AP574A - Indole derivatives. - Google Patents

Indole derivatives. Download PDF

Info

Publication number: AP574A
Authority: AP; ARIPO
Prior art keywords: solution; compound; dichloro; formula; oxo
Prior art date: 1993-10-14

Application number

APAP/P/1994/000685A

Other languages

English (en)

Other versions

AP9400685A0 (en

Inventor

Alfredo Cugola

Romano D-Fabio

Giorgio Pentassuglia

Original Assignee

Glaxo Spa

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.)

1993-10-14

Filing date

1994-10-12

Publication date

1997-01-30

1994-10-12 Application filed by Glaxo Spa filed Critical Glaxo Spa

1994-10-31 Publication of AP9400685A0 publication Critical patent/AP9400685A0/xx

1997-01-30 Application granted granted Critical

1997-01-30 Publication of AP574A publication Critical patent/AP574A/en

Links

150000002475 indoles Chemical class 0.000 title claims description 6
229940054051 antipsychotic indole derivative Drugs 0.000 title description 5
150000001875 compounds Chemical class 0.000 claims abstract description 215
-1 hydroxy, methoxy, amino Chemical group 0.000 claims description 73
238000006243 chemical reaction Methods 0.000 claims description 38
150000003839 salts Chemical class 0.000 claims description 38
150000002148 esters Chemical class 0.000 claims description 30
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
238000000034 method Methods 0.000 claims description 20
125000006239 protecting group Chemical group 0.000 claims description 19
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 12
238000011282 treatment Methods 0.000 claims description 12
125000000217 alkyl group Chemical group 0.000 claims description 11
125000003282 alkyl amino group Chemical group 0.000 claims description 9
HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 claims description 8
125000004663 dialkyl amino group Chemical group 0.000 claims description 8
238000002360 preparation method Methods 0.000 claims description 8
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 claims description 7
108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 claims description 7
125000000753 cycloalkyl group Chemical group 0.000 claims description 7
230000000694 effects Effects 0.000 claims description 7
125000000623 heterocyclic group Chemical group 0.000 claims description 7
HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 claims description 6
150000003950 cyclic amides Chemical class 0.000 claims description 6
239000003814 drug Substances 0.000 claims description 6
230000002461 excitatory amino acid Effects 0.000 claims description 6
239000003257 excitatory amino acid Substances 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 6
125000001072 heteroaryl group Chemical group 0.000 claims description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
102000005962 receptors Human genes 0.000 claims description 5
108020003175 receptors Proteins 0.000 claims description 5
DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 claims description 4
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 4
XLQOULKRIADZTN-FMIVXFBMSA-N 4,6-dichloro-3-[(e)-(2-oxo-1-phenylpiperidin-3-ylidene)methyl]-1h-indole-2-carboxylic acid Chemical compound OC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1\C=C(C1=O)/CCCN1C1=CC=CC=C1 XLQOULKRIADZTN-FMIVXFBMSA-N 0.000 claims description 4
125000003670 adamantan-2-yl group Chemical group [H]C1([H])C(C2([H])[H])([H])C([H])([H])C3([H])C([*])([H])C1([H])C([H])([H])C2([H])C3([H])[H] 0.000 claims description 4
125000001309 chloro group Chemical group Cl* 0.000 claims description 4
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
229910052736 halogen Inorganic materials 0.000 claims description 4
150000002367 halogens Chemical class 0.000 claims description 4
239000001257 hydrogen Substances 0.000 claims description 4
229910052739 hydrogen Inorganic materials 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
VBQCHPIMZGQLAZ-UHFFFAOYSA-N phosphorane Chemical class [PH5] VBQCHPIMZGQLAZ-UHFFFAOYSA-N 0.000 claims description 4
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
ZARBLYLWDMUUQC-ZSOIEALJSA-N 4,6-dichloro-3-[(z)-(2,5-dioxo-1-phenylimidazolidin-4-ylidene)methyl]-1h-indole-2-carboxylic acid Chemical compound OC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1\C=C(C1=O)/NC(=O)N1C1=CC=CC=C1 ZARBLYLWDMUUQC-ZSOIEALJSA-N 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 3
125000002619 bicyclic group Chemical group 0.000 claims description 3
239000000460 chlorine Substances 0.000 claims description 3
229910052801 chlorine Inorganic materials 0.000 claims description 3
125000004093 cyano group Chemical group *C#N 0.000 claims description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
238000002560 therapeutic procedure Methods 0.000 claims description 3
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 3
