanyl)prop-2-enamide Chemical compound C1=CC=C2SC(S/C=C/C(NC3C4CCN(CC4)C3)=O)=NC2=C1 OVBCUYMXSLVZNW-JXMROGBWSA-N 0.000 claims description 2
- DFRCDJNMANEUOX-JXMROGBWSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(1,3-benzoxazol-2-ylsulfanyl)prop-2-enamide Chemical compound C1=CC=C2OC(S/C=C/C(NC3C4CCN(CC4)C3)=O)=NC2=C1 DFRCDJNMANEUOX-JXMROGBWSA-N 0.000 claims description 2
- ISFXODZDHSDPLN-RUDMXATFSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(1-methylimidazol-2-yl)sulfanylprop-2-enamide Chemical compound CN1C=CN=C1S\C=C\C(=O)NC1C(CC2)CCN2C1 ISFXODZDHSDPLN-RUDMXATFSA-N 0.000 claims description 2
- OCAWQQJWTRIKGZ-FPYGCLRLSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(1h-imidazol-2-ylsulfanyl)prop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C\SC1=NC=CN1 OCAWQQJWTRIKGZ-FPYGCLRLSA-N 0.000 claims description 2
- LTYPMDPWOZGHRI-DHZHZOJOSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(2-methoxyphenyl)sulfanylprop-2-enamide Chemical compound COC1=CC=CC=C1S\C=C\C(=O)NC1C(CC2)CCN2C1 LTYPMDPWOZGHRI-DHZHZOJOSA-N 0.000 claims description 2
- VRAGHHQHEMRZLW-WEVVVXLNSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(2-methylfuran-3-yl)sulfanylprop-2-enamide Chemical compound O1C=CC(S\C=C\C(=O)NC2C3CCN(CC3)C2)=C1C VRAGHHQHEMRZLW-WEVVVXLNSA-N 0.000 claims description 2
- KDQHLQDGSUEZLO-DHZHZOJOSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(2-methylphenyl)sulfanylprop-2-enamide Chemical compound CC1=CC=CC=C1S\C=C\C(=O)NC1C(CC2)CCN2C1 KDQHLQDGSUEZLO-DHZHZOJOSA-N 0.000 claims description 2
- JQEIDFKXAIOCOT-RMKNXTFCSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(3-fluorophenyl)sulfanylprop-2-enamide Chemical compound FC1=CC=CC(S\C=C\C(=O)NC2C3CCN(CC3)C2)=C1 JQEIDFKXAIOCOT-RMKNXTFCSA-N 0.000 claims description 2
- KDTOXPBRVFGSBE-JXMROGBWSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(3-methoxyphenyl)sulfanylprop-2-enamide Chemical compound COC1=CC=CC(S\C=C\C(=O)NC2C3CCN(CC3)C2)=C1 KDTOXPBRVFGSBE-JXMROGBWSA-N 0.000 claims description 2
- WLZQYKJPCDLBLY-JXMROGBWSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(3-methylphenyl)sulfanylprop-2-enamide Chemical compound CC1=CC=CC(S\C=C\C(=O)NC2C3CCN(CC3)C2)=C1 WLZQYKJPCDLBLY-JXMROGBWSA-N 0.000 claims description 2
- KTQRXHIDICAXBQ-JXMROGBWSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(4-fluorophenyl)sulfanylprop-2-enamide Chemical compound C1=CC(F)=CC=C1S\C=C\C(=O)NC1C(CC2)CCN2C1 KTQRXHIDICAXBQ-JXMROGBWSA-N 0.000 claims description 2
- SCMNIXVFVRESKS-DHZHZOJOSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(4-methoxyphenyl)sulfanylprop-2-enamide Chemical compound C1=CC(OC)=CC=C1S\C=C\C(=O)NC1C(CC2)CCN2C1 SCMNIXVFVRESKS-DHZHZOJOSA-N 0.000 claims description 2
- HFGGWDUKVDQHAF-DHZHZOJOSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(4-methylphenyl)sulfanylprop-2-enamide Chemical compound C1=CC(C)=CC=C1S\C=C\C(=O)NC1C(CC2)CCN2C1 HFGGWDUKVDQHAF-DHZHZOJOSA-N 0.000 claims description 2
- JWTLOTLUZAUDNW-QPJJXVBHSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]prop-2-enamide Chemical compound S1C(C)=NN=C1S\C=C\C(=O)NC1C(CC2)CCN2C1 JWTLOTLUZAUDNW-QPJJXVBHSA-N 0.000 claims description 2
