ZA200208899B - Phenylglycine derivatives. - Google Patents
Phenylglycine derivatives. Download PDFInfo
- Publication number
- ZA200208899B ZA200208899B ZA200208899A ZA200208899A ZA200208899B ZA 200208899 B ZA200208899 B ZA 200208899B ZA 200208899 A ZA200208899 A ZA 200208899A ZA 200208899 A ZA200208899 A ZA 200208899A ZA 200208899 B ZA200208899 B ZA 200208899B
- Authority
- ZA
- South Africa
- Prior art keywords
- ethoxy
- fluoro
- phenyl
- phenylamino
- acetic acid
- Prior art date
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- 150000005331 phenylglycines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 145
- -1 alkoxyalkoxycarbonyl Chemical group 0.000 claims description 90
- 239000000203 mixture Substances 0.000 claims description 54
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 43
- 239000001257 hydrogen Substances 0.000 claims description 41
- 229910052739 hydrogen Inorganic materials 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 24
- 235000002639 sodium chloride Nutrition 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 19
- 150000002431 hydrogen Chemical class 0.000 claims description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 150000002148 esters Chemical class 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 10
- 206010008190 Cerebrovascular accident Diseases 0.000 claims description 10
- 206010061216 Infarction Diseases 0.000 claims description 10
- 206010061218 Inflammation Diseases 0.000 claims description 10
- 208000006011 Stroke Diseases 0.000 claims description 10
- 208000007536 Thrombosis Diseases 0.000 claims description 10
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 10
- 230000000747 cardiac effect Effects 0.000 claims description 10
- 230000007574 infarction Effects 0.000 claims description 10
- 230000004054 inflammatory process Effects 0.000 claims description 10
- 229910052731 fluorine Inorganic materials 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 238000011282 treatment Methods 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 125000004185 ester group Chemical group 0.000 claims description 7
- 239000012453 solvate Substances 0.000 claims description 7
- DZEPTAZKEKTXAE-UHFFFAOYSA-N 2-(4-carbamimidoylanilino)-2-(3,5-diethoxy-2-fluorophenyl)acetic acid Chemical compound CCOC1=CC(OCC)=C(F)C(C(NC=2C=CC(=CC=2)C(N)=N)C(O)=O)=C1 DZEPTAZKEKTXAE-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 239000013543 active substance Substances 0.000 claims description 6
- 230000000259 anti-tumor effect Effects 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 150000004677 hydrates Chemical class 0.000 claims description 6
- 239000003112 inhibitor Substances 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- DZEPTAZKEKTXAE-QGZVFWFLSA-N (2r)-2-(4-carbamimidoylanilino)-2-(3,5-diethoxy-2-fluorophenyl)acetic acid Chemical compound CCOC1=CC(OCC)=C(F)C([C@@H](NC=2C=CC(=CC=2)C(N)=N)C(O)=O)=C1 DZEPTAZKEKTXAE-QGZVFWFLSA-N 0.000 claims description 5
- 108010000499 Thromboplastin Proteins 0.000 claims description 5
