ES2281007T3 - Derivados de quinazolina. - Google Patents
Derivados de quinazolina. Download PDFInfo
- Publication number
- ES2281007T3 ES2281007T3 ES04768652T ES04768652T ES2281007T3 ES 2281007 T3 ES2281007 T3 ES 2281007T3 ES 04768652 T ES04768652 T ES 04768652T ES 04768652 T ES04768652 T ES 04768652T ES 2281007 T3 ES2281007 T3 ES 2281007T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- formula
- group
- quinazoline
- quinazoline derivative
- 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
- 238000000034 method Methods 0.000 claims abstract description 103
- 230000008569 process Effects 0.000 claims abstract description 57
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 54
- 238000011282 treatment Methods 0.000 claims abstract description 37
- 238000002360 preparation method Methods 0.000 claims abstract description 20
- 238000004519 manufacturing process Methods 0.000 claims abstract description 16
- 230000001028 anti-proliverative effect Effects 0.000 claims abstract description 15
- 239000003814 drug Substances 0.000 claims abstract description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 194
- -1 cyano, nitro, hydroxy, amino, carboxy, sulfamoyl Chemical group 0.000 claims description 115
- 125000000217 alkyl group Chemical group 0.000 claims description 94
- 150000003839 salts Chemical class 0.000 claims description 64
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 56
- 229910052757 nitrogen Inorganic materials 0.000 claims description 47
- 229910052739 hydrogen Inorganic materials 0.000 claims description 40
- 239000001257 hydrogen Substances 0.000 claims description 40
- 229910052736 halogen Inorganic materials 0.000 claims description 37
- 125000006239 protecting group Chemical group 0.000 claims description 36
- 125000001424 substituent group Chemical group 0.000 claims description 36
- 125000001153 fluoro group Chemical group F* 0.000 claims description 35
- 150000002367 halogens Chemical class 0.000 claims description 32
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 29
- 239000000460 chlorine Substances 0.000 claims description 29
- 229910052801 chlorine Inorganic materials 0.000 claims description 29
- 201000011510 cancer Diseases 0.000 claims description 26
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 26
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 21
- 125000000524 functional group Chemical group 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 125000000304 alkynyl group Chemical group 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims description 17
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 16
- 241001465754 Metazoa Species 0.000 claims description 16
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 125000004429 atom Chemical group 0.000 claims description 13
- 125000001589 carboacyl group Chemical group 0.000 claims description 13
- 125000005843 halogen group Chemical group 0.000 claims description 13
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 12
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 11
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 11
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 10
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 10
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 9
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 9
