DE60003709T2 - Substituierte azole - Google Patents
Substituierte azole Download PDFInfo
- Publication number
- DE60003709T2 DE60003709T2 DE60003709T DE60003709T DE60003709T2 DE 60003709 T2 DE60003709 T2 DE 60003709T2 DE 60003709 T DE60003709 T DE 60003709T DE 60003709 T DE60003709 T DE 60003709T DE 60003709 T2 DE60003709 T2 DE 60003709T2
- Authority
- DE
- Germany
- Prior art keywords
- fluorophenyl
- amino
- pyrimidyl
- alkyl
- phenyl
- 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
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- 150000003851 azoles Chemical class 0.000 title description 2
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 title 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 160
- -1 methylene aminoguanidinyl Chemical group 0.000 claims description 146
- 150000001875 compounds Chemical class 0.000 claims description 123
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 67
- 229910052736 halogen Inorganic materials 0.000 claims description 56
- 150000002367 halogens Chemical class 0.000 claims description 53
- 125000002924 primary amino group Chemical class [H]N([H])* 0.000 claims description 33
- 125000001424 substituent group Chemical group 0.000 claims description 33
- 125000003118 aryl group Chemical group 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
- 239000002253 acid Substances 0.000 claims description 23
- 125000001072 heteroaryl group Chemical group 0.000 claims description 23
- 125000005842 heteroatom Chemical group 0.000 claims description 23
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
- 150000002148 esters Chemical class 0.000 claims description 22
- 125000006413 ring segment Chemical group 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 22
- 229910052799 carbon Inorganic materials 0.000 claims description 21
- 125000002915 carbonyl group Chemical class [*:2]C([*:1])=O 0.000 claims description 20
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 19
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 239000002243 precursor Substances 0.000 claims description 14
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 12
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 11
- 125000003368 amide group Chemical group 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 125000004076 pyridyl group Chemical group 0.000 claims description 10
- 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 10
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 9
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 9
- 125000003386 piperidinyl group Chemical group 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 7
- OMOCVUPRTIPABZ-UHFFFAOYSA-N 1-(1h-imidazol-2-yl)piperidine Chemical compound C1CCCCN1C1=NC=CN1 OMOCVUPRTIPABZ-UHFFFAOYSA-N 0.000 claims description 7
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 7
- 125000002757 morpholinyl group Chemical group 0.000 claims description 7
- 125000004193 piperazinyl group Chemical group 0.000 claims description 7
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 6
- 125000001831 (C6-C10) heteroaryl group Chemical group 0.000 claims description 6
- RGEMRXMFQPBDKB-IBGZPJMESA-N 4-[2-(4-fluorophenyl)-4-piperidin-1-ylimidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(N2CCCCC2)N=C1C1=CC=C(F)C=C1 RGEMRXMFQPBDKB-IBGZPJMESA-N 0.000 claims description 6
