CA2446324A1 - Quinoline derivatives as ligands for the neuropeptide y receptor - Google Patents
Quinoline derivatives as ligands for the neuropeptide y receptor Download PDFInfo
- Publication number
- CA2446324A1 CA2446324A1 CA002446324A CA2446324A CA2446324A1 CA 2446324 A1 CA2446324 A1 CA 2446324A1 CA 002446324 A CA002446324 A CA 002446324A CA 2446324 A CA2446324 A CA 2446324A CA 2446324 A1 CA2446324 A1 CA 2446324A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- pyrrolidin
- quinolin
- alkyl
- hydrogen
- 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.)
- Abandoned
Links
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title claims 3
- 239000003446 ligand Substances 0.000 title description 6
- 108050002826 Neuropeptide Y Receptor Proteins 0.000 title description 2
- 102000012301 Neuropeptide Y receptor Human genes 0.000 title description 2
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 94
- 150000003839 salts Chemical class 0.000 claims abstract description 30
- 150000002148 esters Chemical class 0.000 claims abstract description 21
- 238000011282 treatment Methods 0.000 claims abstract description 19
- 208000008589 Obesity Diseases 0.000 claims abstract description 16
- 235000020824 obesity Nutrition 0.000 claims abstract description 15
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 9
- 206010003246 arthritis Diseases 0.000 claims abstract description 8
- 208000030814 Eating disease Diseases 0.000 claims abstract description 5
- 208000019454 Feeding and Eating disease Diseases 0.000 claims abstract description 5
- 235000014632 disordered eating Nutrition 0.000 claims abstract description 5
- 230000002265 prevention Effects 0.000 claims abstract description 4
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 122
- 238000006243 chemical reaction Methods 0.000 claims description 90
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 67
- -1 aryl-SO2-O-alkyl Chemical group 0.000 claims description 54
- 229910052739 hydrogen Inorganic materials 0.000 claims description 52
- 239000001257 hydrogen Substances 0.000 claims description 51
- 125000000217 alkyl group Chemical group 0.000 claims description 47
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 40
- 125000003118 aryl group Chemical group 0.000 claims description 30
- 125000003545 alkoxy group Chemical group 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 27
- 229910052736 halogen Inorganic materials 0.000 claims description 22
- 150000002367 halogens Chemical group 0.000 claims description 21
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 16
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 14
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 11
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical group CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 claims description 11
- 230000008569 process Effects 0.000 claims description 11
- 229940086609 Lipase inhibitor Drugs 0.000 claims description 10
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 10
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 229960001243 orlistat Drugs 0.000 claims description 10
- 229920006395 saturated elastomer Polymers 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 125000006193 alkinyl group Chemical group 0.000 claims description 8
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 8
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 239000003054 catalyst Substances 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 6
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 6
- 125000004104 aryloxy group Chemical group 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 238000011321 prophylaxis Methods 0.000 claims description 6
- 125000001246 bromo group Chemical group Br* 0.000 claims description 5
- 238000009833 condensation Methods 0.000 claims description 5
- 230000005494 condensation Effects 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000005114 heteroarylalkoxy group Chemical group 0.000 claims description 5
