ZA200606594B - Tetrazole compounds and their use as metabotropic glutamate receptor antagonists - Google Patents
Tetrazole compounds and their use as metabotropic glutamate receptor antagonists Download PDFInfo
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- ZA200606594B ZA200606594B ZA200606594A ZA200606594A ZA200606594B ZA 200606594 B ZA200606594 B ZA 200606594B ZA 200606594 A ZA200606594 A ZA 200606594A ZA 200606594 A ZA200606594 A ZA 200606594A ZA 200606594 B ZA200606594 B ZA 200606594B
- Authority
- ZA
- South Africa
- Prior art keywords
- tetrazol
- methyl
- triazol
- phenyl
- ethyl
- Prior art date
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- -1 Tetrazole compounds Chemical class 0.000 title claims description 36
- 108010010914 Metabotropic glutamate receptors Proteins 0.000 title claims description 32
- 102000016193 Metabotropic glutamate receptors Human genes 0.000 title claims description 32
- 239000003825 glutamate receptor antagonist Substances 0.000 title 1
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 43
- 150000001875 compounds Chemical class 0.000 claims description 41
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 37
- 125000000217 alkyl group Chemical group 0.000 claims description 28
- 229910052799 carbon Inorganic materials 0.000 claims description 26
- 229910052717 sulfur Inorganic materials 0.000 claims description 23
- 229910052760 oxygen Inorganic materials 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 125000004429 atom Chemical group 0.000 claims description 19
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 125000005843 halogen group Chemical group 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 16
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 15
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- 208000035475 disorder Diseases 0.000 claims description 13
- 150000003852 triazoles Chemical class 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 7
- 125000004193 piperazinyl group Chemical group 0.000 claims description 7
- 208000002193 Pain Diseases 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 230000001404 mediated effect Effects 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 208000020016 psychiatric disease Diseases 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 5
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 5
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 5
- 208000012902 Nervous system disease Diseases 0.000 claims description 5
- 208000025966 Neurological disease Diseases 0.000 claims description 5
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 229920002554 vinyl polymer Polymers 0.000 claims description 5
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 4
- 230000001684 chronic effect Effects 0.000 claims description 4
- YKJBTFYGGYMXRG-UHFFFAOYSA-N n-[[2-(3-chlorophenyl)tetrazol-5-yl]methyl]-n,4-dimethyl-5-pyridin-4-yl-1,2,4-triazol-3-amine Chemical compound N=1N=C(C=2C=CN=CC=2)N(C)C=1N(C)CC(=N1)N=NN1C1=CC=CC(Cl)=C1 YKJBTFYGGYMXRG-UHFFFAOYSA-N 0.000 claims description 4
- 238000001783 near-resonance Rayleigh scattering spectroscopy Methods 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 150000004677 hydrates Chemical class 0.000 claims description 3