- KZSCMMXQCHXNIV-UXBLZVDNSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-pyridin-2-ylsulfanylprop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C\SC1=CC=CC=N1 KZSCMMXQCHXNIV-UXBLZVDNSA-N 0.000 claims description 2
- PESOSIYLBKVXMY-BJMVGYQFSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-pyridin-4-ylsulfanylprop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C\SC1=CC=NC=C1 PESOSIYLBKVXMY-BJMVGYQFSA-N 0.000 claims description 2
- GJKBMIXSYCLYRG-RUDMXATFSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-pyrimidin-2-ylsulfanylprop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C\SC1=NC=CC=N1 GJKBMIXSYCLYRG-RUDMXATFSA-N 0.000 claims description 2
- WNQKTIKCUDTAKX-WEVVVXLNSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-thiophen-2-ylsulfanylprop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C\SC1=CC=CS1 WNQKTIKCUDTAKX-WEVVVXLNSA-N 0.000 claims description 2
- OVBCUYMXSLVZNW-YFHOEESVSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(1,3-benzothiazol-2-ylsulfanyl)prop-2-enamide Chemical compound C1=CC=C2SC(S\C=C/C(NC3C4CCN(CC4)C3)=O)=NC2=C1 OVBCUYMXSLVZNW-YFHOEESVSA-N 0.000 claims description 2
- DFRCDJNMANEUOX-YFHOEESVSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(1,3-benzoxazol-2-ylsulfanyl)prop-2-enamide Chemical compound C1=CC=C2OC(S\C=C/C(NC3C4CCN(CC4)C3)=O)=NC2=C1 DFRCDJNMANEUOX-YFHOEESVSA-N 0.000 claims description 2
- UAHBYMCLKLVWDR-CLTKARDFSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(1,3-thiazol-2-ylsulfanyl)prop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C/SC1=NC=CS1 UAHBYMCLKLVWDR-CLTKARDFSA-N 0.000 claims description 2
- ISFXODZDHSDPLN-WTKPLQERSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(1-methylimidazol-2-yl)sulfanylprop-2-enamide Chemical compound CN1C=CN=C1S\C=C/C(=O)NC1C(CC2)CCN2C1 ISFXODZDHSDPLN-WTKPLQERSA-N 0.000 claims description 2
- LTYPMDPWOZGHRI-FLIBITNWSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(2-methoxyphenyl)sulfanylprop-2-enamide Chemical compound COC1=CC=CC=C1S\C=C/C(=O)NC1C(CC2)CCN2C1 LTYPMDPWOZGHRI-FLIBITNWSA-N 0.000 claims description 2
- VRAGHHQHEMRZLW-UITAMQMPSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(2-methylfuran-3-yl)sulfanylprop-2-enamide Chemical compound O1C=CC(S\C=C/C(=O)NC2C3CCN(CC3)C2)=C1C VRAGHHQHEMRZLW-UITAMQMPSA-N 0.000 claims description 2
- KDQHLQDGSUEZLO-FLIBITNWSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(2-methylphenyl)sulfanylprop-2-enamide Chemical compound CC1=CC=CC=C1S\C=C/C(=O)NC1C(CC2)CCN2C1 KDQHLQDGSUEZLO-FLIBITNWSA-N 0.000 claims description 2
- JQEIDFKXAIOCOT-TWGQIWQCSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(3-fluorophenyl)sulfanylprop-2-enamide Chemical compound FC1=CC=CC(S\C=C/C(=O)NC2C3CCN(CC3)C2)=C1 JQEIDFKXAIOCOT-TWGQIWQCSA-N 0.000 claims description 2
- KDTOXPBRVFGSBE-YFHOEESVSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(3-methoxyphenyl)sulfanylprop-2-enamide Chemical compound COC1=CC=CC(S\C=C/C(=O)NC2C3CCN(CC3)C2)=C1 KDTOXPBRVFGSBE-YFHOEESVSA-N 0.000 claims description 2
- WLZQYKJPCDLBLY-YFHOEESVSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(3-methylphenyl)sulfanylprop-2-enamide Chemical compound CC1=CC=CC(S\C=C/C(=O)NC2C3CCN(CC3)C2)=C1 WLZQYKJPCDLBLY-YFHOEESVSA-N 0.000 claims description 2