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 101710151321 Melanostatin Proteins 0.000 claims description 4
- 102100028427 Pro-neuropeptide Y Human genes 0.000 claims description 4
- 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 4
- 125000003725 azepanyl group Chemical group 0.000 claims description 4
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 4
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims description 4
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 4
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 125000001769 aryl amino group Chemical group 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 3
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 125000006513 pyridinyl methyl group Chemical group 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- NHXYFTFKSJDZSH-SFHVURJKSA-N 7-[(2-chloropyridin-3-yl)methoxy]-4-[(3s)-3-ethoxypyrrolidin-1-yl]-2-methylquinoline Chemical compound C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(OCC=3C(=NC=CC=3)Cl)=CC=C12 NHXYFTFKSJDZSH-SFHVURJKSA-N 0.000 claims description 2
- 125000002619 bicyclic group Chemical group 0.000 claims description 2
- 238000006664 bond formation reaction Methods 0.000 claims description 2
- 125000002950 monocyclic group Chemical group 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims 2
- HFVCWXRIRISOEA-UHFFFAOYSA-N 2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C(=CC=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 HFVCWXRIRISOEA-UHFFFAOYSA-N 0.000 claims 1
- HTWNTQBDROIOEZ-UHFFFAOYSA-N 2-methyl-4-pyrrolidin-1-ylquinolin-7-ol Chemical compound C=12C=CC(O)=CC2=NC(C)=CC=1N1CCCC1 HTWNTQBDROIOEZ-UHFFFAOYSA-N 0.000 claims 1
- SRCYQRXUBMEAPQ-UHFFFAOYSA-N 3-[[4-(azepan-1-yl)-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C=C(C=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCCCC1 SRCYQRXUBMEAPQ-UHFFFAOYSA-N 0.000 claims 1
- DPMAQIWJJZJKLV-UHFFFAOYSA-N 4-(azepan-1-yl)-2-methyl-7-(pyridin-4-ylmethoxy)quinoline Chemical compound C=12C=CC(OCC=3C=CN=CC=3)=CC2=NC(C)=CC=1N1CCCCCC1 DPMAQIWJJZJKLV-UHFFFAOYSA-N 0.000 claims 1
- NHZYJKKSOGTTMR-UHFFFAOYSA-N 4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 NHZYJKKSOGTTMR-UHFFFAOYSA-N 0.000 claims 1
- NXANOKNNJGBJJU-UHFFFAOYSA-N 4-[(6-fluoro-2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxymethyl]benzonitrile Chemical compound C=12C=C(F)C(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 NXANOKNNJGBJJU-UHFFFAOYSA-N 0.000 claims 1
- ZLJRLUWCTUDGGW-UHFFFAOYSA-N 4-[[4-(azepan-1-yl)-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCCCC1 ZLJRLUWCTUDGGW-UHFFFAOYSA-N 0.000 claims 1
- JAGFRBPZTHOFHK-LJQANCHMSA-N 4-[[4-[(2r)-2-(hydroxymethyl)pyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCC[C@@H]1CO JAGFRBPZTHOFHK-LJQANCHMSA-N 0.000 claims 1
- JAGFRBPZTHOFHK-IBGZPJMESA-N 4-[[4-[(2s)-2-(hydroxymethyl)pyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCC[C@H]1CO JAGFRBPZTHOFHK-IBGZPJMESA-N 0.000 claims 1
- OVIOWFMKGQXDFO-GOSISDBHSA-N 4-[[4-[(3r)-3-hydroxypyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CC[C@@H](O)C1 OVIOWFMKGQXDFO-GOSISDBHSA-N 0.000 claims 1
- OVIOWFMKGQXDFO-SFHVURJKSA-N 4-[[4-[(3s)-3-hydroxypyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CC[C@H](O)C1 OVIOWFMKGQXDFO-SFHVURJKSA-N 0.000 claims 1
- QJPGZZBMFWSTCX-FQEVSTJZSA-N 4-[[4-[(3s)-3-methoxypyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C1[C@@H](OC)CCN1C1=CC(C)=NC2=CC(OCC=3C=CC(=CC=3)C#N)=CC=C12 QJPGZZBMFWSTCX-FQEVSTJZSA-N 0.000 claims 1
- XHQZQRBRMJGODJ-UHFFFAOYSA-N 6-fluoro-7-[(2-fluoropyridin-3-yl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=C(F)C(OCC=3C(=NC=CC=3)F)=CC2=NC(C)=CC=1N1CCCC1 XHQZQRBRMJGODJ-UHFFFAOYSA-N 0.000 claims 1
- PBVJXDHCRUNAMA-UHFFFAOYSA-N 7-[(2-chloropyridin-3-yl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(OCC=3C(=NC=CC=3)Cl)=CC2=NC(C)=CC=1N1CCCC1 PBVJXDHCRUNAMA-UHFFFAOYSA-N 0.000 claims 1
