SK281941B6 - Deriváty kyseliny indol-2-karboxylovej, ich použitie, spôsob ich prípravy a farmaceutický prípravok s ich obsahom - Google Patents

Deriváty kyseliny indol-2-karboxylovej, ich použitie, spôsob ich prípravy a farmaceutický prípravok s ich obsahom Download PDF

Info

Publication number: SK281941B6
Authority: SK; Slovakia
Prior art keywords: carboxylic acid; ethenyl; indole; dichloroindole; formula
Prior art date: 1992-04-16

Application number

SK1241-94A

Other languages

English (en)

Slovak (sk)

Other versions

SK124194A3 (en

Inventor

Alfredo Cugola

Giovanni Gaviraghi

Simone Giacobbe

Original Assignee

Glaxo S. P. A

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1992-04-16

Filing date

1993-04-15

Publication date

2001-09-11

1993-04-15 Application filed by Glaxo S. P. A filed Critical Glaxo S. P. A

1995-05-10 Publication of SK124194A3 publication Critical patent/SK124194A3/sk

2001-09-11 Publication of SK281941B6 publication Critical patent/SK281941B6/sk

Links

HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical class C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 title claims abstract description 14
150000001875 compounds Chemical class 0.000 claims abstract description 139
239000000203 mixture Substances 0.000 claims abstract description 49
150000003839 salts Chemical class 0.000 claims abstract description 33
150000002148 esters Chemical class 0.000 claims abstract description 26
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims abstract description 21
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 20
238000000034 method Methods 0.000 claims abstract description 19
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 14
239000000460 chlorine Substances 0.000 claims abstract description 10
238000002360 preparation method Methods 0.000 claims abstract description 10
102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 claims abstract description 9
108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 claims abstract description 9
230000000694 effects Effects 0.000 claims abstract description 8
125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims abstract description 8
125000003545 alkoxy group Chemical group 0.000 claims abstract description 7
150000002475 indoles Chemical class 0.000 claims abstract description 7
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 7
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims abstract description 6
230000003042 antagnostic effect Effects 0.000 claims abstract description 6
229910052801 chlorine Inorganic materials 0.000 claims abstract description 6
230000002461 excitatory amino acid Effects 0.000 claims abstract description 6
239000003257 excitatory amino acid Substances 0.000 claims abstract description 6
125000001153 fluoro group Chemical group F* 0.000 claims abstract description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 6
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 6
125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 5
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
238000004519 manufacturing process Methods 0.000 claims abstract description 3
230000001225 therapeutic effect Effects 0.000 claims abstract description 3
-1 hydroxy- Chemical class 0.000 claims description 42
238000006243 chemical reaction Methods 0.000 claims description 23
230000002503 metabolic effect Effects 0.000 claims description 20
125000000217 alkyl group Chemical group 0.000 claims description 17
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 10
125000006239 protecting group Chemical group 0.000 claims description 10
238000011282 treatment Methods 0.000 claims description 10
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
229910052739 hydrogen Inorganic materials 0.000 claims description 8
239000001257 hydrogen Substances 0.000 claims description 8
239000003814 drug Substances 0.000 claims description 5
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 5
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
229910052698 phosphorus Inorganic materials 0.000 claims description 4
239000011574 phosphorus Substances 0.000 claims description 4
XLMJSBMZZPMBBS-BQYQJAHWSA-N 4,6-dichloro-3-[(e)-3-(4-ethoxyanilino)-3-oxoprop-1-enyl]-1h-indole-2-carboxylic acid Chemical compound C1=CC(OCC)=CC=C1NC(=O)\C=C\C1=C(C(O)=O)NC2=CC(Cl)=CC(Cl)=C12 XLMJSBMZZPMBBS-BQYQJAHWSA-N 0.000 claims description 3
COOHMTPXHBZYNI-GQCTYLIASA-N 4,6-dichloro-3-[(e)-3-(4-methoxy-2-methylanilino)-3-oxoprop-1-enyl]-1h-indole-2-carboxylic acid Chemical compound CC1=CC(OC)=CC=C1NC(=O)\C=C\C1=C(C(O)=O)NC2=CC(Cl)=CC(Cl)=C12 COOHMTPXHBZYNI-GQCTYLIASA-N 0.000 claims description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
159000000000 sodium salts Chemical class 0.000 claims description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
WWMNVMSKSYHEAW-UHFFFAOYSA-N 3-(3-anilino-3-oxoprop-1-ynyl)-4,6-dichloro-1h-indole-2-carboxylic acid Chemical compound OC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1C#CC(=O)NC1=CC=CC=C1 WWMNVMSKSYHEAW-UHFFFAOYSA-N 0.000 claims description 2
GGFGLRLJUIGKJY-DUXPYHPUSA-N 4,6-dichloro-3-[(e)-3-(2,4-difluoroanilino)-3-oxoprop-1-enyl]-1h-indole-2-carboxylic acid Chemical compound OC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1\C=C\C(=O)NC1=CC=C(F)C=C1F GGFGLRLJUIGKJY-DUXPYHPUSA-N 0.000 claims description 2
VVMOWYUCNPJIPE-DUXPYHPUSA-N 4,6-dichloro-3-[(e)-3-(2-hydroxy-5-nitroanilino)-3-oxoprop-1-enyl]-1h-indole-2-carboxylic acid Chemical compound OC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1\C=C\C(=O)NC1=CC([N+]([O-])=O)=CC=C1O VVMOWYUCNPJIPE-DUXPYHPUSA-N 0.000 claims description 2
WQVZUMRYVXXYQS-GQCTYLIASA-N 4,6-dichloro-3-[(e)-3-(3,4-dimethoxyanilino)-3-oxoprop-1-enyl]-1h-indole-2-carboxylic acid Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)\C=C\C1=C(C(O)=O)NC2=CC(Cl)=CC(Cl)=C12 WQVZUMRYVXXYQS-GQCTYLIASA-N 0.000 claims description 2
BOYUWVOTYKNCDE-BQYQJAHWSA-N 4,6-dichloro-3-[(e)-3-oxo-3-(2-propan-2-ylanilino)prop-1-enyl]-1h-indole-2-carboxylic acid Chemical compound CC(C)C1=CC=CC=C1NC(=O)\C=C\C1=C(C(O)=O)NC2=CC(Cl)=CC(Cl)=C12 BOYUWVOTYKNCDE-BQYQJAHWSA-N 0.000 claims description 2
150000001336 alkenes Chemical class 0.000 claims description 2
JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims description 2
239000000969 carrier Substances 0.000 claims 1
WZBNEZWCNKUOSM-VOTSOKGWSA-N gavestinel Chemical compound OC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1\C=C\C(=O)NC1=CC=CC=C1 WZBNEZWCNKUOSM-VOTSOKGWSA-N 0.000 claims 1
125000006018 1-methyl-ethenyl group Chemical group 0.000 abstract description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 66
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 64
239000007787 solid Substances 0.000 description 44
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
239000000243 solution Substances 0.000 description 30
239000000543 intermediate Substances 0.000 description 29
