JP2005506292A5 - - Google Patents
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- JP2005506292A5 JP2005506292A5 JP2002571458A JP2002571458A JP2005506292A5 JP 2005506292 A5 JP2005506292 A5 JP 2005506292A5 JP 2002571458 A JP2002571458 A JP 2002571458A JP 2002571458 A JP2002571458 A JP 2002571458A JP 2005506292 A5 JP2005506292 A5 JP 2005506292A5
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- JP
- Japan
- Prior art keywords
- lower alkyl
- group
- independently
- alkyl
- aryl
- 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.)
- Pending
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- 125000000217 alkyl group Chemical group 0.000 claims description 394
- 229910052731 fluorine Inorganic materials 0.000 claims description 207
- 229910052739 hydrogen Inorganic materials 0.000 claims description 203
- 229910052801 chlorine Inorganic materials 0.000 claims description 152
- 229910052740 iodine Inorganic materials 0.000 claims description 149
- 150000001875 compounds Chemical class 0.000 claims description 147
- -1 2,6-difluorophenyl Chemical group 0.000 claims description 144
- 229910052794 bromium Inorganic materials 0.000 claims description 144
- 125000003118 aryl group Chemical group 0.000 claims description 124
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 73
- 229910052760 oxygen Inorganic materials 0.000 claims description 68
- 229910052717 sulfur Inorganic materials 0.000 claims description 68
- 239000000203 mixture Substances 0.000 claims description 39
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 claims description 38
- 238000000034 method Methods 0.000 claims description 38
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 28
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 28
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 28
- 210000005013 brain tissue Anatomy 0.000 claims description 26
- 239000000047 product Substances 0.000 claims description 25
- 230000002829 reductive effect Effects 0.000 claims description 16
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 claims description 14
- 230000000694 effects Effects 0.000 claims description 14
- 230000001575 pathological effect Effects 0.000 claims description 14
- MQPUAVYKVIHUJP-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)ethanamine Chemical compound NCCC1=CC=C(Cl)C(Cl)=C1 MQPUAVYKVIHUJP-UHFFFAOYSA-N 0.000 claims description 13
- 229910052786 argon Inorganic materials 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 230000004770 neurodegeneration Effects 0.000 claims description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N 2-propanol Substances CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 6
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 6
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 6
- 230000000903 blocking effect Effects 0.000 claims description 6