- KMROVFJWJQHRLB-KRWDZBQOSA-N 7-[(2-chloropyridin-3-yl)methoxy]-4-[(2s)-2-(methoxymethyl)pyrrolidin-1-yl]-2-methylquinoline Chemical compound COC[C@@H]1CCCN1C1=CC(C)=NC2=CC(OCC=3C(=NC=CC=3)Cl)=CC=C12 KMROVFJWJQHRLB-KRWDZBQOSA-N 0.000 claims 1
- NFLYDVKEEWHEKP-UHFFFAOYSA-N 7-[(3-chlorophenyl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(OCC=3C=C(Cl)C=CC=3)=CC2=NC(C)=CC=1N1CCCC1 NFLYDVKEEWHEKP-UHFFFAOYSA-N 0.000 claims 1
- AGTMGARQEGRFBT-UHFFFAOYSA-N 7-[(3-methoxyphenyl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound COC1=CC=CC(COC=2C=C3N=C(C)C=C(C3=CC=2)N2CCCC2)=C1 AGTMGARQEGRFBT-UHFFFAOYSA-N 0.000 claims 1
- NUXDJOBRDWPOTK-UHFFFAOYSA-N 7-[(4-chlorophenyl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(OCC=3C=CC(Cl)=CC=3)=CC2=NC(C)=CC=1N1CCCC1 NUXDJOBRDWPOTK-UHFFFAOYSA-N 0.000 claims 1
- AJOLWRGXBPZAIK-INIZCTEOSA-N [(2s)-1-[7-[(2-chloropyridin-3-yl)methoxy]-2-methylquinolin-4-yl]pyrrolidin-2-yl]methanol Chemical compound C=12C=CC(OCC=3C(=NC=CC=3)Cl)=CC2=NC(C)=CC=1N1CCC[C@H]1CO AJOLWRGXBPZAIK-INIZCTEOSA-N 0.000 claims 1
- HOVZPQYOIGUXKT-INIZCTEOSA-N [(2s)-1-[7-[(2-fluoropyridin-3-yl)methoxy]-2-methylquinolin-4-yl]pyrrolidin-2-yl]methanol Chemical compound C=12C=CC(OCC=3C(=NC=CC=3)F)=CC2=NC(C)=CC=1N1CCC[C@H]1CO HOVZPQYOIGUXKT-INIZCTEOSA-N 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 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 1
- 208000024172 Cardiovascular disease Diseases 0.000 abstract description 5
- 208000001647 Renal Insufficiency Diseases 0.000 abstract description 4
- 201000006370 kidney failure Diseases 0.000 abstract description 4
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 3
- 239000007787 solid Substances 0.000 description 110
- 239000000047 product Substances 0.000 description 58
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical class N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 44
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 41
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
- 239000002253 acid Substances 0.000 description 38
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 35
- 238000001819 mass spectrum Methods 0.000 description 33
- 238000001228 spectrum Methods 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- 239000000243 solution Substances 0.000 description 23
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 20
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 20
- 239000002904 solvent Substances 0.000 description 20
- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- 239000002585 base Substances 0.000 description 16
- 239000000203 mixture Substances 0.000 description 15
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- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 10
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 10
- 239000010410 layer Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 8
- 229910052731 fluorine Inorganic materials 0.000 description 8
- 125000001072 heteroaryl group Chemical group 0.000 description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 8
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- SMUQFGGVLNAIOZ-UHFFFAOYSA-N quinaldine Chemical compound C1=CC=CC2=NC(C)=CC=C21 SMUQFGGVLNAIOZ-UHFFFAOYSA-N 0.000 description 7
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 6
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- 239000003480 eluent Substances 0.000 description 6
- 238000005984 hydrogenation reaction Methods 0.000 description 6
- 150000002500 ions Chemical class 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 5
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- 229910052698 phosphorus Inorganic materials 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
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- 125000000369 oxido group Chemical group [*]=O 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
