ES2204295B1 - Nuevos derivados de quinuclidina-amida. - Google Patents
Nuevos derivados de quinuclidina-amida.Info
- Publication number
- ES2204295B1 ES2204295B1 ES200201539A ES200201539A ES2204295B1 ES 2204295 B1 ES2204295 B1 ES 2204295B1 ES 200201539 A ES200201539 A ES 200201539A ES 200201539 A ES200201539 A ES 200201539A ES 2204295 B1 ES2204295 B1 ES 2204295B1
- Authority
- ES
- Spain
- Prior art keywords
- hydroxy
- group
- octane
- azoniabicyclo
- azabicyclo
- 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 - Fee Related
Links
- OZCJTNLELXWUTQ-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octane-2-carboxamide Chemical class C1CN2C(C(=O)N)CC1CC2 OZCJTNLELXWUTQ-UHFFFAOYSA-N 0.000 title claims abstract description 9
- 238000000034 method Methods 0.000 claims abstract description 83
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 102000007202 Muscarinic M3 Receptor Human genes 0.000 claims abstract description 8
- 108010008405 Muscarinic M3 Receptor Proteins 0.000 claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims description 139
- -1 hydroxy, methyl Chemical group 0.000 claims description 63
- 239000000203 mixture Substances 0.000 claims description 44
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 21
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 17
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 16
- 201000010099 disease Diseases 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 125000005843 halogen group Chemical group 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 13
- 125000004122 cyclic group Chemical group 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 125000004429 atom Chemical group 0.000 claims description 9
- ZJSWMRJWTWJORH-ZDUSSCGKSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-2-hydroxy-2,2-dithiophen-2-ylacetamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 ZJSWMRJWTWJORH-ZDUSSCGKSA-N 0.000 claims description 9
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 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 description 7
- 239000003814 drug Substances 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 7
- PSFULERNVNPNAD-UHFFFAOYSA-N n-(1-azabicyclo[2.2.2]octan-3-yl)-9-hydroxyfluorene-9-carboxamide Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1(O)C(=O)NC1C(CC2)CCN2C1 PSFULERNVNPNAD-UHFFFAOYSA-N 0.000 claims description 7
- RRBQMQSYNDZVOX-UHFFFAOYSA-N n-(1-azabicyclo[2.2.2]octan-3-yl)-9h-xanthene-9-carboxamide Chemical compound C12=CC=CC=C2OC2=CC=CC=C2C1C(=O)NC1C(CC2)CCN2C1 RRBQMQSYNDZVOX-UHFFFAOYSA-N 0.000 claims description 7
- RRBQMQSYNDZVOX-KRWDZBQOSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-9h-xanthene-9-carboxamide Chemical compound C12=CC=CC=C2OC2=CC=CC=C2C1C(=O)N[C@@H]1C(CC2)CCN2C1 RRBQMQSYNDZVOX-KRWDZBQOSA-N 0.000 claims description 7
- RRBQMQSYNDZVOX-QGZVFWFLSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-9h-xanthene-9-carboxamide Chemical compound C12=CC=CC=C2OC2=CC=CC=C2C1C(=O)N[C@H]1C(CC2)CCN2C1 RRBQMQSYNDZVOX-QGZVFWFLSA-N 0.000 claims description 7
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical group C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 claims description 7
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- 150000001450 anions Chemical class 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000001072 heteroaryl group Chemical group 0.000 claims description 6