- 102000002262 Thromboplastin Human genes 0.000 claims description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- AWHKSYNTYWNWAP-UHFFFAOYSA-N ethyl 2-[5-ethoxy-2-fluoro-4-(2-hydroxyethoxy)phenyl]-2-[4-(n'-hydroxycarbamimidoyl)anilino]acetate Chemical compound C=1C(OCC)=C(OCCO)C=C(F)C=1C(C(=O)OCC)NC1=CC=C(C(=N)NO)C=C1 AWHKSYNTYWNWAP-UHFFFAOYSA-N 0.000 claims description 5
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 claims description 5
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 5
- 230000004962 physiological condition Effects 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 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 5
- 230000001225 therapeutic effect Effects 0.000 claims description 5
- ZZJWEGGRVSDXNY-UHFFFAOYSA-N 2-(4-carbamimidoylanilino)-2-(2-fluoro-3,5-dimethoxyphenyl)acetic acid Chemical compound COC1=CC(OC)=C(F)C(C(NC=2C=CC(=CC=2)C(N)=N)C(O)=O)=C1 ZZJWEGGRVSDXNY-UHFFFAOYSA-N 0.000 claims description 4
- 206010028980 Neoplasm Diseases 0.000 claims description 4
- 125000005225 alkynyloxycarbonyl group Chemical group 0.000 claims description 4
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 4
- 125000005199 aryl carbonyloxy group Chemical group 0.000 claims description 4
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 125000005170 cycloalkyloxycarbonyl group Chemical group 0.000 claims description 4
- NKKOJKWWLSWHRG-HXUWFJFHSA-N ethyl (2r)-2-[5-ethoxy-2-fluoro-4-(2-hydroxyethoxy)phenyl]-2-[4-[(z)-n'-(2,2,2-trichloroethoxycarbonyl)carbamimidoyl]anilino]acetate Chemical compound N([C@@H](C(=O)OCC)C=1C(=CC(OCCO)=C(OCC)C=1)F)C1=CC=C(C(N)=NC(=O)OCC(Cl)(Cl)Cl)C=C1 NKKOJKWWLSWHRG-HXUWFJFHSA-N 0.000 claims description 4
- SIPDVTKTWHWBKX-DHYQBIDMSA-N ethyl 2-(4-carbamimidoylanilino)-2-[5-ethoxy-2-fluoro-3-[(3r)-oxolan-3-yl]oxyphenyl]acetate;hydrochloride Chemical compound Cl.C=1C(OCC)=CC(O[C@H]2COCC2)=C(F)C=1C(C(=O)OCC)NC1=CC=C(C(N)=N)C=C1 SIPDVTKTWHWBKX-DHYQBIDMSA-N 0.000 claims description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000002560 nitrile group Chemical group 0.000 claims description 4
- 238000011321 prophylaxis Methods 0.000 claims description 4
- LYTQWYMDFRNFGJ-UHFFFAOYSA-N 2-(3,5-diethoxy-2-fluorophenyl)-2-[4-(n'-hydroxycarbamimidoyl)anilino]acetic acid Chemical compound CCOC1=CC(OCC)=C(F)C(C(NC=2C=CC(=CC=2)C(=N)NO)C(O)=O)=C1 LYTQWYMDFRNFGJ-UHFFFAOYSA-N 0.000 claims description 3
- 108010039209 Blood Coagulation Factors Proteins 0.000 claims description 3
- 102000015081 Blood Coagulation Factors Human genes 0.000 claims description 3
- 108010054265 Factor VIIa Proteins 0.000 claims description 3
- 108090000190 Thrombin Proteins 0.000 claims description 3
- 125000005195 alkyl amino carbonyloxy group Chemical group 0.000 claims description 3
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 3
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
- XFJXXYQMXPGEKY-XMMPIXPASA-N benzyl (2r)-2-[5-ethoxy-2-fluoro-4-(2-hydroxyethoxy)phenyl]-2-[4-[(z)-n'-hydroxycarbamimidoyl]anilino]acetate Chemical compound C1=C(OCCO)C(OCC)=CC([C@@H](NC=2C=CC(=CC=2)C(=N)NO)C(=O)OCC=2C=CC=CC=2)=C1F XFJXXYQMXPGEKY-XMMPIXPASA-N 0.000 claims description 3
- 239000003114 blood coagulation factor Substances 0.000 claims description 3
