NO315272B1 - 6,7-asymmetriske disubstituerte kinoksalinkarboksylsyrederivater, intermediater for deres fremstilling og antagonist mot eksitatoriskeaminosyrereseptorerinneholdende forbindelsene - Google Patents
6,7-asymmetriske disubstituerte kinoksalinkarboksylsyrederivater, intermediater for deres fremstilling og antagonist mot eksitatoriskeaminosyrereseptorerinneholdende forbindelsene Download PDFInfo
- Publication number
- NO315272B1 NO315272B1 NO20001046A NO20001046A NO315272B1 NO 315272 B1 NO315272 B1 NO 315272B1 NO 20001046 A NO20001046 A NO 20001046A NO 20001046 A NO20001046 A NO 20001046A NO 315272 B1 NO315272 B1 NO 315272B1
- Authority
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- Norway
- Prior art keywords
- group
- denotes
- general formula
- alkyl
- phenyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 499
- UPUZGXILYFKSGE-UHFFFAOYSA-N quinoxaline-2-carboxylic acid Chemical class C1=CC=CC2=NC(C(=O)O)=CN=C21 UPUZGXILYFKSGE-UHFFFAOYSA-N 0.000 title claims abstract description 36
- 102000018899 Glutamate Receptors Human genes 0.000 title claims abstract description 13
- 108010027915 Glutamate Receptors Proteins 0.000 title claims abstract description 13
- 239000005557 antagonist Substances 0.000 title claims description 9
- 239000000543 intermediate Substances 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title description 2
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 93
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 83
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 71
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 68
- 125000001424 substituent group Chemical group 0.000 claims abstract description 63
- 125000005843 halogen group Chemical group 0.000 claims abstract description 43
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 42
- 125000003118 aryl group Chemical group 0.000 claims abstract description 41
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 38
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 37
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims abstract description 29
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 29
- 239000001301 oxygen Substances 0.000 claims abstract description 29
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 28
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 27
- 150000003839 salts Chemical class 0.000 claims abstract description 26
- 102000003678 AMPA Receptors Human genes 0.000 claims abstract description 22
- 108090000078 AMPA Receptors Proteins 0.000 claims abstract description 22
- 230000008485 antagonism Effects 0.000 claims abstract description 21
- 125000003277 amino group Chemical group 0.000 claims abstract description 19
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 17
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 15
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 4
- 239000004615 ingredient Substances 0.000 claims abstract 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 1020
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 78
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 57
- 229910052736 halogen Inorganic materials 0.000 claims description 53
- 150000002367 halogens Chemical class 0.000 claims description 53
- -1 (Ci-C6 )-Alkoxy Inorganic materials 0.000 claims description 49
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 45