- DPVHQPGVGADSNV-UHFFFAOYSA-N n,4-dimethyl-n-[[2-(3-methylphenyl)tetrazol-5-yl]methyl]-5-pyridin-4-yl-1,2,4-triazol-3-amine Chemical compound N=1N=C(C=2C=CN=CC=2)N(C)C=1N(C)CC(=N1)N=NN1C1=CC=CC(C)=C1 DPVHQPGVGADSNV-UHFFFAOYSA-N 0.000 claims description 3
- YXVILKGFMGECJM-UHFFFAOYSA-N n-[1-[2-(3-chlorophenyl)tetrazol-5-yl]ethyl]-n,4-dimethyl-5-pyridin-4-yl-1,2,4-triazol-3-amine Chemical compound N1=NN(C=2C=C(Cl)C=CC=2)N=C1C(C)N(C)C(N1C)=NN=C1C1=CC=NC=C1 YXVILKGFMGECJM-UHFFFAOYSA-N 0.000 claims description 3
- SHJRYGHPCXSPDP-UHFFFAOYSA-N 3-[5-[1-(3-pyridin-4-yl-6,7-dihydro-5h-[1,2,4]triazolo[4,3-a]pyrimidin-8-yl)ethyl]tetrazol-2-yl]benzonitrile Chemical compound N1=NN(C=2C=C(C=CC=2)C#N)N=C1C(C)N1CCCN2C1=NN=C2C1=CC=NC=C1 SHJRYGHPCXSPDP-UHFFFAOYSA-N 0.000 claims description 2
- GKPBQXKXCXURER-UHFFFAOYSA-N 3-[5-[1-[methyl-(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)amino]ethyl]tetrazol-2-yl]benzonitrile Chemical compound N1=NN(C=2C=C(C=CC=2)C#N)N=C1C(C)N(C)C(N1C)=NN=C1C1=CC=NC=C1 GKPBQXKXCXURER-UHFFFAOYSA-N 0.000 claims description 2
- YNYJLGIRFUGDEY-UHFFFAOYSA-N 3-[5-[[methyl-(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)amino]methyl]tetrazol-2-yl]benzonitrile Chemical compound N=1N=C(C=2C=CN=CC=2)N(C)C=1N(C)CC(=N1)N=NN1C1=CC=CC(C#N)=C1 YNYJLGIRFUGDEY-UHFFFAOYSA-N 0.000 claims description 2
- GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 claims description 2
- BZTXEMPYJURSGN-UHFFFAOYSA-N 4-[4-cyclopropyl-5-[1-[2-(2-fluoro-5-methylphenyl)tetrazol-5-yl]ethoxy]-1,2,4-triazol-3-yl]pyridine Chemical compound N1=NN(C=2C(=CC=C(C)C=2)F)N=C1C(C)OC(N1C2CC2)=NN=C1C1=CC=NC=C1 BZTXEMPYJURSGN-UHFFFAOYSA-N 0.000 claims description 2
- ADYINAWGQYFZDK-UHFFFAOYSA-N 4-[4-methyl-5-[[2-(3-methylphenyl)tetrazol-5-yl]methoxy]-1,2,4-triazol-3-yl]pyridine Chemical compound CC1=CC=CC(N2N=C(COC=3N(C(C=4C=CN=CC=4)=NN=3)C)N=N2)=C1 ADYINAWGQYFZDK-UHFFFAOYSA-N 0.000 claims description 2
- AVXFPSCDBCQXJF-UHFFFAOYSA-N 4-[5-[1-[2-(2-fluoro-5-methylphenyl)tetrazol-5-yl]ethoxy]-4-methyl-1,2,4-triazol-3-yl]pyridine Chemical compound N1=NN(C=2C(=CC=C(C)C=2)F)N=C1C(C)OC(N1C)=NN=C1C1=CC=NC=C1 AVXFPSCDBCQXJF-UHFFFAOYSA-N 0.000 claims description 2
- IUJVCUPZEAGDSU-UHFFFAOYSA-N 4-[5-[1-[2-(3-chlorophenyl)tetrazol-5-yl]ethylsulfanyl]-4-cyclopropyl-1,2,4-triazol-3-yl]pyridine Chemical compound N1=NN(C=2C=C(Cl)C=CC=2)N=C1C(C)SC(N1C2CC2)=NN=C1C1=CC=NC=C1 IUJVCUPZEAGDSU-UHFFFAOYSA-N 0.000 claims description 2
- ZRPKSYNMJBJRIX-UHFFFAOYSA-N 4-[5-[[2-(2-fluoro-5-methylphenyl)tetrazol-5-yl]methoxy]-4-methyl-1,2,4-triazol-3-yl]pyridine Chemical compound CC1=CC=C(F)C(N2N=C(COC=3N(C(C=4C=CN=CC=4)=NN=3)C)N=N2)=C1 ZRPKSYNMJBJRIX-UHFFFAOYSA-N 0.000 claims description 2
- NEXXZJKDYDTXEJ-UHFFFAOYSA-N 4-[5-[[2-(5-chloro-2-fluorophenyl)tetrazol-5-yl]methylsulfanyl]-4-methyl-1,2,4-triazol-3-yl]pyridine Chemical compound N=1N=C(C=2C=CN=CC=2)N(C)C=1SCC(=N1)N=NN1C1=CC(Cl)=CC=C1F NEXXZJKDYDTXEJ-UHFFFAOYSA-N 0.000 claims description 2
- BSWZFKOFLUNZSS-UHFFFAOYSA-N 5-[1-[[5-(3,5-difluorophenyl)-4-ethyl-1,2,4-triazol-3-yl]sulfanyl]ethyl]-2-(3-methylphenyl)tetrazole Chemical compound N=1N=C(C=2C=C(F)C=C(F)C=2)N(CC)C=1SC(C)C(=N1)N=NN1C1=CC=CC(C)=C1 BSWZFKOFLUNZSS-UHFFFAOYSA-N 0.000 claims description 2
