KR100599134B1 - 양성 전립선 비대증에 대한 ｎｋ-1 수용체 길항물질의 용도 - Google Patents
양성 전립선 비대증에 대한 ｎｋ-1 수용체 길항물질의 용도 Download PDFInfo
- Publication number
- KR100599134B1 KR100599134B1 KR1020037013798A KR20037013798A KR100599134B1 KR 100599134 B1 KR100599134 B1 KR 100599134B1 KR 1020037013798 A KR1020037013798 A KR 1020037013798A KR 20037013798 A KR20037013798 A KR 20037013798A KR 100599134 B1 KR100599134 B1 KR 100599134B1
- Authority
- KR
- South Korea
- Prior art keywords
- methyl
- trifluoromethyl
- bis
- tolyl
- 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 - Lifetime
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- 239000002464 receptor antagonist Substances 0.000 title claims abstract description 52
- 229940044551 receptor antagonist Drugs 0.000 title claims abstract description 52
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 title claims abstract description 37
- 208000004403 Prostatic Hyperplasia Diseases 0.000 title claims abstract description 37
- -1 3,5-bis-trifluoromethyl-phenyl Chemical group 0.000 claims abstract description 119
- 102000002002 Neurokinin-1 Receptors Human genes 0.000 claims abstract description 54
- 108010040718 Neurokinin-1 Receptors Proteins 0.000 claims abstract description 54
- 150000001875 compounds Chemical class 0.000 claims abstract description 52
- 238000011282 treatment Methods 0.000 claims abstract description 25
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 230000002265 prevention Effects 0.000 claims abstract description 14
- 239000002253 acid Substances 0.000 claims abstract description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 10
- VJYRMMZALMMXPM-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[6-(1,1-dioxo-1,4-thiazinan-4-yl)-4-(2-methylphenyl)pyridin-3-yl]-n,2-dimethylpropanamide Chemical compound C=1N=C(N2CCS(=O)(=O)CC2)C=C(C=2C(=CC=CC=2)C)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 VJYRMMZALMMXPM-UHFFFAOYSA-N 0.000 claims abstract 2
- 125000000217 alkyl group Chemical group 0.000 claims description 46
- 239000001257 hydrogen Substances 0.000 claims description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- 150000002431 hydrogen Chemical group 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 229940047889 isobutyramide Drugs 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 229960002715 nicotine Drugs 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 3
- 125000004122 cyclic group Chemical group 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- WSLIVRZOMVURHI-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-2-methyl-n-[4-(2-methylphenyl)-6-morpholin-4-ylpyridin-3-yl]propanamide Chemical compound CC1=CC=CC=C1C1=CC(N2CCOCC2)=NC=C1NC(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 WSLIVRZOMVURHI-UHFFFAOYSA-N 0.000 claims description 2
- AYUFHVKOYVDQHJ-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-2-methyl-n-[4-(2-methylphenyl)pyridin-3-yl]propanamide Chemical compound CC1=CC=CC=C1C1=CC=NC=C1NC(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 AYUFHVKOYVDQHJ-UHFFFAOYSA-N 0.000 claims description 2
- GAQODNYPHMBYHB-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n,2-dimethyl-n-[4-(2-methylphenyl)-6-(4-pyrimidin-2-ylpiperazin-1-yl)pyridin-3-yl]propanamide Chemical compound C=1N=C(N2CCN(CC2)C=2N=CC=CN=2)C=C(C=2C(=CC=CC=2)C)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 GAQODNYPHMBYHB-UHFFFAOYSA-N 0.000 claims description 2