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 45
- 239000001257 hydrogen Substances 0.000 claims description 37
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 33
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 31
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 24
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 22
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 22
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 22
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 21
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 19
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 19
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- 229920006395 saturated elastomer Polymers 0.000 claims description 15
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 14
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 13
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 13
- 125000003172 aldehyde group Chemical group 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 12
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 12
- 125000001041 indolyl group Chemical group 0.000 claims description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 12
- 125000005493 quinolyl group Chemical group 0.000 claims description 12
- 125000001544 thienyl group Chemical group 0.000 claims description 12
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims description 11
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 11
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims description 9
- 125000005862 (C1-C6)alkanoyl group Chemical group 0.000 claims description 8
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- OCZBQXHPIJUPKN-UHFFFAOYSA-N 7-[3-[[(4-carboxyphenyl)carbamoylamino]methyl]pyrrol-1-yl]-3-oxo-6-(trifluoromethyl)-4h-quinoxaline-2-carboxylic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC(=O)NCC1=CN(C=2C(=CC=3NC(=O)C(C(O)=O)=NC=3C=2)C(F)(F)F)C=C1 OCZBQXHPIJUPKN-UHFFFAOYSA-N 0.000 claims description 3
- AEFZZVQZPBFFPN-UHFFFAOYSA-N 7-[4-[(4-carboxyphenyl)carbamoyloxymethyl]imidazol-1-yl]-3-oxo-6-(trifluoromethyl)-4h-quinoxaline-2-carboxylic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC(=O)OCC1=CN(C=2C(=CC=3NC(=O)C(C(O)=O)=NC=3C=2)C(F)(F)F)C=N1 AEFZZVQZPBFFPN-UHFFFAOYSA-N 0.000 claims description 3
- KEPYXBRRBZFMQU-UHFFFAOYSA-N 7-[4-[[(4-carboxyphenyl)carbamoylamino]methyl]imidazol-1-yl]-3-oxo-6-(trifluoromethyl)-4h-quinoxaline-2-carboxylic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC(=O)NCC1=CN(C=2C(=CC=3NC(=O)C(C(O)=O)=NC=3C=2)C(F)(F)F)C=N1 KEPYXBRRBZFMQU-UHFFFAOYSA-N 0.000 claims description 3
- FNKPZJWJVGFKNS-UHFFFAOYSA-N 7-[5-[(4-carboxyphenyl)carbamoyloxymethyl]-1h-imidazol-2-yl]-6-nitro-3-oxo-4h-quinoxaline-2-carboxylic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC(=O)OCC1=CN=C(C=2C(=CC=3NC(=O)C(C(O)=O)=NC=3C=2)[N+]([O-])=O)N1 FNKPZJWJVGFKNS-UHFFFAOYSA-N 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims 19
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 2
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 2
- 238000003786 synthesis reaction Methods 0.000 claims 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 57
- 125000003545 alkoxy group Chemical group 0.000 abstract description 3
- 125000004450 alkenylene group Chemical group 0.000 abstract 1
- 125000004419 alkynylene group Chemical group 0.000 abstract 1