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 28
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
238000005160 1H NMR spectroscopy Methods 0.000 description 23
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 21
238000003756 stirring Methods 0.000 description 21
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
229910052757 nitrogen Chemical group 0.000 description 17
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
239000000725 suspension Substances 0.000 description 15
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 14
238000001914 filtration Methods 0.000 description 14
239000002904 solvent Substances 0.000 description 14
239000002244 precipitate Substances 0.000 description 13
238000009472 formulation Methods 0.000 description 11
239000003826 tablet Substances 0.000 description 11
239000004480 active ingredient Substances 0.000 description 10
238000010790 dilution Methods 0.000 description 9
239000012895 dilution Substances 0.000 description 9
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
239000012044 organic layer Substances 0.000 description 9
239000004471 Glycine Substances 0.000 description 7
239000002585 base Substances 0.000 description 7
235000019441 ethanol Nutrition 0.000 description 7
239000000843 powder Substances 0.000 description 7
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
241000699670 Mus sp. Species 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 6
239000002775 capsule Substances 0.000 description 6
239000007795 chemical reaction product Substances 0.000 description 6
239000008101 lactose Substances 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
230000003389 potentiating effect Effects 0.000 description 6
NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 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 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
239000000010 aprotic solvent Substances 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical class C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 5
229920000168 Microcrystalline cellulose Polymers 0.000 description 4
229940054051 antipsychotic indole derivative Drugs 0.000 description 4
239000012267 brine Substances 0.000 description 4
238000004440 column chromatography Methods 0.000 description 4
125000004494 ethyl ester group Chemical group 0.000 description 4
238000003818 flash chromatography Methods 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
239000007788 liquid Substances 0.000 description 4
239000008108 microcrystalline cellulose Substances 0.000 description 4
229940016286 microcrystalline cellulose Drugs 0.000 description 4
235000019813 microcrystalline cellulose Nutrition 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
229920006395 saturated elastomer Polymers 0.000 description 4
239000011734 sodium Substances 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
239000000126 substance Substances 0.000 description 4
HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 4
239000003981 vehicle Substances 0.000 description 4
WZBNEZWCNKUOSM-UHFFFAOYSA-N 3-(3-anilino-3-oxoprop-1-enyl)-4,6-dichloro-1H-indole-2-carboxylic acid Chemical compound OC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1C=CC(=O)NC1=CC=CC=C1 WZBNEZWCNKUOSM-UHFFFAOYSA-N 0.000 description 3
206010010904 Convulsion Diseases 0.000 description 3
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 3
108010010803 Gelatin Proteins 0.000 description 3
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 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
239000002253 acid Substances 0.000 description 3
125000005041 acyloxyalkyl group Chemical group 0.000 description 3
125000005907 alkyl ester group Chemical group 0.000 description 3
239000003194 amino acid receptor blocking agent Substances 0.000 description 3
125000004103 aminoalkyl group Chemical group 0.000 description 3
239000005557 antagonist Substances 0.000 description 3
239000000839 emulsion Substances 0.000 description 3
230000032050 esterification Effects 0.000 description 3
238000005886 esterification reaction Methods 0.000 description 3
239000008273 gelatin Substances 0.000 description 3
229920000159 gelatin Polymers 0.000 description 3
235000019322 gelatine Nutrition 0.000 description 3
235000011852 gelatine desserts Nutrition 0.000 description 3
YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
238000002844 melting Methods 0.000 description 3
230000008018 melting Effects 0.000 description 3
230000004770 neurodegeneration Effects 0.000 description 3
208000015122 neurodegenerative disease Diseases 0.000 description 3
231100000189 neurotoxic Toxicity 0.000 description 3
230000002887 neurotoxic effect Effects 0.000 description 3
239000003921 oil Substances 0.000 description 3
235000019198 oils Nutrition 0.000 description 3
238000007911 parenteral administration Methods 0.000 description 3
239000012071 phase Substances 0.000 description 3
229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
239000000047 product Substances 0.000 description 3
238000000746 purification Methods 0.000 description 3
238000010992 reflux Methods 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
239000000600 sorbitol Substances 0.000 description 3
235000010356 sorbitol Nutrition 0.000 description 3
239000008107 starch Substances 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
229940032147 starch Drugs 0.000 description 3
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
206010021143 Hypoxia Diseases 0.000 description 2
235000010643 Leucaena leucocephala Nutrition 0.000 description 2
240000007472 Leucaena leucocephala Species 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
238000005481 NMR spectroscopy Methods 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
239000000443 aerosol Substances 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
150000001340 alkali metals Chemical class 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
238000003556 assay Methods 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
150000001735 carboxylic acids Chemical class 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
238000001816 cooling Methods 0.000 description 2
239000012043 crude product Substances 0.000 description 2
125000004663 dialkyl amino group Chemical group 0.000 description 2
229920001971 elastomer Polymers 0.000 description 2
DGXMYSHVJMOWMA-CMDGGOBGSA-N ethyl 3-[(e)-3-anilino-3-oxoprop-1-enyl]-4,6-dichloro-1h-indole-2-carboxylate Chemical compound CCOC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1\C=C\C(=O)NC1=CC=CC=C1 DGXMYSHVJMOWMA-CMDGGOBGSA-N 0.000 description 2
FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
229910052731 fluorine Inorganic materials 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
239000011521 glass Substances 0.000 description 2
239000008103 glucose Substances 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
150000002367 halogens Chemical class 0.000 description 2