- XDBPPWPUXFQUBP-UHFFFAOYSA-N 9-[1-[2-(3-chlorophenyl)tetrazol-5-yl]ethyl]-3-pyridin-4-yl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a][1,3]diazepine Chemical compound N1=NN(C=2C=C(Cl)C=CC=2)N=C1C(C)N1CCCCN2C1=NN=C2C1=CC=NC=C1 XDBPPWPUXFQUBP-UHFFFAOYSA-N 0.000 claims description 2
- XUNQTJIRDMBDPR-UHFFFAOYSA-N 9-[1-[2-(3-methylphenyl)tetrazol-5-yl]ethyl]-3-pyridin-4-yl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a][1,3]diazepine Chemical compound N1=NN(C=2C=C(C)C=CC=2)N=C1C(C)N1CCCCN2C1=NN=C2C1=CC=NC=C1 XUNQTJIRDMBDPR-UHFFFAOYSA-N 0.000 claims description 2
- DZDODDUVZQOUAR-UHFFFAOYSA-N 9-[[2-(3-chlorophenyl)tetrazol-5-yl]methyl]-3-pyridin-4-yl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a][1,3]diazepine Chemical compound ClC1=CC=CC(N2N=C(CN3C=4N(C(=NN=4)C=4C=CN=CC=4)CCCC3)N=N2)=C1 DZDODDUVZQOUAR-UHFFFAOYSA-N 0.000 claims description 2
- 208000000094 Chronic Pain Diseases 0.000 claims description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 2
- 208000005298 acute pain Diseases 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- HOUFSJNBIFUWKT-UHFFFAOYSA-N ethyl 4-[[2-(2-fluoro-5-methylphenyl)tetrazol-5-yl]methyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1CC1=NN(C=2C(=CC=C(C)C=2)F)N=N1 HOUFSJNBIFUWKT-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- OYNCUSOSFPTOOL-UHFFFAOYSA-N n-[1-[2-(3-iodophenyl)tetrazol-5-yl]ethyl]-n,4-dimethyl-5-pyridin-4-yl-1,2,4-triazol-3-amine Chemical compound N1=NN(C=2C=C(I)C=CC=2)N=C1C(C)N(C)C(N1C)=NN=C1C1=CC=NC=C1 OYNCUSOSFPTOOL-UHFFFAOYSA-N 0.000 claims description 2
- QNSSPKJKXZTNBR-UHFFFAOYSA-N n-[[2-(3-iodophenyl)tetrazol-5-yl]methyl]-n,4-dimethyl-5-pyridin-4-yl-1,2,4-triazol-3-amine Chemical compound N=1N=C(C=2C=CN=CC=2)N(C)C=1N(C)CC(=N1)N=NN1C1=CC=CC(I)=C1 QNSSPKJKXZTNBR-UHFFFAOYSA-N 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 3
- 125000001963 4 membered heterocyclic group Chemical group 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- ZQOTYMUJVHFJMO-UHFFFAOYSA-N 1-[2-(3-chlorophenyl)tetrazol-5-yl]-2-(4-cyclopropyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)ethanol Chemical compound N1=NN(C=2C=C(Cl)C=CC=2)N=C1C(O)CC(N1C2CC2)=NN=C1C1=CC=NC=C1 ZQOTYMUJVHFJMO-UHFFFAOYSA-N 0.000 claims 1
- PKDPUENCROCRCH-UHFFFAOYSA-N 1-piperazin-1-ylethanone Chemical compound CC(=O)N1CCNCC1 PKDPUENCROCRCH-UHFFFAOYSA-N 0.000 claims 1
- BKKWKXDUSCUVDZ-UHFFFAOYSA-N 2-(3-chlorophenyl)-5-(1-phenylprop-1-en-2-yl)tetrazole Chemical compound N1=NN(C=2C=C(Cl)C=CC=2)N=C1C(C)=CC1=CC=CC=C1 BKKWKXDUSCUVDZ-UHFFFAOYSA-N 0.000 claims 1
- BMOGSBKIRGTSIJ-SNVBAGLBSA-N 2-(3-chlorophenyl)-5-[(1r)-1-[[5-(3,5-difluorophenyl)-4-methyl-1,2,4-triazol-3-yl]oxy]ethyl]tetrazole Chemical compound O([C@H](C)C1=NN(N=N1)C=1C=C(Cl)C=CC=1)C(N1C)=NN=C1C1=CC(F)=CC(F)=C1 BMOGSBKIRGTSIJ-SNVBAGLBSA-N 0.000 claims 1
- YRKGWCXYMUDYGM-UHFFFAOYSA-N 2-[2-(3-chlorophenyl)tetrazol-5-yl]-1-(4-cyclopropyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)ethanol Chemical compound N=1N=C(C=2C=CN=CC=2)N(C2CC2)C=1C(O)CC(=N1)N=NN1C1=CC=CC(Cl)=C1 YRKGWCXYMUDYGM-UHFFFAOYSA-N 0.000 claims 1