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 1
- 229910001868 water Inorganic materials 0.000 description 233
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 206
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 192
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 182
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 171
- 239000000203 mixture Substances 0.000 description 165
- 239000000243 solution Substances 0.000 description 162
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 160
- 239000002904 solvent Substances 0.000 description 158
- 239000000843 powder Substances 0.000 description 151
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 144
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 117
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 114
- 239000011541 reaction mixture Substances 0.000 description 108
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 100
- 235000011941 Tilia x europaea Nutrition 0.000 description 100
- 239000004571 lime Substances 0.000 description 100
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 99
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
- 238000001914 filtration Methods 0.000 description 89
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 84
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 81
- 238000005481 NMR spectroscopy Methods 0.000 description 79
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 70
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 70
- 239000002244 precipitate Substances 0.000 description 70
- 238000005160 1H NMR spectroscopy Methods 0.000 description 62
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 54
- 238000001816 cooling Methods 0.000 description 54
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
- 238000010898 silica gel chromatography Methods 0.000 description 49
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 38
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 36
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 36
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 35
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 30
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 27
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 24
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 21
- 239000002198 insoluble material Substances 0.000 description 20
- 239000002585 base Substances 0.000 description 19
- 239000013078 crystal Substances 0.000 description 19
- 238000001035 drying Methods 0.000 description 19
- 229910000027 potassium carbonate Inorganic materials 0.000 description 19
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 18
- 150000007530 organic bases Chemical class 0.000 description 17
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 16
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 16
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 15
- 229910000029 sodium carbonate Inorganic materials 0.000 description 15
- 239000012312 sodium hydride Substances 0.000 description 15
- 229910000104 sodium hydride Inorganic materials 0.000 description 15
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 14
- 239000000706 filtrate Substances 0.000 description 13
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- 239000003054 catalyst Substances 0.000 description 12