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- AIHIHVZYAAMDPM-QMMMGPOBSA-N [(2s)-oxiran-2-yl]methyl 3-nitrobenzenesulfonate Chemical compound [O-][N+](=O)C1=CC=CC(S(=O)(=O)OC[C@H]2OC2)=C1 AIHIHVZYAAMDPM-QMMMGPOBSA-N 0.000 claims description 5
- BMURNNVCEDFRDD-AWEZNQCLSA-N n-[2-[(2s)-3-[2-(3,4-dichlorophenyl)ethylamino]-2-hydroxypropoxy]phenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC=C1OC[C@@H](O)CNCCC1=CC=C(Cl)C(Cl)=C1 BMURNNVCEDFRDD-AWEZNQCLSA-N 0.000 claims description 5
- JWEPJKHYSIKQNJ-CQSZACIVSA-N (2r)-1-[2-(3,4-dichlorophenyl)ethylamino]-3-(4-nitrophenoxy)propan-2-ol Chemical compound C([C@@H](O)COC=1C=CC(=CC=1)[N+]([O-])=O)NCCC1=CC=C(Cl)C(Cl)=C1 JWEPJKHYSIKQNJ-CQSZACIVSA-N 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 4
- 206010018338 Glioma Diseases 0.000 claims description 4
- 206010021143 Hypoxia Diseases 0.000 claims description 4
- 239000012359 Methanesulfonyl chloride Substances 0.000 claims description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 4
- WWGZWGCAWTUHCL-UHFFFAOYSA-N N-[4-[3-[2-(3,4-dichlorophenyl)ethyl-[(3-fluorophenyl)methyl]amino]-2-hydroxypropoxy]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1OCC(O)CN(CC=1C=C(F)C=CC=1)CCC1=CC=C(Cl)C(Cl)=C1 WWGZWGCAWTUHCL-UHFFFAOYSA-N 0.000 claims description 4
- 230000007954 hypoxia Effects 0.000 claims description 4
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 claims description 4
- 210000000278 spinal cord Anatomy 0.000 claims description 4
- 230000009529 traumatic brain injury Effects 0.000 claims description 4
- FTJXZACAQRDRNT-UHFFFAOYSA-N (4-fluorophenyl)-[1-(4-phenylbutyl)-4-piperidinyl]methanone Chemical compound C1=CC(F)=CC=C1C(=O)C1CCN(CCCCC=2C=CC=CC=2)CC1 FTJXZACAQRDRNT-UHFFFAOYSA-N 0.000 claims description 3
- BATPBOZTBNNDLN-UHFFFAOYSA-N (8-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)-dipropylazanium;bromide Chemical compound Br.C1=CC(O)=C2CC(N(CCC)CCC)CCC2=C1 BATPBOZTBNNDLN-UHFFFAOYSA-N 0.000 claims description 3
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 claims description 3
- RFNFFVDVGWOSNZ-UHFFFAOYSA-N 2-(1-benzofuran-2-yl)-4,5-dihydro-1h-imidazole;hydrochloride Chemical compound Cl.N1CCN=C1C1=CC2=CC=CC=C2O1 RFNFFVDVGWOSNZ-UHFFFAOYSA-N 0.000 claims description 3
- HFVRPDJQMMPXJJ-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-n-methylethanamine Chemical compound CNCCC1=CC=C(Cl)C(Cl)=C1 HFVRPDJQMMPXJJ-UHFFFAOYSA-N 0.000 claims description 3
- KCLWVAYPAFNJFB-UHFFFAOYSA-N 2-(4-chloroanilino)-4-(4-phenylpiperazin-1-yl)cyclopent-2-en-1-one Chemical compound C1=CC(Cl)=CC=C1NC1=CC(N2CCN(CC2)C=2C=CC=CC=2)CC1=O KCLWVAYPAFNJFB-UHFFFAOYSA-N 0.000 claims description 3
- IQUPABOKLQSFBK-UHFFFAOYSA-N 2-nitrophenol Chemical compound OC1=CC=CC=C1[N+]([O-])=O IQUPABOKLQSFBK-UHFFFAOYSA-N 0.000 claims description 3