- SGZLSBWGNCQYJP-UHFFFAOYSA-N 2-[5-(5-methylfuran-2-yl)tetrazol-2-yl]-n-(2-phenylbenzotriazol-5-yl)acetamide Chemical compound O1C(C)=CC=C1C1=NN(CC(=O)NC2=CC3=NN(N=C3C=C2)C=2C=CC=CC=2)N=N1 SGZLSBWGNCQYJP-UHFFFAOYSA-N 0.000 claims 1
- ZXCMVOMJHFQABJ-CYBMUJFWSA-N 3-[4-[(1r)-1-[2-(3-chlorophenyl)tetrazol-5-yl]ethyl]piperazin-1-yl]pyrazine-2-carbonitrile Chemical compound C1CN([C@H](C)C2=NN(N=N2)C=2C=C(Cl)C=CC=2)CCN1C1=NC=CN=C1C#N ZXCMVOMJHFQABJ-CYBMUJFWSA-N 0.000 claims 1
- ZXCMVOMJHFQABJ-ZDUSSCGKSA-N 3-[4-[(1s)-1-[2-(3-chlorophenyl)tetrazol-5-yl]ethyl]piperazin-1-yl]pyrazine-2-carbonitrile Chemical compound C1CN([C@@H](C)C2=NN(N=N2)C=2C=C(Cl)C=CC=2)CCN1C1=NC=CN=C1C#N ZXCMVOMJHFQABJ-ZDUSSCGKSA-N 0.000 claims 1
- YKMQYRLZYIFWBU-UHFFFAOYSA-N 3-[5-[(3-pyridin-4-yl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a][1,3]diazepin-9-yl)methyl]tetrazol-2-yl]benzonitrile Chemical compound N#CC1=CC=CC(N2N=C(CN3C=4N(C(=NN=4)C=4C=CN=CC=4)CCCC3)N=N2)=C1 YKMQYRLZYIFWBU-UHFFFAOYSA-N 0.000 claims 1
- KNUPDYJEUFQYLB-UHFFFAOYSA-N 3-[5-[(3-pyridin-4-yl-6,7-dihydro-5h-[1,2,4]triazolo[4,3-a]pyrimidin-8-yl)methyl]tetrazol-2-yl]benzonitrile Chemical compound N#CC1=CC=CC(N2N=C(CN3C=4N(C(=NN=4)C=4C=CN=CC=4)CCC3)N=N2)=C1 KNUPDYJEUFQYLB-UHFFFAOYSA-N 0.000 claims 1
- QAWNJLHEHASGJD-UHFFFAOYSA-N 3-[5-[(4-cyclopropyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)sulfanylmethyl]tetrazol-2-yl]benzonitrile Chemical compound N#CC1=CC=CC(N2N=C(CSC=3N(C(C=4C=CN=CC=4)=NN=3)C3CC3)N=N2)=C1 QAWNJLHEHASGJD-UHFFFAOYSA-N 0.000 claims 1
- KUWCVGDHTYYBSL-UHFFFAOYSA-N 4-[4-cyclopropyl-5-[1-[2-(2-fluoro-5-methylphenyl)tetrazol-5-yl]ethylsulfanyl]-1,2,4-triazol-3-yl]pyridine Chemical compound N1=NN(C=2C(=CC=C(C)C=2)F)N=C1C(C)SC(N1C2CC2)=NN=C1C1=CC=NC=C1 KUWCVGDHTYYBSL-UHFFFAOYSA-N 0.000 claims 1
- HMBGXKUWLFCCOG-UHFFFAOYSA-N 4-[4-cyclopropyl-5-[1-[2-(3-iodophenyl)tetrazol-5-yl]ethoxy]-1,2,4-triazol-3-yl]pyridine Chemical compound N1=NN(C=2C=C(I)C=CC=2)N=C1C(C)OC(N1C2CC2)=NN=C1C1=CC=NC=C1 HMBGXKUWLFCCOG-UHFFFAOYSA-N 0.000 claims 1
- RLOOOHWJTLPJOK-UHFFFAOYSA-N 4-[4-cyclopropyl-5-[[2-(3-iodophenyl)tetrazol-5-yl]methoxy]-1,2,4-triazol-3-yl]pyridine Chemical compound IC1=CC=CC(N2N=C(COC=3N(C(C=4C=CN=CC=4)=NN=3)C3CC3)N=N2)=C1 RLOOOHWJTLPJOK-UHFFFAOYSA-N 0.000 claims 1
- OPRJFHQMQBEOEB-UHFFFAOYSA-N 4-[4-cyclopropyl-5-[[2-(3-methylphenyl)tetrazol-5-yl]methoxy]-1,2,4-triazol-3-yl]pyridine Chemical compound CC1=CC=CC(N2N=C(COC=3N(C(C=4C=CN=CC=4)=NN=3)C3CC3)N=N2)=C1 OPRJFHQMQBEOEB-UHFFFAOYSA-N 0.000 claims 1
- RAYPHVILNUIXPW-UHFFFAOYSA-N 4-[4-cyclopropyl-5-[[2-(3-methylphenyl)tetrazol-5-yl]methylsulfanyl]-1,2,4-triazol-3-yl]pyridine Chemical compound CC1=CC=CC(N2N=C(CSC=3N(C(C=4C=CN=CC=4)=NN=3)C3CC3)N=N2)=C1 RAYPHVILNUIXPW-UHFFFAOYSA-N 0.000 claims 1
- HBTWXQLKSAOIPA-NSHDSACASA-N 4-[5-[(1s)-1-[2-(3-chlorophenyl)tetrazol-5-yl]ethoxy]-4-methyl-1,2,4-triazol-3-yl]pyridine Chemical compound O([C@@H](C)C1=NN(N=N1)C=1C=C(Cl)C=CC=1)C(N1C)=NN=C1C1=CC=NC=C1 HBTWXQLKSAOIPA-NSHDSACASA-N 0.000 claims 1
- ANOCVGIRTXMBMF-UHFFFAOYSA-N 4-[5-[1-[2-(5-chloro-2-fluorophenyl)tetrazol-5-yl]ethylsulfanyl]-4-methyl-1,2,4-triazol-3-yl]pyridine Chemical compound N1=NN(C=2C(=CC=C(Cl)C=2)F)N=C1C(C)SC(N1C)=NN=C1C1=CC=NC=C1 ANOCVGIRTXMBMF-UHFFFAOYSA-N 0.000 claims 1