- ZGNPLCMMVKCTHM-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n,2-dimethyl-n-[4-(2-methylphenyl)-6-morpholin-4-ylpyridin-3-yl]propanamide Chemical compound C=1N=C(N2CCOCC2)C=C(C=2C(=CC=CC=2)C)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 ZGNPLCMMVKCTHM-UHFFFAOYSA-N 0.000 claims description 2
- SRVSDBHUBFLSFE-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n,2-dimethyl-n-[4-(2-methylphenyl)-6-piperazin-1-ylpyridin-3-yl]propanamide Chemical compound C=1N=C(N2CCNCC2)C=C(C=2C(=CC=CC=2)C)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 SRVSDBHUBFLSFE-UHFFFAOYSA-N 0.000 claims description 2
- HPYVATHTKDMNGH-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n,2-dimethyl-n-[4-(2-methylphenyl)pyridin-3-yl]propanamide Chemical compound C=1N=CC=C(C=2C(=CC=CC=2)C)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 HPYVATHTKDMNGH-UHFFFAOYSA-N 0.000 claims description 2
- DSBGAUHQEXISAQ-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n,2-dimethyl-n-[6-[methyl(2-morpholin-4-ylethyl)amino]-4-(2-methylphenyl)pyridin-3-yl]propanamide Chemical compound C=1C(C=2C(=CC=CC=2)C)=C(N(C)C(=O)C(C)(C)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)C=NC=1N(C)CCN1CCOCC1 DSBGAUHQEXISAQ-UHFFFAOYSA-N 0.000 claims description 2
- ZTAFOCSGKWFNFP-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[4-(2-chlorophenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]-n,2-dimethylpropanamide Chemical compound C=1N=C(N2CCN(C)CC2)C=C(C=2C(=CC=CC=2)Cl)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 ZTAFOCSGKWFNFP-UHFFFAOYSA-N 0.000 claims description 2
- RASOIHZMMKUJFL-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[4-(2-chlorophenyl)-6-(dimethylamino)pyridin-3-yl]-2-methylpropanamide Chemical compound C1=NC(N(C)C)=CC(C=2C(=CC=CC=2)Cl)=C1NC(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 RASOIHZMMKUJFL-UHFFFAOYSA-N 0.000 claims description 2
- MVEWHIDMBLIQIL-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[4-(2-chlorophenyl)pyridin-3-yl]-n,2-dimethylpropanamide Chemical compound C=1N=CC=C(C=2C(=CC=CC=2)Cl)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 MVEWHIDMBLIQIL-UHFFFAOYSA-N 0.000 claims description 2
- DDEKDUUKRLYOQI-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[4-(4-fluoro-2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-yl]-n,2-dimethylpropanamide Chemical compound C=1N=C(N2CCN(C)CC2)C=C(C=2C(=CC(F)=CC=2)C)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 DDEKDUUKRLYOQI-UHFFFAOYSA-N 0.000 claims description 2
- PSFZPLRNIVTYMJ-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[6-(1,1-dioxo-1,4-thiazinan-4-yl)-4-(4-fluoro-2-methylphenyl)pyridin-3-yl]-n,2-dimethylpropanamide Chemical compound C=1N=C(N2CCS(=O)(=O)CC2)C=C(C=2C(=CC(F)=CC=2)C)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 PSFZPLRNIVTYMJ-UHFFFAOYSA-N 0.000 claims description 2
- NYRFYXWZUVSHOA-OAQYLSRUSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[6-[(3r)-3-hydroxypyrrolidin-1-yl]-4-(2-methylphenyl)pyridin-3-yl]-n,2-dimethylpropanamide Chemical compound C=1N=C(N2C[C@H](O)CC2)C=C(C=2C(=CC=CC=2)C)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 NYRFYXWZUVSHOA-OAQYLSRUSA-N 0.000 claims description 2
- IWQYMFHSVCMCNX-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[6-[2-hydroxyethyl(methyl)amino]-4-(2-methylphenyl)pyridin-3-yl]-n,2-dimethylpropanamide Chemical compound C1=NC(N(CCO)C)=CC(C=2C(=CC=CC=2)C)=C1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 IWQYMFHSVCMCNX-UHFFFAOYSA-N 0.000 claims description 2