- ZJSWMRJWTWJORH-UHFFFAOYSA-N n-(1-azabicyclo[2.2.2]octan-3-yl)-2-hydroxy-2,2-dithiophen-2-ylacetamide Chemical compound C1N(CC2)CCC2C1NC(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 ZJSWMRJWTWJORH-UHFFFAOYSA-N 0.000 claims description 6
- MRVIDGHWQMMOKY-LBAQZLPGSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-2,3-diphenylpropanamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)C(C=1C=CC=CC=1)CC1=CC=CC=C1 MRVIDGHWQMMOKY-LBAQZLPGSA-N 0.000 claims description 6
- KAAGSRJOWSBERT-LROBGIAVSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-2-cyclopentyl-2-hydroxy-2-phenylacetamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)C(C=1C=CC=CC=1)(O)C1CCCC1 KAAGSRJOWSBERT-LROBGIAVSA-N 0.000 claims description 6
- MFPPFFMHFODFQO-KNVGNIICSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-2-hydroxy-2-thiophen-2-ylpent-4-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)C(CC=C)(O)C1=CC=CS1 MFPPFFMHFODFQO-KNVGNIICSA-N 0.000 claims description 6
- JWODCCLBIXEZOF-OGZJWECNSA-N n-[(3s)-1-(cyclohexylmethyl)-1-azoniabicyclo[2.2.2]octan-3-yl]-9h-xanthene-9-carboxamide;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@H](C(CC1)CC2)NC(=O)C3C4=CC=CC=C4OC4=CC=CC=C43)[N+]21CC1CCCCC1 JWODCCLBIXEZOF-OGZJWECNSA-N 0.000 claims description 6
- ZJSWMRJWTWJORH-CYBMUJFWSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-2-hydroxy-2,2-dithiophen-2-ylacetamide Chemical compound N([C@H]1C2CCN(CC2)C1)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 ZJSWMRJWTWJORH-CYBMUJFWSA-N 0.000 claims description 6
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims description 6
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 6
- KTLRLWOABDNXBI-UHFFFAOYSA-N 9-hydroxy-n-(1-methyl-1-azoniabicyclo[2.2.2]octan-3-yl)fluorene-9-carboxamide;bromide Chemical compound [Br-].C12=CC=CC=C2C2=CC=CC=C2C1(O)C(=O)NC(C1)C2CC[N+]1(C)CC2 KTLRLWOABDNXBI-UHFFFAOYSA-N 0.000 claims description 5
- 125000003368 amide group Chemical group 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 208000035475 disorder Diseases 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- MDSAFGBQDVEKGD-ZDUSSCGKSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-2,2-dithiophen-2-ylacetamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)C(C=1SC=CC=1)C1=CC=CS1 MDSAFGBQDVEKGD-ZDUSSCGKSA-N 0.000 claims description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 5
- 229920002554 vinyl polymer Polymers 0.000 claims description 5
- HMMFYOXCKMHKFL-JXJWEVJGSA-N 2-hydroxy-n-[(3r)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl]-2,2-dithiophen-2-ylacetamide;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)NC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CCCOC1=CC=CC=C1 HMMFYOXCKMHKFL-JXJWEVJGSA-N 0.000 claims description 4
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 4
- 230000008485 antagonism Effects 0.000 claims description 4
- 229910052749 magnesium Inorganic materials 0.000 claims description 4
- 230000000241 respiratory effect Effects 0.000 claims description 4
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 claims description 3
- YZCFWWYSYVLNNC-DVWUEADGSA-N 2-hydroxy-2,2-dithiophen-2-yl-n-[(3r)-1-(3-thiophen-2-ylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl]acetamide;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)NC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CCCC1=CC=CS1 YZCFWWYSYVLNNC-DVWUEADGSA-N 0.000 claims description 3