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
- 150000007942 carboxylates Chemical class 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 5
- JHLCOEDXIFANHS-HNNXBMFYSA-N 2-(4-fluorophenyl)-1-[5-(methylideneamino)-1h-imidazol-2-yl]-1-[2-[[(1s)-1-phenylethyl]amino]pyrimidin-4-yl]guanidine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N(C=1NC(N=C)=CN=1)C(N)=NC1=CC=C(F)C=C1 JHLCOEDXIFANHS-HNNXBMFYSA-N 0.000 claims description 4
- 239000003018 immunosuppressive agent Substances 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000004953 trihalomethyl group Chemical group 0.000 claims description 4
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
- 229920002554 vinyl polymer Polymers 0.000 claims description 4
- SDEWHSLEPTWRAI-UHFFFAOYSA-N 4-[1-[2-(cyclohexylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)imidazol-4-yl]-1-methylpiperidin-4-ol Chemical compound C1CN(C)CCC1(O)C1=CN(C=2N=C(NC3CCCCC3)N=CC=2)C(C=2C=CC(F)=CC=2)=N1 SDEWHSLEPTWRAI-UHFFFAOYSA-N 0.000 claims description 3
- NTPLIHVIDFWRGV-UHFFFAOYSA-N 4-[1-[2-(cyclopentylamino)pyrimidin-4-yl]-2-[3-(trifluoromethyl)phenyl]imidazol-4-yl]-1-methylpiperidin-4-ol Chemical compound C1CN(C)CCC1(O)C1=CN(C=2N=C(NC3CCCC3)N=CC=2)C(C=2C=C(C=CC=2)C(F)(F)F)=N1 NTPLIHVIDFWRGV-UHFFFAOYSA-N 0.000 claims description 3
- YNFVASWJENHSNL-UHFFFAOYSA-N 4-[1-[2-(cyclopropylamino)pyrimidin-4-yl]-2-[3-(trifluoromethyl)phenyl]imidazol-4-yl]-1-methylpiperidin-4-ol Chemical compound C1CN(C)CCC1(O)C1=CN(C=2N=C(NC3CC3)N=CC=2)C(C=2C=C(C=CC=2)C(F)(F)F)=N1 YNFVASWJENHSNL-UHFFFAOYSA-N 0.000 claims description 3
- WOZNUFNHHCRSBL-IBGZPJMESA-N 4-[2-(4-fluorophenyl)-1-[2-[[(1s)-1-phenylethyl]amino]pyrimidin-4-yl]imidazol-4-yl]-1-methylpiperidin-4-ol Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(C2(O)CCN(C)CC2)N=C1C1=CC=C(F)C=C1 WOZNUFNHHCRSBL-IBGZPJMESA-N 0.000 claims description 3
- XOFQUNFVZPBJMU-IBGZPJMESA-N 4-[2-(4-fluorophenyl)-4-(4-methoxyphenyl)imidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound C1=CC(OC)=CC=C1C1=CN(C=2N=C(N[C@@H](C)C=3C=CC=CC=3)N=CC=2)C(C=2C=CC(F)=CC=2)=N1 XOFQUNFVZPBJMU-IBGZPJMESA-N 0.000 claims description 3
- NMIIJPIOVJUYGH-KRWDZBQOSA-N 4-[2-(4-fluorophenyl)-4-(furan-2-yl)imidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(C=2OC=CC=2)N=C1C1=CC=C(F)C=C1 NMIIJPIOVJUYGH-KRWDZBQOSA-N 0.000 claims description 3
- GKNRTYXCNFXLIQ-SFHVURJKSA-N 4-[2-(4-fluorophenyl)-4-pyridin-2-ylimidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(C=2N=CC=CC=2)N=C1C1=CC=C(F)C=C1 GKNRTYXCNFXLIQ-SFHVURJKSA-N 0.000 claims description 3
- BLNLTPFOJOESQM-SFHVURJKSA-N 4-[2-(4-fluorophenyl)-4-pyridin-4-ylimidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(C=2C=CN=CC=2)N=C1C1=CC=C(F)C=C1 BLNLTPFOJOESQM-SFHVURJKSA-N 0.000 claims description 3
- YHXGGIIVEZOFIA-KRWDZBQOSA-N 4-[2-(4-fluorophenyl)-4-thiophen-2-ylimidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(C=2SC=CC=2)N=C1C1=CC=C(F)C=C1 YHXGGIIVEZOFIA-KRWDZBQOSA-N 0.000 claims description 3
- HPTDTEXEPXTGON-KRWDZBQOSA-N 4-[2-(4-fluorophenyl)-4-thiophen-3-ylimidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(C2=CSC=C2)N=C1C1=CC=C(F)C=C1 HPTDTEXEPXTGON-KRWDZBQOSA-N 0.000 claims description 3
