SK280336B6 - Farmaceutická kompozícia obsahujúca pyridazino[4,5 - Google Patents

Info

Publication number

SK280336B6

SK280336B6 SK1396-92A SK139692A SK280336B6 SK 280336 B6 SK280336 B6 SK 280336B6 SK 139692 A SK139692 A SK 139692A SK 280336 B6 SK280336 B6 SK 280336B6

Authority

SK

Slovakia

Prior art keywords

group

formula

compound

dione

alkyl

Prior art date

1991-05-09

Links

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• 238000000034 method Methods 0.000 title claims abstract description 135
• 238000002360 preparation method Methods 0.000 title claims abstract description 19
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 11
• BWGUQNLLOGKYEI-UHFFFAOYSA-N pyridazino[4,5-b]quinoline Chemical class C1=NN=CC2=CC3=CC=CC=C3N=C21 BWGUQNLLOGKYEI-UHFFFAOYSA-N 0.000 title abstract 3
• 150000003839 salts Chemical class 0.000 claims abstract description 19
• 208000012902 Nervous system disease Diseases 0.000 claims abstract description 6
• 208000025966 Neurological disease Diseases 0.000 claims abstract description 5
• 150000001875 compounds Chemical class 0.000 claims description 342
• -1 amino, hydrazino, hydroxy Chemical group 0.000 claims description 161
• 229910052739 hydrogen Inorganic materials 0.000 claims description 47
• 239000001257 hydrogen Substances 0.000 claims description 45
• 125000000217 alkyl group Chemical group 0.000 claims description 43
• 125000004432 carbon atom Chemical group C* 0.000 claims description 36
• 238000006243 chemical reaction Methods 0.000 claims description 27
• 229910052757 nitrogen Inorganic materials 0.000 claims description 27
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
• 150000005690 diesters Chemical class 0.000 claims description 23
• 125000001424 substituent group Chemical group 0.000 claims description 20
• 150000002431 hydrogen Chemical class 0.000 claims description 18
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 17
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
• QZWYCFYTWWTGQD-UHFFFAOYSA-N 7-chloro-3,5-dihydro-2h-pyridazino[4,5-b]quinoline-1,4,10-trione Chemical compound C=1C(Cl)=CC=C(C2=O)C=1NC1=C2C(=O)NNC1=O QZWYCFYTWWTGQD-UHFFFAOYSA-N 0.000 claims description 14
• 229920006395 saturated elastomer Polymers 0.000 claims description 14
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
• 230000008569 process Effects 0.000 claims description 12
• 239000003795 chemical substances by application Substances 0.000 claims description 11
• 125000002252 acyl group Chemical group 0.000 claims description 9
• 125000003545 alkoxy group Chemical group 0.000 claims description 9
• 229910052736 halogen Inorganic materials 0.000 claims description 9
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
• 150000002367 halogens Chemical class 0.000 claims description 8
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
• 150000002429 hydrazines Chemical class 0.000 claims description 7
• 125000003277 amino group Chemical group 0.000 claims description 6
• 150000002148 esters Chemical class 0.000 claims description 6
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 6
• 125000005190 thiohydroxy group Chemical group 0.000 claims description 6
• XQHDNGHMKWHGRH-UHFFFAOYSA-N 7-chloro-9-methyl-3,5-dihydro-2h-pyridazino[4,5-b]quinoline-1,4,10-trione Chemical compound O=C1C=2C(C)=CC(Cl)=CC=2NC2=C1C(=O)NNC2=O XQHDNGHMKWHGRH-UHFFFAOYSA-N 0.000 claims description 5
• WTVQNVIRGFXAOP-UHFFFAOYSA-N 9-ethyl-3,5-dihydro-2h-pyridazino[4,5-b]quinoline-1,4,10-trione Chemical compound O=C1C=2C(CC)=CC=CC=2NC2=C1C(=O)NNC2=O WTVQNVIRGFXAOP-UHFFFAOYSA-N 0.000 claims description 5
• 239000002168 alkylating agent Substances 0.000 claims description 5
• 229940100198 alkylating agent Drugs 0.000 claims description 5
• 239000003085 diluting agent Substances 0.000 claims description 5
• 125000003884 phenylalkyl group Chemical group 0.000 claims description 5