- JAHBCKUCQCXRRL-UHFFFAOYSA-N 4-[5-[[2-(5-chloro-2-fluorophenyl)tetrazol-5-yl]methylsulfanyl]-4-cyclopropyl-1,2,4-triazol-3-yl]pyridine Chemical compound FC1=CC=C(Cl)C=C1N1N=C(CSC=2N(C(C=3C=CN=CC=3)=NN=2)C2CC2)N=N1 JAHBCKUCQCXRRL-UHFFFAOYSA-N 0.000 claims 1
- ZOMNBCKZYULUDN-CQSZACIVSA-N 6-[4-[(1r)-1-[2-(3-chlorophenyl)tetrazol-5-yl]ethyl]piperazin-1-yl]pyridine-3-carbonitrile Chemical compound C1CN([C@H](C)C2=NN(N=N2)C=2C=C(Cl)C=CC=2)CCN1C1=CC=C(C#N)C=N1 ZOMNBCKZYULUDN-CQSZACIVSA-N 0.000 claims 1
- ZOMNBCKZYULUDN-AWEZNQCLSA-N 6-[4-[(1s)-1-[2-(3-chlorophenyl)tetrazol-5-yl]ethyl]piperazin-1-yl]pyridine-3-carbonitrile Chemical compound C1CN([C@@H](C)C2=NN(N=N2)C=2C=C(Cl)C=CC=2)CCN1C1=CC=C(C#N)C=N1 ZOMNBCKZYULUDN-AWEZNQCLSA-N 0.000 claims 1
- DIOOLZYLVLEVNL-UHFFFAOYSA-N 8-[1-[2-(3-iodophenyl)tetrazol-5-yl]ethyl]-3-(2-methoxypyridin-4-yl)-6,7-dihydro-5h-[1,2,4]triazolo[4,3-a]pyrimidine Chemical compound C1=NC(OC)=CC(C=2N3CCCN(C3=NN=2)C(C)C2=NN(N=N2)C=2C=C(I)C=CC=2)=C1 DIOOLZYLVLEVNL-UHFFFAOYSA-N 0.000 claims 1
- DQZBCKPXVHZVHT-UHFFFAOYSA-N 9-[[2-(3-iodophenyl)tetrazol-5-yl]methyl]-3-pyridin-4-yl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a][1,3]diazepine Chemical compound IC1=CC=CC(N2N=C(CN3C=4N(C(=NN=4)C=4C=CN=CC=4)CCCC3)N=N2)=C1 DQZBCKPXVHZVHT-UHFFFAOYSA-N 0.000 claims 1
- MPRZKCDFPSPVSI-UHFFFAOYSA-N 9-[[2-(3-methylphenyl)tetrazol-5-yl]methyl]-3-pyridin-4-yl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a][1,3]diazepine Chemical compound CC1=CC=CC(N2N=C(CN3C=4N(C(=NN=4)C=4C=CN=CC=4)CCCC3)N=N2)=C1 MPRZKCDFPSPVSI-UHFFFAOYSA-N 0.000 claims 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 1
- DOLWUAMIJZGVTC-UHFFFAOYSA-N [1,2,4]triazolo[4,3-a]pyrimidine Chemical compound N1=CC=CN2C=NN=C21 DOLWUAMIJZGVTC-UHFFFAOYSA-N 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
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- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/08—Antiepileptics; Anticonvulsants
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
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- 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
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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
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- 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
-
- 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
- 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
- C07D403/06—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 linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D403/12—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 linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
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- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
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- General Health & Medical Sciences (AREA)
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- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US54529104P | 2004-02-18 | 2004-02-18 |
Publications (1)
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| ZA200606594B true ZA200606594B (en) | 2007-11-28 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| ZA200606594A ZA200606594B (en) | 2004-02-18 | 2006-08-08 | Tetrazole compounds and their use as metabotropic glutamate receptor antagonists |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US20070197549A1 (ru) |
