ES2240829T3 - Derivados de piridina como ligandos receptores de nmda. - Google Patents
Derivados de piridina como ligandos receptores de nmda.Info
- Publication number
- ES2240829T3 ES2240829T3 ES02787541T ES02787541T ES2240829T3 ES 2240829 T3 ES2240829 T3 ES 2240829T3 ES 02787541 T ES02787541 T ES 02787541T ES 02787541 T ES02787541 T ES 02787541T ES 2240829 T3 ES2240829 T3 ES 2240829T3
- Authority
- ES
- Spain
- Prior art keywords
- formula
- pyridin
- dihydro
- isoquinolin
- compounds
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 title claims description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 169
- 239000002253 acid Substances 0.000 claims abstract description 32
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 24
- 239000001257 hydrogen Substances 0.000 claims abstract description 24
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract description 11
- 238000002360 preparation method Methods 0.000 claims abstract description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 8
- 201000010099 disease Diseases 0.000 claims abstract description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 7
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 claims abstract description 6
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 claims abstract description 6
- 229910052736 halogen Chemical group 0.000 claims abstract description 4
- 150000002367 halogens Chemical group 0.000 claims abstract description 4
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 4
- AZKCYSCBPAJCPT-UHFFFAOYSA-N 2-(3,4-dihydro-1h-isoquinolin-2-yl)pyridin-4-amine Chemical compound NC1=CC=NC(N2CC3=CC=CC=C3CC2)=C1 AZKCYSCBPAJCPT-UHFFFAOYSA-N 0.000 claims description 17
- 239000000460 chlorine Substances 0.000 claims description 15
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 230000004770 neurodegeneration Effects 0.000 claims description 11
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 230000001154 acute effect Effects 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 7
- KZFAWZANSXHSCN-UHFFFAOYSA-N 4-(3,4-dihydro-1h-isoquinolin-2-yl)-6-methylpyridin-2-amine Chemical compound NC1=NC(C)=CC(N2CC3=CC=CC=C3CC2)=C1 KZFAWZANSXHSCN-UHFFFAOYSA-N 0.000 claims description 6
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 6
- 235000019253 formic acid Nutrition 0.000 claims description 6
- AWSWSDJGJTXACL-UHFFFAOYSA-N 2-(3,4-dihydro-1h-isoquinolin-2-yl)-5-methylpyridin-4-amine Chemical compound C1=C(N)C(C)=CN=C1N1CC2=CC=CC=C2CC1 AWSWSDJGJTXACL-UHFFFAOYSA-N 0.000 claims description 5
- YSDYZWDWFNMKFW-UHFFFAOYSA-N 2-(3,4-dihydro-1h-isoquinolin-2-yl)-6-methylpyridin-4-amine Chemical compound CC1=CC(N)=CC(N2CC3=CC=CC=C3CC2)=N1 YSDYZWDWFNMKFW-UHFFFAOYSA-N 0.000 claims description 5
- 208000002193 Pain Diseases 0.000 claims description 5
- 230000001684 chronic effect Effects 0.000 claims description 5
- 235000019256 formaldehyde Nutrition 0.000 claims description 5
- 102000005962 receptors Human genes 0.000 claims description 5
- 108020003175 receptors Proteins 0.000 claims description 5
- UPWCCXZYHXYHRR-UHFFFAOYSA-N 2-(3,4-dihydro-1h-isoquinolin-2-yl)-6-ethylpyridin-4-amine Chemical compound CCC1=CC(N)=CC(N2CC3=CC=CC=C3CC2)=N1 UPWCCXZYHXYHRR-UHFFFAOYSA-N 0.000 claims description 4
