UA75589C2

UA75589C2 - 1,2-diaryl benzimidazoles for treating illnesses associated with a microglia activation

1,2-diaryl benzimidazoles for treating illnesses associated with a microglia activation Download PDF

Info

Publication number: UA75589C2
Authority: UA; Ukraine
Prior art keywords: benzimidazol; phenyl; oxy; hexanoic acid; group
Prior art date: 2000-01-14

Application number

UA2002086720A

Other languages

English (en)

Ukrainian (uk)

Original Assignee

Schering Ag

Priority date

2000-01-14

Filing date

2001-12-01

Publication date

2006-05-15

2001-12-01 Application filed by Schering Ag filed Critical Schering Ag

2006-05-15 Publication of UA75589C2 publication Critical patent/UA75589C2/uk

Links

210000000274 microglia Anatomy 0.000 title claims abstract description 27
230000004913 activation Effects 0.000 title claims abstract description 24
238000011282 treatment Methods 0.000 claims abstract description 12
FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 446
GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 claims description 442
WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 439
150000001875 compounds Chemical class 0.000 claims description 323
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 286
-1 tetrahydro-2,5 -dioxopyrrol-1-yl Chemical group 0.000 claims description 145
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 137
150000004702 methyl esters Chemical class 0.000 claims description 115
NUKZAGXMHTUAFE-UHFFFAOYSA-N methyl hexanoate Chemical compound CCCCCC(=O)OC NUKZAGXMHTUAFE-UHFFFAOYSA-N 0.000 claims description 108
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 107
ALBYIUDWACNRRB-UHFFFAOYSA-N hexanamide Chemical compound CCCCCC(N)=O ALBYIUDWACNRRB-UHFFFAOYSA-N 0.000 claims description 94
125000001424 substituent group Chemical group 0.000 claims description 85
239000002253 acid Substances 0.000 claims description 80
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 79
125000000217 alkyl group Chemical group 0.000 claims description 78
125000000753 cycloalkyl group Chemical group 0.000 claims description 70
125000001072 heteroaryl group Chemical group 0.000 claims description 67
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 62
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 49
229910052799 carbon Inorganic materials 0.000 claims description 46
125000003118 aryl group Chemical group 0.000 claims description 42
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 38
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 36
125000002950 monocyclic group Chemical group 0.000 claims description 33
125000004433 nitrogen atom Chemical group N* 0.000 claims description 33
125000001589 carboacyl group Chemical group 0.000 claims description 32
125000004432 carbon atom Chemical group C* 0.000 claims description 30
229910052760 oxygen Inorganic materials 0.000 claims description 30
125000002619 bicyclic group Chemical group 0.000 claims description 28
125000005842 heteroatom Chemical group 0.000 claims description 28
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 26
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 22
125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 22
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 19
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 16
125000004429 atom Chemical group 0.000 claims description 15
229910052739 hydrogen Inorganic materials 0.000 claims description 15
239000001257 hydrogen Substances 0.000 claims description 15
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 13
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
239000012634 fragment Substances 0.000 claims description 12
229910052740 iodine Inorganic materials 0.000 claims description 12
125000004430 oxygen atom Chemical group O* 0.000 claims description 12
125000000623 heterocyclic group Chemical group 0.000 claims description 11
HNBDRPTVWVGKBR-UHFFFAOYSA-N methyl pentanoate Chemical compound CCCCC(=O)OC HNBDRPTVWVGKBR-UHFFFAOYSA-N 0.000 claims description 11
239000001301 oxygen Substances 0.000 claims description 11
235000019260 propionic acid Nutrition 0.000 claims description 11
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 11
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
229910052757 nitrogen Inorganic materials 0.000 claims description 10
229910052717 sulfur Inorganic materials 0.000 claims description 10
125000003831 tetrazolyl group Chemical group 0.000 claims description 10
125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 9
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
150000007513 acids Chemical class 0.000 claims description 9
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 9
239000011593 sulfur Substances 0.000 claims description 9
125000001931 aliphatic group Chemical group 0.000 claims description 8
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
125000000896 monocarboxylic acid group Chemical group 0.000 claims description 7