- 150000002148 esters Chemical class 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 238000004896 high resolution mass spectrometry Methods 0.000 description 11
- 239000005457 ice water Substances 0.000 description 11
- 239000012074 organic phase Substances 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- 239000003463 adsorbent Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 9
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 9
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 239000012267 brine Substances 0.000 description 9
- 150000007529 inorganic bases Chemical class 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- 230000003068 static effect Effects 0.000 description 9
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- FHHZOYXKOICLGH-UHFFFAOYSA-N dichloromethane;ethanol Chemical compound CCO.ClCCl FHHZOYXKOICLGH-UHFFFAOYSA-N 0.000 description 8
- CFEPCPHKICBCJV-UHFFFAOYSA-N ethyl 4-isocyanatobenzoate Chemical compound CCOC(=O)C1=CC=C(N=C=O)C=C1 CFEPCPHKICBCJV-UHFFFAOYSA-N 0.000 description 8
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 8
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 8
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 8
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 7
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 7
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 7
- 230000002490 cerebral effect Effects 0.000 description 7
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 7
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 7
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical compound NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 6
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 6
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 6
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- 238000007605 air drying Methods 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 6
- DBKKFIIYQGGHJO-UHFFFAOYSA-N diethyl 2-oxopropanedioate Chemical compound CCOC(=O)C(=O)C(=O)OCC DBKKFIIYQGGHJO-UHFFFAOYSA-N 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 235000013922 glutamic acid Nutrition 0.000 description 6
- 239000004220 glutamic acid Substances 0.000 description 6
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 6
- 210000002569 neuron Anatomy 0.000 description 6
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 6
- 239000003513 alkali Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- JKDMLDODMVQTQL-UHFFFAOYSA-N ethyl 3-ethoxy-7-fluoro-6-nitroquinoxaline-2-carboxylate Chemical compound FC1=C([N+]([O-])=O)C=C2N=C(OCC)C(C(=O)OCC)=NC2=C1 JKDMLDODMVQTQL-UHFFFAOYSA-N 0.000 description 5
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 5
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 5
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 5
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 5
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- JVHCLPQTUHQCMC-UHFFFAOYSA-N ethyl 3-ethoxy-7-[5-(hydroxymethyl)-1h-imidazol-2-yl]-6-nitroquinoxaline-2-carboxylate Chemical compound [O-][N+](=O)C=1C=C2N=C(OCC)C(C(=O)OCC)=NC2=CC=1C1=NC=C(CO)N1 JVHCLPQTUHQCMC-UHFFFAOYSA-N 0.000 description 1
- IXCKPFRLNGKENS-UHFFFAOYSA-N ethyl 3-ethoxy-7-[5-[(2-ethoxycarbonylphenyl)carbamoyloxymethyl]-1h-imidazol-2-yl]-6-nitroquinoxaline-2-carboxylate Chemical compound CCOC(=O)C1=CC=CC=C1NC(=O)OCC1=CN=C(C=2C(=CC3=NC(OCC)=C(C(=O)OCC)N=C3C=2)[N+]([O-])=O)N1 IXCKPFRLNGKENS-UHFFFAOYSA-N 0.000 description 1