- NLCMEPOEDTUKDY-UHFFFAOYSA-N 2-(3,4-dihydro-1h-isoquinolin-2-yl)-n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC(N2CC3=CC=CC=C3CC2)=C1 NLCMEPOEDTUKDY-UHFFFAOYSA-N 0.000 claims description 4
- BHXPHZOOSSXCHR-UHFFFAOYSA-N 2-(3,4-dihydro-1h-isoquinolin-2-yl)-n-methylpyridin-4-amine Chemical compound CNC1=CC=NC(N2CC3=CC=CC=C3CC2)=C1 BHXPHZOOSSXCHR-UHFFFAOYSA-N 0.000 claims description 4
- BCHRZZNYEZLETK-UHFFFAOYSA-N [4-amino-6-(3,4-dihydro-1h-isoquinolin-2-yl)pyridin-2-yl]methanol Chemical compound NC1=CC(CO)=NC(N2CC3=CC=CC=C3CC2)=C1 BCHRZZNYEZLETK-UHFFFAOYSA-N 0.000 claims description 4
- 230000001580 bacterial effect Effects 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- CLOBRFOJYSYUJF-UHFFFAOYSA-N 2-[[2-(3,4-dihydro-1h-isoquinolin-2-yl)-5-methylpyridin-4-yl]amino]ethanol Chemical compound C1=C(NCCO)C(C)=CN=C1N1CC2=CC=CC=C2CC1 CLOBRFOJYSYUJF-UHFFFAOYSA-N 0.000 claims description 3
- HOPVAQQEEJHKLT-UHFFFAOYSA-N 2-[[4-(3,4-dihydro-1h-isoquinolin-2-yl)-6-methylpyridin-2-yl]amino]ethanol Chemical compound OCCNC1=NC(C)=CC(N2CC3=CC=CC=C3CC2)=C1 HOPVAQQEEJHKLT-UHFFFAOYSA-N 0.000 claims description 3
- SNEWDBZYBSANKX-UHFFFAOYSA-N 4-(3,4-dihydro-1h-isoquinolin-2-yl)pyridin-2-amine Chemical compound C1=NC(N)=CC(N2CC3=CC=CC=C3CC2)=C1 SNEWDBZYBSANKX-UHFFFAOYSA-N 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- 208000000094 Chronic Pain Diseases 0.000 claims description 3
- 208000023105 Huntington disease Diseases 0.000 claims description 3
- 208000018737 Parkinson disease Diseases 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- RLTYKBNDXIAOJH-UHFFFAOYSA-N 2-(4-methyl-3,4-dihydro-1h-isoquinolin-2-yl)pyridin-4-amine Chemical compound C1C2=CC=CC=C2C(C)CN1C1=CC(N)=CC=N1 RLTYKBNDXIAOJH-UHFFFAOYSA-N 0.000 claims description 2
- MLZJNABNOIALND-UHFFFAOYSA-N 2-[[2-(3,4-dihydro-1h-isoquinolin-2-yl)-6-methylpyridin-4-yl]amino]ethanol Chemical compound CC1=CC(NCCO)=CC(N2CC3=CC=CC=C3CC2)=N1 MLZJNABNOIALND-UHFFFAOYSA-N 0.000 claims description 2
- BWIGAKMTCNFCFE-UHFFFAOYSA-N 2-[[2-(3,4-dihydro-1h-isoquinolin-2-yl)pyridin-4-yl]amino]ethanol Chemical compound OCCNC1=CC=NC(N2CC3=CC=CC=C3CC2)=C1 BWIGAKMTCNFCFE-UHFFFAOYSA-N 0.000 claims description 2
- QEURGWHXVHPBGV-UHFFFAOYSA-N 2-[[4-(3,4-dihydro-1h-isoquinolin-2-yl)-6-methylpyridin-2-yl]amino]-2-oxoacetic acid Chemical compound OC(=O)C(=O)NC1=NC(C)=CC(N2CC3=CC=CC=C3CC2)=C1 QEURGWHXVHPBGV-UHFFFAOYSA-N 0.000 claims description 2
- 208000024827 Alzheimer disease Diseases 0.000 claims description 2
- 208000035143 Bacterial infection Diseases 0.000 claims description 2
- 206010008190 Cerebrovascular accident Diseases 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 2
- 208000036142 Viral infection Diseases 0.000 claims description 2
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 2
- 230000002490 cerebral effect Effects 0.000 claims description 2
- 230000006726 chronic neurodegeneration Effects 0.000 claims description 2
- 208000015181 infectious disease Diseases 0.000 claims description 2
- 208000014674 injury Diseases 0.000 claims description 2
- 230000008733 trauma Effects 0.000 claims description 2
- 230000009385 viral infection Effects 0.000 claims description 2
- 230000003612 virological effect Effects 0.000 claims description 2
- OVSKIKFHRZPJSS-UHFFFAOYSA-N 2,4-D Chemical compound OC(=O)COC1=CC=C(Cl)C=C1Cl OVSKIKFHRZPJSS-UHFFFAOYSA-N 0.000 claims 1