- DWVCIXHAUWGUCG-IBGZPJMESA-N 4-[4-(1-benzofuran-2-yl)-2-(4-fluorophenyl)imidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(C=2OC3=CC=CC=C3C=2)N=C1C1=CC=C(F)C=C1 DWVCIXHAUWGUCG-IBGZPJMESA-N 0.000 claims description 3
- KHUGAMVMXXVEPI-KRWDZBQOSA-N 4-[4-(3-chloro-4-fluorophenyl)-2-(4-fluorophenyl)imidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(C=2C=C(Cl)C(F)=CC=2)N=C1C1=CC=C(F)C=C1 KHUGAMVMXXVEPI-KRWDZBQOSA-N 0.000 claims description 3
- VADIUNQAYZTCLW-SFHVURJKSA-N 4-[4-(3-chlorophenyl)-2-(4-fluorophenyl)imidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(C=2C=C(Cl)C=CC=2)N=C1C1=CC=C(F)C=C1 VADIUNQAYZTCLW-SFHVURJKSA-N 0.000 claims description 3
- WQFMURNIPAFPJC-KRWDZBQOSA-N 4-[4-(4-fluorophenyl)-2-piperazin-1-yl-1,3-oxazol-5-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1C=1OC(N2CCNCC2)=NC=1C1=CC=C(F)C=C1 WQFMURNIPAFPJC-KRWDZBQOSA-N 0.000 claims description 3
- HEYFMIPJWRNZOJ-UHFFFAOYSA-N 4-[4-bromo-2-[3-(trifluoromethyl)phenyl]imidazol-1-yl]-n-cyclopentylpyrimidin-2-amine Chemical compound FC(F)(F)C1=CC=CC(C=2N(C=C(Br)N=2)C=2N=C(NC3CCCC3)N=CC=2)=C1 HEYFMIPJWRNZOJ-UHFFFAOYSA-N 0.000 claims description 3
- GURHPKMAUZMMMN-UHFFFAOYSA-N 4-[4-bromo-2-[3-(trifluoromethyl)phenyl]imidazol-1-yl]-n-cyclopropylpyrimidin-2-amine Chemical compound FC(F)(F)C1=CC=CC(C=2N(C=C(Br)N=2)C=2N=C(NC3CC3)N=CC=2)=C1 GURHPKMAUZMMMN-UHFFFAOYSA-N 0.000 claims description 3
- YYEFWHDWSRRIOJ-UHFFFAOYSA-N 4-[4-bromo-2-[4-(fluoromethyl)phenyl]imidazol-1-yl]-n-cyclohexylpyrimidin-2-amine Chemical compound C1=CC(CF)=CC=C1C1=NC(Br)=CN1C1=CC=NC(NC2CCCCC2)=N1 YYEFWHDWSRRIOJ-UHFFFAOYSA-N 0.000 claims description 3
- KBONZBOHMUFXCB-INIZCTEOSA-N 4-[4-ethenyl-2-(4-fluorophenyl)imidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(C=C)N=C1C1=CC=C(F)C=C1 KBONZBOHMUFXCB-INIZCTEOSA-N 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 150000002576 ketones Chemical class 0.000 claims description 3
- 125000002971 oxazolyl group Chemical group 0.000 claims description 3
- ITGCQBSBVQWQFS-IBGZPJMESA-N 4-[2-(4-ethylpiperazin-1-yl)-4-(4-fluorophenyl)-1,3-oxazol-5-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound C1CN(CC)CCN1C1=NC(C=2C=CC(F)=CC=2)=C(C=2N=C(N[C@@H](C)C=3C=CC=CC=3)N=CC=2)O1 ITGCQBSBVQWQFS-IBGZPJMESA-N 0.000 claims description 2
- OBGCSBYRWKZXLY-SFHVURJKSA-N 4-[2-(4-fluorophenyl)-4-pyridin-3-ylimidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(C=2C=NC=CC=2)N=C1C1=CC=C(F)C=C1 OBGCSBYRWKZXLY-SFHVURJKSA-N 0.000 claims description 2
- JSHSLFORZWNNNH-IBGZPJMESA-N 4-[4-(4-fluorophenyl)-2-(4-methylpiperidin-1-yl)-1,3-oxazol-5-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1C=1OC(N2CCC(C)CC2)=NC=1C1=CC=C(F)C=C1 JSHSLFORZWNNNH-IBGZPJMESA-N 0.000 claims description 2
- GOYRICSRRPAVRO-INIZCTEOSA-N 4-[4-(5-chlorothiophen-2-yl)-2-(4-fluorophenyl)imidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(C=2SC(Cl)=CC=2)N=C1C1=CC=C(F)C=C1 GOYRICSRRPAVRO-INIZCTEOSA-N 0.000 claims description 2
- CNPURSDMOWDNOQ-UHFFFAOYSA-N 4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound COC1=NC(N)=NC2=C1C=CN2 CNPURSDMOWDNOQ-UHFFFAOYSA-N 0.000 claims description 2
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical group NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 claims description 2