- KAMDIYYBDDEUPF-UHFFFAOYSA-N 2-hydroxy-n-(1-methyl-1-azoniabicyclo[2.2.2]octan-3-yl)-2,2-dithiophen-2-ylacetamide;bromide Chemical compound [Br-].C1C[N+](C)(C2)CCC1C2NC(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 KAMDIYYBDDEUPF-UHFFFAOYSA-N 0.000 claims description 3
- QTQTVZHMXYTWLO-OUIHKFQYSA-N 2-hydroxy-n-[(3r)-1-(2-phenoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl]-2,2-dithiophen-2-ylacetamide;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)NC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CCOC1=CC=CC=C1 QTQTVZHMXYTWLO-OUIHKFQYSA-N 0.000 claims description 3
- FCKGLDDAFOKBPB-XPTDNKBGSA-N 2-hydroxy-n-[(3r)-1-(2-phenylmethoxyethyl)-1-azoniabicyclo[2.2.2]octan-3-yl]-2,2-dithiophen-2-ylacetamide;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)NC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CCOCC1=CC=CC=C1 FCKGLDDAFOKBPB-XPTDNKBGSA-N 0.000 claims description 3
- ZOQNBZKVHYFHGD-XPTDNKBGSA-N 2-hydroxy-n-[(3r)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl]-2,2-dithiophen-2-ylacetamide;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)NC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CCCC1=CC=CC=C1 ZOQNBZKVHYFHGD-XPTDNKBGSA-N 0.000 claims description 3
- UODVIQPJYLVBDW-IZDPNCFFSA-N 2-hydroxy-n-[(3r)-1-methyl-1-azoniabicyclo[2.2.2]octan-3-yl]-2,2-dithiophen-2-ylacetamide;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.N([C@@H]1C2CC[N+](CC2)(C1)C)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 UODVIQPJYLVBDW-IZDPNCFFSA-N 0.000 claims description 3
- HMMFYOXCKMHKFL-PIJXPWFJSA-N 2-hydroxy-n-[(3s)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl]-2,2-dithiophen-2-ylacetamide;bromide Chemical compound [Br-].C([C@H](C(CC1)CC2)NC(=O)C(O)(C=3SC=CC=3)C=3SC=CC=3)[N+]21CCCOC1=CC=CC=C1 HMMFYOXCKMHKFL-PIJXPWFJSA-N 0.000 claims description 3
- HMMFYOXCKMHKFL-UHFFFAOYSA-N 2-hydroxy-n-[1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl]-2,2-dithiophen-2-ylacetamide;bromide Chemical compound [Br-].C=1C=CSC=1C(C=1SC=CC=1)(O)C(=O)NC(C(CC1)CC2)C[N+]21CCCOC1=CC=CC=C1 HMMFYOXCKMHKFL-UHFFFAOYSA-N 0.000 claims description 3
- IBDTWHHILKDNOJ-UHFFFAOYSA-N 9-hydroxy-n-[1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl]fluorene-9-carboxamide;bromide Chemical compound [Br-].C12=CC=CC=C2C2=CC=CC=C2C1(O)C(=O)NC(C(CC1)CC2)C[N+]21CCCOC1=CC=CC=C1 IBDTWHHILKDNOJ-UHFFFAOYSA-N 0.000 claims description 3
- 239000002168 alkylating agent Substances 0.000 claims description 3
- 229940100198 alkylating agent Drugs 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 230000002496 gastric effect Effects 0.000 claims description 3
- PMGRKYSNXBOJBZ-UHFFFAOYSA-N n-(1-methyl-1-azoniabicyclo[2.2.2]octan-3-yl)-9h-xanthene-9-carboxamide;bromide Chemical compound [Br-].C12=CC=CC=C2OC2=CC=CC=C2C1C(=O)NC(C1)C2CC[N+]1(C)CC2 PMGRKYSNXBOJBZ-UHFFFAOYSA-N 0.000 claims description 3
- WVXIGPWCHZXWDZ-JXJWEVJGSA-N n-[(3r)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl]-2,2-dithiophen-2-ylacetamide;bromide Chemical compound [Br-].C([C@@H](C(CC1)CC2)NC(=O)C(C=3SC=CC=3)C=3SC=CC=3)[N+]21CCCOC1=CC=CC=C1 WVXIGPWCHZXWDZ-JXJWEVJGSA-N 0.000 claims description 3