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- HCTVWSOKIJULET-LQDWTQKMSA-M phenoxymethylpenicillin potassium Chemical compound [K+].N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)COC1=CC=CC=C1 HCTVWSOKIJULET-LQDWTQKMSA-M 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- VUNPWIPIOOMCPT-UHFFFAOYSA-N piperidin-3-ylmethanol Chemical compound OCC1CCCNC1 VUNPWIPIOOMCPT-UHFFFAOYSA-N 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
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- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000004549 quinolin-4-yl group Chemical group N1=CC=C(C2=CC=CC=C12)* 0.000 description 1
- WINWAFCAQPFBQA-UHFFFAOYSA-N quinoline-7-carbaldehyde Chemical compound C1=CC=NC2=CC(C=O)=CC=C21 WINWAFCAQPFBQA-UHFFFAOYSA-N 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
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- 101150110872 ric-3 gene Proteins 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 102220287733 rs1555526988 Human genes 0.000 description 1
- 102220254284 rs755928199 Human genes 0.000 description 1
- 102220097796 rs876659415 Human genes 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229940080313 sodium starch Drugs 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
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- 241000894007 species Species 0.000 description 1
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- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
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- 150000008163 sugars Chemical class 0.000 description 1
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- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
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- 229940086542 triethylamine Drugs 0.000 description 1
- 125000005289 uranyl group Chemical group 0.000 description 1
- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- 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
- C07D405/02—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 two hetero rings
- C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Quinoline Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01112370.0 | 2001-05-21 | ||
| EP01112370 | 2001-05-21 | ||
| PCT/EP2002/005120 WO2002094789A1 (en) | 2001-05-21 | 2002-05-08 | Quinoline derivatives as ligands for the neuropeptide y receptor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2446324A1 true CA2446324A1 (en) | 2002-11-28 |
Family
ID=8177497
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002446324A Abandoned CA2446324A1 (en) | 2001-05-21 | 2002-05-08 | Quinoline derivatives as ligands for the neuropeptide y receptor |
Country Status (19)
| Country | Link |
|---|---|
| US (2) | US6818767B2 (OSRAM) |
| EP (1) | EP1395564B1 (OSRAM) |
| JP (1) | JP3715280B2 (OSRAM) |
| KR (1) | KR100621287B1 (OSRAM) |
| CN (1) | CN100376557C (OSRAM) |
| AR (1) | AR035979A1 (OSRAM) |
| AT (1) | ATE387428T1 (OSRAM) |
| AU (1) | AU2002338896B2 (OSRAM) |
| BR (1) | BR0209957A (OSRAM) |
| CA (1) | CA2446324A1 (OSRAM) |
| DE (1) | DE60225274T2 (OSRAM) |
| ES (1) | ES2300478T3 (OSRAM) |
| GT (1) | GT200200090A (OSRAM) |
| MX (1) | MXPA03010565A (OSRAM) |
| PA (1) | PA8545301A1 (OSRAM) |
| PE (1) | PE20021155A1 (OSRAM) |
| UY (1) | UY27300A1 (OSRAM) |
| WO (1) | WO2002094789A1 (OSRAM) |
| ZA (1) | ZA200308783B (OSRAM) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009062289A1 (en) * | 2007-11-15 | 2009-05-22 | Boehringer Ingelheim International Gmbh | Inhibitors of human immunodeficiency virus replication |
| US8354429B2 (en) | 2007-11-16 | 2013-01-15 | Gilead Sciences, Inc. | Inhibitors of human immunodeficiency virus replication |
Families Citing this family (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6900226B2 (en) * | 2000-09-06 | 2005-05-31 | Hoffman-La Roche Inc. | Neuropeptide Y antagonists |
| JP2005519876A (ja) * | 2001-11-27 | 2005-07-07 | メルク エンド カムパニー インコーポレーテッド | ２−アミノキノリン化合物 |
| MXPA04007502A (es) | 2002-02-04 | 2004-11-10 | Hoffmann La Roche | Derivados de quinolina como antagonistas de neuropeptido y (npy). |