- RHDNHDHIJPHLRC-UHFFFAOYSA-N N,N-diethyl-2H-1,3-oxazol-3-amine Chemical compound C(C)N(N1COC=C1)CC RHDNHDHIJPHLRC-UHFFFAOYSA-N 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- SWRKLVQDHBENAP-IBGZPJMESA-N ethyl 4-[4-(4-fluorophenyl)-5-[2-[[(1s)-1-phenylethyl]amino]pyrimidin-4-yl]-1,3-oxazol-2-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1C1=NC(C=2C=CC(F)=CC=2)=C(C=2N=C(N[C@@H](C)C=3C=CC=CC=3)N=CC=2)O1 SWRKLVQDHBENAP-IBGZPJMESA-N 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 15
- FHMNRQWWQTWZMQ-OOJLDXBWSA-N 4-[3-bromo-2-(4-fluorophenyl)-2h-imidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=CN(Br)C1C1=CC=C(F)C=C1 FHMNRQWWQTWZMQ-OOJLDXBWSA-N 0.000 claims 1
- 230000003110 anti-inflammatory effect Effects 0.000 claims 1
- 229960003444 immunosuppressant agent Drugs 0.000 claims 1
- 230000001861 immunosuppressant effect Effects 0.000 claims 1
- 239000011734 sodium Substances 0.000 description 78
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 71
- 238000005160 1H NMR spectroscopy Methods 0.000 description 68
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 53
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 44
- 239000012074 organic phase Substances 0.000 description 44
- 239000011541 reaction mixture Substances 0.000 description 44
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 43
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 38
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- 229910004298 SiO 2 Inorganic materials 0.000 description 32
- 239000013078 crystal Substances 0.000 description 32
- 239000000243 solution Substances 0.000 description 32
- 239000006260 foam Substances 0.000 description 31
- 239000000203 mixture Substances 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- 239000012047 saturated solution Substances 0.000 description 29
- 239000003795 chemical substances by application Substances 0.000 description 25
- 235000019439 ethyl acetate Nutrition 0.000 description 24
- 238000004587 chromatography analysis Methods 0.000 description 23
- 238000000746 purification Methods 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 18
- 239000011780 sodium chloride Substances 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- 239000000047 product Substances 0.000 description 16
- 102100040247 Tumor necrosis factor Human genes 0.000 description 15
- 238000007792 addition Methods 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- 239000008346 aqueous phase Substances 0.000 description 13
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 12
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 11
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 10
- 238000011282 treatment Methods 0.000 description 10
- FAXGTGUOQXVMMD-AWEZNQCLSA-N 4-[4-bromo-2-(4-fluorophenyl)imidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(Br)N=C1C1=CC=C(F)C=C1 FAXGTGUOQXVMMD-AWEZNQCLSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 229910052786 argon Inorganic materials 0.000 description 9
- 150000001540 azides Chemical class 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- 229910052708 sodium Inorganic materials 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 201000010099 disease Diseases 0.000 description 8
- 239000002158 endotoxin Substances 0.000 description 8
