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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| EP1436258A4 (en) * | 2001-03-08 | 2005-03-23 | Univ Emory | PH VALVE DEPENDENT NMDA RECEPTOR ANTAGONISTS |
| CN100522946C (zh) * | 2001-12-06 | 2009-08-05 | 法布罗根股份有限公司 | 低氧诱导因子(HIF)α的稳定化 |
| JP2004123562A (ja) * | 2002-09-30 | 2004-04-22 | Japan Science & Technology Corp | 神経細胞死抑制作用を有する化合物を用いた医薬 |
| US7732162B2 (en) * | 2003-05-05 | 2010-06-08 | Probiodrug Ag | Inhibitors of glutaminyl cyclase for treating neurodegenerative diseases |
| WO2005089430A2 (en) * | 2004-03-17 | 2005-09-29 | Neurorecovery, Inc. | System and method for neurological injury detection, classification and subsequent injury amelioration |
| WO2006023957A1 (en) * | 2004-08-23 | 2006-03-02 | Emory University | Improved selection of-ph dependent compounds for in vivo therapy |
| WO2007076875A2 (en) * | 2006-01-06 | 2007-07-12 | Aarhus Universitet | Compounds acting on the serotonin transporter |
| US8278345B2 (en) | 2006-11-09 | 2012-10-02 | Probiodrug Ag | Inhibitors of glutaminyl cyclase |
| DK2091948T3 (da) | 2006-11-30 | 2012-07-23 | Probiodrug Ag | Nye inhibitorer af glutaminylcyclase |
| EA200901140A1 (ru) | 2007-03-01 | 2010-04-30 | Пробиодруг Аг | Новое применение ингибиторов глутаминилциклазы |
| WO2008116092A1 (en) | 2007-03-20 | 2008-09-25 | Brandeis University | Compositions and methods for the diagnosis, treatment, and prevention of amyotrophic lateral sclerosis and related neurological diseases |
| WO2008120655A1 (ja) | 2007-03-30 | 2008-10-09 | Institute Of Medicinal Molecular Design, Inc. | Ｉ型１１βヒドロキシステロイド脱水素酵素阻害活性を有するオキサゾリジノン誘導体 |
| DK2142514T3 (da) | 2007-04-18 | 2015-03-23 | Probiodrug Ag | Thioureaderivater som glutaminylcyclase-inhibitorer |
| JP2010532382A (ja) | 2007-06-29 | 2010-10-07 | エモリー・ユニバーシテイ | 神経保護のためのｎｍｄａ受容体拮抗薬 |
| AU2008323877A1 (en) * | 2007-11-06 | 2009-05-14 | Emory University | Methods of identifying safe NMDA receptor antagonists |
| JP2011520815A (ja) * | 2008-05-09 | 2011-07-21 | エモリー・ユニバーシテイ | 精神神経障害治療のためのｎｍｄａ受容体拮抗薬 |
| KR101755737B1 (ko) | 2009-09-11 | 2017-07-07 | 프로비오드룩 아게 | 글루타미닐 사이클라제의 억제제로서 헤테로사이클릭 유도체 |
| CA2788656A1 (en) | 2010-02-16 | 2011-08-25 | Pfizer Inc. | (r)-4-((4-((4-(tetrahydrofuran-3-yloxy)benzo[d]isoxazol-3-yloxy)methyl)piperidin-1-yl)methyl)tetrahydro-2h-pyran-4-ol, a partial agonist of 5-ht4 receptors |
| ES2586231T3 (es) | 2010-03-03 | 2016-10-13 | Probiodrug Ag | Inhibidores de glutaminil ciclasa |
| WO2011110613A1 (en) | 2010-03-10 | 2011-09-15 | Probiodrug Ag | Heterocyclic inhibitors of glutaminyl cyclase (qc, ec 2.3.2.5) |
| WO2011131748A2 (en) | 2010-04-21 | 2011-10-27 | Probiodrug Ag | Novel inhibitors |
| WO2012123563A1 (en) | 2011-03-16 | 2012-09-20 | Probiodrug Ag | Benz imidazole derivatives as inhibitors of glutaminyl cyclase |
| 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 |
| ES2843724T3 (es) | 2015-11-30 | 2021-07-20 | Inst Nat Sante Rech Med | Antagonistas de NMDAR para el tratamiento de la angiogénesis tumoral |
| PL3461819T3 (pl) | 2017-09-29 | 2020-11-30 | Probiodrug Ag | Inhibitory cyklazy glutaminylowej |
| AU2020322218A1 (en) * | 2019-07-31 | 2022-02-24 | Sea4Us - Biotecnologia E Recursos Marinhos, Lda. | Kv1.3 antagonists for use in the treatment of chronic and acute pain |
| AU2020320115A1 (en) | 2019-07-31 | 2022-02-24 | Sea4Us - Biotecnologia E Recursos Marinhos, Lda. | Nitenin analogue compounds and their use in the treatment of chronic and acute pain |
| AU2022339672B2 (en) | 2021-09-02 | 2025-10-16 | Emory University | Glun2b-subunit selective antagonists of the n-methyl-d-aspartate receptors with enhanced potency at acidic ph |
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-
2002
- 2002-03-08 EP EP02719157A patent/EP1436258A4/en not_active Withdrawn
- 2002-03-08 AU AU2002250256A patent/AU2002250256B2/en not_active Ceased
- 2002-03-08 CA CA002440284A patent/CA2440284A1/en not_active Abandoned
- 2002-03-08 US US10/469,824 patent/US7375136B2/en not_active Expired - Fee Related
- 2002-03-08 WO PCT/US2002/007033 patent/WO2002072542A2/en not_active Ceased
- 2002-03-08 JP JP2002571458A patent/JP2005506292A/ja active Pending
-
2008
- 2008-05-08 US US12/151,633 patent/US20090023791A1/en not_active Abandoned
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