- MCKIVQDSUKIVKB-CBTJMOJFSA-N n-[(3r)-1-heptyl-1-azoniabicyclo[2.2.2]octan-3-yl]-2-hydroxy-2,2-dithiophen-2-ylacetamide;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.N([C@@H]1C2CC[N+](CC2)(C1)CCCCCCC)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 MCKIVQDSUKIVKB-CBTJMOJFSA-N 0.000 claims description 3
- YTFWEOSNHWESFV-ZFFIDOFDSA-N n-[(3s)-1-(3-cyclohexylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl]-9h-xanthene-9-carboxamide;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@H](C(CC1)CC2)NC(=O)C3C4=CC=CC=C4OC4=CC=CC=C43)[N+]21CCCC1CCCCC1 YTFWEOSNHWESFV-ZFFIDOFDSA-N 0.000 claims description 3
- RYPRTVDFRFJHLK-CMYKPJMLSA-N n-[(3s)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl]-9h-xanthene-9-carboxamide;bromide Chemical compound [Br-].C([C@H](C(CC1)CC2)NC(=O)C3C4=CC=CC=C4OC4=CC=CC=C43)[N+]21CCCOC1=CC=CC=C1 RYPRTVDFRFJHLK-CMYKPJMLSA-N 0.000 claims description 3
- QDUZTLAXEGKHHE-SIMUOUHCSA-N n-[(3s)-1-[3-(5,6,7,8-tetrahydronaphthalen-2-yloxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl]-9h-xanthene-9-carboxamide;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C12=CC=CC=C2OC2=CC=CC=C2C1C(=O)N[C@H]1C(CC2)CC[N+]2(CCCOC=2C=C3CCCCC3=CC=2)C1 QDUZTLAXEGKHHE-SIMUOUHCSA-N 0.000 claims description 3
- ZOKIJORBLPTITO-WWTZQNKJSA-N n-[(3s)-1-[5-(2,6-dimethylphenoxy)pentyl]-1-azoniabicyclo[2.2.2]octan-3-yl]-9h-xanthene-9-carboxamide;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.CC1=CC=CC(C)=C1OCCCCC[N+]1(C[C@H]2NC(=O)C3C4=CC=CC=C4OC4=CC=CC=C43)CCC2CC1 ZOKIJORBLPTITO-WWTZQNKJSA-N 0.000 claims description 3
- FCFNFLWTBVTCIX-OGZJWECNSA-N n-[(3s)-1-heptyl-1-azoniabicyclo[2.2.2]octan-3-yl]-9h-xanthene-9-carboxamide;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C12=CC=CC=C2OC2=CC=CC=C2C1C(=O)N[C@H](C1)C2CC[N+]1(CCCCCCC)CC2 FCFNFLWTBVTCIX-OGZJWECNSA-N 0.000 claims description 3
- RYPRTVDFRFJHLK-UHFFFAOYSA-N n-[1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl]-9h-xanthene-9-carboxamide;bromide Chemical compound [Br-].C12=CC=CC=C2OC2=CC=CC=C2C1C(=O)NC(C(CC1)CC2)C[N+]21CCCOC1=CC=CC=C1 RYPRTVDFRFJHLK-UHFFFAOYSA-N 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 125000006017 1-propenyl group Chemical group 0.000 claims description 2
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 2
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 150000003840 hydrochlorides Chemical class 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- LBUPGUUEUUAALH-UHFFFAOYSA-N n-(1-azabicyclo[2.2.2]octan-3-yl)-2-oxo-2-thiophen-2-ylacetamide Chemical compound C1N(CC2)CCC2C1NC(=O)C(=O)C1=CC=CS1 LBUPGUUEUUAALH-UHFFFAOYSA-N 0.000 claims description 2
- LBUPGUUEUUAALH-SNVBAGLBSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-2-oxo-2-thiophen-2-ylacetamide Chemical compound N([C@H]1C2CCN(CC2)C1)C(=O)C(=O)C1=CC=CS1 LBUPGUUEUUAALH-SNVBAGLBSA-N 0.000 claims description 2
- 125000002524 organometallic group Chemical group 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 239000008024 pharmaceutical diluent Substances 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 3
- 230000001575 pathological effect Effects 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 22
- 239000005557 antagonist Substances 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 3
- 238000002560 therapeutic procedure Methods 0.000 abstract description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 38
- 239000000243 solution Substances 0.000 description 26