- 229920006008 lipopolysaccharide Polymers 0.000 description 8
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- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Physical Education & Sports Medicine (AREA)
- Diabetes (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Dermatology (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Endocrinology (AREA)
- Biomedical Technology (AREA)
- Ophthalmology & Optometry (AREA)
- Neurosurgery (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Gastroenterology & Hepatology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9908532.6A GB9908532D0 (en) | 1999-04-14 | 1999-04-14 | Organic compounds |
| GB9908531 | 1999-04-14 | ||
| GBGB9908531.8A GB9908531D0 (en) | 1999-04-14 | 1999-04-14 | Organic compounds |
| GB9908532 | 1999-04-14 | ||
| PCT/EP2000/003290 WO2000063204A2 (en) | 1999-04-14 | 2000-04-12 | Substituted azoles |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60003709D1 DE60003709D1 (de) | 2003-08-07 |
| DE60003709T2 true DE60003709T2 (de) | 2004-12-23 |
Family
ID=26315413
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60003709T Expired - Fee Related DE60003709T2 (de) | 1999-04-14 | 2000-04-12 | Substituierte azole |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US6579874B2 (https=) |
| EP (1) | EP1224180B1 (https=) |
| JP (1) | JP2003503311A (https=) |
| KR (1) | KR20010108504A (https=) |
| CN (1) | CN1378544A (https=) |
| AR (1) | AR023465A1 (https=) |
| AT (1) | ATE244236T1 (https=) |
| AU (1) | AU4295300A (https=) |
| BR (1) | BR0010598A (https=) |
| CA (1) | CA2370417A1 (https=) |
| CO (1) | CO5170501A1 (https=) |
| CZ (1) | CZ20013696A3 (https=) |
| DE (1) | DE60003709T2 (https=) |
| DK (1) | DK1224180T3 (https=) |
| ES (1) | ES2202114T3 (https=) |
| HU (1) | HUP0302747A2 (https=) |
| IL (1) | IL145836A0 (https=) |
| MX (1) | MXPA01010434A (https=) |
| NO (1) | NO20014987L (https=) |
| PE (1) | PE20010031A1 (https=) |
| PL (1) | PL364789A1 (https=) |
| PT (1) | PT1224180E (https=) |
| SK (1) | SK14562001A3 (https=) |
| TR (1) | TR200102967T2 (https=) |
| WO (1) | WO2000063204A2 (https=) |
Families Citing this family (56)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MXPA02003436A (es) | 1999-10-07 | 2002-08-20 | Amgen Inc | Inhibidores de triazina cinasa. |
| AU7922900A (en) * | 1999-10-27 | 2001-05-08 | Novartis Ag | Thiazole and imidazo (4,5-b) pyridine compounds and their pharmaceutical use |
| AU3704101A (en) * | 2000-02-17 | 2001-08-27 | Amgen Inc | Kinase inhibitors |
| BR0116452A (pt) | 2000-12-21 | 2003-09-30 | Glaxo Group Ltd | Composto, composição farmacêutica, uso de um composto |
| WO2002051442A1 (en) * | 2000-12-26 | 2002-07-04 | Takeda Chemical Industries, Ltd. | Concomitant drugs |
| US7199124B2 (en) | 2001-02-02 | 2007-04-03 | Takeda Pharmaceutical Company Limited | JNK inhibitor |
| AP2002002460A0 (en) | 2001-03-09 | 2002-06-30 | Pfizer Prod Inc | Novel benzimidazole anti-inflammatory compounds. |
| HUP0303415A2 (hu) | 2001-03-09 | 2004-01-28 | Pfizer Products Inc. | Triazolopiridinek, mint gyulladásgátló anyagok és ezeket tartalmazó gyógyszerkészítmények |
| DE60205974T2 (de) | 2001-04-04 | 2006-06-29 | Pfizer Products Inc., Groton | Neue Benzotriazole mit entzündungshemmender Wirkung |