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- OPBJJFYRTBAOMF-UHFFFAOYSA-N 2-pyrrolidin-1-ylethyl 4-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidine-1-carboxylate Chemical compound C=12C=C(OC3CCN(CC3)C(=O)OCCN3CCCC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F OPBJJFYRTBAOMF-UHFFFAOYSA-N 0.000 claims description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- HRQAEZQBAMRCSA-UHFFFAOYSA-N methyl 4-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC)CCC1OC(C(=CC1=NC=N2)OC)=CC1=C2NC1=CC=CC(Cl)=C1F HRQAEZQBAMRCSA-UHFFFAOYSA-N 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 8
- LLOAHEIQGBGGTQ-UHFFFAOYSA-N 2-(diethylamino)ethyl 4-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OCCN(CC)CC)CCC1OC(C(=CC1=NC=N2)OC)=CC1=C2NC1=CC=CC(Cl)=C1F LLOAHEIQGBGGTQ-UHFFFAOYSA-N 0.000 claims description 7
- UGPGIBUJVVDLOA-UHFFFAOYSA-N 2-morpholin-4-ylethyl 4-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidine-1-carboxylate Chemical compound C=12C=C(OC3CCN(CC3)C(=O)OCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F UGPGIBUJVVDLOA-UHFFFAOYSA-N 0.000 claims description 7
- CFYLMJJPWKHYLO-UHFFFAOYSA-N 2-piperidin-1-ylethyl 4-[4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidine-1-carboxylate Chemical compound C=12C=C(OC3CCN(CC3)C(=O)OCCN3CCCCC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1F CFYLMJJPWKHYLO-UHFFFAOYSA-N 0.000 claims description 7
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 7
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 7
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 7
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 7
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 7
- MGTBTQYQBPWHRY-UHFFFAOYSA-N 2-piperidin-1-ylethyl 4-[4-(3-chloro-2,4-difluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidine-1-carboxylate Chemical compound C=12C=C(OC3CCN(CC3)C(=O)OCCN3CCCCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1F MGTBTQYQBPWHRY-UHFFFAOYSA-N 0.000 claims description 6
- MTUHLNORBDFEJP-UHFFFAOYSA-N 2-pyrrolidin-1-ylethyl 4-[4-(3-chloro-2,4-difluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidine-1-carboxylate Chemical compound C=12C=C(OC3CCN(CC3)C(=O)OCCN3CCCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1F MTUHLNORBDFEJP-UHFFFAOYSA-N 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- NDXVVVPOQKIUGG-UHFFFAOYSA-N methyl 4-[4-(3-chloro-2,4-difluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC)CCC1OC(C(=CC1=NC=N2)OC)=CC1=C2NC1=CC=C(F)C(Cl)=C1F NDXVVVPOQKIUGG-UHFFFAOYSA-N 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
- 125000005153 alkyl sulfamoyl group Chemical group 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- DQORBCOTYYJLTB-UHFFFAOYSA-N propan-2-yl 4-[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidine-1-carboxylate Chemical compound C=12C=C(OC3CCN(CC3)C(=O)OC(C)C)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 DQORBCOTYYJLTB-UHFFFAOYSA-N 0.000 claims description 4
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 4
- 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 claims description 4
- LLTCDTSMNWDXIP-UHFFFAOYSA-N tert-butyl 4-[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidine-1-carboxylate Chemical compound C=12C=C(OC3CCN(CC3)C(=O)OC(C)(C)C)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 LLTCDTSMNWDXIP-UHFFFAOYSA-N 0.000 claims description 4
- QAKBRNPYOXEUPZ-UHFFFAOYSA-N 2-pyrrolidin-1-ylethyl 4-[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-6-yl]oxypiperidine-1-carboxylate Chemical compound C=12C=C(OC3CCN(CC3)C(=O)OCCN3CCCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 QAKBRNPYOXEUPZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 125000003107 substituted aryl group Chemical group 0.000 claims description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 3