- WWMGICLNRLIPHK-UHFFFAOYSA-N butyl 2-[5-ethoxy-2-fluoro-4-(2-hydroxyethoxy)phenyl]-2-[4-(n'-hydroxycarbamimidoyl)anilino]acetate Chemical compound C=1C(OCC)=C(OCCO)C=C(F)C=1C(C(=O)OCCCC)NC1=CC=C(C(=N)NO)C=C1 WWMGICLNRLIPHK-UHFFFAOYSA-N 0.000 claims description 3
- SZVXFIATBBBFJY-RUZDIDTESA-N ethyl (2r)-2-[4-(n'-benzoylcarbamimidoyl)anilino]-2-[5-ethoxy-2-fluoro-4-(2-hydroxyethoxy)phenyl]acetate Chemical compound N([C@@H](C(=O)OCC)C=1C(=CC(OCCO)=C(OCC)C=1)F)C(C=C1)=CC=C1C(N)=NC(=O)C1=CC=CC=C1 SZVXFIATBBBFJY-RUZDIDTESA-N 0.000 claims description 3
- AWHKSYNTYWNWAP-LJQANCHMSA-N ethyl (2r)-2-[5-ethoxy-2-fluoro-4-(2-hydroxyethoxy)phenyl]-2-[4-[(z)-n'-hydroxycarbamimidoyl]anilino]acetate Chemical compound N([C@@H](C(=O)OCC)C=1C(=CC(OCCO)=C(OCC)C=1)F)C1=CC=C(C(=N)NO)C=C1 AWHKSYNTYWNWAP-LJQANCHMSA-N 0.000 claims description 3
- NKKOJKWWLSWHRG-FQEVSTJZSA-N ethyl (2s)-2-[5-ethoxy-2-fluoro-4-(2-hydroxyethoxy)phenyl]-2-[4-[(z)-n'-(2,2,2-trichloroethoxycarbonyl)carbamimidoyl]anilino]acetate Chemical compound N([C@H](C(=O)OCC)C=1C(=CC(OCCO)=C(OCC)C=1)F)C1=CC=C(C(N)=NC(=O)OCC(Cl)(Cl)Cl)C=C1 NKKOJKWWLSWHRG-FQEVSTJZSA-N 0.000 claims description 3
- GQPONXGDRFRIBB-UHFFFAOYSA-N ethyl 2-(3,5-diethoxy-2-fluorophenyl)-2-[4-(n'-hydroxycarbamimidoyl)anilino]acetate Chemical compound C=1C(OCC)=CC(OCC)=C(F)C=1C(C(=O)OCC)NC1=CC=C(C(=N)NO)C=C1 GQPONXGDRFRIBB-UHFFFAOYSA-N 0.000 claims description 3
- LBLIAXOZFNTXAC-UHFFFAOYSA-N ethyl 2-(3,5-diethoxy-2-fluorophenyl)-2-[4-[(z)-n'-(2-methylpropoxycarbonyl)carbamimidoyl]anilino]acetate Chemical compound C=1C(OCC)=CC(OCC)=C(F)C=1C(C(=O)OCC)NC1=CC=C(C(N)=NC(=O)OCC(C)C)C=C1 LBLIAXOZFNTXAC-UHFFFAOYSA-N 0.000 claims description 3
- ZWJWIGHEXIBQSS-UHFFFAOYSA-N ethyl 2-[4-[n'-(3,4-dimethoxybenzoyl)carbamimidoyl]anilino]-2-[5-ethoxy-2-fluoro-4-(2-hydroxyethoxy)phenyl]acetate Chemical compound C=1C(OCC)=C(OCCO)C=C(F)C=1C(C(=O)OCC)NC(C=C1)=CC=C1C(N)=NC(=O)C1=CC=C(OC)C(OC)=C1 ZWJWIGHEXIBQSS-UHFFFAOYSA-N 0.000 claims description 3
- DRKZMUNPACVHEZ-UHFFFAOYSA-N ethyl 2-[4-[n'-(3,5-dimethoxybenzoyl)carbamimidoyl]anilino]-2-[5-ethoxy-2-fluoro-4-(2-hydroxyethoxy)phenyl]acetate Chemical compound C=1C(OCC)=C(OCCO)C=C(F)C=1C(C(=O)OCC)NC(C=C1)=CC=C1C(N)=NC(=O)C1=CC(OC)=CC(OC)=C1 DRKZMUNPACVHEZ-UHFFFAOYSA-N 0.000 claims description 3
- WYVHQTYMHZIWJY-UHFFFAOYSA-N ethyl 2-[5-ethoxy-2-fluoro-4-(2-hydroxyethoxy)phenyl]-2-[4-[(z)-n'-prop-2-ynoxycarbonylcarbamimidoyl]anilino]acetate Chemical compound C=1C(OCC)=C(OCCO)C=C(F)C=1C(C(=O)OCC)NC1=CC=C(C(N)=NC(=O)OCC#C)C=C1 WYVHQTYMHZIWJY-UHFFFAOYSA-N 0.000 claims description 3
- VQGRZMVDIHFRLH-UHFFFAOYSA-N ethyl 2-[5-ethoxy-2-fluoro-4-(2-hydroxyethoxy)phenyl]-2-[4-[n'-(3-fluorobenzoyl)carbamimidoyl]anilino]acetate Chemical compound C=1C(OCC)=C(OCCO)C=C(F)C=1C(C(=O)OCC)NC(C=C1)=CC=C1C(N)=NC(=O)C1=CC=CC(F)=C1 VQGRZMVDIHFRLH-UHFFFAOYSA-N 0.000 claims description 3
- OIXIVRIFAZEMKJ-UHFFFAOYSA-N ethyl 2-[5-ethoxy-2-fluoro-4-(2-hydroxyethoxy)phenyl]-2-[4-[n'-[4-(trifluoromethyl)benzoyl]carbamimidoyl]anilino]acetate Chemical compound C=1C(OCC)=C(OCCO)C=C(F)C=1C(C(=O)OCC)NC(C=C1)=CC=C1C(N)=NC(=O)C1=CC=C(C(F)(F)F)C=C1 OIXIVRIFAZEMKJ-UHFFFAOYSA-N 0.000 claims description 3