| EP1402900A1 (en) * | 2001-06-11 | 2004-03-31 | Takeda Chemical Industries, Ltd. | Medicinal compositions |
| TWI231757B (en) * | 2001-09-21 | 2005-05-01 | Solvay Pharm Bv | 1H-Imidazole derivatives having CB1 agonistic, CB1 partial agonistic or CB1-antagonistic activity |
| US7109216B2 (en) | 2001-09-21 | 2006-09-19 | Solvay Pharmaceuticals B.V. | 1H-imidazole derivatives having CB1 agonistic, CB1 partial agonistic or CB1-antagonistic activity |
| KR100903760B1 (ko) | 2001-09-21 | 2009-06-19 | 솔베이 파마슈티칼스 비. 브이 | Ｃｂ1-길항 작용을 가지는 신규한4,5-디하이드로-1ｈ-피라졸 유도체 |
| US7473695B2 (en) * | 2001-10-22 | 2009-01-06 | Mitsubishi Tanabe Pharma Corporation | 4-imidazolin-2-one compounds |
| WO2003053922A2 (en) * | 2001-12-19 | 2003-07-03 | Merck & Co., Inc. | Heteroaryl substituted imidazole modulators of metabotropic glutamate receptor-5 |
| AR039241A1 (es) * | 2002-04-04 | 2005-02-16 | Biogen Inc | Heteroarilos trisustituidos y metodos para su produccion y uso de los mismos |
| ES2278170T3 (es) | 2002-07-09 | 2007-08-01 | BOEHRINGER INGELHEIM PHARMA GMBH & CO.KG | Composiciones farmaceuticas de anticolinergicos e inhibidores de la quinasa p38 en el tratamiento de enfermedades respiratorias. |
| US7074809B2 (en) | 2002-08-09 | 2006-07-11 | Astrazeneca Ab | Compounds |
| TW200424183A (en) * | 2002-08-09 | 2004-11-16 | Nps Pharma Inc | New compounds |
| WO2004014881A2 (en) | 2002-08-09 | 2004-02-19 | Astra Zeneca Ab | '1,2,4'oxadiazoles as modulators of metabotropic glutamate receptor-5 |
| US7012143B2 (en) | 2002-08-30 | 2006-03-14 | Dombroski Mark A | Cycloalkyl-[4-(difluorophenyl)-oxazol-5-yl]-triazolo-pyridines |
| US7037923B2 (en) | 2002-08-30 | 2006-05-02 | Pfizer, Inc. | Alkyl-[4-(trifluorophenyl)-oxazol-5-yl]-triazolo-pyridines |
| WO2004020438A2 (en) * | 2002-08-30 | 2004-03-11 | Pfizer Products Inc. | Novel processes and intermediates for preparing triazolo-pyridines |
| US7005523B2 (en) | 2002-08-30 | 2006-02-28 | Pfizer Inc. | Cycloalkyl-[4-(trifluorophenyl)-oxazol-5yl]-triazolo-pyridines |
| US6949652B2 (en) | 2002-08-30 | 2005-09-27 | Pfizer, Inc. | Crystalline forms of 3-isopropyl-6-[4-(2,5-difluoro-phenyl)-oxazol-5-yl]-[1,2,4]triazolo-[4,3-A]pyridine |
| PA8579601A1 (es) | 2002-08-30 | 2004-05-07 | Pfizer Prod Inc | Compuestos antiinflamatorios de di y trifloruro-triazolo-piridinas |
| UA80295C2 (en) * | 2002-09-06 | 2007-09-10 | Biogen Inc | Pyrazolopyridines and using the same |
| AU2003300076C1 (en) | 2002-12-30 | 2010-03-04 | Angiotech International Ag | Drug delivery from rapid gelling polymer composition |
| US7622471B2 (en) | 2003-02-07 | 2009-11-24 | Daiichi Pharmaceutical Co., Ltd. | Pyrazole derivatives having a pyridazine and pyridine functionality |
| EP1601672B1 (en) | 2003-02-14 | 2006-07-26 | Pfizer Products Inc. | Triazolo-pyridines as anti-inflammatory compounds |
| TWI326282B (en) * | 2004-04-28 | 2010-06-21 | Mitsubishi Tanabe Pharma Corp | Heterocyclic compound |
| US7858800B2 (en) | 2004-06-30 | 2010-12-28 | Banyu Pharmaceutical Co., Ltd. | Biaryl derivatives |
| US20060035893A1 (en) | 2004-08-07 | 2006-02-16 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions for treatment of respiratory and gastrointestinal disorders |