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
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- BUVFUKGWZXJAOZ-DONHNUADSA-N n-[(3r)-1-(3-amino-3-oxopropyl)-1-azoniabicyclo[2.2.2]octan-3-yl]-2-hydroxy-2-thiophen-2-ylpent-4-enamide;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.N([C@@H]1C2CC[N+](CC2)(C1)CCC(=O)N)C(=O)C(O)(CC=C)C1=CC=CS1 BUVFUKGWZXJAOZ-DONHNUADSA-N 0.000 description 1
- LDIDOSSNHCVRLI-GFUFQGNZSA-N n-[(3r)-1-(3-cyanopropyl)-1-azoniabicyclo[2.2.2]octan-3-yl]-2-hydroxy-2-phenyl-2-thiophen-2-ylacetamide;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.N([C@@H]1C2CC[N+](CC2)(CCCC#N)C1)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CS1 LDIDOSSNHCVRLI-GFUFQGNZSA-N 0.000 description 1
- XVAGDUYMEKIXPM-AFQVKWIVSA-N n-[(3r)-1-[3-(1,3-benzothiazol-2-yloxy)propyl]-1-azoniabicyclo[2.2.2]octan-3-yl]-2-hydroxy-2-phenyl-2-thiophen-2-ylacetamide;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.N([C@@H]1C2CC[N+](CC2)(CCCOC=2SC3=CC=CC=C3N=2)C1)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CS1 XVAGDUYMEKIXPM-AFQVKWIVSA-N 0.000 description 1
- ODMATUGAOCKIGY-SJEMYQCASA-N n-[(3r)-1-[4-(4-fluorophenyl)-4-oxobutyl]-1-azoniabicyclo[2.2.2]octan-3-yl]-9-hydroxyfluorene-9-carboxamide;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C([C@@H](C(CC1)CC2)NC(=O)C3(O)C4=CC=CC=C4C4=CC=CC=C43)[N+]21CCCC(=O)C1=CC=C(F)C=C1 ODMATUGAOCKIGY-SJEMYQCASA-N 0.000 description 1
- UMZFFLLCFIKQSR-DJZRFWRSSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-2-(5-bromothiophen-2-yl)-2-(4-fluoro-3-methylphenyl)-2-hydroxyacetamide Chemical compound C1=C(F)C(C)=CC(C(O)(C(=O)N[C@@H]2C3CCN(CC3)C2)C=2SC(Br)=CC=2)=C1 UMZFFLLCFIKQSR-DJZRFWRSSA-N 0.000 description 1
- QSFVQDXXWKQPKI-MBIQTGHCSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-2-(furan-3-yl)-2-hydroxy-2-thiophen-2-ylacetamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)C(O)(C=1SC=CC=1)C=1C=COC=1 QSFVQDXXWKQPKI-MBIQTGHCSA-N 0.000 description 1
- QKYYSDPGTMVINO-KKFHFHRHSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-2-cyclohexyl-2-hydroxy-2-thiophen-3-ylacetamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)C(C1=CSC=C1)(O)C1CCCCC1 QKYYSDPGTMVINO-KKFHFHRHSA-N 0.000 description 1
- LGZKEUFXLRXCRP-UCFFOFKASA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-2-hydroxy-2-phenyl-2-thiophen-2-ylacetamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)C(O)(C=1C=CC=CC=1)C1=CC=CS1 LGZKEUFXLRXCRP-UCFFOFKASA-N 0.000 description 1
- PSFULERNVNPNAD-IBGZPJMESA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-9-hydroxyfluorene-9-carboxamide Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1(O)C(=O)N[C@@H]1C(CC2)CCN2C1 PSFULERNVNPNAD-IBGZPJMESA-N 0.000 description 1
- SLPKWZVKESFSQR-UHFFFAOYSA-M n-methyl-n-[1-(3-pyrrol-1-ylpropyl)-1-azoniabicyclo[2.2.2]octan-3-yl]-9h-xanthene-9-carboxamide;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C12=CC=CC=C2OC2=CC=CC=C2C1C(=O)N(C)C(C(CC1)CC2)C[N+]21CCCN1C=CC=C1 SLPKWZVKESFSQR-UHFFFAOYSA-M 0.000 description 1
- 230000001272 neurogenic effect Effects 0.000 description 1
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- 239000012299 nitrogen atmosphere Substances 0.000 description 1
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- 231100000252 nontoxic Toxicity 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