- LVUFASMERAWDRB-UHFFFAOYSA-N ethyl 3-ethoxy-7-[5-[(4-ethoxycarbonyl-2-fluorophenyl)carbamoyloxymethyl]-1h-imidazol-2-yl]-6-nitroquinoxaline-2-carboxylate Chemical compound FC1=CC(C(=O)OCC)=CC=C1NC(=O)OCC1=CN=C(C=2C(=CC3=NC(OCC)=C(C(=O)OCC)N=C3C=2)[N+]([O-])=O)N1 LVUFASMERAWDRB-UHFFFAOYSA-N 0.000 description 1
- ZXHQSSAJUVDGPV-UHFFFAOYSA-N ethyl 3-ethoxy-7-[5-[(4-ethoxycarbonylphenyl)carbamoyloxymethyl]-1h-imidazol-2-yl]-6-nitroquinoxaline-2-carboxylate Chemical compound C1=CC(C(=O)OCC)=CC=C1NC(=O)OCC1=CN=C(C=2C(=CC3=NC(OCC)=C(C(=O)OCC)N=C3C=2)[N+]([O-])=O)N1 ZXHQSSAJUVDGPV-UHFFFAOYSA-N 0.000 description 1
- PJKVHWHQXKBJSW-UHFFFAOYSA-N ethyl 3-ethoxy-7-[5-[(5-ethoxycarbonyl-2-fluorophenyl)carbamoyloxymethyl]-1h-imidazol-2-yl]-6-nitroquinoxaline-2-carboxylate Chemical compound CCOC(=O)C1=CC=C(F)C(NC(=O)OCC=2NC(=NC=2)C=2C(=CC3=NC(OCC)=C(C(=O)OCC)N=C3C=2)[N+]([O-])=O)=C1 PJKVHWHQXKBJSW-UHFFFAOYSA-N 0.000 description 1
- TUADRUMWRMGMOO-UHFFFAOYSA-N ethyl 3-ethoxy-7-fluoro-6-methylsulfonylquinoxaline-2-carboxylate Chemical compound FC1=C(S(C)(=O)=O)C=C2N=C(OCC)C(C(=O)OCC)=NC2=C1 TUADRUMWRMGMOO-UHFFFAOYSA-N 0.000 description 1
- PUJOHYXQQWWACU-UHFFFAOYSA-N ethyl 3-ethoxy-7-methyl-6-nitroquinoxaline-2-carboxylate Chemical compound CC1=C([N+]([O-])=O)C=C2N=C(OCC)C(C(=O)OCC)=NC2=C1 PUJOHYXQQWWACU-UHFFFAOYSA-N 0.000 description 1
- RXDDBPMKGAJCNK-UHFFFAOYSA-N ethyl 3-ethoxy-7-nitro-6-(trifluoromethyl)quinoxaline-2-carboxylate Chemical compound [O-][N+](=O)C1=C(C(F)(F)F)C=C2N=C(OCC)C(C(=O)OCC)=NC2=C1 RXDDBPMKGAJCNK-UHFFFAOYSA-N 0.000 description 1
- ISZXPQJUPZAYSU-UHFFFAOYSA-N ethyl 3-methoxy-7-methyl-6-nitroquinoxaline-2-carboxylate Chemical compound CC1=C([N+]([O-])=O)C=C2N=C(OC)C(C(=O)OCC)=NC2=C1 ISZXPQJUPZAYSU-UHFFFAOYSA-N 0.000 description 1
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- MVBLGZDHTWMFTK-UHFFFAOYSA-N ethyl 3-oxo-7-pyrrol-1-yl-6-(trifluoromethyl)-4h-quinoxaline-2-carboxylate Chemical compound FC(F)(F)C=1C=C2NC(=O)C(C(=O)OCC)=NC2=CC=1N1C=CC=C1 MVBLGZDHTWMFTK-UHFFFAOYSA-N 0.000 description 1
- WGGYSTXWAAPNMA-UHFFFAOYSA-N ethyl 4-[[1-[2,3-diamino-6-(trifluoromethyl)phenyl]imidazol-4-yl]methylcarbamoylamino]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1NC(=O)NCC1=CN(C=2C(=CC=C(N)C=2N)C(F)(F)F)C=N1 WGGYSTXWAAPNMA-UHFFFAOYSA-N 0.000 description 1
- FXGFRZKFUPJCCY-UHFFFAOYSA-N ethyl 6-amino-7-fluoro-3-methoxyquinoxaline-2-carboxylate Chemical compound FC1=C(N)C=C2N=C(OC)C(C(=O)OCC)=NC2=C1 FXGFRZKFUPJCCY-UHFFFAOYSA-N 0.000 description 1
- AZFHCCLEHOBBFQ-UHFFFAOYSA-N ethyl 7-(1h-imidazol-2-yl)-3-oxo-6-(trifluoromethyl)-4h-quinoxaline-2-carboxylate Chemical compound FC(F)(F)C=1C=C2NC(=O)C(C(=O)OCC)=NC2=CC=1C1=NC=CN1 AZFHCCLEHOBBFQ-UHFFFAOYSA-N 0.000 description 1
- OANPTYJKNIVQNF-UHFFFAOYSA-N ethyl 7-(3-formylpyrrol-1-yl)-3-oxo-6-(trifluoromethyl)-2,4-dihydro-1h-quinoxaline-2-carboxylate Chemical compound FC(F)(F)C=1C=C2NC(=O)C(C(=O)OCC)NC2=CC=1N1C=CC(C=O)=C1 OANPTYJKNIVQNF-UHFFFAOYSA-N 0.000 description 1
- IXYLTAUOOCDYBY-UHFFFAOYSA-N ethyl 7-[(dimethylamino)methyl]-3-methoxy-6-nitroquinoxaline-2-carboxylate Chemical compound CN(C)CC1=C([N+]([O-])=O)C=C2N=C(OC)C(C(=O)OCC)=NC2=C1 IXYLTAUOOCDYBY-UHFFFAOYSA-N 0.000 description 1