| PE20060777A1 (es) | 2004-12-24 | 2006-10-06 | Boehringer Ingelheim Int | Derivados de indolinona para el tratamiento o la prevencion de enfermedades fibroticas |
| EP3143926B1 (en) * | 2006-02-08 | 2020-07-01 | The General Hospital Corporation | Methods, arrangements and systems for obtaining information associated with an anatomical sample using optical microscopy |
| ES2301380B1 (es) | 2006-08-09 | 2009-06-08 | Laboratorios Almirall S.A. | Nuevos derivados de 1,7-naftiridina. |
| ES2320955B1 (es) | 2007-03-02 | 2010-03-16 | Laboratorios Almirall S.A. | Nuevos derivados de 3-((1,2,4)triazolo(4,3-a)piridin-7-il)benzamida. |
| ES2329639B1 (es) | 2007-04-26 | 2010-09-23 | Laboratorios Almirall S.A. | Nuevos derivados de 4,8-difenilpoliazanaftaleno. |
| NZ580660A (en) | 2007-04-30 | 2012-02-24 | Abbott Lab | Inhibitors of diacylglycerol o-acyltransferase type 1 enzyme |
| EP1992344A1 (en) | 2007-05-18 | 2008-11-19 | Institut Curie | P38 alpha as a therapeutic target in pathologies linked to FGFR3 mutation |
| US9029411B2 (en) | 2008-01-25 | 2015-05-12 | Millennium Pharmaceuticals, Inc. | Thiophenes and uses thereof |
| EP2108641A1 (en) | 2008-04-11 | 2009-10-14 | Laboratorios Almirall, S.A. | New substituted spiro[cycloalkyl-1,3'-indo]-2'(1'H)-one derivatives and their use as p38 mitogen-activated kinase inhibitors |
| EP2113503A1 (en) | 2008-04-28 | 2009-11-04 | Laboratorios Almirall, S.A. | New substituted indolin-2-one derivatives and their use as p39 mitogen-activated kinase inhibitors |
| WO2010090716A1 (en) | 2009-01-30 | 2010-08-12 | Millennium Pharmaceuticals, Inc. | Heteroaryls and their use as pi3k inhibitors |
| US9090601B2 (en) | 2009-01-30 | 2015-07-28 | Millennium Pharmaceuticals, Inc. | Thiazole derivatives |
| US8796314B2 (en) | 2009-01-30 | 2014-08-05 | Millennium Pharmaceuticals, Inc. | Heteroaryls and uses thereof |
| MX2011012343A (es) * | 2009-05-19 | 2011-12-14 | Dow Agrosciences Llc | Compuestos y metodos para controlar hongos. |
| EP2322176A1 (en) | 2009-11-11 | 2011-05-18 | Almirall, S.A. | New 7-phenyl-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one derivatives |
| WO2012021611A1 (en) | 2010-08-11 | 2012-02-16 | Millennium Pharmaceuticals, Inc. | Heteroaryls and uses thereof |
| TW201217365A (en) | 2010-08-11 | 2012-05-01 | Millennium Pharm Inc | Heteroaryls and uses thereof |
| US8859768B2 (en) | 2010-08-11 | 2014-10-14 | Millennium Pharmaceuticals, Inc. | Heteroaryls and uses thereof |
| TW201307309A (zh) | 2010-10-13 | 2013-02-16 | Millennium Pharm Inc | 雜芳基化合物及其用途 |
| AR086113A1 (es) | 2011-04-30 | 2013-11-20 | Abbott Lab | Isoxazolinas como agentes terapeuticos |
| US20190060286A1 (en) | 2016-02-29 | 2019-02-28 | University Of Florida Research Foundation, Incorpo | Chemotherapeutic Methods |
| WO2018159650A1 (ja) * | 2017-02-28 | 2018-09-07 | 東レ株式会社 | グアニジン誘導体及びその医薬用途 |
| US12441707B2 (en) | 2019-12-30 | 2025-10-14 | Tyra Biosciences, Inc. | Indazole compounds |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0727998B1 (en) * | 1993-11-08 | 2004-01-21 | Smithkline Beecham Corporation | Oxazoles for treating cytokine mediated diseases |
| US5739143A (en) * | 1995-06-07 | 1998-04-14 | Smithkline Beecham Corporation | Imidazole compounds and compositions |