- OGJGQVFWEPNYSB-UHFFFAOYSA-N 3-[[4-(4-chlorophenyl)-1-piperazinyl]methyl]-1H-pyrrolo[2,3-b]pyridine Chemical compound C1=CC(Cl)=CC=C1N1CCN(CC=2C3=CC=CN=C3NC=2)CC1 OGJGQVFWEPNYSB-UHFFFAOYSA-N 0.000 claims description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 3
- ARVWXTTUXSMAMS-UHFFFAOYSA-N 5-[(4-aminophenoxy)methyl]-2-phenyl-n-(2-phenylethyl)-1,3-oxazolidin-3-amine Chemical compound C1=CC(N)=CC=C1OCC1OC(C=2C=CC=CC=2)N(NCCC=2C=CC=CC=2)C1 ARVWXTTUXSMAMS-UHFFFAOYSA-N 0.000 claims description 3
- SBOWBHMARAESGX-UHFFFAOYSA-N 5-[(4-nitrophenoxy)methyl]-2-phenyl-n-(2-phenylethyl)-1,3-oxazolidin-3-amine Chemical compound C1=CC([N+](=O)[O-])=CC=C1OCC1OC(C=2C=CC=CC=2)N(NCCC=2C=CC=CC=2)C1 SBOWBHMARAESGX-UHFFFAOYSA-N 0.000 claims description 3
- DEYFWGXTPWNADC-UHFFFAOYSA-N 6-[2-phenylethyl(propyl)amino]-5,6,7,8-tetrahydronaphthalen-1-ol Chemical compound C1CC2=C(O)C=CC=C2CC1N(CCC)CCC1=CC=CC=C1 DEYFWGXTPWNADC-UHFFFAOYSA-N 0.000 claims description 3
- 208000032612 Glial tumor Diseases 0.000 claims description 3
- 208000002193 Pain Diseases 0.000 claims description 3
- CXYDYDCHYJXOEY-MRVPVSSYSA-N [(2r)-oxiran-2-yl]methyl 4-nitrobenzenesulfonate Chemical compound C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)OC[C@@H]1OC1 CXYDYDCHYJXOEY-MRVPVSSYSA-N 0.000 claims description 3
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 3
- IVVQFDKQRZADPE-UHFFFAOYSA-N [1-[acetyl-[2-(3,4-dichlorophenyl)ethyl]amino]-3-[4-(methanesulfonamido)phenoxy]propan-2-yl] acetate Chemical compound C=1C=C(Cl)C(Cl)=CC=1CCN(C(C)=O)CC(OC(=O)C)COC1=CC=C(NS(C)(=O)=O)C=C1 IVVQFDKQRZADPE-UHFFFAOYSA-N 0.000 claims description 3
- QAUVAHYHKLRJCQ-UHFFFAOYSA-N benoxathian Chemical compound COC1=CC=CC(OC)=C1OCCNCC1OC2=CC=CC=C2SC1 QAUVAHYHKLRJCQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- UCAIEVHKDLMIFL-UHFFFAOYSA-N clobenpropit Chemical compound C1=CC(Cl)=CC=C1CNC(=N)SCCCC1=CNC=N1 UCAIEVHKDLMIFL-UHFFFAOYSA-N 0.000 claims description 3
- 229940043279 diisopropylamine Drugs 0.000 claims description 3
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 claims description 3
- 229960003878 haloperidol Drugs 0.000 claims description 3
- 208000014674 injury Diseases 0.000 claims description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 3
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 claims description 3
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 208000005809 status epilepticus Diseases 0.000 claims description 3
- 238000001356 surgical procedure Methods 0.000 claims description 3
- 230000008733 trauma Effects 0.000 claims description 3
- SMKKEOQDQNCTGL-SSDOTTSWSA-N (2r)-2-[(2-nitrophenoxy)methyl]oxirane Chemical compound [O-][N+](=O)C1=CC=CC=C1OC[C@@H]1OC1 SMKKEOQDQNCTGL-SSDOTTSWSA-N 0.000 claims description 2
- JWEPJKHYSIKQNJ-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenyl)ethylamino]-3-(4-nitrophenoxy)propan-2-ol Chemical compound C=1C=C([N+]([O-])=O)C=CC=1OCC(O)CNCCC1=CC=C(Cl)C(Cl)=C1 JWEPJKHYSIKQNJ-UHFFFAOYSA-N 0.000 claims description 2