XJELZLGPIDHDLI-UXBLZVDNSA-N 4,6-dichloro-3-[(e)-(2,5-dioxo-1-phenylpyrrolidin-3-ylidene)methyl]-1h-indole-2-carboxylic acid Chemical compound OC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1\C=C(C1=O)/CC(=O)N1C1=CC=CC=C1 XJELZLGPIDHDLI-UXBLZVDNSA-N 0.000 claims description 2
101150047265 COR2 gene Proteins 0.000 claims description 2
101100467189 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) QCR2 gene Proteins 0.000 claims description 2
CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 claims description 2
150000002431 hydrogen Chemical group 0.000 claims description 2
230000001678 irradiating effect Effects 0.000 claims description 2
238000002955 isolation Methods 0.000 claims description 2
230000001225 therapeutic effect Effects 0.000 claims description 2
125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 3
150000002332 glycine derivatives Chemical class 0.000 claims 3
241000124008 Mammalia Species 0.000 claims 1
229940124597 therapeutic agent Drugs 0.000 claims 1
239000000243 solution Substances 0.000 description 192
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 177
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 169
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 148
239000000543 intermediate Substances 0.000 description 121
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 103
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 76
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 74
229940093499 ethyl acetate Drugs 0.000 description 59
235000019439 ethyl acetate Nutrition 0.000 description 59
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 55
229960004132 diethyl ether Drugs 0.000 description 55
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 54
239000000203 mixture Substances 0.000 description 47
239000007787 solid Substances 0.000 description 43
238000005160 1H NMR spectroscopy Methods 0.000 description 41
239000002904 solvent Substances 0.000 description 41
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 40
239000002253 acid Substances 0.000 description 36
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 32
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 32
239000011541 reaction mixture Substances 0.000 description 32
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 28
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 23
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 23
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 20
239000012074 organic phase Substances 0.000 description 18
239000012267 brine Substances 0.000 description 17
238000010898 silica gel chromatography Methods 0.000 description 17
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
229910000027 potassium carbonate Inorganic materials 0.000 description 16
238000001665 trituration Methods 0.000 description 16
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 15
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
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 15
239000000725 suspension Substances 0.000 description 15
150000001299 aldehydes Chemical class 0.000 description 14
235000019441 ethanol Nutrition 0.000 description 14
IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 14
229910052757 nitrogen Chemical group 0.000 description 13
235000019270 ammonium chloride Nutrition 0.000 description 12
239000002585 base Substances 0.000 description 12
FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 12
239000004480 active ingredient Substances 0.000 description 11
238000003818 flash chromatography Methods 0.000 description 11
239000006260 foam Substances 0.000 description 11
239000000047 product Substances 0.000 description 11
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
239000000843 powder Substances 0.000 description 10
INUNLMUAPJVRME-UHFFFAOYSA-N 3-chloropropanoyl chloride Chemical compound ClCCC(Cl)=O INUNLMUAPJVRME-UHFFFAOYSA-N 0.000 description 9
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
238000005481 NMR spectroscopy Methods 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
239000000741 silica gel Substances 0.000 description 9
229910002027 silica gel Inorganic materials 0.000 description 9
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 8
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
239000007864 aqueous solution Substances 0.000 description 8
150000001732 carboxylic acid derivatives Chemical class 0.000 description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
239000012044 organic layer Substances 0.000 description 8
238000010992 reflux Methods 0.000 description 8
QMGVPVSNSZLJIA-FVWCLLPLSA-N strychnine Chemical compound O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 QMGVPVSNSZLJIA-FVWCLLPLSA-N 0.000 description 8
239000003826 tablet Substances 0.000 description 8
238000001035 drying Methods 0.000 description 7
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
229910000041 hydrogen chloride Inorganic materials 0.000 description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
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