| EP (1) | EP1716125B1 (ru) |
| JP (1) | JP5084269B2 (ru) |
| KR (1) | KR20070027504A (ru) |
| CN (2) | CN101845023A (ru) |
| AR (1) | AR047812A1 (ru) |
| AU (1) | AU2005214379B2 (ru) |
| BR (1) | BRPI0507498A (ru) |
| CA (1) | CA2556263A1 (ru) |
| IL (1) | IL177056A0 (ru) |
| MX (1) | MXPA06009019A (ru) |
| MY (1) | MY145075A (ru) |
| NO (1) | NO20063470L (ru) |
| RU (1) | RU2372347C2 (ru) |
| SG (1) | SG150539A1 (ru) |
| TW (1) | TW200533664A (ru) |
| UA (1) | UA85576C2 (ru) |
| UY (1) | UY28763A1 (ru) |
| WO (1) | WO2005080356A1 (ru) |
| ZA (1) | ZA200606594B (ru) |
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| SG150539A1 (en) * | 2004-02-18 | 2009-03-30 | Astrazeneca Ab | Tetrazole compounds and their use as metabotropic glutamate receptor antagonists |
| AU2005214380A1 (en) | 2004-02-18 | 2005-09-01 | Astrazeneca Ab | Fused hetrocyclic compounds and their use as metabotropic receptor antagonists for the treatment of gastrointestinal disorders |
| GB0420722D0 (en) | 2004-09-17 | 2004-10-20 | Addex Pharmaceuticals Sa | Novel allosteric modulators |
| JPWO2006080533A1 (ja) * | 2005-01-31 | 2008-06-19 | 持田製薬株式会社 | ３−アミノ−１，２，４−トリアゾール誘導体 |
| US7964619B2 (en) * | 2005-06-03 | 2011-06-21 | The University Of North Carolina At Chapel Hill | Teraryl components as antiparasitic agents |
| AU2006202083A1 (en) * | 2005-06-03 | 2006-12-21 | Reto Brun | Linear dicationic terphenyls and their aza analogues as antiparasitic agents |
| UY29796A1 (es) | 2005-09-29 | 2007-04-30 | Astrazeneca Ab | Nuevos compuestos para el tratamiento de trastornos neurológicos, psiquiátricos o del dolor |
| HUP0500921A2 (en) * | 2005-10-05 | 2007-07-30 | Richter Gedeon Nyrt | Tetrazole derivatives, process for their preparation and their use |
| AR059898A1 (es) * | 2006-03-15 | 2008-05-07 | Janssen Pharmaceutica Nv | Derivados de 3-ciano-piridona 1,4-disustituida y su uso como moduladores alostericos de los receptores mglur2 |
| TW200808800A (en) * | 2006-05-05 | 2008-02-16 | Astrazeneca Ab | MGluR5 modulators V |
| TW200811157A (en) | 2006-05-05 | 2008-03-01 | Astrazeneca Ab | mGluR5 modulators I |
| TW200811179A (en) * | 2006-05-05 | 2008-03-01 | Astrazeneca Ab | mGluR5 modulators VI |
| TW200900065A (en) * | 2007-03-07 | 2009-01-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives |
| TW200845978A (en) | 2007-03-07 | 2008-12-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives |
| TW200900391A (en) * | 2007-03-07 | 2009-01-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-phenyl-piperidin-1-yl)-pyridin-2-one derivatives |
| AU2008297876B2 (en) | 2007-09-14 | 2011-07-07 | Addex Pharma S.A. | 1,3-disubstituted 4-(aryl-x-phenyl)-1h-pyridin-2-ones |
| PT2203439E (pt) | 2007-09-14 | 2011-02-11 | Ortho Mcneil Janssen Pharm | 4-fenil-3,4,5,6-tetra-hidro-2h,1'h-[1,4']bipiridinil-2'- onas 1',3'-dissubstituídas |
| JP5433579B2 (ja) * | 2007-09-14 | 2014-03-05 | ジャンセン ファーマシューティカルズ， インコーポレイテッド． | １，３−二置換−４−フェニル−１ｈ−ピリジン−２−オン |