- MWAGUKZCDDRDCS-UHFFFAOYSA-N 1-nitro-4-(4-nitrophenoxy)benzene Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC1=CC=C([N+]([O-])=O)C=C1 MWAGUKZCDDRDCS-UHFFFAOYSA-N 0.000 claims description 2
- 125000006508 2,6-difluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C(F)=C1[H])C([H])([H])* 0.000 claims description 2
- 125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- CEZWHBSRAZAKQA-UHFFFAOYSA-N 3,4-dichloro-n-ethylpentan-1-amine Chemical compound CCNCCC(Cl)C(C)Cl CEZWHBSRAZAKQA-UHFFFAOYSA-N 0.000 claims description 2
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims description 2
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 2
- SVZCHDXRIPMIIX-UHFFFAOYSA-N C1=CC(NS(=O)(=O)C)=CC=C1OCC(O)CN(CC=1C(=C(F)C(F)=CC=1)F)CCC1=CC=C(Cl)C(Cl)=C1 Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1OCC(O)CN(CC=1C(=C(F)C(F)=CC=1)F)CCC1=CC=C(Cl)C(Cl)=C1 SVZCHDXRIPMIIX-UHFFFAOYSA-N 0.000 claims description 2
- KQGYIJNPHWXNEA-UHFFFAOYSA-N C1=CC(NS(=O)(=O)C)=CC=C1OCC(O)CN(CC=1C(=CC=CC=1F)F)CCC1=CC=C(Cl)C(Cl)=C1 Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1OCC(O)CN(CC=1C(=CC=CC=1F)F)CCC1=CC=C(Cl)C(Cl)=C1 KQGYIJNPHWXNEA-UHFFFAOYSA-N 0.000 claims description 2
- 208000000094 Chronic Pain Diseases 0.000 claims description 2
- 206010065390 Inflammatory pain Diseases 0.000 claims description 2
- REAHNDOSRQJMDW-UHFFFAOYSA-N N-[4-[3-[2-(3,4-dichlorophenyl)ethyl-[(2-fluorophenyl)methyl]amino]-2-hydroxypropoxy]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1OCC(O)CN(CC=1C(=CC=CC=1)F)CCC1=CC=C(Cl)C(Cl)=C1 REAHNDOSRQJMDW-UHFFFAOYSA-N 0.000 claims description 2
- BQBSHJUQVIWEFM-UHFFFAOYSA-N N-[4-[3-[2-(3,4-dichlorophenyl)ethyl-methylamino]-2-hydroxypropoxy]phenyl]methanesulfonamide Chemical compound C=1C=C(NS(C)(=O)=O)C=CC=1OCC(O)CN(C)CCC1=CC=C(Cl)C(Cl)=C1 BQBSHJUQVIWEFM-UHFFFAOYSA-N 0.000 claims description 2
- BYXDWEZFFJZFFM-UHFFFAOYSA-N N-[4-[[3-(3,4-dichlorophenyl)-4-ethyl-4-methyl-2-oxo-1,3-oxazolidin-5-yl]oxy]phenyl]methanesulfonamide Chemical compound ClC=1C=C(C=CC=1Cl)N1C(OC(C1(C)CC)OC1=CC=C(C=C1)NS(=O)(=O)C)=O BYXDWEZFFJZFFM-UHFFFAOYSA-N 0.000 claims description 2
- 206010038669 Respiratory arrest Diseases 0.000 claims description 2
- 201000004810 Vascular dementia Diseases 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 2
- 208000028867 ischemia Diseases 0.000 claims description 2
- IIWOUNLDWKZMQI-UHFFFAOYSA-N n'-[(2-methoxyphenyl)methyl]-n-[2-[2-[6-[(2-methoxyphenyl)methylamino]hexylamino]ethyldisulfanyl]ethyl]hexane-1,6-diamine Chemical compound COC1=CC=CC=C1CNCCCCCCNCCSSCCNCCCCCCNCC1=CC=CC=C1OC IIWOUNLDWKZMQI-UHFFFAOYSA-N 0.000 claims description 2
- BMURNNVCEDFRDD-CQSZACIVSA-N n-[2-[(2r)-3-[2-(3,4-dichlorophenyl)ethylamino]-2-hydroxypropoxy]phenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC=C1OC[C@H](O)CNCCC1=CC=C(Cl)C(Cl)=C1 BMURNNVCEDFRDD-CQSZACIVSA-N 0.000 claims description 2