- NZDKVQHFSLOGOP-UHFFFAOYSA-N ethyl 7-[3-(aminomethyl)pyrrol-1-yl]-3-oxo-6-(trifluoromethyl)-2,4-dihydro-1h-quinoxaline-2-carboxylate;hydrochloride Chemical compound Cl.FC(F)(F)C=1C=C2NC(=O)C(C(=O)OCC)NC2=CC=1N1C=CC(CN)=C1 NZDKVQHFSLOGOP-UHFFFAOYSA-N 0.000 description 1
- AZKSFLIWMQIEFL-UHFFFAOYSA-N ethyl 7-[3-[[(3-fluorophenyl)carbamoylamino]methyl]pyrrol-1-yl]-3-oxo-6-(trifluoromethyl)-4h-quinoxaline-2-carboxylate Chemical compound FC(F)(F)C=1C=C2NC(=O)C(C(=O)OCC)=NC2=CC=1N(C=1)C=CC=1CNC(=O)NC1=CC=CC(F)=C1 AZKSFLIWMQIEFL-UHFFFAOYSA-N 0.000 description 1
- MWRWBHQTGQTXRB-UHFFFAOYSA-N ethyl 7-[3-[[(4-bromophenyl)carbamoylamino]methyl]pyrrol-1-yl]-3-oxo-6-(trifluoromethyl)-4h-quinoxaline-2-carboxylate Chemical compound FC(F)(F)C=1C=C2NC(=O)C(C(=O)OCC)=NC2=CC=1N(C=1)C=CC=1CNC(=O)NC1=CC=C(Br)C=C1 MWRWBHQTGQTXRB-UHFFFAOYSA-N 0.000 description 1
- YUWULLQMAQOVIM-UHFFFAOYSA-N ethyl 7-[3-[[(4-ethoxycarbonyl-2-fluorophenyl)carbamoylamino]methyl]pyrrol-1-yl]-3-oxo-6-(trifluoromethyl)-2,4-dihydro-1h-quinoxaline-2-carboxylate Chemical compound FC(F)(F)C=1C=C2NC(=O)C(C(=O)OCC)NC2=CC=1N(C=1)C=CC=1CNC(=O)NC1=CC=C(C(=O)OCC)C=C1F YUWULLQMAQOVIM-UHFFFAOYSA-N 0.000 description 1
- IDJYHLJOIUGSKY-UHFFFAOYSA-N ethyl 7-[3-[[(4-ethoxycarbonyl-2-fluorophenyl)carbamoylamino]methyl]pyrrol-1-yl]-3-oxo-6-(trifluoromethyl)-4h-quinoxaline-2-carboxylate Chemical compound FC1=CC(C(=O)OCC)=CC=C1NC(=O)NCC1=CN(C=2C(=CC=3NC(=O)C(C(=O)OCC)=NC=3C=2)C(F)(F)F)C=C1 IDJYHLJOIUGSKY-UHFFFAOYSA-N 0.000 description 1
- QUWDUIAOFQGSGJ-UHFFFAOYSA-N ethyl 7-[3-[[(4-ethoxycarbonylphenyl)carbamoylamino]methyl]pyrrol-1-yl]-3-oxo-6-(trifluoromethyl)-4h-quinoxaline-2-carboxylate Chemical compound C1=CC(C(=O)OCC)=CC=C1NC(=O)NCC1=CN(C=2C(=CC=3NC(=O)C(C(=O)OCC)=NC=3C=2)C(F)(F)F)C=C1 QUWDUIAOFQGSGJ-UHFFFAOYSA-N 0.000 description 1
- MXNCDWYBLXXQKM-UHFFFAOYSA-N ethyl 7-[3-[[(4-fluorophenyl)carbamoylamino]methyl]pyrrol-1-yl]-3-oxo-6-(trifluoromethyl)-4h-quinoxaline-2-carboxylate Chemical compound FC(F)(F)C=1C=C2NC(=O)C(C(=O)OCC)=NC2=CC=1N(C=1)C=CC=1CNC(=O)NC1=CC=C(F)C=C1 MXNCDWYBLXXQKM-UHFFFAOYSA-N 0.000 description 1
- CAEYUHOLGCVUIU-UHFFFAOYSA-N ethyl 7-[4-[[(4-ethoxycarbonylphenyl)carbamoylamino]methyl]imidazol-1-yl]-3-oxo-6-(trifluoromethyl)-4h-quinoxaline-2-carboxylate Chemical compound C1=CC(C(=O)OCC)=CC=C1NC(=O)NCC1=CN(C=2C(=CC=3NC(=O)C(C(=O)OCC)=NC=3C=2)C(F)(F)F)C=N1 CAEYUHOLGCVUIU-UHFFFAOYSA-N 0.000 description 1
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- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- YNVOMSDITJMNET-UHFFFAOYSA-N thiophene-3-carboxylic acid Chemical compound OC(=O)C=1C=CSC=1 YNVOMSDITJMNET-UHFFFAOYSA-N 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/12—Oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/335—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D233/61—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms not forming part of a nitro radical, attached to ring nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/70—One oxygen atom
-
- 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
- C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
- C07D241/40—Benzopyrazines
- C07D241/44—Benzopyrazines with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D403/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Coloring (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP25131397 | 1997-09-01 | ||
JP19010998 | 1998-07-06 | ||
JP19010898 | 1998-07-06 | ||