- UEOWRBUHJNVLTL-YFHOEESVSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(4-chlorophenyl)sulfanylprop-2-enamide Chemical compound C1=CC(Cl)=CC=C1S\C=C/C(=O)NC1C(CC2)CCN2C1 UEOWRBUHJNVLTL-YFHOEESVSA-N 0.000 claims description 2
- KTQRXHIDICAXBQ-YFHOEESVSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(4-fluorophenyl)sulfanylprop-2-enamide Chemical compound C1=CC(F)=CC=C1S\C=C/C(=O)NC1C(CC2)CCN2C1 KTQRXHIDICAXBQ-YFHOEESVSA-N 0.000 claims description 2
- SCMNIXVFVRESKS-FLIBITNWSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(4-methoxyphenyl)sulfanylprop-2-enamide Chemical compound C1=CC(OC)=CC=C1S\C=C/C(=O)NC1C(CC2)CCN2C1 SCMNIXVFVRESKS-FLIBITNWSA-N 0.000 claims description 2
- HFGGWDUKVDQHAF-FLIBITNWSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(4-methylphenyl)sulfanylprop-2-enamide Chemical compound C1=CC(C)=CC=C1S\C=C/C(=O)NC1C(CC2)CCN2C1 HFGGWDUKVDQHAF-FLIBITNWSA-N 0.000 claims description 2
- ICLMIHKBDLBDCI-UITAMQMPSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-([1,3]thiazolo[4,5-b]pyridin-2-ylsulfanyl)prop-2-enamide Chemical compound C1=CC=C2SC(S\C=C/C(NC3C4CCN(CC4)C3)=O)=NC2=N1 ICLMIHKBDLBDCI-UITAMQMPSA-N 0.000 claims description 2
- UFEDAHQDKOLAQK-YWEYNIOJSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-[4-(trifluoromethyl)pyrimidin-2-yl]sulfanylprop-2-enamide Chemical compound FC(F)(F)C1=CC=NC(S\C=C/C(=O)NC2C3CCN(CC3)C2)=N1 UFEDAHQDKOLAQK-YWEYNIOJSA-N 0.000 claims description 2
- VRUSTLVHEAFHJV-QBFSEMIESA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-phenylsulfanylbut-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)/C=C(/C)SC1=CC=CC=C1 VRUSTLVHEAFHJV-QBFSEMIESA-N 0.000 claims description 2
- KZSCMMXQCHXNIV-POHAHGRESA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-pyridin-2-ylsulfanylprop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C/SC1=CC=CC=N1 KZSCMMXQCHXNIV-POHAHGRESA-N 0.000 claims description 2
- PESOSIYLBKVXMY-YHYXMXQVSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-pyridin-4-ylsulfanylprop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C/SC1=CC=NC=C1 PESOSIYLBKVXMY-YHYXMXQVSA-N 0.000 claims description 2
- GJKBMIXSYCLYRG-WTKPLQERSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-pyrimidin-2-ylsulfanylprop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C/SC1=NC=CC=N1 GJKBMIXSYCLYRG-WTKPLQERSA-N 0.000 claims description 2
- WNQKTIKCUDTAKX-UITAMQMPSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-thiophen-2-ylsulfanylprop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C/SC1=CC=CS1 WNQKTIKCUDTAKX-UITAMQMPSA-N 0.000 claims description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 101100240516 Caenorhabditis elegans nhr-10 gene Proteins 0.000 claims description 2
- 208000018737 Parkinson disease Diseases 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 239000003701 inert diluent Substances 0.000 claims description 2
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 2
- 230000005586 smoking cessation Effects 0.000 claims description 2
- 230000000391 smoking effect Effects 0.000 claims description 2
- 208000009829 Lewy Body Disease Diseases 0.000 claims 4
- 201000002832 Lewy body dementia Diseases 0.000 claims 4
- 230000004913 activation Effects 0.000 claims 2