238000002513 implantation Methods 0.000 description 2
UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
JIKUXBYRTXDNIY-UHFFFAOYSA-N n-methyl-n-phenylformamide Chemical compound O=CN(C)C1=CC=CC=C1 JIKUXBYRTXDNIY-UHFFFAOYSA-N 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
239000011591 potassium Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
229940069328 povidone Drugs 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
239000000651 prodrug Substances 0.000 description 2
229940002612 prodrug Drugs 0.000 description 2
239000003380 propellant Substances 0.000 description 2
102000005962 receptors Human genes 0.000 description 2
108020003175 receptors Proteins 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
238000010898 silica gel chromatography Methods 0.000 description 2
239000012453 solvate Substances 0.000 description 2
125000001424 substituent group Chemical group 0.000 description 2
239000000375 suspending agent Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
239000006188 syrup Substances 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
238000005809 transesterification reaction Methods 0.000 description 2
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 2
SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
ONGVVYOIHPXURB-UHFFFAOYSA-N (2-amino-2-oxoethyl)-[2-(4-ethoxyphenyl)phenyl]-diphenylphosphanium chloride Chemical compound [Cl-].C(C)OC1=CC=C(C=C1)C1=C(C=CC=C1)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)CC(=O)N ONGVVYOIHPXURB-UHFFFAOYSA-N 0.000 description 1
LORJLEXVRAHTFL-UHFFFAOYSA-N (2-anilino-2-oxoethyl)-triphenylphosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1NC(=O)C[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 LORJLEXVRAHTFL-UHFFFAOYSA-N 0.000 description 1
LDDMACCNBZAMSG-BDVNFPICSA-N (2r,3r,4s,5r)-3,4,5,6-tetrahydroxy-2-(methylamino)hexanal Chemical compound CN[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO LDDMACCNBZAMSG-BDVNFPICSA-N 0.000 description 1
BDXZOJVMTJOAPS-UHFFFAOYSA-N (3,5-dichlorophenyl)hydrazine;hydron;chloride Chemical compound Cl.NNC1=CC(Cl)=CC(Cl)=C1 BDXZOJVMTJOAPS-UHFFFAOYSA-N 0.000 description 1
RMHGCKSCDKUSLM-UHFFFAOYSA-N (5z)-5-diazo-2,3,4,4a,6,7,8,9-octahydrobenzo[7]annulene Chemical compound [N-]=[N+]=C1CCCCC2=CCCCC12 RMHGCKSCDKUSLM-UHFFFAOYSA-N 0.000 description 1
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 1
ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
SKDFWEPBABSFMG-UHFFFAOYSA-N 1,2-dichloro-1,1-difluoroethane Chemical compound FC(F)(Cl)CCl SKDFWEPBABSFMG-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
HDROJQNEUPUFCP-UHFFFAOYSA-N 1-chloroethyl cyclohexanecarboxylate Chemical compound CC(Cl)OC(=O)C1CCCCC1 HDROJQNEUPUFCP-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
KKFDCBRMNNSAAW-UHFFFAOYSA-N 2-(morpholin-4-yl)ethanol Chemical compound OCCN1CCOCC1 KKFDCBRMNNSAAW-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
CDYKOUYRAOOTCV-UHFFFAOYSA-N 3,4-dichloro-1h-indole-2-carboxylic acid Chemical compound C1=CC(Cl)=C2C(Cl)=C(C(=O)O)NC2=C1 CDYKOUYRAOOTCV-UHFFFAOYSA-N 0.000 description 1
SKRBFNVEUNPJQQ-UHFFFAOYSA-N 3-(2-bromoethynyl)-4,6-dichloro-1-(2-trimethylsilylethoxymethyl)indole-2-carboxylic acid Chemical compound C1=C(Cl)C=C2N(COCC[Si](C)(C)C)C(C(O)=O)=C(C#CBr)C2=C1Cl SKRBFNVEUNPJQQ-UHFFFAOYSA-N 0.000 description 1
QTLWFRINMXAUQZ-UHFFFAOYSA-N 3-(3-anilino-2-methyl-3-oxoprop-1-enyl)-4,6-dichloro-1h-indole-2-carboxylic acid Chemical compound OC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1C=C(C)C(=O)NC1=CC=CC=C1 QTLWFRINMXAUQZ-UHFFFAOYSA-N 0.000 description 1
ZIQJQHZHAGWXCU-AATRIKPKSA-N 4,6-dichloro-3-[(e)-3-(2-nitroanilino)-3-oxoprop-1-enyl]-1h-indole-2-carboxylic acid Chemical compound OC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1\C=C\C(=O)NC1=CC=CC=C1[N+]([O-])=O ZIQJQHZHAGWXCU-AATRIKPKSA-N 0.000 description 1
UGKRSAAXXZPTLK-VOTSOKGWSA-N 4,6-dichloro-3-[(e)-3-oxo-3-[n-(trifluoromethyl)anilino]prop-1-enyl]-1h-indole-2-carboxylic acid Chemical compound OC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1\C=C\C(=O)N(C(F)(F)F)C1=CC=CC=C1 UGKRSAAXXZPTLK-VOTSOKGWSA-N 0.000 description 1
WQVZUMRYVXXYQS-UHFFFAOYSA-N 4,6-dichloro-3-[3-(3,4-dimethoxyanilino)-3-oxoprop-1-enyl]-1h-indole-2-carboxylic acid Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)C=CC1=C(C(O)=O)NC2=CC(Cl)=CC(Cl)=C12 WQVZUMRYVXXYQS-UHFFFAOYSA-N 0.000 description 1
OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 1
125000006163 5-membered heteroaryl group Chemical group 0.000 description 1
125000006164 6-membered heteroaryl group Chemical group 0.000 description 1
206010053164 Alcohol withdrawal syndrome Diseases 0.000 description 1
235000019489 Almond oil Nutrition 0.000 description 1
208000024827 Alzheimer disease Diseases 0.000 description 1
206010002660 Anoxia Diseases 0.000 description 1
241000976983 Anoxia Species 0.000 description 1
208000019901 Anxiety disease Diseases 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
206010003497 Asphyxia Diseases 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
206010005052 Bladder irritation Diseases 0.000 description 1
201000006474 Brain Ischemia Diseases 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
ISTHXAQULGVNRC-UHFFFAOYSA-N C(C)C=1C(=C2C(=C(N(C2=CC1Cl)COCC[Si](C)(C)C)C(=O)O)C=O)Cl Chemical compound C(C)C=1C(=C2C(=C(N(C2=CC1Cl)COCC[Si](C)(C)C)C(=O)O)C=O)Cl ISTHXAQULGVNRC-UHFFFAOYSA-N 0.000 description 1
QEEMFNCVGFLSRZ-OUKQBFOZSA-N C1(CCCCC1)OC(=O)OC(C)OC(=O)C=1NC2=CC(=CC(=C2C=1\C=C\C(=O)NC1=CC=CC=C1)Cl)Cl Chemical compound C1(CCCCC1)OC(=O)OC(C)OC(=O)C=1NC2=CC(=CC(=C2C=1\C=C\C(=O)NC1=CC=CC=C1)Cl)Cl QEEMFNCVGFLSRZ-OUKQBFOZSA-N 0.000 description 1
OCAMNVOOTVBZEG-MDZDMXLPSA-N CC(C)(C)C(=O)OCOC(=O)C1=C(C2=C(N1)C=C(C=C2Cl)Cl)/C=C/C(=O)NC3=CC=CC=C3 Chemical compound CC(C)(C)C(=O)OCOC(=O)C1=C(C2=C(N1)C=C(C=C2Cl)Cl)/C=C/C(=O)NC3=CC=CC=C3 OCAMNVOOTVBZEG-MDZDMXLPSA-N 0.000 description 1
HHSOTDRZNPJVLS-ZHACJKMWSA-N CCN(CC)CCOC(=O)C1=C(C2=C(N1)C=C(C=C2Cl)Cl)/C=C/C(=O)NC3=CC=CC=C3 Chemical compound CCN(CC)CCOC(=O)C1=C(C2=C(N1)C=C(C=C2Cl)Cl)/C=C/C(=O)NC3=CC=CC=C3 HHSOTDRZNPJVLS-ZHACJKMWSA-N 0.000 description 1
DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
206010008120 Cerebral ischaemia Diseases 0.000 description 1
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
208000034656 Contusions Diseases 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
239000004338 Dichlorodifluoromethane Substances 0.000 description 1
206010013654 Drug abuse Diseases 0.000 description 1
XXRCUYVCPSWGCC-UHFFFAOYSA-N Ethyl pyruvate Chemical compound CCOC(=O)C(C)=O XXRCUYVCPSWGCC-UHFFFAOYSA-N 0.000 description 1
KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
208000010496 Heart Arrest Diseases 0.000 description 1
208000016988 Hemorrhagic Stroke Diseases 0.000 description 1
208000023105 Huntington disease Diseases 0.000 description 1
239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