- QJQCSXAKSADYBA-UHFFFAOYSA-N tert-butyl 4-[4-(3-ethynylanilino)-7-methoxyquinazolin-6-yl]oxypiperidine-1-carboxylate Chemical compound C=12C=C(OC3CCN(CC3)C(=O)OC(C)(C)C)C(OC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 QJQCSXAKSADYBA-UHFFFAOYSA-N 0.000 claims description 3
- RQZNUDVCDCQOEL-UHFFFAOYSA-N 2-pyrrolidin-1-ylethyl 4-[4-(3-chloroanilino)-7-methoxyquinazolin-6-yl]oxypiperidine-1-carboxylate Chemical compound C=12C=C(OC3CCN(CC3)C(=O)OCCN3CCCC3)C(OC)=CC2=NC=NC=1NC1=CC=CC(Cl)=C1 RQZNUDVCDCQOEL-UHFFFAOYSA-N 0.000 claims description 2
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 150000003246 quinazolines Chemical class 0.000 claims 48
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 5
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 abstract description 43
- 230000005764 inhibitory process Effects 0.000 abstract description 21
- 102000001301 EGF receptor Human genes 0.000 abstract description 12
- 108060006698 EGF receptor Proteins 0.000 abstract description 12
- 239000003795 chemical substances by application Substances 0.000 abstract description 6
- 230000002265 prevention Effects 0.000 abstract description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 80
- 238000006243 chemical reaction Methods 0.000 description 62
- 210000004027 cell Anatomy 0.000 description 42
- 239000002904 solvent Substances 0.000 description 30
- 150000001335 aliphatic alkanes Chemical class 0.000 description 29
- 230000000694 effects Effects 0.000 description 28
- 239000000203 mixture Substances 0.000 description 26
- 239000000243 solution Substances 0.000 description 25
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 239000002585 base Substances 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 239000002253 acid Substances 0.000 description 21
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 19
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 19
- 238000012360 testing method Methods 0.000 description 19
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 18
- 241000282414 Homo sapiens Species 0.000 description 17
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 17
- 238000001819 mass spectrum Methods 0.000 description 17
- 239000002953 phosphate buffered saline Substances 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
- 239000003112 inhibitor Substances 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 125000003118 aryl group Chemical group 0.000 description 14
- 238000001704 evaporation Methods 0.000 description 14
- 230000008020 evaporation Effects 0.000 description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 14
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 13
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 13
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- 241000699670 Mus sp. Species 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- 150000001299 aldehydes Chemical class 0.000 description 12
- 238000003556 assay Methods 0.000 description 12
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 10
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- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 10
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
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- 125000002252 acyl group Chemical group 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 8
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- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
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- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/622—Forming processes; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/626—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B
- C04B35/63—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