• 125000004076 pyridyl group Chemical group 0.000 claims description 5
• NXBDYHNALJUVHY-UHFFFAOYSA-N 9-chloro-7-methyl-3,5-dihydro-2h-pyridazino[4,5-b]quinoline-1,4,10-trione Chemical compound C=1C(C)=CC(Cl)=C(C2=O)C=1NC1=C2C(=O)NNC1=O NXBDYHNALJUVHY-UHFFFAOYSA-N 0.000 claims description 4
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
• 229910052799 carbon Inorganic materials 0.000 claims description 4
• 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 4
• 229910052717 sulfur Inorganic materials 0.000 claims description 4
• 125000004434 sulfur atom Chemical group 0.000 claims description 4
• MUBUVSOVCWEGGH-UHFFFAOYSA-N (7-chloro-4,10-dioxo-3,5-dihydropyridazino[4,5-b]quinolin-1-yl) 3-phenylpropanoate Chemical compound Oc1c2ccc(Cl)cc2nc2c1c(OC(=O)CCc1ccccc1)n[nH]c2=O MUBUVSOVCWEGGH-UHFFFAOYSA-N 0.000 claims description 3
• VCAFYGHTTLRWID-UHFFFAOYSA-N 10-amino-2,3-dihydropyridazino[4,5-b]quinoline-1,4-dione Chemical compound O=C1NNC(=O)C2=C1C(N)=C1C=CC=CC1=N2 VCAFYGHTTLRWID-UHFFFAOYSA-N 0.000 claims description 3
• OKESGPHZYDVCCJ-UHFFFAOYSA-N 7-bromo-9-ethyl-3,5-dihydro-2h-pyridazino[4,5-b]quinoline-1,4,10-trione Chemical compound O=C1C=2C(CC)=CC(Br)=CC=2NC2=C1C(=O)NNC2=O OKESGPHZYDVCCJ-UHFFFAOYSA-N 0.000 claims description 3
• VCESISKHPBQXOF-UHFFFAOYSA-N 7-chloro-2,3-dihydropyridazino[4,5-b]quinoline-1,4-dione Chemical compound O=C1NNC(=O)C=2C1=NC1=CC(Cl)=CC=C1C=2 VCESISKHPBQXOF-UHFFFAOYSA-N 0.000 claims description 3
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
• 238000006798 ring closing metathesis reaction Methods 0.000 claims description 3
• MWXQWKXCRRLZMD-UHFFFAOYSA-N (3-acetyl-7,9-dichloro-4,10-dioxo-5H-pyridazino[4,5-b]quinolin-1-yl) acetate Chemical compound CC(=O)Oc1nn(C(C)=O)c(=O)c2nc3cc(Cl)cc(Cl)c3c(O)c12 MWXQWKXCRRLZMD-UHFFFAOYSA-N 0.000 claims description 2
• CTKBWFDNPZUOEL-UHFFFAOYSA-N 7,9-dibromo-3,5-dihydro-2h-pyridazino[4,5-b]quinoline-1,4,10-trione Chemical compound C=1C(Br)=CC(Br)=C(C2=O)C=1NC1=C2C(=O)NNC1=O CTKBWFDNPZUOEL-UHFFFAOYSA-N 0.000 claims description 2
• TXWYVTBDIIVFQW-UHFFFAOYSA-N 7-chloro-9-iodo-3,5-dihydro-2h-pyridazino[4,5-b]quinoline-1,4,10-trione Chemical compound C=1C(Cl)=CC(I)=C(C2=O)C=1NC1=C2C(=O)NNC1=O TXWYVTBDIIVFQW-UHFFFAOYSA-N 0.000 claims description 2
• 238000005804 alkylation reaction Methods 0.000 claims description 2
• 150000001768 cations Chemical class 0.000 claims description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
• 238000006389 diacetylation reaction Methods 0.000 claims description 2
• 230000007062 hydrolysis Effects 0.000 claims description 2
• 238000006460 hydrolysis reaction Methods 0.000 claims description 2
• 230000003301 hydrolyzing effect Effects 0.000 claims description 2
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
• ODYWLIZMVJEOER-UHFFFAOYSA-N quinoline-2,3-dicarbohydrazide Chemical compound C1=CC=C2N=C(C(=O)NN)C(C(=O)NN)=CC2=C1 ODYWLIZMVJEOER-UHFFFAOYSA-N 0.000 claims description 2
• VHUKRVUZPALOFM-UHFFFAOYSA-N 7-bromo-9-methyl-3,5-dihydro-2h-pyridazino[4,5-b]quinoline-1,4,10-trione Chemical compound O=C1C=2C(C)=CC(Br)=CC=2NC2=C1C(=O)NNC2=O VHUKRVUZPALOFM-UHFFFAOYSA-N 0.000 claims 1
• 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims 1
• 239000000203 mixture Substances 0.000 abstract description 139
• 239000007787 solid Substances 0.000 description 188
• 238000000451 chemical ionisation Methods 0.000 description 153
• 238000001819 mass spectrum Methods 0.000 description 152
• 239000000047 product Substances 0.000 description 144
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 142
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 141
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 139
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 131
• 238000000921 elemental analysis Methods 0.000 description 129
• 238000002844 melting Methods 0.000 description 112
• 230000008018 melting Effects 0.000 description 112
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 108