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
239000002775 capsule 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
229920006395 saturated elastomer Polymers 0.000 description 6
ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 6
239000004471 Glycine Substances 0.000 description 5
238000009472 formulation Methods 0.000 description 5
238000010438 heat treatment Methods 0.000 description 5
230000007062 hydrolysis Effects 0.000 description 5
238000006460 hydrolysis reaction Methods 0.000 description 5
229910052751 metal Inorganic materials 0.000 description 5
239000002184 metal Substances 0.000 description 5
239000003921 oil Substances 0.000 description 5
235000019198 oils Nutrition 0.000 description 5
150000003333 secondary alcohols Chemical class 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 4
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 4
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 4
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
241001279009 Strychnos toxifera Species 0.000 description 4
239000003513 alkali Substances 0.000 description 4
239000005557 antagonist Substances 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
230000006378 damage Effects 0.000 description 4
235000019253 formic acid Nutrition 0.000 description 4
229920000159 gelatin Polymers 0.000 description 4
235000019322 gelatine Nutrition 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
230000004770 neurodegeneration Effects 0.000 description 4
208000015122 neurodegenerative disease Diseases 0.000 description 4
230000003389 potentiating effect Effects 0.000 description 4
238000003756 stirring Methods 0.000 description 4
229960005453 strychnine Drugs 0.000 description 4
KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 4
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
206010010904 Convulsion Diseases 0.000 description 3
229920002785 Croscarmellose sodium Polymers 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
229920000168 Microcrystalline cellulose Polymers 0.000 description 3
241000699670 Mus sp. Species 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
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 3
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 3
125000005041 acyloxyalkyl group Chemical group 0.000 description 3
125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
125000004103 aminoalkyl group Chemical group 0.000 description 3
239000000010 aprotic solvent Substances 0.000 description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 3
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
229960001681 croscarmellose sodium Drugs 0.000 description 3
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 3
239000012043 crude product Substances 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
239000000839 emulsion Substances 0.000 description 3
238000001914 filtration Methods 0.000 description 3
239000008273 gelatin Substances 0.000 description 3
235000011852 gelatine desserts Nutrition 0.000 description 3
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229910052700 potassium Inorganic materials 0.000 description 1
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230000002335 preservative effect Effects 0.000 description 1
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MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
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WSZXVTUONBUSSM-UHFFFAOYSA-M sodium;1h-indole-2-carboxylate Chemical compound [Na+].C1=CC=C2NC(C(=O)[O-])=CC2=C1 WSZXVTUONBUSSM-UHFFFAOYSA-M 0.000 description 1
VTTXBAOGWURAIC-NBYYMMLRSA-M sodium;4,6-dichloro-3-[(e)-(2-oxo-1-phenylpiperidin-3-ylidene)methyl]-1h-indole-2-carboxylate Chemical compound [Na+].[O-]C(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1\C=C(C1=O)/CCCN1C1=CC=CC=C1 VTTXBAOGWURAIC-NBYYMMLRSA-M 0.000 description 1
QHGFBRVHKFAYAP-YGCVIUNWSA-M sodium;4,6-dichloro-3-[(e)-(2-oxo-1-phenylpyrrolidin-3-ylidene)methyl]-1h-indole-2-carboxylate Chemical compound [Na+].[O-]C(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1\C=C(C1=O)/CCN1C1=CC=CC=C1 QHGFBRVHKFAYAP-YGCVIUNWSA-M 0.000 description 1
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125000001424 substituent group Chemical group 0.000 description 1
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UOUFRTFWWBCVPV-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-1H-thieno[3,2-d]pyrimidin-3-yl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)n1c(=O)[nH]c2ccsc2c1=O UOUFRTFWWBCVPV-UHFFFAOYSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 1
238000010998 test method Methods 0.000 description 1
238000012360 testing method Methods 0.000 description 1
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
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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
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RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- 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