208000013016 Hypoglycemia Diseases 0.000 description 1
VLSMHEGGTFMBBZ-OOZYFLPDSA-M Kainate Chemical compound CC(=C)[C@H]1C[NH2+][C@H](C([O-])=O)[C@H]1CC([O-])=O VLSMHEGGTFMBBZ-OOZYFLPDSA-M 0.000 description 1
102000000079 Kainic Acid Receptors Human genes 0.000 description 1
108010069902 Kainic Acid Receptors Proteins 0.000 description 1
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
229920000715 Mucilage Polymers 0.000 description 1
208000005314 Multi-Infarct Dementia Diseases 0.000 description 1
208000000693 Neurogenic Urinary Bladder Diseases 0.000 description 1
206010029279 Neurogenic bladder Diseases 0.000 description 1
208000026251 Opioid-Related disease Diseases 0.000 description 1
208000002193 Pain Diseases 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
241000700159 Rattus Species 0.000 description 1
XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
208000006011 Stroke Diseases 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
201000004810 Vascular dementia Diseases 0.000 description 1
HYIHBOPYOYYNOA-UHFFFAOYSA-N [2-oxo-2-[4-(trifluoromethyl)anilino]ethyl]-triphenylphosphanium;chloride Chemical compound [Cl-].C1=CC(C(F)(F)F)=CC=C1NC(=O)C[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 HYIHBOPYOYYNOA-UHFFFAOYSA-N 0.000 description 1
AXJQPRYNEQDOTB-UHFFFAOYSA-N [Cl-].C(C)(C)C1=C(C=CC=C1)C=1C(=C(C=CC1)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)CC1=CC=CC=C1)C(N)=O Chemical compound [Cl-].C(C)(C)C1=C(C=CC=C1)C=1C(=C(C=CC1)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)CC1=CC=CC=C1)C(N)=O AXJQPRYNEQDOTB-UHFFFAOYSA-N 0.000 description 1
MQRBDWPSKAXQEI-UHFFFAOYSA-N [Cl-].CC1=C(C=CC(=C1)OC)C1=C(C=CC=C1)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)CC(=O)N Chemical compound [Cl-].CC1=C(C=CC(=C1)OC)C1=C(C=CC=C1)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)CC(=O)N MQRBDWPSKAXQEI-UHFFFAOYSA-N 0.000 description 1
JCFLSBXJDBJIRT-UHFFFAOYSA-N [Cl-].COC=1C=C(C=CC=1OC)C1=C(C=CC=C1)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)CC(=O)N Chemical compound [Cl-].COC=1C=C(C=CC=1OC)C1=C(C=CC=C1)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)CC(=O)N JCFLSBXJDBJIRT-UHFFFAOYSA-N 0.000 description 1
XMCPDPBAWMMJDN-UHFFFAOYSA-N [Cl-].FC1=C(C=CC(=C1)F)C1=C(C=CC=C1)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)CC(=O)N Chemical compound [Cl-].FC1=C(C=CC(=C1)F)C1=C(C=CC=C1)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)CC(=O)N XMCPDPBAWMMJDN-UHFFFAOYSA-N 0.000 description 1
RSKUGYLHCWCIGK-UHFFFAOYSA-N [Cl-].FC1=C(C=CC(=C1)[N+](=O)[O-])C1=C(C=CC=C1)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)CC(=O)N Chemical compound [Cl-].FC1=C(C=CC(=C1)[N+](=O)[O-])C1=C(C=CC=C1)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)CC(=O)N RSKUGYLHCWCIGK-UHFFFAOYSA-N 0.000 description 1
NPRFBDVRXCNWRF-UHFFFAOYSA-N [Cl-].OC1=C(C=CC=C1)C1=C(C=CC=C1)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)CC(=O)N Chemical compound [Cl-].OC1=C(C=CC=C1)C1=C(C=CC=C1)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)CC(=O)N NPRFBDVRXCNWRF-UHFFFAOYSA-N 0.000 description 1
PSJPZKUAOHLLQG-UHFFFAOYSA-N [Cl-].[N+](=O)([O-])C1=C(C=CC=C1)C1=C(C=CC=C1)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)CC(N)=O Chemical compound [Cl-].[N+](=O)([O-])C1=C(C=CC=C1)C1=C(C=CC=C1)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)CC(N)=O PSJPZKUAOHLLQG-UHFFFAOYSA-N 0.000 description 1
239000013543 active substance Substances 0.000 description 1
125000005042 acyloxymethyl group Chemical group 0.000 description 1
239000000654 additive Substances 0.000 description 1
239000000853 adhesive Substances 0.000 description 1
208000029650 alcohol withdrawal Diseases 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
150000001345 alkine derivatives Chemical class 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
125000003282 alkyl amino group Chemical group 0.000 description 1
239000008168 almond oil Substances 0.000 description 1
CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
229940063655 aluminum stearate Drugs 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
230000007953 anoxia Effects 0.000 description 1
230000036506 anxiety Effects 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
210000001367 artery Anatomy 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
125000005002 aryl methyl group Chemical group 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
229940049706 benzodiazepine Drugs 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
125000002843 carboxylic acid group Chemical group 0.000 description 1
239000008112 carboxymethyl-cellulose Substances 0.000 description 1
235000010980 cellulose Nutrition 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
208000015114 central nervous system disease Diseases 0.000 description 1
206010008118 cerebral infarction Diseases 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 1
VVSOPDGZIBGWJL-UHFFFAOYSA-N chloromethoxymethyl(trimethyl)silane Chemical compound C[Si](C)(C)COCCl VVSOPDGZIBGWJL-UHFFFAOYSA-N 0.000 description 1
GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
238000000576 coating method Methods 0.000 description 1
229960003920 cocaine Drugs 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
239000003240 coconut oil Substances 0.000 description 1
235000019864 coconut oil Nutrition 0.000 description 1
230000036461 convulsion Effects 0.000 description 1
230000002920 convulsive effect Effects 0.000 description 1
239000013256 coordination polymer Substances 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
239000013058 crude material Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
239000003405 delayed action preparation Substances 0.000 description 1
230000002939 deleterious effect Effects 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
125000005265 dialkylamine group Chemical group 0.000 description 1
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
238000007865 diluting Methods 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
LFPLOYLKHHNDLO-UHFFFAOYSA-N disodium;trimethylsilylazanide Chemical compound [Na+].[Na+].C[Si](C)(C)[NH-].C[Si](C)(C)[NH-] LFPLOYLKHHNDLO-UHFFFAOYSA-N 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
206010013663 drug dependence Diseases 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000008157 edible vegetable oil Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
SEACYXSIPDVVMV-UHFFFAOYSA-L eosin Y Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 SEACYXSIPDVVMV-UHFFFAOYSA-L 0.000 description 1
206010015037 epilepsy Diseases 0.000 description 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
YLAHLUPONQVSOT-UHFFFAOYSA-N ethyl 4,6-dichloro-1h-indole-2-carboxylate Chemical compound C1=C(Cl)C=C2NC(C(=O)OCC)=CC2=C1Cl YLAHLUPONQVSOT-UHFFFAOYSA-N 0.000 description 1
KKLOZNWEUDCOFR-UHFFFAOYSA-N ethyl 4,6-dichloro-3-(2,2-dibromoethenyl)-1-[ethoxy(trimethylsilyl)methyl]indole-2-carboxylate Chemical compound C1=C(Cl)C=C2N(C(OCC)[Si](C)(C)C)C(C(=O)OCC)=C(C=C(Br)Br)C2=C1Cl KKLOZNWEUDCOFR-UHFFFAOYSA-N 0.000 description 1