- 230000009286 beneficial effect Effects 0.000 claims 2
- 230000007278 cognition impairment Effects 0.000 claims 2
- 231100000863 loss of memory Toxicity 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 38
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 40
- 239000002253 acid Substances 0.000 description 31
- 239000000203 mixture Substances 0.000 description 26
- 230000015572 biosynthetic process Effects 0.000 description 24
- 239000003480 eluent Substances 0.000 description 24
- OXHBMBUYHWMWKM-UHFFFAOYSA-N n-(4-bromo-2-methoxyphenyl)acetamide Chemical compound COC1=CC(Br)=CC=C1NC(C)=O OXHBMBUYHWMWKM-UHFFFAOYSA-N 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 23
- 238000004587 chromatography analysis Methods 0.000 description 23
- 239000000741 silica gel Substances 0.000 description 23
- 229910002027 silica gel Inorganic materials 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- 239000002904 solvent Substances 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 229930182840 (S)-nicotine Natural products 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
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- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
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- 239000005977 Ethylene Substances 0.000 description 1
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- 125000004122 cyclic group Chemical group 0.000 description 1
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- 238000002474 experimental method Methods 0.000 description 1
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- 238000004108 freeze drying Methods 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
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- 239000011541 reaction mixture Substances 0.000 description 1
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
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- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
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- 235000011152 sodium sulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
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- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 239000004149 tartrazine Substances 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
-
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Psychology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9903760A SE9903760D0 (sv) | 1999-10-18 | 1999-10-18 | New compounds |
| SE9903760 | 1999-10-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2204711T3 true ES2204711T3 (es) | 2004-05-01 |
Family
ID=20417402
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES00971959T Expired - Lifetime ES2204711T3 (es) | 1999-10-18 | 2000-10-13 | Acrilamidas de quinuclidina. |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US6642246B1 (https=) |
| EP (1) | EP1235826B1 (https=) |
| JP (1) | JP2003512374A (https=) |
| AT (1) | ATE248837T1 (https=) |
| AU (1) | AU1069001A (https=) |
| CO (1) | CO5271691A1 (https=) |
| DE (1) | DE60005054T2 (https=) |
| DK (1) | DK1235826T3 (https=) |
| ES (1) | ES2204711T3 (https=) |
| HK (1) | HK1048313B (https=) |