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 103
• 239000000243 solution Substances 0.000 description 102
• 239000007858 starting material Substances 0.000 description 98
• 239000011541 reaction mixture Substances 0.000 description 94
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 93
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 79
• 229910001868 water Inorganic materials 0.000 description 77
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 60
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 54
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 51
• 238000010992 reflux Methods 0.000 description 49
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
• 239000013078 crystal Substances 0.000 description 44
• 238000005160 1H NMR spectroscopy Methods 0.000 description 42
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 40
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 38
• 239000002244 precipitate Substances 0.000 description 38
• 238000001953 recrystallisation Methods 0.000 description 38
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 36
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
• 239000000538 analytical sample Substances 0.000 description 34
• 238000012360 testing method Methods 0.000 description 34
• 239000000741 silica gel Substances 0.000 description 32
• 229910002027 silica gel Inorganic materials 0.000 description 32
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 30
• 235000019341 magnesium sulphate Nutrition 0.000 description 30
• 229960000583 acetic acid Drugs 0.000 description 28
• 239000003921 oil Substances 0.000 description 27
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 26
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 23
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
• 239000000284 extract Substances 0.000 description 23
• QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 22
• 239000000460 chlorine Substances 0.000 description 20
• 239000000843 powder Substances 0.000 description 20
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 20
• 239000000725 suspension Substances 0.000 description 18
• 238000001816 cooling Methods 0.000 description 17
• 239000002904 solvent Substances 0.000 description 16
• 238000003756 stirring Methods 0.000 description 16
• 238000004587 chromatography analysis Methods 0.000 description 15
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 14
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 14
• 239000012299 nitrogen atmosphere Substances 0.000 description 14
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 13
• 238000005481 NMR spectroscopy Methods 0.000 description 13
• 239000000706 filtrate Substances 0.000 description 13
• 239000012258 stirred mixture Substances 0.000 description 13
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
• 239000004471 Glycine Substances 0.000 description 12
• 229960001760 dimethyl sulfoxide Drugs 0.000 description 12
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 11
• 229930195712 glutamate Natural products 0.000 description 11
• MYKHANQTTIRZJK-UHFFFAOYSA-N pyridazine-3,4-dione Chemical class O=C1C=CN=NC1=O MYKHANQTTIRZJK-UHFFFAOYSA-N 0.000 description 11
• NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 10
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 10
• VHILMKFSCRWWIJ-UHFFFAOYSA-N dimethyl acetylenedicarboxylate Chemical compound COC(=O)C#CC(=O)OC VHILMKFSCRWWIJ-UHFFFAOYSA-N 0.000 description 10
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 9
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 9
• 239000002585 base Substances 0.000 description 9
• 230000008602 contraction Effects 0.000 description 9
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
• 210000001320 hippocampus Anatomy 0.000 description 9
• 239000012265 solid product Substances 0.000 description 9