| CL2008003085A1 (es) * | 2007-10-19 | 2009-10-09 | Astrazeneca Ab | Compuestos derivados de 4-metil-5-[1-(2-(3-metilfenil)-2h-tetrazol-5-il)etoxi]-4h-1,2,4-triazol-3-il moduladores del receptor mglur5; composiciones farmceuticas que los contienen; compuestos intermediarios; y su uso en la preparacion de un medicamento util en el tratamiento de desordenes neurologicos, psiquiatricos o gastrointestinales. |
| WO2009054785A1 (en) * | 2007-10-26 | 2009-04-30 | Astrazeneca Ab | 1,2,4-triazole ether derivatives as modulators of mglur5 |
| CN101918399A (zh) * | 2007-10-26 | 2010-12-15 | 阿斯利康(瑞典)有限公司 | 作为mglur5调节剂的氨基1,2,4-三唑衍生物 |
| RU2492170C9 (ru) | 2007-11-14 | 2013-12-27 | Орто-Макнейл-Янссен Фармасьютикалз, Инк. | Имидазо[1,2-а]пиридиновые производные и их применение в качестве положительных аллостерических модуляторов рецепторов mglur2 |
| SI2767537T1 (sl) | 2008-08-06 | 2017-08-31 | Medivation Technologies, Inc. | Dihidropiridoftalazinonski inhibitorji poli(adp-riboza) polimeraze (parp) |
| RU2510396C2 (ru) | 2008-09-02 | 2014-03-27 | Янссен Фармасьютикалз, Инк. | 3-азабицикло[3.1.0]гексильные производные в качестве модуляторов метаботропных глутаматных рецепторов |
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| AU2009319387B2 (en) | 2008-11-28 | 2012-05-10 | Addex Pharma S.A. | Indole and benzoxazine derivatives as modulators of metabotropic glutamate receptors |
| MX2011005981A (es) * | 2008-12-12 | 2011-06-27 | Astrazeneca Ab | Nuevo proceso para preparar 4-[4-metil-5-(alquiltio c1-10/aril c5-10-alquilto c1-6)-4h-1,2,4-triazol-3-il]piridinas. |
| US20110306768A1 (en) * | 2008-12-18 | 2011-12-15 | Astrazeneca Ab | Processes for the manufacture of 3--pyridine, 4-methyl-3-methylthio-5-(3-pyridyl)-l,2,4-triazole, and (1r)-1-[2-(3-methylphenyl)-2h-tetrazol-5-yl]ethanol |
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| AR080055A1 (es) | 2010-02-01 | 2012-03-07 | Novartis Ag | Derivados de pirazolo-[5,1-b]-oxazol como antagonistas de los receptores de crf -1 |
| CN102753527B (zh) | 2010-02-02 | 2014-12-24 | 诺华股份有限公司 | 用作crf受体拮抗剂的环己基酰胺衍生物 |
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| EP3431106B1 (en) | 2014-01-21 | 2020-12-30 | Janssen Pharmaceutica NV | Combinations comprising positive allosteric modulators of metabotropic glutamatergic receptor subtype 2 and their use |
| KR20200126026A (ko) | 2014-01-21 | 2020-11-05 | 얀센 파마슈티카 엔.브이. | 대사 조절형 글루탐산 작동성 수용체 제2아형의 양성 알로스테릭 조절제 또는 오르토스테릭 작동제를 포함하는 조합 및 그 용도 |
| CN111269192A (zh) * | 2020-02-25 | 2020-06-12 | 成都睿智化学研究有限公司 | 一种5-羟甲基四氮唑及其衍生物的合成方法 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3509153A (en) * | 1967-03-24 | 1970-04-28 | Miles Lab | 5-phenyl (or 5-phenylalkyl)-2-(omega-(4-phenyl-1-piperazinyl)alkyl)tetrazoles |
| US4663332A (en) * | 1985-10-10 | 1987-05-05 | Hoffman-La Roche Inc. | 5-substituted N-alkylated tetrazoles |
| WO1993002677A1 (en) | 1991-08-03 | 1993-02-18 | Smithkline Beecham Plc | 5-ht4 receptor antagonists |
| DE10023430A1 (de) | 2000-05-12 | 2001-11-15 | Bayer Ag | Substituierte N-Benzoyl-N'-(tetrazolylphenyl)-harnstoffe |
| GB0115862D0 (en) | 2001-06-28 | 2001-08-22 | Smithkline Beecham Plc | Compounds |
| GB0121033D0 (en) | 2001-08-30 | 2001-10-24 | Novartis Ag | Organic compounds |
| JP4303109B2 (ja) * | 2001-10-04 | 2009-07-29 | メルク エンド カムパニー インコーポレーテッド | 代謝共役型グルタミン酸受容体−５のヘテロアリール置換テトラゾール調節剤 |