- ZHSWCMJZNQYJJJ-MRVPVSSYSA-N n-[2-[[(2r)-oxiran-2-yl]methoxy]phenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC=C1OC[C@@H]1OC1 ZHSWCMJZNQYJJJ-MRVPVSSYSA-N 0.000 claims description 2
- JBMYYJHKNSMSBI-UHFFFAOYSA-N n-[3-[3-[2-(3,4-dichlorophenyl)ethylamino]-2-hydroxypropoxy]phenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC(OCC(O)CNCCC=2C=C(Cl)C(Cl)=CC=2)=C1 JBMYYJHKNSMSBI-UHFFFAOYSA-N 0.000 claims description 2
- CYNFCGYKMNBNLR-UHFFFAOYSA-N n-[4-[3-[2-(3,4-dichlorophenyl)ethyl-(2-hydroxyethyl)amino]-2-hydroxypropoxy]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1OCC(O)CN(CCO)CCC1=CC=C(Cl)C(Cl)=C1 CYNFCGYKMNBNLR-UHFFFAOYSA-N 0.000 claims description 2
- DUYHOUPHQKVIPQ-UHFFFAOYSA-N n-[4-[3-[2-(3,4-dichlorophenyl)ethyl-[(2,3,4,5,6-pentafluorophenyl)methyl]amino]-2-hydroxypropoxy]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1OCC(O)CN(CC=1C(=C(F)C(F)=C(F)C=1F)F)CCC1=CC=C(Cl)C(Cl)=C1 DUYHOUPHQKVIPQ-UHFFFAOYSA-N 0.000 claims description 2
- CGABCYQENPATFM-UHFFFAOYSA-N n-[4-[3-[2-(3,4-dichlorophenyl)ethylamino]-2-hydroxypropoxy]phenyl]benzenesulfonamide Chemical compound C=1C=C(NS(=O)(=O)C=2C=CC=CC=2)C=CC=1OCC(O)CNCCC1=CC=C(Cl)C(Cl)=C1 CGABCYQENPATFM-UHFFFAOYSA-N 0.000 claims description 2
- GEFDXUZHLNJUMR-UHFFFAOYSA-N n-[4-[3-[2-(3,4-dichlorophenyl)ethylamino]-2-hydroxypropoxy]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1OCC(O)CNCCC1=CC=C(Cl)C(Cl)=C1 GEFDXUZHLNJUMR-UHFFFAOYSA-N 0.000 claims description 2
- XFGNLELAXLYWEJ-UHFFFAOYSA-N n-[4-[4-(methanesulfonamido)phenoxy]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1OC1=CC=C(NS(C)(=O)=O)C=C1 XFGNLELAXLYWEJ-UHFFFAOYSA-N 0.000 claims description 2
- 208000004296 neuralgia Diseases 0.000 claims description 2
- 208000021722 neuropathic pain Diseases 0.000 claims description 2
- 201000011461 pre-eclampsia Diseases 0.000 claims description 2
- ODNDMTWHRYECKX-UHFFFAOYSA-N 7-(dipropylamino)-5,6,7,8-tetrahydronaphthalen-2-ol;hydrobromide Chemical compound Br.C1=C(O)C=C2CC(N(CCC)CCC)CCC2=C1 ODNDMTWHRYECKX-UHFFFAOYSA-N 0.000 claims 2
- 239000007795 chemical reaction product Substances 0.000 claims 2
- 230000003247 decreasing effect Effects 0.000 claims 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 2
- DSYNOKVSDSJMLB-UHFFFAOYSA-N 7-[2-(1h-imidazol-5-yl)ethylamino]-n-[4-(trifluoromethyl)phenyl]octanamide Chemical compound C=1NC=NC=1CCNC(C)CCCCCC(=O)NC1=CC=C(C(F)(F)F)C=C1 DSYNOKVSDSJMLB-UHFFFAOYSA-N 0.000 claims 1
- XQPLBOPPSBAOCM-UHFFFAOYSA-N N-[4-[3-[benzyl-[2-(3,4-dichlorophenyl)ethyl]amino]-2-hydroxypropoxy]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1OCC(O)CN(CC=1C=CC=CC=1)CCC1=CC=C(Cl)C(Cl)=C1 XQPLBOPPSBAOCM-UHFFFAOYSA-N 0.000 claims 1
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| WO2008055945A1 (en) | 2006-11-09 | 2008-05-15 | Probiodrug Ag | 3-hydr0xy-1,5-dihydr0-pyrr0l-2-one derivatives as inhibitors of glutaminyl cyclase for the treatment of ulcer, cancer and other diseases |