IMBDRULRCQBFDB-BQYQJAHWSA-N ethyl 4,6-dichloro-3-[(e)-3-(2-nitroanilino)-3-oxoprop-1-enyl]-1h-indole-2-carboxylate Chemical compound CCOC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1\C=C\C(=O)NC1=CC=CC=C1[N+]([O-])=O IMBDRULRCQBFDB-BQYQJAHWSA-N 0.000 description 1
QJFKMZYJGJBPNS-SOFGYWHQSA-N ethyl 4,6-dichloro-3-[(e)-3-(3,4-dimethoxyanilino)-3-oxoprop-1-enyl]-1h-indole-2-carboxylate Chemical compound CCOC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1\C=C\C(=O)NC1=CC=C(OC)C(OC)=C1 QJFKMZYJGJBPNS-SOFGYWHQSA-N 0.000 description 1
VUKWFXAZLUCXPN-MDZDMXLPSA-N ethyl 4,6-dichloro-3-[(e)-3-(4-ethoxyanilino)-3-oxoprop-1-enyl]-1h-indole-2-carboxylate Chemical compound CCOC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1\C=C\C(=O)NC1=CC=C(OCC)C=C1 VUKWFXAZLUCXPN-MDZDMXLPSA-N 0.000 description 1
KPWPSLWVUFHVFZ-SOFGYWHQSA-N ethyl 4,6-dichloro-3-[(e)-3-(4-methoxy-2-methylanilino)-3-oxoprop-1-enyl]-1h-indole-2-carboxylate Chemical compound CCOC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1\C=C\C(=O)NC1=CC=C(OC)C=C1C KPWPSLWVUFHVFZ-SOFGYWHQSA-N 0.000 description 1
NFILHPVBZNKVNP-UHFFFAOYSA-N ethyl 4,6-dichloro-3-formyl-1h-indole-2-carboxylate Chemical compound ClC1=CC(Cl)=C2C(C=O)=C(C(=O)OCC)NC2=C1 NFILHPVBZNKVNP-UHFFFAOYSA-N 0.000 description 1
229960003750 ethyl chloride Drugs 0.000 description 1
PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
229940117360 ethyl pyruvate Drugs 0.000 description 1
239000000284 extract Substances 0.000 description 1
239000003925 fat Substances 0.000 description 1
235000019197 fats Nutrition 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
239000000945 filler Substances 0.000 description 1
239000010419 fine particle Substances 0.000 description 1
ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
239000000499 gel Substances 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
238000007429 general method Methods 0.000 description 1
208000015362 glutaric aciduria Diseases 0.000 description 1
125000005456 glyceride group Chemical group 0.000 description 1
239000008187 granular material Substances 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
125000001072 heteroaryl group Chemical group 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
239000003906 humectant Substances 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
230000002218 hypoglycaemic effect Effects 0.000 description 1
230000007954 hypoxia Effects 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
238000001802 infusion Methods 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
QWXYZCJEXYQNEI-OSZHWHEXSA-N intermediate I Chemical compound COC(=O)[C@@]1(C=O)[C@H]2CC=[N+](C\C2=C\C)CCc2c1[nH]c1ccccc21 QWXYZCJEXYQNEI-OSZHWHEXSA-N 0.000 description 1
208000020658 intracerebral hemorrhage Diseases 0.000 description 1
208000001286 intracranial vasospasm Diseases 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
230000001057 ionotropic effect Effects 0.000 description 1
208000028867 ischemia Diseases 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
239000012948 isocyanate Substances 0.000 description 1
239000010410 layer Substances 0.000 description 1
229910000464 lead oxide Inorganic materials 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
210000001259 mesencephalon Anatomy 0.000 description 1
QABLOFMHHSOFRJ-UHFFFAOYSA-N methyl 2-chloroacetate Chemical compound COC(=O)CCl QABLOFMHHSOFRJ-UHFFFAOYSA-N 0.000 description 1
OHKAPCLENKAVMN-UHFFFAOYSA-N methyl 3-(3-anilino-3-oxoprop-1-ynyl)-4,6-dichloro-1h-indole-2-carboxylate Chemical compound COC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1C#CC(=O)NC1=CC=CC=C1 OHKAPCLENKAVMN-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
GTWJETSWSUWSEJ-UHFFFAOYSA-N n-benzylaniline Chemical compound C=1C=CC=CC=1CNC1=CC=CC=C1 GTWJETSWSUWSEJ-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000000324 neuroprotective effect Effects 0.000 description 1
229960002715 nicotine Drugs 0.000 description 1
SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
125000006502 nitrobenzyl group Chemical group 0.000 description 1
231100000957 no side effect Toxicity 0.000 description 1
239000002687 nonaqueous vehicle Substances 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
201000000988 opioid abuse Diseases 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
YEXPOXQUZXUXJW-UHFFFAOYSA-N oxolead Chemical compound [Pb]=O YEXPOXQUZXUXJW-UHFFFAOYSA-N 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
230000036407 pain Effects 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
230000009984 peri-natal effect Effects 0.000 description 1
DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
229950010765 pivalate Drugs 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
239000003880 polar aprotic solvent Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920000137 polyphosphoric acid Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
230000002265 prevention Effects 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
LZFIOSVZIQOVFW-UHFFFAOYSA-N propyl 2-hydroxybenzoate Chemical class CCCOC(=O)C1=CC=CC=C1O LZFIOSVZIQOVFW-UHFFFAOYSA-N 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
SVOOVMQUISJERI-UHFFFAOYSA-K rhodium(3+);triacetate Chemical compound [Rh+3].CC([O-])=O.CC([O-])=O.CC([O-])=O SVOOVMQUISJERI-UHFFFAOYSA-K 0.000 description 1
201000000980 schizophrenia Diseases 0.000 description 1
229910052710 silicon Inorganic materials 0.000 description 1
239000010703 silicon Substances 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
235000020374 simple syrup Nutrition 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
239000008109 sodium starch glycolate Substances 0.000 description 1
229940079832 sodium starch glycolate Drugs 0.000 description 1
229920003109 sodium starch glycolate Polymers 0.000 description 1
239000001593 sorbitan monooleate Substances 0.000 description 1
235000011069 sorbitan monooleate Nutrition 0.000 description 1
229940035049 sorbitan monooleate Drugs 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
239000007858 starting material Substances 0.000 description 1
208000005809 status epilepticus Diseases 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
208000011117 substance-related disease Diseases 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000011593 sulfur Chemical group 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000002511 suppository base Substances 0.000 description 1
230000008961 swelling Effects 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
238000011287 therapeutic dose Methods 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
229940029284 trichlorofluoromethane Drugs 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
238000001665 trituration Methods 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
239000008215 water for injection Substances 0.000 description 1