- 208000005298 acute pain Diseases 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 79
- 239000000203 mixture Substances 0.000 description 40
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 34
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 31
- 239000000243 solution Substances 0.000 description 31
- 238000007429 general method Methods 0.000 description 30
- 239000012458 free base Substances 0.000 description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 25
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 22
- -1 4-methyl-3,4-dihydro-1H-isoquinolin-2-yl Chemical group 0.000 description 21
- 239000012074 organic phase Substances 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- 239000000463 material Substances 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- 238000002425 crystallisation Methods 0.000 description 14
- 230000008025 crystallization Effects 0.000 description 14
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 13
- 238000004587 chromatography analysis Methods 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 239000007832 Na2SO4 Substances 0.000 description 11
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
- 229910052938 sodium sulfate Inorganic materials 0.000 description 11
- 235000011152 sodium sulphate Nutrition 0.000 description 11
- 125000001424 substituent group Chemical group 0.000 description 11
- 239000012280 lithium aluminium hydride Substances 0.000 description 10
- 238000010992 reflux Methods 0.000 description 9
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 239000002178 crystalline material Substances 0.000 description 8
- 229910052681 coesite Inorganic materials 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 229910052906 cristobalite Inorganic materials 0.000 description 7
- 239000000377 silicon dioxide Substances 0.000 description 7
- 235000012239 silicon dioxide Nutrition 0.000 description 7
- 229910052682 stishovite Inorganic materials 0.000 description 7
- 229910052905 tridymite Inorganic materials 0.000 description 7
- 229910004298 SiO 2 Inorganic materials 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- PWRLUVIRGGDEJK-UHFFFAOYSA-N 2-(3,4-dihydro-1h-isoquinolin-2-yl)-n-ethylpyridin-4-amine Chemical compound CCNC1=CC=NC(N2CC3=CC=CC=C3CC2)=C1 PWRLUVIRGGDEJK-UHFFFAOYSA-N 0.000 description 5
- TYOSQEKDQKYBLX-UHFFFAOYSA-N 2-bromo-6-ethylpyridine Chemical compound CCC1=CC=CC(Br)=N1 TYOSQEKDQKYBLX-UHFFFAOYSA-N 0.000 description 5
- 125000004494 ethyl ester group Chemical group 0.000 description 5
- 239000001530 fumaric acid Substances 0.000 description 5
- FTLLNKOZZWBNGQ-UHFFFAOYSA-N (4-amino-6-bromopyridin-2-yl)methanol Chemical compound NC1=CC(Br)=NC(CO)=C1 FTLLNKOZZWBNGQ-UHFFFAOYSA-N 0.000 description 4
- VQDXOAYANIFNNZ-UHFFFAOYSA-N 2-[[2-(3,4-dihydro-1h-isoquinolin-2-yl)-6-methylpyridin-4-yl]amino]-2-oxoacetic acid Chemical compound CC1=CC(NC(=O)C(O)=O)=CC(N2CC3=CC=CC=C3CC2)=N1 VQDXOAYANIFNNZ-UHFFFAOYSA-N 0.000 description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 4
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
- RLVQGJIROUBSPL-UHFFFAOYSA-N ethyl 2-[[4-(3,4-dihydro-1h-isoquinolin-2-yl)-6-methylpyridin-2-yl]amino]-2-oxoacetate Chemical compound CC1=NC(NC(=O)C(=O)OCC)=CC(N2CC3=CC=CC=C3CC2)=C1 RLVQGJIROUBSPL-UHFFFAOYSA-N 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