- AHHIIEQZKJBQFY-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-methyl-n-[4-(2-methylphenyl)-6-morpholin-4-ylpyridin-3-yl]acetamide Chemical compound C=1N=C(N2CCOCC2)C=C(C=2C(=CC=CC=2)C)C=1N(C)C(=O)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 AHHIIEQZKJBQFY-UHFFFAOYSA-N 0.000 claims description 2
- FZXNGEHWLDLVOH-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-methyl-n-[4-(2-methylphenyl)pyridin-3-yl]acetamide Chemical compound C=1N=CC=C(C=2C(=CC=CC=2)C)C=1N(C)C(=O)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 FZXNGEHWLDLVOH-UHFFFAOYSA-N 0.000 claims description 2
- RKPZFEFLRSLJGS-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-methyl-n-[4-(2-methylphenyl)pyridin-3-yl]propanamide Chemical compound C=1C(C(F)(F)F)=CC(C(F)(F)F)=CC=1C(C)C(=O)N(C)C1=CN=CC=C1C1=CC=CC=C1C RKPZFEFLRSLJGS-UHFFFAOYSA-N 0.000 claims description 2
- LSJBBBAVALKOER-UHFFFAOYSA-N ethyl 1-[5-[[3,5-bis(trifluoromethyl)phenyl]methyl-methylcarbamoyl]-4-(2-methylphenyl)pyridin-2-yl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C1=CC(C=2C(=CC=CC=2)C)=C(C(=O)N(C)CC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)C=N1 LSJBBBAVALKOER-UHFFFAOYSA-N 0.000 claims description 2
- FZVTYGCDSKDACX-UHFFFAOYSA-N ethyl 2-[4-[5-[[3,5-bis(trifluoromethyl)phenyl]methyl-methylcarbamoyl]-4-(2-methylphenyl)pyridin-2-yl]piperazin-1-yl]acetate Chemical compound C1CN(CC(=O)OCC)CCN1C1=CC(C=2C(=CC=CC=2)C)=C(C(=O)N(C)CC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)C=N1 FZVTYGCDSKDACX-UHFFFAOYSA-N 0.000 claims description 2
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- CVEVEUXWJPBHBP-UHFFFAOYSA-N n-[(3,5-dichlorophenyl)methyl]-n-methyl-4-(2-methylphenyl)pyridine-3-carboxamide Chemical compound C=1N=CC=C(C=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(Cl)=CC(Cl)=C1 CVEVEUXWJPBHBP-UHFFFAOYSA-N 0.000 claims description 2
- IFYBTLIOKGFJHM-UHFFFAOYSA-N n-[(3,5-difluorophenyl)methyl]-n-methyl-4-(2-methylphenyl)pyridine-3-carboxamide Chemical compound C=1N=CC=C(C=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(F)=CC(F)=C1 IFYBTLIOKGFJHM-UHFFFAOYSA-N 0.000 claims description 2
- MEPYIKQCUYZUJC-UHFFFAOYSA-N n-[1-[3,5-bis(trifluoromethyl)phenyl]ethyl]-n-methyl-4-(2-methylphenyl)pyridine-3-carboxamide Chemical compound C=1C(C(F)(F)F)=CC(C(F)(F)F)=CC=1C(C)N(C)C(=O)C1=CN=CC=C1C1=CC=CC=C1C MEPYIKQCUYZUJC-UHFFFAOYSA-N 0.000 claims description 2
- XTUGEGDIPNFCHX-UHFFFAOYSA-N n-[2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropyl]-4-(4-fluoro-2-methylphenyl)-n-methyl-6-(4-methylpiperazin-1-yl)pyridin-3-amine Chemical compound C=1N=C(N2CCN(C)CC2)C=C(C=2C(=CC(F)=CC=2)C)C=1N(C)CC(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 XTUGEGDIPNFCHX-UHFFFAOYSA-N 0.000 claims description 2
- JKHCSKNIYWXLNC-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-(2-chlorophenyl)-n-methylpyridine-3-carboxamide Chemical compound C=1N=CC=C(C=2C(=CC=CC=2)Cl)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 JKHCSKNIYWXLNC-UHFFFAOYSA-N 0.000 claims description 2
- OFNUQLHUVSTYKN-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-(2-fluorophenyl)-n-methylpyridine-3-carboxamide Chemical compound C=1N=CC=C(C=2C(=CC=CC=2)F)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 OFNUQLHUVSTYKN-UHFFFAOYSA-N 0.000 claims description 2
- LXCMOQGQIBFNJJ-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-(2-methoxyphenyl)-n-methylpyridine-3-carboxamide Chemical compound COC1=CC=CC=C1C1=CC=NC=C1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 LXCMOQGQIBFNJJ-UHFFFAOYSA-N 0.000 claims description 2