Classifications

- 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
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Psychiatry (AREA)
Hospice & Palliative Care (AREA)
Addiction (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Indole Compounds (AREA)

SK1241-94A 1992-04-16 1993-04-15 Deriváty kyseliny indol-2-karboxylovej, ich použitie, spôsob ich prípravy a farmaceutický prípravok s ich obsahom SK281941B6 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB929208492A GB9208492D0 (en)	1992-04-16	1992-04-16	Heterocyclic compounds
PCT/EP1993/000938 WO1993021153A1 (en)	1992-04-16	1993-04-15	Indole-2-carboxylic acid derivatives

Publications (2)

Publication Number	Publication Date
SK124194A3 SK124194A3 (en)	1995-05-10
SK281941B6 true SK281941B6 (sk)	2001-09-11

Family

ID=10714220

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1241-94A SK281941B6 (sk)	1992-04-16	1993-04-15	Deriváty kyseliny indol-2-karboxylovej, ich použitie, spôsob ich prípravy a farmaceutický prípravok s ich obsahom

Country Status (41)

Country	Link
US (4)	US5374649A (pt)
EP (1)	EP0568136A1 (pt)
JP (2)	JPH07505407A (pt)
KR (1)	KR100264114B1 (pt)
CN (1)	CN1042331C (pt)
AP (1)	AP480A (pt)
AT (1)	AT403917B (pt)
AU (1)	AU666927B2 (pt)
BE (1)	BE1006343A5 (pt)
BG (1)	BG62136B1 (pt)
BR (1)	BR1100323A (pt)
CA (3)	CA2094075A1 (pt)
CH (1)	CH685630A5 (pt)
CY (1)	CY2038B1 (pt)
CZ (1)	CZ285799B6 (pt)
DK (1)	DK169890B1 (pt)
ES (1)	ES2105924B1 (pt)
FI (1)	FI106198B (pt)
FR (1)	FR2690919B1 (pt)
GB (2)	GB9208492D0 (pt)
GE (1)	GEP19991704B (pt)
GR (1)	GR1001619B (pt)
HK (1)	HK95797A (pt)
HU (2)	HU217964B (pt)
IL (1)	IL105412A (pt)
IS (1)	IS3994A (pt)
IT (1)	IT1265325B1 (pt)
LU (1)	LU88248A1 (pt)
MX (1)	MX9302195A (pt)
MY (1)	MY112232A (pt)
NO (1)	NO301879B1 (pt)
NZ (1)	NZ247413A (pt)
OA (1)	OA10103A (pt)
PL (1)	PL176451B1 (pt)
RO (1)	RO113242B1 (pt)
RU (1)	RU2129544C1 (pt)
SE (1)	SE504336C2 (pt)
SK (1)	SK281941B6 (pt)
TW (1)	TW224457B (pt)
WO (1)	WO1993021153A1 (pt)
ZA (1)	ZA932642B (pt)