| MY (1) | MY136240A (https=) |
| PT (1) | PT1235826E (https=) |
| SE (1) | SE9903760D0 (https=) |
| WO (1) | WO2001029034A1 (https=) |
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6486172B2 (en) | 2000-08-18 | 2002-11-26 | Pharmacia & Upjohn Company | Quinuclidine-substituted aryl compounds for treatment of disease |
| US6479510B2 (en) | 2000-08-18 | 2002-11-12 | Pharmacia & Upjohn Company | Quinuclidine-substituted aryl compounds for treatment of disease |
| US6492386B2 (en) * | 2000-08-18 | 2002-12-10 | Pharmacia & Upjohn Company | Quinuclidine-substituted aryl compounds for treatment of disease |
| PE20021019A1 (es) | 2001-04-19 | 2002-11-13 | Upjohn Co | Grupos azabiciclicos sustituidos |
| BR0212101A (pt) | 2001-08-24 | 2004-08-24 | Pharmacia & Up John Company | 7-aza [2.2.1] biciclo-heptanos substituìdos com heteroarila para o tratamento de doenças |
| AU2002339810A1 (en) * | 2001-10-16 | 2003-04-28 | Astrazeneca Ab | Azabicyclic compounds for the treatment of fibromyalgia syndrome |
| US6951868B2 (en) | 2001-11-09 | 2005-10-04 | Pfizer Inc. | Azabicyclic-phenyl-fused-heterocyclic compounds for treatment of disease |
| DE10164139A1 (de) | 2001-12-27 | 2003-07-10 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
| US6852716B2 (en) | 2002-02-15 | 2005-02-08 | Pfizer Inc | Substituted-aryl compounds for treatment of disease |
| JP2005523288A (ja) | 2002-02-19 | 2005-08-04 | ファルマシア・アンド・アップジョン・カンパニー・エルエルシー | 疾病治療用の縮合した二環式−ｎ−架橋−複素環式芳香族カルボキサミド |
| GB0220581D0 (en) | 2002-09-04 | 2002-10-09 | Novartis Ag | Organic Compound |
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| PE20060437A1 (es) | 2004-06-18 | 2006-06-08 | Novartis Ag | COMPUESTOS AZA-BICICLONONANOS COMO LIGANDOS COLINERGICOS DE nAChR |
| GB0415746D0 (en) | 2004-07-14 | 2004-08-18 | Novartis Ag | Organic compounds |
| GB0424564D0 (en) | 2004-11-05 | 2004-12-08 | Novartis Ag | Organic compounds |
| RU2418797C2 (ru) | 2004-12-22 | 2011-05-20 | Мемори Фармасьютиклз Корпорейшн | Лиганды никотинового рецептора альфа-7, их получение и применение |
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| GB0521508D0 (en) | 2005-10-21 | 2005-11-30 | Novartis Ag | Organic compounds |
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| GB0525673D0 (en) | 2005-12-16 | 2006-01-25 | Novartis Ag | Organic compounds |
| RS52561B (sr) * | 2008-04-15 | 2013-04-30 | Eisai R&D Management Co., Ltd. | Jedinjenje 3-fenilpirazolo[5,1-b]tiazol |
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| EP2243476A1 (en) * | 2009-04-17 | 2010-10-27 | Centre National de la Recherche Scientifique | Compounds for the treatment of mitochondrial diseases |
| AR078521A1 (es) * | 2009-10-08 | 2011-11-16 | Eisai R&D Man Co Ltd | Compuesto pirazolotiazol |
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| GB201111705D0 (en) | 2011-07-07 | 2011-08-24 | Takeda Pharmaceutical | Compounds and their use |
| JO3115B1 (ar) | 2011-08-22 | 2017-09-20 | Takeda Pharmaceuticals Co | مركبات بيريدازينون واستخدامها كمثبطات daao |
| CA2872005A1 (en) | 2012-05-08 | 2013-11-14 | Forum Pharmaceuticals, Inc. | Methods of maintaining, treating or improving cognitive function |
| GB201209587D0 (en) | 2012-05-30 | 2012-07-11 | Takeda Pharmaceutical | Therapeutic compounds |