- MSNWNSMQEMQKEP-UHFFFAOYSA-N ethyl 2-[5-ethoxy-2-fluoro-4-[2-(2,2,2-trichloroethoxycarbonyloxy)ethoxy]phenyl]-2-[4-[(z)-n'-(2,2,2-trichloroethoxycarbonyl)carbamimidoyl]anilino]acetate Chemical compound C=1C(OCC)=C(OCCOC(=O)OCC(Cl)(Cl)Cl)C=C(F)C=1C(C(=O)OCC)NC1=CC=C(C(N)=NC(=O)OCC(Cl)(Cl)Cl)C=C1 MSNWNSMQEMQKEP-UHFFFAOYSA-N 0.000 claims description 3
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 3
- 229940012414 factor viia Drugs 0.000 claims description 3
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 3
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 3
- OVRJEFAOMUMCIS-UHFFFAOYSA-N propan-2-yl 2-(3,5-diethoxy-2-fluorophenyl)-2-[4-[(z)-n'-hydroxycarbamimidoyl]anilino]acetate Chemical compound CCOC1=CC(OCC)=C(F)C(C(NC=2C=CC(=CC=2)C(=N)NO)C(=O)OC(C)C)=C1 OVRJEFAOMUMCIS-UHFFFAOYSA-N 0.000 claims description 3
- NXQIVQYBQRMZOC-UHFFFAOYSA-M sodium;2-[5-ethoxy-2-fluoro-4-(2-hydroxyethoxy)phenyl]-2-[4-(n'-hydroxycarbamimidoyl)anilino]acetic acid;chloride Chemical compound [Na+].[Cl-].C1=C(OCCO)C(OCC)=CC(C(NC=2C=CC(=CC=2)C(=N)NO)C(O)=O)=C1F NXQIVQYBQRMZOC-UHFFFAOYSA-M 0.000 claims description 3
- 229960004072 thrombin Drugs 0.000 claims description 3
- PGYOHIAQCFZQDK-AUUYWEPGSA-N (2r)-({4-[amino(imino)methyl]phenyl}amino){5-ethoxy-2-fluoro-3-[(3r)-tetrahydrofuran-3-yloxy]phenyl}aceticacid Chemical compound FC=1C([C@@H](NC=2C=CC(=CC=2)C(N)=N)C(O)=O)=CC(OCC)=CC=1O[C@@H]1CCOC1 PGYOHIAQCFZQDK-AUUYWEPGSA-N 0.000 claims description 2
- LYTQWYMDFRNFGJ-QGZVFWFLSA-N (2r)-2-(3,5-diethoxy-2-fluorophenyl)-2-[4-[(z)-n'-hydroxycarbamimidoyl]anilino]acetic acid Chemical compound CCOC1=CC(OCC)=C(F)C([C@@H](NC=2C=CC(=CC=2)C(=N)NO)C(O)=O)=C1 LYTQWYMDFRNFGJ-QGZVFWFLSA-N 0.000 claims description 2
- SPRCXIFJYSPLSK-QGZVFWFLSA-N (2r)-2-[5-ethoxy-2-fluoro-4-(2-hydroxyethoxy)phenyl]-2-[4-[(z)-n'-hydroxycarbamimidoyl]anilino]acetic acid Chemical compound C1=C(OCCO)C(OCC)=CC([C@@H](NC=2C=CC(=CC=2)C(=N)NO)C(O)=O)=C1F SPRCXIFJYSPLSK-QGZVFWFLSA-N 0.000 claims description 2
- DZEPTAZKEKTXAE-KRWDZBQOSA-N (2s)-2-(4-carbamimidoylanilino)-2-(3,5-diethoxy-2-fluorophenyl)acetic acid Chemical compound CCOC1=CC(OCC)=C(F)C([C@H](NC=2C=CC(=CC=2)C(N)=N)C(O)=O)=C1 DZEPTAZKEKTXAE-KRWDZBQOSA-N 0.000 claims description 2
- 125000006334 2,4-difluoro benzoyl group Chemical group [H]C1=C([H])C(C(*)=O)=C(F)C([H])=C1F 0.000 claims description 2
- LDQYJMFGBNUUFM-UHFFFAOYSA-N 2-methylpropyl 2-[5-ethoxy-2-fluoro-4-(2-hydroxyethoxy)phenyl]-2-[4-[(z)-n'-hydroxycarbamimidoyl]anilino]acetate Chemical compound C1=C(OCCO)C(OCC)=CC(C(NC=2C=CC(=CC=2)C(=N)NO)C(=O)OCC(C)C)=C1F LDQYJMFGBNUUFM-UHFFFAOYSA-N 0.000 claims description 2
- 241001465754 Metazoa Species 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims description 2
- 125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 claims description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 2
- WWMGICLNRLIPHK-OAQYLSRUSA-N butyl (2r)-2-[5-ethoxy-2-fluoro-4-(2-hydroxyethoxy)phenyl]-2-[4-[(z)-n'-hydroxycarbamimidoyl]anilino]acetate Chemical compound N([C@@H](C(=O)OCCCC)C=1C(=CC(OCCO)=C(OCC)C=1)F)C1=CC=C(C(=N)NO)C=C1 WWMGICLNRLIPHK-OAQYLSRUSA-N 0.000 claims description 2