| ES2295441T3 (es) * | 2001-12-18 | 2008-04-16 | MERCK & CO., INC. | Moduladores de pirazol heteroaril sustituido de receptor 5 metabotropico de glutamato. |
| WO2003077918A1 (en) * | 2002-03-12 | 2003-09-25 | Merck & Co., Inc. | Di-aryl substituted tetrazole modulators of metabotropic glutamate receptor-5 |
| SG150539A1 (en) * | 2004-02-18 | 2009-03-30 | Astrazeneca Ab | Tetrazole compounds and their use as metabotropic glutamate receptor antagonists |
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2005
- 2005-02-17 SG SG200901214-7A patent/SG150539A1/en unknown
- 2005-02-17 CN CN201010113361A patent/CN101845023A/zh active Pending
- 2005-02-17 KR KR1020067015943A patent/KR20070027504A/ko not_active Application Discontinuation
- 2005-02-17 TW TW094104641A patent/TW200533664A/zh unknown
- 2005-02-17 US US10/588,756 patent/US20070197549A1/en not_active Abandoned
- 2005-02-17 MX MXPA06009019A patent/MXPA06009019A/es active IP Right Grant
- 2005-02-17 JP JP2006554236A patent/JP5084269B2/ja not_active Expired - Fee Related
- 2005-02-17 RU RU2006127573/04A patent/RU2372347C2/ru not_active IP Right Cessation
- 2005-02-17 EP EP05713793.7A patent/EP1716125B1/en active Active
- 2005-02-17 CA CA002556263A patent/CA2556263A1/en not_active Abandoned
- 2005-02-17 UA UAA200608678A patent/UA85576C2/ru unknown
- 2005-02-17 CN CN2005800043701A patent/CN1918137B/zh not_active Expired - Fee Related
- 2005-02-17 MY MYPI20050601A patent/MY145075A/en unknown
- 2005-02-17 BR BRPI0507498-3A patent/BRPI0507498A/pt not_active IP Right Cessation
- 2005-02-17 AU AU2005214379A patent/AU2005214379B2/en not_active Expired - Fee Related
- 2005-02-17 WO PCT/US2005/005217 patent/WO2005080356A1/en active Application Filing
- 2005-02-18 UY UY28763A patent/UY28763A1/es unknown
- 2005-02-18 US US11/060,463 patent/US7691892B2/en not_active Expired - Fee Related
- 2005-02-18 AR ARP050100615A patent/AR047812A1/es unknown
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2006
- 2006-07-25 IL IL177056A patent/IL177056A0/en unknown
- 2006-07-28 NO NO20063470A patent/NO20063470L/no not_active Application Discontinuation
- 2006-08-08 ZA ZA200606594A patent/ZA200606594B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| MY145075A (en) | 2011-12-15 |
| WO2005080356A1 (en) | 2005-09-01 |
| US20060004021A1 (en) | 2006-01-05 |
| TW200533664A (en) | 2005-10-16 |
| SG150539A1 (en) | 2009-03-30 |
| NO20063470L (no) | 2006-11-17 |
| JP2007523182A (ja) | 2007-08-16 |
| US7691892B2 (en) | 2010-04-06 |
| AU2005214379A1 (en) | 2005-09-01 |
| CN1918137B (zh) | 2012-08-01 |
| CN1918137A (zh) | 2007-02-21 |
| AR047812A1 (es) | 2006-02-22 |
| UA85576C2 (ru) | 2009-02-10 |
| BRPI0507498A (pt) | 2007-07-10 |
| US20070197549A1 (en) | 2007-08-23 |
| RU2372347C2 (ru) | 2009-11-10 |
| AU2005214379B2 (en) | 2012-03-22 |
| CN101845023A (zh) | 2010-09-29 |
| EP1716125B1 (en) | 2013-06-19 |
| IL177056A0 (en) | 2006-12-10 |
| UY28763A1 (es) | 2005-06-30 |
| JP5084269B2 (ja) | 2012-11-28 |
| MXPA06009019A (es) | 2007-03-08 |
| CA2556263A1 (en) | 2005-09-01 |
| RU2006127573A (ru) | 2008-03-27 |
| KR20070027504A (ko) | 2007-03-09 |
| EP1716125A1 (en) | 2006-11-02 |
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