| WO2014122474A1 (en) | 2013-02-07 | 2014-08-14 | Takeda Pharmaceutical Company Limited | Piperidin-1 -yl and azepin-1 -yl carboxylates as muscarinic m4 receptor agonists |
| HK1219722A1 (zh) | 2013-06-21 | 2017-04-13 | Takeda Pharmaceutical Company Limited | 1-磺酰基派啶衍生物作为前动力蛋白受体的调节剂 |
| GB201314286D0 (en) | 2013-08-08 | 2013-09-25 | Takeda Pharmaceutical | Therapeutic Compounds |
| GB201318222D0 (en) | 2013-10-15 | 2013-11-27 | Takeda Pharmaceutical | Novel compounds |
| GB201320905D0 (en) | 2013-11-27 | 2014-01-08 | Takeda Pharmaceutical | Therapeutic compounds |
| TW201613864A (en) | 2014-02-20 | 2016-04-16 | Takeda Pharmaceutical | Novel compounds |
| CN103923105B (zh) * | 2014-04-17 | 2016-08-24 | 北京大学 | 2-中氮茚甲酰胺类化合物及其制备和用途 |
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| JP2021138648A (ja) | 2020-03-04 | 2021-09-16 | 武田薬品工業株式会社 | 経口固形製剤 |
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Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1255467B (it) | 1992-07-29 | 1995-11-02 | Dompe Farmaceutici Spa | Ammidi acriliche farmacologicamente attive |
| GB9304500D0 (en) | 1993-03-05 | 1993-04-21 | Glaxo Spa | Heterocyclic compounds |
| US5981525A (en) | 1995-01-10 | 1999-11-09 | Smithkline Beecham Corporation | Indole derivatives useful in the treatment of osteoporosis |
| JPH11512443A (ja) * | 1995-09-22 | 1999-10-26 | ノボ ノルディスク アクティーゼルスカブ | 新規な置換アザ環式またはアザ二環式化合物 |
| ES2229375T3 (es) * | 1996-07-09 | 2005-04-16 | Nikem Research S.R.L. | Derivados del indol para el tratamiento de la osteoporosis. |
-
1999
- 1999-10-18 SE SE9903760A patent/SE9903760D0/xx unknown
-
2000
- 2000-10-13 JP JP2001531833A patent/JP2003512374A/ja active Pending
- 2000-10-13 DK DK00971959T patent/DK1235826T3/da active
- 2000-10-13 AT AT00971959T patent/ATE248837T1/de active
- 2000-10-13 HK HK03100456.4A patent/HK1048313B/en not_active IP Right Cessation
- 2000-10-13 EP EP00971959A patent/EP1235826B1/en not_active Expired - Lifetime
- 2000-10-13 WO PCT/SE2000/001993 patent/WO2001029034A1/en not_active Ceased
- 2000-10-13 AU AU10690/01A patent/AU1069001A/en not_active Abandoned
- 2000-10-13 ES ES00971959T patent/ES2204711T3/es not_active Expired - Lifetime
- 2000-10-13 PT PT00971959T patent/PT1235826E/pt unknown
- 2000-10-13 US US10/110,663 patent/US6642246B1/en not_active Expired - Fee Related
- 2000-10-13 DE DE60005054T patent/DE60005054T2/de not_active Expired - Lifetime
- 2000-10-16 MY MYPI20004849A patent/MY136240A/en unknown
- 2000-10-17 CO CO00078738A patent/CO5271691A1/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| AU1069001A (en) | 2001-04-30 |
| EP1235826A1 (en) | 2002-09-04 |
| SE9903760D0 (sv) | 1999-10-18 |
| MY136240A (en) | 2008-08-29 |
| WO2001029034A1 (en) | 2001-04-26 |
| DE60005054D1 (de) | 2003-10-09 |
| CO5271691A1 (es) | 2003-04-30 |
| PT1235826E (pt) | 2004-01-30 |
| HK1048313A1 (en) | 2003-03-28 |
| ATE248837T1 (de) | 2003-09-15 |
| HK1048313B (en) | 2003-12-24 |
| DE60005054T2 (de) | 2004-07-08 |
| JP2003512374A (ja) | 2003-04-02 |
| EP1235826B1 (en) | 2003-09-03 |
| US6642246B1 (en) | 2003-11-04 |
| DK1235826T3 (da) | 2003-11-24 |
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