- WWMGICLNRLIPHK-NRFANRHFSA-N butyl (2s)-2-[5-ethoxy-2-fluoro-4-(2-hydroxyethoxy)phenyl]-2-[4-[(z)-n'-hydroxycarbamimidoyl]anilino]acetate Chemical compound N([C@H](C(=O)OCCCC)C=1C(=CC(OCCO)=C(OCC)C=1)F)C1=CC=C(C(=N)NO)C=C1 WWMGICLNRLIPHK-NRFANRHFSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- WGPFQUALDICQFQ-UHFFFAOYSA-N ethyl 2-(3,5-diethoxy-2-fluorophenyl)-2-[4-[(z)-n'-ethoxycarbonylcarbamimidoyl]anilino]acetate Chemical compound C1=CC(C(N)=NC(=O)OCC)=CC=C1NC(C(=O)OCC)C1=CC(OCC)=CC(OCC)=C1F WGPFQUALDICQFQ-UHFFFAOYSA-N 0.000 claims description 2
- AHRSELPVONXXCJ-UHFFFAOYSA-N ethyl 2-(3,5-diethoxy-2-fluorophenyl)-2-[4-[n'-(2,2,2-trichloroethoxycarbonyl)carbamimidoyl]anilino]acetate Chemical compound C=1C(OCC)=CC(OCC)=C(F)C=1C(C(=O)OCC)NC1=CC=C(C(N)=NC(=O)OCC(Cl)(Cl)Cl)C=C1 AHRSELPVONXXCJ-UHFFFAOYSA-N 0.000 claims description 2
- AVZJTKZIEQWHTA-UHFFFAOYSA-N ethyl 2-(3,5-diethoxy-2-fluorophenyl)-2-[4-[n'-(4-fluorobenzoyl)carbamimidoyl]anilino]acetate Chemical compound C=1C(OCC)=CC(OCC)=C(F)C=1C(C(=O)OCC)NC(C=C1)=CC=C1C(N)=NC(=O)C1=CC=C(F)C=C1 AVZJTKZIEQWHTA-UHFFFAOYSA-N 0.000 claims description 2
- CGZWIDGYLZLRQJ-UHFFFAOYSA-N ethyl 2-(3,5-diethoxy-2-fluorophenyl)-2-[4-[n'-(4-fluorophenoxy)carbonylcarbamimidoyl]anilino]acetate Chemical compound C=1C(OCC)=CC(OCC)=C(F)C=1C(C(=O)OCC)NC(C=C1)=CC=C1C(N)=NC(=O)OC1=CC=C(F)C=C1 CGZWIDGYLZLRQJ-UHFFFAOYSA-N 0.000 claims description 2
- ILJMBQZQGFYOQA-UHFFFAOYSA-N ethyl 2-(4-carbamimidoylanilino)-2-(2-fluoro-3,5-dimethoxyphenyl)acetate Chemical compound C=1C(OC)=CC(OC)=C(F)C=1C(C(=O)OCC)NC1=CC=C(C(N)=N)C=C1 ILJMBQZQGFYOQA-UHFFFAOYSA-N 0.000 claims description 2
- WTGXIUGUPPZHKK-UHFFFAOYSA-N ethyl 2-[4-[(z)-n'-ethoxycarbonylcarbamimidoyl]anilino]-2-[5-ethoxy-2-fluoro-4-(2-hydroxyethoxy)phenyl]acetate Chemical compound C1=CC(C(N)=NC(=O)OCC)=CC=C1NC(C(=O)OCC)C1=CC(OCC)=C(OCCO)C=C1F WTGXIUGUPPZHKK-UHFFFAOYSA-N 0.000 claims description 2
- KDIPYMAJSPCXKE-UJONTBEJSA-N ethyl 2-[5-ethoxy-2-fluoro-3-[(3r)-oxolan-3-yl]oxyphenyl]-2-[4-(n'-hydroxycarbamimidoyl)anilino]acetate Chemical compound C=1C(OCC)=CC(O[C@H]2COCC2)=C(F)C=1C(C(=O)OCC)NC1=CC=C(C(=N)NO)C=C1 KDIPYMAJSPCXKE-UJONTBEJSA-N 0.000 claims description 2
- NFIIIGSWZNFSKT-UHFFFAOYSA-N ethyl 2-[5-ethoxy-2-fluoro-4-(2-hydroxyethoxy)phenyl]-2-[4-[(e)-n'-methoxycarbonylcarbamimidoyl]anilino]acetate Chemical compound C=1C(OCC)=C(OCCO)C=C(F)C=1C(C(=O)OCC)NC1=CC=C(C(N)=NC(=O)OC)C=C1 NFIIIGSWZNFSKT-UHFFFAOYSA-N 0.000 claims description 2
- NKKOJKWWLSWHRG-UHFFFAOYSA-N ethyl 2-[5-ethoxy-2-fluoro-4-(2-hydroxyethoxy)phenyl]-2-[4-[(z)-n'-(2,2,2-trichloroethoxycarbonyl)carbamimidoyl]anilino]acetate Chemical compound C=1C(OCC)=C(OCCO)C=C(F)C=1C(C(=O)OCC)NC1=CC=C(C(N)=NC(=O)OCC(Cl)(Cl)Cl)C=C1 NKKOJKWWLSWHRG-UHFFFAOYSA-N 0.000 claims description 2
- KGRZSEIICXKDER-UHFFFAOYSA-N ethyl 2-[5-ethoxy-2-fluoro-4-(2-hydroxyethoxy)phenyl]-2-[4-[(z)-n'-(phenylcarbamoyl)carbamimidoyl]anilino]acetate Chemical compound C=1C(OCC)=C(OCCO)C=C(F)C=1C(C(=O)OCC)NC(C=C1)=CC=C1C(N)=NC(=O)NC1=CC=CC=C1 KGRZSEIICXKDER-UHFFFAOYSA-N 0.000 claims description 2
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- XFJXXYQMXPGEKY-DEOSSOPVSA-N benzyl (2s)-2-[5-ethoxy-2-fluoro-4-(2-hydroxyethoxy)phenyl]-2-[4-[(z)-n'-hydroxycarbamimidoyl]anilino]acetate Chemical compound C1=C(OCCO)C(OCC)=CC([C@H](NC=2C=CC(=CC=2)C(=N)NO)C(=O)OCC=2C=CC=CC=2)=C1F XFJXXYQMXPGEKY-DEOSSOPVSA-N 0.000 claims 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/32—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D317/34—Oxygen atoms