- C04B35/632—Organic additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—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
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Ceramic Engineering (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Manufacturing & Machinery (AREA)
- Epidemiology (AREA)
- Materials Engineering (AREA)
- Structural Engineering (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP03292308 | 2003-09-19 | ||
| EP03292308 | 2003-09-19 | ||
| EP04291249 | 2004-05-14 | ||
| EP04291249 | 2004-05-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2281007T3 true ES2281007T3 (es) | 2007-09-16 |
Family
ID=34379391
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES04768652T Expired - Lifetime ES2281007T3 (es) | 2003-09-19 | 2004-09-15 | Derivados de quinazolina. |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20070037837A1 (OSRAM) |
| EP (1) | EP1670782B1 (OSRAM) |
| JP (1) | JP2007505878A (OSRAM) |
| CN (1) | CN1882570B (OSRAM) |
| AT (1) | ATE353888T1 (OSRAM) |
| DE (1) | DE602004004811T2 (OSRAM) |
| ES (1) | ES2281007T3 (OSRAM) |
| WO (1) | WO2005028470A1 (OSRAM) |
Families Citing this family (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE423104T1 (de) * | 2001-11-03 | 2009-03-15 | Astrazeneca Ab | Quinazolin derivate als antitumor-mittel |
| GB0126433D0 (en) * | 2001-11-03 | 2002-01-02 | Astrazeneca Ab | Compounds |
| TW200813014A (en) * | 2002-03-28 | 2008-03-16 | Astrazeneca Ab | Quinazoline derivatives |
| US6924285B2 (en) | 2002-03-30 | 2005-08-02 | Boehringer Ingelheim Pharma Gmbh & Co. | Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them |
| GB0309009D0 (en) * | 2003-04-22 | 2003-05-28 | Astrazeneca Ab | Quinazoline derivatives |
| GB0309850D0 (en) * | 2003-04-30 | 2003-06-04 | Astrazeneca Ab | Quinazoline derivatives |
| GB0317665D0 (en) | 2003-07-29 | 2003-09-03 | Astrazeneca Ab | Qinazoline derivatives |
| WO2005026151A1 (en) * | 2003-09-16 | 2005-03-24 | Astrazeneca Ab | Quinazoline derivatives as tyrosine kinase inhibitors |
| EP1664030A1 (en) * | 2003-09-16 | 2006-06-07 | AstraZeneca AB | Quinazoline derivatives |
| CA2539049A1 (en) * | 2003-09-16 | 2005-03-24 | Astrazeneca Ab | Quinazoline derivatives |
| DK1667991T3 (da) | 2003-09-16 | 2008-08-18 | Astrazeneca Ab | Quinazolinderivater som tyrosinkinaseinhibitorer |
| GB0321648D0 (en) * | 2003-09-16 | 2003-10-15 | Astrazeneca Ab | Quinazoline derivatives |
| DE602004004553T2 (de) * | 2003-09-19 | 2007-10-25 | Astrazeneca Ab | Chinazolinderivate |
| EP1670786A1 (en) * | 2003-09-25 | 2006-06-21 | Astrazeneca AB | Quinazoline derivatives |
| GB0322409D0 (en) * | 2003-09-25 | 2003-10-29 | Astrazeneca Ab | Quinazoline derivatives |
| GB0326459D0 (en) | 2003-11-13 | 2003-12-17 | Astrazeneca Ab | Quinazoline derivatives |
| EP1713781B1 (en) * | 2004-02-03 | 2008-11-05 | AstraZeneca AB | Quinazoline derivatives |
| CA2567832A1 (en) * | 2004-06-04 | 2005-12-15 | Astrazeneca Ab | Quinazoline derivatives as erbb receptor tyrosine kinases |
| DE602005026865D1 (de) * | 2004-12-14 | 2011-04-21 | Astrazeneca Ab | Pyrazolopyrimidinverbindungen als antitumormittel |
| ATE521603T1 (de) * | 2005-02-26 | 2011-09-15 | Astrazeneca Ab | Chinazolinderivate als tyrosinkinaseinhibitoren |
| GB0504474D0 (en) * | 2005-03-04 | 2005-04-13 | Astrazeneca Ab | Chemical compounds |
| GB0508717D0 (en) * | 2005-04-29 | 2005-06-08 | Astrazeneca Ab | Chemical compounds |
| GB0508715D0 (en) * | 2005-04-29 | 2005-06-08 | Astrazeneca Ab | Chemical compounds |
| EP1928861B1 (en) * | 2005-09-20 | 2010-11-17 | AstraZeneca AB | 4- (ih-indazol-5-yl-amino)-quinazoline compounds as erbb receptor tyrosine kinase inhibitors for the treatment of cancer |