• 241001465754 Metazoa Species 0.000 description 8
• 238000003556 assay Methods 0.000 description 8
• 229910052801 chlorine Inorganic materials 0.000 description 8
• SLPCQFBJADHSKZ-UHFFFAOYSA-N dimethyl 7-chloro-4-oxo-1h-quinoline-2,3-dicarboxylate Chemical compound ClC1=CC=C2C(O)=C(C(=O)OC)C(C(=O)OC)=NC2=C1 SLPCQFBJADHSKZ-UHFFFAOYSA-N 0.000 description 8
• 238000001035 drying Methods 0.000 description 8
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 8
• 239000004381 Choline salt Substances 0.000 description 7
• 239000002253 acid Substances 0.000 description 7
• 235000011089 carbon dioxide Nutrition 0.000 description 7
• 235000019417 choline salt Nutrition 0.000 description 7
• 230000006378 damage Effects 0.000 description 7
• 238000001914 filtration Methods 0.000 description 7
• 238000009472 formulation Methods 0.000 description 7
• 230000000302 ischemic effect Effects 0.000 description 7
• 239000011777 magnesium Substances 0.000 description 7
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
• 150000003248 quinolines Chemical class 0.000 description 7
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
• 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 6
• 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 6
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 6
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
• 230000037396 body weight Effects 0.000 description 6
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 6
• 239000007789 gas Substances 0.000 description 6
• 125000005843 halogen group Chemical group 0.000 description 6
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
• 238000005984 hydrogenation reaction Methods 0.000 description 6
• JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 6
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
• 239000010410 layer Substances 0.000 description 6
• UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 6
• MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 description 5
• 229930195711 D-Serine Natural products 0.000 description 5
• 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 5
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
• 150000008064 anhydrides Chemical class 0.000 description 5
• 230000027455 binding Effects 0.000 description 5
• 210000004556 brain Anatomy 0.000 description 5
• 239000012267 brine Substances 0.000 description 5
• 239000003054 catalyst Substances 0.000 description 5
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical group C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 5
• WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• 239000012259 ether extract Substances 0.000 description 5
• 239000012362 glacial acetic acid Substances 0.000 description 5
• 239000011521 glass Substances 0.000 description 5
• 102000005962 receptors Human genes 0.000 description 5
• 108020003175 receptors Proteins 0.000 description 5
• 229910052938 sodium sulfate Inorganic materials 0.000 description 5
• 235000011152 sodium sulphate Nutrition 0.000 description 5
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
• 210000001519 tissue Anatomy 0.000 description 5
• HMBHAQMOBKLWRX-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-3-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)COC2=C1 HMBHAQMOBKLWRX-UHFFFAOYSA-N 0.000 description 4
• HVPQMLZLINVIHW-UHFFFAOYSA-N 6-bromo-1h-indole-2,3-dione Chemical compound BrC1=CC=C2C(=O)C(=O)NC2=C1 HVPQMLZLINVIHW-UHFFFAOYSA-N 0.000 description 4
• PHKAOEGXBSERHX-UHFFFAOYSA-N 6-iodo-1h-indole-2,3-dione Chemical compound IC1=CC=C2C(=O)C(=O)NC2=C1 PHKAOEGXBSERHX-UHFFFAOYSA-N 0.000 description 4
• LKECUUGNLPIWBL-UHFFFAOYSA-N 7-bromo-3,5-dihydro-2h-pyridazino[4,5-b]quinoline-1,4,10-trione Chemical compound C=1C(Br)=CC=C(C2=O)C=1NC1=C2C(=O)NNC1=O LKECUUGNLPIWBL-UHFFFAOYSA-N 0.000 description 4
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
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