- 235000005985 organic acids Nutrition 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 229920000075 poly(4-vinylpyridine) Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- RKIIRJKCZOGESH-QVOXVMGDSA-N s-[3-[(3r)-3-[[2-(5-bromothiophen-2-yl)-2-(4-fluoro-3-methylphenyl)-2-hydroxyacetyl]amino]-1-azoniabicyclo[2.2.2]octan-1-yl]propyl] ethanethioate;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.N([C@@H]1C2CC[N+](CC2)(C1)CCCSC(=O)C)C(=O)C(O)(C=1C=C(C)C(F)=CC=1)C1=CC=C(Br)S1 RKIIRJKCZOGESH-QVOXVMGDSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000016160 smooth muscle contraction Effects 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 230000016978 synaptic transmission, cholinergic Effects 0.000 description 1
- 229940095064 tartrate Drugs 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
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 229960004847 urologicals Drugs 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Urology & Nephrology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Priority Applications (25)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES200201539A ES2204295B1 (es) | 2002-07-02 | 2002-07-02 | Nuevos derivados de quinuclidina-amida. |
| DE60332534T DE60332534D1 (de) | 2002-07-02 | 2003-06-25 | Chinuclidinamidderivate |
| CA002492535A CA2492535A1 (en) | 2002-07-02 | 2003-06-25 | New quinuclidine amide derivatives |
| US10/518,714 US7488735B2 (en) | 2002-07-02 | 2003-06-25 | Quinuclidine amide derivatives |
| EP03762514A EP1519933B1 (en) | 2002-07-02 | 2003-06-25 | Quinuclidine amide derivatives |
| UAA200500839A UA80832C2 (en) | 2002-07-02 | 2003-06-25 | Quinuclidine amide derivatives |
| BR0312216-6A BR0312216A (pt) | 2002-07-02 | 2003-06-25 | Composto, processo para a produção de um composto, composição farmacêutica, uso do composto, método para o tratamento de um sujeito que sofre de uma doença ou condição patológica e combinação de produto |
| CNB03820648XA CN100404533C (zh) | 2002-07-02 | 2003-06-25 | 奎宁环酰胺衍生物 |
| PCT/EP2003/006708 WO2004005285A1 (en) | 2002-07-02 | 2003-06-25 | New quinuclidine amide derivatives |
| NZ537341A NZ537341A (en) | 2002-07-02 | 2003-06-25 | Quinuclidine amide derivatives as antimuscarinic agents to treat respiratory disorders |
| MXPA04012271A MXPA04012271A (es) | 2002-07-02 | 2003-06-25 | Nuevos derivados de quinuclidina-amida. |
| RU2005102585/04A RU2314306C2 (ru) | 2002-07-02 | 2003-06-25 | Производные хинуклидинамида, способ их получения и их применение, фармацевтическая композиция, комбинированный продукт и способ ингибирования мускариновых рецепторов |
| JP2004518575A JP2005533826A (ja) | 2002-07-02 | 2003-06-25 | 新規なるキヌクリジンアミド誘導体 |
| AU2003242757A AU2003242757B2 (en) | 2002-07-02 | 2003-06-25 | New quinuclidine amide derivatives |
| AT03762514T ATE467631T1 (de) | 2002-07-02 | 2003-06-25 | Chinuclidinamidderivate |
| UY27870A UY27870A1 (es) | 2002-07-02 | 2003-06-27 | Nuevos derivados de quinuclidina-amida |
| PE2003000662A PE20040644A1 (es) | 2002-07-02 | 2003-06-30 | Nuevos derivados de quinuclidina-amina |
| ARP030102368A AR040351A1 (es) | 2002-07-02 | 2003-06-30 | Derivados de quinuclidina-amida, composicion farmaceutica, procedimiento de preparacion del compuesto y su uso para fabricar medicamentos |
| MYPI20032447A MY130803A (en) | 2002-07-02 | 2003-06-30 | New quinuclidine amide derivatives |