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- 239000007787 solid Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000003039 volatile agent Substances 0.000 description 4
- OBNFILXMXHDTDL-UHFFFAOYSA-N 2-(3-nitropyridin-2-yl)-3,4-dihydro-1h-isoquinoline Chemical compound [O-][N+](=O)C1=CC=CN=C1N1CC2=CC=CC=C2CC1 OBNFILXMXHDTDL-UHFFFAOYSA-N 0.000 description 3
- RONIWAGPHUJCBD-UHFFFAOYSA-N 2-[[2-(3,4-dihydro-1h-isoquinolin-2-yl)-5-methylpyridin-4-yl]amino]-2-oxoacetic acid Chemical compound C1=C(NC(=O)C(O)=O)C(C)=CN=C1N1CC2=CC=CC=C2CC1 RONIWAGPHUJCBD-UHFFFAOYSA-N 0.000 description 3
- MEHBHPUXVNCAKR-UHFFFAOYSA-N 2-[[2-(3,4-dihydro-1h-isoquinolin-2-yl)pyridin-4-yl]amino]-2-oxoacetic acid Chemical compound OC(=O)C(=O)NC1=CC=NC(N2CC3=CC=CC=C3CC2)=C1 MEHBHPUXVNCAKR-UHFFFAOYSA-N 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- YVRZVKHQLKVEGW-UHFFFAOYSA-N 2-bromo-4-nitro-5,6,7,8-tetrahydroquinoline Chemical compound C1CCCC2=C1N=C(Br)C=C2[N+](=O)[O-] YVRZVKHQLKVEGW-UHFFFAOYSA-N 0.000 description 3
- CLNAWSBQGFCTHZ-UHFFFAOYSA-N 2-bromo-5,6,7,8-tetrahydroquinolin-4-amine Chemical compound C1CCCC2=C1N=C(Br)C=C2N CLNAWSBQGFCTHZ-UHFFFAOYSA-N 0.000 description 3
- IZRVDFKQZGMQEM-UHFFFAOYSA-N 2-bromo-6-ethyl-4-nitropyridine Chemical compound CCC1=CC([N+]([O-])=O)=CC(Br)=N1 IZRVDFKQZGMQEM-UHFFFAOYSA-N 0.000 description 3
- WMGGGRSAPQTRAA-UHFFFAOYSA-N 2-bromo-6-ethylpyridin-4-amine Chemical compound CCC1=CC(N)=CC(Br)=N1 WMGGGRSAPQTRAA-UHFFFAOYSA-N 0.000 description 3
- GNTGEMWEXKBWBX-UHFFFAOYSA-N 2-bromopyridin-4-amine Chemical compound NC1=CC=NC(Br)=C1 GNTGEMWEXKBWBX-UHFFFAOYSA-N 0.000 description 3
- BYYGANJGMXVLND-UHFFFAOYSA-N 4-bromo-6-methylpyridin-2-amine Chemical compound CC1=CC(Br)=CC(N)=N1 BYYGANJGMXVLND-UHFFFAOYSA-N 0.000 description 3
- HMVNAWXRCMGFGP-UHFFFAOYSA-N 6-(3,4-dihydro-1h-isoquinolin-2-yl)pyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=CC(N2CC3=CC=CC=C3CC2)=N1 HMVNAWXRCMGFGP-UHFFFAOYSA-N 0.000 description 3
- YQBRMUXRAFVSPK-UHFFFAOYSA-N 6-bromo-4-nitropyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC(Br)=N1 YQBRMUXRAFVSPK-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
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- 239000008187 granular material Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- JHKKCDOQENTIHK-UHFFFAOYSA-N n-[2-(3,4-dihydro-1h-isoquinolin-2-yl)pyridin-4-yl]acetamide Chemical compound CC(=O)NC1=CC=NC(N2CC3=CC=CC=C3CC2)=C1 JHKKCDOQENTIHK-UHFFFAOYSA-N 0.000 description 3
- MNXKPYGCTXTCRR-UHFFFAOYSA-N n-[2-(3,4-dihydro-1h-isoquinolin-2-yl)pyridin-4-yl]benzamide Chemical compound C=1C=NC(N2CC3=CC=CC=C3CC2)=CC=1NC(=O)C1=CC=CC=C1 MNXKPYGCTXTCRR-UHFFFAOYSA-N 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 235000017550 sodium carbonate Nutrition 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- BVBRVPXLHHOEMP-UHFFFAOYSA-N 2-bromo-6-methyl-4-nitropyridine Chemical compound CC1=CC([N+]([O-])=O)=CC(Br)=N1 BVBRVPXLHHOEMP-UHFFFAOYSA-N 0.000 description 2
- BAQKUNMKVAPWGU-UHFFFAOYSA-N 4-bromopyridin-2-amine Chemical compound NC1=CC(Br)=CC=N1 BAQKUNMKVAPWGU-UHFFFAOYSA-N 0.000 description 2
- BSDGZUDFPKIYQG-UHFFFAOYSA-N 4-bromopyridine Chemical compound BrC1=CC=NC=C1 BSDGZUDFPKIYQG-UHFFFAOYSA-N 0.000 description 2
- MPZMVUQGXAOJIK-UHFFFAOYSA-N 4-bromopyridine;hydron;chloride Chemical compound Cl.BrC1=CC=NC=C1 MPZMVUQGXAOJIK-UHFFFAOYSA-N 0.000 description 2
