NO965553L - Nye amidokinoksalindioner, deres fremstilling og anvendelse - Google Patents
Nye amidokinoksalindioner, deres fremstilling og anvendelseInfo
- Publication number
- NO965553L NO965553L NO965553A NO965553A NO965553L NO 965553 L NO965553 L NO 965553L NO 965553 A NO965553 A NO 965553A NO 965553 A NO965553 A NO 965553A NO 965553 L NO965553 L NO 965553L
- Authority
- NO
- Norway
- Prior art keywords
- mmol
- alkyl
- product
- hydrogen
- dmso
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 150000002431 hydrogen Chemical class 0.000 claims description 17
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 229910052794 bromium Inorganic materials 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 239000000460 chlorine Substances 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 210000003169 central nervous system Anatomy 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 230000004770 neurodegeneration Effects 0.000 claims description 4
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 208000007125 Neurotoxicity Syndromes Diseases 0.000 claims description 3
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 230000037396 body weight Effects 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 238000007912 intraperitoneal administration Methods 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- SMBZJSVIKJMSFP-UHFFFAOYSA-N trifluoromethyl hypofluorite Chemical compound FOC(F)(F)F SMBZJSVIKJMSFP-UHFFFAOYSA-N 0.000 claims description 2
- 208000019901 Anxiety disease Diseases 0.000 claims 1
- 208000020401 Depressive disease Diseases 0.000 claims 1
- 210000004556 brain Anatomy 0.000 claims 1
- 206010015037 epilepsy Diseases 0.000 claims 1
- 238000001990 intravenous administration Methods 0.000 claims 1
- 230000003902 lesion Effects 0.000 claims 1
- 210000000278 spinal cord Anatomy 0.000 claims 1
- 230000000472 traumatic effect Effects 0.000 claims 1
- 239000000047 product Substances 0.000 description 87
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 70
- 238000005160 1H NMR spectroscopy Methods 0.000 description 67
- 238000002844 melting Methods 0.000 description 57
- 230000008018 melting Effects 0.000 description 57
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 53
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 46
- 239000000126 substance Substances 0.000 description 42
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- 239000012528 membrane Substances 0.000 description 23
- 229960000583 acetic acid Drugs 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000012362 glacial acetic acid Substances 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 238000000034 method Methods 0.000 description 15
- 239000000203 mixture Substances 0.000 description 15
- 239000002244 precipitate Substances 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 239000000706 filtrate Substances 0.000 description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 238000010992 reflux Methods 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 239000004471 Glycine Substances 0.000 description 9
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- 235000019441 ethanol Nutrition 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 239000012071 phase Substances 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 239000005557 antagonist Substances 0.000 description 8
- 230000027455 binding Effects 0.000 description 8
- 150000002168 ethanoic acid esters Chemical class 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 7
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 7
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 7
- -1 avetonitrile Substances 0.000 description 7
- 239000012148 binding buffer Substances 0.000 description 7
- 238000005119 centrifugation Methods 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 241000551547 Dione <red algae> Species 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 239000013543 active substance Substances 0.000 description 6