Families Citing this family (41)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9304500D0 (en) *	1993-03-05	1993-04-21	Glaxo Spa	Heterocyclic compounds
KR100314482B1 (ko) *	1993-05-27	2002-02-28	메렐 파마슈티칼스 인크.	3-(인돌-3-일)프로페노산유도체
US5519048A (en) *	1993-05-27	1996-05-21	Merrell Pharmaceuticals Inc.	3-(indol-3-yl)-propenoic acid derivatives and pharmaceutical compositions thereof
GB9319243D0 (en) *	1993-09-17	1993-11-03	Glaxo Spa	Heterocyclic compounds
GB9321221D0 (en) *	1993-10-14	1993-12-01	Glaxo Spa	Heterocyclic compounds
TW280819B (pt) *	1993-11-17	1996-07-11	Sumitomo Pharma
US5563157B1 (en)	1994-10-31	1999-02-02	Hoecst Marion Roussel Inc	Heterocycle substituted propenoic acid derivatives and pharmaceutical compositions thereof
GB9502695D0 (en) *	1995-02-11	1995-03-29	Glaxo Spa	Pharmaceutical composition
GB9504361D0 (en) *	1995-03-04	1995-04-26	Glaxo Spa	Heterocyclic compounds
US6030968A (en) *	1996-09-17	2000-02-29	The Regents Of The University Of California	Positive AMPA receptor modulation to enhance brain neurotrophic factor expression
DE69734594T2 (de) *	1996-09-30	2006-07-06	Aventis Pharmaceuticals Inc.	Nmda (n-methyl-d-aspartate) antagonists
US5922752A (en) *	1997-06-11	1999-07-13	Hoechst Marion Roussell, Inc.	NMDA (n-methyl-d-aspartate) antagonists
KR100440553B1 (ko) *	1998-03-26	2004-07-15	후지사와 야꾸힝 고교 가부시키가이샤	서방성 제제
WO2003039540A2 (en) *	2001-11-09	2003-05-15	Sepracor Inc.	D-amino acid oxidase inhibitors for learning and memory
US7582657B2 (en) *	2001-12-10	2009-09-01	Amgen Inc.	Vanilloid receptor ligands and their use in treatments
PA8579701A1 (es) *	2002-08-23	2005-05-24	Pfizer Prod Inc	Profarmaco inhibidor de beta-lactamasa
DE10306202A1 (de) *	2003-02-13	2004-08-26	Grünenthal GmbH	Arzneimittel enthaltend substituierte 2-Aryl-Aminoessigsäure-Verbindungen und/oder substituierte 2-Heteroaryl-Aminoessigsäure-Verbindungen
EP1636240A1 (en) *	2003-06-05	2006-03-22	Pfizer Products Inc.	Beta-lactamase inhibitor prodrug
JP4864719B2 (ja) *	2003-11-26	2012-02-01	ファイザー・プロダクツ・インク	Ｇｓｋ−３インヒビターとしてのアミノピラゾール誘導体
US7488747B2 (en) *	2003-12-29	2009-02-10	Sepracor Inc.	Pyrrole and pyrazole DAAO inhibitors
US20060002999A1 (en) *	2004-06-17	2006-01-05	Forest Laboratories, Inc.	Immediate release formulations of 1-aminocyclohexane compounds, memantine and neramexane
EP1904066B1 (en)	2005-07-06	2018-05-23	Sunovion Pharmaceuticals Inc.	COMBINATIONS OF ESZOPICLONE AND TRANS 4-(3,4-DICHLOROPHENYL)-1,2,3,4-TETRAHYDRO-N-METHYL-1-NAPTHALENAMINE OR TRANS 4-(3,4-DICHLOROPHENYL)-1,2,3,4-TETRAHYDRO-1-NAPTHALENAMINE, for treating MENOPAUSE, perimenopause AND COGNITIVE DISORDERS
CA2636275C (en)	2006-01-06	2013-02-12	Sepracor Inc.	Tetralone-based monoamine reuptake inhibitors
CN101394847B (zh)	2006-01-06	2017-05-24	塞普拉柯公司	作为单胺重摄取抑制剂的环烷基胺类
JP5377285B2 (ja)	2006-03-31	2013-12-25	サノビオンファーマシューティカルズインク	キラルアミドおよびキラルアミンの調製
US7884124B2 (en) *	2006-06-30	2011-02-08	Sepracor Inc.	Fluoro-substituted inhibitors of D-amino acid oxidase
US7579370B2 (en) *	2006-06-30	2009-08-25	Sepracor Inc.	Fused heterocycles
US20080082066A1 (en) *	2006-10-02	2008-04-03	Weyerhaeuser Co.	Crosslinked carboxyalkyl cellulose fibers having non-permanent and temporary crosslinks
EP1942104A1 (en)	2006-12-20	2008-07-09	sanofi-aventis	Heteroarylcyclopropanecarboxamides and their use as pharmaceuticals
MX2009007410A (es) *	2007-01-18	2009-09-09	Sepracor Inc	Inhibidores de d-aminoacido oxidasa.
US7902252B2 (en) *	2007-01-18	2011-03-08	Sepracor, Inc.	Inhibitors of D-amino acid oxidase
CN103936605B (zh)	2007-05-31	2017-09-01	赛诺维信制药公司	苯基取代的环烷胺作为一元胺再摄取抑制剂
US20090247644A1 (en) *	2008-03-28	2009-10-01	Forest Laboratories Holdings Limited	Memantine formulations
US20100120740A1 (en) *	2008-08-07	2010-05-13	Sepracor Inc.	Prodrugs of fused heterocyclic inhibitors of d-amino acid oxidase
US20110319463A1 (en) *	2009-03-10	2011-12-29	Saten Pharamaceuticals Co., Ltd.	Preventive or therapeutic agents for optic nerve disorders comprising 4,6-dichloro-1h-indole-2-carboxylic acid derivatives or salts thereof as active ingredients
US20110034434A1 (en) *	2009-08-07	2011-02-10	Sepracor Inc.	Prodrugs of fused heterocyclic inhibitors of d-amino acid oxidase
US9737531B2 (en)	2012-07-12	2017-08-22	Glytech, Llc	Composition and method for treatment of depression and psychosis in humans
IL248567B (en)	2014-04-30	2022-08-01	Univ Nat Taiwan	Use of known compounds as d-amino acid oxidase inhibitors
IL307576B1 (en)	2016-09-14	2025-02-01	Yufeng Jane Tseng	History of new modified benzimidazoles as D-amino acid oxidase (DAAO) inhibitors
JP7305560B2 (ja)	2017-06-12	2023-07-10	グリテック，エルエルシー	Ｎｍｄａアンタゴニスト及びｄ２／５ｈｔ２ａ又は選択的５ｈｔ２ａアンタゴニストによるうつ病の治療
CN112707874A (zh) *	2020-12-29	2021-04-27	广东中科药物研究有限公司	一种抗病毒化合物及其制备方法

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3010971A (en) *	1960-08-04	1961-11-28	Smith Kline French Lab	Cyclopropylamine derivatives and processes for their preparation
DK500285A (da) *	1984-11-02	1986-05-03	Glaxo Group Ltd	Cephalosporinantibiotika
US4960786A (en) *	1989-04-24	1990-10-02	Merrell Dow Pharmaceuticals Inc.	Excitatory amino acid antagonists
JPH0347123A (ja) *	1989-05-05	1991-02-28	G D Searle & Co	インドール―２―カルボキシレート化合物類を含有するｃｎｓ疾患治療用組成物
KR0178469B1 (ko) *	1990-07-16	1999-03-20	메이나드 알. 존슨	흥분성 아미노산 길항제
US5284862A (en) *	1991-03-18	1994-02-08	Warner-Lambert Company	Derivatives of 2-carboxyindoles having pharmaceutical activity
US5145845A (en) *	1991-05-14	1992-09-08	Warner-Lambert Co.	Substituted 2-carboxylindoles having pharmaceutical activity