- GLWUUJAEACZDNZ-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-6-(4-formylpiperazin-1-yl)-n-methyl-4-(2-methylphenyl)pyridine-3-carboxamide Chemical compound C=1N=C(N2CCN(CC2)C=O)C=C(C=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 GLWUUJAEACZDNZ-UHFFFAOYSA-N 0.000 claims description 2
- BXXGEOWRMSJJAJ-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-6-[4-(cyanomethyl)piperazin-1-yl]-n-methyl-4-(2-methylphenyl)pyridine-3-carboxamide Chemical compound C=1N=C(N2CCN(CC#N)CC2)C=C(C=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 BXXGEOWRMSJJAJ-UHFFFAOYSA-N 0.000 claims description 2
- VQHCPDADMQPSJL-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-6-[4-[2-(2-hydroxyethoxy)ethyl]piperazin-1-yl]-n-methyl-4-(2-methylphenyl)pyridine-3-carboxamide Chemical compound C=1N=C(N2CCN(CCOCCO)CC2)C=C(C=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 VQHCPDADMQPSJL-UHFFFAOYSA-N 0.000 claims description 2
- HQMNLEYZUWNHDL-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-cyclopropyl-4-(2-methylphenyl)pyridine-3-carboxamide Chemical compound CC1=CC=CC=C1C1=CC=NC=C1C(=O)N(C1CC1)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 HQMNLEYZUWNHDL-UHFFFAOYSA-N 0.000 claims description 2
- FNGXRBAWNZYBIM-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-ethyl-4-(2-methylphenyl)pyridine-3-carboxamide Chemical compound C=1N=CC=C(C=2C(=CC=CC=2)C)C=1C(=O)N(CC)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 FNGXRBAWNZYBIM-UHFFFAOYSA-N 0.000 claims description 2
- LENPPWYNSXXLIB-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-2-(2-methylphenyl)-4-(4-methylpiperazin-1-yl)benzamide Chemical compound C=1C=C(N2CCN(C)CC2)C=C(C=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 LENPPWYNSXXLIB-UHFFFAOYSA-N 0.000 claims description 2
- MUQYNWRDIOWJMA-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenyl)-6-(1-oxo-1,4-thiazinan-4-yl)pyridine-3-carboxamide Chemical compound C=1N=C(N2CCS(=O)CC2)C=C(C=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 MUQYNWRDIOWJMA-UHFFFAOYSA-N 0.000 claims description 2
- HCNNJLLLMSVTFH-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridine-3-carboxamide Chemical compound C=1N=C(N2CCN(C)CC2)C=C(C=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 HCNNJLLLMSVTFH-UHFFFAOYSA-N 0.000 claims description 2
- HINABYJPTBAFEL-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenyl)-6-(4-propylpiperazin-1-yl)pyridine-3-carboxamide Chemical compound C1CN(CCC)CCN1C1=CC(C=2C(=CC=CC=2)C)=C(C(=O)N(C)CC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)C=N1 HINABYJPTBAFEL-UHFFFAOYSA-N 0.000 claims description 2
- DGRVWNYJJZUMSS-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenyl)-6-morpholin-4-ylpyridine-3-carboxamide Chemical compound C=1N=C(N2CCOCC2)C=C(C=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 DGRVWNYJJZUMSS-UHFFFAOYSA-N 0.000 claims description 2
- HZBSJCLPYPJTHM-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenyl)-6-piperazin-1-ylpyridine-3-carboxamide Chemical compound C=1N=C(N2CCNCC2)C=C(C=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 HZBSJCLPYPJTHM-UHFFFAOYSA-N 0.000 claims description 2
- BMXZBYOYLNTJRL-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenyl)-6-thiomorpholin-4-ylpyridine-3-carboxamide Chemical compound C=1N=C(N2CCSCC2)C=C(C=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 BMXZBYOYLNTJRL-UHFFFAOYSA-N 0.000 claims description 2