- 239000007853 buffer solution Substances 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- MGRVRXRGTBOSHW-UHFFFAOYSA-N (aminomethyl)phosphonic acid Chemical compound NCP(O)(O)=O MGRVRXRGTBOSHW-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 5
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 5
- XGEGHDBEHXKFPX-UHFFFAOYSA-N N-methylthiourea Natural products CNC(N)=O XGEGHDBEHXKFPX-UHFFFAOYSA-N 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 229910052763 palladium Inorganic materials 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- ABJFBJGGLJVMAQ-UHFFFAOYSA-N 1,4-dihydroquinoxaline-2,3-dione Chemical class C1=CC=C2NC(=O)C(=O)NC2=C1 ABJFBJGGLJVMAQ-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 150000001408 amides Chemical group 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- XGEGHDBEHXKFPX-NJFSPNSNSA-N methylurea Chemical compound [14CH3]NC(N)=O XGEGHDBEHXKFPX-NJFSPNSNSA-N 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- SHVQTVUFXYPLGB-UHFFFAOYSA-N (2,5-dimethoxyoxolan-3-yl)methanamine Chemical compound COC1CC(CN)C(OC)O1 SHVQTVUFXYPLGB-UHFFFAOYSA-N 0.000 description 3
- UYCUMNRCCJNSBR-UHFFFAOYSA-N 2-ethoxy-2-oxoacetic acid;hydrochloride Chemical class Cl.CCOC(=O)C(O)=O UYCUMNRCCJNSBR-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- 102000018899 Glutamate Receptors Human genes 0.000 description 3
- 108010027915 Glutamate Receptors Proteins 0.000 description 3
- 229940122459 Glutamate antagonist Drugs 0.000 description 3
- 102000000079 Kainic Acid Receptors Human genes 0.000 description 3
- 108010069902 Kainic Acid Receptors Proteins 0.000 description 3
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical group 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 239000003194 amino acid receptor blocking agent Substances 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 238000006073 displacement reaction Methods 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- CFEPCPHKICBCJV-UHFFFAOYSA-N ethyl 4-isocyanatobenzoate Chemical compound CCOC(=O)C1=CC=C(N=C=O)C=C1 CFEPCPHKICBCJV-UHFFFAOYSA-N 0.000 description 3
- 239000003257 excitatory amino acid Substances 0.000 description 3
- 230000002461 excitatory amino acid Effects 0.000 description 3
- 229930195712 glutamate Natural products 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 3
- 239000002798 polar solvent Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- SEPKUNXLGWMPHL-UHFFFAOYSA-N quinoxaline-2,3-dione Chemical class C1=CC=CC2=NC(=O)C(=O)N=C21 SEPKUNXLGWMPHL-UHFFFAOYSA-N 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
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- 229910002027 silica gel Inorganic materials 0.000 description 3
- 235000011121 sodium hydroxide Nutrition 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- 238000000844 transformation Methods 0.000 description 3
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 2
- IQXXEPZFOOTTBA-UHFFFAOYSA-N 1-benzylpiperazine Chemical compound C=1C=CC=CC=1CN1CCNCC1 IQXXEPZFOOTTBA-UHFFFAOYSA-N 0.000 description 2
- GFNKTLQTQSALEJ-UHFFFAOYSA-N 1-isocyanato-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(N=C=O)C=C1 GFNKTLQTQSALEJ-UHFFFAOYSA-N 0.000 description 2
- GFISDBXSWQMOND-UHFFFAOYSA-N 2,5-dimethoxyoxolane Chemical compound COC1CCC(OC)O1 GFISDBXSWQMOND-UHFFFAOYSA-N 0.000 description 2
- OJVAMHKKJGICOG-UHFFFAOYSA-N 2,5-hexanedione Chemical compound CC(=O)CCC(C)=O OJVAMHKKJGICOG-UHFFFAOYSA-N 0.000 description 2
- 102000003678 AMPA Receptors Human genes 0.000 description 2
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
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- 229920002873 Polyethylenimine Polymers 0.000 description 2
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- 230000003556 anti-epileptic effect Effects 0.000 description 2