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

APAP/P/1994/000685A 1993-10-14 1994-10-12 Indole derivatives. AP574A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB939321221A GB9321221D0 (en)	1993-10-14	1993-10-14	Heterocyclic compounds

Publications (2)

Publication Number	Publication Date
AP9400685A0 AP9400685A0 (en)	1994-10-31
AP574A true AP574A (en)	1997-01-30

Family

ID=10743550

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
APAP/P/1994/000685A AP574A (en)	1993-10-14	1994-10-12	Indole derivatives.

Country Status (27)

Country	Link
US (3)	US5760059A (bg)
EP (1)	EP0723541A1 (bg)
JP (1)	JPH09503770A (bg)
CN (1)	CN1070490C (bg)
AP (1)	AP574A (bg)
AU (1)	AU681194B2 (bg)
BG (1)	BG61839B1 (bg)
CA (1)	CA2171449A1 (bg)
CO (1)	CO4290355A1 (bg)
CZ (1)	CZ92396A3 (bg)
FI (1)	FI961628A0 (bg)
GB (1)	GB9321221D0 (bg)
HU (1)	HU219710B (bg)
IL (1)	IL111294A (bg)
IS (1)	IS4219A (bg)
MY (1)	MY112411A (bg)
NO (1)	NO309861B1 (bg)
NZ (1)	NZ274179A (bg)
OA (1)	OA10578A (bg)
PE (1)	PE21995A1 (bg)
PL (1)	PL179568B1 (bg)
RU (1)	RU2144535C1 (bg)
SG (1)	SG49013A1 (bg)
SK (1)	SK44996A3 (bg)
TW (1)	TW283144B (bg)
WO (1)	WO1995010517A1 (bg)
ZA (1)	ZA947948B (bg)

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GB9704499D0 (en) *	1997-03-05	1997-04-23	Glaxo Wellcome Spa	Method of manufacture
AU3195600A (en) *	1999-03-23	2000-10-09	Sumitomo Pharmaceuticals Company, Limited	Tricyclic indole-2-carboxylic acid compound used as nmda receptor antagonist
RU2209041C2 (ru) *	2000-06-15	2003-07-27	Новосибирский научно-исследовательский институт травматологии и ортопедии	Способ лечения церебрального вазоспазма
DE10153346A1 (de)	2001-10-29	2004-04-22	Grünenthal GmbH	Substituierte Indole
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WO2007006003A2 (en)	2005-07-06	2007-01-11	Sepracor 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, and methods of treatment of menopause and mood, anxiety, and cognitive disorders
CA2631232A1 (en) *	2005-12-01	2007-06-07	F. Hoffmann-La Roche Ag	Novel vinylogous acids derivatives
KR101294014B1 (ko)	2006-01-06	2013-08-09	선오비온 파마슈티컬스 인코포레이티드	모노아민 재흡수 저해제로서의 시클로알킬아민
US8053603B2 (en) *	2006-01-06	2011-11-08	Sunovion Pharmaceuticals Inc.	Tetralone-based monoamine reuptake inhibitors
DK2816024T3 (en)	2006-03-31	2017-10-30	Sunovion Pharmaceuticals Inc	CHIRALE AMINER
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
US7902252B2 (en) *	2007-01-18	2011-03-08	Sepracor, Inc.	Inhibitors of D-amino acid oxidase
US20090099248A1 (en) *	2007-01-18	2009-04-16	Sepracor Inc.	Inhibitors of d-amino acid oxidase
MX2009012685A (es)	2007-05-31	2009-12-14	Sepracor Inc	Cicloalquilaminas sustituidas con fenilo como inhibidores de la reabsorcion de monoamina.
WO2010017418A1 (en) *	2008-08-07	2010-02-11	Sepracor Inc.	Prodrugs of fused heterocyclic inhibitors of d-amino acid oxidase
JP2010235597A (ja) *	2009-03-10	2010-10-21	Santen Pharmaceut Co Ltd	４，６−ジクロロ−１ｈ−インドール−２−カルボン酸誘導体又はその塩を有効成分として含有する視神経障害の予防又は治療剤
WO2011017634A2 (en) *	2009-08-07	2011-02-10	Sepracore Inc.	Prodrugs of fused heterocyclic inhibitors of d-amino acid oxidase
AU2012321345B2 (en)	2011-10-03	2016-03-17	The University Of Utah Research Foundation	Application of 5-HT6 receptor antagonists for the alleviation of cognitive deficits of down syndrome
SG10202102125SA (en)	2014-04-30	2021-04-29	Yufeng Tseng	Use of known compounds as d-amino acid oxidase inhibitors
EP4289425A3 (en)	2016-09-14	2024-08-07	Yufeng Jane Tseng	Novel substituted benzimidazole derivatives as d-amino acid oxidase (daao) inhibitors