- GTBUTLFXQOBLCG-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenyl)pyridine-3-carboxamide Chemical compound C=1N=CC=C(C=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 GTBUTLFXQOBLCG-UHFFFAOYSA-N 0.000 claims description 2
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- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000008012 organic excipient Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- DZOJBGLFWINFBF-UMSFTDKQSA-N osanetant Chemical compound C([C@](C1)(CCCN2CCC(CC2)(N(C(C)=O)C)C=2C=CC=CC=2)C=2C=C(Cl)C(Cl)=CC=2)CCN1C(=O)C1=CC=CC=C1 DZOJBGLFWINFBF-UMSFTDKQSA-N 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 230000010254 physiological adaptation Effects 0.000 description 1
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940072254 proscar Drugs 0.000 description 1
- 229960003447 pseudoephedrine hydrochloride Drugs 0.000 description 1
- BALXUFOVQVENIU-KXNXZCPBSA-N pseudoephedrine hydrochloride Chemical compound [H+].[Cl-].CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 BALXUFOVQVENIU-KXNXZCPBSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- HOHWYQSDLRTVDK-UHFFFAOYSA-N pyrimido[1,2-a]benzimidazole Chemical compound N1=CC=CN2C3=CC=CC=C3N=C21 HOHWYQSDLRTVDK-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 210000005000 reproductive tract Anatomy 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 239000012419 sodium bis(2-methoxyethoxy)aluminum hydride Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- PODWXQQNRWNDGD-UHFFFAOYSA-L sodium thiosulfate pentahydrate Chemical compound O.O.O.O.O.[Na+].[Na+].[O-]S([S-])(=O)=O PODWXQQNRWNDGD-UHFFFAOYSA-L 0.000 description 1
- 108700023329 spantide II Proteins 0.000 description 1
- 108700032228 spantide III Proteins 0.000 description 1
- AZZJAARMZMEIHY-BBKUSFMUSA-N spantide ii Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCC)C(=O)N(C(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCCNC(=O)C=1C=NC=CC=1)C(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](N)CC=1C=C(Cl)C(Cl)=CC=1)C1=CC=CC=C1 AZZJAARMZMEIHY-BBKUSFMUSA-N 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000003594 spinal ganglia Anatomy 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000002466 tachykinin receptor agonist Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000004571 thiomorpholin-4-yl group Chemical group N1(CCSCC1)* 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 208000029584 urinary system neoplasm Diseases 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
Classifications
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01109853 | 2001-04-23 | ||
| EP01109853.0 | 2001-04-23 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20040007503A KR20040007503A (ko) | 2004-01-24 |
| KR100599134B1 true KR100599134B1 (ko) | 2006-07-12 |
Family
ID=8177209
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020037013798A Expired - Lifetime KR100599134B1 (ko) | 2001-04-23 | 2002-02-02 | 양성 전립선 비대증에 대한 ｎｋ-1 수용체 길항물질의 용도 |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US20030004157A1 (https=) |
| EP (1) | EP1385577B1 (https=) |
| JP (1) | JP4146730B2 (https=) |
| KR (1) | KR100599134B1 (https=) |
| CN (1) | CN100398106C (https=) |
| AR (1) | AR035935A1 (https=) |
| AT (1) | ATE323531T1 (https=) |
| AU (1) | AU2002250876B2 (https=) |
| BR (1) | BR0209151A (https=) |
| CA (1) | CA2444395C (https=) |
| DE (1) | DE60210760T2 (https=) |
| DK (1) | DK1385577T3 (https=) |
| ES (1) | ES2261657T3 (https=) |
| MX (1) | MXPA03009720A (https=) |
| PT (1) | PT1385577E (https=) |
| WO (1) | WO2002085458A2 (https=) |