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- 239000000935 antidepressant agent Substances 0.000 description 2
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- 230000000949 anxiolytic effect Effects 0.000 description 2
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- WARCRYXKINZHGQ-UHFFFAOYSA-N benzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1 WARCRYXKINZHGQ-UHFFFAOYSA-N 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- OKTJSMMVPCPJKN-YPZZEJLDSA-N carbon-10 atom Chemical compound [10C] OKTJSMMVPCPJKN-YPZZEJLDSA-N 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000004359 castor oil Substances 0.000 description 2
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- 239000003054 catalyst Substances 0.000 description 2
- 210000004720 cerebrum Anatomy 0.000 description 2
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- 230000000694 effects Effects 0.000 description 2
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- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 239000012948 isocyanate Substances 0.000 description 2
- 150000002513 isocyanates Chemical class 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000004323 potassium nitrate Substances 0.000 description 2
- 235000010333 potassium nitrate Nutrition 0.000 description 2
- 239000012286 potassium permanganate Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006268 reductive amination reaction Methods 0.000 description 2
- 238000003345 scintillation counting Methods 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
- 239000000052 vinegar Substances 0.000 description 2
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- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 1
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- XYKIUTSFQGXHOW-UHFFFAOYSA-N propan-2-one;toluene Chemical compound CC(C)=O.CC1=CC=CC=C1 XYKIUTSFQGXHOW-UHFFFAOYSA-N 0.000 description 1
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- 239000011701 zinc Substances 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- 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
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
- C07D241/50—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to ring nitrogen atoms
- C07D241/54—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4422036 | 1994-06-22 | ||
| DE4428152A DE4428152A1 (de) | 1994-06-22 | 1994-08-09 | Neue Amido-chinoxalindione, ihrer Herstellung und Verwendung |
| PCT/EP1995/002324 WO1995035289A1 (de) | 1994-06-22 | 1995-06-16 | Neue amido-chinoxalindione, ihre herstellung und verwendung |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO965553D0 NO965553D0 (no) | 1996-12-23 |
| NO965553L true NO965553L (no) | 1997-02-20 |
Family
ID=6521350
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO965553A NO965553L (no) | 1994-06-22 | 1996-12-23 | Nye amidokinoksalindioner, deres fremstilling og anvendelse |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US5773439A (ja) |
| EP (1) | EP0873321A1 (ja) |
| JP (1) | JPH10501801A (ja) |
| CN (1) | CN1152918A (ja) |
| AU (1) | AU2883595A (ja) |
| BG (1) | BG101114A (ja) |
| BR (1) | BR9508112A (ja) |
| CA (1) | CA2193732A1 (ja) |
| DE (1) | DE4428152A1 (ja) |
| FI (1) | FI965172A (ja) |
| HR (1) | HRP950339A2 (ja) |
| HU (1) | HUT76472A (ja) |
| IL (1) | IL114161A0 (ja) |
| MX (1) | MX9700113A (ja) |
| NO (1) | NO965553L (ja) |
| PL (1) | PL317967A1 (ja) |
| SI (1) | SI9520076A (ja) |
| WO (1) | WO1995035289A1 (ja) |
| ZA (1) | ZA955128B (ja) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19521058A1 (de) * | 1995-06-09 | 1996-12-12 | Basf Ag | Verfahren zur Herstellung von Aromaten enthaltenden Polyetherpolyolen |
| DE19532050A1 (de) * | 1995-08-31 | 1997-03-06 | Basf Ag | Pyrrolyl-tetrahydrochinoxalindione, ihre Herstellung und Verwendung zur Bekämpfung von Krankheiten |
| DE19624808A1 (de) * | 1996-06-21 | 1998-01-02 | Basf Ag | Pyrrolylchinoxalindione, ihre Herstellung und Verwendung |