UUIQMZJEGPQKFD-UHFFFAOYSA-N Methyl butyrate Chemical group CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 claims description 6
125000005010 perfluoroalkyl group Chemical group 0.000 claims description 6
229910052698 phosphorus Inorganic materials 0.000 claims description 6
RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical group CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 claims description 5
125000003342 alkenyl group Chemical group 0.000 claims description 5
125000000304 alkynyl group Chemical group 0.000 claims description 5
201000010099 disease Diseases 0.000 claims description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
229940126601 medicinal product Drugs 0.000 claims description 5
238000002360 preparation method Methods 0.000 claims description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 4
230000006806 disease prevention Effects 0.000 claims description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
230000009471 action Effects 0.000 claims description 3
239000000969 carrier Substances 0.000 claims description 3
SHZIWNPUGXLXDT-UHFFFAOYSA-N ethyl hexanoate Chemical group CCCCCC(=O)OCC SHZIWNPUGXLXDT-UHFFFAOYSA-N 0.000 claims description 3
125000005843 halogen group Chemical group 0.000 claims description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
AWQSAIIDOMEEOD-UHFFFAOYSA-N 5,5-Dimethyl-4-(3-oxobutyl)dihydro-2(3H)-furanone Chemical compound CC(=O)CCC1CC(=O)OC1(C)C AWQSAIIDOMEEOD-UHFFFAOYSA-N 0.000 claims description 2
125000002877 alkyl aryl group Chemical group 0.000 claims description 2
125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 2
229910052796 boron Inorganic materials 0.000 claims description 2
150000002400 hexanoic acid esters Chemical class 0.000 claims description 2
150000002466 imines Chemical class 0.000 claims description 2
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 2
150000001556 benzimidazoles Chemical class 0.000 claims 11
YZGQDNOIGFBYKF-UHFFFAOYSA-N Ethoxyacetic acid Chemical compound CCOCC(O)=O YZGQDNOIGFBYKF-UHFFFAOYSA-N 0.000 claims 2
125000004453 alkoxycarbonyl group Chemical group 0.000 claims 2
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 claims 1
DBNJSZYFWVVQBO-UHFFFAOYSA-N SOOS Chemical compound SOOS DBNJSZYFWVVQBO-UHFFFAOYSA-N 0.000 claims 1
210000005056 cell body Anatomy 0.000 claims 1
210000003746 feather Anatomy 0.000 claims 1
AEDIXYWIVPYNBI-UHFFFAOYSA-N heptanamide Chemical compound CCCCCCC(N)=O AEDIXYWIVPYNBI-UHFFFAOYSA-N 0.000 claims 1
239000008177 pharmaceutical agent Substances 0.000 claims 1
125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims 1
238000012876 topography Methods 0.000 claims 1
229910052721 tungsten Inorganic materials 0.000 claims 1
125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 abstract description 27
229940058303 antinematodal benzimidazole derivative Drugs 0.000 abstract description 6
239000003814 drug Substances 0.000 abstract description 5
238000011321 prophylaxis Methods 0.000 abstract 1
238000007429 general method Methods 0.000 description 323
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 154
230000003993 interaction Effects 0.000 description 127
238000005160 1H NMR spectroscopy Methods 0.000 description 112
238000006243 chemical reaction Methods 0.000 description 101
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 67
235000011152 sodium sulphate Nutrition 0.000 description 59
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 58
229910052938 sodium sulfate Inorganic materials 0.000 description 58
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 56
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 56
239000000741 silica gel Substances 0.000 description 54
229910002027 silica gel Inorganic materials 0.000 description 54
239000000203 mixture Substances 0.000 description 53
239000000243 solution Substances 0.000 description 52
238000005481 NMR spectroscopy Methods 0.000 description 49
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 48
238000000034 method Methods 0.000 description 48
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 47
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 41
150000001793 charged compounds Chemical class 0.000 description 36
239000012074 organic phase Substances 0.000 description 34
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
239000000284 extract Substances 0.000 description 32
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
238000007363 ring formation reaction Methods 0.000 description 26
239000012047 saturated solution Substances 0.000 description 25
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 24
238000001816 cooling Methods 0.000 description 23
238000003756 stirring Methods 0.000 description 23
235000002639 sodium chloride Nutrition 0.000 description 21
ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 20
210000004027 cell Anatomy 0.000 description 19
239000000047 product Substances 0.000 description 19
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 18