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- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005550 wet granulation Methods 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01126467 | 2001-11-09 | ||
| EP01126467 | 2001-11-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2240829T3 true ES2240829T3 (es) | 2005-10-16 |
Family
ID=8179179
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES02787541T Expired - Lifetime ES2240829T3 (es) | 2001-11-09 | 2002-11-02 | Derivados de piridina como ligandos receptores de nmda. |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US6831087B2 (enExample) |
| EP (1) | EP1448547B1 (enExample) |
| JP (1) | JP4188837B2 (enExample) |
| KR (1) | KR100589995B1 (enExample) |
| CN (1) | CN100516061C (enExample) |
| AR (1) | AR037221A1 (enExample) |
| AT (1) | ATE293619T1 (enExample) |
| AU (1) | AU2002351816B8 (enExample) |
| BR (1) | BR0213977A (enExample) |
| CA (1) | CA2467973C (enExample) |
| DE (1) | DE60203820T2 (enExample) |
| ES (1) | ES2240829T3 (enExample) |
| MX (1) | MXPA04004308A (enExample) |
| PL (1) | PL369544A1 (enExample) |
| RU (1) | RU2303037C2 (enExample) |
| WO (1) | WO2003040128A1 (enExample) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007008816A (ja) * | 2003-10-15 | 2007-01-18 | Ube Ind Ltd | 新規イソキノリン誘導体 |
| US20050089559A1 (en) * | 2003-10-23 | 2005-04-28 | Istvan Szelenyi | Combinations of potassium channel openers and sodium channel inhibitors or sodium channel-influencing active compounds for treating pains |
| RU2320654C1 (ru) * | 2006-05-24 | 2008-03-27 | Государственное образовательное учреждение высшего профессионального образования "Пермская государственная фармацевтическая академия Федерального агентства по здравоохранению и социальному развитию" (ГОУ ВПО ПГФА Росздрава) | 2,2-ДИМЕТИЛ-4-(4,6-ДИМЕТИЛ-2-ПИРИДОН-3-ИЛ)-1,2-ДИГИДРО-БЕНЗО[f]ИЗОХИНОЛИНА ГИДРОХЛОРИД, ПРОЯВЛЯЮЩИЙ ПРЯМОЕ АНТИКОАГУЛЯНТНОЕ ДЕЙСТВИЕ |
| US8722929B2 (en) * | 2006-10-10 | 2014-05-13 | Valeant Pharmaceuticals International | N-[2-amino-4-(phenylmethoxy)phenyl] amides and related compounds as potassium channel modulators |
| US8367684B2 (en) * | 2007-06-13 | 2013-02-05 | Valeant Pharmaceuticals International | Derivatives of 4-(N-azacycloalkyl) anilides as potassium channel modulators |
| US8563566B2 (en) * | 2007-08-01 | 2013-10-22 | Valeant Pharmaceuticals International | Naphthyridine derivatives as potassium channel modulators |
| US7786146B2 (en) * | 2007-08-13 | 2010-08-31 | Valeant Pharmaceuticals International | Derivatives of 5-amino-4,6-disubstituted indole and 5-amino-4,6-disubstituted indoline as potassium channel modulators |
| EP2065381A1 (de) | 2007-10-18 | 2009-06-03 | Boehringer Ingelheim Pharma GmbH & Co. KG | CGRP Antagonisten |
| NZ585347A (en) | 2007-10-18 | 2011-09-30 | Boehringer Ingelheim Int | Cgrp antagonists |
| EP2062889A1 (de) * | 2007-11-22 | 2009-05-27 | Boehringer Ingelheim Pharma GmbH & Co. KG | Verbindungen |
| CA2705405A1 (en) | 2007-11-22 | 2009-05-28 | Boehringer Ingelheim International Gmbh | New compounds |
| CA2705599A1 (en) * | 2007-11-22 | 2009-05-28 | Boehringer Ingelheim International Gmbh | New compounds |