| ZA (1) | ZA200308110B (https=) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2002259147A1 (en) * | 2001-05-08 | 2002-11-18 | Schering Corporation | Use of neurokinin receptor antagonists to treat androgen-dependent diseases |
| US6849624B2 (en) | 2001-07-31 | 2005-02-01 | Hoffmann-La Roche Inc. | Aromatic and heteroaromatic substituted amides |
| ATE366576T1 (de) * | 2003-01-31 | 2007-08-15 | Hoffmann La Roche | Neue kristallmodifikation von 2-(3,5-bis- trifluormethyl-phenyl)-n-6-(1,1-dioxo-1lamda-6- |
| SI1643998T1 (sl) * | 2003-07-03 | 2007-12-31 | Hoffmann La Roche | Dvojni nk1/nk3 antagonisti za zdravljenje shizofrenije |
| ES2246687B2 (es) * | 2004-02-11 | 2006-11-16 | Miguel Muñoz Saez | Utilizacion de antagonistas no peptidicos de receptores nk1 para la produccion de apoptosis en celulas tumorales. |
| CN1984891B (zh) | 2004-07-06 | 2012-08-08 | 弗·哈夫曼-拉罗切有限公司 | 用作合成nk-1受体拮抗剂的中间体的甲酰胺吡啶衍生物的制备方法 |
| US20060030600A1 (en) * | 2004-08-06 | 2006-02-09 | Patrick Schnider | Dual NK1/NK3 receptor antagonists for the treatment of schizophrenia |
| JP2008531509A (ja) | 2005-02-25 | 2008-08-14 | エフ．ホフマン−ラ ロシュ アーゲー | 医薬品成分の改良された分散性を有する錠剤 |
| CN102775396B (zh) | 2005-11-08 | 2014-10-08 | 沃泰克斯药物股份有限公司 | Atp-结合弹夹转运蛋白的杂环调控剂 |
| US7671221B2 (en) | 2005-12-28 | 2010-03-02 | Vertex Pharmaceuticals Incorporated | Modulators of ATP-Binding Cassette transporters |
| US7754739B2 (en) | 2007-05-09 | 2010-07-13 | Vertex Pharmaceuticals Incorporated | Modulators of CFTR |
| WO2008090114A1 (en) | 2007-01-24 | 2008-07-31 | Glaxo Group Limited | Pharmaceutical compositions comprising 2-methoxy-5- (5-trifluoromethyl-tetrazol-i-yl-benzyl) - (2s-phenyl-piperidin-3s-yl-) |
| CN104447716A (zh) | 2007-05-09 | 2015-03-25 | 沃泰克斯药物股份有限公司 | Cftr调节剂 |
| MX365732B (es) | 2007-12-07 | 2019-06-12 | Vertex Pharma | Procesos para producir acidos cicloalquilcarboxamido-piridin benzoicos. |
| EP3683218B1 (en) | 2007-12-07 | 2024-09-18 | Vertex Pharmaceuticals Incorporated | Solid forms of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl) benzoic acid |
| NZ720282A (en) | 2008-02-28 | 2017-12-22 | Vertex Pharma | Heteroaryl derivatives as cftr modulators |
| GB0808747D0 (en) | 2008-05-14 | 2008-06-18 | Glaxo Wellcome Mfg Pte Ltd | Novel compounds |
| WO2010106988A1 (ja) | 2009-03-17 | 2010-09-23 | 第一三共株式会社 | アミド誘導体 |
| WO2010119347A1 (en) * | 2009-04-14 | 2010-10-21 | Helsinn Healthcare S.A. | Netupitant for use in treating bladder dysfunction |
| US20120196901A1 (en) * | 2009-10-29 | 2012-08-02 | Merck Sharp & Dohme Corp. | Tertiary amide orexin receptor antagonists |
| JP2013523833A (ja) | 2010-04-07 | 2013-06-17 | バーテックス ファーマシューティカルズ インコーポレイテッド | ３−（６−（１−（２，２−ジフルオロベンゾ［ｄ］［１，３］ジオキソール−５−イル）シクロプロパンカルボキサミド）−３−メチルピリジン−２−イル）安息香酸の医薬組成物およびその投与 |
| NZ727015A (en) | 2012-01-25 | 2017-12-22 | Vertex Pharma | Formulations of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid |
| RU2673084C2 (ru) | 2013-11-08 | 2018-11-22 | Киссеи Фармасьютикал Ко., Лтд. | Производное карбоксиметилпиперидина |
| AU2014349010C1 (en) | 2013-11-12 | 2020-08-06 | Vertex Pharmaceuticals Incorporated | Process of preparing pharmaceutical compositions for the treatment of CFTR mediated diseases |
| TWI649307B (zh) | 2014-05-07 | 2019-02-01 | 日商橘生藥品工業股份有限公司 | Cyclohexylpyridine derivative |
| RU2691136C2 (ru) | 2014-11-18 | 2019-06-11 | Вертекс Фармасьютикалз Инкорпорейтед | Способ проведения высокопроизводительной тестовой высокоэффективной жидкостной хроматографии |