| US7105526B2 (en) | 2002-06-28 | 2006-09-12 | Banyu Pharmaceuticals Co., Ltd. | Benzimidazole derivatives |
| RU2296757C2 (ru) | 2002-07-05 | 2007-04-10 | Ф.Хоффманн-Ля Рош Аг | Производные хиназолина |
| BR0313278A (pt) | 2002-08-07 | 2005-07-05 | Hoffmann La Roche | Compostos, processo para a preparação de um composto, composição farmacêutica que compreende o mesmo e sua utilização, método para o tratamento e profilaxia de enfermidades e obesidade e utilização dos compostos |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| JP2006519846A (ja) * | 2003-03-10 | 2006-08-31 | シェーリング コーポレイション | 複素環式キナーゼインヒビター：使用および合成の方法 |
| JP4765627B2 (ja) | 2003-09-22 | 2011-09-07 | Ｍｓｄ株式会社 | 新規ピペリジン誘導体 |
| JP2007510745A (ja) | 2003-11-10 | 2007-04-26 | シンタ ファーマシューティカルズ コーポレーション | 縮合複素環式化合物 |
| US20080125403A1 (en) | 2004-04-02 | 2008-05-29 | Merck & Co., Inc. | Method of Treating Men with Metabolic and Anthropometric Disorders |
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2002
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- 2002-05-08 MX MXPA03010565A patent/MXPA03010565A/es active IP Right Grant
- 2002-05-08 CN CNB028104013A patent/CN100376557C/zh not_active Expired - Fee Related
- 2002-05-08 CA CA002446324A patent/CA2446324A1/en not_active Abandoned
- 2002-05-08 DE DE60225274T patent/DE60225274T2/de not_active Expired - Fee Related
- 2002-05-08 ES ES02771639T patent/ES2300478T3/es not_active Expired - Lifetime
- 2002-05-08 AT AT02771639T patent/ATE387428T1/de not_active IP Right Cessation
- 2002-05-08 AU AU2002338896A patent/AU2002338896B2/en not_active Ceased
- 2002-05-08 EP EP02771639A patent/EP1395564B1/en not_active Expired - Lifetime
- 2002-05-08 BR BR0209957-8A patent/BR0209957A/pt not_active IP Right Cessation
- 2002-05-08 KR KR1020037015121A patent/KR100621287B1/ko not_active Expired - Fee Related
- 2002-05-08 WO PCT/EP2002/005120 patent/WO2002094789A1/en not_active Ceased
- 2002-05-16 PA PA20028545301A patent/PA8545301A1/es unknown
- 2002-05-17 AR ARP020101836A patent/AR035979A1/es not_active Application Discontinuation
- 2002-05-17 PE PE2002000425A patent/PE20021155A1/es not_active Application Discontinuation
- 2002-05-20 US US10/151,505 patent/US6818767B2/en not_active Expired - Fee Related
- 2002-05-20 GT GT200200090A patent/GT200200090A/es unknown
- 2002-05-21 UY UY27300A patent/UY27300A1/es not_active Application Discontinuation
-
2003
- 2003-11-11 ZA ZA200308783A patent/ZA200308783B/en unknown
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2009062289A1 (en) * | 2007-11-15 | 2009-05-22 | Boehringer Ingelheim International Gmbh | Inhibitors of human immunodeficiency virus replication |
| US8377960B2 (en) | 2007-11-15 | 2013-02-19 | Gilead Sciences, Inc. | Inhibitors of human immunodeficiency virus replication |
| US8354429B2 (en) | 2007-11-16 | 2013-01-15 | Gilead Sciences, Inc. | Inhibitors of human immunodeficiency virus replication |
| US8710230B2 (en) | 2007-11-16 | 2014-04-29 | Gilead Sciences, Inc. | Inhibitors of human immunodeficiency virus replication |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1395564A1 (en) | 2004-03-10 |
| KR100621287B1 (ko) | 2006-09-13 |
| PE20021155A1 (es) | 2002-12-17 |
| US20020198194A1 (en) | 2002-12-26 |
| ATE387428T1 (de) | 2008-03-15 |
| US6818767B2 (en) | 2004-11-16 |
| US20050049413A1 (en) | 2005-03-03 |
| GT200200090A (es) | 2003-06-19 |
| JP2004536066A (ja) | 2004-12-02 |
| WO2002094789A1 (en) | 2002-11-28 |
| JP3715280B2 (ja) | 2005-11-09 |
| EP1395564B1 (en) | 2008-02-27 |
| AU2002338896B2 (en) | 2006-04-27 |
| BR0209957A (pt) | 2004-03-30 |
| PA8545301A1 (es) | 2003-01-24 |
| DE60225274T2 (de) | 2009-03-26 |
| ZA200308783B (en) | 2005-02-11 |
| KR20030096416A (ko) | 2003-12-24 |
| MXPA03010565A (es) | 2004-03-02 |
| UY27300A1 (es) | 2002-11-29 |
| ES2300478T3 (es) | 2008-06-16 |
| AR035979A1 (es) | 2004-07-28 |
| DE60225274D1 (de) | 2008-04-10 |
| CN1522249A (zh) | 2004-08-18 |
| CN100376557C (zh) | 2008-03-26 |
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