BQFPCTXLBRVFJL-UHFFFAOYSA-N triethoxymethylbenzene Chemical compound CCOC(OCC)(OCC)C1=CC=CC=C1 BQFPCTXLBRVFJL-UHFFFAOYSA-N 0.000 description 18
229960000583 acetic acid Drugs 0.000 description 15
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
239000011780 sodium chloride Substances 0.000 description 15
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
235000011054 acetic acid Nutrition 0.000 description 14
238000004440 column chromatography Methods 0.000 description 14
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 13
ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical compound CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 description 13
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 12
239000004305 biphenyl Substances 0.000 description 12
QWHCQJHSPOLDLA-UHFFFAOYSA-N 1,2-diphenylbenzimidazol-5-amine Chemical compound N=1C2=CC(N)=CC=C2N(C=2C=CC=CC=2)C=1C1=CC=CC=C1 QWHCQJHSPOLDLA-UHFFFAOYSA-N 0.000 description 11
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 11
229910052708 sodium Inorganic materials 0.000 description 11
239000011734 sodium Substances 0.000 description 11
238000003828 vacuum filtration Methods 0.000 description 11
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
238000010992 reflux Methods 0.000 description 10
IECKAVQTURBPON-UHFFFAOYSA-N trimethoxymethylbenzene Chemical compound COC(OC)(OC)C1=CC=CC=C1 IECKAVQTURBPON-UHFFFAOYSA-N 0.000 description 10
ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 4-chlorobenzenesulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C=C1 ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 0.000 description 9
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 9
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 9
239000003518 caustics Substances 0.000 description 9
239000012141 concentrate Substances 0.000 description 9
239000012312 sodium hydride Substances 0.000 description 9
229910000104 sodium hydride Inorganic materials 0.000 description 9
CSSGKHVRDGATJL-UHFFFAOYSA-N 3-fluoro-4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C(F)=C1 CSSGKHVRDGATJL-UHFFFAOYSA-N 0.000 description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 8
239000007864 aqueous solution Substances 0.000 description 8
210000004556 brain Anatomy 0.000 description 8
150000001732 carboxylic acid derivatives Chemical class 0.000 description 8
239000012043 crude product Substances 0.000 description 8
238000002425 crystallisation Methods 0.000 description 8
230000008025 crystallization Effects 0.000 description 8
210000002540 macrophage Anatomy 0.000 description 8
239000011541 reaction mixture Substances 0.000 description 8
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INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 7
239000007858 starting material Substances 0.000 description 7
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
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241000700159 Rattus Species 0.000 description 6
239000008346 aqueous phase Substances 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
238000001035 drying Methods 0.000 description 6
SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 6
KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
230000009467 reduction Effects 0.000 description 6
150000003839 salts Chemical class 0.000 description 6
229920006395 saturated elastomer Polymers 0.000 description 6
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
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239000003826 tablet Substances 0.000 description 6
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150000001408 amides Chemical class 0.000 description 5
238000004587 chromatography analysis Methods 0.000 description 5
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230000002518 glial effect Effects 0.000 description 5
239000002609 medium Substances 0.000 description 5
HVAMZGADVCBITI-UHFFFAOYSA-N pent-4-enoic acid Chemical compound OC(=O)CCC=C HVAMZGADVCBITI-UHFFFAOYSA-N 0.000 description 5
235000015497 potassium bicarbonate Nutrition 0.000 description 5
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238000012545 processing Methods 0.000 description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
238000010898 silica gel chromatography Methods 0.000 description 5
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239000002904 solvent Substances 0.000 description 5
CBCKQZAAMUWICA-UHFFFAOYSA-N 1,4-phenylenediamine Chemical compound NC1=CC=C(N)C=C1 CBCKQZAAMUWICA-UHFFFAOYSA-N 0.000 description 4
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BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 4
BBNIUIKAOVCOGV-UHFFFAOYSA-N 5-methoxy-n-(3-methylphenyl)-2-nitroaniline Chemical compound COC1=CC=C([N+]([O-])=O)C(NC=2C=C(C)C=CC=2)=C1 BBNIUIKAOVCOGV-UHFFFAOYSA-N 0.000 description 4
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206010008190 Cerebrovascular accident Diseases 0.000 description 4
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