| TW092118081A TW200402420A (en) | 2002-07-02 | 2003-07-02 | New quinuclidine amide derivatives |
| IL165923A IL165923A (en) | 2002-07-02 | 2004-12-22 | Quinuclidine amide derivatives, process for producing, uses, compositions and combination products comprising them |
| ZA200410404A ZA200410404B (en) | 2002-07-02 | 2004-12-23 | New quinuclidine amide derivatives. |
| EC2004005519A ECSP045519A (es) | 2002-07-02 | 2004-12-29 | Nuevos derivados de quinuclidina-amida |
| NO20050164A NO20050164L (no) | 2002-07-02 | 2005-01-12 | Nye quinuklidin-amid-derivater |
| US11/970,698 US7718670B2 (en) | 2002-07-02 | 2008-01-08 | Quinuclidine amide derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES200201539A ES2204295B1 (es) | 2002-07-02 | 2002-07-02 | Nuevos derivados de quinuclidina-amida. |
Publications (2)
| Publication Number | Publication Date |
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| ES2204295A1 ES2204295A1 (es) | 2004-04-16 |
| ES2204295B1 true ES2204295B1 (es) | 2005-08-01 |
Family
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| ES200201539A Expired - Fee Related ES2204295B1 (es) | 2002-07-02 | 2002-07-02 | Nuevos derivados de quinuclidina-amida. |
Country Status (24)
| Country | Link |
|---|---|
| US (2) | US7488735B2 (https=) |
| EP (1) | EP1519933B1 (https=) |
| JP (1) | JP2005533826A (https=) |
| CN (1) | CN100404533C (https=) |
| AR (1) | AR040351A1 (https=) |
| AT (1) | ATE467631T1 (https=) |
| AU (1) | AU2003242757B2 (https=) |
| BR (1) | BR0312216A (https=) |
| CA (1) | CA2492535A1 (https=) |
| DE (1) | DE60332534D1 (https=) |
| EC (1) | ECSP045519A (https=) |
| ES (1) | ES2204295B1 (https=) |
| IL (1) | IL165923A (https=) |
| MX (1) | MXPA04012271A (https=) |
| MY (1) | MY130803A (https=) |
| NO (1) | NO20050164L (https=) |
| NZ (1) | NZ537341A (https=) |
| PE (1) | PE20040644A1 (https=) |
| RU (1) | RU2314306C2 (https=) |
| TW (1) | TW200402420A (https=) |
| UA (1) | UA80832C2 (https=) |
| UY (1) | UY27870A1 (https=) |
| WO (1) | WO2004005285A1 (https=) |
| ZA (1) | ZA200410404B (https=) |
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| ES2165768B1 (es) | 1999-07-14 | 2003-04-01 | Almirall Prodesfarma Sa | Nuevos derivados de quinuclidina y composiciones farmaceuticas que los contienen. |
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| GB0401334D0 (en) | 2004-01-21 | 2004-02-25 | Novartis Ag | Organic compounds |
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| CA2945212A1 (en) | 2014-04-24 | 2015-10-29 | Novartis Ag | Amino pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors |
| BR112016024484A2 (pt) | 2014-04-24 | 2017-08-15 | Novartis Ag | derivados de aminopiridina como inibidores de fosfatidilinositol 3-quinase |
| US9862711B2 (en) | 2014-04-24 | 2018-01-09 | Novartis Ag | Pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors |
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| AU2020290094B2 (en) | 2019-06-10 | 2024-01-18 | Novartis Ag | Pyridine and pyrazine derivative for the treatment of CF, COPD, and bronchiectasis |
| AU2020338971B2 (en) | 2019-08-28 | 2023-11-23 | Novartis Ag | Substituted 1,3-phenyl heteroaryl derivatives and their use in the treatment of disease |
| CN110759904B (zh) * | 2019-10-21 | 2023-03-14 | 河南科技大学 | 9r-酰氧基奎宁类衍生物及其制备方法、奎宁或其衍生物的应用、植物源杀虫剂 |