- C07D317/36—Alkylene carbonates; Substituted alkylene carbonates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
- C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
- C07C257/18—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/12—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. N-hydroxyamidines
- C07C259/18—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. N-hydroxyamidines having carbon atoms of hydroxamidine groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/18—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/20—Oxygen atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Furan Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00110881 | 2000-05-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200208899B true ZA200208899B (en) | 2004-02-19 |
Family
ID=8168800
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200208899A ZA200208899B (en) | 2000-05-23 | 2002-11-01 | Phenylglycine derivatives. |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US6548694B2 (fr) |
| EP (1) | EP1289939A1 (fr) |
| JP (1) | JP3842132B2 (fr) |
| KR (1) | KR100569517B1 (fr) |
| CN (1) | CN1305839C (fr) |
| AR (1) | AR028596A1 (fr) |
| AU (2) | AU2001281774B2 (fr) |
| BR (1) | BR0110998A (fr) |
| CA (1) | CA2408602C (fr) |
| EC (1) | ECSP024360A (fr) |
| HU (1) | HUP0302073A2 (fr) |
| IL (1) | IL152581A0 (fr) |
| MA (1) | MA26905A1 (fr) |
| MX (1) | MXPA02011466A (fr) |
| NO (1) | NO20025590L (fr) |
| NZ (1) | NZ522412A (fr) |
| PE (1) | PE20011314A1 (fr) |
| PL (1) | PL361355A1 (fr) |
| RU (1) | RU2268257C2 (fr) |
| UY (1) | UY26721A1 (fr) |
| WO (1) | WO2001090051A1 (fr) |
| YU (1) | YU83602A (fr) |
| ZA (1) | ZA200208899B (fr) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100473966B1 (ko) * | 1998-12-14 | 2005-03-08 | 에프. 호프만-라 로슈 아게 | 페닐글리신 유도체 |
| DE10300049A1 (de) * | 2003-01-03 | 2004-07-15 | Morphochem AG Aktiengesellschaft für kombinatorische Chemie | Neue Verbindungen, die Faktor VIIa inhibieren |
| US6642386B2 (en) * | 2002-02-06 | 2003-11-04 | Hoffmann-La Roche Inc. | N-(4-carbamimidoyl-phenyl)-glycine derivatives |
| GB0211931D0 (en) * | 2002-05-23 | 2002-07-03 | Univ Liverpool | Methods & device utilizing adsorption of molecules at a surface or interface |
| TW200410921A (en) * | 2002-11-25 | 2004-07-01 | Hoffmann La Roche | Mandelic acid derivatives |
| US7122559B2 (en) | 2003-02-11 | 2006-10-17 | Bristol-Myers Squibb Company | Phenylglycine derivatives useful as serine protease inhibitors |
| JP2006517589A (ja) | 2003-02-11 | 2006-07-27 | ブリストル−マイヤーズ スクイブ カンパニー | セリンプロテアーゼ・インヒビターとして有用なベンゼンアセトアミド化合物 |
| DE10306202A1 (de) * | 2003-02-13 | 2004-08-26 | Grünenthal GmbH | Arzneimittel enthaltend substituierte 2-Aryl-Aminoessigsäure-Verbindungen und/oder substituierte 2-Heteroaryl-Aminoessigsäure-Verbindungen |
| US7917130B1 (en) | 2003-03-21 | 2011-03-29 | Stratosaudio, Inc. | Broadcast response method and system |