PCT/JP1998/003832 WO1999011632A1 (fr) | 1997-09-01 | 1998-08-28 | Derives d'acide quinoxalinecarboxylique disubstitues en position 6,7-asymetrique, sels d'addition de ces derives, et procedes de preparation de ces derives et de ces sels |
Publications (3)
Publication Number | Publication Date |
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NO20001046D0 NO20001046D0 (no) | 2000-03-01 |
NO20001046L NO20001046L (no) | 2000-05-02 |
NO315272B1 true NO315272B1 (no) | 2003-08-11 |
Family
ID=27326284
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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NO20001046A NO315272B1 (no) | 1997-09-01 | 2000-03-01 | 6,7-asymmetriske disubstituerte kinoksalinkarboksylsyrederivater, intermediater for deres fremstilling og antagonist mot eksitatoriskeaminosyrereseptorerinneholdende forbindelsene |
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US (1) | US6348461B1 (de) |
EP (1) | EP1020453B1 (de) |
KR (1) | KR100588247B1 (de) |
CN (1) | CN1161344C (de) |
AT (1) | ATE267176T1 (de) |
AU (1) | AU744540B2 (de) |
BR (1) | BR9811739A (de) |
CA (1) | CA2302161A1 (de) |
DE (1) | DE69824025T2 (de) |
HU (1) | HUP0002853A3 (de) |
NO (1) | NO315272B1 (de) |
NZ (1) | NZ503076A (de) |
WO (1) | WO1999011632A1 (de) |
Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2000309585A (ja) * | 1999-02-26 | 2000-11-07 | Kyorin Pharmaceut Co Ltd | 6−置換ヘテロキノリンカルボン酸誘導体とその付加塩及びそれらの製造方法 |
JP2000309586A (ja) * | 1999-02-26 | 2000-11-07 | Kyorin Pharmaceut Co Ltd | 6−置換−7−ヘテロキノキサリンカルボン酸誘導体とその付加塩及びそれらの製造方法 |
EP1601665A2 (de) * | 2003-03-07 | 2005-12-07 | Glaxo Group Limited | Harnstoff-derivate und deren verwendung als vanilloidrezeptorantagonisten zur behandlung von schmerzen |
CA2548172A1 (en) * | 2003-12-04 | 2005-06-23 | Vertex Pharmaceuticals Incorporated | Quinoxalines useful as inhibitors of protein kinases |
WO2008153385A1 (en) * | 2007-06-11 | 2008-12-18 | Valletta Health B.V. | Urocanic acid derivatives useful for the treatment of immune-related and inflammatory diseases |
MX2010001240A (es) | 2007-08-01 | 2010-04-30 | Kumiai Chemical Industry Co | Derivado de oxopirazina y herbicida. |
CN101952258B (zh) | 2008-03-05 | 2014-03-19 | 默克专利有限公司 | 作为胰岛素分泌刺激剂的喹喔啉酮衍生物、获得它们的方法及其在治疗糖尿病中的用途 |
EP2324013B3 (de) | 2008-07-21 | 2014-10-22 | Purdue Pharma LP | Verbrückte piperidinverbindungen vom substituierten chinoxalintyp und anwendungen davon |
EP2261211A1 (de) * | 2009-05-20 | 2010-12-15 | Université de Lille 2 Droit et Santé | 1,4-Dihydropyridin-Derivate und deren Verwendungen |
WO2010150548A1 (ja) | 2009-06-26 | 2010-12-29 | イハラケミカル工業株式会社 | ケトマロン酸化合物又はその抱水体の製造法 |
KR101117129B1 (ko) * | 2009-09-14 | 2012-02-24 | 한국화학연구원 | 신규한 퀴녹살린 유도체 및 이를 포함하는 줄기세포의 신경세포로의 분화유도용 조성물 |
CN104053442B (zh) | 2011-08-26 | 2017-06-23 | 润新生物公司 | 某些化学实体、组合物及方法 |
US9518029B2 (en) | 2011-09-14 | 2016-12-13 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
EP2757885B1 (de) | 2011-09-21 | 2017-03-15 | Neupharma, Inc. | Bestimmte chemische stoffe, zusammensetzungen und verfahren |
WO2013049701A1 (en) | 2011-09-30 | 2013-04-04 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
US9670180B2 (en) | 2012-01-25 | 2017-06-06 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
WO2014047648A1 (en) | 2012-09-24 | 2014-03-27 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
EP2916838B1 (de) | 2012-11-12 | 2019-03-13 | Neupharma, Inc. | Bestimmte chemische stoffe, zusammensetzungen und verfahren |