| TW202140550A (zh) | 2020-01-29 | 2021-11-01 | 瑞士商諾華公司 | 使用抗ｔｓｌｐ抗體治療炎性或阻塞性氣道疾病之方法 |
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-
2002
- 2002-07-02 ES ES200201539A patent/ES2204295B1/es not_active Expired - Fee Related
-
2003
- 2003-06-25 CN CNB03820648XA patent/CN100404533C/zh not_active Expired - Fee Related
- 2003-06-25 RU RU2005102585/04A patent/RU2314306C2/ru not_active IP Right Cessation
- 2003-06-25 US US10/518,714 patent/US7488735B2/en not_active Expired - Fee Related
- 2003-06-25 EP EP03762514A patent/EP1519933B1/en not_active Expired - Lifetime
- 2003-06-25 AU AU2003242757A patent/AU2003242757B2/en not_active Ceased
- 2003-06-25 JP JP2004518575A patent/JP2005533826A/ja active Pending
- 2003-06-25 UA UAA200500839A patent/UA80832C2/uk unknown
- 2003-06-25 NZ NZ537341A patent/NZ537341A/xx unknown
- 2003-06-25 WO PCT/EP2003/006708 patent/WO2004005285A1/en not_active Ceased
- 2003-06-25 AT AT03762514T patent/ATE467631T1/de not_active IP Right Cessation
- 2003-06-25 DE DE60332534T patent/DE60332534D1/de not_active Expired - Fee Related
- 2003-06-25 CA CA002492535A patent/CA2492535A1/en not_active Abandoned
- 2003-06-25 MX MXPA04012271A patent/MXPA04012271A/es active IP Right Grant
- 2003-06-25 BR BR0312216-6A patent/BR0312216A/pt not_active IP Right Cessation
- 2003-06-27 UY UY27870A patent/UY27870A1/es not_active Application Discontinuation
- 2003-06-30 PE PE2003000662A patent/PE20040644A1/es not_active Application Discontinuation
- 2003-06-30 AR ARP030102368A patent/AR040351A1/es unknown
- 2003-06-30 MY MYPI20032447A patent/MY130803A/en unknown
- 2003-07-02 TW TW092118081A patent/TW200402420A/zh unknown
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2004
- 2004-12-22 IL IL165923A patent/IL165923A/en not_active IP Right Cessation
- 2004-12-23 ZA ZA200410404A patent/ZA200410404B/xx unknown
- 2004-12-29 EC EC2004005519A patent/ECSP045519A/es unknown
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2005
- 2005-01-12 NO NO20050164A patent/NO20050164L/no not_active Application Discontinuation
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2008
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Also Published As
| Publication number | Publication date |
|---|---|
| NZ537341A (en) | 2006-04-28 |
| WO2004005285A1 (en) | 2004-01-15 |
| AR040351A1 (es) | 2005-03-30 |
| AU2003242757A1 (en) | 2004-01-23 |
| UA80832C2 (en) | 2007-11-12 |
| ATE467631T1 (de) | 2010-05-15 |
| IL165923A0 (en) | 2006-01-15 |
| ZA200410404B (en) | 2005-09-05 |
| AU2003242757B2 (en) | 2009-01-08 |
| DE60332534D1 (de) | 2010-06-24 |
| NO20050164L (no) | 2005-04-04 |
| MXPA04012271A (es) | 2005-04-08 |
| ECSP045519A (es) | 2005-03-10 |
| US7718670B2 (en) | 2010-05-18 |
| TW200402420A (en) | 2004-02-16 |
| CA2492535A1 (en) | 2004-01-15 |
| CN100404533C (zh) | 2008-07-23 |
| MY130803A (en) | 2007-07-31 |
| BR0312216A (pt) | 2005-04-12 |
| CN1678610A (zh) | 2005-10-05 |
| EP1519933B1 (en) | 2010-05-12 |
| US20080234316A1 (en) | 2008-09-25 |
| RU2314306C2 (ru) | 2008-01-10 |
| ES2204295A1 (es) | 2004-04-16 |
| IL165923A (en) | 2010-06-30 |
| UY27870A1 (es) | 2003-10-31 |
| PE20040644A1 (es) | 2004-09-18 |
| EP1519933A1 (en) | 2005-04-06 |
| JP2005533826A (ja) | 2005-11-10 |
| US7488735B2 (en) | 2009-02-10 |
| US20060167042A1 (en) | 2006-07-27 |
| RU2005102585A (ru) | 2005-10-10 |
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