| US7776804B2 (en) * | 2005-03-16 | 2010-08-17 | The Lubrizol Corporation | Viscosity improver compositions providing improved low temperature characteristics to lubricating oil |
| US7056932B2 (en) | 2003-12-19 | 2006-06-06 | Hoffman-La Roche Inc. | Heterocyclyl substituted 1-alkoxy acetic acid amides |
| WO2006041119A1 (fr) * | 2004-10-13 | 2006-04-20 | Eisai R & D Management Co., Ltd. | Dérivés d’hydrazide |
| WO2006045010A2 (fr) * | 2004-10-20 | 2006-04-27 | Resverlogix Corp. | Stilbenes et chalcones utilises pour la prevention et le traitement de maladies cardio-vasculaires |
| WO2006076246A2 (fr) | 2005-01-10 | 2006-07-20 | Bristol-Myers Squibb Company | Derives de phenylglycinamide utilises comme anticoagulants |
| WO2007002313A2 (fr) * | 2005-06-24 | 2007-01-04 | Bristol-Myers Squibb Company | Derives de phenylglycinamide et pyridylglycinamide utiles en tant que anticoagulants |
| US8044242B2 (en) | 2006-03-09 | 2011-10-25 | Bristol-Myers Squibb Company | 2-(aryloxy) acetamide factor VIIa inhibitors useful as anticoagulants |
| SI2000465T1 (sl) * | 2006-03-24 | 2011-04-29 | Eisai R&D Man Co Ltd | Derivat triazolona |
| US7855194B2 (en) | 2006-03-27 | 2010-12-21 | Hoffmann-La Roche Inc. | Pyrimidine, quinazoline, pteridine and triazine derivatives |
| KR101444489B1 (ko) | 2007-02-01 | 2014-09-24 | 리스버로직스 코퍼레이션 | 심혈관 질환을 예방 및 치료하기 위한 화합물 |
| EP1967522A1 (fr) * | 2007-03-07 | 2008-09-10 | Novo Nordisk A/S | Nouveaux inhibiteurs de coagulation sanguine |
| US7807690B2 (en) * | 2007-09-21 | 2010-10-05 | Eisai R&D Management Co., Ltd. | 2,3-dihydro-iminoisoindole derivatives |
| WO2009079417A1 (fr) | 2007-12-14 | 2009-06-25 | Stratosaudio, Inc. | Systèmes et procédés de programmation de supports et d'événements interactifs |
| EP2346837B8 (fr) | 2008-06-26 | 2015-04-15 | Resverlogix Corporation | Procédés de préparation de dérivés de quinazolinone |
| US8952021B2 (en) | 2009-01-08 | 2015-02-10 | Resverlogix Corp. | Compounds for the prevention and treatment of cardiovascular disease |
| JP5795304B2 (ja) | 2009-03-18 | 2015-10-14 | レスバーロジックス コーポレイション | 新規抗炎症剤 |
| PT2421533T (pt) | 2009-04-22 | 2019-01-21 | Resverlogix Corp | Novos agentes anti-inflamatórios |
| CN102887836B (zh) * | 2011-07-18 | 2014-03-26 | 西南大学 | L-苯甘氨酸衍生物及其应用 |
| CA2851996C (fr) | 2011-11-01 | 2020-01-07 | Resverlogix Corp. | Compositions pharmaceutiques pour des quinazolinones substituees |
| GB201118876D0 (en) * | 2011-11-01 | 2011-12-14 | Astex Therapeutics Ltd | Pharmaceutical compounds |
| WO2014080290A2 (fr) | 2012-11-21 | 2014-05-30 | Rvx Therapeutics Inc. | Amines cycliques servant d'inhibiteurs de bromodomaines |
| US9765039B2 (en) | 2012-11-21 | 2017-09-19 | Zenith Epigenetics Ltd. | Biaryl derivatives as bromodomain inhibitors |
| CN105073744B (zh) | 2012-12-21 | 2019-11-08 | 齐尼思表观遗传学有限公司 | 作为溴结构域抑制剂的新型杂环化合物 |
| EP3268007B1 (fr) | 2015-03-13 | 2022-11-09 | Resverlogix Corp. | Compositions et procédés thérapeutiques pour le traitement de maladies associées au complément |
| CN111072562B (zh) * | 2019-11-07 | 2021-12-07 | 中山大学 | 一种四氢异喹啉衍生物及其制备方法和应用 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK0921116T3 (da) | 1997-12-04 | 2003-10-06 | Hoffmann La Roche | N-(4-carbamimido-phenyl)-glycinamidderivater |