| IL118544A (en) * | 1995-06-07 | 2001-08-08 | Smithkline Beecham Corp | History of imidazole, the process for their preparation and the pharmaceutical preparations containing them |
| JP3294616B2 (ja) * | 1995-08-10 | 2002-06-24 | メルク エンド カンパニー インコーポレーテッド | ２−置換アリールピロール、このような化合物を含む組成物及び使用方法 |
| US6492516B1 (en) * | 1999-05-14 | 2002-12-10 | Merck & Co., Inc. | Compounds having cytokine inhibitory activity |
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2000
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- 2000-04-12 DK DK00922630T patent/DK1224180T3/da active
- 2000-04-12 PL PL00364789A patent/PL364789A1/xx not_active Application Discontinuation
- 2000-04-12 KR KR1020017013086A patent/KR20010108504A/ko not_active Withdrawn
- 2000-04-12 CZ CZ20013696A patent/CZ20013696A3/cs unknown
- 2000-04-12 AU AU42953/00A patent/AU4295300A/en not_active Abandoned
- 2000-04-12 PT PT00922630T patent/PT1224180E/pt unknown
- 2000-04-12 PE PE2000000337A patent/PE20010031A1/es not_active Application Discontinuation
- 2000-04-12 MX MXPA01010434A patent/MXPA01010434A/es unknown
- 2000-04-12 EP EP00922630A patent/EP1224180B1/en not_active Expired - Lifetime
- 2000-04-12 JP JP2000612294A patent/JP2003503311A/ja active Pending
- 2000-04-12 AT AT00922630T patent/ATE244236T1/de not_active IP Right Cessation
- 2000-04-12 BR BR0010598-8A patent/BR0010598A/pt not_active IP Right Cessation
- 2000-04-12 TR TR2001/02967T patent/TR200102967T2/xx unknown
- 2000-04-12 WO PCT/EP2000/003290 patent/WO2000063204A2/en not_active Ceased
- 2000-04-12 DE DE60003709T patent/DE60003709T2/de not_active Expired - Fee Related
- 2000-04-12 IL IL14583600A patent/IL145836A0/xx unknown
- 2000-04-12 HU HU0302747A patent/HUP0302747A2/hu unknown
- 2000-04-12 ES ES00922630T patent/ES2202114T3/es not_active Expired - Lifetime
- 2000-04-12 CA CA002370417A patent/CA2370417A1/en not_active Abandoned
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- 2000-04-12 SK SK1456-2001A patent/SK14562001A3/sk unknown
- 2000-04-12 AR ARP000101686A patent/AR023465A1/es unknown
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2001
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- 2001-10-12 NO NO20014987A patent/NO20014987L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| CZ20013696A3 (cs) | 2002-02-13 |
| BR0010598A (pt) | 2002-02-05 |
| WO2000063204A2 (en) | 2000-10-26 |
| PT1224180E (pt) | 2003-11-28 |
| US6579874B2 (en) | 2003-06-17 |
| JP2003503311A (ja) | 2003-01-28 |
| AR023465A1 (es) | 2002-09-04 |
| NO20014987L (no) | 2001-12-14 |
| PE20010031A1 (es) | 2001-02-23 |
| US20020049220A1 (en) | 2002-04-25 |
| IL145836A0 (en) | 2002-07-25 |
| AU4295300A (en) | 2000-11-02 |
| HUP0302747A2 (hu) | 2003-12-29 |
| MXPA01010434A (es) | 2002-03-27 |
| NO20014987D0 (no) | 2001-10-12 |
| DE60003709D1 (de) | 2003-08-07 |
| EP1224180B1 (en) | 2003-07-02 |
| ES2202114T3 (es) | 2004-04-01 |
| SK14562001A3 (sk) | 2002-03-05 |
| DK1224180T3 (da) | 2003-10-20 |
| WO2000063204A3 (en) | 2002-05-23 |
| ATE244236T1 (de) | 2003-07-15 |
| TR200102967T2 (tr) | 2002-01-21 |
| PL364789A1 (en) | 2004-12-13 |
| CO5170501A1 (es) | 2002-06-27 |
| EP1224180A2 (en) | 2002-07-24 |
| KR20010108504A (ko) | 2001-12-07 |
| CA2370417A1 (en) | 2000-10-26 |
| CN1378544A (zh) | 2002-11-06 |
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