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WO1992016205A2 (en) *	1991-03-18	1992-10-01	Warner-Lambert Company	Novel derivatives of 2-carboxyndoles having pharmaceutical activity
EP0587377A2 (en) *	1992-09-10	1994-03-16	Eli Lilly And Company	Thiazolidinone derivatives as hypoglycemic agents and for treating Alzheimer's disease

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EP0545478A1 (en) *	1991-12-03	1993-06-09	MERCK SHARP & DOHME LTD.	Heterocyclic compounds as tachykinin antagonists
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GB9321221D0 (en) *	1993-10-14	1993-12-01	Glaxo Spa	Heterocyclic compounds

1993
- 1993-10-14 GB GB939321221A patent/GB9321221D0/en active Pending
1994
- 1994-10-10 IS IS4219A patent/IS4219A/is unknown
- 1994-10-11 MY MYPI94002695A patent/MY112411A/en unknown
- 1994-10-12 EP EP94928893A patent/EP0723541A1/en not_active Withdrawn
- 1994-10-12 HU HU9600969A patent/HU219710B/hu not_active IP Right Cessation
- 1994-10-12 WO PCT/EP1994/003359 patent/WO1995010517A1/en not_active Ceased
- 1994-10-12 AU AU78133/94A patent/AU681194B2/en not_active Ceased
- 1994-10-12 SG SG1996005195A patent/SG49013A1/en unknown
- 1994-10-12 CA CA002171449A patent/CA2171449A1/en not_active Abandoned
- 1994-10-12 SK SK449-96A patent/SK44996A3/sk unknown
- 1994-10-12 CZ CZ96923A patent/CZ92396A3/cs unknown
- 1994-10-12 ZA ZA947948A patent/ZA947948B/xx unknown
- 1994-10-12 US US08/619,510 patent/US5760059A/en not_active Expired - Fee Related
- 1994-10-12 PL PL94313969A patent/PL179568B1/pl unknown
- 1994-10-12 NZ NZ274179A patent/NZ274179A/en unknown
- 1994-10-12 RU RU96108920A patent/RU2144535C1/ru active
- 1994-10-12 JP JP7511283A patent/JPH09503770A/ja active Pending
- 1994-10-12 PE PE1994252640A patent/PE21995A1/es not_active Application Discontinuation
- 1994-10-12 CN CN94193759A patent/CN1070490C/zh not_active Expired - Fee Related
- 1994-10-12 AP APAP/P/1994/000685A patent/AP574A/en active
- 1994-10-12 CO CO94046673A patent/CO4290355A1/es unknown
- 1994-10-13 IL IL11129494A patent/IL111294A/en not_active IP Right Cessation
- 1994-11-18 TW TW083110700A patent/TW283144B/zh active
1996
- 1996-04-09 OA OA60812A patent/OA10578A/en unknown
- 1996-04-12 FI FI961628A patent/FI961628A0/fi unknown
- 1996-04-12 NO NO961475A patent/NO309861B1/no not_active IP Right Cessation
- 1996-04-16 BG BG100511A patent/BG61839B1/bg unknown
1998
- 1998-05-29 US US09/086,522 patent/US5962496A/en not_active Expired - Lifetime
1999
- 1999-08-16 US US09/374,982 patent/US6100289A/en not_active Expired - Lifetime