| EP1940825A1 (en) * | 2005-09-20 | 2008-07-09 | Astra Zeneca AB | Quinazoline derivatives as anticancer agents |
| JP5688877B2 (ja) * | 2005-11-11 | 2015-03-25 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 癌疾患の治療用キナゾリン誘導体 |
| JP2009517450A (ja) * | 2005-12-02 | 2009-04-30 | アストラゼネカ アクチボラグ | チロシンキナーゼ阻害薬としての4−アニリノ置換キナゾリン誘導体 |
| EP1960371B1 (en) * | 2005-12-02 | 2009-09-16 | AstraZeneca AB | Quinazoleine derivatives used as inhibitors of erbb tyrosine kinase |
| KR20080077009A (ko) * | 2005-12-12 | 2008-08-20 | 베링거 인겔하임 인터내셔날 게엠베하 | 바이사이클릭 헤테로사이클, 당해 화합물을 함유하는 약제,이의 용도 및 이의 제조방법 |
| EP1921070A1 (de) * | 2006-11-10 | 2008-05-14 | Boehringer Ingelheim Pharma GmbH & Co. KG | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstelllung |
| AU2008212999A1 (en) | 2007-02-06 | 2008-08-14 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, drugs containing said compounds, use thereof, and method for production thereof |
| EP2245026B1 (de) | 2008-02-07 | 2012-08-01 | Boehringer Ingelheim International GmbH | Spirocyclische heterocyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung |
| AU2009247782C1 (en) * | 2008-05-13 | 2013-09-19 | Astrazeneca Ab | Fumarate salt of 4- (3-chloro-2-fluoroanilino) -7-methoxy-6- { [1- (N-methylcarbamoylmethyl) piperidin- 4-yl] oxy } quinazoline |
| CA2733153C (en) | 2008-08-08 | 2016-11-08 | Boehringer Ingelheim International Gmbh | Cyclohexyloxy substituted heterocycles, pharmaceutical compositions containing these compounds and processes for preparing them |
| JP5963672B2 (ja) | 2009-07-06 | 2016-08-03 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Bibw2992、その塩及びこの活性成分を含む固体医薬製剤の乾燥方法 |
| KR101217526B1 (ko) * | 2010-06-11 | 2013-01-02 | 한미사이언스 주식회사 | 아마이드 유도체 또는 이의 약학적으로 허용 가능한 염을 포함하는 약제학적 조성물 |
| KR101317809B1 (ko) | 2011-06-07 | 2013-10-16 | 한미약품 주식회사 | 암세포의 성장을 억제하는 아마이드 유도체 및 비금속염 활택제를 포함하는 약학 조성물 |
| KR101272613B1 (ko) * | 2011-10-05 | 2013-06-10 | 한미사이언스 주식회사 | 1-(4-(4-(3,4-디클로로-2-플루오로페닐아미노)-7-메톡시퀴나졸린-6-일옥시)피페리딘-1-일)프로프-2-엔-1-온 염산염의 제조 방법 및 이에 사용되는 중간체 |
| US9546179B2 (en) * | 2011-12-20 | 2017-01-17 | Wei Qian | Heterocycle amido alkyloxy substituted quinazoline derivative and use thereof |
| KR20140096571A (ko) * | 2013-01-28 | 2014-08-06 | 한미약품 주식회사 | 1-(4-(4-(3,4-디클로로-2-플루오로페닐아미노)-7-메톡시퀴나졸린-6-일옥시)피페리딘-1-일)프로프-2-엔-1-온의 제조방법 |
| MY186126A (en) | 2013-03-06 | 2021-06-24 | Astrazeneca Ab | Quinazoline inhibitors of activating mutant forms of epidermal growth factor receptor |
| US9242965B2 (en) | 2013-12-31 | 2016-01-26 | Boehringer Ingelheim International Gmbh | Process for the manufacture of (E)-4-N,N-dialkylamino crotonic acid in HX salt form and use thereof for synthesis of EGFR tyrosine kinase inhibitors |
| CN108558854A (zh) * | 2017-06-10 | 2018-09-21 | 曹艳 | 一种治疗革兰氏阳性菌引起的感染的药物及其合成方法 |
| CN107033138B (zh) * | 2017-06-10 | 2018-06-08 | 徐晓东 | 一种治疗恶性肿瘤的药物 |
| CN107226815B (zh) * | 2017-06-22 | 2018-07-31 | 徐州市第一人民医院 | 喹唑啉类化合物及其在抗肿瘤药物中的应用 |
| CN110357858B (zh) * | 2018-04-09 | 2022-02-18 | 威尚(上海)生物医药有限公司 | 具有穿过血脑屏障能力的5取代二氟哌啶化合物 |
| CN114031563A (zh) * | 2021-12-01 | 2022-02-11 | 武汉科技大学 | 一种环丁喹噁啉类化合物及其应用 |
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| US3985749A (en) * | 1975-12-22 | 1976-10-12 | Eastman Kodak Company | Process for preparation of 4-aminoquinazoline |
| JPS5538325A (en) * | 1978-09-11 | 1980-03-17 | Sankyo Co Ltd | 4-anilinoquinazoline derivative and its preparation |
| US4335127A (en) * | 1979-01-08 | 1982-06-15 | Janssen Pharmaceutica, N.V. | Piperidinylalkyl quinazoline compounds, composition and method of use |