| EA014100B1 (ru) * | 2008-02-21 | 2010-08-30 | Общество С Ограниченной Ответственностью "Валексфарм" | Производные 2,4-диаминопиридина, фармацевтическая композиция, лекарственное средство на их основе для лечения или предупреждения заболеваний и нарушений, вызванных гиперактивацией nmda-рецепторов и/или в качестве стимуляторов когнитивных функций и способ лечения |
| RU2438672C1 (ru) * | 2010-04-30 | 2012-01-10 | Общество с ограниченной ответственностью "Клевер Фарм" | Агент, проявляющий свойства активатора когнитивных функций (варианты) |
| WO2025124571A1 (zh) * | 2023-12-14 | 2025-06-19 | 斯莱普泰(上海)生物医药科技有限公司 | Nmda受体拮抗剂及其用途 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA9610738B (en) | 1995-12-22 | 1997-06-24 | Warner Lambert Co | Subtype selective nmda receptor ligands and the use thereof |
| ATE524440T1 (de) * | 1998-05-25 | 2011-09-15 | Abbott Gmbh & Co Kg | Heterocyclische substituierte amide, deren herstellung und anwendung |
| DK1088818T3 (da) | 1999-10-01 | 2005-03-14 | Hoffmann La Roche | Quinolin-4-yl-derivater |
| US6440995B1 (en) * | 1999-10-01 | 2002-08-27 | Hoffman-La Roche Inc. | Quinolin-4-yl derivatives |
| US6339093B1 (en) * | 1999-10-08 | 2002-01-15 | Hoffmann-La Roche Inc. | Isoquinoline derivatives |
-
2002
- 2002-10-29 US US10/282,365 patent/US6831087B2/en not_active Expired - Fee Related
- 2002-11-02 ES ES02787541T patent/ES2240829T3/es not_active Expired - Lifetime
- 2002-11-02 WO PCT/EP2002/012240 patent/WO2003040128A1/en not_active Ceased
- 2002-11-02 PL PL02369544A patent/PL369544A1/xx unknown
- 2002-11-02 KR KR1020047007031A patent/KR100589995B1/ko not_active Expired - Fee Related
- 2002-11-02 CA CA002467973A patent/CA2467973C/en not_active Expired - Fee Related
- 2002-11-02 BR BR0213977-4A patent/BR0213977A/pt not_active IP Right Cessation
- 2002-11-02 AU AU2002351816A patent/AU2002351816B8/en not_active Ceased
- 2002-11-02 JP JP2003542174A patent/JP4188837B2/ja not_active Expired - Fee Related
- 2002-11-02 MX MXPA04004308A patent/MXPA04004308A/es active IP Right Grant
- 2002-11-02 RU RU2004117595/04A patent/RU2303037C2/ru not_active IP Right Cessation
- 2002-11-02 CN CNB028222512A patent/CN100516061C/zh not_active Expired - Fee Related
- 2002-11-02 AT AT02787541T patent/ATE293619T1/de not_active IP Right Cessation
- 2002-11-02 EP EP02787541A patent/EP1448547B1/en not_active Expired - Lifetime
- 2002-11-02 DE DE60203820T patent/DE60203820T2/de not_active Expired - Lifetime
- 2002-11-06 AR ARP020104227A patent/AR037221A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DE60203820D1 (de) | 2005-05-25 |
| JP4188837B2 (ja) | 2008-12-03 |
| KR20050042252A (ko) | 2005-05-06 |
| CN100516061C (zh) | 2009-07-22 |
| EP1448547B1 (en) | 2005-04-20 |
| US6831087B2 (en) | 2004-12-14 |
| CA2467973C (en) | 2009-09-01 |
| RU2303037C2 (ru) | 2007-07-20 |
| MXPA04004308A (es) | 2004-08-11 |
| US20030119870A1 (en) | 2003-06-26 |
| RU2004117595A (ru) | 2006-01-10 |
| BR0213977A (pt) | 2004-08-31 |
| AU2002351816B2 (en) | 2008-03-06 |
| KR100589995B1 (ko) | 2006-06-19 |
| ATE293619T1 (de) | 2005-05-15 |
| CN1585762A (zh) | 2005-02-23 |
| AR037221A1 (es) | 2004-10-27 |
| JP2005513004A (ja) | 2005-05-12 |
| EP1448547A1 (en) | 2004-08-25 |
| PL369544A1 (en) | 2005-05-02 |
| DE60203820T2 (de) | 2006-02-23 |
| AU2002351816B8 (en) | 2008-04-03 |
| WO2003040128A1 (en) | 2003-05-15 |
| CA2467973A1 (en) | 2003-05-15 |
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