Patent Citations (3)

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WO1992016205A2 (en) *	1991-03-18	1992-10-01	Warner-Lambert Company	Novel derivatives of 2-carboxyndoles having pharmaceutical activity
US5145845A (en) *	1991-05-14	1992-09-08	Warner-Lambert Co.	Substituted 2-carboxylindoles having pharmaceutical activity
EP0587377A2 (en) *	1992-09-10	1994-03-16	Eli Lilly And Company	Thiazolidinone derivatives as hypoglycemic agents and for treating Alzheimer's disease

Also Published As

Publication number	Publication date
IL111294A (en)	1998-12-06
AU7813394A (en)	1995-05-04
AP9400685A0 (en)	1994-10-31
IS4219A (is)	1995-04-15
CN1070490C (zh)	2001-09-05
NZ274179A (en)	1998-01-26
MY112411A (en)	2001-06-30
ZA947948B (en)	1995-05-23
EP0723541A1 (en)	1996-07-31
NO961475D0 (no)	1996-04-12
GB9321221D0 (en)	1993-12-01
TW283144B (bg)	1996-08-11
BG100511A (bg)	1996-11-29
NO309861B1 (no)	2001-04-09
JPH09503770A (ja)	1997-04-15
NO961475L (no)	1996-04-12
HU219710B (hu)	2001-06-28
US5962496A (en)	1999-10-05
OA10578A (en)	2002-06-07
IL111294A0 (en)	1994-12-29
RU2144535C1 (ru)	2000-01-20
AU681194B2 (en)	1997-08-21
CO4290355A1 (es)	1996-04-17
CN1133042A (zh)	1996-10-09
FI961628A7 (fi)	1996-04-12
PL179568B1 (pl)	2000-09-29
PL313969A1 (en)	1996-08-05
US5760059A (en)	1998-06-02
BG61839B1 (bg)	1998-07-31
FI961628A0 (fi)	1996-04-12
US6100289A (en)	2000-08-08
SK44996A3 (en)	1997-01-08
CZ92396A3 (en)	1996-08-14
SG49013A1 (en)	1998-05-18
HUT76065A (en)	1997-06-30
PE21995A1 (es)	1995-08-14
HU9600969D0 (en)	1996-06-28
CA2171449A1 (en)	1995-04-20
WO1995010517A1 (en)	1995-04-20

Publication	Publication Date	Title
AU681194B2 (en)	1997-08-21	Indole derivatives as NMDA antagonists
AP480A (en)	1996-03-22	3-Substituted indole 2-carboxylic acid derivatives.
US5686461A (en)	1997-11-11	Indole derivatives
AU708291B2 (en)	1999-07-29	Indole derivatives as EAA antagonists
AP877A (en)	2000-09-27	Tetrahydroquinoline derivatives as EAA antagonists.
MXPA97006605A (en)	1998-02-01	Indol derivatives as antagonists of amino acids exited
WO1995007887A1 (en)	1995-03-23	Indole derivatives as antagonists of excitatory amino acids