| GB2160201B (en) * | 1984-06-14 | 1988-05-11 | Wyeth John & Brother Ltd | Quinazoline and cinnoline derivatives |
| US4921863A (en) * | 1988-02-17 | 1990-05-01 | Eisai Co., Ltd. | Cyclic amine derivatives |
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| US5252586A (en) * | 1990-09-28 | 1993-10-12 | The Du Pont Merck Pharmaceutical Company | Ether derivatives of alkyl piperidines and pyrrolidines as antipsychotic agents |
| US5721237A (en) * | 1991-05-10 | 1998-02-24 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Protein tyrosine kinase aryl and heteroaryl quinazoline compounds having selective inhibition of HER-2 autophosphorylation properties |
| AU661533B2 (en) * | 1992-01-20 | 1995-07-27 | Astrazeneca Ab | Quinazoline derivatives |
| TW321649B (OSRAM) * | 1994-11-12 | 1997-12-01 | Zeneca Ltd | |
| GB9508538D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
| WO1996033977A1 (en) * | 1995-04-27 | 1996-10-31 | Zeneca Limited | Quinazoline derivatives |
| US5747498A (en) * | 1996-05-28 | 1998-05-05 | Pfizer Inc. | Alkynyl and azido-substituted 4-anilinoquinazolines |
| US6046206A (en) * | 1995-06-07 | 2000-04-04 | Cell Pathways, Inc. | Method of treating a patient having a precancerous lesions with amide quinazoline derivatives |
| GB9624482D0 (en) * | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
| AU1721697A (en) * | 1996-01-31 | 1997-08-22 | Gist-Brocades B.V. | Use of compositions comprising stabilized biologically effective compounds |
| GB9603095D0 (en) * | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline derivatives |
| GB9607729D0 (en) * | 1996-04-13 | 1996-06-19 | Zeneca Ltd | Quinazoline derivatives |
| US6004967A (en) * | 1996-09-13 | 1999-12-21 | Sugen, Inc. | Psoriasis treatment with quinazoline compounds |
| GB9718972D0 (en) * | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
| US6225318B1 (en) * | 1996-10-17 | 2001-05-01 | Pfizer Inc | 4-aminoquinazolone derivatives |
| US5929080A (en) * | 1997-05-06 | 1999-07-27 | American Cyanamid Company | Method of treating polycystic kidney disease |
| US6384223B1 (en) * | 1998-07-30 | 2002-05-07 | American Home Products Corporation | Substituted quinazoline derivatives |
| US6297258B1 (en) * | 1998-09-29 | 2001-10-02 | American Cyanamid Company | Substituted 3-cyanoquinolines |
| CZ20013079A3 (cs) * | 1999-02-27 | 2001-11-14 | Boehringer Ingelheim Pharma Kg | Deriváty 4-aminochinazolinu a chinolinu |
| US6080747A (en) * | 1999-03-05 | 2000-06-27 | Hughes Institute | JAK-3 inhibitors for treating allergic disorders |
| DE19911509A1 (de) * | 1999-03-15 | 2000-09-21 | Boehringer Ingelheim Pharma | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| WO2000068203A1 (en) * | 1999-05-07 | 2000-11-16 | Takeda Chemical Industries, Ltd. | Cyclic compounds and uses thereof |
| US6126917A (en) * | 1999-06-01 | 2000-10-03 | Hadasit Medical Research Services And Development Ltd. | Epidermal growth factor receptor binding compounds for positron emission tomography |
| SK287010B6 (sk) * | 1999-06-21 | 2009-09-07 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyklické heterocyklické zlúčeniny, spôsob ich prípravy, farmaceutický prostriedok s ich obsahom a ich použitie |
| US6617329B2 (en) * | 2000-08-26 | 2003-09-09 | Boehringer Ingelheim Pharma Kg | Aminoquinazolines and their use as medicaments |
| US6653305B2 (en) * | 2000-08-26 | 2003-11-25 | Boehringer Ingelheim Pharma Kg | Bicyclic heterocycles, pharmaceutical compositions containing them, their use, and processes for preparing them |
| US6740651B2 (en) * | 2000-08-26 | 2004-05-25 | Boehringer Ingelheim Pharma Kg | Aminoquinazolines which inhibit signal transduction mediated by tyrosine kinases |