| EP2338492A1 (en) | 2009-12-24 | 2011-06-29 | Universidad del Pais Vasco | Methods and compositions for the treatment of alzheimer |
| EP3184507A1 (en) * | 2015-12-22 | 2017-06-28 | Nederlandse Organisatie voor toegepast- natuurwetenschappelijk onderzoek TNO | Preparation of phenyl compounds |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE66149B1 (en) * | 1986-09-16 | 1995-12-13 | Novo Nordisk As | Quinoxaline compounds and their preparation and use |
| NL8702608A (nl) * | 1987-11-02 | 1989-06-01 | Philips Nv | Electronische correctie van fotodiode stralingsgevoeligheid. |
| NO179551C (no) * | 1987-11-10 | 1996-10-30 | Novo Nordisk As | Analogifremgangsmåte for fremstilling av terapeutisk virksomme kinoxalinforbindelser |
| DK716188D0 (da) * | 1988-12-22 | 1988-12-22 | Ferrosan As | Quinoxalinforbindelser, deres fremstilling og anvendelse |
| DK715888D0 (da) * | 1988-12-22 | 1988-12-22 | Ferrosan As | Quinoxalinforbindelser, deres fremstilling og anvendelse |
| DK69790D0 (da) * | 1990-03-16 | 1990-03-16 | Novo Nordisk As | Heterocykliske forbindelser, deres fremstilling af anvendelse |
| EP0556393B1 (en) * | 1990-11-06 | 2000-07-26 | Yamanouchi Pharmaceutical Co. Ltd. | Fused pyrazine derivative |
| PT101004B (pt) * | 1991-10-26 | 1999-10-29 | Schering Ag | Derivados da quinoxalina, processo para a sua preparacao e composicoes farmaceuticas que os contem |
| DE4135871A1 (de) * | 1991-10-26 | 1993-04-29 | Schering Ag | Chinoxalinderivate, deren herstellung und verwendung in arzneimitteln |
| DE4217952A1 (de) * | 1992-05-30 | 1993-12-02 | Basf Ag | Chinoxalin-2,3(1H,4H)-dione |
| AU672617B2 (en) * | 1992-06-22 | 1996-10-10 | Regents Of The University Of California, The | Glycine receptor antagonists and the use thereof |
| DE4340045A1 (de) * | 1993-11-24 | 1995-06-01 | Basf Ag | Neue Chinoxaline und Arzneimittel daraus |
-
1994
- 1994-08-09 DE DE4428152A patent/DE4428152A1/de not_active Withdrawn
-
1995
- 1995-06-15 IL IL11416195A patent/IL114161A0/xx unknown
- 1995-06-15 HR HRP4428152.8A patent/HRP950339A2/xx not_active Application Discontinuation
- 1995-06-16 AU AU28835/95A patent/AU2883595A/en not_active Abandoned
- 1995-06-16 SI SI9520076A patent/SI9520076A/sl unknown
- 1995-06-16 EP EP95924247A patent/EP0873321A1/de not_active Withdrawn
- 1995-06-16 PL PL95317967A patent/PL317967A1/xx unknown
- 1995-06-16 HU HU9603544A patent/HUT76472A/hu unknown
- 1995-06-16 CA CA002193732A patent/CA2193732A1/en not_active Abandoned
- 1995-06-16 MX MX9700113A patent/MX9700113A/es unknown
- 1995-06-16 WO PCT/EP1995/002324 patent/WO1995035289A1/de not_active Application Discontinuation
- 1995-06-16 CN CN95194177A patent/CN1152918A/zh active Pending
- 1995-06-16 US US08/765,260 patent/US5773439A/en not_active Expired - Fee Related
- 1995-06-16 BR BR9508112A patent/BR9508112A/pt not_active Application Discontinuation
- 1995-06-16 JP JP8501651A patent/JPH10501801A/ja not_active Abandoned
- 1995-06-21 ZA ZA955128A patent/ZA955128B/xx unknown
-
1996
- 1996-12-20 FI FI965172A patent/FI965172A/fi unknown
- 1996-12-23 NO NO965553A patent/NO965553L/no unknown
-
1997
- 1997-01-06 BG BG101114A patent/BG101114A/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HRP950339A2 (en) | 1997-08-31 |
| WO1995035289A1 (de) | 1995-12-28 |
| US5773439A (en) | 1998-06-30 |
| ZA955128B (en) | 1996-12-23 |
| IL114161A0 (en) | 1995-10-31 |
| PL317967A1 (en) | 1997-05-12 |
| CA2193732A1 (en) | 1995-12-28 |
| CN1152918A (zh) | 1997-06-25 |
| MX9700113A (es) | 1997-12-31 |
| SI9520076A (en) | 1997-08-31 |
| FI965172A (fi) | 1997-02-21 |
| BR9508112A (pt) | 1997-08-12 |
| EP0873321A1 (de) | 1998-10-28 |
| FI965172A0 (fi) | 1996-12-20 |
| JPH10501801A (ja) | 1998-02-17 |
| NO965553D0 (no) | 1996-12-23 |
| HUT76472A (en) | 1997-09-29 |
| HU9603544D0 (en) | 1997-02-28 |
| DE4428152A1 (de) | 1996-01-04 |
| BG101114A (en) | 1998-04-30 |
| AU2883595A (en) | 1996-01-15 |
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