| AU2300699A (en) * | 1998-02-17 | 1999-08-30 | Ono Pharmaceutical Co. Ltd. | Amidino derivatives and drugs containing the same as the active ingredient |
| KR100473966B1 (ko) * | 1998-12-14 | 2005-03-08 | 에프. 호프만-라 로슈 아게 | 페닐글리신 유도체 |
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2001
- 2001-05-16 US US09/858,535 patent/US6548694B2/en not_active Expired - Fee Related
- 2001-05-17 KR KR1020027015798A patent/KR100569517B1/ko not_active IP Right Cessation
- 2001-05-17 RU RU2002133215/04A patent/RU2268257C2/ru active
- 2001-05-17 CN CNB018099297A patent/CN1305839C/zh not_active Expired - Fee Related
- 2001-05-17 HU HU0302073A patent/HUP0302073A2/hu unknown
- 2001-05-17 AU AU2001281774A patent/AU2001281774B2/en not_active Ceased
- 2001-05-17 CA CA002408602A patent/CA2408602C/fr not_active Expired - Fee Related
- 2001-05-17 BR BR0110998-7A patent/BR0110998A/pt not_active IP Right Cessation
- 2001-05-17 AU AU8177401A patent/AU8177401A/xx active Pending
- 2001-05-17 EP EP01960221A patent/EP1289939A1/fr not_active Withdrawn
- 2001-05-17 PL PL36135501A patent/PL361355A1/xx not_active Application Discontinuation
- 2001-05-17 YU YU83602A patent/YU83602A/sh unknown
- 2001-05-17 JP JP2001586241A patent/JP3842132B2/ja not_active Expired - Fee Related
- 2001-05-17 NZ NZ522412A patent/NZ522412A/en unknown
- 2001-05-17 MX MXPA02011466A patent/MXPA02011466A/es active IP Right Grant
- 2001-05-17 IL IL15258101A patent/IL152581A0/xx unknown
- 2001-05-17 PE PE2001000442A patent/PE20011314A1/es not_active Application Discontinuation
- 2001-05-17 WO PCT/EP2001/005633 patent/WO2001090051A1/fr active IP Right Grant
- 2001-05-21 AR ARP010102385A patent/AR028596A1/es not_active Application Discontinuation
- 2001-05-22 UY UY26721A patent/UY26721A1/es not_active Application Discontinuation
-
2002
- 2002-11-01 ZA ZA200208899A patent/ZA200208899B/en unknown
- 2002-11-21 NO NO20025590A patent/NO20025590L/no not_active Application Discontinuation
- 2002-11-22 EC EC2002004360A patent/ECSP024360A/es unknown
- 2002-11-22 MA MA26921A patent/MA26905A1/fr unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP3842132B2 (ja) | 2006-11-08 |
| EP1289939A1 (fr) | 2003-03-12 |
| KR100569517B1 (ko) | 2006-04-07 |
| CA2408602C (fr) | 2008-01-08 |
| PE20011314A1 (es) | 2002-01-04 |
| MXPA02011466A (es) | 2003-04-25 |
| PL361355A1 (en) | 2004-10-04 |
| US20020004608A1 (en) | 2002-01-10 |
| NO20025590D0 (no) | 2002-11-21 |
| NZ522412A (en) | 2004-05-28 |
| YU83602A (sh) | 2006-05-25 |
| RU2268257C2 (ru) | 2006-01-20 |
| IL152581A0 (en) | 2003-05-29 |
| MA26905A1 (fr) | 2004-12-20 |
| UY26721A1 (es) | 2001-12-28 |
| HUP0302073A2 (hu) | 2003-09-29 |
| US6548694B2 (en) | 2003-04-15 |
| CN1305839C (zh) | 2007-03-21 |
| ECSP024360A (es) | 2003-03-31 |
| CA2408602A1 (fr) | 2001-11-29 |
| NO20025590L (no) | 2002-11-21 |
| CN1430599A (zh) | 2003-07-16 |
| BR0110998A (pt) | 2003-04-08 |
| AR028596A1 (es) | 2003-05-14 |
| AU8177401A (en) | 2001-12-03 |
| JP2003534311A (ja) | 2003-11-18 |
| WO2001090051A1 (fr) | 2001-11-29 |
| KR20030007678A (ko) | 2003-01-23 |
| AU2001281774B2 (en) | 2005-03-10 |
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