| US20020082270A1 (en) * | 2000-08-26 | 2002-06-27 | Frank Himmelsbach | Aminoquinazolines which inhibit signal transduction mediated by tyrosine kinases |
| US6656946B2 (en) * | 2000-08-26 | 2003-12-02 | Boehringer Ingelheim Pharma Kg | Aminoquinazolines which inhibit signal transduction mediated by tyrosine kinases |
| US20030158196A1 (en) * | 2002-02-16 | 2003-08-21 | Boehringer Ingelheim Pharma Gmbh Co. Kg | Pharmaceutical compositions based on anticholinergics and EGFR kinase inhibitors |
| US7019012B2 (en) * | 2000-12-20 | 2006-03-28 | Boehringer Ingelheim International Pharma Gmbh & Co. Kg | Quinazoline derivatives and pharmaceutical compositions containing them |
| ATE475652T1 (de) * | 2001-02-21 | 2010-08-15 | Mitsubishi Tanabe Pharma Corp | Chinazolinderivate |
| US6562319B2 (en) * | 2001-03-12 | 2003-05-13 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Radiolabeled irreversible inhibitors of epidermal growth factor receptor tyrosine kinase and their use in radioimaging and radiotherapy |
| EP1396488A1 (en) * | 2001-05-23 | 2004-03-10 | Mitsubishi Pharma Corporation | Fused heterocyclic compound and medicinal use thereof |
| PL371486A1 (en) * | 2002-02-01 | 2005-06-13 | Astrazeneca Ab | Quinazoline compounds |
| DE10204462A1 (de) * | 2002-02-05 | 2003-08-07 | Boehringer Ingelheim Pharma | Verwendung von Tyrosinkinase-Inhibitoren zur Behandlung inflammatorischer Prozesse |
| TW200813014A (en) * | 2002-03-28 | 2008-03-16 | Astrazeneca Ab | Quinazoline derivatives |
| US6924285B2 (en) * | 2002-03-30 | 2005-08-02 | Boehringer Ingelheim Pharma Gmbh & Co. | Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them |
| PL371188A1 (en) * | 2002-03-30 | 2005-06-13 | Boehringer Ingelheim Pharma Gmbh & Co.Kg | 4-(n-phenylamino)-quinazolines / quinolines as tyrosine kinase inhibitors |
| US20040044014A1 (en) * | 2002-04-19 | 2004-03-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for the preparation thereof |
| GB0317665D0 (en) * | 2003-07-29 | 2003-09-03 | Astrazeneca Ab | Qinazoline derivatives |
| KR20060054388A (ko) * | 2003-07-29 | 2006-05-22 | 아스트라제네카 아베 | 티로신 키나아제 억제제로서의 피페리딜-퀴나졸린 유도체 |
| WO2005026151A1 (en) * | 2003-09-16 | 2005-03-24 | Astrazeneca Ab | Quinazoline derivatives as tyrosine kinase inhibitors |
| DE602004004553T2 (de) * | 2003-09-19 | 2007-10-25 | Astrazeneca Ab | Chinazolinderivate |
| EP1670786A1 (en) * | 2003-09-25 | 2006-06-21 | Astrazeneca AB | Quinazoline derivatives |
-
2004
- 2004-09-15 EP EP04768652A patent/EP1670782B1/en not_active Expired - Lifetime
- 2004-09-15 DE DE602004004811T patent/DE602004004811T2/de not_active Expired - Lifetime
- 2004-09-15 CN CN2004800339104A patent/CN1882570B/zh not_active Expired - Fee Related
- 2004-09-15 ES ES04768652T patent/ES2281007T3/es not_active Expired - Lifetime
- 2004-09-15 WO PCT/GB2004/004109 patent/WO2005028470A1/en not_active Ceased
- 2004-09-15 AT AT04768652T patent/ATE353888T1/de not_active IP Right Cessation
- 2004-09-15 US US10/572,048 patent/US20070037837A1/en not_active Abandoned
- 2004-09-15 JP JP2006526702A patent/JP2007505878A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| HK1091486A1 (en) | 2007-01-19 |
| CN1882570A (zh) | 2006-12-20 |
| CN1882570B (zh) | 2010-12-08 |
| DE602004004811T2 (de) | 2007-11-22 |
| US20070037837A1 (en) | 2007-02-15 |
| EP1670782A1 (en) | 2006-06-21 |
| DE602004004811D1 (de) | 2007-03-29 |
| JP2007505878A (ja) | 2007-03-15 |
| WO2005028470A1 (en) | 2005-03-31 |
| ATE353888T1 (de) | 2007-03-15 |
| EP1670782B1 (en) | 2007-02-14 |
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