| EP2091948B1 (en) | 2006-11-30 | 2012-04-18 | Probiodrug AG | Novel inhibitors of glutaminyl cyclase |
| CN101668525A (zh) | 2007-03-01 | 2010-03-10 | 前体生物药物股份公司 | 谷氨酰胺酰环化酶抑制剂的新用途 |
| EP3085367A3 (en) * | 2007-03-20 | 2017-01-25 | Brandeis University | Compositions for the diagnosis, treatment, and prevention of amyotrophic lateral sclerosis and related |
| EP2141154A4 (en) | 2007-03-30 | 2011-06-01 | Inst Med Molecular Design Inc | OXAZOLIDINONE DERIVATIVITY WITH HEMMETIC EFFECT ON TYPE I 11-HYDROXYSTEROIDDEHYDROGENASE |
| US9656991B2 (en) | 2007-04-18 | 2017-05-23 | Probiodrug Ag | Inhibitors of glutaminyl cyclase |
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| EP2212694A4 (en) * | 2007-11-06 | 2011-10-12 | Univ Emory | METHOD OF IDENTIFYING SAFE NMDA RECEPTOR ANTAGONISTS |
| CA2722776A1 (en) * | 2008-05-09 | 2009-11-12 | Emory University | Nmda receptor antagonists for the treatment of neuropsychiatric disorders |
| ES2548913T3 (es) | 2009-09-11 | 2015-10-21 | Probiodrug Ag | Derivados heterocíclicos como inhibidores de glutaminil ciclasa |
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| WO2011107530A2 (en) | 2010-03-03 | 2011-09-09 | Probiodrug Ag | Novel inhibitors |
| CA2789440C (en) | 2010-03-10 | 2020-03-24 | Probiodrug Ag | Heterocyclic inhibitors of glutaminyl cyclase (qc, ec 2.3.2.5) |
| JP5945532B2 (ja) | 2010-04-21 | 2016-07-05 | プロビオドルグ エージー | グルタミニルシクラーゼの阻害剤としてのベンゾイミダゾール誘導体 |
| US8530670B2 (en) | 2011-03-16 | 2013-09-10 | Probiodrug Ag | Inhibitors |
| CN104490872A (zh) * | 2014-12-11 | 2015-04-08 | 温州医科大学附属第一医院 | 2-(2-苯并呋喃基)-2-咪唑啉治疗神经系统线粒体损伤疾病中的用途 |
| WO2017093354A1 (en) | 2015-11-30 | 2017-06-08 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Nmdar antagonists for the treatment of diseases associated with angiogenesis |
| EP3461819B1 (en) | 2017-09-29 | 2020-05-27 | Probiodrug AG | Inhibitors of glutaminyl cyclase |
| MX2022001186A (es) | 2019-07-31 | 2022-05-11 | Sea4Us Biotecnologia E Recursos Marinhos Lda | Compuestos analogos de nitenina y su uso en el tratamiento de dolor cronico y agudo. |
| US20220280474A1 (en) * | 2019-07-31 | 2022-09-08 | Sea4Us - Biotecnologia E Recursos Marinhos, Lda. | Kv1.3 antagonists for use in the treatment of chronic and acute pain |
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-
2002
- 2002-03-08 US US10/469,824 patent/US7375136B2/en not_active Expired - Fee Related
- 2002-03-08 JP JP2002571458A patent/JP2005506292A/ja active Pending
- 2002-03-08 EP EP02719157A patent/EP1436258A4/en not_active Withdrawn
- 2002-03-08 CA CA002440284A patent/CA2440284A1/en not_active Abandoned
- 2002-03-08 AU AU2002250256A patent/AU2002250256B2/en not_active Ceased
- 2002-03-08 WO PCT/US2002/007033 patent/WO2002072542A2/en not_active Ceased
-
2008
- 2008-05-08 US US12/151,633 patent/US20090023791A1/en not_active Abandoned
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