1992
- 1992-04-16 GB GB929208492A patent/GB9208492D0/en active Pending
1993
- 1993-04-14 ZA ZA932642A patent/ZA932642B/xx unknown
- 1993-04-15 GR GR930100154A patent/GR1001619B/el not_active IP Right Cessation
- 1993-04-15 CA CA002094075A patent/CA2094075A1/en not_active Abandoned
- 1993-04-15 MX MX9302195A patent/MX9302195A/es not_active IP Right Cessation
- 1993-04-15 KR KR1019940703668A patent/KR100264114B1/ko not_active IP Right Cessation
- 1993-04-15 SE SE9301241A patent/SE504336C2/sv not_active IP Right Cessation
- 1993-04-15 NZ NZ247413A patent/NZ247413A/en unknown
- 1993-04-15 IT IT93RM000236A patent/IT1265325B1/it active IP Right Grant
- 1993-04-15 FR FR9304452A patent/FR2690919B1/fr not_active Expired - Fee Related
- 1993-04-15 MY MYPI93000690A patent/MY112232A/en unknown
- 1993-04-15 US US08/047,430 patent/US5374649A/en not_active Expired - Fee Related
- 1993-04-15 HU HU9402975A patent/HU217964B/hu not_active IP Right Cessation
- 1993-04-15 LU LU88248A patent/LU88248A1/fr unknown
- 1993-04-15 ES ES09300771A patent/ES2105924B1/es not_active Expired - Lifetime
- 1993-04-15 RO RO94-01658A patent/RO113242B1/ro unknown
- 1993-04-15 SK SK1241-94A patent/SK281941B6/sk unknown
- 1993-04-15 IL IL105412A patent/IL105412A/en not_active IP Right Cessation
- 1993-04-15 WO PCT/EP1993/000938 patent/WO1993021153A1/en active IP Right Grant
- 1993-04-15 CN CN93105797A patent/CN1042331C/zh not_active Expired - Fee Related
- 1993-04-15 US US08/046,947 patent/US5373018A/en not_active Expired - Fee Related
- 1993-04-15 CA CA002094073A patent/CA2094073A1/en not_active Abandoned
- 1993-04-15 GB GB9307808A patent/GB2266091B/en not_active Expired - Fee Related
- 1993-04-15 BE BE9300371A patent/BE1006343A5/fr active
- 1993-04-15 DK DK043193A patent/DK169890B1/da active
- 1993-04-15 PL PL93305554A patent/PL176451B1/pl unknown
- 1993-04-15 JP JP5517997A patent/JPH07505407A/ja active Pending
- 1993-04-15 IS IS3994A patent/IS3994A/is unknown
- 1993-04-15 EP EP93201103A patent/EP0568136A1/en not_active Withdrawn
- 1993-04-15 RU RU94045915A patent/RU2129544C1/ru active
- 1993-04-15 AU AU36923/93A patent/AU666927B2/en not_active Ceased
- 1993-04-15 CH CH1133/93A patent/CH685630A5/fr not_active IP Right Cessation
- 1993-04-15 AT AT0075293A patent/AT403917B/de not_active IP Right Cessation
- 1993-04-15 US US08/047,429 patent/US5374648A/en not_active Expired - Fee Related
- 1993-04-15 JP JP5088844A patent/JPH0649027A/ja active Pending
- 1993-04-15 CA CA002094076A patent/CA2094076A1/en not_active Abandoned
- 1993-04-15 CZ CZ942543A patent/CZ285799B6/cs not_active IP Right Cessation
- 1993-04-16 GE GEAP19932602A patent/GEP19991704B/en unknown
- 1993-04-16 AP APAP/P/1993/000524A patent/AP480A/en active
- 1993-05-06 TW TW082103531A patent/TW224457B/zh active
1994
- 1994-10-10 OA OA60570A patent/OA10103A/en unknown
- 1994-10-12 FI FI944800A patent/FI106198B/fi active
- 1994-10-14 BG BG99111A patent/BG62136B1/bg unknown
- 1994-10-14 NO NO943913A patent/NO301879B1/no not_active IP Right Cessation
- 1994-12-08 US US08/351,762 patent/US5510367A/en not_active Expired - Fee Related
1995
- 1995-06-29 HU HU95P/P00538P patent/HU211826A9/hu unknown
1997
- 1997-04-22 BR BR1100323-5A patent/BR1100323A/pt active IP Right Grant
- 1997-06-26 HK HK95797A patent/HK95797A/xx not_active IP Right Cessation
1998
- 1998-04-30 CY CY9802038A patent/CY2038B1/xx unknown

Also Published As

Publication number	Publication date
CY2038B1 (en)	1998-04-30
AP480A (en)	1996-03-22
MY112232A (en)	2001-05-31
SE504336C2 (sv)	1997-01-13
CA2094073A1 (en)	1993-10-17
CN1042331C (zh)	1999-03-03
CZ254394A3 (en)	1995-07-12
TW224457B (pt)	1994-06-01
FI944800A0 (fi)	1994-10-12
NO943913L (no)	1994-12-14
AU666927B2 (en)	1996-02-29
US5510367A (en)	1996-04-23
JPH07505407A (ja)	1995-06-15
ATA75293A (de)	1997-11-15
CN1085212A (zh)	1994-04-13
CA2094075A1 (en)	1993-10-17
HUT70526A (en)	1995-10-30
NZ247413A (en)	1995-12-21
HU9402975D0 (en)	1995-02-28
GB2266091B (en)	1995-08-09
US5374648A (en)	1994-12-20
CA2094076A1 (en)	1993-10-17
ITRM930236A1 (it)	1994-10-15
AP9300524A0 (en)	1993-04-30
NO301879B1 (no)	1997-12-22
WO1993021153A1 (en)	1993-10-28
BG99111A (bg)	1995-05-31
OA10103A (en)	1996-12-18
HU217964B (hu)	2000-05-28
CH685630A5 (fr)	1995-08-31
DK43193A (da)	1993-10-17
IL105412A0 (en)	1993-08-18
DK169890B1 (da)	1995-03-27
DK43193D0 (da)	1993-04-15
HK95797A (en)	1997-08-08
RU2129544C1 (ru)	1999-04-27
IS3994A (is)	1993-10-17
GB9307808D0 (en)	1993-06-02
GEP19991704B (en)	1999-08-05
GB9208492D0 (en)	1992-06-03
GR1001619B (el)	1994-07-29
US5373018A (en)	1994-12-13
BR1100323A (pt)	2000-06-27
FI944800A (fi)	1994-10-12
BE1006343A5 (fr)	1994-07-26
NO943913D0 (no)	1994-10-14
PL176451B1 (pl)	1999-05-31
AU3692393A (en)	1993-10-21
EP0568136A1 (en)	1993-11-03
ITRM930236A0 (it)	1993-04-15
IL105412A (en)	1998-02-22
IT1265325B1 (it)	1996-10-31
SK124194A3 (en)	1995-05-10
BG62136B1 (bg)	1999-03-31
ES2105924A1 (es)	1997-10-16
FI106198B (fi)	2000-12-15
GB2266091A (en)	1993-10-20
FR2690919A1 (fr)	1993-11-12
LU88248A1 (fr)	1994-03-01
SE9301241D0 (sv)	1993-04-15
MX9302195A (es)	1994-03-31
KR100264114B1 (ko)	2000-11-01
ZA932642B (en)	1994-01-10
ES2105924B1 (es)	1998-07-01
SE9301241L (sv)	1993-10-17
US5374649A (en)	1994-12-20
FR2690919B1 (fr)	1995-05-05
RO113242B1 (ro)	1998-05-29
AT403917B (de)	1998-06-25
JPH0649027A (ja)	1994-02-22
CZ285799B6 (cs)	1999-11-17
RU94045915A (ru)	1996-09-10
HU211826A9 (en)	1995-12-28

Publication	Publication Date	Title
SK281941B6 (sk)	2001-09-11	Deriváty kyseliny indol-2-karboxylovej, ich použitie, spôsob ich prípravy a farmaceutický prípravok s ich obsahom
AU2009331179B2 (en)	2014-09-18	Novel bicyclic heterocyclic compound
AP877A (en)	2000-09-27	Tetrahydroquinoline derivatives as EAA antagonists.
US6372735B1 (en)	2002-04-16	Tricyclic triazolobenzazepine derivatives, process for producing the same, and antiallergic
SK44996A3 (en)	1997-01-08	Indole derivatives, manufacturing process thereof and pharmaceutical composition containing them
US5977136A (en)	1999-11-02	Tetrahydroquinolines as NMDA antagonists
KR19980702735A (ko)	1998-08-05	Ｅａａ 길항제로서의 인돌 유도체
JPS6396187A (ja)	1988-04-27	インドローピラジノーベンゾジアゼピン誘導体
CZ20002757A3 (cs)	2001-01-17	2.3.4.5-tetrahydro-lH/l,4/-benzodiazepin-3- hydroxamové kyseliny
CZ340599A3 (cs)	2000-03-15	Derivát kyseliny chinolin-2-karboxylové