| AU2019215801B2 (en) * | 2018-02-02 | 2024-09-19 | Eustralis Pharmaceuticals Limited (Trading As Pressura Neuro) | Parenteral formulations and uses thereof |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6175013B1 (en) * | 1994-06-10 | 2001-01-16 | Eli Lilly And Company | Imidazolinyl tachykinin receptor antagonists |
| FR2729951B1 (fr) * | 1995-01-30 | 1997-04-18 | Sanofi Sa | Nouveaux composes heterocycliques, procede pour leur preparation et compositions pharmaceutiques en contenant |
| IL134155A0 (en) * | 1997-08-06 | 2001-04-30 | Lilly Co Eli | 2-acylaminopropanamines as tachykinin receptor antagonists |
| CN1272842A (zh) * | 1997-08-06 | 2000-11-08 | 伊莱利利公司 | 作为速激肽受体拮抗剂的2－酰氨基丙胺类化合物 |
| JPH11322748A (ja) * | 1998-03-19 | 1999-11-24 | Takeda Chem Ind Ltd | 複素環化合物、その製造法および用途 |
| EP1394150B1 (en) * | 1999-02-24 | 2011-01-19 | F. Hoffmann-La Roche AG | 4-Phenylpyridine derivatives and their use as NK-1 receptor antagonists |
| WO2000067742A2 (en) * | 1999-05-05 | 2000-11-16 | Warner-Lambert Company | Use of gaba analogues for the modulation of substance p |
| PT1303490E (pt) * | 2000-07-14 | 2008-09-04 | Hoffmann La Roche | Óxidos de aminas como pró-fármacos de antagonistas dosreceptores nk1, de derivados de 4-fenil-piridina |
| US6849624B2 (en) * | 2001-07-31 | 2005-02-01 | Hoffmann-La Roche Inc. | Aromatic and heteroaromatic substituted amides |
-
2002
- 2002-02-02 AT AT02719751T patent/ATE323531T1/de active
- 2002-02-02 BR BR0209151-8A patent/BR0209151A/pt not_active Application Discontinuation
- 2002-02-02 ES ES02719751T patent/ES2261657T3/es not_active Expired - Lifetime
- 2002-02-02 EP EP02719751A patent/EP1385577B1/en not_active Expired - Lifetime
- 2002-02-02 CA CA2444395A patent/CA2444395C/en not_active Expired - Lifetime
- 2002-02-02 AU AU2002250876A patent/AU2002250876B2/en not_active Expired
- 2002-02-02 CN CNB028087305A patent/CN100398106C/zh not_active Expired - Lifetime
- 2002-02-02 PT PT02719751T patent/PT1385577E/pt unknown
- 2002-02-02 JP JP2002583031A patent/JP4146730B2/ja not_active Expired - Lifetime
- 2002-02-02 DK DK02719751T patent/DK1385577T3/da active
- 2002-02-02 DE DE60210760T patent/DE60210760T2/de not_active Expired - Lifetime
- 2002-02-02 MX MXPA03009720A patent/MXPA03009720A/es active IP Right Grant
- 2002-02-02 KR KR1020037013798A patent/KR100599134B1/ko not_active Expired - Lifetime
- 2002-02-02 WO PCT/EP2002/001085 patent/WO2002085458A2/en not_active Ceased
- 2002-02-07 AR ARP020100393A patent/AR035935A1/es unknown
- 2002-02-08 US US10/071,570 patent/US20030004157A1/en not_active Abandoned
-
2003
- 2003-10-17 ZA ZA2003/08110A patent/ZA200308110B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ZA200308110B (en) | 2005-03-30 |
| CA2444395C (en) | 2010-12-21 |
| WO2002085458A2 (en) | 2002-10-31 |
| JP2004529931A (ja) | 2004-09-30 |
| AR035935A1 (es) | 2004-07-28 |
| JP4146730B2 (ja) | 2008-09-10 |
| DE60210760T2 (de) | 2006-11-23 |
| MXPA03009720A (es) | 2004-01-29 |
| ES2261657T3 (es) | 2006-11-16 |
| DK1385577T3 (da) | 2006-08-21 |
| CA2444395A1 (en) | 2002-10-31 |
| US20030004157A1 (en) | 2003-01-02 |
| ATE323531T1 (de) | 2006-05-15 |
| PT1385577E (pt) | 2006-08-31 |
| DE60210760D1 (de) | 2006-05-24 |
| BR0209151A (pt) | 2004-07-13 |
| CN1503684A (zh) | 2004-06-09 |
| EP1385577A2 (en) | 2004-02-04 |
| AU2002250876B2 (en) | 2005-03-03 |
| KR20040007503A (ko) | 2004-01-24 |
| CN100398106C (zh) | 2008-07-02 |
| WO2002085458A3 (en) | 2003-10-30 |
| EP1385577B1 (en) | 2006-04-19 |
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