JP5921500B2 (ja) | 2013-07-19 | 2016-05-24 | イハラケミカル工業株式会社 | ケトマロン酸化合物の製造方法 |
KR102134407B1 (ko) | 2014-02-17 | 2020-07-15 | 구미아이 가가쿠 고교 가부시키가이샤 | 유통 반응기를 사용한 케토말론산 화합물의 연속 제조방법 |
CN108570038B (zh) * | 2017-03-08 | 2021-09-28 | 中国科学院上海药物研究所 | 二氢喹喔啉类溴结构域识别蛋白抑制剂及制备方法和用途 |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GR72941B (de) * | 1978-10-20 | 1984-01-16 | Lilly Co Eli | |
US4210647A (en) * | 1979-06-18 | 1980-07-01 | Eli Lilly And Company | Antiviral combinations |
US4252954A (en) * | 1979-10-25 | 1981-02-24 | Eli Lilly And Company | Salts of dihalo-3,4-dihydro-3-oxo-2-quinoxaline carboxylic acids and hindered amines |
WO1992011245A1 (en) * | 1990-12-20 | 1992-07-09 | Warner-Lambert Company | 2-acylamido derivatives of 3,4-dihydro-3-oxo-quinoxaline having pharmaceutical activity |
GB9125485D0 (en) * | 1991-11-29 | 1992-01-29 | Merck Sharp & Dohme | Therapeutic agents |
IL109397A0 (en) * | 1993-04-28 | 1994-07-31 | Schering Ag | Quinoxalinedione derivatives, processes for the preparation thereof and pharmaceutical compositions containing the same |
DE4340045A1 (de) * | 1993-11-24 | 1995-06-01 | Basf Ag | Neue Chinoxaline und Arzneimittel daraus |
AU688459B2 (en) * | 1994-04-08 | 1998-03-12 | Shionogi & Co., Ltd. | Oxopyridinylquinoxaline derivative |
DE19504226A1 (de) * | 1995-02-09 | 1996-08-22 | Hoechst Ag | Substituierte Chinoxaline, ihre Herstellung und ihre Verwendung als Arzneimittel |
DE19624808A1 (de) * | 1996-06-21 | 1998-01-02 | Basf Ag | Pyrrolylchinoxalindione, ihre Herstellung und Verwendung |
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1998
- 1998-08-28 AU AU88864/98A patent/AU744540B2/en not_active Ceased
- 1998-08-28 AT AT98940594T patent/ATE267176T1/de not_active IP Right Cessation
- 1998-08-28 BR BR9811739-4A patent/BR9811739A/pt not_active Application Discontinuation
- 1998-08-28 CA CA002302161A patent/CA2302161A1/en not_active Abandoned
- 1998-08-28 HU HU0002853A patent/HUP0002853A3/hu unknown
- 1998-08-28 WO PCT/JP1998/003832 patent/WO1999011632A1/ja active IP Right Grant
- 1998-08-28 KR KR1020007002183A patent/KR100588247B1/ko not_active IP Right Cessation
- 1998-08-28 US US09/485,716 patent/US6348461B1/en not_active Expired - Fee Related
- 1998-08-28 EP EP98940594A patent/EP1020453B1/de not_active Expired - Lifetime
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- 1998-08-28 NZ NZ503076A patent/NZ503076A/xx unknown
- 1998-08-28 CN CNB988087642A patent/CN1161344C/zh not_active Expired - Fee Related
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2000
- 2000-03-01 NO NO20001046A patent/NO315272B1/no not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
EP1020453B1 (de) | 2004-05-19 |
NZ503076A (en) | 2002-10-25 |
KR20010023535A (ko) | 2001-03-26 |
AU744540B2 (en) | 2002-02-28 |
WO1999011632A1 (fr) | 1999-03-11 |
CN1161344C (zh) | 2004-08-11 |
HUP0002853A2 (hu) | 2001-05-28 |
ATE267176T1 (de) | 2004-06-15 |
HUP0002853A3 (en) | 2001-12-28 |
EP1020453A1 (de) | 2000-07-19 |
BR9811739A (pt) | 2000-09-19 |
EP1020453A4 (de) | 2000-11-08 |
DE69824025T2 (de) | 2005-06-16 |
CN1269794A (zh) | 2000-10-11 |
KR100588247B1 (ko) | 2006-06-13 |
US6348461B1 (en) | 2002-02-19 |
CA2302161A1 (en) | 1999-03-11 |
DE69824025D1 (de) | 2004-06-24 |
NO20001046D0 (no) | 2000-03-01 |
NO20001046L (no) | 2000-05-02 |
AU8886498A (en) | 1999-03-22 |
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